CallousDisregard

AutismandVaccines-TheTruthBehindaTragedy

AndrewWakefield,MB,BS,FRCS,FRCPath

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LibraryofCongressCataloging-in-PublicationData

Wakefield,AndrewJ.Callousdisregard:Autismandvaccines—thetruthbehindatragedy/AndrewJ.Wakefield.p.;cm.Othertitle:Autismandvaccines—thetruthbehindatragedyIncludesbibliographicalreferences.

9781616081690

1.Autisminchildren--Etiology.2.MMRvaccine--Sideeffects.I.Lancet.II.

Title.III.Title:Autismandvaccines—thetruthbehindatragedy.

[DNLM:1.AutisticDisorder--etiology--PersonalNarratives.2.Child.3.HealthPolicy--PersonalNarratives.4.Measles-Mumps-RubellaVaccine-adverse

effects--PersonalNarratives.WM203.5W147c2010]

RJ506.A9W3532010

618.92’85882071--dc22

2010017228

PrintedintheUnitedStatesofAmerica

Thisbookisdedicatedtomyinspirationalandlong-sufferingwife,Carmel,andtoourwonderfulchildren,

James,Sam,Imogen,andCorin-cherishyourmindsandusethemwell.

Acknowledgements

Iwouldliketoexpressmyenormousgratitudetothosedirectlyinvolvedintheproductionofthisbook.Theyincludemywife,Carmel;myeditorTeriArranga;my designer FionaMayne; JimMoodywithwhom I co-wrote“Ethics, Evidence, and the Death of Medicine,” which appears as theafterwordtothisbook;Dr.CarolStottwhoassistedwithChapter1;PollyTommeyforhersupportandallowingaccesstoherteamandpermissiontoreprintarticles fromTheAutismFile; theeditorsofAgeofAutism forpermission to reprint Chapter 13; Wendy Fournier for designing thewebsite www.callous-disregard.com; and all of those individuals andorganizations thathaveprovideda link to thiswebsite. I amparticularlygrateful toDr.PeterFletcher, JennyMcCarthy,andJimMoodyfor theircommentaries aswell as those providing additional remarks.My thanksarealsoduetoTonyLyonsofSkyhorsePublishingandtoKimStaglianoformakingtheintroduction.

Beyond this isanarmyofsupportersandfellow travelers towhomIamrelatedbyblood,sweat,andtears;mysincerethanksareextendedtoyoualso.

TableofContents

TitlePageCopyrightPageDedicationAcknowledgementsPREFACEFOREWORDDRAMATISPERSONAEWhyPROLOGUE-CallousDisregardCHAPTERONE-ThatPaperCHAPTERTWO-TheChildrenCHAPTERTHREE-TheDean’sDilemmaCHAPTERFOUR-TheWhistleblowerCHAPTERFIVE-EthicsandtheMassesCHAPTERSIX-TheDean’sPressBriefingCHAPTERSEVEN-HortonandTheLancetCHAPTEREIGHT-Horton’sEvidenceCHAPTERNINE-TheDevil’sintheDetailCHAPTERTEN-BedlamorBonaparteCHAPTERELEVEN-DisclosureCHAPTERTWELVE-DeerCHAPTERTHIRTEEN-PoisoningYoungMindsAFTERWORD-Ethics,EvidenceandtheDeathofMedicineEpiloguePostscriptBIOGRAPHY

PREFACE

Letter from Dr. Peter Fletcher, Ex-Principal Medical Officer withresponsibility for the UK’s Committee on Safety ofMedicines and laterSeniorPrincipalMedicalOfficerandChiefScientificOfficer

My first commenton this excellent book is in respect ofwhether or notthis whole catastrophe could have been avoided by action taken yearsearlierthanTheLancetpaper.Byabout1987 in theUK,product licence(PL)submissionsforthreeMMRvaccineshadbeeninitiatedandwerethesubject of discussion by the Joint Committee on Vaccination andImmunisation(JCVI).MypastpositionofPrincipalMedicalOfficerwithresponsibilityforthemainCommitteeonSafetyofMedicines(CSM)anditssub-Committeesleadsmetotheconclusionthatagreatdealcouldhavebeendone.

Itwouldhave come tomyattention fromminutesof the JCVI that theywereurgingrapidgrantingofPLsforthethreevaccines.Thatnewswouldhave been alarming because the JCVIwas a purely advisory committee(i.e., not a Section 4 committee under the Medicines Act) and had nopowersinthegrantingorrefusalofPLs.

InthepasttherewouldhavebeennowayinwhichtheCSMwouldhaverecommendedthegrantingofPLsonsuchscantyevidenceofsafetyinthesubmissions. By 1988/9 the only evidence available was a handful ofclinical trialseachhavingnomorethan7-800subjectsandnoneofthem

conductedintheUK.HadIstillbeenthereIwouldhaverequiredatleast10,000 patients in each submissionwith active safety surveillance for aminimumof3monthswith thepossibility that this couldbeextended ifuntowardfindingsshouldbereported.

This wouldmost probably have solved our current problem as we nowknow that at least 35 cases of “autism” had been officially reported byabout1993.

Mysecondcommentistoemphasisethegreatimportanceofthe“positiverechallenge”caseswhich, forallpracticalpurposes,provecausality.TheCSMhasalwaysacceptedthatpositiverechallengeintheabsenceofotherequivalentandcrediblecauseshastobeacceptedasacausalrelationship.

My third comment concerns the analysis of anaphylaxis as a seriousadverseeffect.Thishasbeenmuchneglectedandcarefullyavoidedwhenmortality of vaccines is discussed. This is of primary importance whenbenefits and risks of vaccination are considered and compared withmortalityofinfections.If,forexample,pre-vaccinationfiguresforannualmortality due to measles (about 50 in 1967) are to be compared withannual mortality due to vaccines then, in developed countries whereimprovementsinsocialconditionsandstandardsofhealthcarehavebeenachieved,thedifferencesbecomeuncomfortablyclose.

Myfourthcommentrelatestothesafetyevaluationofmedicinalproductsintended for healthy people. The two biggest examples are hormonalcontraceptives and vaccines. The differences between the two aremindboggling. The contraceptives have been evaluatedmore intensivelythananyothergroupofmedicinalproductsbothinhumansandanimals.Incontrast,vaccineshavebeenminimallyinvestigatedandthereseemstobe

nohopeofanimprovementinthefuture.

My fifth comment is related to the overall conduct of theGMCa case. Ihavenowbeeninvolvedinfivedifferentlegalcases,andinallIhavebeenin varying levels of despair when faced with the medical and scientificignoranceof the lawyers (solicitors andbarristers)onboth sides.This isquiteunderstandable sinceamedical educationextendsovermanyyearsand,althoughthelawyersdoquitewellonthespecificsofthecase,theyarelostwhenitcomestothebiggerpicture.Thisisreferredtoverynicelyonpage143withCharcotetal.,andtosomeextent,itexcusestheoverallfeelingof thecasedescending intoanundignifiedcatalogueofbickeringbetweenveryirritatingacademics.

Lastly,Iwouldliketomentionthegeneralclinicalpicture(s)presentedbythese childrenwhich, inmyview, constitutes a complex new syndrome.The differing clinical observations cannot each have a different andseparated pathological cause. It may be that two or just possibly threedifferentpathologicalprocessesareinvolved,buttherootcausehastobeasingleinitiatingfactor—almostcertainlyvaccines.

FOREWORD

I’m so glad Andy Wakefield finally has the chance to tell his story.Perhaps no debate on the planet right now is more confusing, moreconflicting,ormoremaddeningforparentsthanthedebateoverthecausesandtreatmentsofautism.

Astheparentofachildwhoregressedintoautismafterhisvaccinations,Ihave always consideredAndyWakefield to represent the kind of doctorandscientistwhowillultimatelyhelpusendtheepidemicofchildrenwithautism.

IfyouunderstandAndy’sstorycompletely,Ithinkyouwillquicklyrealizethat he did the sort of thing most of us expect out of our doctors andsomethingmostofusweretaughtbythetimewewereinkindergarten:helistenedcloselytothestoriesofparentsandhetoldthetruth.

Ireallywishtheprimarytriggerforautismwassomethingeveryonecoulddislikelikecigarettesorratpoison.Itwouldmakeendingthisepidemicsomucheasier.Unfortunately,itappearsthataproductintendedforgood—vaccines—alsohasadarkside,whichis theabilitytodoharmincertainchildren.Thisabilitytodoharmhasunfortunatelyincreasedquiteabitinthe last fewdecadesbecausechildren today receive somanymore shotsthanwhenmostparentswerekids.

Iunderstandthataportionofthepopulationwillcontinuetobelievethatallofusparentsarecrazyandthatvaccinescouldn’tpossiblydoanyharm.I really wish some of these people could have sat withme through thethousandsofconversationsIhavehadwithparentsofchildrenwithautismwhohavealltoldmethesamestory:theirchildwasdevelopingnormally,andaftereachvaccineappointment thingsgotworseuntil theyendedupwith autism. You hear this story once, it’s disturbing, a dozen times itstartstofeellikeapattern,athousandtimesandyoubegintowonderwhythisisstilladebate.

AndyWakefielddid thesame thing.He listened toparentswhoreportedtwo things: their childrenwith autismwere suffering from severe bowelpain,andthechildrenregressedintoautismaftervaccination.Helistened,hestudied,andhepublishedwhathelearned.

IbelievehistorywillbeverykindtoAndyWakefield.Forthemoment,heisthesymbolofaveryunfortunatereality,arealitythatamedicalsystemtryingtodogoodmayhavedonejusttheopposite.Withtime,Ibelievehewill also be the symbol of someone who stood up for truth, despiteextremepressuretostanddown.

Forhundredsof thousandsofparentsaround theworld,myself included,AndyWakefieldisasymbolofstrengthandconvictionthatallparentsofchildrenwithautismcanuse tofight for truthand thebest livespossiblefortheirkids.

JennyMcCarthyApril22,2010LosAngeles,CA

DRAMATISPERSONAE

Why

Another north-easterly wind insinuated its futile energies between themassivebrickpiersofHoundsGhyllviaduct.Althoughthewindendured,the earlier downpour had turned to a light drizzle — light for CountyDurham,inthefarnorthofEngland—astheirjourneycametoanend.

As if for the first time, Mark seemed attuned to his mother’s sense ofpurpose andheofferedno resistance.Hedidnot scream,or fight, orhithimselfintheface;hedidnotbitehisscarredandscabbyarmsorsuddenlycollapsetothegroundasifinvisibleguy-ropescouldnolongerholdhim.Instead, entranced by the raindrops and in awe of the viaduct’s orderedbrickwork, hemouthed in silentwonder at it all.At themidpoint of theviaductshe turned to thenorth, thedeepvalleybeforeher - inplaces itswallssheer,glisteningblack,cutbyrelentlesswatersthatwerenowbarelyvisibleinthefadinglightfar,farbelow.Marklookedupintohismother’sface; beyond its years, alone, harassed, pursued, and he understood herunhappiness.Helovedher,althoughhehadnoway—nowiring—thatallowedhimtoexpressthis.

Withtheaidofsomeoldtimbersshehelpedhimontotheparapet,hergripsofirmthatithurtthemboth.Thiswasthehardestpart,thelichenedstonewet and perilous, her fear of heights. Standing there at last, against thewind and against theworld, he looked at her and she at him. “No,” shethought,“thisisthehardestpart.”Withoutaword,withoutanotherthoughtshesteppedintooblivion,hermostpreciouspossessiontakenwithher,torankindeathwithEgyptianqueens.Theywerenotequaltothewindandinone finaleffort itgusted into them, threatening tosmash thewaif-like

Mark into themerciless viaduct. She knew.Shewas ready. Falling everfaster,shepulledhimtoher,loveandinstinctkeepinghimsafe.

PROLOGUE

CallousDisregard1Ifautismdoesnotaffectyour familynow, itwill. If somethingdoesnotchange— and change soon— this is almost a mathematical certainty.Thisbookaffectsyoualso. It isnotaparochial lookat a trivialmedicalspatintheUK,butdispatchesfromthebattlefrontinamajorconfrontation–astruggleagainstcompromiseinmedicine,corruptionofscience,andarealandpresentthreattochildrenintheinterestsofpolicyandprofit.Itisa story of how “the system” deals with dissent among its doctors andscientists.

This book is composed of a series of essays that deal with the nowinfamouspaper–ahumblecaseseries–writtenbydoctorsat theRoyalFreeHospitalandpublishedinTheLancetinFebruary1998.2Theessayswereoriginallyintendedtostandaloneandsomerepetitionisinevitable.

TheLancetpaperdescribedtheclinicalhistoryandfindingsinagroupof12 children, referred to in these essays as The Lancet 12. The childrenpresented with autistic regression and gastrointestinal symptoms. Wheninvestigateddiligentlyandappropriately,theyturnedouttohaveintestinalinflammation,andtherearereasonstobelievethatthisinflammationmay,inturn,belinkedtotheirneurologicaldisorder.Thus, thepapercapturedtheessentialelementsofanewdiseasesyndrome–apotentiallytreatablesyndrome–and that shouldhavebeencause forsomesmallcelebration.Had the children’s regression followed natural chicken pox, this book

wouldneverhavebeenwritten.Itdidn’t;forninechildren(asitturnsout),behavioral changes and subsequent developmental regression followedexposuretotheMMRvaccineandtherebyhangsthistale.

Inthespringof1982,Iwasaveryjuniordoctor,undertakingmysecond6-monthrotationasahouseman(intern)inmedicineatSt.Mary’sHospital,myalmamater,inPaddington,WestLondon.Takingabriefwalkoutsideat lunchtime to get a sandwich, I heard a huge explosion. Immediately,instinctively,Iknewitwasabomb.

At that time, hostilities in Northern Ireland had intensified, anddisaffectionwithintheranksoftheIrishRepublicanArmyhadledtotheformationofthemoremilitantIrishNationalLiberationArmy.Allatoncethere was movement; I found myself bundled into the back of anambulance and headed at breakneck speed to who-knows-where. TheambulancemaninthepassengerseatshoutedbacktothetwonursesandmethatwewereheadedforabombinginRegent’sPark.Inamutedeffortatprofessionalism,wewentthroughaninventoryoftheequipmentwehadavailable;intruth,wewereterrified.

ThesceneinRegent’sParkhadasurrealquality.AgainstthebackdropofagentleEnglishsummer’sday,thebandstandandthebandoftheregimentof Royal Green Jackets had been blown to pieces. Sheet music blewamong flattened deck chairs and fallen bandsmen. The bomb had beenplacedunderthefloorboardsinthecenterofthebandstand.Suchwerethekinetics of the explosion that those sitting on top of the bombhad beenblown up to 50 feet away, while mercifully, those not 3 yards away“escaped”withperforatedeardrumsandshock.

As it turnedout,allbuta fewof the injuredhadalreadybeenevacuatedandonlyafewsoldierswithminorinjuriesremained,awaitingtransporttohospitalforacheck-upandeardrops.Therewasnothingforustodo,savetour the devastationwith a seniormember of the emergency services todeclareasdeadblackenedlimbsandtorsos.

When itcame time to leave, I turnedone last timebeforeclimbingbackintotheambulance.IdidsoinordertoreinforcethatIshouldneverforgetwhathadhappenedthatday.Ifeltanoverwhelmingsenseoffutilityandfailure;mymedicaltraininghadcountedfornothing,therewasnothingtobe done − nothing. In contrast, when in 1995 I was approached byRosemary Kessick, portending the first ripples of the coming autismtsunami,IdeterminedthattherejustmightbesomethingIcoulddo.AndsoIdidbecausesomethingismorethannothing.

Whathashappenedinthemeantimeisastorythatwaswrittenlongbeforeanyofuswereborn.Itisthestoryofhowthepowerfuldealwiththreatstotheirinterests.ItwasrecentlysuggestedtomeinaninterviewwithamajorUS network that this was really just conspiracy theory. As it happened,earlier that week, internal memos from the pharmaceutical giantMerckweredisclosedtotheAustraliancourtintheVioxxlitigation.Theytalkedof how Merck had to “neutralise” dissent from those doctors whoquestionedthesafetyof thisdrug.Inrelationto theseconcerneddoctors,oneofthee-mailsread:

Wemay need to seek them out and destroy themwhere theylive.3

Itwouldseemthatratherthanbeingconspiracytheory,thiscansometimes

becorporatepolicy.

Tothevaccineindustry,theregulators,publichealthofficialsanddoctors,pediatricians,andBillandMelindaGates,7Iwouldsaythis:thesuccessofvaccinationprogramsrequiresthewillingparticipationofconsumers.Keyto any success, therefore, is public confidence in the scientists, doctors,andpolicymakers(includingindustry)thatshapetheseprograms.Inturn,thekey to that confidence is a safety first vaccine agenda.Thosewhosepriorityissafetyfirstarenotanti-vaccine.Byanalogy,thosewhoorderedthe recall ofmultipleToyotabrands for stickinggaspedals arenot anti-car.ThefollowingfromtheExaminermayprovidesomecontext:

ToyotaRecallAn investigation by the Federal government has uncoveredwhatappearstobepresentationdocumentsfromJulyof2009where Toyota boasts about saving $100million because theywere able to negotiate a limited equipment recall for theToyotaCamryandLexusESvehiclesinsteadofamoreseriousandcostlyproblemwiththecars.Thepointwaslistedunderasectioncalled“wins.”

The federal regulators, the National Highway Traffic SafetyAdministration(NHTSA),hadthistosayaboutToyota:

Safety is everybody’s responsibility… It’s not just the federalgovernment’s job to catch safety defects… It’s theresponsibilityofautomakers tocome forwardwhen there isaproblem.Unfortunately, this document is very telling…we’regoing toholdToyota’s feet to the fireandmake sure theydowhat’s necessary to make their cars safe for the drivingpublic.4

Who,here,isultimatelyanti-caror,tobemorespecific,anti-Toyotabrandcar?Inafreemarket,withoutmandates,whathashappenedatToyota isunlikely to boost public confidence and, therefore, the company’s salesandprofitability.Liability fordeaths and injuries is likely tohaunt themformanyyearstocome.

Andwhataboutthecomplicityofex-regulators?

ToyotaUsedEx-RegulatorstoHelpKillProbes5

Toyota (TM) hired ex-government regulators to kill at leastfourinvestigationsintoproblemswithitscarsintheU.S.

Thosewhoareathreattopublicconfidence,thosewhodonotmandateasafetyfirstagenda,arethegreatestthreattothevaccineprogram;theyareultimatelyanti-vaccine.

So,wheredoyou–theregulatorsandthevaccineindustry–standin2010with your costly PR programs; your ruthless, pragmatic exorcism ofdissent;yourpublicconfidencerating?

Study:1in4parentsthinkvaccinescauseautism6

Anewstudysaysthat54percentofparentsareworriedaboutserious adverse effects causedbyvaccines, and25percent ofparentsbelievethatvaccinescancauseautism.

Youhavefailed.

To the parents I would say, trust your instincts above all else. Whenconsidering how to vaccinate your children, read, get educated, anddemandfullyinformedconsentandanswerstoyourquestions.Whenyouare stonewalled or these answers are not to your satisfaction, trust your

instinct.Isaythisassomeonewhohasstudiedandengagedinthescienceand who has become aware of the limitations of our knowledge andunderstandingofvaccinesafety issues.Maternal instinct, incontrast,hasbeen a steady hand upon the tiller of evolution; we would not be herewithoutit.

Ascorroborationof this instinct, itmaynot comeasa surprise that as amatter of fact, the US vaccine court began compensating for cases ofvaccine-causedautismstartingin1991,8andtheUSDepartmentofHealthand Human Services has been secretly settling cases of vaccine-causedautism without a hearing also since 1991. For example, we offer thefollowingfromcbsnews.com:

AsCBSNewshas reported, thegovernmenthasbeen settlingvaccine injuries that resulted in autism and/or autisticsymptoms since at least the early 1990’s, while at the sametimetellingthepublicthereisnocauseforconcern.Notallofthecasesarepublished,butsomeofthemareandcanbefoundbysearchinglegalcasedatabases.9

Nontheless,questioningthesafetyofavaccineled,bytwistsandturns,toa disciplinary hearing for me and two coauthors of The Lancet paperbefore theUK’smedicalregulator, theGeneralMedicalCouncil (GMC).During the GMC hearing, I went back to Regent’s Park − to the crimescene.Itwaswinter;therewasnoband,nomusic,andnochildrenrunningamongdeckchairs.Therewerenodeckchairs.Butforallthat,youcouldnot have guessed at the history of this place. And as I was leaving, Iturned,andtherewerebodieseverywhere.Ilookedback,notinanger,butwithalmostthesamesenseoffutilityandfailurethatIhadfeltsometimebefore.Wecannotallowourselvessuchfeelings;thereisajobtodo.

What follows is dry, factual, and unbecoming prose. There is not the

luxuryforanythingmoreintheteethofthestorm.Itmighthavebeenthelogofadoomedcaptainwritteninthecabinofawar-tornfrigate,tackingonshreddedsails,runningfromanother—perhapsfinal—broadside.Butit isnot; itwaswrittenfromthebridge, thehelmsecure, thewindatourbacks, and the sails full as the aggressor slips back below an uncertainhorizon.ThedaywillbelongtoReason.

Endnotes1 AttheGMCIwasaccusedandfoundguiltyof“callousdisregard”forthesufferingofchildren.

2 Wakefield,AJ,MurchSH,AnthonyA,Linnell J,CassonDM,MalikM, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A,Davies SE,Walker-Smith JA. Ileal lymphoid nodular hyperplasia, non-specific colitis and pervasive developmental disorder in children. TheLancet.1998;351:637-641.[retracted]

3 RoutM.(2009,April1).VioxxmakerMerckandCodrewupdoctorhit list. Retrieved fromhttp://aftermathnews.wordpress.com/2009/04/27/vioxx-maker-merck-and-codrew-up-doctor-hit-list/

4 Stone M. (2010, February 22). Toyota recall investigation uncoversdocuments = saving money better than saving lives. examiner.com.Retrieved from: http://www.examiner.com/examiner/x-19632-Salt-Lake-City-Headlines-Examiner~y2010m2d22-Toyota-recall-investigation-uncovers-documents--saving-money-better-than-savings-lives.

5 McIntyre D. (2010, February 12). Daily Finance. Toyota Used Ex-Regulators to Help Kill Probes. Retrieved from:http://www.dailyfinance.com/story/company-news/toyotaused-ex-regulators-to-help-kill-probes/19355607/

6 FreedG,ClarkS,ButchartA, SingerD,Davis,M.ParentalVaccineSafety Concerns in 2009. Pediatrics. 2010;125(4);654-659. Retrievedfrom:http://pediatrics.aappublications.org/cgi/reprint/peds.2009-1962vl.

7 Bill and Melinda Gates Foundation. (2010, January 29). Bill andMelindaGatesPledge$10BillioninCallforDecadeofVaccines.Retrieved from http://www.gatesfoundation.org/press-

releases/Pages/decade-ofvaccines-wec-announcement-100129aspx.

8 Age ofAutism. (2009, February 27).Why is theMedia Ignoring theBailey Banks Autism Vaccine Decision? Retrieved fromhttp://www.ageofautism.com/2009/02/whyis-the-mediaignoring-the-bailey-banks-autism-vaccine-decisionhtml.SeealsoBaileyBanks,byhis fatherKennethBanksvs.Secretaryof theDepartmentofHealthandHumanServices.UnitedStatesCourtofFederalClaims. 20 July 2007. Retrieved fromhttp://www.uscfc.uscourts.gov/sites/default/files/Abell.BANKS.02-0738Vpdf.

9 AttkissonS.(2008,June19).VaccineWatch.CBSNewsInvestigates:Primary Source. Retrieved from http://www.cbsnews.com/8301-501263_162-4194102-501263.html. See also Afterword, “Ethics,Evidence,andtheDeathofMedicine.”

CHAPTERONE

ThatPaperOn February 28, 1998, twelve colleagues and I published a case seriespaper inTheLancet, a respectedmedical journal, asan“EarlyReport.”1The paper described the clinical findings in 12 childrenwith an autisticspectrumdisorder(ASD)occurringinassociationwithamild-to-moderateinflammation of the large intestine (colitis). This was accompanied byswelling of the lymph glands in the intestinal lining (lymphoid nodularhyperplasia),predominantlyinthelastpartofthesmallintestine(terminalileum). Contemporaneously, parents of 9 children associated onset ofsymptomswithmeasles,mumps,andrubella(MMR)vaccineexposure,8ofwhomwerereportedonintheoriginalpaper(seealsoChildPH’sstoryon following page). The significance of these findings has beenovershadowed by misunderstanding, misrepresentation, and a concerted,systematic effort to discredit the work. This effort, and specifically thecomplaintofafreelancejournalistandanintensepoliticaldesiretosubvertenquiryintoissuesofvaccinesafetyandlegalredressforvaccinedamage,culminated in the longest runningandmost expensive fitness topracticecase ever to come before the United Kingdom’s medical regulator, theGeneralMedicalCouncil.Atthispoint,theguiltyverdictisin.Now,andonlynow,withallof thecontemporaneousdocumentationavailable, is ittimelytoreviewboththeoriginalpaperanditslegacy.

BackgroundFrom the late 1980s, my team at the Royal Free Hospital School ofMedicine, the Inflammatory Bowel Disease Study Group, publishedextensively on possible causes and mechanisms of inflammatory bowel

disease (e.g., Crohn’s disease). This involved examination of a possiblecausalroleformeaslesandmeaslesvaccine.InMay1995,parentsstartedcontacting me with the story that their normally developing child hadregressedintoautismoranautism-likestate,withonsetinthemajorityofcasessoonafterMMRvaccine.Ataroundthesametime,thechildrenhaddeveloped chronic gastrointestinal (GI) symptoms similar to thosedescribedbyDr.LennyGonzalezintheJuly2009editionofTheAutismFile.2 Despite what were often debilitating intestinal symptoms, manyindicative of abdominal pain, few of these children had undergonephysical examination, let alone been investigated.Mention of theMMRvaccinehadoften alienatedparents further from their child’shealth careproviders.Manydoctorsattributed theonsetofsymptomstocoincidenceand were content to leave it at that. Conversely, at the Royal Free asystematicplanofclinicalcareandresearchwasdesignedinordertohelpaffectedchildren.

ChildPH’s*story,asoriginallytoldbyhismother,didnotciteMMRas theculprit.Eighteenmonthsofnormaldevelopmentwasfollowedbyregression,givingrisetowhatseveraldoctorslabeled“secondaryautism.”Lossofdevelopmentalmilestoneswasaccompaniedby lossofcoordination (hecouldno longerthrow and catch a ball), his gait became, “awkward and stifflike an oldman,” and he could no longer go from sitting tostandingunaided.Helostthe20wordsthathehadgainedanddevelopedsecondaryfecalincontinence.At18monthsofage,severeepisodesofabdominalpainstartedthatwereassociatedwith screaming and drawing his knees to his chest. Hedeveloped a pattern of chronic loose bowel motions withundigested food from 2 years of age.Hewent from the 97thcentileforweightat1yearofagetothe50thbyage2.Hisdietwentfrombeingvariedtoveryrestricted,consistingofrefinedcarbohydrates and at least ten 200 ml cartons of orange-flavoreddrinkperday.

What Child PH’s mother did not tell us in 1996 was that,contemporaneously,shetoohadlinkedherson’sproblemstoMMR vaccine. Our description of this child in The Lancetfaithfully reiterated the onset of symptoms following anepisodeofotitismediaashismotherhadreportedbutmadenomention of theMMR.The reason for this discordance in thenarrativeprovidesavaluablelesson:thereactionofsuccessivedoctorstothesuggestionthatMMRmighthavebeeninvolvedranged from patronizingly dismissive to outright hostile.Mentioning the vaccine was beginning to negatively impacttheirabilitytogethelpfortheirson.BythetimetheycametotheRoyal FreeHospital, the father had urged hiswife not tomention theMMR again in order to avoid discrimination bydoctorswhoconsideredhertobecrazy.

So it was that a potentially important element of the clinicalhistory in this child had been corrupted by the arrogance ofthosewho“knewbetter.”

*Initialshavebeenchanged.

StudydesignThe Lancet paper— the first in a series of related papers— is a caseseries: This is stated explicitly in the first line of the paper: “…aconsecutive series of children with chronic entero-colitis and regressivedevelopmental disorder.”1 A typical example of how basicepidemiological textbooks define and describe a case series is found inHennekensandBuring:3

Caseseriesstudiesdescribe theexperienceofasinglepatientoragroupofpatientswithasimilardiagnosis.Thesetypesofstudy, in which typically an astute clinician identifies anunusualfeatureofadiseaseorapatient’shistory,mayleadto

formulation of a newhypothesis…At that time an analyticstudy (most frequently using a case-control approach), can[then]bedonetoinvestigatepossiblecausalfactors.

The crucial design feature that differentiates the case series from otherdesigns is its lack of requirement to select participants on the basis ofeithertheexposure(e.g.,MMR)ortheoutcomeofinterest(e.g.,autism).Acaseseriesdoesnotrequire–andshouldnotemploy–strictinclusionorexclusion criteria. Rather, it should function to observe similarpresentations in groups of patients that appear to share other commonfeatures in order to raise hypotheses that later may be tested in theappropriatestudydesignframework(e.g.,acase-controlstudy).

TheLancetpaperdoesexactlywhat is requiredofacaseseries. It statesimmediatelywhat the report sets out to do: no particular developmentaldisorderwasstated,noparticularfeaturesortimingofonsetwererequired,no particular initial exposure was necessary, no specific outcome waspredicted,andnocausalassociationwasclaimed.

Ofnote,wehavebeencriticizedfornothavingcontrolsinthestudy;thatis, developmentally normal children included for the purpose ofcomparison.Whilecontrolsarenotusuallypartofacaseseries,wewentbeyond what would normally be required and did include comparisongroups – 19 age-matched children (5 for microscopic examination oftissues and14 formeasurementof urinarymethylmalonic acid [MMA]).Thiswouldhavebeenevidentuponaproperreadingofthepaper.

Finally,HennekensandBuringmakethecrucialpointthatthepurposeofacaseseriesistogeneratenewhypothesesaboutpotentialcausation.Itis

not designed to investigate possible causality. The Lancet paper washypothesisgenerating;itstimulatedaseriesofsubsequentpapers—rarelyif ever acknowledged by critics— that confirmed and characterized thebowel disease as novel, relatively frequent, and potentially treatable andtested ideas about causation.4 Among the critics there has been someconfusiononthispoint,whichisevident,forexample,inawidelyquotedanalysis of the paper by Professor Trisha Greenhalgh5 that raises andattemptstoansweraseriesofquestions,including:

Wastheresearchhypothesisclearlystated?Sheobserves,“Thepaperdoesnotstatearesearchhypothesisatall.”Thisisquitetrue.Caseseriesstudiesareneitherrequirednorexpectedtodoso.Having established that there was no hypothesis, Professor Greenhalghgoesontoposetheridiculousquestion:

Wasthisdesignanappropriatewaytotesttheresearchhypothesis?Sheconcludesthatthestudydesignwasnotanappropriatewaytotest“theresearch hypothesis.” However, since she has already identified the factthat no hypothesis was stated, she rather begs the question as to whichhypothesisthestudywasnotdesignedtotest.Itsoonbecomesclearthatitwas her hypothesis that the study did not test. Her conclusion that “thestudy designwas incapable of proving the [MMR] link oneway or theother” is, of course, entirely accurate aswehad already indicated in thepaperonpage641,paragraph2,lines1and2:1

Wedidnotproveanassociationbetweenmeasles,mumpsandrubellavaccineandthesyndromedescribed….

andparagraph5,lines4-6:

Further investigations are needed to examine this syndromeanditspossiblerelationtothevaccine.

ProfessorGreenhalghventuresevenfurtheroffcoursewhensheasks:

Werethestudy’sconclusionssupportedbythedata?It is not clearwhether ProfessorGreenhalgh is referring to theauthors’conclusions—i.e.,thatthedatadonotdemonstrateacausallinkbetweenthedisorderandMMRexposureand that further research is required,orwhether she is asking if the data support the hypothesis that she haseroneously imputed to the study authors. In the former case, the dataclearly support our conclusions. Not surprisingly, they do not supportProfessor Greenhalgh’s contrived hypothesis — that MMR causes thesyndromedescribed.

Shecontinues:

If the answer to [the question above] is “no,” would amore robuststudy design have been practically possible to test the study’smainhypothesis?

Continuingtobuildanargumentonahypothesisofherownconstruction,ProfessorGreenhalghanswersherquestionwitharesounding“yes.”Thatshedoesappearsatisfied,onthebasisofwhatcanonlybedescribedasacomplete misunderstanding of The Lancet study’s design, is cause forconcern. In turn, the failureof theDepartmentofHealth (whosewebsitedirectedpeopleviatheNationalHealthServiceExecutivetoheranalysis)toappreciate thepotential impactof thisdeeply flaweddocumenton theperceptionsofmanythousandsofworriedparentsisalarming.

Notwithstanding Professor Greenhalgh’s follies, one should never

underestimate the importance of the case series as a starting point formedical discovery. It is the tried and tested mode of the description ofhuman disease syndromes, including Kanner’s autism, Asperger’ssyndrome, andHeller’s disease (disintegrative disorder).One finalwordonthematterendorsesthisperspective:

Clinicalsituations inwhichacasereportorcaseseries isanappropriate type of study include the following: a doctornoticesthattwobabiesborninhishospitalhaveabsentlimbs(phocomelia). Both mothers had taken a new drug(thalidomide) in early pregnancy. The doctor wishes to alerthis colleagues worldwide to the possibility of drug relateddamageasquicklyaspossible(McBride,inTheLancet1961).Anyone who thinks ‘quick and dirty’ case reports are neverscientificallyjustifiedshouldrememberthisexample.

Andthesourceofthisinvaluablepieceofadvice?Dr.TrishaGreenhalgh,authorof“HowtoReadaPaper.”6

“Coincidence”

Coincidence—often the first resortof skepticalphysicians—refers, inthis context, to the chance occurrence of autistic symptoms beingidentified in thesecondyearof life,ataroundthesametimeasMMRisgiven. Regularly advanced as an explanation for the parents’ story,coincidenceisaconclusionoflastresort—onethatshouldbearrivedatonly after diagnostic due diligence has excluded alternative causes forneurologicaldeterioration inachild.Meticulousattentionshouldbepaidto the parental history, and the practice of claiming coincidencewithoutfirstexcludingpossiblecauseshasnoplaceinclinicalmedicine.Whereaninfection such as herpes simplex or Epstein-Barr virus (mono) haspreceded autistic regression, the medical literature shows that extensive

testing has been undertaken, the cause identified, and the child treatedaccordingly.7 In contrast, whenMMR vaccination has preceded autisticregression, little, if any, attempt has been made to investigate childrenappropriately. The case of Bailey Banks is one of those rare instanceswhere this has beendone and forwhom theUnitedStates vaccine courtruledthatMMRcausedhisASD.8Bailey’sMRI,performed16dayspost-MMR for encephalopathy, revealed abnormalities of brain myelinconsistent with acute disseminated encephalomyelitis (ADEM), anautoimmune brain inflammation that can follow measles or a measlesvaccine. The lesson is that every attempt should be made to evaluatechildren during the course of their regression since, as in the case ofADEM,abnormalitiesofbrainmyelinmaybetransientandnotevidentonanMRIperformed2yearsafterexposure.ThefactthattheparentsofTheLancet childrendescribed lossof fecal and/orurinary continence in fourcasesandataxia(clumsiness)inatleastsix—thelatterbeingareportedadverse reaction toMMRvaccine— ismore thanenough indication forthorough neurological workup. The history of regression with loss ofacquired skills in a previously normal or near-normal child should ringalarmbellsand initiateasystematicapproach todifferentialdiagnosis. Itwas with this in mind that ProfessorWalker-Smith, one of the world’sleading pediatric gastroenterologists and senior author of The Lancetpaper,wrotein1997:

[Thesechildren]havenothad the levelof investigationwhichwewouldregardasadequateforachildpresentingwithsuchadevastatingcondition.9

Despiteevidentneurologicalsymptoms,despitetheproximityofonsettoaviralexposure,anddespiteadditionalphysicalsymptomssuchaspainanddiarrhea,adiagnosisofautismtrumpedtheneedforanythingbutminimalinvestigation by “mainstream” autism practitioners for the majority ofthesechildren.

Coincidenceandrechallenge

Whereachildwithregressiveautismhasreceivedmorethanonedoseofameasles-containing vaccine (MCV), exacerbation of existing symptomsand/or recurrenceof transient symptomsassociatedwith the first dose isfrequently reported. Properly documented, the Institute of Medicine’sVaccineSafetyCommitteeacceptsthe“rechallenge”effectasevidenceofcausation.10 Inorder to examine this in the settingofMMRandautisticenterocolitisand toovercometheconcernaboutparental recallofeventsthat may have occurred many years before, we conducted a studycomparingtheseverityofintestinal inflammationbetweenchildrenonce-vaccinatedandthosetwice-vaccinatedwithanMCV.Ourhypothesiswasthat the disease should be more severe in those exposed twice if thedisease were caused by the vaccine.11 There was a significantly higherprevalenceofactivechroniccolitis(involvingpus-formingcells)inthosechildren given anMMRormeasles and rubella (MR) booster comparedwith thosereceivingonlyonedose,supportingacausalassociation.Thisapparent rechallenge effect is currently being examined in a largepopulationofUSchildrentoseeifthefindingisreproducible.

Rechallengewithameaslesvaccine

ChildRT*wasmonitoredcloselyinhisfirstyearduetowidebridging of his nose. He was discharged from follow-up asdevelopmentally and physically normal by 15months of age.Helaterreceivedasinglemeaslesvaccinefollowingwhichhestopped“cruising”aroundfurnitureandregressedtocrawling.His learningplateauedand,by20months,hehad lostwords;soonthereafter,hestoppedtalkingaltogether.Generalillhealthdeveloped in his second year with ear, chest, and throatinfections,anddiarrheawithabdominalpain.Accordingtohismother’sstory,2weeksafteranMMRvaccine,at4.5yearsof

age,he“disappeared”and“lostallskillsandcommunication.”Whileat10monthsofagehehadbeenabletobuildatowerofbricks,hisplayskillsdeclinedtothepointthat,“nowhe[was]lost as to what to do with them.” In addition, he becameclumsy, started head banging, and developed repetitivebehaviors.He losthisself-helpskills; forexample,before theMMRboosterhecould feedhimselfwithaspoon,afterwardshecouldnolongerevenholdacup.

ThehistoryofChildRT’sGIproblemsisalsoinstructive.Hisrecordsstate:“Thediarrhoeabecameaproblematbetween1-1½ years of age [after his single measles vaccine]… itgenerally contains undigested food. His diarrhea becamesignificantlyworse from4½yearsof age [afterhisMMR]...”Failure to thrive, a cardinal sign of pediatric inflammatorybowel disease, was evident from the GP’s records; he wasreported to be “dropping off centile charts.” This failure tothrive continued and took another downturn at the same timethathisdiarrheaworsened,whenhewasnotedtohavedroppedfromthe9thtothe2ndcentileforweight.

Further examination of MMR rechallenge is currently underway.

*Initialshavebeenchanged.

DiligentscienceThe quest for precision can become a hostage to fortune, as themicroscopicanalysisofTheLancetchildren’stissueswastoprove.TherearefewpeopleintheworldwithProfessorWalker-Smith’sknowledgeofthemicroscopic appearances of inflammatory disease of the intestine inchildren.Soitwasthat,intheabsenceofapediatricpathologistexpertinthis fieldat theRoyalFree,ProfessorWalker-Smithconductedaweeklyreviewofhispatients’tissuesandidentifiedthefactthatdiseasewasbeing

missedinsomechildren.Inordertoreducethisriskandtostandardizethereporting of the ASD children’s biopsies, all tissues were subsequentlyexaminedby a single senior pathologistwith expertise in bowel disease.His findings were recorded on a specially designed chart to documentspecificfeaturesoftissuedamage.12ThisrecordformedthebasisofwhatwassubsequentlyreportedinTheLancet.Fewcaseseriesgotothislevelofprecision.

In the hands of someone determined to discredit the work, however,discrepanciesbetween the routineclinical report (whichmayhavecome,for example, from a pathologist with an interest in brain disease orgynecologicalpathology)andthestandardizedexpertanalysiswerefalselyreported in thenationalmedia as “fixing”of thedata. Iwas specificallyaccusedofthis,althoughIhadnopartinscoringthereviews.Itisnotablethatdespite5yearsof investigationby theGMC,nochargeofscientificfraudhasbeenmadeagainstanyofthedefendants.TheallegationoffraudwasmadebythesamefreelancejournalistwhohadactuallyalsoinitiatedtheGMCenquiry, continuing his litany of false allegations. There is noevidence at all that the data had been “fixed” as was alleged, and thenewspaperinquestionhasfailedtoproduceany,despitearequesttodosofromthePressComplaintsCommission.Paradoxically, thepricepaidfordiligentsciencehasbeenaheadlineproclaimingfraud.Inmyopinion,theintendedgoal—toreinforcethefalsebeliefthattheworkisdiscredited–hasbeenachieved.

Thedamagedone

Thedamagedonetomyreputationandtothatofmycolleaguesaswellasthepersonalpriceforpursuingavalidscientificquestionwhileputtingthepatients’ interestsaboveallothers is trivialcomparedwith the impactofthese falsehoods on the children’s access to appropriate and necessary

care.Myexperienceservesasacynicalexampletodiscourageothers.Asaconsequence,manyphysicians in theUnitedKingdomandUnitedStateswill not risk providing the care that is due to these children. There is apervasive and openly stated bias against funding and publication of thiswork, and I have been excluded from presenting at meetings on theinstructions of the sponsoring pharmaceutical company. This episode inmedical history has been an effective exercise in public relations andsellingnewspapers.Butitwillfail—itwillfailbecausenaturecannotbedeceived.

Ithasalwaysbeenaprivilegeworkingonbehalfofchildrenwithautismandtheirfamilies.Itismyhopethatbeforetoolongthetidewillturnandthat,inaddition,myteacherandmentorProfessorSirStanleyPeart,FRS,willcometorealizethatIhaveneverforsakenhisinstruction.

Myths

TheLancetpaperwasfundedbytheLegalAidBoard(LAB)13

False—NotonepennyofLABmoneywasspentonTheLancetpaper.ALABgrantwas provided for a separate viral detection study. This latterstudy,completedin1999,doesdisclosethesourceoffunding.TheLancetpaperhadbeensubmittedforpublicationbeforetheLABgrantwasevenavailabletobespent.

Myinvolvementasamedicalexpertwaskept“secret”14

False — at least 1 year before publication, I informed my seniorcoauthors,15theheadofthedepartment,thedeanofthemedicalschool,16and theCEOof the hospital.This factwas also reported in the nationalpress15monthspriortopublication.17

Children were “sourced” by lawyers to sue vaccinemanufacturers14

False—Childrenwerereferred,evaluated,andinvestigatedon thebasisof their clinical symptoms alone, following referral from the child’sphysician.18

Childrenwerelitigants19

False—atthetimeoftheirreferraltotheRoyalFree,thetimematerialtotheirinclusioninTheLancetpaper,noneofthechildrenwerelitigants.

Ihadanundisclosedconflictofinterest20

False—TheLancet’sdisclosurepolicyat that timewas followed to theletter. Documentary evidence confirms that the editorial staff of TheLancetwasfullyawarethatIwasworkingasanexpertonMMRlitigationwellinadvanceofthepaper’spublication.21

Didnothaveethicscommittee(EC)approval14

False—Theresearchelementofthepaperthatrequiredsuchanapproval,detailedsystematicanalysisofchildren’s intestinalbiopsies,wascoveredbythenecessaryECapproval.22

I“fixed”dataandmisreportedclinicalfindings23

False—Thereisabsolutelynobasisinfactforthisclaimandithasbeenexposedasfalse.24

Findingshavenotbeenindependentlyreplicated21

False— The key findings of lymphoid nodular hyperplasia (LNH) andcolitis in ASD children have been independently confirmed in fivedifferentcountries.25

Hasbeenretractedbymostoftheauthors26

False — 11 of 13 authors issued a retraction of the interpretation thatMMR is a possible trigger for syndrome described. This remains apossibilityandapossibilitycannotberetracted.

Theworkisdiscredited27

False—Thoseattempingtodiscredittheworkhaverelieduponthemythsabove.Thefindingsdescribedinthepaperarenovelandimportant.4

ThelegacyofTheLancetpaperThefirstdemonstrationofintestinalpathologyinASDGI symptoms are common in childrenwith autism, and these symptomsarefrequentlyassociatedwithintestinalinflammation.

TreatmentofGI inflammationmay lead to symptomatic improvement inbothGIandbehavioralsymptoms.28

ThefirstdemonstrationofabnormalvitaminB12metabolisminASDNowthesubjectofmajorclinicalandresearchactivitiesinautism,rangingfrom study of genetic differences in B12/folatemetabolism to treatmentwithactiveformsofB12.

The first study toreportarechallengeeffectofameaslescontainingvaccine(MCV)Follow-up indicates that intestinal inflammation is significantlyworse inrechallengeASDchildrenthanchildrenreceivingonlyoneMCV.11

First study to seek evidence of a mitochondrial disorder bymeasurementoflactatetopyruvateratioincerebrospinalfluid“Mito”disordersappeartobecommoninASDchildrenandmaybeacquired.TheUSgovernmentconcededthatvaccinestriggeredautisminHannahPoling,achildwith“mito”disorder.29

Didtheyreadthepaper?AriBrown,MD.Spokespersonfor theAmericanAcademyofPediatricsandtheImmunizationActionCoalition

“This flawed study concluded that the rise in autism wasrelated to giving the combination vaccine ofmeasles-mumps-rubella(MMR).”30

ProfessorSirMichaelRutter,FRS.ExpertprosecutionwitnessGMC,expertwitnessonbehalfofMMRvaccinemanufacturers

“Publicationofastudyclaimingacasualrelationshipbetweenmeasles, mumps and rubella (MMR) vaccine and autismspectrumdisorders(ASD)sparkedaheateddebate…”31

ProfessorEric Fombonne.Expertwitness on behalf ofMMRvaccinemanufacturers

“Recent reports claim to have identified another variant ofautism(called‘autisticenterocolitis’)inchildrenreferredtoagastroenterology department. The hypothesis has involved 3separateclaims:1)thatanewphenotypeofautismassociatedwithdevelopmentalregressionandgastro-intestinalsymptomshas emerged as a consequence of measles-mumps-rubellavaccination…”32

Endnotes1 Wakefield A, et al. Ileal lymphoid nodular hyperplasia, non-specificcolitis and pervasive developmental disorder in children. The Lancet1998;351:637-641.[retracted]

2 GonzalezL.GastrointestinalPathologyinAutismSpectrumDisorders:theVenezuelanExperience.TheAutismFile.2009;32:34-37.

3 HennekensC,Buring, J. (1987)Epidemiology inMedicine.Mayrent,SL(Ed.),Philadelphia,PA:Lippincott,WilliamsandWilkins.

4 Horvath K, et al. High prevalence of gastrointestinal symptoms inchildrenwith autistic spectrum disorder (ASD). J Pediatr GastroenterolNutr2000,31:S174.Melmed R, et al. Metabolic markers and gastrointestinal symptoms inchildrenwith autismand relateddisorders.JPediatrGastroenterolNutr2000,31:S31-S32.Horvath K, Perman J. Autistic disorder and gastrointestinal disease.CurrentOpinioninPediatrics2002;14:583-587.Furlano R, et al. Quantitative immunohistochemistry shows colonicepithelial pathology and γδ-T cell infiltration in autistic enterocolitis. JPediatrics 2001;138:366-372. Torrente F, et al. Enteropathywith T cellinfiltrationandepithelialIgGdepositioninautism.MolecularPsychiatry.2002;7:375-382.Torrente F, et al. Focal-enhanced gastritis in regressive autism withfeatures distinct from Crohn’s and helicobacter pylori gastritis. Am. J.Gastroenterol. 2004;4:598-605.Ashwood P, et al. Intestinal lymphocytepopulations in children with regressive autism: Evidence for extensivemucosalimmunopathology.J.Clin.Immunol.2003;23:504-517.AshwoodP, et al. Spontaneous mucosal lymphocyte cytokine profiles in childrenwith regressive autism and gastrointestinal symptoms:Mucosal immuneactivation and reduced counter regulatory interleukin-10. Journal ofClinicalImmunology.2004:24:664-673.

WakefieldA.Entero-colonicencephalopathy, autismandopioid receptorligands.AlimentaryPharmacology&Therapeutics.2002;16:663-674.UhlmannV, et al. Potential viral pathogenicmechanism for newvariantinflammatoryboweldisease.MolecularPathology2002;55:84-90.SabraA,etal.Ileal-lymphoid-nodularhyperplasia,non-specificcolitisandpervasivedevelopmentaldisorder inchildren.TheLancet,1998;352:234-235.Sabra A, et al. Linkage of ileal-lymphoid-nodular hyperplasia (ILNH),foodallergyandCNSdevelopmental:evidenceforanon-IgEassociation.AnnAllergyAsthmaImmunol,1999;82:8.Valicenti-McDermottM,etal.Frequencyofgastrointestinalsymptomsinchildren with autistic spectrum disorders and association with familyhistoryofautoimmunedisease.DevelopmentalandBehavioralPediatrics.2006;27:128-136.RichlerJ,Luyster,R,RisiS,HsuW,DawsonG,Bernier,R,etal.Istherea‘regressivephenotype’ofautisticspectrumdisorderassociatedwiththemeasles-mumps-rubella vaccine? A CPEA study.Autism Dev Dis 2006,36:299-316.Sandler R. Short-term benefit from oral vancomycin treatment ofregressive-onsetautism.JChildNeurol.2000;15:429-435.Parracho H. Differences between the gut flora of children with autisticspectrum disorders and that of healthy children. Journal of MedicalMicrobiology.2005;54:987-991.

5 Greenhalgh T. A critical appraisal of the Wakefield et al paper.Retrievedfromhttp://briandeer.com/mmr/lancet-greenhalgh.htm

6 GreenhalghT.HowtoReadaPaper.BMJ2001;326:106-106.

7 DeLong R, et al. Acquired reversible autistic syndrome in acuteencephalopathicillnessinchildren.ChildNeurology.1981;38:191-194.GillbergC.Briefreport:onsetatage14ofatypicalautisticsyndrome.Acase report of a girl with herpes simplex encephalitis. J Aut Dev Dis.1986;16:369-375.

Shenoy S, et al. Response to steroid therapy in autism secondary toautoimmune lympho-proliferative syndrome J Pediatrics. 2000;136:682-687.

8 Age of Autism. (2009, February 27).Why is theMedia Ignoring theBailey Banks Autism Vaccine Decision? Retrieved fromhttp://www.ageofautism.com/2009/02/why-is-the-mediaignoring-the-bailey-banks-autism-vaccine-decisionhtml.

9 Correspondence: Walker-Smith JA to Pegg M. (Chairman EthicalPracticesCommittee).November11,1996.

10 StrattonK, et al. (1994).AdverseEventsAssociatedwithChildhoodVaccines: Evidence Bearing on Causality. Washington, D.C.: NationalAcademiesPress.

11 Wakefield, A. Gastrointestinal co-morbidity, autistic regression andmeasles-containingvaccines:positivere-challengeandbiologicalgradienteffects.MedicalVeritas2006;3:796-802.

12 WakefieldA. Enterocolitis in childrenwith developmental disorder.AmericanJournalofGastroenterology2000;95:2285-2295.Wakefield A. Autistic enterocolitis: Is it a histological entity?Histopathology2006;50:380-384.

13 Allegation by Brian Deer to The Lancet editor Richard Horton,February2004andJanuary2008.GeneralCertificateofSchoolEducation(GCSE) Biology exam (higher tier). Assessment and QualificationsAlliance. http://www.aqa.org.uk/ (home page). See also Chapter 13,“PoisoningYoungMinds”inthisbook.

14 Revealed:MMRResearchScandalBrianDeer. (2004,February22).TheSundayTimes.

15 CorrespondencebetweenDr.WakefieldandProfessorWalker-Smith,

February3,1997andFebruary20,1997.

16 CorrespondencebetweenDr.WakefieldandProfessorAJZuckerman,March24,1997.

17 Langdon-DownG.(1996,November27).“Law:AshotintheDark.”TheIndependent.Page25.

18 StatementofWalker-SmithJ.TheLancet2004;363:822-823.

19 The Sunday Times. February 2004 and January 2008. GeneralCertificate of School Education (GCSE) Biology exam (higher tier).AssessmentandQualificationsAlliance.http://www.aqa.org.uk/ (home page). See also Chapter 13, “PoisoningYoungMinds”inthisbook.

20 Revealed:MMRResearchScandalBrianDeer. (2004,February22).The Sunday Times. Also, Horton R, A statement by the editors of TheLancet.TheLancet2004;363:820-821.

21 MoodyJ.ComplainttoGMCvsHortonR.,ZuckermanA.,PeggM.,andSalisburyD.(complaintfiledandpending).

22 Carroll,M.toWalker-Smith,J.EthicalPracticesCommitteeapproval162/95.DateofapprovalSeptember5,1995.

23 Deer B. (2009, February 8)MMR doctor AndrewWakefield fixeddataonautism.TheSundayTimes.

24 Complaint toPressComplaintsCommission.WakefieldvsDeerandTheSundayTimes.(seewww.cryshame.org).

25 InadditiontotheUK:GonzalezL,etal.EndoscopicandHistologicalCharacteristicsof theDigestiveMucosa inAutisticChildrenwithgastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25. And

BalzolaF, et al.Panenteric IBD-likedisease in apatientwith regressiveautismshownforthefirst timebywirelesscapsuleenteroscopy:Anotherpiece in the jig-saw of the gut-brain syndrome? American Journal ofGastroenterology,2005.100(4):979-981.Krigsman A, et al.http://www.cevs.ucdavis.edu/Cofred/Public/Aca/WebSeccfm?confid=238&webid=1245.(lastaccessedJune2007)[nolongeravailable;fullpapernowpublishedbelowas:Galiatsatos P, Gologan A, Lamoureux E. Autistic enterocolitis: fact orfiction.CanadianJournalofGastroenterology.2009;23:95-98.Krigsman A, Boris M, Goldblatt A, Stott C. Clinical Presentation andHistologicFindingsatIleocolonoscopyinChildrenwithAutisticSpectrumDisorder and Chronic Gastrointestinal Symptoms. Autism Insights.2009;1:1-11.ChenB,GirgisS,El-MataryW.Childhoodautismandeosinophiliccolitis.Digestion.2010;81:127-9.Epub2010Jan9].

26 EvidenceofHortonR, to theGeneralMedicalCouncil;statementofHortonR,TheLancet2004;363:820-821.

27 briandeer.com. Six year media investigation forces the Lancetretraction of fraudulent research. Retrieved fromhttp://briandeer.com/mmr/lancet-retraction.htm

28 Walker-SmithJ,etal.Ileo-caecallymphoidnodularhyperplasia,ileo-colitis with regressive behavioural disorder and food intolerance: a casestudy. J. Paediatric gastroenterology and Nutrition. 1997;25:Suppl48:A31.Balzola F, et al. Beneficial behavioural effects of IBD therapy andgluten/casein-free diet in an Italian cohort of patients with autisticenterocolitisfollowedoveroneyear.Gastroenterology:2008;4:S1364.

29 PolingJ,PolingT.(2008,April5).Vaccines,autismandourdaughterHannah.TheNewYorkTimes.

PolingJ,etal.Developmentalregressionandmitochondrialdysfunctioninachildwithautism.JChildNeurol,2006;21(2):170-2.OliveiraG,et al.Epidemiologyofautismspectrumdisorder inPortugal:Prevalence, clinical characterization, and medical conditions. Dev MedChild Neurol. 2007;49(10):726-33. Elliot H, et al. PathogenicmitochondrialDNAmutationsarecommoninthegeneralpopulation.AmJHumanGenetics2008;83:254-60.Filipek P, et al. Mitochondrial dysfunction in autistic patients with 15qinvertedduplication.AnnNeurol,2003;53:801-4.

30 BrownA, FieldsD. (2005).Baby411. Boulder, CO:Windsor PeakPress.

31 HondaH,ShimizuY,RutterM.NoeffectofMMRwithdrawalontheincidenceofautism:atotalpopulationstudy.JChildPsycholPsychiatry,2005;46(6):572-9.

32 Fombonne E, Chakrabarti S. No evidence for a new variant ofmeasles-mumps-rubellainduced autism.Pediatrics 2001;108:4. The 1998paperinTheLancetmakesnoreferencetoautisticenterocolitisandmakesnoclaims relating toanewvariantautism. It doesn’tclaim that thenewphenotype isaconsequenceofMMR.WakefieldA,etal.,2000,doesn’tmentionMMRorvaccinationatall.

CHAPTERTWO

TheChildrenThischapterdescribes theclinicalpresentationof the first childrenwithautism spectrum disorder (ASD) and intestinal symptoms of unknownoriginwhowereseenat theRoyalFreeHospital. Inalesscompromisedworld, these presentations (and those in many thousands more childrenworldwide)andthepatternthatemergedfromthecommonalitiesintheirsymptomsandclinical findingsshouldhaveinitiatedacascadeofurgentclinical research that would have led through an iterative process todiscovery—discoveryofcause,treatment,andprevention.Sadly,thishasnotbeenthecase.

Fornow,let’sstartwiththechildren.InMay1995,Ireceivedthesentinelcall fromRosemaryKessick (inaccordancewith theGMC’sanonymouscoding, she is the mother of Child 2). Intelligent and articulate,Rosemary’s motive was to improve her son’s well-being rather than toapportion blame. She was of the considered conviction that her child’sregression into autism, his long-standing diarrhea and food intolerances,and the simultaneous fluctuations in behavioral and intestinal symptomsmeant that they were linked. Moreover, she had come to the prescientconclusions that an abnormality of vitamin B12 might somehow beinvolved and that this whole process had been triggered by his MMRvaccine.Rosemarywasawareofmanychildrenwithasimilarstory.

ItwasobviousthatwhateverelseChild2needed,hisgastrointestinal(GI)symptoms required investigation. I recommended that she seeka referral

from her son’s doctor to John Walker-Smith who was, at that time, aprofessor of pediatric gastroenterology at St. Bartholomew’s Hospital,within the walls of the old City of London. In autumn 1995, with St.Bartholomew’s under threat of closure, Walker-Smith and his teamtransferredtotheRoyalFreeHospitalwherechildrenwithdevelopmentaldisorders and intestinal issues were referred to his care in increasingnumbers, adding a physically and emotionally demanding clinicalcommitment to what was already the busiest pediatric gastroenterologyserviceintheUK.Inmanycases,theparentsmadeinitialcontactwithme,and after listening to their stories, if it transpired that their child hadGIproblems,IwouldrecommendthattheyseekanappointmentwithWalker-Smith. I offered to talk to the child’s doctor if further information wasrequiredonwhatitwasthatweconsideredmightbethelinkbetweentheintestine and the neurological injury in this population of children. Thedoctor, so informed,was in a position toweigh themerits ofmaking aclinical referral.Aswill be discussed, this process, however benign andhelpfulitmighthavebeen,wastobetransmutedintosomethingsinisterattheGMChearing.

InJuly1996,itwasbyvirtueofaquirkoftiming−amix-upwithaschoolholiday−thatthefirstpatient,Rosemary’sson,wasnotthefirstofthesechildrentoundergocolonoscopy.Anotheryoungboy(Child1)wastobethe first child investigated byWalker-Smith and his team. Child 1 haddevelopednormally to18monthsof ageand regressed soonafterMMRwith a clearly delineated onset with loss of words, comprehension, andsocial interaction plus secondary fecal and urinary incontinence. In hishistory, the passage of blood and undigested food in his feces providedmore than enough indication for ileocolonoscopy. I was away at aconference during his admission and visited the department of pediatricgastroenterologywithsometrepidationuponmyreturn.Wouldtherebearecordofsomeformofintestinalinflammationinthischildthatmightbeamenabletotreatmentandsymptomaticrelief?

In the UK, it is routine practice for all patients to have a dischargesummary prepared soon after they leave the hospital. This documentsummarizesthepatient’sstayinthehospital,outliningfindings,treatmentrecommendations,etc.,andisintendedtokeepthepatient’sfamilydoctorandotherdoctorsinvolvedinthepatient’scarefullyup-to-datewiththeirpatient. Child 1’s discharge summary − prepared by a junior doctor −statedthatotherthanlymphoidnodularhyperplasia(LNH)noabnormalitywas found in his colon. I read this with a mixture of surprise anddisappointment;hadthewrongcallbeenmade,leavingnonewavenuesofpotentialbenefitforthischild?Icheckedthepathologyreportagainstthedetailed clinical records documented at the time of colonoscopy. Theydescribed a definite ulcer in the rectum, the lowest part of the largeintestine.When I read the report of themicroscopic examination of hisintestinalbiopsies,Isawthatthepathologisthaddescribedchronicactiveinflammation−notdefinitivelyCrohn’sdiseaseorulcerativecolitis−butclear evidence of disease. In addition, levels of digestive enzymesmeasured in samples taken fromhisupper intestinewereuniformly low,providing an explanation for the appearance of undigested food in hisstool.After alertingWalker-Smith to this important discrepancy, he hadthedischarge summary amended to reflect the facts.Child1wasputonanti-inflammatory medication (Salazopyrin6) of the sort that is usedroutinely to treat inflammatoryboweldisease.He respondedbeyondourexpectations. Six months later he was discharged from the clinic. Theentryinhisrecordsreads:

…definiteimprovement,bothingastrointestinalsymptomsandcognition/communication/behaviors.

William (Child 2) was admitted to the hospital in September 1996. Hisstory was not the course of typical autism, but one of progressivedeterioration thathadbeendocumentedbyexperts fromseveraldifferent

institutions.Onehadstated:

…sadlyboththeratingscalescoresandtherepeatassessmentsdemonstrate thatWilliamhas lost skillsover the last3years.Thispatternofongoingregressionisnotonewhichisnormallyobserved in childrenwith autism even among the groupwhohaveanearlylossofskillsinthelatterhalfofthe2ndyear.Theexpectedcourse for childrenwithautism isoneof continuingprogress…inthelightofthissituationitnowseemsimportantto investigateWilliam for the full rangeofneurodegenerativeconditions.

William had been seen previously by a pediatric neurologist at GreatOrmond Street Hospital, one of the UK’s foremost children’s hospitals.Having seen him, the pediatric neurologist wrote to the referringphysician:

Thankyouforlettingmeseethis8-year-oldboywhonowhasfeatures of a child with classic infantile autism. What isunusual is that there have been three episodes of regressioneach preceded by some months of increased activity andmisery. Following each episode of regression he has neverregainedtheskillslost…IamafraidIdonotrecognizethisasadefinedneurometabolicorimmunologicaldisorder.HoweverI do think reinvestigation is necessary… I would suggest thefollowinginvestigation:MRI,1EEG,2metabolic investigations,detailed immunological investigations of both T and B cellfunctionand immunologicalconsultation,andgastrointestinalconsultation.

Intheinterim,aspartofRosemary’sstrategyofleavingnostoneunturned,she had anticipated the need for further input into William’s intestinal

symptoms and had taken him to see an adult gastroenterologist inCambridge, an expert in the use of nutrition and the manipulation ofintestinalbacteriatotreatintestinalinflammation.Heprescribedprobiotics−goodbacteria,whichapparentlyhadimprovedWilliam’sgastrointestinalsymptoms. At the same time, this doctor had identified a raisedinflammatory marker in William’s blood, namely the erythrocytesedimentation rate (sed rate or ESR) at 40mm/hr3 when the normal rateshould be 0-15mm/hr. The GMC’s prosecution witness was later tointerpret William’s symptomatic improvement on probiotics as acontraindication to him undergoing colonoscopy. On the contrary, thispositivebeneficialresponsetoboweltreatmentcombinedwithhishighsedratewasconfirmationofanintestinaldiseaseuntilprovenotherwise.

Thiswasconfirmedatcolonoscopywhereonedefiniteulcerwasseen,andthecolonand the ileumshowedmarked swellingof the intestinal lymphglands (referred to earlier as lymphoid nodular hyperplasia or LNH).Microscopicexaminationoftheintestinalbiopsiesshowedchronicactiveinflammationof thebowel liningwith thepresenceof pus-forming cells(neutrophils) in themucus-producingglandsof thecolon (cryptitis)witharchitectural damage to the crypts. These are findings that are seencommonlyininflammatoryboweldiseaseandwereevidentinmanyoftheautistic children. The patchy distribution of this inflammation and theinvolvementoftheterminalileumwereconsideredtobeconsistentwithadiagnosisofCrohn’sdisease.Onthebasisofthisdiagnosis,Williamwasenteredintoaclinicaltrialofaspecialnutritionalformula(polymericdiet).He made a dramatic response both from the bowel and behavioralperspective. I rememberhis delightedmother tellingus that her sonhadstarted laughing and playing again, something that he had not done foryears.SoimpressivewasWilliam’scasethatthefindingswerepresentedto an international meeting of pediatric gastroenterologists by Walker-Smithin1997.4

And so the pattern continued: Child 3’s history was of normaldevelopment followed by sudden changes in behavior just 2 days afterMMR vaccination at 14 months, when he started head-bangingaccompanied by fever and rash. At 15 months of age he underwent adramatic deterioration in behavior, with hand flapping (a very commonfeatureofautism),aggression,anddeteriorationinspeech.Bythetimehewas 2 years old, he could no longer speak. From the very outset, hismotherwasconvincedoftheassociationbetweenherchild’sdeteriorationand MMR vaccination. His bowel problems started with diarrhea andprogressed to chronic laxative-dependent constipation, pain, and thepassageofbloodinhisfeces.Walker-Smithwrotethistomeafterseeingthischildinitiallyintheoutpatientclinic:

…there is a clear history of this child having been perfectlywelluntiltheageof14monthsandthenthe2nddayaftertheMMR injection there was a change in behavior which haspersisted thereafter and he has been diagnosed of havingbehavioralproblemsofautisticnature.

Child3’slocalpediatricneurologist,whowaslatertoactasanexpertonbehalf of the vaccine manufacturers in the MMR litigation, was of adifferentopinion.Hewrote:

[Child3’smother]isdevastatedatthechangein[Child3]thatoccurredataround14monthsofage.ShesaysthiscoincidedwithMMR immunizationwhich she thereforeblames…she isvery sad and is looking both for somebody or something toblameandalsoforspecifictreatmentsfor[Child3].

In further correspondence he wrote, with authority but, in my opinion,

withoutappropriateinvestigation:

Ihave told them [Child3’sparents] that [Child3’s]acquiredautistic problems in my opinion have occurred quiteincidentally to his MMR immunisation rather than that theyhavebeencausedbythisprocedure.

InherreferrallettertoWalker-Smith,Child3’sgeneralpractitioner(GP)wasnotsodismissive:

[Child 3] developed behavioural problems of autistic nature,severe constipation and learning difficulties after MMRvaccination. The batch incriminatedwasD1433, incidentally,whichwasthediscontinuedbatchfollowingadversereactions.

Child3wasdischargedfromtheRoyalFreeafteronlyonefollow-upvisitdue to thefinancialconstraints imposedbyhisreferringhealthauthority.Walker-SmithwrotetotheGPstating:

Our final diagnosis is of indeterminate ileocolitis5 withlymphoidnodularhyperplasia

Sadly, this child’s neurologist was as dismissive of the expertinterpretation of the intestinal findings as he had been of the mother’soriginalstory;helaterdeclinedtoprovideaprescriptionforChild3’santi-inflammatorymedication,writing:

…clearly what Mrs. [3] wanted was a re-prescription forSalazopyrin6…thisIamafraidIamnotpreparedtodo…mydifficulty is…theconceptualoneofnotacceptingtheconceptofautisticenterocolitis.7

PlanswereputinplacetofollowupChild3locallyinhishometown,butthisprovedunsatisfactoryduetolackofadequateservices.Hiscontinuingstoryreflectsthetragedyofmanyofthesechildren.Hisownparticularcridecoeur— his attempt to communicate his pain and distress to others,whichhadstartedwithhishead-bangingasaninfant,furtherprogressedbythetimehewasplacedattheageof12intopermanentcare:

[Child 3’s] behavior is extremely challenging by anystandard…hisbehavior includespublicmasturbation,puttinghisfingeruphisanusandattemptingtolickhisfingers,spittingdirectly at people, biting his lip and spitting blood, hittingchildrenandstaff,formingaclenchedfistandhitting,targetingwomen’s breasts by hitting and pinching, kicking people andobjects as he passes by, always throwing food or drink atpeople once he has sampled it, self-injurious hitting of upperarms and big toe, urinating on the carpet and furniture,smearingurineandfecesonhisbody,breakingandtearingallobjects including 1 TV, 4 cassette players, 2windows, and 1wallunit.[Child3’s]behaviorisincessant…

Wewill neverknowhowmuchof thisbehaviorhad its roots in chronicphysicalpainandthefailureofthosearoundhimtorecognizethisandactuponit.Myexperienceofseveralthousandsimilarlyaffectedchildrenhaspersuaded me that a great deal of the behavioral component of thisdisorder is a response to pain − intestinal pain in particular. Time andagain,Ihaveseenthesebehaviorsabatewhentheboweldiseasehasbeentreated.

As stated in Chapter 1 (“That Paper”), Child 4 has a particularlyinterestingandinformativehistory.Asababy,itwasnotedthathehadanunusuallywidebridgingofhisnose.Hewas, therefore, followedclosely

forpossibleevidenceofacongenitaldisorder,but thiswasexcludedandhe was discharged from follow-up as developmentally and physicallynormalby15monthsofage.He later receivedasinglemeaslesvaccine,following which he stopped cruising around furniture and regressed tocrawling.Heappearedtoplateauinhislearning,andby20months,hehadlost the words that he had learned. Soon thereafter, he stopped talkingaltogether.Generalillhealthdevelopedinhissecondyearwithear,chest,and throat infections and loose bowel motions with abdominal pain.Accordingtohismother’sstory,2weeksfollowinganMMRvaccine,at4½yearsofage,he“disappeared”and“lostallskillsandcommunication.”Whereasat10monthsofagehewasable tobuilda towerofbricks,hisplay skills declined to the point that, according to his mother, “now he[was] lost as towhat to dowith them.” In addition, he became clumsy,startedhead-banging,anddevelopedrepetitivebehaviorstypicalofautism.He lost his self-help skills such that,whereasbefore theMMRhe couldfeedhimselfwithaspoon,afterwardshecouldnolongerevenholdacup.

Child4’sGPhighlightedthedifficultiesinprovidingadiagnosticlabeltothisgroupofchildren,particularlythoseshowingprogressivedeteriorationover time, when in seeking help from an expert at the local universityhospitalhewrote:

[Child4’smother]feelsthatheachievedcertainmilestonesinthe first year or two which were then lost subsequently butcertainly by the age of four it was clear that [Child 4] hadseveredevelopmentdelay.Nospecificdiagnosishaseverbeenreachedalthoughassessmentbyapsychiatristhasagreedthathe has many autistic tendencies… has also had recurrentproblemswithdiarrhoeaandhasonoccasionshad infectionswhichhavebeendifficulttotreat.

Thisdiagnosticuncertainty is also reflected inhispediatrician’s letter tothelocaldoctorinthelocaldepartmentofCommunityChildHealth.Herewe see others proposing a possible childhood disintegrative disorder(CDD)diagnosis (formoreabout thisseeChapter9,“TheDevil’s in theDetail”)whenshewrote:

“…thehistorydoessuggestfeaturestosuggestadisintegrativepsychosisandtherearecertainlysomeautistic features inhisbehavior.” Another pediatrician later wrote: “As [Child 4]grew older, it became clear that he had autism… However,suchadiagnosis is notmade instantly in the early yearsandboth health professionals and parents seek alternativeexplanations.Also[Child4]hadavarietyofrashes,abdominalpainsanddiarrhoea…”

In fact, the diagnosis of autismwas notmade because, by virtue of theprogressiveandunusualnatureofhisdeterioration,alternative“medical”explanationsweremore likely.Despite the clear clues, it does not seemthat the search for alternative explanationswas adequate. The history ofChild4’sintestinalproblemswasalsoinstructive.Hisrecordsstated:

Thediarrhoeabecameaproblematbetween1-1½yearsofage[in fact, after his single measles vaccine]… it generallycontains undigested food.His diarrhoea became significantlyworsefrom4½yearsofage[afterhisMMR]…

Failuretothrive,acardinalsignofpediatricinflammatoryboweldisease,wasevidentfromthefamilydoctor’srecordswherehewasreportedtobe“dropping off centile charts.” This failure to thrive continued and tookanother downturn at the same time his diarrheaworsened,when hewasnotedtohavedroppedfromthe9thtothe2ndcentileforweight.

Child 4 is particularly significant since he represents a possiblerechallenge case.Rechallenge is the termused todescribe a situation inwhichsymptomsdevelopafteranexposure,andafterre-exposuretoeitherthesameorasimilarfactor(e.g.,ameasles-containingvaccine),thereisanobvious recurrenceorworseningof thosesymptoms.Thisspecificsetofcircumstances is considered by the US Institute of Medicine to bepowerfulevidenceofcausation8andcannotbedismissedascoincidence.Despitethisworryingsequenceofeventsandtheprogressivedeteriorationofthislittleboy,noneofthisappearedtobeoftheleastconcerntoanyoneotherthanhisparentsandsomeofthedoctorsattheRoyalFree.

Child 5’s fathermade contactwithme after reading a newspaper articleaboutmywork.His sonhaddevelopednormallyuntil hewas18monthold.ThatwastheageatwhichhewasgivenanMMRvaccine.Within2months,hestartedmakingstrangenoisesandlostnormalspeech.Helostinterest in his surroundings and became socially unresponsive. From 2yearsofagehedevelopedchronicalternatingconstipationanddiarrheaaswellasfailuretothrive.AcontrastX-rayofhisintestineattheRoyalFreeidentified a narrowing of his terminal ileum (the last part of his smallintestine), which failed to dilate during the extended period of theinvestigation.WhiletheappearanceswereconsistentwithCrohn’sdisease,theX-rayfindingsprovidedsomediagnosticdifficulties.Hiscolonoscopy,however,confirmedthepresenceofachronicinflammation.

Child6andChild7arebrothers.Child6,theolderbrother,sufferedonsetofrash,fever,drowsiness,aggressivebehavior,andconvulsionswithin2weeks of the MMR vaccine, followed by developmental regression. Inaddition,havingbeenpreviouslypotty-trained,hebecameincontinentandhis coordination deteriorated.9 At the same time, he began to haveabdominalpain,bloatingandpassageofmucus (a signof inflammation)andbloodperrectum,withalternatingconstipationanddiarrhea.Hisblood

markers of inflammation were raised,10 and a colonoscopy revealed amarkedcolitis.BecauseofherconcernsabouttheMMRvaccineandwhatappeared to have happened to her older son following vaccination, themotherofChild7decidednottogiveheryoungersontheMMRuntilhewas 21 months old. She was finally persuaded that she was anirresponsibleparentwhowasputtingherinfantboyatriskbynothavinghimvaccinated.Tormentedbyguilt andstill trustingofdoctorsoverherown instincts, she took him for the vaccine. Within 1 month, he hadbecomeuncoordinated and had started losing skills.Like his brother, hehad chronic unexplained alternating constipation and diarrhea withassociatedpassageof blood andmucus.His blood tests revealed that hewas anemic, and his inflammatory markers were raised.11 Notably,however, his colonoscopy showedno evidence of inflammation, and theonly finding at this stage was marked LNH of the ileum. Hisgastrointestinalsymptomsworsenedovertheyearsand,unabletogetthenecessaryinvestigationsdoneintheUK,Mrs.7flewhimtoAustin,Texas,wherehewasreinvestigatedatThoughtfulHouseCenterforChildren.Hehad a colonoscopy, and his biopsies were examined at an independentpathology laboratory. This time it was found that he had chronic activeinflammationinhiscolonandstomach.Itispossiblebutunlikelythatthishad been missed when he had his first colonoscopy at the Royal Free.Whatismorelikely,inthelightofexperience,isthateitherin1996bowelinflammationwassomewhereotherthanhiscolonorthatinsomechildrenthe disease progresses over time, potentially evolving on occasions intofull-blownCrohn’sdisease.

Child8’shistoryrequiredparticularlycarefulattention.Inherfirstyearoflife,Child8’smotherbecameconcerned that shewasnot developing asrapidly as had her older sister. When she was 10 months old, she wasreferred toadevelopmentalpediatrician.Hisexpertopinionwas thatherdevelopmental trajectory was normal. She was later diagnosed withcoarctationof theaorta (anarrowingof themainartery leadingfromthe

heart). This was corrected bymajor surgery and shemade an excellentrecovery. From this point on, shemade rapid gains in speech and otheraspects of her development. Contemporaneous records described hermother as having been “delighted” with her subsequent progress. ShereceivedherMMRattheageof18months.Twenty-fourhourslater,shedeveloped a rash and fever and started having febrile convulsions,requiringhospitalizationfor5days.Herregressionfollowedimmediatelywithbehavioraldeterioration, lossofwords andvocalization, screaming,hyperacusis(anexcessivesensitivitytosounds),lossofcoordination3andnocturnal muscle jerks. There are multiple references in her medicalrecords of her mother’s clear association between her daughter’sMMRvaccineandherdramaticdeterioration.Interestingly,herGPhadreferredherfordevelopmentalfollow-upat17monthsofage,just1monthbeforeher vaccine. The developmental pediatrician had assessed her andconcludedthatshewasstilldevelopingnormally,albeitattheslowerendoftherange,whichwasunsurprisinginviewofheraorticcoarctationandmajorsurgery.Whatisstrikingisthatwhenshewasreviewedagainbythesame developmental pediatrician a matter of weeks after her MMRvaccine,heconsideredhertobe

…globally developmentally delayed functioning at about theoneyearlevel.

So it was that within the space of 1 month, Child 8 had gone fromfunctioningataroundthe17-monthleveldowntothe12-monthlevel,yetvery little, if any, attention seems to have been paid to this. What isperhaps more surprising is that Professor Sir Michael Rutter, emeritusprofessorofchildpsychiatryandexpertprosecutionwitnessattheGMC,never having seen the child, felt able to offer the opinion that herregressionwas

…fromaverylowlevel.12

This was despite the fact that Child 8’s developmental pediatrician haddeclaredherslowbutdevelopmentallynormalat17monthsofage.Child8’s reaction to the MMR was acknowledged but received no furtherconsideration and no appropriate investigation until she arrived at theRoyalFree.Hergastrointestinalsymptomsfollowedapatternthatwas,bynow,becomingfamiliar,withtheonsetofchronicdiarrhea.Herpediatriccardiologistnotedmom’sconcernthat

…shewrithesandrollsaroundinhercot.Hermotherwondersifsomethingwas“painingher.”

AndanentryintheGP’srecordsdocumentedthefollowing:

…screamingconstantly.Mumatendoftether…

Hermedical recordscontainnumerousadditional references toChild8’scontinuing gastrointestinal issues, about which there was otherwiseprecious littleprofessional interestuntilshemadecontactwith theRoyalFree.

Child 8was assessed by a child psychiatrist at theRoyal FreewhowascandidaboutthelikelyroleofMMRinthischild’sregression:

…Inote that following the vaccination therewas a period offever,diarrhoeaanddevelopmentalregression.Iamthereforeleft wondering whether in fact she had post vaccinationencephalitis…

Atthattime,hedidnotconsiderhertobeautistic,althoughshewaslaterdiagnosed independently with autism at another university hospital.Despiteadocumented lossof5monthsofdevelopment in just1month,RutterwasunimpressedbyChild8’sdevelopmentalcourse,ascapturedin

hisreport:13

The slight regression followingMMRwas, understandably, acause for concern for the parents but was not of a form ordegreethatcarriedmuchclinicalmeaning.14

As the MMR issue later reached a political fever pitch, there was anexchangeofcorrespondencebetweenChild8’sGPandherdevelopmentalpediatricianwhowrote,inastateofalmosttangibleagitation:

…On reviewing her records I find that the concern about[Child8’s]developmentaldelaywasexpressedbyhermotherandyourself inMay1994,longbeforetheMMRwasgiveninJanuary or February 1995. The fever-associated convulsionwhich she had in February 1995 was in the context of adiarrhoeal illness associated with fever two weeks after herMMRimmunisation.IfeelthereforethatitisextremelyunlikelythattheMMRwasthecauseofherpresentproblems…

ThispediatricianappearstohaveignoredhisownassessmentsofChild8thatshowedcleardeteriorationafterthevaccine.TheearlyconcernsaboutChild8’sdevelopmentwerereportedaccuratelyinTheLancet.Inspiteofthis,however,inherevidencetotheGMC,Child8’sGPfeltable,withouthavingreadthepaper indetail (assheadmitted), tovoiceherconcerntotheprosecutionthatwehadreportedthislittlegirl’searlydevelopmentas“normal.”We had not. Despite having no basis in fact, this effectivelyamountedtoanallegationofscientificfraud.

Child 9’s mother was friendly with Rosemary Kessick. His story is afurtherindictmentofthemedicalprofession.Asitwasoriginallytoldtousbyhismother,Child9’sstorywasoneofnormaldevelopmentfollowedby

developmental regression from18monthsofageafterone ina seriesofmany episodes of middle ear infection. His regression, described byseveral doctors as “secondary autism”15 consisted of a gradualdeteriorationwithphysicalregressionandlossofcoordination—hecouldnolongerthrowandcatchaball,hisgaitbecame“awkwardandstifflikeanoldman,”andhecouldnolongergofromsittingtostandingunaided.He lost the 20words that he had gained and developed secondary fecalincontinence. His play skills evaporated, leaving his older sister feelingconfused and rejected. He began to have episodes of severe abdominalpainassociatedwithscreamingandwithbringinghiskneesuptohischestand rolling fromone sideof thebed to theother.Fromapproximately2years of age, he developed a pattern of chronic loose bowel motionscontainingundigested food.Hefell fromthe97thcentile forweightat1yearoldtothe50thby2yearsold.Hisdietwentfrombeingvariedtoveryrestricted, consisting of refined carbohydrates and at least ten 200 mlcartonsofasyntheticorange-flavoreddrinkperday.

Duringoneparticularlysevereboutofabdominalpain, thefamilydoctorwascalled.SheattemptedtoexamineChild9’sabdomenonthebasisthatthiswasevidentlythesourceofhispain.Unableto,sheexaminedhisears,declared one eardrum “pink” and prescribed a powerful broadspectrumantibiotic for a presumed ear infection, ignoring the abdominal problemaltogether. The GP continued in this way, prescribing antibiotics on amonthlybasis,untilChild9’smotherstoppedconsultingthisdoctor.Shesaid:

I stopped consulting her as her attitude as with many otherdoctorshadbecome“heisautistic”hisproblemisbehaviouralnotpain.

As explained previously in Chapter 1 (“That Paper”), what Child 9’s

mother did not tell us in 1996 was that she, too, had linked her son’sproblems contemporaneously to MMR vaccine. Our description of thischildinTheLancet faithfully reiterated theonsetofsymptomsfollowinganepisodeofotitismediaandmadenomentionoftheMMR.Thereasonforthediscordancebetweenthesetwoaspectsofthenarrativeprovidesavaluablelesson.Whenshehadfirstapproachedherson’spediatricianwiththe possibility that his problems stemmed from MMR, he had beendismissive.Other doctors had reacted in the sameway.WhenChild 9’sparentstooktheirsontobeassessedbyadevelopmentalpediatricianatauniversityhospital,hesaidwithcertainty,

Mydear,IhavesatontheVaccineDamageBoardforseveralyearsandvaccinesdonotcauseautism.

Hedidofferthefamilyanalternative:iftheylookedbackintotheirfamilyhistories, thentheywouldprobablyfindat leastonefamilymemberwhohadsimilarsymptoms.Diligently, theydidso.Child9’smotherwasoneof eight children and both of her parents were one of ten children. Hermaternal grandfather was one of fifteen boys. Her husband’s paternalgrandmotherwasoneoftwenty-onechildren.Inspiteofsuchenthusiasticprocreation, neither autism nor anything resembling it had ever been anissueon either side of the family.Nonetheless, beyond that point,Child9’s father urged his wife not to mention theMMR again since doctorsconsideredhertobecrazy.

Herewas a situationwhere themother’s original narrative − thatwhichshouldhavebeenkeytounderstandingtheoriginofherson’sproblems−had been dismissed or scorned, causing her to modify her story (quiteunderstandably, but to Medicine’s enduring shame) in order not tocompromiseherson’saccesstoclinicalcare.

Child10 receivedhisMMRat12monthsofageanddevelopedentirelynormallyforafurther4months.Afteranapparentmeaslesinfectionat16monthsofage,hedevelopedarash,fever,vomiting,andreducedlevelofconsciousness. Over the following 4 months he progressively lost eyecontact, verbal skills, interest in play and socialization, and developedrepetitivebehaviors.Aconsultantpediatricneurologistwrote:

It seems that [Child 10’s] strange behaviour started after hehad an illness which was considered likely to have beenmeaslesandwhichoccurredinJune1994.

As was commonplace in the diagnostic maze of child psychiatry, onseparateoccasionshewasdiagnosedvariouslywithautism,disintegrativedisorder, and encephalitis leading to generalized brain disorder. Onceagain, in parallel with his developmental regression he developedabdominalpain,diarrhea,andintoleranceforcertainfoods.

Despitethefactthatnodefinitivetestshadbeenperformedatthetimeofhis possiblemeasles infection at 16months, a strong indication that thisdiagnosiswas, in fact, correctwashis hugely elevatedmeasles antibodylevel.LevelssuchasthoseinChild10(thathaveremainedhighformanyyears) are only seen in a rare form of measles encephalitis,16 althoughtherehasbeennofurtherindicationthatthisiswhathehas.Ifcorrect,thenhis physical and immunological reaction may have occurred followingnatural exposure at 16months due to a primary vaccine failure (i.e., hisMMRdidnotprotecthim),orhismeaslesinfectionat16monthswas,infact,areactivationofvaccinevirusinfection.

InassessingChild10attheRoyalFree,ourchildpsychiatristdocumented:

He is far too affectionate by his father’s account for a child

with full blown autism… I thought the most likely diagnosiswas in fact an encephalitic episode, which led to some lowgradegeneralizedbraindamage.

Despite this, he subsequently received an autism diagnosis from severalotherexperts.For theRoyalFreechildpsychiatrist, thedemonstrationofaffectionappearedtobeastickingpoint.InpsychiatristandphysicianLeoKanner’s original description of autism in 1943 and in much of theliterature thereafter, children with autism are characterized as aloof andrelatively undemonstrative. Thismay be the casewhen their autism hasfollowedanexposureinthewomborinperinatallifewhentherehasbeennoopportunity tobondorexperience the shared rewardsofaffection. If,however,achild’semotionshavedevelopednormallyfor16months,thenwhileother aspects of cognitionmay regress andbehaviors change, it isquite possible that affection − by this stage firmly entrenched − stillremains.

Austrian educatorTheodoreHeller’s original description in 1908 revealsthatchildrenwithCDDmaybecapableofexpressingaffection.17A1996paperfromRussoandcolleaguesthatdetailedacaseofCDDandprovidedareviewofthemedicalliteratureonthisdiseasediscussesthepresentationof theconditionandthecloseoverlapwiththesymptomsofautism.Thekey features they describe in the child’s history included normal earlydevelopment, progressive loss of speech and language, development ofrestricted interests, repetitive behaviors, secondary urinary and fecalincontinence, spontaneous inconsolablecryingepisodes,and lossof self-helpskills.Despitethis,heremainedaffectionateandwashappybetweencryingepisodes.

Inaddition toChild10’sdisplaysofaffection,hispresentationwasverymuch like that of Russo’s case, and this was characterized incorrespondence from his local consultant community pediatrician. He

wrote:

[Child 10’s GP] asked me to see [him] urgently because ofconcernsabouthisdevelopmentgoingbackwardsandbecauseheseemstohavelostsomespeechandsocialskills…hewasaperfectly normal healthy lad until June 1994… following hisepisodeofmeasles[Child10]appearedtoloseeyecontact,hefellintohisownworld,lostinterestinhistoysandbooks,andceased almost all interaction with other people. His earlyvocalizationsceased,hismotherwasn’tsureifhewasdeaforsimplynotunderstanding…developedahabitofbouncingupand down, jiggling, clinging, and running in circles andbanging and kicking in the cot for an hour or so… it isinterestingthathehasintermittentepisodesofwaterydiarrheaandhasepisodesofscreamingwhenheclutcheshisabdomenwhichcouldberelatedtoabdominalpain.

Therewas little, ifanything, thatdistinguished thischild fromtheothersseen at the Royal Free. While the onset of CDD after measles isrecognized in themedical literature, the littleknownfact thatonsetafterimmunization has also been described quite independently of the RoyalFreewillnotsurprisetheparentsofaffectedchildren.18

Child10likewiseturnedouttohavealow-gradecolitisandLNH.Ontheanti-inflammatorySalazopyrin,hisdiarrheaandpainwerereportedinhischarttobe“muchimproved.”

Child11wasourfirstreferralfromtheUS.Hecametouswithahistoryof developmental regression starting at 18 months of age; this includedloss of speech, repetitive handmovements, and reduced eye contact and

progressedtocompletelossofspeechby30monthsofage.At3yearsoldhewas described as having the cognitive function of a 6-month-old.Hewasparticularlyintolerantofcertainfoods,withworseningofbehaviorsinresponse to bread, dairy products, and confectionary. His findings atcolonoscopy of LNH and a low-grade colitis were consistent with theemergingpatternseeninother,similarlyaffectedchildren.

Child12’smothermet themotherofChild6andChild7ataplaygroupfor special needs children. They talked about their children and, inparticular, the latter mother’s experience at the Royal Free. Child 12’smother subsequently made contact with me by telephone. Her son haddevelopednormallytojustover16monthsofagewhenhehadaseriesofnonspecific illnessessuggestiveofviral infection.ThishadbeendetailedaspartoftheSouthThamesDevelopment&CommunicationStudybeingundertaken at Guy’s Hospital in London, where he was given hisdevelopmentaldiagnosis.HehadreceivedhisMMRvaccineat15monthsof age, but his mother did not link this to his subsequent regression.However,hisGPnotedthisinChild12’smedicalrecords:

…frequentillnessessinceMMR.

Child 12 also developed a measles-like disease at 20 months of age,althoughnoattempt toconfirmorrefute thiswasmade.Susceptibility torecurrentinfectionswasafeatureofmanyaffectedchildrenandreinforcedthe impression of a fundamental problem with their immune systems.Child 12’s developmental diagnosis was Asperger’s syndrome,19 aconditionontheautismcontinuumthatisoftenreferredtoasbeingatthehigh-functioningendofthespectrum.AfundamentalaspectofAsperger’sthatdistinguishesitfromautismisthenormalacquisitionofspeech,andadiagnosis of Asperger’s requires cognitive function within the normalrangeforage.

ItwouldbeamistaketoconsiderAsperger’ssyndrometobeamildformof autism. Dr.Marcel Kinsbourne, a pediatric neurologist and someonewhohasdonemoretosupportthecauseofvaccine-damagedchildrenthananyone else, pointed this error out to me. Asperger’s sufferers attendregular school, where they may well excel academically. However,mainstreamschoolcanbeabrutalenvironmentforthosewhoaresociallyisolated, lackempathy,andmissthecuesandcluesthatdesignateoneas“cool.”Towear a virtual badge that says “odd” in the teenage years, inparticular−andtoknowit−isaheavycrosstobear.

Child12’sdevelopmentalregressionstartedwithlossofspeech,decreasedsocial awareness and interaction, and deteriorating coordination at 16monthsofage.Atthesametime,hesufferedonsetofunexplainedchronicabdominalpain,constipation,secondaryfecalincontinence,vomiting,andloss of appetite. His bowel movements were pale, loose, and veryoffensive, which are characteristic features of malabsorption. Consistentwithadiagnosisofmalabsorptionwashisfailure,accordingtohischart,“togroworputonweight.”Bloodmarkers,measuredbeforeandafterhisadmission to the Royal Free, showed evidence of inflammation. Hisbiopsiesshowedamildcolitis,andherespondedwelltoanti-inflammatorymedication.

So, what were we to make of these stories? From modern medicine’sclassical roots, pattern recognition has been a fundamental part of goodmedical practice and essential in the detection and description of newdisease syndromes. Emergent patterns will have been evident to thosereading the children’s stories above. Genius is not required, but skilled,unbiased attention to the history and clinical findings is. Unlike familydoctors, who may only have seen one or two autistic children in their

practicebythemid-‘90s,fromJuly1996,we,inatertiaryreferralcenter,had the advantage of a repetitious and intensive exposure to themyriadproblemsfromwhichthesechildrensuffered.Assuch,itwasourdutyaswell as readily within our grasp to recognize and document emergentpatternsofdiseasepresentation.

Patternsalsoemergein,forexample,bloodtests,whichwhenviewedasawhole are more meaningful than when observed in isolation. Irondeficiencyofamildbutconsistentdegreewaspresent inmanychildren,indicativeofeitherlowdietaryironintake,malabsorptionfromadiseasedintestine,orbloodloss.VitaminB12levelswere,infact,highinthebloodplasmaofthesechildren.OtherthaninthecaseofChild9,theproblemdidnotappear tobeoneof impairedB12absorptionfromtheintestinebutamoresubtleabnormalityofB12metabolisminthebody’scells.TheB12inthechildren’sblood,althoughhigh,wasinauseless,inactiveformandwasraisedbecause,whennotcomplexed20insidethecells,itleaksoutofthecellsintothebloodplasma.Dr.JohnLinnell,abiochemistontheteam,identified an abnormally high level of the vitamin B12 metabolitemethylmalonicacid(MMA)inthechildren’surine.TheraisedMMAlevelreflected an abnormal B12 metabolism. What is fascinating is that thisfact, unearthed by theRoyal Free teamback in the late 1990s, has nowcaptured the interest of many in the autism scientific and medicalcommunities; this has led to therapeutic trials of the active formofB12thatareunderwayinhopesofovercomingthisproblem.

Therearealso those idiosyncraticfeaturesof thechildren’sbehavior thatturned out to be related to gastrointestinal distress. They includedposturing,abehaviorthatofteninvolvedleaningforhoursatatimeovertheedgeofapieceoffurniturethatwas,asitturnedout,doneinordertoapply pressure to the abdomen and relieve their pain. Such behaviorscontinuetobemisinterpretedas“Oh,that’sjusthisautism,”when,infact,

theyareentirelyappropriateforachildwithabdominalpainwhocanfindnoother formofexpressionor relief.Manychildrenbecameparticularlyagitatedwhentheyneededtogotothetoilet,whencharacteristicfeaturesofautismsuchashandflappingwouldintensify.

Other behaviors included food refusal or selectivity, with a particularpreferenceforlargevolumesofcow’smilkandrefinedcarbohydrates,andextreme thirst. Paradoxically, the past medical history often involvedintolerance of cow’s milk in infancy, with reflux21 (heartburn) andprojectilevomiting.Sleepdisturbances,oftenassociatedwithreflux,wereverycommon,illustratedbychildrenwhohadpreviouslysleptthroughthenightfallingintoapatternofwakingfrequentlyindistress.

Mostinterestingmechanisticallywastheaberrantoraggravatedbehavioralresponsetocertainfoodsand,asalogicalextensiontothis,thebeneficialeffect of excluding these foods from the child’s diet. Gluten, a proteinderivedfromcereals,andcaseinfromcow’smilk,seemedtwoofthemostfrequently cited culprits. Whatever the mechanism or mechanisms, wewere rapidly persuaded by video and other evidence that the effect ofwithdrawingthesesubstratesfromthedietcouldleadtobenefit.Followinginadvertentreintroductionofthesefoodstuffs,thesubsequentdeteriorationinsymptoms−arechallengephenomenon—hasconvincedmefurtheroftheirbiologicaleffectinmanyaffectedchildren.

Multiplecoursesofantibiotics,givenroutinelyasapanaceaforpresumedmiddleearinfections,werealsoarecurringfeature.This,combinedwithafrequenthistoryofeczema,hayfever,andsurgery to remove tonsilsandadenoids,suggestedstronglythattherewasanunderlyingimmunologicalvulnerabilityinmanyofthesechildren.

Also striking were parental reports of cognitive improvement and even“normalization” during periods of high fever. The story was far toocommonandconsistentamongdisparategroupsofparentstobesimplyachance occurrence. This change in behavior with fever has since beendocumented in the medical literature by autism researchers at KennedyKrieger Institute and JohnsHopkins inBaltimore.22 Itprovidesacrucialclue as to the reversibility of aspects of a disease previously deemedirreversiblebymany“experts.”

ChangesinsensoryperceptionwerealsoissuesthatIhadnotencounteredin themedical textbooks. On a hot day, the childwould bewrapped inthree layers of clothes, and yet on a freezing cold day, they would berunningaroundnakedinthesnow.Changesinachild’sperceptionofpainwere common,with an extremelyhigh threshold inmanycases.A childmightburnthemselvesonanelectricringoraboilingkettleandyetbarelyacknowledge the fact. There is no easy explanation for such changesalthoughmanymoreorlessplausiblemechanismshavebeenposited.

TurningtothevexedsubjectofMMRvaccine,certainconsistentfeaturesemergedovertheyearsthat,whiledifficulttointerpretintheabsenceofanon-autistic comparison group, certainly raised questions about acauseeffect relationship. Affected children had often been vaccinatedwhile unwell with fever or while on antibiotics. Some had mistakenlyreceivedtwodosesofthevaccineinquicksuccessionorweregivenmanyvaccines,includingMMR,onthesameday—intheabsenceofanysafetystudies—merelyforthesakeofconvenience.Manyofthemoreseverelyaffectedchildrenwererechallengecaseswho,despiteregressionfollowingthe first dose, had been given a booster MMR with catastrophicconsequences. Iwas later todiscover, tomydismay, that this applied to

Child2.Incombingthroughhisrecords,Ifoundasignedconsentformforan MMR vaccination when he was only 4 months of age. Given theknowledgethatrisksfrommanyvirusessuchasmeaslesaregreatestintheveryyoung, this vaccination strategyborderson insanity.My suspicionsarethathewaspartofanexperimentaltrialthatwentbadlywrongandhasnever been reported. I suspect this because at that time, anothermotherfromthesamepartofthecountryasChild2wasinvitedtohaveherownson participate in an experimental trial of MMR vaccine in infants.Apparently,thisvaccinetrialwasabandoned,andwhenoneofthenursesinvolvedinthetrialofferedtodisclosethedetailstothismother,shewasthreatenedwithlossofherjob.

Clumsinesswasasignificantsymptominseveralrespects,firstlybecauseitconfirmedanencephalopathy—braindysfunction—inthesechildrenthatwentwaybeyondbehavioralaberrations.Secondly,aparticularformof clumsiness, cerebellar ataxia (incoordination originating due tomalfunctioning of a part of the brain called the cerebellum), has beendescribed as a complication of MMR vaccination. This pattern ofclumsinesswas consistentwith the problems suffered by these children.CerebellarataxiawasfirstreportedasapossiblecomplicationofMMRbyDr. Anne-Marie Plesner in Denmark.23 This association had not beendetectedwithanyothervaccineadministeredtochildrenofthesameage,including the single measles vaccine, indicating that a novel adversereactionmightbeassociatedwiththecombinedMMRvaccine.Inamorerecent follow-up of the mandatory passive reporting system operated inDenmark,Plesnernotonlyconfirmed this association,but also indicatedthatthemoresevereataxiasfollowingMMRwereassociatedwithresidualcognitive deficits in some children.24 This sounds suspiciously like ourownexperience.

Thentherearethosecompletelyunexpectedsymptompatternsthatemergebyvirtueofone’s investigationand treatment that,whilenotanticipated,provide an exquisite insight into, for example, the relationship betweenbowel,brain,andbehavior.When thechildrenwere firstadmitted to theRoyal Free as outpatients, we anticipated mayhem on the wards.Colonoscopyrequiresabowelprepthatclearsoutthecolonandallowstheentire length of the large intestine to be visualized. Although childrenusually tolerate this preparation very well, we had anticipated problemsandabigcleaningbillfromgivingpowerfullaxativestononpotty-trainedchildren who were in a state of perpetual motion. To our surprise,however,parentsreportedthattheirchildhadneverbeencalmerandtheirstayinhospitalwith theirchildwaslikeaholiday.Restingthebowelbynoteatingfor24hourscombinedwithbowelclearanceofsubstancesthatwerepotentiallyinflammatoryortoxicmightexplainthisphenomenon.Itcertainly reinforced to us the reality of a gut-brain interaction in thisdisease. The same beneficial effect on both bowel and behavioralsymptomswas seenwith anti-inflammatorymedication used to treat theintestinal inflammation. This benefit was very common − although notuniversal,andwhenitoccurred,itseemedtogobeyondthesimplereliefofpain.We tried foryears toexamine thiseffect inacontrolledclinicaltrial,butbythistimeandforvariousreasons,fundingwasbecomingmoreandmoredifficulttocomeby.

Thethingaboutpatternrecognitionis that,fortheprocesstobeenabled,onehastoallowthelineofenquiry;thatis,onehastoexploreasymptomorpursueanaspectofthepastmedicalhistorythroughthenarrativemazetoa final, considereddeterminationof its significance.Thereare severalconstraintson thisprocess, noneofwhichmake forgoodmedicine.Thefirst is the view that the “doctor knows best,” even for a disease likeautismaboutwhichsomuchremainstobediscovered.Thedoctorseemsdeaf,evenhostile,toanythingoutsidehisorherspecificrealmofinterestor belief system.The second constraint is the sheer, unmitigated fear of

callingMMRvaccinesafetyintoquestion.

So,where are these children now? I am sad to say that despite our bestefforts and some early symptomatic improvement, the prognosis for atleastthemajorityofthesechildrenremainsveryguarded.Somehavebeeninstitutionalized, and for the rest of them, this is a possibility unlesssomethingdramaticchanges.Whateverhappens,nonewillfunctionandbesafe independently outside of long-term supervision in a protectedenvironment.Atleastfourhavedevelopedepilepsy.Forothers,likeChild7, the bowel disease appears to have progressed.Who knows how theywould be now had they not been treated? Their prognosis was − andremains − an unknown quantity, particularly since we do not know thenaturalhistoryoftheintestinalinflammation.TheissueofprognosiswasraisedwhenourapplicationtotheethicscommitteewasfirstreviewedandwasonethatwastoresurfaceintheGMChearingintheguiseofallegedprofessionalmisconduct.

Backin1996, inresponsetoaquestionfromalaymemberof theRoyalFree Hospital’s ethics committee about whether an intensive regime ofinvestigationwas justified,Walker-Smith replied,with the sincerity of amanwhohasdevotedhisprofessionallifetothecareofsickchildren:

These children suffer from a disease with a “hopelessprognosis”inrelationtotheircerebraldisintegrativedisorder.They have often not had the level of investigation which wewould regard as adequate for a child presentingwith such adevastatingcondition.

Hewasgenerousinhisrestraintwhenstating:

In relation to their gastrointestinal symptoms, which will bepresentinallthechildrenweinvestigate,thesehaveoftenbeenunder-investigated.

The integrity and compassion that underpinned his position should havebeenunassailable.Nonetheless,attheGMChearingmanyyearslater,theprosecutionaccusedWalker-Smithofhavingsoughttomisleadtheethicscommittee in order to advance “experimentation” on these children bymisrepresenting their long-term outcome. Unrestrainedly cynical, theprosecutingcounsel,SallieSmith,QC,paintedapictureoftheexploitationof desperate children, labeled falsely byWalker-Smithwith a “hopelessprognosis.”SmithwassupportedinhercasebyRutter,despitethefactthatbyhisownadmission,noneofthechildrenhadshownanysignsoflastingneurological recovery. Indeed, many had deteriorated further from analreadyseverestate.

Walker-Smith was right; without help— help in the broadest sense ofpainstaking medical enquiry and multiple levels of intervention —“hopeless” anticipated a lifetime of isolation, incarceration, and pain. Inhis response to the ethics committee,Walker-Smith captured,with vividclarity,thesechildren’sfutures.

Nonetheless,thereishope,andthisisgrowingasthemedicalcommunitywakesuptoitsresponsibilities.Thelegacyofthechildreninthevanguardofthesediscoveriesisabetterchanceforthosewhohavefollowedthem.Ihave hope, not least because I have come to believe that the disease isdeceptive: it creates the illusion of a brain injury that appears morepervasiveandintractablethanitreallyis.Sometimes,ifwecareto,wecanacceptaninsightofferedinthemoment,asimportantasit isevanescent.

Once,at thehouseofafriendinSacramento,California,wewerebythepoolinthelateafternoonwhenheaskedhisprofoundlyautisticsonifhewantedtogotoapopularrestaurantfordinner.Theboystoppeddeadinhistracks;hispersistentrepetitivehandmovementsceased;andhefocused−tangiblyfocused—onfindingawayofgettinghisanswerout.Hehadunderstoodthequestionandhewantedtotakehisfatherupontheoffer,buthehadnowayof tellinghim.Thewiringthat linkedhishearingandunderstanding of the question to the brain centers responsible forarticulating and vocalizing his answer was shorting out at some point.Eventually,hetookhisfatherbythehandandledhimtothecar;hehadfoundaway.Andwe,too,mustfindaway.

PostscriptAt the GMC, my response to the parents’ pleas for help − arecommendation that theyseek referral toWalker-Smithandmyoffer toprovide some explanation to their family doctor by way of collegialcommunication—was somehow twisted and repackaged to appear as acynicalmisdemeanor.Whatwasnomorethanaprofessionalandhumaneresponse to a cry from the heart became part of a grand conspiracy to“cherry-pick”childrenforthepurposeofexperimentation.

Thealternativecoursetome,havinglistenedtotheparentsofTheLancet12 and many more besides, and having acknowledged their desperateplight, the various violations of their children’s rights, the willfulignorance that often confronted their insights and suspicions, and theirtears—wouldhavebeentotellthemtogoawayandnottobothermeanyfurther. Ironically, this behavior, while it might smack of “callousdisregard”would,itappears,havebeenpreferabletotheGMCandwouldnothavebroughtmetoitsdoors.

Endnotes1 Magneticresonanceimagingofthebrain.

2 Electroencephalogram:electricalrecordingofthebrain.

3 SeenbyDr.JohnHunterwhowritestoJWS.ESR40.

4 Walker-SmithJA,etal.Ileo-caecallymphoidnodularhyperplasianon-specific ileocolitis with regressive behavioural disorder and foodintolerance:Acasestudy.JPediatrGastroenterolNutr.1997;25(Suppl1):S48.

5 Inflammationofthesmallandlargeintestine.

6 AKAsulfasalazine.

7 Autistic enterocolitis is the name given to the pattern of bowelinflammationinchildrenwithautism.

8 StrattonKetal.AdverseEventsAssociatedwithChildhoodVaccines:Evidence Bearing on Causality. Washington, D.C.: National AcademyPress,1994.

9 For further information on ataxia following MMR vaccination see:Plesner AM. Gait disturbance after measles mumps rubella vaccine.Lancet1995;345:316.Thiswaslaterconfirmedinfollow-upstudy:PlesnerAM,HansenFJ,TaadonK,etal.GaitdisturbanceinterpretedascerebellarataxiaafterMMRvaccinationat15monthsofage:afollow-upstudy.ActaPaediatrica.2000;89:58-63.

10 RaisedESR(31);raisedplateletcount(480).

11 January 28, 1997 (scope January 26, 1997): Hemoglobin 10.6/9.4[1.97 on ward] (persistent microcytic anaemia); WBC 17.2, ESR 16.

platelets340,bariummealandFT(29.1.97.LNH).

12 RutterreporttoFieldFisherWaterhouse.May7,2007.Page4.

13 RutterreporttoFieldFisherWaterhouse.May7,2007.Page5.

14 Emphasisadded.

15 Autismoccurringinapreviouslydevelopmentallynormalchild.

16 Subacutesclerosingpanencephalitis.

17 Heller T. Dementia infantilis, Zeitschrift fur die Erforschung undBehandlungdesJugenlichenSchwansinns.1908;2:141-165.

18 Inareportof12casesinIndiaseenbetween1989and1998,MalhotraandGupta note onset in 4 cases following infectious/vaccine exposures,including fever with seizures, acute gastroenteritis and vaccination. Thetype of vaccine is not stated. See:Malhotra S andGupta N. Childhooddisintegrativedisorder.Re-examinationofthecurrentconcept.EurJChildandAdolescentPsych.2002;11:108-114.

19 AspergerpublishedthefirstdefinitionofAspergersyndromein1944.Infourboys,heidentifiedapatternofbehaviorandabilitiesthathecalled“autistic psychopathy,” meaning autism (self) and psychopathy(personalitydisease).Thepatternincluded“alackofempathy,littleabilitytoformfriendships,one-sidedconversation,intenseabsorptioninaspecialinterest,andclumsymovements.”The term “Asperger’s syndrome” was popularized in a 1981 paper byBritishresearcherLornaWing,whichchallengedthepreviouslyacceptedmodelofautismpresentedbyLeoKanner in1943.UnlikeKanner,HansAsperger’sfindingswereignoredanddisregardedintheEnglish-speakingworldinhislifetime.Seealso:AspergerH.[Onthedifferentialdiagnosisof early infantile autism] (inGerman).ActaPaedopsychiatr. 1968;35(4):136-45.

20 Asmethylcobalamin.

21 Gastroesophageal reflux involves an abnormal backward flow ofgastric juices (acid) into the esophagus, causing inflammation and pain.Thisisparticularlylikelytooccuratnightcausingwakinganddistress.

22 CurranLK.et al.BehaviorsAssociatedwithFever inChildrenwithAutismSpectrumDisorders.Pediatrics.2007:120(6);e1386-e1392.

23 PlesnerAM.Gait disturbance aftermeaslesmumps rubella vaccine.TheLancet1995;345:316,andPlesnerAM,HansenFJ,TaadonK,NielsonLH, Larsen CB, Pedersen E. Gait disturbance interpreted as cerebellarataxiaafterMMRvaccinationat15monthsofage:afollow-upstudy.ActaPaediatrica.2000;89:58-63.

24 PlesnerAM,HansenFJ,TaadonK,NielsonLH,LarsenCB,PedersenE.GaitdisturbanceinterpretedascerebellarataxiaafterMMRvaccinationat15monthsofage:afollow-upstudy.ActaPaediatrica.2000;89:58-63.

CHAPTERTHREE

TheDean’sDilemmaAnd then there was the spawning of what was rapidly to become aruthlessly pragmatic effort to put an end to my group’s vaccine safetyresearch. Therewere at least two shades of irony that played out in theunfolding drama.Onewas behind the scenes, the covert action thatwasunknowntomeat thetime.Theotherinvolvedthemechanismbywhichthiscovertactionwasrevealed—noneofitwouldeverhavecometolightwereitnotfortheallegationsmadebythefreelancejournalistBrianDeerand his complaints to the GMC. The disclosures included documents −thousandsofthem−thatsomemusthavehopedwouldneversurface.Butsurface they did, like bloated corpses from the river bed. The evidencerevealedcollusionat thehighest levelsof themedicalestablishment (seebelowandChapter6,“TheDean’sPressBriefing”).

During the first half of 1996, I was asked for help by Richard Barr ofDawbarn’s law firm and lead attorney on the UK MMR cases.Specifically, I was asked to review the safety of measles-containingvaccines (MCV) and, separately, to design a study that would helpdeterminewhether therewas orwas not a likely case in law against themanufacturersofMCV.Barr’sinitialinterestwasinCrohn’sdiseaseasapossibleadverseoutcome,butautisminchildrenwithintestinalsymptomsrapidly took center stage. I prepared a research proposal for Barr’ssubmission to theLegalAidBoard (LAB), ameans-tested, government-funded legal assistance program to which Barr was contracted for thevaccine work. The proposal focused upon laboratory-based detection ofmeasles virus in the diseased intestinal tissues of childrenwith Crohn’s

disease and thosewith developmental disorder and intestinal symptoms,should they come to colonoscopy. I anticipated that the laboratoryworkwouldtake1year;intheevent,itrequired2years.

When confirmation of the award of the LAB research grant came fromBarrinAugust1996,Iwasoutofthecountry.Uponmyreturn,Iwrotetoa Dave Wilson in the finance department of the Royal Free HospitalSchoolofMedicineonSeptember26tosay,

…wehaverecentlybeenawardedagrant from theLegalAidBoardtofundresearchintomeaslesvirusandIBD.

So,nosecretthere.1IattachedtheletterofawardthattheLABhadwrittentothelawfirm,Dawbarns,andconfirmedthatthefirst£25,000.00shouldbe paid into a designated research account as was standard practice forresearchgrants.Onthesameday,IwrotetoBarraskingifthefundscouldbetransferredtothemedicalschool.

But inSeptember 1996,what I did not knowwas that toProfessorArieZuckerman,thedeanofthemedicalschool,myagreementtoactonbehalfofvaccine-damagedchildrenwasoldnews.Infact,hehadknownaboutitforsomemonths,havingbeeninformedbyProfessorSirDavidHull, thethen-chairmanof the JointCommittee onVaccination and Immunisation(JCVI)andanotherpersonat theUK’sDepartmentofHeath (DoH) .2 ItappearstheDoHwaseagerforZuckermantoknowofmyintentionsandwantedhim tobring tobearwhateverpressurehecould inorder to stopme.

InearlyMarch1997,IreceivedacallfromZuckerman.Thedetailsofthisconversationcanbegleaned fromour subsequent correspondenceon thematter.InaletterdatedMarch10,1997,Isoughttorespondtothemattersthat he had raised. He was under the impression that there was aparliamentaryselectcommittee(theequivalentofanoversightcommitteehearing) being convened to address the subject of measles vaccine andCrohn’sdiseaseand, seemingly,my linkwith thesolicitors,Dawbarns. Iwillsetoutverbatimtheremainderofmyresponsehere:

You mentioned a conflict of interest when we spoke. This issomethingwhichhasexercisedmymindgreatlyintheinterim.IfeelImustgoonrecordasstatingthatIdonotseehowanyconflictof interestexists. It is,as Iamsureyouwouldagree,our joint and several responsibilities as members of themedical profession to use our training and expertiseappropriately. In the context of the current measles vaccinesafety/ consequences debate, I am providing independentexpert guidance based on facts available to me. I do this incommonwithcolleaguesworldwide…

…In theparticularcircumstanceswithwhich Iamdealing,thereis,Ibelieve,anevenhighermoralobligationtoactasanexpert adviser.Weare facedwith a situationwhere themostvulnerable category of patients, i.e. children, may be put atrisk.Itisrightandproperthereforetoreviewthefacts,assessthem,andofferguidance.

I hope these comments are helpful. Please do feel free tocontactmeifyouwishtodiscussmyrolefurther.

Inourtelephoneexchange,Zuckermanappearedtormentedbytheissueofconflictofinterestbutfailedtospecifywhatthisconflictmightbe.InhisresponseofMarch13,hedenied thereeverhavingbeenaparliamentaryselectcommitteeenquiryonthismatter.Hecontinued:

Idonotthinkthatthereisanyconflictbetweendutyofcaretopatients or the provision of independent expert advice tolawyers.However,itisadifferentmatterwhenlawyersfundaparticular piece of research where a specific action iscontemplated.Thissurelysuggeststhatsomepreliminarylegaldiscussions have taken place and that a specific action iscontemplated.Ifso,thentheinterpretationmustsurelybethataconflictofinterestmaywellexist.TheSchoolmust,therefore,seekexpertadvice,butinthemeantimeyoushouldknowofmyconcern.4

At the time, I did not understand his rather convoluted reasoning. Myinferencewasthatheobjectedfundamentallytothefundingofresearchbylawyersactingonbehalfofchildrenwhomighthavebeendamagedbyavaccine.

Clinical trialsofvaccinesanddrugsare fundedby themanufacturers fortheprincipalpurposeofprofit.Thisisnotajudgmentoracriticism,butaneconomicrealityforanindustrythatisanswerablefirstandforemosttoitsstockholders.Itappearedtomethat,unspoken,Zuckermanwasprofferingtheethicalparadoxofmedicalacademiaendorsing−indeedembracing−the conduct of clinical trials funded by the pharmaceutical industry, butdenouncing as something distasteful and prohibitively conflicted17 theinvestigationofchildrenwhoselivesmayhavebeenirreparablydamagedbyaninadequatelytestedvaccine.

Letme dealwith the specifics of his reasoning: “it is a differentmatterwhenlawyersfundaparticularpieceofresearchwhereaspecificactioniscontemplated.” In the context of a drug trial, the “piece of research,”wouldbethedrugtrial,andwhena“specificactioniscontemplated,”thiswouldconstitutethepotentialforsubsequentmarketingofthedrug.Let’smove on to hiswords “This surely suggests that somepreliminary legaldiscussionshave takenplace and that a specific action is contemplated.”One can apply the same logic to a drug trial: preliminary discussionsinevitablytakeplaceintheassessmentofthetrial’sfeasibility,onceagain,intheanticipationthatifthetrialgoesaheadandissuccessful,aprofitabledrugwillbebroughttomarket.

The “conflict of interest” is properly dealt with in any presentation andpublicationof the study’s resultsbydisclosing the fact that the trialwasfundedbyapharmaceuticalcompany.Wasthereanythingotherthanprofitversus compensation that separated these two seemingly concordantresearch strategies? What was actually troubling Zuckerman soprofoundly? Perhaps I wasmissing something. Confused by his lack ofclarity over this supposed conflict, I wrote again onMarch 24, 1997. Ienclosed all the documents relevant to the grant, including the proposal,the letters from theLAB,and the relevantprotocols—onceagain therewasnosecrecyintermsoffranklytellingthedeanwhatwasproposed.Inanefforttoassuagehisfears,Icontinued:

I got the impression from Roy [Professor Pounder] that youwere concerned that we were being contracted to provide aspecific answer − that is, that measles vaccine or the MMRvaccinewasthecauseofthisdisease.Thatisabsolutelynotthecase. We are being funded to conduct a piece of scientificresearch toestablishorrefute the linkbetweenMMRvaccineand the disease. There are absolutely no preconditions

concerning the outcome. If this were the case, you may restassuredIwouldhaveneverbeeninvolvedinthefirstinstance.Thesciencemustleadandeverythingelsefollows.Aswiththemedical expert’s opinion elsewhere, I am being asked toprovide my opinion, whether that opinion is positive ornegative.Itisonthisbasis,andonlyonthisbasis,thatIhaveagreed to assist in this matter. I hope that his issue can beresolved as quickly as possible and my group is working toachievethisend.

ItwasyearslaterthatIfoundoutthereasoningbehindZuckerman’sfearsand why the DoH was so highly motivated to stop the vaccine safetyresearch.Thatreasonwasmostalarming−theDoHstoodtobesued.Forreasonsunknowntome,Barrandhislegalteam,theLAB,andtheparentswhowerecontemplating legal redress for theirchildren’s injuries, itwasnot just bigpharmabut a departmentofHerMajesty’sGovernment thatwasinthefiringline.

But back in 1996 this informationwas not intended forme.None of uswereintendedtoknowthen.Noneofuswereeverintendedtoknow.Thisis evident inasmuch as it was never spontaneously disclosed. So it wasthat, rather than raise any concerns about the LAB grant with me,Zuckermanhadbeenhardatworkexploringpossiblegroundsforrefusingthe funding,whichwouldhave then compromised this specific research,something that would have pleased his political friends. As his line ofattack, he chose the ethical implications of the LAB funding a piece ofmedicalresearch.OnOctober11,1996,hewrotetoDr.MacArmstrong,chairman of the ethics committee of the British Medical Association(BMA),3theUK’sprofessionalorganizationfordoctors:

I should be grateful for your advice on a potentially difficult

situation in which the Royal Free finds itself and on whichthereforeImusttakeadecisiononthepositionadoptedbytheMedical School. A senior member of the School’s clinicalacademicstaff isengaged inwork thathasbecomesomewhatcontroversialinthatheissuggestingacausallinkbetweenthemeasles virus and in particular vaccination against measlesand the onset of Crohn’s disease and inflammatory boweldisorders. Arising from recent widespread publicity given tothis research, the Legal Aid Board has provided fundingthrough a firm of solicitors representing Crohn’s diseasesufferersandwehavebeenasked tomakeanappointment tothestaffoftheMedicalSchoolspecificallytoundertakeapilotstudy of selected patients.Clearly this could lead to a caseagainsttheGovernmentfordamages.7

HereZuckerman’smotive—preventingacaseagainst thegovernment -was revealed, but why this little known fact should have been clear toArmstrongatthisstageisuncertain.IncontrastwiththeUS,wherelegalclaims for possible vaccine damage are routinely filed against thegovernment, this is not the case in the UK where the anticipated legalactionwastohavebeenagainstthevaccinemanufacturer.

Zuckermancontinued:

MydilemmaisthattheMedicalSchoolmightbeseentoutiliseitsresourceswhicharelargelyfundedfromthepublicpursetotake sides in litigation before there has been a finding. It isquitecommonofcourseforclinicalacademicstafftobecalledasexpertwitnesses incasescriminalandcivilwhere theyactas individuals although their reputation is clearly based inlarge measure upon their academic and professional

appointments. This is however a somewhat different situationandIwouldfindithelpfulifyoucouldletmeknowwhetheryouhave come across parallels elsewhere that might provide aprecedentandalsoadvisemeontheethicalandlegalpositionoftheMedicalSchool.

Not surprisingly Armstrong was somewhat bemused and wrote toZuckermanonOctober15,1996,totryandgainsomefurtherinformationuponwhichtobasehisadvice.

While thiswasallgoingonbehind thescenes, thecheckfromtheLAB,viaDawbarns,wassent tomeonDecember6,1996.Asoutlinedearlier,unaware of themachinations that had been set in place, I forwarded thechecktoWilsoninfinance,reiteratingthesourceandpurposeofthefunds.Wilsonthencopiedthistothemedicalschoolsecretary,BrianBlatch,onDecember12withamemothatread:

Following on from our discussion yesterday I thought itprudent thatyoushouldhavepreviouscorrespondenceon theissuesraisedsofarsothatyouareawareofthepresentstateofplay.

Clearly this source of funding had enlivened the finance department.Although working like a well-oiled machine when dealing with checksfrom the pharmaceutical industry, theywere thrown into confusion by aresearch grant from the LAB. Annotations that were added toWilson’smemoinananxioushandread:

“We cannot code the cheque. We may have to return it.”Beneath that, someone called Renee had written, “We havealreadybankedcheck.”

Infact,Zuckerman,whilesolicitingtheexpertadviceoftheBMA’sethicscommittee, had put a block on the research by placing the funds in aninaccessiblesuspenseaccount.Iknewnothingofthisandwasjustwaitingfor the go-ahead. Uncertain quite what to do, Wilson wrote again toBlatch, seekingguidanceonwhether thegrant hadbeen acceptedor notanddeclaringhimselftobe“inaquandarywiththisone.”

Also unknown to me at that time was the fact that Zuckerman was incontactwiththeChiefMedicalOfficer(CMO),oneofthechiefarchitectsofUKMMRvaccinepolicy,SirKennethCalman,5informinghimthatheandhiscolleaguesremained:

…very concerned about the unwelcome controversysurroundingtheworkonCrohn’sdiseasewhichiscarriedoutatthisSchoolbyDrAndrewWakefieldandhisgroup.

Zuckerman reassuredCalman that hewould stay in touchon thismatterwithDr.DavidSalisbury,theDoH’sdirectorofimmunization.Ironically,on the very same day that Zuckerman confirmed to the CMO that hewouldbeinformingonmyactivities,IwrotetoZuckermanadvisinghimthatbecauseofmyconcernsaboutapossibleMMR-autismconnection,Ihadproactivelyarrangedameetingwithrepresentativesof theJCVI forthepurposeofcommunicatingtheseconcerns.TheJCVIisacommitteeintheUKchargedwithofferingindependentadvicetotheDoHonvaccinesandtheirsafety.Inrecentyears,ithasbeenrevealedthat−farfrombeingindependent − many of the committee members have links to variouspharmaceuticalcompaniesintheformsofgrantsandconsultancies.6

Meanwhile,theRoyalFree’sfinancedepartmentcontinuedtowrestlewith

thatcheck.Wilsonwrotetothemedicalschoolaccountant,Mr.Tarhan,onFebruary1,1997.Itwasalong,handwrittennoteconfirmingthathehadreceivedtheadviceofBlatchwho“felt[themedicalschool]hadnooptionbut to accept the funding. He said we should make it clear to Dr AWakefield that it isdonereluctantlybecauseof thecontentiousnatureofhis research.” Scribbled across the bottom by Tarhan were the tellingwords:

we spoke since— BAB [BryanA. Blatch]will reconsider inviewofPoliticalovertones.7

Blatch,themedicalschoolsecretary,hadreversedhispositionpresumablyontheinstructionofZuckerman;for“Political”reasonstherehadbeenachangeofplan.Theissuesofacademicfreedomandthechildren’swelfarehad been subverted because of “overtones” — including a secret thatthreatenedgovernmentinterests.

Zuckerman’s holy grail — Armstrong’s anticipated support for hisposition from the ethics committee of the BMA — was still awaited.Blatchwasdesignatedtonudgeitalong,anditwashewhocontinuedthecorrespondence with Armstrong. He wrote on February 24, 1997,8confirming that theLABhadprovided a researchgrant “to facilitate thesetting up of the clinical and scientific study proposed by Dr AWakefield,” the purpose of which was to “search for measles virus insamples obtained from legally aided patients.” Dr. Armstrongacknowledged receipt of this letter and confirmed that he would takeadviceandbeintouchshortly.9

Meanwhile,blissfullyignorantthatIhadsetthe“catamongthepigeons,”Iwas in correspondence with Zuckerman; I had been seeking to answer

Zuckerman’s question about the government’s select committeeinvestigationonvaccinesandCrohn’sdisease.Inhindsight, itseemsthatthisclaimmayhavebeensomekindofstrangeruseonthepartofHulltoheighten Zuckerman’s anxieties and encourage him to move decisivelyagainstme.Atthattime,notprivytotheprobablereasonforZuckerman’sconcern over conflict of interest (i.e., that the government stood to besued),Iwentontodisputethatonmoral,ethical,andscientificgroundsnoconflictexistedinmyassistingthesechildreningettingaccesstothedueprocessofjustice.

Zuckerman responded tome, brushing off thematter of the nonexistentselect committee10 as a misunderstanding. He argued again that thefundingrepresentedaconflictofinterestbutdidnotprovideanycoherentbasisforhispositionandcopiedhislettertoArmstrongattheBMA,11 towhomhealsowrote:

Isuspectthatthelegalclaimwillbeonthebasisthatmeaslesvaccine and the combined MMR may cause Crohn’s diseaseand inflammatory bowel disease and the safety of thesepreparationshasnotbeenestablished.ExpertopinionandtheadviceofWHOandJCVIisthatthereisnoconfirmedevidenceof an association with immunisation against measles (andrubellaandmumps)andinflammatoryboweldiseaseandthattheepidemiologicaldataareflawed.

WhileIwouldnotwishtoattempttobalancetheargumentsforacademic freedom and the public interest with respect to theprotection of children against infection, the position of themedical school is difficult.Further I amdeeply concernedbythe unconventional funding of research work by interested

lawyersactingonbehalfofchildrenwith inflammatoryboweldisease.

Knowing nothing at this time of Zuckerman’s correspondence withArmstrongattheBMA,Iwrotebacktohimreaffirmingmypositionandseeking to reassure him that the LAB study would be handled like anyother research project. The filed copy of this letter bears Zuckerman’swordsinthedatestamp:

Thisdoesconfirmmyworstfears.

Armstrong’s long awaited response arrived on Zuckerman’s desk onMarch26,1997.Itwouldbeanunderstatementtosaythatitwasneitherwhat he had hoped for, nor expected. The letter ran to three pages andcarried a resounding message. Armstrong identified the central ethicalquestionas

…whether the research project was scientifically sound andhas been approved by an ethics committee…The question ofwhetherhealthprofessionalsmaybeinvolvedinlitigationisamattertobeborneinmindwithregardtopublicationoruseofdatabutshouldnotdeterminewhethertheresearchitselfisinavalidproject.

Hepointedouttheobviousethicalrequirementsthat

“…thereshouldbefullandinformedconsentfromtheparentsofchildren,”andthat“theirconfidentialinformationshouldbeprotected.”

Interestingly, and in complete accordancewithmyapproach since1992,

Armstrongadvisedthat

…theDepartmentofHeathshouldbeinformed[ofthefindings]ingoodtime.

OnthematterofresearchfundedbytheLAB,theletterwentontostate,quitebluntly,thatitwas

…quite logical for theLegalAidBoard, as a publicly fundedbody to fund research on relevant issues in law, usinggovernment money essentially to sue other governmentdepartments. Independently conducted researchmayestablishwhetherornottheyhavecaseainlawandisnodifferentfromcommissioningamedicalexperttoprovideaview.

Onequestion thathad taxedZuckerman− thefundingof researchwherethere was a “clear financial interest in the outcome” − was dealt withsuccinctly:Armstrongwrote,

…funding of research by special interest groups iscommonplaceandaslongasthefindings,orusestowhichthedataisput,arenotinfluencedbythewishesofthefunders,thisshouldnotbeproblematic.

AsafinalslapinthefacetoZuckerman,Armstrongconcludedthat

…todelayordeclinetoconductresearchwhichappearstobeinthepublicinterestonthegroundsthatitmayembarrassthegovernmentoraparticularhealth facility doesnot appear tobeasoundmoralargument.

Zuckermanhadshothimselfinthefoot.Forhispart,ArmstrongfinishedbyaddingalittlesalttoZuckerman’sangrywound:

…whereas I do not imagine these comments solve yourproblemsIhopewecanindicatethatadetailedprotocolneedstobedevelopedoutliningthemainethicalandpracticalissuesateachstage…notonlyforthesepatientsbutformanyotherswhomaycomeforwardlater.

Zuckermanhadwaitedfor6monthsforareplythathadeffectivelyblownhis case. In the event that Armstrong’s response fell into my hands, itwouldnotonlyderailhisplansforputtinganendtoscientificscrutinyofMMRvaccineattheRoyalFree,butwouldactuallybeusedtoendorsetheethical imperative for undertaking such research. In contrast with hisanticipatedarmor-platedendorsementfromArmstrongtostopafinancialand political threat to the British government, Zuckerman had receivedwhatamountedtoareprimandfromtheBMA.

Zuckermanmanagedashortbutgraciousresponse,thankingtheBMAfortheir “helpful comments” and indicating that he would now explore theissueswith thelocalethicscommitteeat thehospital.Hedulydidsobutnot before he had placedArmstrong’s letter at the back of a deep, darkdrawerwhere presumably he hoped itwould remain forever, andwhere(metaphorically)itdidremainuntiltheGMCinvestigationin2004causedittobedisclosed.

TheBMA’smessagewasclear:nottoconductvalidresearchforpoliticalreasonswouldbeunethical.Despite thisandwithouteverdisclosinganydetails,Zuckerman regularlymade reference to their authoritativeadviceinawaythatcausedmetoinferthattheBMAsharedhisconcernsabout

the work and its source of funding. The categoric advice of the UKmedicalprofession’sethicsexpertswasnot,however,goingtodeflecthiseffortstostopmyresearchfromgoingaheadonhiswatch.

ZuckermanturnedhisattentiontothelocalethicscommitteeattheRoyalFreeHospital.Hewrote to the chairman,Dr.Michael Pegg, onApril 2,1997.12 In the light of what we now know, the letter was quite simplybizarre.RememberhowZuckermanhadsentmeoffonafutilequestforaselectcommitteethatdidnotexistandthenwrotetotellmethattherewas,infact,nosuchselectcommittee?Well,itwouldappearthathecontinuedthisrusewithPegg,addingpoliticalgravitastohisconcernsbyimplyingsomethreattothemedicalschool.Hewrote:

ProfessorSirDavidHull,ChairmanoftheJCVIwrotetomeinFebruary 1997 that Dawbarns solicitors had made asubmission to the House of Commons Select Committee thatthey are working with Mr Wakefield of the Royal FreeinvestigatingCrohn’s.

WhenitcametotheBMA’sadvice,itwasasifithadallbeenjustabaddream,thedetailsofwhichwerebestforgotten.Zuckermanacknowledgedthat hehad received their advice, but hekept that advice tohimself.Hereiterated some of the same concerns to Peggwithwhich theBMAhadalreadycomprehensivelydealt:

“Thedilemmawhich the School faces iswhether it is ethicalfor lawyers to fund a particular piece of research where aspecific action in law is contemplated rather than ascientifically-based research project.” Professor Zuckermancontinued,askingDr.Pegg,“Wasitethicalforlawyerstofundresearchwherea specificaction in lawwascontemplated? It

has been suggested that I explore with you whether thecommitteeconsideredtheseissues.”

Hisletterendedreassuringly:

…theMedicalSchooldoesnotquestionthescientificvalidityofthe project, the independence of the research, the academicfreedom of the staff and publication in learned scientificjournals.

Zuckerman, a virologist and head of the medical school, had notquestionedthescientificvalidityoftheresearchproject.Inthecontextofthe advice from the BMA’s ethics committee as perArmstrong’s letter,withanethicalandmoralwindatmyback,mypositionshouldhavebeenunassailable. Pegg responded toZuckerman onApril 15, 1997,13 statingthathewasnotawareofanyLABfunding.HeaskedifIhadmadeafalsestatementtotheethicscommittee.Zuckermanrespondedbyreturn:14

…there is absolutely no suggestion of any misconduct by DrAndrewWakefield.

Zuckermanreiteratedlaboriouslythattheissuewasanethicalmatteron“apossibleconflictofinterestanddataprotectionintheeventoflitigation.”Theseletterswereneversenttome.Iknewnothingofthisexchange.NoquestionwaseverraisedwithmebyeitherPeggorZuckermanthroughoutthisentireperiodalthoughitwouldhavebeenaneasymatterforeitherofthemtohaveaskedme,andformetohaveansweredtheirquestions.Ihadmade my position clear to Zuckerman; there were no secrets from myperspective, and Iwould have been happy for these discussions to havetaken place. But in Zuckerman’s furtive game, this might have meantshowinghishand,thatis,Armstrong’sopinion,andthatwasnotabouttohappen.Thatwaswherethematterrestedinthespringof1997.

Asbecamecommonplacewith thewitnessesproviding statements to theGMCintheirprosecution,Pegg’spositionhadchangedby2005andwasaltogethermorecritical.AlthoughhehadbeenaskedspecificquestionsbyZuckerman at the material time and had declined to “assist” with hisdilemma, when interviewed by the GMC lawyers, Pegg stated: “InretrospectIbelievethefailuretodisclosetheexistenceofthelegalactionwasamaterialnondisclosure.”Infact,in1996,therewasnorequirementforsuchadisclosure.Asitturnedout,Pegg’sconcernwasbaseduponthemistakenbeliefthattheLABfundshadbeenpaiddirectlytomeandwerebeingadministeredfrommy“backpocket.”Hewentontomakeitclearinhis oral testimony before the GMC in 2007 that if the funds had beenadministered by the Special Trustees and, therefore, approved by them,thenhewouldhaveneedednofurtherknowledgeoftheirprovenancesincetheywould have been appropriately vetted and legitimized. Since this isexactly what did happen, as far as Pegg and the Royal Free ethicscommitteewereconcerned,Ihadactedappropriately.

ByMay1997,IhadgrowntiredofthewholefiascoovertheLABfundinganddecided to seek fundingelsewhere.Exasperated, I asked the financedepartment to return the funds in full to the lawyers. Tarhan, head offinance,wroteamemotoZuckermanandBlatch15explainingthis.Butattheeleventhhour,therewasachangeofheartwithoutwhichtheseessaysmightneverhavebeenwritten—historycouldhavebeenverydifferent.As it was, at the bottom of that memo in Zuckerman’s writing are thewords:

Transferred to Special Trustees. They are aware of thesituationandtheoverspend?DiscusswithMartinElse

Thus, it was that the LAB grant, deemed too ethically and politicallychallengingtobeadministeredbythemedicalschool,wasacceptabletobehandledbyanaccountmanagedbyahospitalcharityfor thepurposesofconducting valid and ethical research. Perhaps troubled by some vaguemoralangst,thedean−althoughhewastodenyitlaterunderoathbeforethe GMC − had allowed the research to go ahead, while seeminglywashingthemedicalschool’shandsofthedeed.

In2007attheGMC,Zuckerman’smemoryofeventsprovedfickle,evenwhenjoggedbythecontemporaneouslydocumentedfacts.Inhisevidence,he blundered into one carefully prepared trap after another, eventuallythreateningtowalkoutandgethisownlawyer.Atonestage,whenaskedhowtheLABgrantcametobetransferredtotheSpecialTrusteesaccounthesaid:16

DrWakefieldwasconsulted.Hesaidreturnittothesolicitors.Whyitwasnotreturnedto thesolicitorsIhavenoideabut itwould have stopped the matter in its tracks, right there andthen.SubsequentlyitwasreferredtotheSpecialTrusteesofthehospital.

Apparentlyreferring to theGMC’sprosecutionofmeandmycolleagueshecontinued:

If it hadbeen returned toDawbarnsnoneof thiswouldhavematerialised.

Thiscomment is telling: if theLAB-fundedstudyofpotentiallyvaccine-damaged children had been successfully stopped in its tracks,would theBritish government have dodged a bullet and theGMCwitch-hunt havethenbecomeunnecessary?

Zuckermanwasthenaskedbymyseniorcounsel,Mr.KieranCoonan,QC,

aboutthememodealingwiththetransferofthecheck:

Q:Atthebottomofthepage,isthatyourwriting?

A:Itismywriting,yes.

Q: It looks as if therefore a scheme or arrangement wasentered intowhereby themoneywas then tobe transferred totheSpecialTrusteesatthehospital.

A:Well,toputthisincontext,ImetwithMrTarhantodiscussthisandheinformedmethatthiswastransferredtotheSpecialTrustees.HetoldmethattheywereawareofthesituationandIalsomadeanotethatalthoughMrTarhanwasveryconcernedabout the overspend byDrWakefield, I noted that but I alsomadean issueofwhether todiscuss itwithMrElse.The factthatitwastransferredtotheSpecialTrusteeswasnotknowntomeuntilmyattentionwasdrawntothisbythefinanceofficer,MrTarhan.

In fact, it was Zuckerman himself who had signed the check18 thatenabledthetransferofthesefunds.Itcouldnothavehappenedwithouthisauthorityorhis signature.Givenhisvolatileemotional stateat theGMChearing, the check was not presented to him in evidence by my seniorcounsel,Mr.KieranCoonan,QC.Thismomentoflegaldramawasdeniedtotheassembledcompany.

Although Zuckerman had known of the potential liability of the Britishgovernment forMMR vaccine damage back in 1996, it was some timebeforeIwasgiventhissamemessage.However,thiswastocomefromaverydifferentsourceandforaverydifferentreason.

Endnotes1 “The Sunday Times has now established that four, probably five, ofthese childrenwere covered by the legal aid study. AndWakefield hadbeen awarded up to £55,000 to assist their case by finding scientificevidence of a link. Wakefield did not tell his colleagues or medicalauthoritiesof thisconflictof interesteitherduringorafter the research.”Deer B. (2004, February 22). Revealed: MMR research scandal. TheSundayTimes.

2 GMCvs.Wakefield,Walker-Smith,andMurch.EvidenceofProfessorArieZuckerman.Tr.15:p.4.

Smith[prosecutioncounsel]:Doyourecall,Professor—andpleasetellusifyoudonot—whetheryouknewwhothefirmof solicitors Dawbarns was in that letter and whether youpickeduponitatthetime?

Zuckerman:Icertainlypickeduponitatthetime.Theactualtiming is very difficult because I heard about this firm ofsolicitors from at least two different sources, one was theDepartment of Health and the other one was by letter fromProfessor Sir David Hull, so it is difficult for me to saychronologicallywhenwas the first time that I heard about itunless I see all the documents together, but I was certainlyawareoftheinvolvementofagroupofsolicitorsanditdidgiverisetoalotofconcern.(emphasisadded)

AndDay16:

Q: You had become aware by this stage that the Legal AidBoard had provided funding through a firm of solicitors

representing Crohn’s disease sufferers. Where did you getthatinformationfrom?

A:As I recall it, I received it from theDepartmentofHealthandfromProfessorSirDavidHull.(emphasisadded)

Q: When you say the Department of Health, any particularpersonattheDepartmentofHealth?

A:Ithinkitwillbedifficultformetosaythatbecause,asyouprobably know, I have been an adviser to theDepartment ofHealth continuously for 38 years and, therefore, I hadnumerous contacts there. It could well have been either DrJeremyMettersorDrSalisbury,Iamnotsurewho.(emphasisadded)

3 ZuckermantoArmstrong,Letter.October11,1996.

4 ZuckermantoWakefield,Letter.March13,1997.

5 ZuckermantoCalman.Letter.January22,1997.

6 Child Health Safety (2009, March 8). UK Government Hands DrugIndustry Control of Childhood Vaccination. Message posted tohttp://childhealthsafety.wordpresscom/2009/03/08/pharma-decide-uk-vaccination/.

7 Emphasisadded.

8 BrianBlatchtoArmstrongatBMA.Letter.February24,1997.

9 ArmstrongtoBrianBlatch.Letter.February27,1997.

10 ZuckermantoWakefield.Letter.March13,1997.

11 ZuckermantoArmstrong.Letter.March13,1997.

12 ZuckermantoMichaelPegg.Letter.April2,1997.

13 PeggtoZuckerman.Letter.April15,1997.

14 ZuckermantoPegg.Letter.April17,1997.

15 TarhantoZuckermanandBlatch.Letter.May20,1997.

16 GMC vs Wakefield, Walker-Smith and Murch. Zuckerman’sevidence.Tr.15&16.

17 In1997whileexpressinghisconcernaboutsuchconflictwithregardtoLABfundingforascientificstudy,ZuckermanwroteaneditorialfortheNewEnglandJournalofMedicine (NEJM) stronglysupportinguniversaluseofhepatitisBvaccinationoftheworld’sinfants.Atthattime,hewasanamedinventoronapatentrelatedtothehepatitisBvaccineand,assuch,might have stood to benefit financially from the policy endorsed in hiseditorial.At the time, in 1996, strict rules existed for theNEJMbarringpatentholdersfromwritingeditorials.

18 Pictureofcheckavailableatwww.callous-disregard.com.

CHAPTERFOUR

TheWhistleblower

Whistleblower. [Noun] An employee, former employee, ormember of an organization, especially a business orgovernment agency, who reports misconduct to people orentities thathave thepowerandpresumedwillingness to takecorrectiveaction.

Kirsten Limb was a paralegal at the law firm Dawbarn’s. OnMonday,April27,1998, shecalledme from theirKingsLynnoffice ina stateofconsiderable excitement.Thepreviousday, she andBarrhad traveled toNewcastletomeetinsecretwithsomeonewho,inseveralanonymouscallsto their office, had referred to himself as a “whistleblower”; no furtherinformation had been forthcoming. Newcastle is a considerable journeyfromNorfolk,particularlyonaSundaywhentrackrepairsanddoubletimepayforrailwaystaffcandragoutajourneytoseemingeternity.AtexactlynoonatthecoffeeshoponPlatform2ofNewcastlestation,theymetwith“George.”“George”wasanassumednameandtheonlyonebywhichhewouldbeidentified.Hewas,apparently,neatandnervous–everyinchacivil servant. (Kirsten’s attendance notes documenting George’sdisclosuresareprovidedinitalicsonpages66-72.)

George claimed that he was acting on behalf of a colleague − a seniormedicalofficerintheScottishOffice,whichispartoftheUKgovernment(apparentlyGeorgehimselfwasaveryhighrankingcivilservant,althoughhis positionwas not explained). In fact, George and hismedical officer

“friend”were one and the same, a detail thatwas disclosed at a secondmeetingalsoatNewcastlestation1yearlater.1

George hadmoved to theUK fromCanada, where he hadworked as aprincipal program immunization advisor in Ontario and was closelyinvolved with the MMR vaccination program. He had been activelyrecruitedtojointheScottishOfficeasaseniormedicalofficer,particularlytoadviseonevolvingUKMMRvaccinationpolicy.

Atthattime,abrandoftheMMRvaccinehadbeenwithdrawninCanadabecauseitwasunsafe;CanadahadintroducedanMMRvaccinecontainingtheUrabeAM-9mumpsvirus(Trivirix)in1986.2Itsoonbecameapparentthat this vaccine caused unacceptably high rates of meningitis.3 Georgewas invited to sit on the UK’s Joint Committee on Vaccination andImmunisation (JCVI) as its Scottish representative. In Canada, he hadcollatedextensive informationabout theMMRhazard; therefore,hewasin an excellent position to advise the DoH and, particularly, Dr. DavidSalisbury, the UK’s chief MMR strategist,4 on the introduction of theMMR.Georgeclaimed:

…he was very cautious not to openly release the damningevidence that he had retained from Canada regarding thesafetyoftheMMRvaccine…

Apparently, however, his attempts to pass this crucial information on tothe members of the JCVI were, to his astonishment, rebutted. Georgepointedout:

CanadahadbeenusingtheJerylLynn5[Merck’smumpsstrain

intheirMMRvaccineMMR2]MMRbeforetheystartedusingtheUrabestrain.Theyhadagoodmonitoringsysteminplaceand, had no axe to grind about the newUrabe vaccines. Yetdespite using the Jeryl Lynn MMR for 15 years, theyimmediately withdrew Urabe after 6 months, because thesurveillancesystemhadpickedupthesideeffects[meningitis].

At the UK’s Department of Health, George and other members of theJCVIexpressedtheir

…grave disquiet about public documents being issued whichwere designed to portray the MMR vaccine as ‘totally safe’whenclearly,itwasnot.

Georgefelt:

…itwasmadnesstouseavaccinewhichwasunproven.

He made this point strongly to the JCVI in late spring of 1988. HissuperiorsontheJCVIapparentlyrejectedhisadvice.

When thedecisionwas taken to introduceMMR in theUK,SmithKlineFrench-Beecham (SKFB), as the British company was apparently thencalled,didnothavealicensedproductintheUK.Infact,theirownUrabe-containingMMRvaccine,soldunderthenameofTrivirix,waswithdrawninCanadaforsafetyreasonsinJuly1998,inthesamemonththatthesamevaccineunderadifferentname(Pluserix)wasgrantedalicenseintheUK.On the other hand, Merck Sharp & Dohme (MSD) had a safer MMRvaccine (MMR II) containing the Jeryl Lynn strain of mumps that hadbeen sold for many years in the US without reports of meningitis.6

However,Merck’svaccinewasexpensivesince,asGeorgeputit,

…theyhadtorecovertheircosts.

Georgeexplained:

It was this that promoted the introduction of the Pluserixvaccine, as a competitor to encourage MSD to lower theirprices.

Ominously, having withdrawn Trivirix in Canada, SmithKline Beecham(SKB)simplyrepackagedtheidenticalvaccineingredientsasPluserixforuseintheUK,apparentlyirrespectiveoftherisktochildren,

“…therewasadeterminationtosella[cheaper]MMRvaccinefromSmithKlineFrenchBeecham[sic],”aBritishcompany.

Georgestressed:

…atthetimetheyannouncedtheMMRvaccinationcampaign,Pluserix was not actually licensed to be used in [the UK].Nonetheless, the Government had certainly internallyannounced that it was going to be used and its licensingprocedurewasrushedthroughona‘fast track’basis…safetytrialswerecircumventedtoallowthe[Pluserix]vaccinetobelicensedandwidelyused.

Again,ominously,Georgeexpressed:

…absolutelynodoubtthatshortcutsweretaken.7

Buttherewasa“problem,”asGeorgeputit:

…introductionoftheMMRvaccineintheUnitedKingdomhadbeen delayed for four months because SmithKline FrenchBeecham [sic]were very reluctant to obtain a license for theproductintheUnitedKingdom.Theywereawareofthesafetyconcerns based on the experience in Canada and Japan inparticular,andwereextremelyconcernedabouttheirliability.

ThekeytothemysteryofZuckerman’sfearsfortheBritishgovernment,asoutlinedinChapter3,“TheDean’sDilemma,”maylieinthemannerinwhich theUKvaccinemanufacturer’s concernswere dealtwith.Georgecontinued:

ItwouldappearthatalegalwaiverwasofferedbetweenSmithKlineFrenchBeecham [sic]and theDepartmentofHealth…themanufacturerswereveryconcernedabouttryingtoobtaina license for theMMR in theUnitedKingdom, inviewof theproblemswith it in Canada.He [George]and his colleaguesfeltthatthemanufacturers,beingveryastuteandhavingtheirownlegaladvisors,wouldhavehadsomesortofagreementinwritingabouttheirliability.

This was confirmed when George raised the issue with a femalerepresentative of what had then become SmithKline Beecham. Sherespondedwiththewords,

we are immunising the children and the Government isimmunisingus.

He took this as confirmation that a deal had been struck whereby thegovernment had assumed SKB’s liability for damage to children arising

outofthehigh-riskstrategyofusingPluserixvaccine.Unknowingly,thetaxpayerwasonthehookfora“dirty”vaccine.

And concerns about liabilitywere not confined toSKB;George pointedoutthatthequestionoflegalliabilityovertheuseofanunsafevaccinehadbeenraisedattheJCVIsince,asheputit,

Membersofthecommitteewereanxiousabouttheirownstatusbearinginmindthewarningsthat[George]hadgiven.

Howcouldsuchasituationhavearisen?GeorgeinformedBarrandLimbthat

…the JCVI was envisaged as being a committee with anentirelyadvisoryrole.However, theywereactingbeyond thisbrief. Therewere a small number of ‘hard core’members ofthe JCVI who were absolutely not interested [about safetyconcerns]andwerereallypoliticalanimals.

Influenceoverthecommittee’sproceedingsappearstohavebeenexertedby this “hard core” in part by controlling access to information.Georgeexplained:

…whenevertherewasameetingoftheJCVI,theminutesofthemeetingwerealwaysabout6monthslateinbeingcirculated.

Itappearsthatcommitteemembersreceived,asGeorgeputit,these“verysanitized”minutesjustthedaybeforethenextmeeting.Limb’sattendancenote captured the disquiet among some JCVI members over thecommittee’sdecision-makingprocess.

When [George] mentioned his concerns about the [MMR]vaccineandbroughttheinformationhehadtotheattentionofthecommittee (includingmedical literatureetc thathadcometo his attention on Ontario) some JCVI members expressedconcernsandwantedmoreinformation…thesememberswereseriouslyconcernedandaskingrepeatedlyforcautionandforfurther information to be supplied. However, because theseminutes of meetings were six months late in circulating,decisionswerebeingimplemented [bythe“hardcore”]beforeinformationhadcomethrough.

George insisted that theremust be internal documents detailing this.Hecontinued,

Worrieswerediscussedatthemeetings,butagaintheminutesofthemeetingdown-playedthis.

Georgeindicatedthathehadretainedmanyrelevantdocuments,althoughhefeltsurethatmanyofthoseheldattheDoHwouldhavebeenillegallydestroyed.While the government had made it a major offense for civilservantstodestroyevidenceinthisway,Georgeadmitted:

…theycouldnotreallystopitgoingon.

George also said that there was a big row about the change incontraindicationstothevaccineandthatcertainmembersoftheJCVIfeltthatmillionsofBritishchildrenhadbeenusedin“onebigexperiment.”Heconfirmed that once thegovernmentwasbeyond the tokenclinical trialsinvolvingthesechildren,

…thenextdecisionwastoimplementtheMMRvaccine.

George went on to identify the individuals whom he considered to beculpable. The medical secretariat of the JCVI was singled out. Thesecretariat was responsible for the minutes of meetings and, therefore,controlledinformation.Hedescribedoneseniormemberas“averydrivenman”and“anexceptionallyarrogantman…determinedtogethimselfupthe ladder.” But, apparently, the problems were not confined to oneperson.Georgeclaimedthat

…in fact thewhole environment in public health at that timewasborderingonthefascist.

He identifiedcertainmembersof theScottishOfficeand theMinistryofHealthwhomheclaimed

…wereveryrabidlyrightwing.Thiswasthecharacteroftheseofficesatthetime.

GeorgecontinuedbywarningBarr,Limb,andmethat

…someofthekeypeopleinthismaynotstopatanything.

SodespitebeingbroughtintoadviseontheintroductionofMMRintheUK,George’sexpertconcernswereignored.Infact,thehighriskPluserixvaccinewastotakethelion’sshareoftheUKMMRmarket.Inlightofitsknown dangers, one would have expected that vigilant surveillance ofadverseeventswouldhavebeenput inplace.Georgeand the restof theScottishCommitteestronglyadvocatedforsuchsurveillanceand

…pressed for an increase in funding to allow more activesurveillance.

Activesurveillance(asopposedtopassivesurveillance,whichisawaitingspontaneous reports of adverse reactions from doctors) involves theprospectiveascertainmentof adverse reactions throughactivecanvassingofdatafromprimarycaredoctors.Georgewasinvolvedintryingtosetupsome sort of surveillance system, but nomoneywas given to him to dothis. According to George, the money had to come through a seniormember of themedical secretariatwho controlledmillions of pounds toimplementthevaccinationprogrambutwasveryresistanttospendinganymoneyonmonitoringsafety.Georgecontinuedtotrytopressthispersonfor funds in order to provide adequate surveillance of side effects, butdespitehisrepeatedefforts,thiswasdenied.

Therestofthestorywas,inevitably,arewriteoftheCanadian,Japanese,and Australian experiences. As increasing numbers of reports ofmeningitis following Pluserix immunization came in, George describedhow

…eventuallyothermembersoftheJCVIbegantorealisewhatwas happening, and began putting increasing pressure onSalisbury, to lookmore closelyat adverse eventsafterMMR.Salisbury gave a very small amount of money to the PublicHealth Laboratory Service (PHLS), really expecting them toprove that therewasnoproblemwith thevaccine. Instead,asweknow,theyfoundproblems.Thewholethingblewupoveraweekend,andPluserixhad tobewithdrawn.Salisburyhad toflytotheUnitedStatesonSaturdayofthatweekend,andgotosee Merck Sharp Dohme senior management. He had to go‘cap in hand’ and ask them to divert some of the worldwideMMRvaccine to theUnitedKingdom, to cover the enormousgapcreatedbythewithdrawalofPluserix.

Georgefeltstronglythatbetweentheyearsof1988and1992,theclinicalindicatorsoftheproblemwithPluserixweredefinitelytherebutwerenotbeing noted. It was not just the Scottish Office that was expressingconcerns.VariousdoctorsalsoraisedconcernsintheUK.Georgepointedoutthat,asadamagelimitationexercise,oneseniormedicalmember

…soughttoreassurehiscolleaguesintheJCVI,thatthebraininflammation that many of the children were experiencingwould not leave any long term effects, and that also anymeningitis that developed was “aseptic” [non-bacterial] asthoughthismadeitallalright.

In fact, George was convinced that some children suffered permanentdamagefromPluserix.Priortohispublichealthcareer,Georgedisclosedthathe

“… had been a paediatrician who specialised in therehabilitationofbrain injuredchildren, sohedidhavedirectexperience of the awful situation that parents of childrenaffected by the MMR found themselves in.” He appeared tohold“a very strong view that there should be justice for thechildren that had been damaged by the vaccine.” Clearly hefelt somewhat guilty that “instead of going to the top andexposingallthis,hedidnotdothatatthetime,butstayedquietbecausehehadchildrentosupportatUniversity.”

Georgecontinued:

“… the present government [Labour] has vowed to improvethings, but unfortunately it had inherited the same CivilServants,”presumablywiththesameinterestsatheart.

Apparently, in order to ensure continued mutual protection, the weekbefore they left office just before the election, the Conservativegovernment

…gavefive-yearcontractstotheirCivilServantsthatcouldbeenforced if anyone tried to get them out subsequently. In theeventtheylosttheelection,theonlywayforanincomingpartytogetridofthemwouldbetogiveoutvasthandouts,andthentheywouldbeaccusedofwastingpublicfunds.

OneyearlaterGeorgewasstillstrugglingwithhisconscience.Atasecondmeeting— one that I attended and also atNewcastle station − hewentover the same ground and confirmed the facts covered in the previousmeeting,except thatat this secondmeeting these factsweredisclosed inthefirstperson.Forthatreason,Limbwrote,

…whathesaidcarriedverymuchmoreweight.

He told again how he had repeatedly given direct warnings to seniormedicalmembersabouttherisksovertheUrabe-containingMMRvaccine− warnings which they had ignored. I was later able to corroborate thecontents of the attendance note taken byLimb.ForGeorge, therewas apricetopayforhisdissent.Atthematerialtime,circa1988,hewasinhisearly50s,hehadtwochildrenatuniversity,and

… he felt very loyal to the Civil Service and the job he hadwithinit.

He had put himself in a difficult position by criticizing JCVI decisions.AccordingtoGeorge,withDr.KennethCalman’smovefromScotlandtoLondonastheUK’snewChiefMedicalOfficer,hehadbeennextinlineforCalman’spositioninScotlandbuthadbeenpassedoverforthis.Itwas

ofgreaterconcerntoGeorgethathewasasignatorytotheOfficialSecretsAct,which forbade him from taking home copies of official documents.HewasworriedthatifitwerefoundoutthathehadbeeninbreachofthisAct, he would likely to go to prison. In her attendance note, Limbdocumented:

“Heobviously remainedveryunhappy throughouthis time intheCivilService,grapplingwithhisduty tohis familyon theonehandandhisanxietyoverthesafetyofthevaccinesontheother.”Elsewhereshenoted,“Heisobviouslyaveryunhappyman,trappedwithanachingconscienceandratherterrifiedattheconsequencesofwhathehasdone.”

Hewas,notunreasonably,concernedforhisownsafety.Whencontactedlater, he stated that he did not wish to be the “next David Kelly.” Dr.DavidKellywasascientist in theUK’sMinistryofDefencewho,manybelieve,wasmurderedforthreateningtodisclosethefactthatIraqwasnotinpossessionofweaponsofmassdestruction.8

So there, in a railway station café in the far north of England, wassomebody who was once one of the most senior medical officials inScotland, blowing the whistle on, at the very least, the attitude towardsafety and children’swelfareof someof theUK’s topmedical officials.Heindicatedthathewaspreparedtoprovideadetailedstatement.Noonehadanydoubtatallthathewastellingthetruth,andtherewaslittledoubtthathewouldbebelievedshouldhecomebeforeacourtorparliamentaryselect committee despitewhatever attemptsweremade to discredit him.AshehadcrossedtheRubicon,heacknowledgedthattherewaslittlepointinkeepinghisidentitycompletelysecret.Indeed,Limbconsideredthathewas quite relieved for someone to have known exactly who he was.George’s real name is Dr. Alistair Thores. He lives in Edinburgh,

Scotland. He would do well to realize sooner rather than later that awhistleblowerismuchsaferoncehehasgonepublicinthepublicinterest.If he has ever watched The Insider, he will know that information isdangerousonlyaslongasyouaretheonlyonewhoknowsit.

ThereismuchmorethatcanandwillbewrittenabouttheUrabeepisode.Ihaveconfinedthischaptertomystateofknowledgein1996-7sinceitwasthe insights provided by George’s disclosures that were, in part, mymotivationtofightforasafetyfirstvaccinepolicy.Thisstoryhighlightssomanyof theproblemswithin theUK’svaccinepolitburo,not leastofwhicharethedisproportionateinfluenceofafewindividuals,theapparentmanipulation of information and access to it, and above all, where theperception of the importance of vaccine safety ranks in the priorities ofthose who are charged with looking out for our children. The Urabeepisode throws these issues into sharp relief. Against expert advice, adangerous vaccine was given preferred status. Children were theexperimental marketplace. Shortcuts were apparently taken to fast-trackthe licensing process for this vaccine. Despite warnings, adverse eventssurveillanceoperatedatabareminimumonasortof“ifwedon’tlook,wewon’tsee”policy.TheUKsafetystudieslastedonly3weeks,whereastheCanadianswere reporting that inmanycasesvaccine-inducedmeningitisdidn’t even start until after this period.9 The vaccinemanufacturers andJCVImembershad reasonable fears that theymightbe liable, andSKB,fortheirpart,appeartohavebeengivena“GetOutofJailFree”cardbyHerMajesty’sGovernment.ConfirmationofthiswaslatertoappearintheJCVIminutesofMay7,1993,whereitstates:

…SKBcontinuetoselltheUrabeMMRwithoutliability.10

ThevaccineprovedtobeunsafeforUKchildren, justas ithadforotherchildrenaroundtheworld.Permanentdamagetochildrenwasdeniedand

thisdenialcontinues.Yearslater,Salisburywastodenyanyknowledgeofanindemnity11(initially,atleast)inspiteofthefactthattheJCVIminutesare unambiguous and entirely consistent with George’s firsthandexperience.Thematterclearlyneedstoberesolved,andIsuspectthereisconsiderablefearofpublicscrutiny.

One of the enduringmysteries is the issue of the respective costs of thedifferent MMR vaccines. As Martin Walker noted in “The UrabeFarrago,”12JCVIminutesandallotheravailabledatarecordedhowMMRIIwas 3-4 timesmore costly thanPluserix, but more recent documentsidentifytheMMRIIproductat£1intheearlycatchupphase(whenMMRwas first introduced) going up to £2 after that, whereas the supplyagreement forPluserix records thecostof thisvaccineat£3.80plus tax.Wasthishighpricenegotiatedaspartofthedeal?

In 1997, while I sought to bringmy safety concerns to the attention ofmembersoftheJCVI,behindthescenesthesesamedoctorswererunningwith a parallel agenda. Hull of the JCVI had alerted Zuckerman to mywork with Barr; he had seemingly exercised Zuckerman about anonexistent government select committee, and later sought to questionWalker-Smith’s clinical care of children and the associated research bymakingmisleading claims about it.13 Might it be coincidental that HullwasalsoontheJCVIthatwasresponsibleforadvisingontheuseof thePluserixMMRvaccine?

Zuckerman had tried to prevent the LegalAidBoard pilot study on thebasisof“conflictofinterest,”butdidnotdisclosetomethatthisconflictwasthefactthatitwastheUKgovernmentthatwas(andpresumablystillis)liableforSKB’s14MMRvaccinedamage.

The gulf between my perception of MMR vaccine safety and that ofSalisbury,theheadoftheUK’simmunizationprogram,isexemplifiedinoneoftheconcludingparagraphsofhisstatementtotheGMC’slawyers:15

It is hard to quantify how much the DH has expendedfinancially to deal with this [public concerns over MMRsafety]. Huge resources have been spent in communicationinitiatives entirely for the purpose of restoring public andprofessionalconfidenceforavaccinewithanexemplarysafetyrecord.16

TwooftheUK’sthreelicensedbrands,introducedin1988andwithdrawnforsafetyreasonsin1992—“exemplary”?Thehugeresourcescouldhavebeenbetterspent.

Endnotes1 February28,1999.

2 Initially as Institute Armand-Frappier, Quebec, later as SmithKlineFrench-Beecham.

3 Champagneetal.CanDisWeeklyRep.1987;13:155-157

4 Curriculum Vitae of Dr. David Salisbury. Under “personalachievements”itreads:“StrategydesignandpolicyimplementationMMRvaccination1988.”

5 Jeryl Lynn was the name of Dr. Maurice Hilleman’s daughter fromwhomthismumpsstrainwasisolated.HillemanwasinchargeofMerck’svaccineprogram.

6 See Martin Walker’s article titled “The Urabe Farrago.” Retrievedfrom:http://www.wesupportandywakefield.com/documents/The%20Urabe%20Farrago.pdf

7 Thereareatleasttwopartstothis:firstly,accordingtotheminutesoftheworking party to discuss the introduction ofMMRvaccine (January23, 1987), data from other countries (the US and Finland) that usedMerck’sMMRIIthatcontainedtheJeryl-LynnmumpsstrainandnottheUrabe-containingMMR,were accepted as a proxy for the safety of theUrabe-containingvaccine.Secondly,theUK“trial”ofMMRlastedonly3weeks. Meningitis following the Urabe-containing MMR is rarely seenbefore21dayspost-vaccinationandcanoccurupto35dayslater.TheUK“trial”wouldhavemissedit.

8 Goslett M. (2010, January 25) David Kelly post mortem to be keptsecret for 70 years as doctors accuse Lord Hutton of concealing vitalinformation. Retrieved from: http://www.dailymail.co.uk/news/article-

1245599/David-Kelly-post-mortem-kept-secret-70-years-doctors-accuse-Lord-Hutton-concealing-vital-informationhtml.

9 Seealsoendnotenumber7forthischapter.

10 JCVIminutesofMay7,1993.

11 Salisbury denies knowledge of indemnity for any manufacturer ofMMR: “As has been stated on innumerable occasions, there was noimmunity/indemnity given toMMRmanufacturers.” E-mail fromDavidSalisburytoCliffordMiller,September13,2006.

12 See Martin Walker’s article titled “The Urabe Farrago,” page 22,footnote 34. Retrieved from:http://www.wesupportandywakefield.com/documents/The%20Urabe%20Farrago.pdf

13 Hull letter to Zuckerman about MRC presentation “Since thesechildrenhavenoevidenceofchronicinflammatoryboweldisease.”July6,1998.Thisisfalse.

14 NowGlaxoSmithKline.

15 GMC vs Wakefield, Walker-Smith, and Murch. Statement of Dr.DavidSalisbury.September20,2006;page29,paragraph150.

16 Emphasisadded.

CHAPTERFIVE

EthicsandtheMasses

Informedconsent is a crucial elementof the foundationuponwhich ethical medical practice rests. Providing patients,parents, or guardians with an honest assessment of the risksandbenefitsofanymedicalprocedurerequiresthephysiciantobe,tothebestofhisorherability,“informed.”1

While sitting in the chamber of the General Medical Council (GMC),accused of ethical violations in the investigation of The Lancet 12 andirresponsiblescaremongeringaboutMMRvaccinesafety, Iwas listeningto theearnest testimonyof theUK’sDoHDirectorof Immunisation,Dr.DavidSalisbury;itwasatthispointthatIdeterminedthatthisbriefessayshouldgoontherecord.Itrelatestoamassvaccinationcampaignusinganexperimental vaccine combination—measles and rubella (MR)— thatwasadministered toapproximately8millionUKschoolchildren2overa1-monthperiodinNovember1994.Thejustificationforthecampaignwasamathematically-predictedmeaslesepidemic.Theprincipal architectsofthecampaignwereSalisburyandhisboss,Dr.KennethCalman,theUK’sChief Medical Officer. Through an intense and frightening advertisingcampaign,3 parentsweremotivated to get their children revaccinated bythethreatofupto50deathsfrommeasles.

There arewell-established side effects frommeasles-containing vaccines(MCV); anaphylaxis is one of these. Anaphylaxis refers to a rapidlydevelopingandpotentiallyseriousallergic reaction thataffectsanumber

of different areas of the body at one time.Severe anaphylactic reactionscanbefatal,andthepubliciswellawareofdeathsinchildrenwithpeanutallergy following inadvertent exposure. While many people experienceallergysymptomsonlyasaminorannoyance,aminorityofallergicpeoplearesusceptibletoareactionthatcanleadtoshock(adramaticreductioninbloodpressure)andevendeath.

Anaphylaxis isoften triggeredbysubstances (allergens) thatare injected(suchasMCV)oringestedandtherebygainaccessintothebloodstream.An explosive reaction involving the skin, lungs, nose, throat, andgastrointestinaltractcanthenresult.Althoughseverecasesofanaphylaxiscan occurwithin seconds orminutes of exposure and be rapidly fatal ifuntreated,manyreactionscanbeendedwithpromptmedicaltherapy.

Anaphylaxis is likely tobemorecommonandmoreseriouswithsecondandsubsequentexposurestoanallergensincethebody’simmunesystemhas been primed by the initial exposure and is capable of reactingmorevigorously.

The best and safest way to deal with anaphylaxis is to (1) be fullyinformedoftherisk;thatis,beawareofthepossibilitythatanaphylaxisisasideeffectoftheexposure;(2)avoidexposuretotheoffendingallergenifthereisanyhistoryofapriorreaction;and(3)haveaccesstoimmediatetreatmentsuchasepinephrine(adrenalin)intheeventofthisreaction.

AsIhavealreadyexplained,anaphylaxisisaknownriskofMCV,anditwaspredictable−withanabsolutecertainty−thatcaseswouldoccurasaconsequence of the MR campaign. Therefore, it was essential for the

vaccine directorate of the DoH to fully evaluate the relevant medicalliterature inorder to adequately assess the extentof the anaphylaxis riskand todecidehow todealwith itwhenplanning this experimentalmassvaccination campaign. In order that the DoH might accurately andethically warn parents and children of this risk and evaluate the risk-benefit ratio of the MR strategy, this comprehensive evaluation of theliteraturewasaprerequisite−failuretodoitwasnotanethicaloption.Inordertoassistinsuchariskassessment,doctorsinNewYorkin1992hadreported their experience of five cases of potentially life-threateninganaphylaxisin2,789boosterdosesofMMR−reactionsthatwereabortedby the timely and potentially lifesaving administration of epinephrine(adrenalin)ordiphenhydramine.4MMRwasthecommondenominator inthe vaccines received by the affected individuals. Importantly, theserecipientswereschool-agechildren,withthreebeing8,8,and9yearsoldrespectively; therefore, according to the prevailingUSvaccine schedule,theywouldhavealreadyreceivedatleastoneMCV.

Without prompt treatment, this reaction, which occurred in 1 in 558recipients of anMCV,might well have been fatal. The data fromNewYork indicate that anaphylaxis is likely to be more common and moresevereinolderchildrenwhohavepreviouslybeenexposedtoanMCV—precisely the childrenwhowere targeted in theUK’sMR revaccinationcampaign.5 For the UK, this figure equated to the potential for up to14,337 cases of a potentially life-threatening complication in thatcampaign.

Butparentswerenotwarned.

There was no mention of anaphylaxis at all in the information leaflet

prepared by the DoH and upon which parents based their consent tovaccination.6

To make matters worse, the same information leaflet claimed thatreactionswereexpectedtobelesslikelywiththeboosterdose.7Iamnotawareofanyevidencethatanaphylaxisislesslikelyorlesssevereonre-exposure.8 The data fromNewYorkwithMCVboosterswould suggestquitetheopposite.

TheMRcampaignwasundertaken largely in thenation’s schools ratherthanindoctors’offices.Despitethis,familydoctorsandnursesweresenttheirowninformationdocumentbySalisbury’sdepartment.Thedocumentconfirmed that the immunizations would take place in school and thatgeneralpractitionerswouldnotbesuppliedwiththeMRvaccineuntilaftertheschool-basedvaccinationprogramhadbeencompleted.

Intheinformationfordoctors,undertheheadingof“ContraindicationstoMR immunisation”9 it states clearly that children with a history ofanaphylaxisfollowingameasles-orrubella-containingvaccineshouldnotbegiventheMRvaccine.

Inthecertainknowledgethatanaphylaxiswould(anddid)10occur,andinlight of thepublished evidence that it couldoccurwith a relativelyhighfrequencyandthatitispotentiallyfatalunlesstreatedpromptly,treatmentfacilitiesshould,withoutadoubt,havebeenavailable(andknowntobebyallinvolved)whereverthevaccinewastobeadministered.Theywerenot,at least atmy children’s school or those of any other parent ofwhom I

haveinquired.

Weshallneverknowwhatactuallyhappened.Itismyopinionthatastateof deliberate ignorance exists.Despite the fact that theMRvaccine hadneverbeenusedbefore,despitethefactthattheUKhadnoexperienceofmass vaccination campaigns, and despite the published risks of apotentially life-threatening reaction, there was no active surveillance todeterminethetruerateofadverseeventsduringtheMRcampaign.Despitetherelianceonthefailedsystemofpassivesurveillance—i.e.,receivingspontaneous doctors’ reports of suspected adverse reactions − the MRcampaignwas associatedwith a high rate of reported adverse reactions.This probably represented no more that 10 percent of the true adversereactionstoanMCVand,basedupontheexperienceoftheUSCentersforDiseaseControlandPrevention,probablyconsiderablyless.11

For cases of anaphylaxis based upon spontaneous reports, the JointCommittee onVaccination and Immunisation (JCVI)minutes ofMay 5,1995,documentthatintheMRcampaign

…fewcaseshadbeensevereorlife-threatening.12

Herewehaveconfirmationof thefact thatsomeparentshadunwittinglyputtheirchildren’slivesatriskbecausetheyhadneverbeentoldthatsuchriskexisted.Theconceptofinformedconsentappearstohavecountedfornothing.Adrenalin—sometimesmultipledoses−wererequiredtoabortsomeoftheseattacks.

InapaperendorsingthemeritsoftheMRcampaign,Dr.FelicityCutts13

reportedthatwithMMRvaccineanaphylaxisoccursinupto1in20,000doses (i.e., an expected 400 anaphylaxis cases following MR vaccine).This is certainly an underestimate because her data was based, almostexclusively, on inadequate surveilliance methods and primary MMRvaccination of 1 year olds. The observation of Kalat et al. of severeanaphylaxisin1in558school-agechildrenreinforcesthefactthattheriskislikelytobeconsiderablygreaterinolderchildrengettingaboosterdose.

It isunthinkable that thoseresponsibleforwriting the information leafletforparentssimplyforgotaboutanaphylaxis,andthis isconfirmedbytheinformation provided to family doctors. Itwould have been negligent ofthemnottohavereviewedtheliteratureexhaustivelyinadvanceofputtingthe campaign into effect.Trying to persuade parents of themerits of anMR campaign on the basis of up to 50 possible measles deaths whileethically warning them of the possibility of up to 14,337 anaphylaxisdeathsfromtheMRvaccinewouldhavedoomedthecampaigntofailure.In my opinion, parents were deliberately frightened by a powerfuladvertising campaign to get their children revaccinated with anexperimental vaccine in an untested mass revaccination strategy. Theoutstandingquestioniswhetherornotadeliberatedecisionwastakennottowarnoftherisksofanaphylaxis.

Iwrote onmultiple occasions to Salisbury andCalman, seeking to alertthem to my concerns about adverse immune effects of MCV and, inparticular,therisksofrevaccination,especiallyinrelationtoinflammatorybowel disease.At the time, Iwas unfamiliarwith the anaphylaxis issue,but the principles are similar. I sought any evidence that any MCV-revaccinationpolicyhadeverbeenstudiedforsafetybutcouldfindnone.Aspartofthisquest,IcontactedDr.Christensononthebasisofherbeingone of the architects of the Swedish vaccine program. SystematicrevaccinationwithMMRstartedinSwedenin1982.14;15Iaskedherabout

her expert knowledge of safety studies of 2-dose MMR schedules. Shereplied:

ImustavowthatIdon’tquiteunderstandwhatyoumeanwithiftherehas[sic]beenanysafetystudiesofthe2-dosemeaslesvaccine schedule.We have followed the 12-year old childrenwithbloodspecimensdrawnbeforevaccinationand2monthsaftervaccination.Thisisaformofsafetystudy.

Clearly,measurement of serum antibodies following revaccination of 12yearoldsisnokindofasafetystudyatall(serumantibodiesat2monthsareameasureofshort-termvaccineefficacy).Christensonlaterconfirmedtome ina telephonecall that therehadbeennosafety studiesof2-doseschedules in Sweden, norwas she aware of any having been performedelsewhere, reinforcing the experimental nature of this policy in theUK.Despite the MR campaign having been a mass experiment on humansubjects,thereisnoindicationthatanethicscommittee(EC)approvalwaseversoughtorgranted.

How does this rank, in my opinion, in the great scheme of ethicalviolations?AttheGMCIwasfoundguiltyofnothavingECapprovalforhavingasampleofbloodtakenfrommyownchildrenandseveraloftheirfriendsatmyson’sbirthdaypartywithfullandinformedconsentfromthechildrenandtheirparents.Thebloodsamplesweretakenforcomparisonwiththosefromchildrenwithautism.Thebloodwastakenbyasuitablyqualifiedmedicalpractitionerwithstandardasepticprecautions.Childrenwere rewardedwith the equivalent of just over$7.The entire procedurepassed off without mishap or complaint. This process did not have theapproval of an EC, which I now accept was naïve, but it was mostcertainlynotunethical.Incontrast,theMRcampaignhadmultipleethicalfailingsonmanylevels,butthemoststaggeringomissionofallseemsto

metohavebeenthefailuretoalertparentstotheknownthreatofsevereadverse reactions — to deny them the fundamental right of informedconsent inmakingadecisionabout theirchild. Itputs thebirthdaypartyinto the shade and rather makes a mockery of the post-GMC headlinesaboutmycallousdisregard.

Endnotes1 WakefieldAJ,BlaxillM,HaleyB,RylandA,HollenbeckD,JohnsonJ,Moody J, Stott C. Response to Dr. Ari Brown and the ImmunizationActionCoalition.MedicalVeritas.2009;6:1907-1924.

2 Cutts F. Revaccination against measles and rubella. BMJ.1996;312:589-590.

3 Minutes of JCVI meeting May 5, 1995; 6.5 para 2. HEAmeasles/Rubellacampaignreport:TheHEA[HealthEducationAuthority]did acknowledge the view that the TV advert used had been a littlefrightening, and also that not enough information on the possible side-effectsofthevaccinehadbeenprovidedforsomepeople.

4 Kalet A, Berger DK, Bateman WB, Dubitsky J, Covitz K. AllergicreactionstoMMRvaccine.Pediatrics.1992;89:168-9.

5 Cutts F. Revaccination against measles and rubella. BMJ.1996;312:589-590.

6 JCVIminutesofNovember3,1995.Insection10.1,paragraph2,itisdisclosedthatanaphylaxishadnotbeenmentionedintheparents’leaflet.”

7 Measles.Whyeverychildinschoolneedstobeprotectedfrommeaslesthisautumn.1994HealthEducationAuthority/DepartmentofHealth

8 With the exception of specific desensitization regimes undertaken byexperts.

9 Measles and Rubella Immunization Campaign. PL CMO(94)12/PLCMO(94)15September271994.Page4.

10 JCVIminutesofJanuary27,1995.Section6.7,paragraph2.

11 Rosenthal S, Chen R. The Reporting Sensitivities of Two PassiveSurveillance Systems for VaccineAdverse Events.Am J PublicHealth.1995;85:1706-1709.

12 JCVIminutesofMay5,1995.Section6.7.

13 Cutts F. Revaccination against measles and rubella. BMJ.1996;312:589-590.

14 Bottiger M, Christenson B, Romanus V, Taranger J, Starndell A.Swedish experience of two dose vaccination programme aiming ateliminatingmeasles,mumps,andrubella.BMJ.1987;295:1264-1267.

15 Letter from Dr. B. Christenson to AJW, referred to also in paperWakefield AJ and Montgomery SM. Measles, mumps, rubella vaccine:throughaglass,darkly.AdverseDrugReactions&ToxicologicalReviews.2000;19:265-283.

CHAPTERSIX

TheDean’sPressBriefingBywinter1997,thecaseseriespaperhadbeenacceptedforpublicationinThe Lancet. In view of some advance publicity and the growingcontroversy that surrounded the vaccine issue in particular, it wasconsidered likely that the paperwould attract considerable interest fromthemedia.

Sincehisappointmentasdean,Zuckermansawmediaattentionasbeingapositivethingforamedicalschoolthathadbeenbecalmedintheacademicdoldrums for some years. In order to “court” news outlets and gainattentionforthemedicalschool,anentityknownastheMediaGrouphadbeen formedunderZuckerman’s chairmanship and includedmembers ofboth themedical school and thehospital aswell asPhillipaHutchinson,theschool’spressofficer.

Asdeanandchairmanofthemediagroup,ZuckermanmadethedecisiontoholdapressbriefingontheforthcomingLancetpublication, timedforthe day before the study appeared in print. While this decision wasinfluenced by a 1995 press briefing onCrohn’s disease and its possiblelink to measles vaccination, Zuckerman and Hutchinson were later toexpress opinions that were polar opposites on the outcome of thatprototypepressbriefing.

Iapproachedtheideaofapressbriefingwithsomeanxieties;bythisstage,I had examined the issue ofMMR vaccine safety in great detail. I hadreviewedallofthepublishedscientificliteratureaboutmeaslesandMMRvaccine safety studies on the basis that, as part of investigating parentalconcerns and before calling into question MMR vaccine safety, it wasessentialtohavedoneso.Onapersonallevel,IwasdismayedthatIhadn’tdonethisresearchbeforevaccinatingmytwoolderchildren.Onagloballevel, it was clear that the safety studies had been wholly inadequate.“George”thewhistleblowerhadmajorconcernsabouttheattitudeofmanyofhispublichealthcolleagues towardconcernsovervaccinesafety.Theforced withdrawal of MMR vaccines that had been “spun” as beingcompletely safe was testament to their failings. In the light of theseconcernsandtheforthcomingpublicity,Iwrotetomycolleagues5weeksbeforepublication,informingthemofmypositionwithrespecttoamediastatementonMMRvaccination.

Re:MMRandAutisticEnteropathy:Forthcomingpublicity1,2

Firstly, the paper has been officially accepted by The Lancetafter someminor revisions. Theywill be sending proofs nextweekandIwillpassoneontoeachoftheauthors.

Ifeltthatinviewoftheimminentpublicityregardingourwork,itwasimportanttowriteandclarifymyownposition.Clearly,pending a press-briefing or other communications with thepress,whichnowseemsinevitable,weneedtohaveconsideredourpointsofview,well inadvanceofpublication.Theremaybepointsuponwhichwedisagree,butIdonotthinkthatthisisa problem, as long as that is made clear. If we can bothrecognizeandrespecteachother’sposition,thenthereshouldbe no ambiguity. I have thought about this issue almostcontinuously over the last 5 years, firstly in a relationship to

inflammatoryboweldisease,and latterlyautistic enteropathy,andIhave tried toset thisoutbelow,asa template formoredetaileddiscussion.

Inadditiontoourownworkandthatofothers,myopinionisalso based upon a comprehensive reviewof all safety studiesperformed on measles, MR and MMR vaccines and re-vaccinationpolicies.Thisnowruns intoareportcompiledbyme of some 250 pages, which I am happy to let you see. Insummary,thesafetystudiesarederisory,andappeartoreflectsequential assumptions about measles vaccine safety, MMRsafety and latterly, two dose vaccine safety, where eachassumption has potentially compounded the dangers inherentinthefirst.

In view of this, ifmy opinion is sought, I cannot support thecontinueduseofthepolyvalent3MMRvaccine.Ihavenodoubtofthevalueofthecontinueduseofthemonovalent4vaccines,andwill continue to support theiruseuntil thecasehasbeenproven one way or another of the measles link to chronicinflammatoryboweldisease.Ibelievethat1998willseesomeconclusivedatainfavourofthemeasleslinkfrombothourownwork and the USA. I recommend that measles vaccination isdeferredinchildrenwithastrongfamilyhistoryofIBD.5

Paradoxically,attemptstosustaincredenceinMMRsafetybyquoting data from a surveillance scheme that is widelyrecognizedtobeinadequate,andtodismissparents’claimsofa link between their child’s disorder and MMR without due

investigation, in breach of the most fundamental rules ofclinicalmedicine,isunacceptable.Thefailureoftheregulatoryauthorities to honour their commitments to MMR vaccinesafetyhascreatedaHouse-of-Cardsthatthreatensallvaccinepolicies.

Whenparentshavetheirclaimsdismissed,outofhand...6theycreate frustration, resentment and distrust; similarlydisaffectedparentsformintoselfhelpgroupssuchasAIAandJABS,manyof themembersofwhicharearticulateandwell-read. Their anger is compounded as the case-numbers growand their anxieties go unheeded. FinallyDoctors such as us,perceive a pattern to the disease and its linkswith theMMRthat becomes self-evident. When the data are presented, theangerofmanyparentsboilsover,thepresshasafieldday,andtheHouseofCardscrashestotheground.

Loss of trust in the regulatory authorities is inevitable andvaccination compliance, across the board, is affected – adifficultanddangeroussituation.Thereisnodoubtinmymindthatresponsibilityforthisvolatilestateofaffairsrests,notwithus,butfirmlyupontheshouldersofthepolicymakers;thatis,theJCVIandtheDepartmentofHealth.TheyhavestartedfromthepositionthattheMMRvaccineissafe,andthatanychangein the policy following claims of adverse events, must be setagainst that position. Their starting point was, and remains,wrong. Any drug, and especially one that involves 3 liveviruses,mustbeconsidereddangerousuntilprovenotherwise:thishasneverbeenprovenand,therefore,allclaimsofadverseevents should have been thoroughly investigated. They havefailedtohonourthisobligation.

In an attempt to avert the House-of-Cards collapsing, I willstrongly recommend the use of monovalent7 vaccines asopposed to thepolyvalent vaccines.Thiswill not compromisechildren by increasing their risk of wild infection, and mayreduce the risk of apparent synergy between the componentvirusesthathavebeenidentifiedbyDr.ScottMontgomeryasariskfactorforinflammatoryboweldisease,andmaywellbeariskforautisminourchildren,currentlyunderinvestigation.

I appreciate that you cannot (or may feel that you cannot)supportthisstance,andIcompletelyrespectthat.Ivalueyouropinionandyourfriendship.

Zuckermanwascopiedinonthisletter.MypositiononMMRwasmadecrystal clear, and the reasons for that position had been laid out.ZuckermanrepliedonJanuary22,1998,saying:

You kindly sent me a copy of your letter of 15th Januaryaddressedtoyourseniorcolleaguesstatingyourownpositionwith regard toMMRand your various studies… I venture tomake the following comments in my capacity as a virologistwith considerable experience in vaccine development andevaluation.Yousupport thecontinueduseof themonovalent4vaccinesandyouwrite thatyouhavenodoubtof theirvalue.Tomyknowledgethishasnotbeenrepeatedbythemedia…Itis vital, in your own interest and that of children, that youclearlystateyoursupportformonovalent4vaccination.

For reasons that are uncertain, both my initial letter to colleagues and

Zuckerman’sresponseweremissingfromZuckerman’sdisclosurestotheGMClawyersduringthepreparationoftheircaseagainstme.

The transcriptof theGMChearing, readverbatim, is a lesson inhow tolandafishwithoutputtingtoomuchofabendontherod.Duringcross-examination,KieranCoonan,QC,myseniorcounsel,ledZuckermanintothecircumstancesofthepressbriefing:

Coonan: There had been something of a track record ofholdingpressconferencesorpressbriefingsattheRoyalFree.Therehadbeenone following thepublicationof thepaperbyDrWakefieldin1995.

Zuckerman:Thatiscorrect.

Coonan: That was following the publication of a paperinvolvingCrohn’sdisease.

Zuckerman:Thatiscorrect.

Coonan:Thatappearedtobeasuccessfulmodelandobviouslywasthoughttoreflectwellontheschool.

Zuckerman:Iamsorry,no.Itdidnotreflectwellontheschoolatallbecausetheresultofthatpressconferencewasanalmost

dramatic fall in immunisation against measles because, onceagain, themeaslesvaccinewasblamed for this.Thepress,ofcourse,foundthisaveryexcitingstory.Itwasnotamodelofapressbriefingandwehadcausetoregretthatittooktheturnofevent…Itwasnotamodelpressbriefing;itwasadisaster.

InherstatementtotheGMC,Hutchinson,thepressofficer,hadpaintedanaltogetherdifferentpicture:

I do recall the team being pleased with the quality of thecoverageasithadconveyedthecomplexitiesofthescienceandgivenabalancedview.Asthefirstpressbriefingwasasuccess,andduetotheoverwhelmingadvancepublicityitwasdecidedto hold another press briefing. It would have been the dean[Zuckerman]whodecidedtoholdapressbriefing.

Referring back to the 1995briefing in cross examination,Coonan askedZuckermantheobviousquestion:

Coonan:Ifthatwassobadinyoureyes,whydidyouallowtheonein1998togoahead?

Zuckerman: It is not a question of me allowing. There is amedia group which is shared between the hospital and theMedicalSchool. I,as theDeanof theMedicalSchool, simplychairedthatcommittee.Whatwasagreedby themediagroupwasthatthechangesinthebowelsofchildrenwithautism,thepathologicalchanges,wereimportantsignificantnewfindings.I,withtherestof themediagroup,agreedthatthisshouldbesubjecttoapressbriefingfortworeasons:wewereawarethatThe Lancet were going to issue a press statement; and,

secondly,wefelt that itwas important that thesepathologicalchanges, and no more than those pathological changes, bepresentedatapressbriefingtomakesurethattheyunderstoodthesignificanceofthepathologicalchanges,nothingtodowithmeaslesvaccines.

In fact, as head of the medical school and the media group, it wasZuckerman’sprerogativetodecidewhetherapressbriefingtookplaceornot.Intheevent,hedecidedthatapressbriefingwastheappropriatewayforward.HisclaimaboutTheLancet’sintentiontoissueapressstatementwasinerror.InfactTheLancetnever issuedapressstatementabout thepaperat thetimeof itspublication,andinevidence,TheLancet’seditor,RichardHorton,toldtheGMCthattherehadneverbeenanintentiontodoso.

Crucially−andmost importantly−neverat any stagewas thereaplan,directive, request, or agreement that the press briefing would make nomentionof vaccines andwouldbe confined to thepathological changes,that is, the intestinal disease in autistic children. There is absolutely nodocumentary evidence to support this and plenty that refutes it.Hutchinson’sstatementprovidesaninsightintothedean’sstateofmindatthematerialtime.Shewrote:

Theaimwas…toensurethatthepublicknewthatopinion[ontheMMR]amongtheauthorswasnotuniform.Itappearedtome that the authors were at one in respect of the scientificfindings [bowel disease] but not in respect of the widerimplications [forvaccination].TheDeanwanted this to comeacross…Irememberthatakeyconcernofhiswastomakeitclearthattherewasadiversityofopinionamongtheauthorsofthe Lancet paper; another was to ensure that journalists

realised that the school fully supportedgovernment policy onimmunisation.8

Hutchinson’srecollectionwasidenticaltomineand,whileIwasnotpartof themedia group, Iwas bound to act on their instruction. The dean’searnest position that the briefingwas to be “nothing to dowithmeaslesvaccines”wasofftoabadstart.CoonanpressedZuckermanfurtheronhismotiveforholdingapressbriefing:

Coonan: Iwant tosuggest toyoutwothings: firstofall, thatyouwerekeentohaveapressbriefingin1998.

Zuckerman:No.

Coonan:Becauseofthehistoryofthepreviousone.

Zuckerman:No.

Coonan:Becauseyou thought itwouldreflectwell, that is tosay the findings in the 1998Lancetwould reflectwell on theMedicalSchool.

Zuckerman:Withthegreatestrespect,theanswertoallthesestatementsarecategoricallyno.MypositionwastodefendtheMedicalSchool’s reputationon flawedresearch.Every time Iwent to Geneva to the World Health Organisation [WHO] I

was challenged why was the Medical School, and I inparticularastheDean,asthedirectoroftheoneofthe[WHO]laboratories, did not challenge and stop this particularpublicitywhichwasdamaging the reputationof the school. Itcertainly was not enhancing the reputation of the MedicalSchool as you allege, it is the reverse. It was extremelydamagingtotheMedicalSchool.

Thedeanhadclearlybeensubjectedtoconsiderablepoliticalpressure.Hisevidenceseguedintohisstatementthatincluded“flawedresearch,”whichhadnotbeenrelevanttothequestion.Coonanpressedon:

Coonan: I am sorry to have to suggest this but yourrecollection and reconstruction of this is inadequate andinaccurate.

Zuckerman: I absolutely reject this. I resent the statement. Ireally do resent this. Mr Chairman, I absolutely object andrejectthis.

Infact,ZuckermanprotestedtotheGMCPanelchairman,Dr.Kumar,thatCoonan was making statements on his behalf rather than putting aquestion.The chairman rejected this. In fact,Zuckerman’s protest led tohimbeingreprimandedbyKumaratwhichpointhethreatenedtobringinhisownlegalrepresentation.

Following a brief discussion,Coonanmoved on to a different tack.Thenew topicwas that of a video news release (VNR).As chairman of themediacommittee,ZuckermanhadcommissionedtheproductionofaVNRfordistributiontointerestedmediaoutlets.Thiswastocontaininterviews

with various authors ofThe Lancet paper, shots of the hospital, and aninterviewwiththeparentsofanaffectedchildwhohadbeentreatedattheRoyal Free. In evidence, Hutchinson recalled that in a press releaseapproved by Zuckerman, at the bottom under “NOTESTOEDITORS,”therewasthestatement“wehaveavailableacolourstillofachildbeingimmunized and a VNR.” One might reasonably ask why the deanapproved the circulation of an image of a child being vaccinatedwhen,apparently,thisthornysubjecthadspecificallybeencensoredbyhim.

Acomparisonoftheunusedmaterial9andZuckerman’stestimonyreflectstheway inwhichZuckerman’s answerswere refashioned over time.OnAugust7,2006,aGMClawyerfromFieldFisherWaterhouse(FFW)putittohimthat

OneofourwitnesseshastoldusthatyoudecidedthataVNRaboutDrWakefield’swork shouldbedistributed to thepresspriortothepressconference.WhydidyouthinkaVNRwouldbeappropriate?10

Zuckerman flatly denied being aware of anyVNR.He claimed to haveseen it only after the press briefing, had “completely disapproved”of it,and insisted thathehadaskedHutchinson tostopanydistributionof theVNRtothepress.

Coonan raised the issue of the VNR at the GMC, leading Zuckermanpatientlyonwardthroughamazeofcontradictionandirrelevance.

Coonan:Therewasprepared,wastherenot,whatwascalledavideonewsrelease?

Zuckerman: I think that the issue of a video was discussedcertainlyandthereisnoquestionthatIagreedtoit.

HavingstatedinAugust2006thatheknewnothingoftheVNR,by2007Zuckermanwas,incontradiction,statingthattherewas“noquestion”thathehad“agreed”toitsproduction.

CoonanmovedontotheVNR’scontent.

Coonan:Areyousayingyoudidnotknowaboutthecontentofthevideonewsreleasebeforethepressconference?

Zuckerman:No.As I say, I knew that therewas going to beoneafter thepressbriefingandsecondly, Ialsosawcaptionsthatweretobeused…Havingseenthesub-headings—andIamended some of them— the press officer from the hospitalwrotetometosaythatthisdidnotmeanthattheseweregoingtobetheultimatesubheadings,becausethewordingsmaywellbechanged.Tomyhorror,infactthewordingswerechangedwhen I saw thevideoafter thepressbriefingand I instructedMrs Hutchison not to release the video because it did notreflecteitherthecontentsofthepressbriefingnordiditreflectthecontentsofTheLancetpaper,butsheunfortunatelytoldmethat the actual video had been released before the pressbriefing,whichsurprisedme.

Zuckerman claimed in evidence that he was surprised by the VNR’scontent and that he was unaware that it had been produced by anindependent company rather than the school’s medical illustrationdepartment.Hutchinson,ontheotherhand,stated:

I would have expected the Dean to be aware of the variousstages and to have seen a draft of the script before it wasfinalised. I remember that he took a close interest in thearrangements.AstheVNRwasfundedbythemedicalschool,Iwould expect that the Dean would have sanctioned theinstruction of Campaign Productions and would have had tohaveapprovedthecosts.

Hutchinsoncontinued:

I do not recall the Dean instructing me not to release thevideo… I am unable to say whether or not I discussed theminutiaewiththeDeanbutIcansaythathedidshowacloseinterestinthearrangementsfortheVNR,pressstatementandthepressbriefing.IdonotrecalltheDeanbeingsurprisedatthetimetheVNRwasproducedorthepressstatementreleased.I do not recall ever being told by the Dean that he was nothappyaboutthesearrangements.

ZuckermandeviatedonthepointofwhoproducedtheVNR.Coonanhadtoputsometensiononthelinetogethimback.

Coonan:Letus just takestock. Iamnot forpresentpurposesconcernedwithwhoproducedit.

Zuckerman:ButIam.

Coonan: I appreciate you might be. With respect, I am justaskingthequestions.Ifyouneedtomentionothermatters,they

canbedealtwithincross-examination.Doyoufollow?Thatistheprocesswehave.Iamjustseekingtoestablishtheextenttowhichyouwereawareofthecontentofthevideonewsreleasebeforethepressbriefing.

Zuckerman:Iwasawareofthesubheadings,notthecontents.Also,Iwastoldthattheseweresubjecttoalteration.

Coonan: Were you sent the script of the video news releasebeforethepressbriefing?

Zuckerman:No.

Coonan took Zuckerman to a memo from Hutchinson to him from theunusedmaterial−thatis,informationthattheprosecutionhad,forobviousreasons,decidednottointroduceinevidence.

Coonan:IhaveaskedyoutolookatthisbecausewhenIaskedyouwhetheryouhadseenacopyofthescriptofthevideonewsrelease,yousaidyouhadnot.

Thememo,dated January28,1998, refers to the fact that a transcriptofthe interviews for theVNRwas to be forwarded to thedean.There is ahandwrittennoteinthedateofreceiptstampthatstated“discussthe28/1pleasereturntoPhillipa.”ItwasinitialedbyZuckerman.

Zuckerman was hauled in toward the boat − toward the keen steel ofCoonan’sgaff.NextcamethecrucialevidencerelatingtomypositiononMMRvaccine.

Coonan: Professor Zuckerman, Iwant to go back, please, tothepreparations for thepressbriefing.When youwerebeingasked about these matters by Field Fisher Waterhouse11 inSeptember of last year, you told them that you did not knowthat Dr Wakefield would suggest the use of monovalentvaccinesinplaceoftheMMRvaccine.

Zuckerman:Thatiscorrect.

Coonan:Thatiscorrect,isit?Youdidnotknowthat?

Zuckerman: I knew that he held that view. I knew that thepressbriefingwastoberestrictedtothepathologicalchangesin the gut. The issue of vaccines was not relevant. I wasreassured on this by Professor Pounder, I was reassured onthis by Dr Wakefield, I was reassured by the letter thatProfessor Pounder wrote to the ChiefMedical Officer on 15January, assuring him that the press briefing would berestricted to pathological changes and therefore the issue ofmonovalent,polyvalentoranyothervaccineswasnotanissueto be discussed at the press briefing,merely the pathologicalchanges.

Roy Pounder,my boss, hadwritten twice to the ChiefMedical Officer.OncewasonJanuary9,1998,offeringtosendhimanadvancecopyofthepaper in line with previous responsible efforts to keep his departmentinformed.Thesecondletterwassent,datedJanuary18,1998,enclosingadraftofthepaperandalsoalertingtheCMOtothefactthatsomemembers

oftheteamwouldbelikelytorecommendsinglevaccines.Itindicatedtohimthathemaywishtohaveenoughsinglevaccinesonhandtodealwithincreaseddemand.InneitherofPounder’sletterswasthereevenahintofreassuranceaboutconfiningthepressbriefingtoadiscussionoftheboweldisease in autistic children as Zuckerman claimed. Similarly, no suchdiscussion had ever taken place between Zuckerman and me. Coonancontinued:

Coonan: Did one of the contents of the material which youwereshownhaveDrWakefield,inaccordancewiththescript,sayingthatthemonovalent,thesinglevaccine,tobe[sic]saferthanthepolyvalentvaccine?

Zuckerman challengedCoonan to produce anydocument supporting thisposition.ButCoonanheldback,stretchingthemomentalittlelonger.

Coonan:Ijustwanttoaskyouthis.Canyouremember,beforethepressbriefing,beingawareofDrWakefield’spositiononthedebatebetweenpolyandmonovalent?

Zuckerman:Yes,indeed,IwasandIhavealreadysaidso.Letme just qualify this. It was an exchange of correspondencebetweenDrWakefieldandIwherehewrotetome,assuringmethathehadconfidenceinpolyvalent12vaccines.

So, according to Zuckerman, there was correspondence, strangely notcontained in thefilessubmittedbyhimto theGMC, thatassuredhimofmyconfidenceinMMRvaccine.Coonantookhimtothatcorrespondencewith the rider “since you have raised it.” Smith, senior prosecutingcounsel, interjected on the basis that Zuckerman needed time to reviewdocuments that had just been “banged in front of him after 11 years.”

Coonan invited Zuckerman to take as much time as he needed.Zuckerman, even before he had received this evidence from the clerkstated, “I amawareofmy reply,but I justneed to see this letter,whichwasnotinmyfile.”LikeanIncapriestpredictingthelong-rangeweatherfromentrails,hewasreadywithareplytoaletterthatwasnotyetinhishand,notinhisfiles,andonewhichhehadn’tapparentlyreadin11years.CoonanpresentedhimwithmylettertoWalker-Smith−thatwascopiedtohimandstatedmypositiononMMR−andZuckerman’sresponse.

Coonan:The correspondence in effect reflects, does it not—these aremywords; youmay disagreewith them and pleasefeel free to do so — the polarisation of view which hademergedbythatstage?Isthatfair?Iamjustseekingaformofwords to summarise the two positions which we see in thesetwodocuments.

Zuckerman: It is stating Dr Wakefield’s position, yes.Absolutely.

Coonan: In relation to the fourth paragraph in the letter toProfessorWalker-Smithwhichwascopiedtoyou,yousee thebeginningoftheparagraph.Itsaysthis:“Inviewofthis,if…”Myemphasis—“…myopinionissought,IcannotsupportthecontinueduseofthepolyvalentMMRvaccine.Ihavenodoubtofthevalueofthecontinueduseofthemonovalent12vaccines,andwill continue to support theiruseuntil thecasehasbeenproven one way or another of the measles link to chronicinflammatoryboweldisease.”

In thecourseofyourevidencea fewminutesago,beforeyoutookafewminutestoreadthecorrespondence,Ithinkyoutoldthe Panel that Dr Wakefield had assured you that he hadconfidence in the polyvalent vaccine. In fact, he did not, didhe?

Zuckerman: So it appears, but from the conversations I hadwith Dr Wakefield, he assured me on three points: thatpolyvalent12 vaccines are useful, that his views onmonovalent12vaccines,whichwerewell-knownanddiscussedwiththepressin1997,nevermind1998,werewell-known,andheassuredmethattheissueofvaccineswillnotbediscussedatthepressbriefing.

Zuckerman had told theGMC that he had had correspondence fromme“assuring [him] that [I] had confidence inpolyvalent12vaccines.”Therewas no such correspondence. Quite the opposite; the correspondenceshowedthat Iwasemphaticaboutmylackofconfidence inMMR.NowZuckermanwas asking thepanel to believe that these reassuranceswerecontained in conversations between us where my position had shifteddramatically.Again,nosuchconversationshadevertakenplace.CoonanputthistoZuckerman:

Coonan: Professor Zuckerman, I have to suggest to you thatthatwasnotanassurance thathegaveyou inJanuary1998,becausethatistheveryoppositeofwhatthatfourthparagraphis saying, is it not? “… if my opinion is sought, I cannotsupportthecontinueduseofthepolyvalentvaccine.”

Zuckerman: I think that you should address this question of

whether he discussed thiswithme toDrWakefield,whowillhavetoansweritunderoath.

Coonan: I am just going to suggest, and contentmyselfwithsuggesting for present purposes, that your recollection is atfault.

Zuckerman:Ihavetodisagreewithyoursuggestion.

When Zuckerman was asked about his response to my letter and, inparticular,hisuseoftheword“monovalent”inthesettingof“Yousupportthecontinueduseofthemonovalentvaccinesandyouwritethatyouhavenodoubtof their value,”he claimed in the interviewwithFFW in2006andagainunderoath inhisdirect evidence to theGMC tohavemadeatypographical error. Apparently, he had intended to use the word“polyvalent”(MMR)instead.Infact,whenhewrote“monovalent”hewasrespondingdirectlytothelineinmyletterthatread“Ihavenodoubtofthevalueofthecontinueduseofthemonovalentvaccines,andwillcontinueto support their use.” Zuckerman was to make the same alleged“typographical”errortwiceinthesameletterwheninthefinalparagraphhe reiterated, “It is vital, in your own interests and that of children, thatyou clearly state your support for monovalent vaccination.” In pressingZuckermanonthereferencetomonovalentvaccinesinPounder’slettertotheCMO,Zuckermanhadameltdown.Inlightofthis,Coonanstartedbutnevergottocompletehisquestion:

Coonan:Atanyrate,knowingwhatwas in,at thevery least,this [Wakefield’s] letter and knowing what was in the

ProfessorPoundercorrespondencewhichyouhadreferredto,thecorrespondencewiththeChiefMedicalOfficer---

Zuckerman:No,no. Ididnotsee that letter.The letter Isawwaswhere hewas talking aboutmonovalent vaccines. I onlysaw the internet more recently. I had no knowledge of thatletter. Iwas referring to the letter that hewrote to theChiefMedical Officer, assuring the Chief Medical Officer thatnothingwould be discussed other than pathological changes.Thatletterisonfilesomewhere.

Coonan tried again, but Zuckerman, in a state of high anxiety, leaptstraightin.

Coonan:ThisisaletterfromProfessorPounderto---

Zuckerman:TheChiefMedicalOfficer.ThesecondletterIdidnotseeuntilIsawitonMrDeer’sinternetsite.

Bynow,CoonanwasgrowingimpatientofZuckerman’sdissembling.

Coonan: We will leave that to one side, because I amconcernedwithyourstateofmindatthetime.

Zuckerman:Mystateofmind?

Coonan:Yes.

Zuckerman: Good heavens. I find this quite offensive. Whatareyouimplying?

WhileCoonanwasreferringtowhatZuckermanwasactuallythinkingin1997,Coonan’sreferencetohis“stateofmind”causedZuckermantoloseit.Hissenseofaffrontcannotbecapturedonapage.Coonanpressedon:

Coonan: The fact is that, knowing what you did from thiscorrespondence, from this exchange of letters between DrWakefield toProfessorWalker-Smithand your reply, youdidnotstopthepressconference.

Zuckerman: No, I did not. I should have done but I wasassuredthatthiswouldnotarise.So,thereweare.

Coonan:Atthepressconference,Iamgoingtosuggesttoyouthat,atsomestage,aparticularjournalistraisedthequestion—and this is a summary, not a verbatimaccount—ofwhatparents should do in relation to MMR and you directed thejournalisttoDrWakefieldforananswer.

Zuckerman: I directed the question to Dr Wakefield for ananswer,yes.

Coonan:AfterDrWakefieldgavehisanswer,youexplainedtothe journalists gathered there the basis of Dr Wakefield’stheory, namely bywhich the immune system is challenged by

thecombinationofthreevaccines.Thatwashistheory.

Zuckerman: What I recall happened is as follows. Thequestion was asked. I certainly directed the question to DrWakefieldforananswer.Whenhegavehisanswer,whichIdidnotexpect…ThereasonwhyIdirectedhisquestion—andletme illustrate to you my state of mind at the time— was asfollows. Single measles vaccines were not available in theUnited Kingdom, were not used in the United Kingdom, andwerenotusedinanyofthewesterncountries,theUnitedStatesorCanada. I knew thatDrWakefield had a young family. Ittherefore was inevitable that they were protected with MMRand the expectation was that he would say, “Yes, I used theMMR to vaccinatemychildren”.Whenhe replied in thewaythat he did, I immediately directed the question toDr SimonMurch, who was the paediatrician, who rejected thatcompletelyandsaidthathehadfullconfidenceinMMR,whichI did as well. That is the position. Unless you show me thevideo,Ireallycannotrememberwordforwordwhathappened,butthatwasthestateofmind,touseyourterm,behindthis.

Infact,thevideoofthepressbriefingwasplayedtotheGMChearing.Itborelittle,ifany,resemblancetoZuckerman’srecollectionofwhathesaidwashis“stateofmind.”Capturedonthevideowastheinevitablequestionof what parents should do about vaccination as Zuckerman’s briefingturned into a free-rangingQ&A.Zuckerman had told FFW in 2006 thatmy statement about splitting theMMR vaccine “had been outrageous.”ThetruthwasthatZuckermanhadknownforsomeweeksexactlywhatmypositiononMMRwas.According toHutchinson,Zuckermanhad calledforapressbriefingpreciselytoreflectthedifferingopinionsonMMR,andasshesaidinherwitnessstatement,“Hecontrolledwhospokeandwhen.”If he hadhad the concerns that he protested to theGMC, then he could

have prevented the briefing, banned me from attending, or, at the veryleast, directed the question to someone else who continued to supportMMR. He did none of these things. He asked me to respond to thejournalist’squestion.Ididsoexactlyinaccordancewithmystatedbeliefsandintentions.

Before the GMC, Zuckerman expressed the surprise that he had feltbecause“singlevaccineswerenotavailableintheUK”;wrong,theywere.Zuckermanhadnobasis for believing thatmychildrenhad received theMMRvaccine.Andhecertainlydidnot, ashe said, “immediatelydirectthequestiontoSimonMurch.”Instead,withthecalmauthorityofamanwhohadpreviouslydescribedhimselftotheGMClawyersas“theworld’sleading virologist in clinical virology,”13 he delivered a preparedexplanationofaplausiblebasisformyconcerns.

Infact,atthepressbriefing,Zuckermanhadstated:

Can I just try and actually answer that question moreprecisely?MMRconsistsof3 liveattenuatedvirus strains. InotherwordsweareadministeringtothechildrenintheMMRthree attenuated vaccine strains against measles, againstmumps, against rubella. A combination of three differentviruses… it is theoretically possible that the immune systemwouldbechallengedby3 separatevirusesand thatwouldbethe rationale I think for Dr Wakefield’s recommendation forgivingthesevaccinesseparatelyandofcoursebeforetheMMRwas introduced these preparations were available asmonovalentvaccines.”[Remainderofrecordinginaudible.]

After a brief interruption from the floor and a statement about how safe

vaccineswere,hecontinued:

Onepossibleexplanationisthatattheageofonetheimmunesystemisnotfullydeveloped.Thereforebychallengingitwiththreeliveviral,liveattenuatedstrainsmaybeassociatedwithsideeffects.

Hehadprovidedsupport formyposition!Itwasonly later thatheaskedMurchforhisopinion.RatherthanZuckerman’sportrayaltotheGMCofMurch’swordssaid to“reject…completely” the idea thatMMRmaybelinked with this new syndrome, Murch had actually endorsed thepossibilitythat,forreasonsofapoorlyfunctioningimmunesystem,somechildren“mayhavedifficultyinhandlingviruses.”

Inreviewingthevideoofthepressbriefing,itwasevidentthatZuckermanwasreferringinhiscommentarytopre-preparednotes.Havingpreviouslytold theGMC that vaccineswere not to be discussed, it seemed curiousthathisnotesatthepressbriefinglikelyincludedthisverytopic.

TherecanbelittledoubtthattheGMCPanelmighthavebeenpersuadedthat,inme,theyweredealingwithatruevillainbaseduponmyex-dean’sdamningindictment.Ifso,theyweremisled.

The GMC’s lawyers had briefed Zuckerman in advance of his oraltestimony,warninghimnot tobecaughtoffguardbyhostileallegationsthathehad“purposefullydirectedaquestiontoDrWakefieldatthepressconference, knowing what his answer would be i.e. that it would becontroversial.”14 Zuckerman described this as “a lie,” but that he couldrespondtoit.Theevidencewouldsuggestotherwise.

Zuckermanwasamanofconflictingagendas;ontheonehand,hisroleasdean had been to support academic freedom. On the other, he was putunder considerablepoliticalpressure from theDepartmentofHealth andWorldHealthOrganization (WHO) in respect ofmy legitimate researchintovaccinesafety(seeendnotes2,3,5,and7ofChapter3,“TheDean’sDilemma”andendnote8ofthischapter).Whileinitiallyusingtheautismwork to promote the medical school in the media, it rapidly became adecayingalbatrossabouthisneck.InaratherclumsyvoltefacebeforetheGMC hearing, Zuckerman’s imperfect memory was exposed. Time andagain, he was undone by the contradictions between his testimony, thedocumentedfacts,andtheopinionsofotherwitnesses.Intheend,hedidprotesttoomuch.

Endnotes1 January 12, 1998 letter from AJW to JohnWalker-Smith, copied toProfessorArieZuckerman,ProfessorRoyPounder,Dr.SimonMurch,Dr.MikeThomson,andDr.MarkBerelowitz.

2 Intestinaldisease.

3 Emphasisadded.

4 Singlevaccines;emphasisadded.

5 IBD—inflammatoryboweldisease.

6 Namesremovedforlegalreasons.

7 Emphasisadded.

8 WitnessstatementofPhillipaHutchinsonforFieldFisherWaterhouse.September18,2006.

9 Informationthattheprosecutiondecidednottointroduceinevidence.

10 AttendancenotefromGMClawyers.August7,2006.Questionspages2and3;answerspage3.

11 GMClawyers.

12 Emphasisadded.

13 Attendance note:Quote fromZuckerman toGMC lawyers inGMC“unusedmaterial.”August7,2006

14 Attendance note:Quote fromZuckerman toGMC lawyers inGMC“unusedmaterial.”May16,2006.Para6.

CHAPTERSEVEN

HortonandTheLancetTexas,February29,2008:Thefilingcabinet’stopdrawerwascrammedandfullyopen,threateningtotopple.Carmel,mylong-sufferingwife,wasoblivious, hermind elsewhere. Shipping theWakefields’ worldly goodsfromKewGardens,London, to professional and political exile inTexashad not been without problems. Two filing cabinets had remained in awarehouseinLondon’sDocklandsandonlythreatoflitigationhadsecuredtheironwardpassagetotheUS.Andthedocumentstheyheldweretobekeyintheunfoldingmystery.Ourlongitudeswerenowreversed:shewasinTexasandIwas inLondonpreparing to take thewitnessstandbeforetheGMC’sFitnesstoPractisePanel.“I’vefoundit!”sheexclaimedoverthephone,“I’vefoundtheoriginal‘Rouseletter.’”

Somuchof themisrepresentation of thework ofmy colleagues andmehasbeencenteredonattemptstodiscreditit,startingwiththeallegationofa “hidden conflict of interest.”Thiswas triggered byBrianDeer’s falseassertionthatTheLancet1998studyhadbeenfundedbytheUK’sLegalAidBoardandthatthis“fact”hadbeenkeptsecretfrombothTheLancetand my colleagues. In my opinion, leading the disorderly vanguard ofthoseseekingtodistancethemselvesfromTheLancetpaperin2004,hasbeentheeditorRichardHorton.

RichardHortonhas been editor ofTheLancet since 1995.As editor, hehas overall responsibility for everything that is published in the journal.Followingsubmissionof“ThatPaper”toTheLancetinmid-1997,1Horton

andhisteamhadsentitouttofourindependentandanonymousreviewers.ThepaperwaspublishedinFebruary1998withanaccompanyingeditorialfromtheUSCentersforDiseaseControlandPrevention(CDC),warninggravely of the dangers of measles. Subsequent exchanges in the“Correspondence” columns of The Lancet were charged as would beexpected. One correspondent was Dr. A. Rouse, a public health doctorfrom thewest ofEngland.His letterwaspublishedonMay2, 1998.Aspublished—andthisiscrucial—itread:

AfterreadingAndrewWakefieldandcolleagues’articleIdidasimple internet search and found the Society for AutisticallyHandicapped.Idownloadeda48pagefactsheetproducedforthesocietybyDawbarnsafirmofsolicitorsinKing’sLynn.ItseemslikelythatsomeofthechildreninvestigatedbyWakefieldetalcametoattentionbecauseof theactivitiesof thissocietyand information from the parents referred in this way wouldsuffer fromrecallbias. It isapity thatWakefieldetaldonotidentifythemannerinwhichthe12childrenwerereferred(e.g.fromlocalGPs,selfreferralviaparentsorsecondary/tertiaryor international referral). Furthermore if some childrenwerereferred directly or indirectly because of the activities of theSociety for the Autistically Handicapped, Wakefield shouldhavedeclaredhiscooperationwiththatorganization.

It is uncertain as to howmuch attentionRouse had actually paid toTheLancet paper itself since, in relation to patient referral, the paper statedquite clearly that the children were “self-referred,” meaning that theparentshad initiated the request tobe seenat theRoyalFree.Thepaperalsodescribedthemodeofreferralviathechild’sdoctor.

WhileIhadneverheardof theSocietyfor theAutisticallyHandicapped,

myroleinthelitigationwasnosecret,havingbeenreportedinthenationalpressasearlyasNovember1996.2Idulyrespondedtothevariousissuesraised by the correspondents. John Walker-Smith and Simon Murch,anxious forpersonal reasonsnot tobeassociatedwithvaccine litigation,approvedmyresponsebutchosetokeeptheirdistance.MyresponsetotheRouseletterread:

A.Rouse suggests that litigation biasmight exist by virtue ofinformationthathehasdownloadedfromtheinternetfromtheSocietyoftheAutisticallyHandicapped.

Pausing there, it would be reasonable to ask why I would refer to“litigation bias.” It is amost unusual term and certainly not included inRouse’sletteraseventuallypublishedinTheLancet.SufficeittosaythatIwas reminded of its actual content 10 years later following Carmel’sdiscovery.

ContinuingwithmyresponsetoTheLancetin1998,IwentontodescribemypastandcontinuinginvolvementintheMMRlitigation:

Only one author (AJW) has agreed to help evaluate a smallnumber of these children on behalf of the Legal Aid Board.These childrenhaveall been seenexpresslyon thebasis thatthey were referred through the normal channels (e.g. fromGPs, child psychiatrist or community paediatricians) on themerit of their symptoms.AJWhadnever heardof theSocietyfor the Autistically Handicapped and no fact sheet has beenprovided for them todistribute to interestedparties.TheonlyfactsheetthatwehaveproducedisforGPswhichdescribesthebackground and protocol for investigation of children withautism and gastrointestinal symptoms. Finally all those

children referred to us (including 53 who have already beeninvestigatedandthoseonawaitinglistthatextendsinto1999)have come through the formal channels described above. Noconflictofinterestexists.

Thatwaswherematters rested in 1998 and, given thatmy involvementwith the lawyers seeking to establish whether there was a case in lawagainst the vaccine manufacturers had been widely reported in the laypressandnowconfirmedinthisexchangeoflettersinTheLancet,as farasIwasconcerned,thereitwouldrest.Clearlyatthetime,Hortondidnotfeelitnecessarytoexplorethismatterfurther.

In the event, as time moved on, the cauldron of litigation, claim, andcounter-claim came to the boil, and by the end of 2001, my career inBritain was over. Over the intervening years there have been furtherpublications,some inTheLancet8 thathavebeenused to support claimsthat any links betweenMMR vaccine and autism have been disproved.ThesepublicationshaveoftenbeenheraldedbyafanfareofpublicityandHorton’sappearanceinthemediaseekingtoexoneratetheMMRvaccine(seebelow)fromanypossiblelinkwithautism.

Horton had been under considerable pressure since the publication of“ThatPaper.”Hewroteabookin2003titledSecondOpinion.TheMMRissueisdescribed.HortonrehearseswhataterribletimehehadfollowingpublicationofTheLancet paper in1998;howhewas telephonedby theformer president of the UK’s Academy ofMedical Sciences “in a furyabout the publication of a paper that raised questions aboutMMR.”Hetellsofadreadfulexperienceatadinnerpartywherehewasasked ifhewould ever be forgiven for this publication and its effects.We agonizewith him as he relives the process of sending the paper for four

independent reviews prior to accepting it, the editing to ensure that thereaders knew there was no proof that MMR vaccine caused “this newsyndrome,” how the preliminary nature of the findingswas emphasized,and how the public was reinformed of the importance of measlesvaccination.Heshareswithusthesometimes“highlypersonal”attacksonhim−“unusual inscientificdebate.”Finally,Hortonconfessesthat,withregardtothepublic’sconcernaboutthesafetyofthevaccine,“despiteourbesteffortsaseditorsasnowballingeffecthappened.”

The drama intensifies as Horton’s readers are told how myrecommendation in Feburary 1998 that parents might opt for singlevaccinesuntiltheissuehadbeenresolvedscientificallywas

…forallpracticalpurposesa recommendation toparentsnotto have their children vaccinated at all since the componentswerenotavailableseparatelyintheU.K.

This is a serious allegation and it is false; single vaccineswere licensedandavailableat thetime.Iknewthiswhenmakingmyrecommendation;otherwiseIwouldnothavemadeit.Theimportationlicenseforthesinglevaccines was withdrawn by the Department of Health in August 1998,meaningchoicewasnolongeravailableviatheNationalHealthService.3Atatimewhendemandwasgreatest,theoptionforconcernedparentshadbeen removed,effectivelyputtingprotectionofMMRvaccinationpolicybeforeprotectionofchildren.

Hortontellsreadershow“embarrassinglynaïve”hisactionswerein1998,how he should have tried to persuade me not to have recommendedsplittingthevaccine,howhewastoo“laissez-faire,”andhowhefailedtomanagethemediaatthattimebuthaslearnednowhowintegralthisisto

his responsibilities. But his book also tells us that he does not regretpublishing the original paper since progress inmedicine depends on the“freeexpressionofnewideas,”andinscienceitwasonlythiscommitmenttofreeexpressionwhich“shookfreethetightgripofreligiononthewayhumansunderstoodtheirworld.”Mywork,hesuggests,hasopenedupanimportantnewfieldofscience−therelationshipbetweenthebrainandtheintestine in autism. He goes on to tell those still awake that I havepublishedextensivelyabouttherisksofMMRandmeaslesinfectionsince1998,butthatothershave

…convincingly refuted any association between the vaccineandautisminlargestudiesacrossdifferentpopulations…NotonepersonorgrouphasconfirmedtheoriginalfindingsintheLancetpaper.

Thisisthemantra,thehungryfalsehood,handeddowntothemediabytheDoH,swallowed,andregurgitatedinthepopularpressonaregularbasis.With respect tomycolleagues,Hortongoeson to say that JohnWalker-Smith

…was and remains sceptical of a direct link with the MMRvaccine but believes that there appears to be a small highlyselectedgroupofchildrenwherethereisarisk.

Horton’s 2003 book concludes with the lessons to be learned from this“sadaffair”that

…has left Wakefield’s reputation unfairly in tatters, virtuallyunemployableintheUKfortheworkhewantedtodo.

Meanwhile,asChristmasapproached,BrianDeerthefreelancejournalist,unknown toallbuta few,was thumbing throughdocumentsprovided to

himinthemostextraordinarycircumstances.Strictlyconfidentialmedicalrecordsofdisabledchildrenhadbeenprovided tohimapparentlyby theNorthLondonSpecialHealthAuthority that hadoversight for theRoyalFree.

On theMondaymorning of February 9, 2004,Carmel, alone in theUKwith our four children, lost her job as medicolegal consultant to StokeMandevilleHospitalduetoregulatorychanges.Intheschoolyard,oneofherfriendstriedtocheerherup:“Wellatleastthingscan’tgetanyworse!”On her return home, she received a call from Abel Hadden, a publicrelations consultant, informing her that Deer was seeking a response tovariousallegationsaboutmeandthathewasabouttogopublicwiththeseallegations. The nub of them was that I had published research in TheLancet in 1998, and that I had been paid £55,000.00 by the Legal AidBoardtodothis,despitethefactthattheclinicalinvestigationsdescribedin thepaperhadbeenpaidforby theNationalHealthService.Deeralsoalleged that none of my colleagues at the Royal Free knew that I washelpinginvestigateapotentialclaimonbehalfofautisticchildrenandthatIhadplottedwith lawyerRichardBarr.Together,according toDeer,wehadcontrivedanMMRprobleminordertosuethevaccinemanufacturers.Additionally, it was Deer’s “clinical” opinion that the tests on thesechildrenwereinappropriate,invasive,andunethical.

Meanwhile,DeerhadtelephonedHortontowhethisappetiteandproposea full face-to-face expose of my wickedness. Horton’s response wasdescribedbyDeerinane-mailtohiscommissioningeditor,PaulNukki,asenthusiasticsaying,“ifthisholdsupintermsofdocumentation,thiscouldbegroundstoretractthepaper.”5Strangelyprescientwordsitwouldseem,asIamwritingthis6yearslaterwhenHortonhasdonethatverything.IflewbackfromtheUSandwalkedintoameetingwithrepresentativesofTheSundayTimeswhileDeertantalizedHortonandcolleagueswitha3-

hourpresentationthatrevealedthefruitsofhislabors—“evidence”ofmyallegedfinancialandethicalimpropriety.

That same afternoon a meeting was hastily arranged at The Lancet’soffices between the senior authors of the paper. I had not seenWalker-Smith, Murch, or Horton for many years. Unfortunately, both of mycolleagueshadgiven interviews toDeer in themeantime that ledhim tobelieve that theyhadhadnoknowledgeofmy involvement in theLegalAidBoardwork.WhilethismisunderstandingmayhavearisenoutofthemannerofDeer’squestioning,ithadtheeffectoffacilitatingwhatwastobecomethelongestGMCinquiryinhistory.

Horton’s precise understanding of what Deer had alleged is importantbecause it is inconsistentwithwhathewas toclaim lateron.Horton setouthisunderstandingoftheallegations.Itwasclearthathewasoperatingon thebasisof theallegation thatTheLancet reporthadbeen fundedbytheLABandthatthisobviousconflictofinteresthadnotbeendisclosed.Paraphrasing here,Horton openedwith the allegations to the effect that:I’vehadareporterfromTheSundayTimesherewithaLiberalDemocratMPbythenameofEvanHarris.Thejournalist—Deerwashisname—alleged that youAndy [wewere on first name terms at this stage]weregiven£55,000bylawyerstoinvestigatesomeofTheLancetchildren,thattheworkreportedinTheLancetwasfundedbylawyersandthisfactwasnotdeclaredtomeordisclosedinthepaper,andthatyoukeptthissecretfromyourcoauthors.

Apparently,Murch’s“jawdropped.”Irespondedthat,infact,TheLancetpaperwasnotfundedbytheLABorbylawyers−thatthefundingwasforanentirelyseparatescientificstudylookingforevidenceofmeaslesvirus

inthediseasedintestineofaffectedchildren.Thechildrenwereallreferredfor clinical investigation of their symptoms, and their referral, whichpredated any legal involvement, had nothing to do with lawyers orlitigation. Istated that, inmyopinion−effectively the testofconflictofinterest requiredof anauthorbyTheLancet at that time− therewasnoconflictofinterest.Presentedwiththisapparentlynewtakeonthematter,Hortonpausedandproposed,witharenewedsenseofpurpose,thattherewas “the possibility of aperceived conflict of interest.” Iwas perplexedand, asHortonwas later to confirm in response to the panel chairman’squestionattheGMC,“surprised.”ThepossibleperceptionsofotherswerenotpartofTheLancet’sdisclosurerequirementsin1996-98.ThechildrenhadnotbeenlitigantsatthetimetheywerereferredtoWalker-Smith,theirclinicalinvestigationwasnotinfluencedbywhethertheymightlitigateatsomefuturetime,andI−theonlymemberoftheRoyalFreeteamtobeinvolved in litigation − played no active part in the interpretation ofclinical findings in these children. My contribution, in addition to theoriginalideas,hadbeenthecollationofthedataanddraftingofthepaperbasedupon the findings of others.Horton and Iwere to argueback andforthonthedefinitionofaconflictformuchoftherestofthemeeting;itfinishedwithuscompletelyatoddsonthisissue.

Further allegations fromDeer hit closer to home forWalker-Smith andMurch.Theaccusationthatchildrenhadbeen“sourced”bylawyersratherthan being clinical referrals from other doctors and the claim that thechildrenhadbeensubjectedtoinvasiveproceduresasanexperimentweredeeplydisturbing.

Horton gave the three of us 48 hours to piece together events that hadtakenplaceupto8yearsearlierandtocomebacktohimwithourwrittenstatementsinorderthatthesecouldbepublishedinTheLancetonlinethatFriday.Assignmentsgiven,themeetinginHorton’sofficebrokeup.What

remainedwas a sense of despair − real despair.One thing that Iwas torecollectmuch laterwas that onHorton’s desk that day, untouched andunreadduringthecourseofourmeeting,wasacopyoftheletterspageofTheLancet—noneotherthantheRouseletterandmyresponsefromMay2,1998.

Forourassignments,Iwastodealwithissuesoflitigationandconflictofinterest; Walker-Smith was to deal with the clinical referral andinvestigation that had taken place; Murch was to address the issue ofethical approval and Professor Hodgson, the clinical dean, with themedicalschool’sposition.Therewasanurgentmeetingofthelatterthree,accompanied by Horton, at the Royal Free the next day to review theclinical records, departmental logs of admissions, and procedures andethicscommitteeapplicationsandapprovals.Iwasnotinvited.Followingmy forced departure from the Royal Free, many documents had beennecessarilydestroyedeitherforreasonsofconfidentialityorsimplyweightofnumbers.Whatremainedhadbeengatheringdustinrandompilesinmygarage.HadtherealRouselettercometolightatthattime,thestorymighthavebeenaverydifferentone.

On the last day of the children’s half-term break, Friday, February 20,Carmeltookthetwoyoungestchildren,ImogenandCorin, toseeSchoolofRock.Inthemiddleofit,IcalledonhercellphonewiththenewsthatIhad just had a telephone call fromHortonwho had toldme howmuchrespecthehadforme,howhedidnotdoubtmyhonestyandintegrity,andhowhesympathizedwiththeinvidiouspositioninwhichIfoundmyself.HeprofessedtobefullofadmirationforthefactthatIhadbeenabletoputupwithsomuchadversityforsolong.Shewassilent.“Whatthehellisheupto?”washer terseresponse.OnlythendidIrealize thatHorton’scallheraldedanewturnofevents−andthatnothinggoodwouldcomeofit.

Within hours of this call, Horton was on every major news channelproclaiming that The Lancet paper of 1998 should never have beenpublished.Hedeclaredthepapertobe“fatallyflawed.”HetoldtheBBC:“…ifwehadknowntheconflictofinterestDrWakefieldhadinthisworkI think that would have strongly affected the peer reviewers about thecredibilityofthisworkandinmyjudgmentitwouldhavebeenrejected.”

Much later I learned, via a friend of one of the deputy editors of TheSundayTimes, thatitwasHortongoingpublicinthiswaythatledtothepaper’s decision to publish Deer’s article. Horton had created a mediamonster thirsty for my blood, and despite anxieties about the article’sfactualbasis,theeditorialteamatTheSundayTimesdecidedtorunit.

HortonappearedthefollowingmorningontheTodayprogram(theUK’sflagship radionewsprogram)with JohnHumphreys, theelder statesmanofBritishmediainquisitors.Hortontoldlistenersthatitwashisviewthatthe work was entirely flawed. Pressed on this by Humphreys, he wasforced toagree that the findingofanewsyndromeofautismandboweldiseasewasnotflawed,rather itneededtobeinvestigatedfurther.WhenquestionedaboutMMR,theseasonedskepticinHumphreyswassurprisedasHortondeclaredthatitwas“absolutelysafe.”

I was headline news in the next day’s edition ofThe Sunday Times onFebruary22.ByMonday,mydetractorswererushingtogivesoundbitesafter The Sunday Times article. Professor Liam Donaldson, the ChiefMedical Officer, took his opportunity on the Today program when heobserved:

Now a darker side of this work has shown through, with theethicalconductoftheresearchandthisissomethingthathastobelookedat.

Meanwhile, on IndependentTelevisionnews,PrimeMinisterTonyBlair(whohadbeensosecretiveaboutthefactthathissonLeohadnothadtheMMR) remarked, “Ihopenow thatpeople see the situation is somewhatdifferentfromwhattheywereledtobelieve.”

Elsewhere, Deer was busy preparing an indignant, public-spiritedcomplaint to the GMC alleging “possible professional misconduct ofAndrewWakefield and his colleaguesWalker-Smith andMurch.” Alsovocal afterTheSundayTimes articlewere ShadowHealthMinister4 Dr.Liam Fox and, once again, the Chief Medical Officer, Dr. LiamDonaldson. Both called for an enquiry by the GMC. Ironically, I hadbeatenthemalltoit.IhadalreadycalledontheGMCforaninvestigationofthemattermyself.

Itwasanother journalist, JeremyLaurence,healthcorrespondent forTheIndependent, who first jogged mymemory when he wrote in his paperlaterthatweektosaythatmyinvolvementinthelitigationwasnothidden,buthadbeendisclosedinTheLanceta fewweeksfollowingpublication.As a result of this revelation I sought an apology fromHorton throughlawyersMessrs.Carter-Ruck.

We have been consulted by our client, Dr AndrewWakefieldwith regard to the statement which you issued on the 20thFebruarywhich togetherwith interviews you have given, hasreceived widespread media attention, as was only to be

expected.

Ourclient,asyouwillknow,entirelyrejectsyourassertionthathis work for the Legal Aid Board gave rise to a conflict ofinterest in relation to the paper published in The Lancet inFebruary1998,letalonethatitleftourclient’swork“fatallyflawed”asyouhavealleged.This,however,isamatterwhichour client considers may be best resolved through a GMCenquiry, which has been proposed and which our clientwelcomes.

Therecan,however,benodisputeconcerningourclient’sgoodfaith.Theplainimplicationsofthestatementyouhavemadeisthatourclient,fornearlysixyears,withheldnotonlyfromTheLancetbutfromhiscolleaguesthathewasalsoengagedbytheLegalAidBoardtoconductresearch.This,asyouknow,isnottrue.Therewasnosecretandourclientmadenosecretofhiswork for theLegalAidBoard. Indeed, the letterpublishedbyourclientintheLanceton2May1998makescrystalclearnotonlythatthefactthatourclientwasengagedinotherresearchwas publicly available on the internet but also that the veryissueofanallegedconflictwasraisedandrefutedbyourclientat the time, ina letterwhich,asEditor,youwereresponsiblefor passing for publication in the Lancet. It is in thesecircumstancesamatterofgraveconcern, that, sixyearsafteralloftherelevantfactswereinyourknowledge,youchosenotonly to dismiss our client’s work but to cast doubt on hishonesty.

Thepurposeofthisletter,whilstreservingallourclient’slegalrights, is to invite you to agree promptly to publish a fullapology to our client, in a form, manner, and terms to beagreedbyhim.We trustwe shallhear fromyouwithin sevendays.

Needlesstosay,weneverreceivedanapologyandwerenotinapositionfinanciallyto takethematterfurther.AppealingtoHorton’ssenseoffairplay had been naïve. His response through Olswang, The Lancet’s lawfirm,isimportantandisreferredtolater.

Horton,however,clearlyremainedtroubledthathehadnotdoneenough.AshehadindicatedtoDeerwhentheallegationswerefirstmade,hemighthavegroundstoretractthepaper—expungeitfromhistory.Intheevent,all that he could manage was a “partial retraction,” i.e., that anyinterpretation of a possible association between the children’s conditionand MMR vaccination was in error. His idea, offered to me over thetelephoneasanolivebranch,was ludicrousonat least twocounts.First,the 1998 paper had never provided the interpretation thatMMR causedautism; second, it is impossible to retract a possibility. I considered thatsucharetractionwouldbedeeply insulting to theparentsof thechildreninvolved, rendering their story somehow invalid, in the absence ofappropriateinvestigation.Tenofthethirteenauthors,someofwhomhadlistened firsthand to the parents’ stories and with good reason believedthem, were persuaded to join the partial retraction of an interpretation.This letter of “retraction of an association” was published onMarch 6,2004, which was 16 days after the matter had first been raised. Themessage inevitably conveyed in themediawas that the entire paper hadbeenretractedandwaseffectivelydiscredited.

Threeof the authors,Dr.PeterHarvey,Dr. JohnLinnell, and I,wrote along and detailed letter toThe Lancet outliningwhywe considered anyretraction to be amockery.We explainedwhy therewas no conflict ofinterest andwhy, in the absenceof a causal interpretationattributable tothe MMR in The Lancet paper, there was nothing to withdraw. Thismeasured anddetailed letter,written by the three dissenters,was sent toThe Lancet at the same time as the retraction letter. In the interests offairness,bothpositionsshouldandcouldhavebeenviewedtogether.Butwhile theretraction letterwaspublished toablazeofpublicity, it tookafurther6weeksforourresponsetoappearonApril17,2004.Whenitdidfinallyappearitwasinserteddiscreetlyhalfwaydowntheletter’spage.

Horton’sdeterminationtowashhishandsofhispartinthepublicationofThe Lancet paper was paying off. This was evidenced in an exchangebetween Member of Parliament Evan Harris (Liberal Democrat) andCrispin Davis, Chairman of Reed-Elsevier, The Lancet’s proprietor andHorton’s boss, which took place at the UK government’s Science andTechnology Committee on March 1, 2004. Referring to the Rouse/Wakefieldexchange,DavistoldHarris:

Youcanimaginethatitisvirtuallyimpossibleforeveryeditortoresearcheverysingleauthorintermsofconflictofinterest,and in this one Dr Wakefield said there was no conflict ofinterest,andinfactthreemonthslaterinwrittenformrepeatedthat therewasno conflict of interest. Inall fairness, I donotholdoureditortoblame.

As an aside, readers may be interested to know that on July 1, 2003,9Crispin Davis wasmade a non-executive director of Glaxo SmithKline,oneof the largestpharmaceutical companies in theworld,manufacturersofMMR,andoneofthecodefendantsintheMMRlitigationwithwhichI

wasassistingtheLAB.Inthesummerof2004,Daviswasknightedforhisservicestotheinformationindustry.10

HortonwastopublishyetanotherbookonhisMMRexperience,chartingtheeventsfromFebruary22throughAugust1,2004.Itwasintheshopsbytheautumn,andhewaspromotingitwithalecturetour.Thenewsofthisliteraryevent,togetherwithfurtherpresscoverageoftheMMRissue,actedasacatalystforCarmeltomakecontactwithHortoninordertoputtherecordstraightbuttolittleavail.OnFriday,September10,2004,Dr.LiamSmeethappearedontelevision, trumpetinghisstudythatpurportedtoshownolinkbetweenMMRandautism.Thisdeeplyflawedpaper,6thatwas conducted in a manner contrary to the authors’ intentions, wasproclaimedbymanyasthe“definitivework”andthe“largeststudy,whichconfirmedthattherewasnobasisforanyconcernsaboutthelinkbetweenMMRandautism.”Hortonwashotonhisheels.HeappearedonChannel5 News on Friday, September 9, 2004, lauding the Smeeth paper,dismissingmyworkas“smokeandmirrors,” reassuring themasseswiththeanecdoteofhisdaughter’svaccination,andcommentingon theradiopollof its listeners.Thepresentermayhavebeenpersuaded,butnot thepublic.

PRESENTER: Well that personal testimony is a veryconvincingargument.Letme tell youaboutour5NewsClubpolltoday.We’reaskingpeopleifthey’reconvincedtheMMRvaccineissafe.17%−Yesconvincedit’ssafe;83%−Nonotconvincedit’ssafe.

Horton, uncertain how the public might ever be persuaded of MMR’ssafety,consideredthistobeadisaster.Hecontinued:

AndcontrarytowhatDrWakefieldsays,hisevidence,hisso-

calledevidence,thatthemeaslesvirusisactuallylinkedtothissyndrome, you can actually find the measles virus in thesechildren, has been refuted time and again in otherinvestigations.

This was an interesting assertion when, at this stage, no otherinvestigationshadbeen reportedon thedetectionofmeaslesvirus in theintestine of autistic children. The presenter explored Horton’s positionfurther:

“Do you think therewill be any surveys, any research done,thatwillsatisfyDrWakefieldthathisoriginalthesismayhavebeenmistaken?”Hortonreplied,“NoIdon’tthinkhewilleverbe satisfied.He’s investedhis entire careerand reputation inthis belief, this hypothesis. For him to refute it now wouldalmostbeanegationofhisentirepersonality…”

Carmel, frustrated with Horton’s treatment of me, e-mailed him,threatening togo tooneofhis lectures to takenotes forabookshewasconsideringwriting.Herepliedbyreturne-mail:11

Youmay know that I too have just finished a book, which isabout to be published — called MMR: Science and Fiction.ObviouslyAndrewmakesrepeatedappearancesinwhatIhavetosay,andIhavetriedveryhardtobeasbalancedasIcan…Ido try to write honestly about Andrew’s role in this wholeaffair.OnethingIdostronglyendorseistheneedtokeepthesedebateswithinthecommunityofscienceandmedicineandnotto punish, censor, or banish individuals who dissent fromorthodoxy.Thetrickisfindingthebestwayofdoingthis.IamtoldthatBrianDeerisnowmakingafilm.Hisroleisfarfromcleartome.ButIdoknowthatheisdangerous…

Onlya fewdaysafter thismessage,Hortonwroteagainaboutme in theBritishpress(ratherthaninthe“communityofscienceandmedicine”thathehadmentioned):

The career assassination ofWakefield cleansed science of anunwiseagentprovocateur.

InHorton’sbookMMRScienceandFiction,itmayhavebeentherapeuticforhim todescribehis “tight coilof suppressed frustration”afterDeer’sallegationsandhowit“wasunwinding inmehavingbeenpressed intoapositionofextraordinarytensionduringtheprecedingsixyears.”7HortonrecountsforthereaderhowhewasabletohelptheGMCindecidingmyprofessional fate — help which may have assisted in this unwindingprocess:

In truth they had not a clue where to begin. At a dinner Iattended on 23 February, one medical regulator and Idiscussed the Wakefield case. He seemed unsure of how theCouncilcouldplayausefulpartinresolvinganyconfusion.Aswe talked over coffee while the other dinner guests weredeparting, he scribbled down some possible lines ofinvestigationandpassedmehiscard,suggestingthatIcontacthimdirectlyifanythingelsecametomind.Heseemedkeentopursue Wakefield, especially given ministerial interest. Herewasprofessionallyledregulationofdoctorsinaction—notesexchangedover liqueurs inabeautifullywood-panelled roomofoneofmedicine’smostvenerableinstitutions.

HortonadvisedtheGMConthewaytobringmetoheel.Thiswastobethe perfect follow-through, with Horton as one of the key prosecutionwitnessesatthetrial.

Horton also sounded a warning of the potential consequences for theprosecutors, should they fail togetaguiltyverdicton their terms.Thereare many soundbites from him, but one in particular bears scrutiny. InApril2006,hewrotea longpiece in theUK’sGuardiannewspaper.Hisopeningparagraphread:

It’shardtoimaginethatanythingusefulcouldstillbewrittenabout the MMR vaccine. Too much has probably been saidalready,mostof it eitherwilfulnonsenseorwild speculation.So I hesitate. And especially because it was I who wasresponsible forpublishing - to theeternaldamnationofmanyof my medical and public-health colleagues — AndrewWakefield’s 1998 paper that fuelled a smoulderingundergroundmovement against the vaccine.A campaign thatwenowknowwaspartlylinkedtoeffortstowinalegalclaimagainstvaccinemanufacturers.

WhenWakefieldwalks into theGMC,hewillhaveanationalstage that has been denied him ever since he used a pressconference to call for the provision of single vaccines. Theoutcomeof theGMC’sproceedingscouldbe lose-lose for theDepartment of Health. For Wakefield’s supporters, he willeitherbevindicatedasaheroorgodownasamartyr tohiscause.

Horton is wrong: there is a great deal more to be written about MMRvaccine. And although he may not wish it, there is more to be writtenaboutHorton’sownroleinthisaffair.AnditstartswiththediscoveryoftheoriginalRouseletter.

Endnotes1 GMCvsWakefield,Walker-Smith,andMurch.StatementofDrJohnBignall(deceased),deputyeditorTheLancet.September13,2005.Page1,paras2-4.Seealso:WakefieldtoElse,Letter.July3,1997.

2 Langdon-DownG. (1996,November27).“Law:Ashot in theDark.”TheIndependent.Page25.

3 Yazbak FE. The MMR and Single Measles, Mumps and RubellaVaccines: The REAL Facts. Retrieved fromhttp://bmj.bmjjournals.com/cgi/eletters/329/7477/1293#92190.BuncombeA. (1998,September 1).Measles jabwithdrawndue to ‘highdemand’. The Independent. Retrieved fromhttp://www.independent.co.uk/news/measles-jabwithdrawn-due-to-high-demand-1195247html.

4 ShadowHealthMinister—theminorityparty’sHealthMinister.

5 DeertoNukkiatTheSundayTimes.E-mail.February17,2004.

6 Dr.CarolMStottBScPhD(Cantab)CPsycholonSmeethetal.:SmeethL,CookC,FombonneE,HeaveyL,RodriguesL,SmithP,HallA.MMRvaccination andpervasivedevelopmental disorders: a case-controlstudy. Lancet 2004; 364:963-969 is a case-control study purportedlydesigned to investigate aputative associationbetweenMMRvaccinationandincreasedriskofpervasivedevelopmentaldisorders(PDD).However,problems in study design operate against the probability of detecting anincrease in risk. Furthermore, there are significant changes from themethodologyfirstproposed2andsubsequentlycitedinthepresentpaper.

Thebasisofacase-controlstudyofthiskindisthatifthehypothesisoftheputativeassociationhasanyvalidity,oneshouldfindadifference(i.e.,an

“effect”) between cases and controls in the proportions exposed to thevaccine.

While it is frequently acknowledged that the “effect size” is likely tobesmall, the consistent error is in the assumption that this derives from asmallriskconferredbyMMRtomanyindividualsratherthanasubstantialrisk to a small number of individuals with a subsequent and specificpresentation.Intheformersituation,case-samplescouldappropriatelybeincreased by adding general PDD cases,while in the latter, case groupsshouldbelimitedto,andonlyincreasedby,theadditionofchildreninthesubgroupof interest. Itwasobviously crucial for the reported study thatcase groups comprised only those children presentingwith regressive orlate-onsetPDD.Smeethetal.stateexplicitly(onpage967)thattheywerenotabletodothis.

Samplesizeisalsoanissueforthisstudy.Conditionallogisticregression(clogit)wasusedappropriatelyforthematched-pair(case-control)design.Crucially, however, the only pairs contributing to such an analysis arethose in which exposure differs across the pairings. Where level ofexposure in thegeneralpopulation ishigh,asubstantialnumberofcase-controlpairswouldsharethesameexposurestatusand,thus,beexcluded.Adequate study power is only maintained, therefore, by ascertainingsamples largeenough toallowsufficientpairs to remain.Anappropriatesamplesizeforamatched-pairdesign3withanestimatedcontrolexposurerateof80%,ap-valueof0.05,ancase-control ratioof1:3,acorrelationcoefficientforcase-controlpairedexposureof0.8,anoddsratio(OR)of1.2andapowerof0.8,wouldbe7,145cases.Inotherwords,tohavea80-20chanceofobservinganORof1.2,almost6timesasmanycaseswouldbeneededaswereusedintheSmeeth,etal.study.Asthecasegroupwaslikely to consist of only 20-50%of the relevant phenotype, the requiredsamplesizeforcasesrisessubstantiallybeyondthis.

Finally, the study is likely to be confounded by factors affectingunderlyingriskofexposurebetweenthegroups.Childrenathighergeneticriskofdisordermay remainunexposedasmaychildrenwithearlyonsetdevelopmentaldifficulties.Thiswouldresult indifferentialexposureriskbetweenthetwogroupssystematicallyactinginfavorofriskofexposureincasesbeinglowerthanincontrols.

References1. SmeethL,CookC,FombonneE,HeaveyL,RodriguesL,SmithP,

HallA.MMRvaccinationandpervasivedevelopmentaldisorders:acase-controlstudy.Lancet2004;364:963-969.

2. SmeethL,HallA,FombonneE,RodriguesL,HuangX,SmithP.Acase-controlstudyofautismandmumps-measles-rubellavaccinationusing the general practice research database: design andmethodology.BMCPublicHealth.(2001)1:2.

3. Dupont, WD. Power calculations for matched case-control studies.Biometrics.1988;44:1157-1168.

7Horton, R.MMR Science and Fiction. London: Granta Books,2004.

8TaylorB,MillerE,FarringtonC,PetropoulousM,Favot-MayaudI, Li J, Waight P. Autism and measles, mumps, and rubellavaccine: no epidemiological evidence for a causal association.TheLancet.1999;353;2026-2029.

9http://uk.reuters.com/business/quotes/officerProfile?symbol=GSK.L&officerId=475638

10http://www.gsk.com/about/bio-davis.htm11E-mailswillbeposted.Seewww.callous-regard.com.

CHAPTEREIGHT

Horton’sEvidenceOnThursday,August7,2007,RichardHortonwalkedintothechamberoftheGMC, affirmed that hewould tell the truth and thewhole truth, andbeganhisevidence.Hiswifesatbehindhiminthepublicgallery.Over2daysoforal testimony,Ms.Smith,SeniorProsecutingCounsel,appearedto be justifiably delightedwith herwitness as she took him through hisevidence-in-chief. It is not necessary to revisit the whole of Horton’sevidence,simplytodealwiththepartthatdealtwiththeRouseletterandhisstateofmindin1997andbeyond.

Smith: Iwant toask youabout oneparticular letter onpage924 from someone called A. Rouse from the Department ofPublic Health Medicine, Wiltshire Health Authority. At thisstage Iwant to take you to that [response] fromWakefield. Iwanttotakeyoutothemiddlesectionwhichbegins:

“ARousesuggests that litigationbiasmightexistbyvirtueofinformationthathehasdownloadedfromtheinternet from the Society for the AutisticallyHandicapped.Only one author (AJW)… has agreedtohelpevaluateasmallnumberofthesechildrenonbehalf of the Legal Aid Board. These children haveall been seen expressly on the basis that they werereferredthroughthenormalchannels(e.g.fromGP,childpsychiatristorcommunitypaediatrician)onthemeritsoftheirsymptoms.AJWhadneverheardoftheSociety for theAutisticallyHandicappedandno fact

sheet has been provided for them to distribute tointerested parties. The only fact sheet that we haveproducedisforGPswhichdescribesthebackgroundandprotocolforinvestigationofchildrenwithautismand gastrointestinal symptoms. Finally, all thosechildren referred to us (including the 53 who havebeen investigated already, and those on thewaitinglist that extended into 1999) have come through theformal channels described above. No conflict ofinterestexists.”

Smith:Whenyoureadthatletter,whatdidyouunderstandDrWakefieldtomeanwhenhesaidoneauthorhasagreedtohelpevaluate a small number of these children on behalf of theLegalAidBoard?

Horton’sreplywasessentiallyareiterationofOlswang’searlierresponseto the letter from lawyersCarter-Ruck (seeChapter 7, “Horton andTheLancet”)withsomekeyadditions.

Horton:WhenIreadthatlettertwostatementsstoodout:first,the assertion that you concluded that paragraph with, “noconflictofinterestexists”.Atthetime,inMay1998,Ihadnoreason, no evidence before me, to suggest that that was anuntruestatementsoItookthatstatementontrust.Withrespecttothesentencethatyouaskaboutspecifically,“hasagreedtohelp evaluate”, I must admit I read that as something thathappened after publication. To my knowledge in February1998 and during the peer review process going back into1997, I was completely unaware of any potential litigationsurrounding the MMR vaccine. I was not aware of theinvolvementofafirmofsolicitorsDawbarns.Icertainlywasnot aware of any activity going on with the Society for the

AutisticallyHandicappedprior to the 1998paper. Iwasnotaware of any other relationship between DrWakefield andDawbarnsandRichardBarr.WhenIreadthosestatementsIsawthisassomethingthatwastriggeredbythepaperratherthanthepaperbeinginsomesensesaculminationofeventsuptoFebruary1998.1

Smith:Lookingatthewordingofthesentenceyoureferredto“only one authorhas1agreed to evaluate a small number ofthesechildrenonbehalfoftheLegalAidBoard”,yousayyoutook that tomeansince thepublicationof thepaper1andwearenowsomethreeorfourmonthsonfrompublicationofthepaper.

Horton:Yes.

Smith: Was there anything in particular about that wordingwhichledyoutothinkthat?

Horton: It is the “has” agreed. I know these are finedistinctions. If it had said “had agreed” then I would havethoughtthatwasmoreinthepasttense.Reading“hasagreed”in combination with the firm assertion that no conflict ofinterestexists,mysuspicionswerenotraisedatthattime.

Smith:Didyouacceptthatletteronitsfacevalue?

Horton:Wecertainlydid,yes.

“Has”and“Had”

The English usage in my letter in response to Rouse was deliberate,grammatically correct, and factually accurate. “One of the authors hasagreed”isinthepresentperfecttense.Thetenseisusedtoemphasizethatsomethingnotonlyhappened but is still true. Thiswas the case formyinvolvementwiththelegalactionatthetimeofwritingmyresponsetoDr.Rousein1998.

Thematterofthetenseisnot,asHortonhasstated,a“finedistinction”butconveys, in this matter, a crucial difference in meaning that, somewhatcuriously,waslostontheeditor-in-chiefofamajormedicaljournal.“Hadagreed” is the past perfect tense; its use would have been neithergrammatically correct nor factually accurate. The use of this tense is toemphasizethatsomethinghappenedbutisnottrueanymore.ThiswasnotthecaseatthetimethatIwrotetoTheLancetinresponsetoRouse.

Let us examine Horton’s position more closely in light of his criticalmisunderstanding of English grammar. First is the response, via hislawyers, to the 2004 letter seeking an apology frommy lawyersCarter-Ruck.

It is apparent that, whilst your client’s [Wakefield’s] letterindeedmakes it clear that he “has agreed to help evaluate”some children on behalf of the Legal Aid Board, it does not

indicatethatinfactsuchworkhadbeencommissionedandwasbeingundertakenbeforethe1998Paperwaspublished.Inlightof this, thenaturalandordinarymeaning2 tobedrawnfromyour client’s letter at the time was that following thepublication of the 1998 Paper he had agreed to carry outevaluations of children included in the 1998 Paper for theLegalAidBoard.

Wrong: their “natural and ordinary meaning” is a mundane error thatconfuses the present perfect and past perfect tenses. Compounding thiserror,Olswang’slettercontinued:

In light of this, and your client’s express statement that noconflict of interest existed, our clients had no reason toinvestigate the position further, untilDrHortonwas recentlyapproached by the Sunday Times journalist, Brian Deer.MrDeer brought toDrHorton’s attention for the first time thatyour client’s relationshipwith theLegalAidBoardpre-datedthepublicationofthe1998Lancetpaperbysomeconsiderabletime.

Apparently, Horton’s understanding was that my relationship with Barrhad startedafter the 1998 paper was published. In his testimony at theGMC,Hortonwas toconfirmthathebelievedmyrelationshipwithBarrhadstarted“sincethepublicationofthepaper”andthatbecauseofthis,hewaspreparedtoacceptthatIhadnoconflictofinterest.Moreover,Smithoffered Horton clear blue water of “three or four months” between thepublicationofTheLancetpaperandthepublicationoftheRouseletter—easily enough time for Barr and me to have established a workingrelationship. Let us step back and examine this in a littlemore forensicdetail.

Texas,February29,2008.BackatthehomesteadinAustin,Carmelheldthe actual Rouse letter − the one that Rouse sent to Horton only oneworking day after the paper’s publication. It was labeled LETTLANC.DOC 04/03/98 − referenced byThe Lancet as having been received onMarch4,1998.TheLancetpaperwaspublishedonFriday,February28.Rouse’sletterwaswritten1daylater;theweekendcameandwent,andtheletterwasfaxedtoTheLancetonMonday,March4.TheLancetfaxedthisletter, with others, to me on April 2, 1998. Crucially, there are criticaldifferences between the original letter from Rouse and that which waspublished byThe Lancet after it had been “edited.” The original Rouseletterreadsasfollows:

Vaccineadverseevents:LitigationbiasmightexistAfterreadingWakefield’sarticleIperformedasimpleinternetsearchandquicklydiscovered theexistenceof the society forTheAutisticallyHandicapped.Extractsfromthisfactsheetareproducedbelow.

Extracts froma48pageVaccinesFACTSHEETpreparedbyDawbarnsforSocietyfortheAutisticallyHandicapped(sic)

Inflammatory bowel disease. We are working with DrAndrew Wakefield of the Royal Free Hospital. He isinvestigatingthiscondition.Page27Inflammatoryboweldiseaseandautism.Ifyourchildhasdeveloped persistent stomach problems (including painsconstipationordiarrhoea) following thevaccination,askusforafactsheetfromDrWakefield.Page44Ifyoubelieveyourchildhasbeendamaged…weproposeto seek proper compensation in the court. We will alsohelp with applications to the vaccine damage tribunal.

Page47-48

RouseprovidedHortonwithaWebaddressidentifyingthesourceofthisinformation.3 The fact sheet towhichRouse referredHorton carried thedateofMay15,19974—afull10monthsbeforethepaper’spublication.

Reading this letter, faxed tome in London bymywife, Iwas suddenlyreminded of Horton’s spontaneous denials at the GMC, unprompted bySmith,theprosecutingbarrister:

TomyknowledgeinFebruary1998andduringthepeerreviewprocessgoingbackinto1997,Iwascompletelyunawareofanypotential litigation surrounding theMMR vaccine. I was notaware of the involvement of a firm of solicitorsDawbarns. Icertainly was not aware of any activity going on with theSociety for the Autistically Handicapped prior to the 1998paper. Iwasnot awareof anyother relationshipbetweenDrWakefieldandDawbarnsandRichardBarr.

Thisevidencewas false. IcalledKirstenLimb,aparalegalwho,back inthemid-‘90s,worked for the plaintiffs’ lawyersDawbarns, the firm thatwasseeking todeterminewhetherornot therewasacase in lawagainstthemanufacturersoftheMMRvaccine.Kirsten’sknowledgeoftheMMRlitigation was and remains encyclopedic, and she was rapidly able toupdatemeonHorton’sactualstateofknowledgebackin1997.Aspartofthe litigation process,Dawbarns produced fact sheets thatwere intendedprimarily for their clients, but requests for copies came from medicalpractitioners, the pharmaceutical industry, and other interested parties.Overtimethefactsheetswereupdatedasfurtherinformationcametolightandthecasesprogressed.

Duringthefirstquarterof1997,theinvestigationsintoTheLancet12werecompleteandthepaperwasbeingwrittenupforsubmissiontothejournal.At the same time a Dr. B.D. Edwards wrote to Horton bringing to hisattention the fact that text and tables from various Lancet papers werebeingreproducedinDawbarns’sfactsheet,implyingbreachofcopyright.Limbwas telephoned by aMs. SarahQuick ofTheLancet. Limb notedthis contact in amemo datedMarch 19, 1997,marked “Urgent.”Quickexplained to Limb that Edwards had been in touch and why. A littledetectiveworkonLimb’spartrevealedthatEdwardswasamemberoftheMedicines Control Agency (MCA) responsible for vaccine licensing.Apparently,hehadchosennottodisclosethisfacttoHortonbywritingtohim on his personal stationery.5 In that telephone conversation, QuickindicatedtoLimbthatDawbarnsshouldapplytoHortonforretrospectivepermissiontoreproduceLancetmaterial;shedoubtedthattherewouldbeanyproblemaboutthegrantingofthispermission.

BarrdulywrotetoHortonexplainingthepositionofDawbarns.Thorough,asever,BarrsenthisdetailedletterbyfaxandmailonApril3,1997.6Inthemailed version, he included his extensive correspondencewith aDr.Wood,alsoof theMCA(nowdeceased),andthecontentiousfactsheet.7Barr’sletterwasexplicit:heworkedforDawbarnssolicitors,andhewasinvolved in litigation related to potential damage to children followingexposure toMMR andMR vaccines.He askedHorton for retrospectivepermission to quote specific Lancet references “contained in the factsheet,” and he identified the four relevant references by providing theirfootnotenumbersinhisletter.Footnotenumber50onpage21ofthefactsheetwasareferencetoapaperthatIhadcoauthored.Thetextassociatedwiththatfootnotereadsasfollows:

There is convincing evidence of a link between [measles]

vaccination and inflammatory bowel disease (includingCrohn’sdisease).50 [Footnote 50 is a reference to one ofmypapers.]Itisaseriouslifelongillnessthathasaffectedalargenumberof thechildrenwearehelping.WeareworkingwithDrAndrewWakefieldoftheRoyalFreeHospitalLondon.Heisinvestigatingthiscondition.8

For the avoidance of doubt, in March 1997 Barr had taken Hortonspecificallyanddeliberatelytothetextinthatfactsheetthatdescribedmyworking relationship with him and his law firm. In the samecorrespondence,Barr referred specifically to exchanges he had hadwithmeandthefactthatIhadgivenhimpermissiontoquotepapersauthoredbymeandpublishedinTheLancet.Intriguingly,inhisletterBarrreferstothesinister“pressurefromtheMCAandtheDepartmentofHealthontheLancettohavetheLancetreferenceswithdrawnfromtheFactSheet.”

Adialoguestarted;HortonrespondedtoBarronApril8,1997,9denyinghim permission to usematerial fromThe Lancet in his fact sheet. Barr,clearlyfrustrated,respondedonApril16,1997,seekingtheintercessionofTheLancet’sombudsman.10Horton replied toBarr onApril 23, 1997,11saying that he would be happy to refer the matter to The Lancet’sombudsman. Barr then wrote again to Horton on April 29, 1997,12enclosinghiscorrespondencewithDr.EdwardsfromtheMCAandaskingto be put in touchwith the ombudsman. Horton responded on June 12,1997,13withinstructionsonhowthisshouldbedone.BarracknowledgedHorton’s letter on June 25, 1997,14 and subsequently correspondedwithThe Lancet’s ombudsman, Professor Sherwood from CambridgeUniversity.15

ThebottomlineisthatSherwoodultimatelyoverruledHorton.Heagreed

thatthetablesandotherreferencesinthefactsheetcouldremain,andheindicatedthathewouldbecommunicatinghisdecisiontoTheLancet.Hedid so, and Barr heard nothing more from Horton. It would seemreasonable toassumethat thiscorrespondence isstillheldonfilebyTheLancet although, for whatever reason, it was not disclosed to the GMClawyerswhentheysoughtHorton’sassistanceinmyprosecution.

Barr’s protracted and contentious exchange with Horton and thesubsequentombudsman’srulingareunusualifnotuniqueinTheLancet’shistory. Beyond any shadow of a doubt, fromMarch 1997 Horton wasawareofanumberoffactsthat,inviewofthenatureandoutcomeofthisexchange,shouldnothaveescapedhismemory.Thematerialsentdirectlyto Horton at that time included information about Barr, the law firmDawbarns,theMMRlitigation,andmyworkingrelationshipwithBarrandDawbarns. These, as you will recall from his testimony, were allspecificallynamedanddeniedbyhimunderoath.

ThecorrespondenceconcerningbreachofcopyrightstartedinMarch1997andcontinuedatleast intoJulyofthatyear.Documentaryevidencefromthe GMC indicates that The Lancet paper had been submitted forconsiderationforpublicationby that time.Thereappears tohavebeenatleast someoverlapbetween thepaper’s submissionand theBarr-Horton-Sherwood exchanges. In my opinion, even if one suspends belief andassumes thatHortonhad forgotten thisexchange, theRouse letter−sentonly days after the paper had been published − and my subsequentconfirmationofmyroleinthelitigationwouldsurelyhavebeenwake-upcalls.

In a nutshell, therefore, it is clear that, as a matter of fact, Hortonwas

awareofthelawfirmDawbarns,wasawareofMr.Barrthelawyerandofhiscentral role in theMMRlitigationonbehalfofDawbarns,wasmadeawareofmyrelationshipwithBarrandmyinvolvementinthelitigation−andallof thishappenedoneyearbefore thepaper’spublication.HewasremindedofthesemattersintheRouseletterandinmyresponse,andwasprovidedwithfullreferencestothesefacts—factsthatwereneversecret—justoneworkingdayafter thepaperwaspublishedinFebruary1998.HewasremindedonceagainbyLaurenceofTheIndependentnewspaperin 2004. Despite all of this, Horton has claimed repeatedly in print, onradioandtelevision,throughthelawfirmOlswang,andunderoathuponthewitness stand at theGMC, that until 2004heknewnothingof thesematters,claiminginsteadthathetookmyresponsetoRousetomeanthattheagreementtoworkwithBarrhadstartedfollowingpublicationofTheLancetpaper.

Thismeritsalittleanalysis:Hortonappearedtobeproposingthatwithinoneworkingdayofpublication(notthe3to4monthsofclearbluewatergrantedbySmith),BarrandImet,reachedanagreement,preparedafactsheet−forsomereasonbearingthelong-pastdateofMarch13,1997—and sent this 48-page document to the Society for the AutisticallyHandicapped,whichdulyuploadedittotheirwebsite.Andallofthiswascompoundedbyanapparent amnesia forhis protracted, contentious, andultimatelylucklessexchangewithBarrandTheLancetombudsmanfromMarchtoJulyof1997.

Afurther importantcontradictionwas toarise fromHorton’sevidenceattheGMCwhenheamplifiedhisfalseclaimofignorance:

Smith: [Beginning discussion of the Brian Deer meeting on2/18/04.]Wasthatthefirstyouheardoftherebeinganissue?

Horton:Thatisright.ThatwasthefirsttimethatIwasmadeawareoftheconnection,bothwiththeLegalAidBoardandthespecificfundingoftheworkthatwasreportedinTheLancet.

At his meeting with Horton at The Lancet offices on the morning ofFebruary 18, 2004, Deer alleged that The Lancet case series had beenfundedbytheLABand,therefore,wasanactualconflictofinterestunderthe then-applicable disclosure rules of The Lancet. I was easily able torefute thatallegationduringmymeetingwithHorton later thatsamedayandsubsequentlyconfirmattheGMCthattheLABfundingwasforanas-yet-unpublished viral detection study,16,17 while The Lancet case serieswasfundedfromtheRoyalFreeHospitalandtheNationalHealthService.

Back in2004,baseduponmyexplanation,Horton immediately retreatedfromthepositionofanactualconflict toaclaimofapossibleperceivedconflictof interest.This led in turn toaheateddebatebetweenus, sincethe then-applicable Lancet disclosure guidelines only applied to actualsources of funding, not perceived conflicts. At the conclusion of hisevidence at the GMC, Horton confirmed that this exchange reflected adifferenceinperceptionandnotdishonestyonmypart.HeconfirmedthatI was genuinely surprised by his reference to disclosure of a perceivedconflict.

The day after this meeting (February 19, 2004), it would appear thatHortonreiteratedDeer’scontentionthatTheLancetpaperhadbeenfundedby theLAB in ameetingwith someof the coauthors at theRoyalFree,including pediatric gastroenterologist Dr. Mike Thompson. ThompsongaveastatementtotheGMC’slawyers,FieldFisherWaterhouse,but,for

reasons that are not clear, was not called by them as a witness. Hisstatementreads:

In 2004, Imetwith RichardHorton the Editor of the LancetalongwithDrMurchandProfessorWalker-Smith.Wewereallveryshockedtohearaboutthefundingofthestudy18and feltvery let down by Dr Wakefield. My knowledge about thefunding of the paper18has put the paper into the realms ofcompetinginterests.Ifeltthataretractionoftheinterpretationofthepaperwasnecessaryandamoralobligation.19

So, despite my explanation the previous day, Horton appears to havepersistedinDeer’sclaimthatTheLancetpaperwasfundedby theLAB.Moreover,Thompsonappearstohavebeenmotivatedtoretractthepaper’sinterpretationbaseduponthisfalsepremise.However,whenHortoncametowritehisbookMMR:ScienceandFiction20the“facts”hadchangedandheassertednowthat,viaDeer,hehadbeenawarefromtheoutsetof“twoquiteseparatestudies”:

DeeralsoprovideduswithevidencesuggestingthatWakefieldwas conducting two quite separate studies21 at the time ofpublication of his 1998 article. One study included the workthatwepublishedintheLancet.TheotherinvestigationwasaLegal Aid Board funded pilot project, agreed between theBoardandWakefieldin1996.

This statement created the appearance that hisobjectionwas andalwayshadbeenbaseduponaperceivedconflict.Inthisstatementheappearstohave concealed the fact that itwasme, notDeer,who informed himonFebruary18,2004,ofresearch−quiteseparatefromTheLancetpaper−thatwasfundedinpartbytheLAB.Inmyopinion,byblurringthecrucialdistinctionbetweenactualandperceivedconflicts,Hortonmadeitappear

tohisreadersthathehadareasonablebasisforbelievingthatIhadfailedtomakearequireddisclosure.

In his GMC testimony, Horton was to change his account of this issueonce again, admitting that what Deer had, in fact, allegedwas thatTheLancetcaseserieswasfundedbytheLAB:22

Smith:Wereallegations-Iwilldealwiththemallbecauseyouset them out very clearly in The Lancet — did they includeallegationsinrelationtofundingissues?

Horton:Yes,theydid.

Smith:Wasthatthefirstyouheardoftherebeinganissue?

Horton:Thatisright.ThatwasthefirsttimethatIwasmadeawareof theconnection,bothwith theLegalAidBoardandthe specific funding of the work that was reported in TheLancet.23

Smith: How did you handle it, Dr Horton, obviously youlistenedtowhattheyhadtosay.Whatdidyoudothereafter?

Horton:WellthepresentationbyBrianDeertooktheformof

him standing up before a group of editors and laying out aseriesofallegations,notjustrelatingtotheLegalAidBoardfunding of thework23but also including theway thework23had been handled by the ethics committee at the Royal FreeHospital–twospecificallegations,one,thattheworkhadnotactually received ethics committee approval and, second, theapprovalthatwasgivenforapieceofworkwasinsomesenseafabrication,thattheworkthattookplaceandwasreportedinTheLancetwasdoneundercoverofanotherethicscommitteeapprovalprocessforanentirelydifferentpieceofworkwhichwasanextraordinarilyseriousallegation.

The“work”towhichHortonrefersisTheLancetcaseseriesandnot theLAB-fundedvirologystudydisclosedtohimbyme(andnotbyDeer).ItisnotablethathadHortonbeenaccurateabouttheconflictsofinterestissueduringtheGMCinvestigation,i.e.,thatIhad,atmost,aperceivedconflict(notaviolationoftheapplicableLancetguidelines),theGMCwouldnothave been able to charge me with an undisclosed actual conflict withrespecttotheLABfunding.

Horton’sfalsetestimonywasrevealedduringmyevidence.Asaresult,hewas asked to provide an explanation, which he did in a supplementalstatement.24Whileheacknowledgedthathepersonallyhandledtheclaimin1997thatDawbarnsinfringedTheLancet’scopyright,hedeniedhavingread aboutmy involvement in the litigation. Inmyopinion, this ismostunlikely since he would have had to examine the alleged infringingdocument personally before deciding whether to grant or deny therequested permission. His denial is limited “to the best of myrecollection.”Hissupplementalstatementdoesnotobviateinanywaytheneedforathoroughinvestigationofhisactions.

Andwhere is theoriginalRouse letter?SurelyamundanesearchofTheLancet archiveswould have revealed it.Hortonwas first approached byFieldFisherWaterhouse(FFW)inthespringof2005.TheymetonMarch31atTheLancetoffices.HortonreiteratedhisunderstandingthattheLABstudyhadbeen“triggeredbythe1998articlebeingpublishedinFebruary1998.”FFW’sattendancenoteofthismeetingcontinued:

Lastly,RH[Horton]saidhewouldlookforanydocumentsthathemighthaveinrelationtothismatter.

ThismeetingwasfolloweduponJune8,2005,andopenedwithHortoninquiringastowhether

DrWakefieldmightbeable tosuehim fordefamationshouldthefinalizedstatementcontainanydefamatorymaterial.

Thisisanoddstatementsincetruthisanabsolutedefenseindefamation.Theirmeetingconcludedasfollows:

[Lawyer]:IaskedRHwhetherhehadfoundanydocumentsinrelationtoDrWakefield’spaperandinparticularanyprivatecorrespondence between The Lancet andWakefield followingthepressinterestinthearticleinFebruary1998.RHsaidthatall25ofTheLancetdocumentswerearchivedinthesameplaceand were now stored off site. He had a search done of thearchivedmaterialandnothinghasbeenfound.

TherewasnosuggestionatanystagethattheRouselettermighthavebeendestroyed. It seems extraordinary, therefore, that what Hortoncategoricallydescribedasa searchofarchivedmaterial containingallofThe Lancet documents, failed to reveal the original Rouse letter— the

veryletterfromwhichanyreferenceto“litigationbias”andmyworkingwithrelationshipwithDawbarnshadbeenedited.

PostscriptHortonhassince issuedafull retractionof the1998Lancetpaperon thebasisoftheGMC’sfindings.Specifically,hehasjustifiedthisonthebasisoftwoissues:firstly,thefindingthattherewasnoethicalapprovalfortheresearchdescribedinTheLancetpaper.ThisissueisfullyaddressedintheAfterword,“Ethics,Evidence,andtheDeathofMedicine.”

ThesecondissueisthefindingthatthedescriptionofthechildreninTheLancet paper as “consecutively referred” is false or misleading. This isbizarre, since it is factually entirely correct — these were the first 12children to be referred to the care of Walker-Smith with a regressivedevelopmentaldisorderandintestinalsymptoms.Thepaperalsoaddsthatthesechildrenwereself-referred,drawingthereader’sattentiontothefactthattherewasthisinherentbiasinthewaycasescametotheRoyalFree.Whathasbeenmisconstruedandgrosslymisrepresentedastothereferralprocess is the fact thatparentsoftenmade initial contactwithme (and IsuggestedanonwardclinicalreferraltoWalker-Smith)andthatonafewoccasionsIspoketothechild’sdoctor,colleaguetocolleague,explainingthebackgroundtowhatwethoughtmightbetheproblem.Thisprocesshasbeen portrayed in someway as a corruption of the referral process.Butpatientsandparentsfrequentlymaketheinitialcontactwithdoctorsbased,for example, on recommendations; doctors often talk to other doctorsabout complex issues. But the current issue is about protecting MMRvaccine,andthatmeansawholenewsetofrules.

It is interesting that the seedsofdoubt about the integrityof the referralprocesswerenourished—ifnotsown—inthemindsoftheGMCPanel,inmyopinion,bynoneotherthanHortonhimself,ultimatelyprovidinga

convenient platform from which to issue his full retraction. A medicalpanelmemberputittohim:26

Q:Onanotherissue,whatismeantby“consecutive”,becauseinthereferralswetalkaboutconsecutivereferrals.Howdoweunderstand, or what is normally understood, if we see“consecutivereferrals”inapaper?

A:Theordinarymeaningofconsecutivereferral, tomymind,wouldliterallymeanasequenceofchildrenreferredoneaftertheothertoaspecialist, individualoraclinicorunit.Thatiscertainlythewayitwaspresentedinthispaper.Whatwefoundout in 2004, both fromwhat BrianDeer presented to us andalso from what Professor Walker Smith discovered andreportedtous,wasthatthatconsecutivereferral,whileitwasto the letter correct, behind that was actually a muchmorecomplexsetofrelationships.27

Sincewhen has the onward referral of sick, non-litigant childrenwhoseparentshavesimplyaskedforhelpmerited thesinister implicationof“amuch more complex set of relationships”? Horton, in making thisallegation, inmyopinion,effectively laid thegroundworkfora later fullretractionofthepaper.

In light of factual errors, inconsistencies, and omissions relating to hisevidence in the matter of the GMC vs Wakefield, Walker-Smith, andMurch, Horton is currently the subject of several complaints to theProfessionalConductCommitteeoftheGMC.28

Readersmaybeinterestedtoknowthat,inadditiontoeditingTheLancetand assisting in the prosecution ofme andmy colleagues by theGMC,Hortonhas,sinceSeptember2007,beenchairingacommitteeattheRoyalCollege of Physicians in London looking at the relationship betweendoctors,patients,andthepharmaceuticalindustry.Thedeliberationsofhisgroup (Innovating for Health: Patients, Physicians, the PharmaceuticalIndustryandtheNHS29)werepublishedinFebruary2009andhavebeenroundly criticized.The suggestion has even beenmade that theworkingparty’srealagendawastorehabilitatetheimageofthedrugindustryandits relations with clinicians and the NHS. There is a short section on“Medicaljournals:victimsorassailants,”whichreadsasfollows:

Editors ofmedical journals report examples ofmanipulation,distortion,bias,secrecy,overtpromotion,andghostwritinginpublishingmedicalresearch.

Thereportgoesontogivedetailedexamplesofthe“excesses”ofindustry.What is surprising (or perhaps not) is that the recommendation of theworking party does not address the fact that it is unacceptable for drugcompaniestoactinthiswaybutratherthejournaleditorsareasked“todomore to strengthenpublicandprofessional confidence.” Is this acaseofthetailwaggingthedog?Icannotsay.Iwonder,however,whetherthetiesbetweenTheLancet,ElsevierandGlaxoSmithKline–aperceivedconflictattheveryleast–wereappropriatelydisclosedinthatreport.

Endnotes1 Emphasisadded.

2 Emphasisadded.

3 Obtained from http://www.mplc.co.uk/eduweb/sites/autism/index.htmlPagenolongeravailable.

4 DawbarnsvaccinefactsheetMay15,1997.

5 Correspondence between Edwards and Horton, noted in note oftelephone conversation between Sarah Quick (Lancet) and Limb(Dawbarns).March19,1997.

6 Barr’sfaxtoHortonofApril3,1997.

7 FactsheetofMarch1997.

8 Emphasisadded.

9 HortontoBarr,LetterApril8,1997.

10 BarrtoHorton,LetterApril16,1997.

11 HortontoBarr,LetterApril23,1997.

12 BarrtoHorton,LetterApril29,1997.

13 HortontoBarr,LetterJune12,1997.

14 BarrtoHorton,LetterJune25,1997.

15 Barr’scorrespondencewithSherwood,JuneandJuly1997.

16 TheLancet children had completed their investigations by February

1997.Due to the fact that theLABgranthadbeenplaced in a suspenseaccount by Dean Arie Zuckerman, it was not transferred by him to theSpecialTrustees of the hospital until September 4, 1997, and, therefore,was not available to be spent on theLAB research project until at leastSeptemberofthatyear.

17 GMCvsWakefield,Walker-SmithandMurch,EvidenceofHortonTr.18,24.

Chairman:Comingtothemeetingthatyouhadwiththethreeauthorswhoarehere,Ithinkyoumentioned,whichImadeanote of, that you told Dr Wakefield that he should havedisclosedLegalAidBoardfunding?

Horton:Correct.

Chairman:WhatwasDrWakefield’sresponse?

Horton: Surprise.He genuinely took the position that he didnot see that as a conflict of interest, for the reasons that wehave heard, that the Legal Aid Board fundingwas funding adifferentstudy to theonereported inTheLancet,and thathehadnotconsideredthatsomethingtobeworthdisclosingtous.

18 Emphasisadded.

19 Statement of Dr. M. Thompson to Field Fisher Waterhouse. May2006.

20 Horton,R.MMRScienceandFiction.London:GrantaBooks,2004.

21 Emphasisadded.

22 GMC vs Wakefield, Walker-Smith and Murch, Evidence of HortonTranscript.17-14D.

23 Emphasisadded.

24 GMCvsWakefield,Walker-Smith, andMurch.Horton supplementalstatement.November26,2008.

25 Emphasisadded.

26 GMC vs Wakefield, Walker-Smith and Murch. Horton Transcript.Tr.18,page31-32.

27 Emphasisadded.

28 ComplaintofMr.J.Moodyonbehalfofvariousautismorganizations,andcomplaintofDr.AndrewWakefield.

29 Royal College of Physicians. Innovating for health: patients,physicians,thepharmaceuticalindustryandtheNHS:Reportofaworkingparty.London:RCP,2009.

CHAPTERNINE

TheDevil’sintheDetail

TheGeneralMedicalCouncilvs.Wakefield,Walker-Smith,andMurch The research reported by you in The Lancet wassubstantially different from that for which approval wasgranted by the Ethical Practices Sub-Committee in that itrelatedto:

i) Children with a diagnosis of autism and not disintegrativedisorder ...Youractionswere ... inappropriate,not in thebestinterestsofpatients, not in accordancewithyourprofessionalethicalobligations, likely tobring themedicalprofession intodisrepute, and fell seriously below the standard of conductexpectedofaregisteredmedicalpractitioner.

BlakeDobson,AssistantRegistrar,GeneralMedicalCouncil

TheforegoingisachargemadebytheGeneralMedicalCouncilin2004.The subjectmatterwas “That Paper”—The Lancet paper of 1998 thatfirstreportedintestinaldiseaseinchildrenwithdevelopmentalregression.Notwithstandingthefactthatinhisenthusiasm,Mr.DobsongotthewrongEthicalSub-Committeeapproval1andthewrongresearchprotocolforthewrongchildren…thereissomuchmoretothisesotericchargethanmeetstheeye,andthe“more”deservesscrutiny.Let’srewindto1995-7,armedwith the enduring adage “if in doubt examine the patient.” Among thepresenting clinical features ofThe Lancet childrenwere some thatwereapparently uncharacteristic of autism, at least as it was generallyunderstoodatthattime.Forall12children,theseincludednormalornear-normal early development, a clearly delineated onset of behavioral/

developmental symptoms, and loss of previously acquired skills. Inaddition, four children had become incontinent after previously havingbeen potty-trained, while at least six children had developed obviousclumsiness(ataxia),amotorsymptomclearlyindicativeofcentralnervoussystemdysfunction(encephalopathy).Incontrastwiththecold,aloofchilddescribed by Kanner, many of these children were affectionate, to theextent that doctors had sometimes been unwilling to make an autismdiagnosis.

Thecombinationoftheseatypicalfeaturesalongwiththefactthat,forthemajority, therewasonset followingan infectious (vaccine)exposure, ledour colleagues in theDepartment of Child Psychiatry at the Royal FreeHospital to suggest that what we were dealing with was not Kanner’sautism,butchildhooddisintegrativedisorder[Panel1].

ChildhoodDisintegrativeDisorderIn1908,manyyearsbeforethepublicationofKanner’sseminalcaseserieson autism, TheodoreHeller, a remedial educator inVienna, described anew syndrome— dementia infantilis (later to become CDD)— in theJournalforResearchandTreatmentofJuvenileFeeblemindedness.2

CDDisapervasivedevelopmentaldisorderthatfulfillsbehavioralcriteriafor childhood autism/autistic disorder, but where the pattern of onset isdifferent.CDDrequiresdocumentednormalornear-normaldevelopment3upto24monthsofagewithsubsequentregressionandlossofskillsinatleast two of the following: expressive/receptive language, play, social/adaptiveskills,continence,andmotorskills[Panel1].

Youmightreasonablyask,“But isn’tCDDjustautismwitha lateronset

and regression?” Later onset following a period of normal developmentmeansthereareskillstobelost.Iftheonsetoccursafterachildispotty-trained,forexample,continencemaybeoneoftheskillsthatsuffer.Andwhere did 24months come from? Surely this is entirely arbitrary— anartifact created to satisfy a need to categorize in the absence of a betterunderstandingof theoriginsof thedisease?Whatdo theexpertshave tosay?

HillandRosenbloomnotedthat“Unlikethevastmajorityofchildrenwithearlyinfantileautism[childrenwithCDD]undoubtedlyshoweda period of early normal development, including the acquisition ofnormallanguageandnormalsocialrelationships.”4They observed that the child usually “comes to look very autistic,suchthattheclinicalpresentation,butnotthehistory[i.e.,regression]is then typicalofachildwithautism.”3RosenbloomcitesProfessorSir Michael Rutter as making age of onset a major criterion fordiagnosisofCDD3indistinguishingitfromautism.IndefianceofRutter,MalhotraandGupta5notedthat“atcloserlookthe age range has varied from 1.2 years (Evans-Jones andRosenbloom,1978) to9years (Corbettetal.,1977).”sAccordingly,they conclude, “it can be hypothesized that disintegrative disorder[CDD]maybealate-onsetvariantofautism.”Russo and colleagues reinforce this view: “Indeed, inmany aspectsthe clinical features [of CDD] are indistinguishable from those ofautism, and the differentiating factor is the period of normal earlydevelopment.”6Malhotra and Gupta noted that “It has been observed that childrenwithCDDhaveaclearlydelineatedonsetandregression,especiallyfor loss of previously acquired skills, which is absent from autisticdisorders.”5The International Classification of Disease [ICD]-10 itselfacknowledges the current “…uncertainty about the extent to whichthiscondition[CDD]differsfromautism…”7The final word goes to Hendry who, in a detailed review of the

subject, concluded that “thevariablesuponwhichCDD is currentlydistinguishedfromAutisticDisorderarenotwellsubstantiated.”8Shecontinued,“CDDshouldnotyetbeconsidereddistinctfromAutisticDisorder,asnotenough informationexists to justify itasaseparatediagnostic category.” Further, she stated that “pervasivedevelopmental disorders could be regarded as a continuum, orspectrumdisorderandCDDcouldbeconsideredapointorrangeofpointsalongthiscontinuumofbehaviouralexpressions.”

In fact, the presenting features of CDD are identical to those of autismwithrespecttothecoresymptoms.Thekeydifferenceliesinthehistoryofnormal or near-normal development and regression. The symptoms ofCDDfitTheLancet12verywell.

So,whileopinionsdiffer,anyresidualdistinctionappears tohangon theflimsy contrivance of age of onset. For Rutter, as a key prosecutionwitness at the GMC hearing, however, thematter was black andwhite.Whenaskedwhether“inembarkingonastudyofchildrenwithbehavioraldisorder,would [he]expectadistinctionbetweenCDDandautism tobemade,”hereplied,“Yes.”Hecontinued,“andtheliteraturewouldsupportdrawingacleardistinctionatthetime[1996].”Itissomewhat

Panel1:CDDorHeller’sDisease

Fromaround the ageof2 through10, acquired skills are lostalmost completely in at least two of the following sixfunctionalareas:

LanguageskillsSocialskills&self-careskillsControloverbowelandbladderReceptivelanguageskillsPlayskillsMotorskills

Lackofnormal functionor impairmentalsooccurs inat leasttwoofthefollowingthreeareas:

SocialinteractionCommunicationRepetitivebehavior&interestpatterns

surprising, therefore, to find thathehadearlierwritten that“Theclinicalpicture[inCDD]afterthephaseofregressionisoftensomewhatsimilartoautismandthedifferentiationmaybedifficult,ifnotimpossible,incaseswithanonsetbefore30months.”9 It isnotable that regressionandonsetbefore30monthsappliestovirtuallyallofTheLancet12.

Also notable among the other clinical features of CDD evident in TheLancet 12 are loss of coordination, secondary incontinence, and, incontrastwith“classical”autism,expressionofaffection.2,6Mightitsimplybethataffection,forexample,doesnotmakeCDDadistinctdiseasebutadifferent expression of the same disease because, unlike the child with

classical autism, the child with CDD has had several years of normaldevelopmentinwhichtoexperienceandenjoyaffection?

It would seem that Rutter is somewhat isolated in his categorization ofchildhooddevelopmentaldisordersbyageofonset.Indeed,itisarguablynaïvetoconceptualizediseaseinthisway,whenageofonsetmaysimplybetter explain differences in presentation. In arguing for splitting autismand CDD, he stated that “although the onset differs from that which isusualinautism,theclinicalpictureinthetwogroupsofconditionsshowsmany similarities. Nevertheless… for the moment it seems highlydesirabletoretain[CDD]asaseparatecategorybecauseitisimportant(a)torecognisethatoftenthesyndromeiscausedbyorganicbraindisease(b)toappreciatethatinsomecasestheaetiologyremainsquiteunknown;and(c) to accept that the nature and extent of the overlap [with atypicalautism]isunknown.”9

Rutter’s reasoning is curious; all threepoints apply equally to autism—atypical or not — and CDD. Both may be caused by organic brainpathology;inmostcasesofCDDandautism,thecauseisunknown;and,since “the nature and extent of the overlap is unknown,” there is littlejustificationforcategorizingthemseparately.

And even now the concept of regression itself appears to bemorphing.Whereas, in the past, regression appeared to have been a keydistinguishingfeaturebetweenautismandCDD,Rutternowmaintainsthatregressionhasalwaysbeenacommonfeatureofautism.

During his expert evidence at the GMC,10 Rutter expressed the opinion

thatforautism“atransientperiodofregressionoccursin25-30%ofcasesandisusuallytemporary.”Thisappearstobeatoddswiththepriorclaimthat regression was not seen “for the vast majority of children withinfantile autism.”4 Rutter may have been referring to temporary loss oflanguage in autism, although this was not clear from his testimony thatappearedtofocusonTheLancet12.

ThedataoftenquotedinsupportofthispositionarethoseofKuritaetal.who reported loss of language in 30% of children with autism.11Interestingly,inasecondstudy,Kuritawentontoshowthatthechildrenwith regressive autism (the 30% with language loss) were clinicallyindistinguishable from CDD .12 In light of their findings, Kurita et al.argued that the validity of CDD being a distinct entity from autisticdisorderwasunprovenand“remainstobestudied.”

Sadly,forTheLancet12,developmentalregressionwaspervasive—notconfinedtolanguagealone.Neitherwasittemporary.

CDD,Autism,andCausation

“Ifautismisaconsequenceofvaccinationitshouldhavebeenaconsequenceofnaturalinfection”

PaulOffit,ininterviewwithMelanieHoward,Babytalkmagazine

At the heart of the GMC hearing is a defense of the MMR vaccine.Steppingbackfromtheperniciouslies,thepoliticalangst,andthecriesforblood,itmaybevaluabletogainsomehistoricalvantagepointfromwhich

to judge scientific concerns about measles virus, vaccines, anddevelopmentaldisorders.TakeforexamplethepresentationofDr.DaynestotheRoyalSocietyofMedicinein1956[Panel2].Hereinhedescribes,for all the world, what we see in a clinical setting on a daily basis;apparentlythereisnothingnew.

Panel2:Measles—bowel—behavior—gluten

Dr.GuyDaynes.BreadandTears—Naughtiness,depression,andfitsduetowheatsensitivity.

RoyalSocietyofMedicine,February15,1956“Typicallyachildbetween1and5yearsbecomesnaughtyanddifficult a few days after the onset of an acute infectiousillness...suchasmeaslesorgastroenteritis.

“Heisirritable,negativistic,andspiteful,sleepisdisturbedandhewakesupinthenightandoftenscreams;hisappetiteispoor,hefailstogainweight,hisabdomenisoftendistendedandthestoolsmaybecomebulky,paleandoffensive.Thiscondition,ifleftuntreated,usuallyrights itselfafteramonthor two,but itmaylastformuchlongerinwhichcaseslightpetitmalattacksmaydevelopinadditiontoworseningoftheothersymptoms.

“Ihavebeenplacingthesechildrenonagluten-freedietattheearliest opportunity and the symptoms respond dramatically,usuallywithin twoor threedays.They relapse if aprematurereturntoanormaldietismade.

“Studyofover40caseshasledmetoformulateasyndrome–pre-coeliacsyndrome.”

It is perhaps unsurprising that a further common denominator for somecasesofautismandCDD is thecausal roleofmeaslesvirus.Thisvirus,eitherinitsnaturalorvaccineforms,hasbeencausallylinkedtochildhooddevelopmental disorders, including autism13;14;15-16 and developmentalregression.17

In utero exposure to measles is associated with autism. Deykin andMacMahoncomparedexposurepatternsof183childrenwithautismand355siblingcontrolstotheencephalitogenic(causingbraininflammation)viruses,measles,mumps,rubella,andchickenpox.Theyfoundthat“totalautistic symptomatologyseems tobeassociatedwithprenatalexperiencewithmeaslesandmumps.”13

Insupportofacausalroleforprenatalmeaslesinautism,Ringetal.,usedsophisticatedstatisticalmodelingof thenumberofautismbirths inIsraelcompared with epidemics of measles, rubella, poliomyelitis, viralmeningitis(inflammationoftheliningofthebrain)andviralencephalitis(inflammationofthebrain)andfoundthatpeaksinthenumberofbirthsofchildren with autism followed peaks of epidemics of measles and viralmeningitis.14

Theauthorsconcludedthat“Autisticbirthpatternsarepartiallyexplainedbytheratesofmeaslesandviralmeningitis[incidentallyafrequentfeatureofmeasles18]inthegeneralpopulation.Thereisastatisticallysignificantenvironmental association between autism and both viralmeningitis andmeaslesthatshouldbefurtherinvestigated.”14

CDD has been reported following natural measles infection, and caseshave been reported in association with subacute sclerosingpanencephalitis,ameasles-relatedencephalitis.19

In the case of CDD and measles, Rutter himself wrote that profoundregression and behavioral disintegration is often accompanied by a

“premonitory period of vague illness, [when] the child becomes restive,irritable, anxious and overactive…Sometimes these conditions come onaftermeasles,encephalitisorotherclear-cutorganicillnesses.”20

AmongfivechildrenwhofitthecriteriaforCDD,Volkmaretal.describedachildwithonsetofbehavioraldeclinefollowingmeaslesencephalitis.21Hudolinreported that,prior toregression,a15-year-oldboywith limitedspeech, stereotyped and repetitive play, and poor self-care skills, etc.,suffered from an unknown strain of measles and high fever atapproximately30months.22MalhotraandGuptaconfirmthatmanycaseshavebeenassociatedwithsomemedicalconditionsuchasmeasles.5

VaccineshavebeenassociatedwithCDD;forexample, inareportof12cases in India seen between 1989 and 1998,Malhotra and Gupta notedonset in fourcaseswithonset followingeither feverwith seizures,acutegastroenteritis,orvaccination.Thetypeofvaccinewasnotstated.23

Dwellingbrieflyupon theclinical featuresofataxia incombinationwithdevelopmentalregression,potentiallynoveladverseeventsassociatedwiththe combined MMR vaccine, rather than the monovalent componentvaccines, have emerged fromPlesner’sDanish studyof ataxia followingMMR.24 Earlier studies had indicated that ataxia with gait disturbancemightoccurinupto1in1000-4000recipientsofMMR.25,26InDenmarkthisassociationhadnotbeendetectedwithanyothervaccineadministeredtochildrenofthesameagepriortotheintroductionofMMRin1987.Inafollow-upof themandatorypassivereportingsystemforvaccineadverseeventsoperated inDenmark,Plesnernot only confirmed this associationbut also indicated that themore severe ataxias followingMMRmay beassociatedwithresidualcognitivedeficitsinsomechildren,24afindingof

specificrelevancetotheMMR-autismdebate.

Rutter remains steadfast, however. On behalf of the defendants in USvaccine court and elsewhere, he has taken the position that vaccines arenot a cause of autism.Given his pre-eminence, this position is likely tohave been highly influential. Meanwhile, the first reported associationbetweenvaccinesandautismcame,notin1998withTheLancetpaper,butin 1993.27,28 This earlier report took a robust position on the vaccine’slikelyculpability,certainlycomparedwiththerestrainedstatementsinTheLancet paper of 1998. In 1993, the authors described 11 children withautismwhowere excluded fromagenetic studybasedon their having a“medical condition of possible aetiological [causal] importance.” Theauthors stated, “Only eight of the cases can be regarded as having aprobablycausalmedicalcondition,[including]achildwithepilepsyanda temporal lobe focus on the EEG who had an onset followingimmunization.”27,28Whilethehopesofmanydesperateparentsliedasheduponthecoldmarbleof thecourthouse, it isbutan ironicpostscript thatProfessorSirMichaelRutter,FRS,wastheseniorauthorofthatpaper.

ConclusionItisproposedthatautismandCDDareonthesamecontinuumofclinicaldisease.MeaslesvirusexposurehasbeenlinkedtobothCDDandautism.Thetimingofthisexposure—i.e.,early(inutero)orlater,inchildhood-maydeterminetheclinicalpresentation,includingthepresenceandextentof regression. Infantile autismwithout regressionmaybe linked to earlyexposure,whereasCDDwithregressionmaybelinkedtolaterexposure.Itis entirely plausible thatmeasles, in combinationwith two other viruseswhichhavethemselvesbeenlinkedindependentlytoautism-asMMR—mayincreasetheriskforthisconditionincertainchildren.WhetherornotMMRisguiltyaschargedremainstobedetermined.

Endnotes1 EthicalPracticesCommittee(EPC)172-96ratherthanEPC162-95.

2 Heller T. Dementia infantilis. Zeitschrift fur die Erforschung undBehandlungdesJugenlichenSchwansinns.1908;2:141-165.

3 Rutter M. et al. A triaxial classification of mental disorders inchildhood.JournalofChildPsychologyandPsychiatry.1969;10:41-61.

4 Hill AE, & Rosenbloom L. Disintegrative psychosis of childhood:teenage follow-up. Developmental Medicine and Child Neurology.1986;28:34-40.

5 MalhotraS,andGuptaNJ.ChildhoodDisintegrativeDisorder.AutismandDevelopmentalDisorders1999;29:491-498.

6 RussoM,PerryR,KolodnyE,GillbergC.Hellersyndromeinapre-schoolboy.Proposedmedical evaluationandhypothesizedpathogenesis.EuropeanChildandAdolescentPsychiatry.1996;5:172-177.

7 http://www.who.int/classifications/icd/en/bluebook.pdf

8 Hendry CN. Childhood Disintegrative Disorder: Should it beconsideredadistinctdiagnosis?ClinicalPsychologyReview.2000;20:77-90.

9 Rutter M. Infantile Autism and Other Pervasive DevelopmentalDisorders in Child and Adolescent Psychiatry: Modern Approaches;Rutter,MandHersov,L(1985)Ch.34,p.545.Emphasisadded.

10 TestimonyofSirMichaelRutteronbehalfoftheprosecution.GeneralMedicalCouncilvs.DrWakefield,ProfessorWalker-Smith,andProfessorSimonMurch.

11 KuritaHetal.Infantileautismwithspeechlossbeforetheageof30months. Journal of the American Academy of Child and AdolescentPsychiatry.1985;24:191-196.

12 KuritaHetal.Acomparativestudyofthedevelopmentofsymptomsamong disintegrative psychosis and infantile autism with and withoutspeech loss. Journal of Autism and Developmental Disorders.1992;22:175-188.

13 DeykinEYandMacMahonB.Viralexposureandautism.AmericanJournalofEpidemiology.1979;109:628-638.

14 RingA,BarakY,TicherA.Evidence for an infectious aetiology inautism.Pathophysiology.1997;4:1485-8.

15 Steiner CE, Guerreiro MM, Marques-De-Faria AP., Genetic andneurological evaluation in a sample of individuals with pervasivedevelopmentaldisorders.ArqNeuropsiquiatr.2003;61:176-80.

16 MouridsenSE,RichB,IsagerT.Epilepsyindisintegrativepsychosisandinfantileautism:along-termvalidationstudy.DevMedChildNeurol.1999;41:110-4.

17 WeibelRE,CasertaV,BenorDE.Acuteencephalopathyfollowedbypermanentbraininjuryordeathassociatedwithfurtherattenuatedmeaslesvaccines: A review of claims submitted to the National Vaccine InjuryCompensationProgram,Paediatrics.1998;101:383-387.

18 MillerHG,StantonJB,GibbonsJL.Para-infectiousencephalomyelitisandrelatedsyndromes.QuarterlyJournalofMedicine.1956;100:427-445.

19 Mouridsen SE, Rich B. & Isager T. Validity of childhooddisintegrativepsychosis:Generalfindingsofalong-termfollow-upstudy.Br J Psychiatry. 1998;172:263-267. Rivinus TM, Jamison DL, andGraham PJ. Childhood organic neurological disease presenting as

psychiatricdisorder.ArchDisChild.1975;50:115-119.

20 Rutter M. Infantile Autism and Other Pervasive DevelopmentalDisorders in Child and Adolescent Psychiatry: Modern Approaches.Rutter,MandHersov,L(1985)Ch.34,p.556.

21 Volkmar F. and Cohen DJ. Disintegrative disorder or “late-onset”autism.JournalofChildPsychologyandPsychiatry.1989;30:717-724.

22 Hudolin V. Dementia infantilis Heller; diagnostic problems with acasereport.JMentalDeficiencyResearch.1957;1:79-90.

23 Malhotra S, Gupta N. Childhood Disintegrative Disorder: Re-examination of the current concept. European Journal of Child andAdolescentPsychiatry.2002;11:108-114.

24 PlesnerAM,HansenFJ,TaadonK,NielsonLH,LarsenCB,PedersenE.GaitdisturbanceinterpretedascerebellarataxiaafterMMRvaccinationat15monthsofage:afollow-upstudy.ActaPaediatrica.2000;89:58-63.

25 PlesnerAM.Gaitdisturbancesaftermeaslesmumpsrubellavaccine.TheLancet1995;345:316.

26 Taranger J,Wiholm BE. Litet antal biverkninger rapporterade eftervaccination mot massling-passguka-roda hund. Lakartidningen.1987;84:958-950.

27 Rutter M et al. Autism and known medical conditions: myth andsubstance.JournalofChildPsychologyandPsychiatry.1994;35:311-322.

28 Rutteretal.(1993)Autism:Syndromedefinitionandpossiblegeneticmechanisms. InR. Plomin&G.E.McLearn (Eds),Nature,NurtureandPsychology.WashingtonDC:AmericanPsychologicalAssociationPress.Emphasisadded.

CHAPTERTEN

Bedlam1orBonaparteIhaveoftenwonderedwhereautismmightbetodayhaditnotfallenintothehandsofchildpsychiatrists.Wouldthingshavebeenverydifferentif,forexample,thefirstchildwithautismpresentedbeforeDrs.GillesdelaTourette,2 Joseph Babinski,3 and Pierre Marie4 at one of the TuesdaylecturesofthegreatFrenchneurologistProfesseurJean-MartinCharcot?5Ithinkso.Charcot,withhissupremediagnosticskillsandclinicalintuition,would, I believe, havedeferred to hismedical training rather thanbeinginfluenced by the emergent psychoanalysts in his audience.6 The debatewouldhavebeenabriefbutinterestingone.

While Charcot, known as the “Napoleon of the neuroses,” and hiscolleagues at thePitié-SalpêtrièreHospital inParis’ 13th arrondissementwerelimitedintheirabilitytotreatthesyndromestheydescribedandthediseases they diagnosed, they were, nonetheless, unsurpassed in theirability to take a medical history, observe and elicit physical signs, andultimately provide uswith seminal descriptions ofmajor diseases of thenervous system.Had autism existed in late 19th century Paris, it woulddoubtlesshavebeendescribed.But it seems thesemenwereunawareofautismaswereotherequallyeminentEuropeanandAmericanphysiciansofthetime.NotwithstandingTheodoreHeller’sreportofCDDin1908,7itwasnotuntil1943thatchildpsychiatristsfirstlaidclaimtoautism.8Andthereitwastoremainformanyyears,anidiosyncrasy,atragicorphan,adevelopmental anomaly that left parentswithout hope or answers. Fromthattimeon,ithasbeenachallengingjourney−thechallengeintensifying

astheautismepidemiclaidsiegetothefondestpreceptsofthiscondition.Part of the challenge − not uncommon in the history ofmedicine − hasbeen the antagonismengenderedbydifferent perceptions of a condition,sometimeswithinthesamemedicalspecialtybutmorecommonlybetweendifferent medical disciplines. This is evidenced by the alternativeapproaches that different medical specialists have taken to theinvestigationofautismspectrumdisorders.

Part of the controversy at the GMC — an essential element of theprosecution’s case against me and my colleagues — was invested inwhetherornotlumbarpuncture(LP),whichisoftencalledspinaltap,wasanappropriatemedicalprocedureinTheLancet12.Thecase,playedoutbetweentheirexpert,ProfessorRutter,andprosecutingcounselwasthat:

The children were investigated as part of a research project ratherthanonthemeritsoftheirclinicalcondition.Their clinical condition was not consistent with the symptoms ofCDDand,therefore,notcompatiblewithapossibleCDDdiagnosis.Autism— thediagnosis that themajorityactually received—doesnotmeritLP.ProfessorWalker-SmithandhisteamwerenotcapableofmakingtheclinicaldecisiononthemeritsofundertakingLP.

Forgoodmeasure,theGMCallegedandthepanelruledthatIwasguiltyof“causing”thechildrentoundergoanLPforthefollowingreasons:1)Ihad suggested to concerned parents that, in light of their children’sintestinalsymptoms,theyshouldseekareferraltoWalker-Smithand2)Ihadtalkedwithsomeofthechildren’sdoctorseitherattheparent’sorthedoctor’s request,providingbackground information.The implicationsforcommunicationinmedicalpracticeareprofound.

Thefirsttwobulletpointsabovehavebeendealtwithinotherpartsofthis

book(seetheAfterword,“Ethics,Evidence,andtheDeathofMedicine,”andChapter9,“TheDevil’sintheDetail”).Itisthelattertwobulletpointswithwhich thischapter isconcerned,particularly the influenceofRutterontheGMCPaneland,morebroadly,theroleofmedicalinvestigationinchildrenwithautismandrelateddisordersintheUK.

LPinvolvestheintroductionofasterileneedlebetweenthelowerlumbarvertebrae into the space between the lower spinal nerves and theircoverings.Asampleofthecerebrospinalfluid(CSF)thatbathesthebrainand spinal cord iswithdrawn,placed into a sterile container, and sent tothelaboratoryforanalysis.Theprocedureisrelativelycommonplaceintheinvestigationofsickchildrenandisconsideredbymostauthoritiestocarryaminimalriskofcomplicationsinexperiencedhands.9,10

LP is undertaken for the purpose of diagnosing inflammation, infection(which may coexist with inflammation), and metabolic abnormalities(derangementsof thebody’sbiochemistry). In1996,metabolicproblemsamenable to diagnosis by analysis of CSF included mitochondrialdisorders (referred to by us in 1996 as “mitochondrial cytopathies”).Congenital or acquired functional defects in the energy factories of thebody’s cells (mitochondria) are associated with impaired utilization ofglucose as an energy source. The body, particularly the brain, reliesincreasinglyonanaerobicmetabolismwiththeaccumulationoflacticacid(lactate).Thisriseinlactatecanbedetectedinspinalfluid,advancingthediagnosisofapossiblemitochondrialdisorder.Inturn,thesedisordersmaybe amenable to treatments that boostmitochondrial function and reduceoxidativestress.

Infection as a source of neurological injury in childrenmost commonly

takestheformofarelativelyrapid-onseteventassociatedwithabacterialorviralinfection.Ontheotherhand,withaviruslikemeasles,protractedandpersistentinfectionsmayoccurthathaveaninsidiousonsetthatmaybe associated with personality change, behavioral problems, andprogressiveneurologicaldeterioration.Evidenceforsuchaninfectionmaybe found by analyzing the CSF. Vaccine-related complications are alsorelevant in this setting; the meningitis associated with the Urabe AM-9strain mumps vaccine that led to withdrawal of SmithKline Beecham’sTrivirixandPluserixMMRvaccines 11 andAventis Pasteur’s ImmravaxMMR vaccine was confirmed by LP and the detection of the mumpsvaccinevirusintheCSF.12

Remainingforthemomentwithviralinfectionsasacauseofneurologicaldeteriorationinchildren,itisestablishedthatvariousvirusesencounteredin unusual circumstances are associated with brain damage(encephalopathy), CDD, and − arguably indistinguishable from CDD −autisticregression.Thesevirusesincludemeaslesandmeasles-containingvaccines,13 mumps and mumps-containing vaccines,14 rubella,15 andvarious Herpesviridae including herpes simplex virus type-I,16Cytomegalovirus,17 and Epstein-Barr virus (mononucleosis).18 Theunusual circumstances thatmay allow thesehistorically commonvirusestobehaveinanunusuallydamagingwaymayincludeexposureveryearlyin life, pre-existing immunodeficiency, and immunization. Immunizationwith three live, modified viruses given together by injection at a muchyounger age than is typical for natural infection is most certainly anunusualcircumstance.

Against thisbackground,notallofwhichwasevident tomein1996, letmecharacterizethesituationthatconfrontedusbackthen.Weencounteredagroupofchildrenwithlong-standingintestinalsymptomswho,takenat

facevalue,presentedwithbehavioralanddevelopmentalregressionafteraperiodofnormalornearnormalearlydevelopment.ThemajorityhadgonedownhillshortlyafteranMMRvaccine.Presentedwithahighlycomplexclinical situation, a team of colleagues was brought together under theclinicalleadershipofWalker-Smithinordertodeterminewhattestsweremeritedforthesechildrenwiththepurposeofsheddingdiagnosticlightontheir condition and, thereby, identifying avenues for possible treatment.This – a multidisciplinary clinical collaboration – is exactly whathappened,anditworked.

How did the use of LP find its way into the clinical protocol for TheLancet 12? First, Dr.Mike Thompson, a pediatric gastroenterologist onWalker-Smith’s team and recently arrived from Birmingham Children’sHospital, drew our attention to a clinical protocol developed at thathospital for the investigation of children suffering from neurologicaldeterioration.Mitochondrialdisorderswereoneofthelisteddiagnosesthatneeded tobe ruledout.TheBirminghamprotocol advised theuseofLPandmeasurementof lactate in theCSFfor thispurpose.After reviewingtheBirminghamprotocol, the children’s histories (nonehadhad anLP),andconsultingwithDr.PeterHarvey,aclinicalneurologist,LPwasaddedtothelistofrecommendedinvestigations.

Later,under thewatchfuleyeofprosecutingcounselMs.SallieSmithattheGMChearing,RutterprovidedarobustdismissalofthemeritsofLPinthe investigationof themajority ofTheLancet 12. Hewas substantiallylesscriticalundercross-examinationbyMr.AdrianHopkins,QC, seniorcounsel for Professor Murch, on the issue of investigation for possiblemitochondrial disorder19 − the principal reason for LP in The Lancetchildren.

Hopkins:What I amputting to you is this: if theRoyalFreepaediatricgastroenterologistsreceivedadvicethatforchildrenwithahistoryofregression,theyshouldbeseekingtoexcludemitochondrialdisorderandtheproperwayofdoingthatwastodo a lumbar puncture: thatwas advice theywere reasonablyentitledtorelyon,isitnot?

Rutter:Yes.

Second,backattheRoyalFreein1996,areviewoftheparentalnarrativesledourcolleaguesintheDepartmentofChildPsychiatrytotheprovisionalopinion that CDD, rather than autism, was themore likely diagnosis inthesechildren.Berelowitz,theleadchildpsychiatrist,advancedthenotionthatsincehismentorRutterhadreportedCDDinassociationwithmeaslesencephalitis (brain inflammation), it was plausible that a measles-containing vaccine might do the same thing. He also pointed out thatautismitselfmayfollowcongenitalrubella(Germanmeasles)infection.Itwasdecided,therefore,tolookforantibodies20,21,22tothesetwovirusesintheCSFinordertoexcludealong-standing(persistent)braininfection.Inlightof theirhistoryofdeteriorationfollowingMMRand theknowledgethat these viruses can cause chronic brain inflammationwith behavioralanddevelopmentalregression,youmightthinkitsomewhatsurprisingthatthisinvestigationhadnotbeenundertakenpreviously.

Finally,theresearchelementoftheCSFanalyses(forwhichIwastoberesponsible) was to look for cytokines − markers of inflammation andimmunesystemactivationinthebrain.Whilethistestwasneverdone,forreasons that are set out below, it is notable that years later theidentification of brain inflammation in autism (neuroinflammation)

includingabnormalcytokinelevelsintheCSFwasreportedbyresearchersat Johns Hopkins Hospital in Baltimore. Cytokine analysis of CSF hassincebeenusedasaclinicalprocedure inotherUScenters.This findinghasopenedupawhollydifferentviewofautismthat,combinedwiththeincreasing evidence for immunological abnormalities and intestinalinflammation inmany affected children, paints an emerging picture of amultisysteminflammatorydisorder.

LPinTheLancet12:Clinicalorresearch?TheGMCarguedwrongly,butsuccessfully,thatLPhadbeenundertakenon Lancet children as part of a research agenda, described in ethicscommittee(EC)application172-96(seetheAfterword,“Ethics,Evidence,andtheDeathofMedicine”).Rutterconcurredwiththisonthebasisthat,inhisopinion, therewasnoclinical justificationforLPinthesechildrenand that thecircumstancesof the individualchildrenwerenot taken intoaccountinprescribingthistest.

Discreetly, Rutter had acknowledged from the outset that it would be a“difficulttaskfortheGMC”presumablytofindfaultwiththeuseofLPin“the clinical treatment” of The Lancet 12 since, as was revealed in anattendancenotefromtheGMClawyers,

SomepeopleinAmericadoadvocategivinglumbarpuncturestochildren[withautism].23

First, let me begin by underscoring the fallacy of the first point. ThedocumentlabeledbytheECas172-96wasaclinicalandresearchprotocolfor the investigation of 25 affected children. If LP had been a researchprocedure,thenitwouldhavebeenundertaken(withparentalconsent)inall25childrentobeadmittedtothisstudy.

For the children reported in The Lancet, LPs were stopped on theclinician’sinstructionsafteronlyeightprocedureshadbeenperformedasitwas not yielding any useful clinical information, i.e., information thatprovided insights into diagnosis and possible treatment.24 The cliniciansmadethedecisionthat thisclinical testwasnolongerjustified.It isself-evidentthatifLPswerebeingperformedaspartofaresearchproject,thentheywouldhavecontinuedinspiteoftheabsenceofanyclinicallypositiveinformationbecauseresearch(i.e.,measurementofCSFcytokines)ratherthan clinical care would have been the priority. No measurements ofcytokinesinCSFwereeverundertakenonanyofthesechildren;theywerenotpartof172-96.Itwasdecidedinsteadtofocusupontheinvestigationoftheintestinaldiseasethatwasyieldingthemoststrikingandpotentiallytreatablefindings.TheargumentthatthechildrenweresubjectedtoanLPfor the purpose of research rather than clinical care can be seen to behopelesslyillogical.

Rutter’s perception of the evaluation of The Lancet 12 as researchappeared tobemotivated largelybyanextraordinaryattitude toward theinvestigation of possible vaccine adverse reactions. At the GMC, whenshown correspondence betweenWalker-Smith and a referring physician,hewasaskedbySmith:25

Q:Again,ProfessorRutter,isthatlettersuggestivetoyouofaresearchoraclinicalinvestigation?

A: It soundsmuchmore likea research investigation. It talksaboutaprogrammeforinvestigatingchildren.Asforthelinkwith immunisation,26 clearly that was a driver for what was

beingdone.Thatwasclear inMrWakefield’swayofdealingwiththings,butthatwouldnotbeordinarilyseenasaclinicalneedinvestigationatthattime.26Thatisthekindofthingthatif research had shown a meaningful association, it couldbecomeso,butthatcertainlywasnotthecaseatthattime.

Hereisanextraordinaryadmission:inRutter’sopinion,apossibleseriousadversevaccinereactioninachilddidnotmeritclinicalinvestigation.

This exchange also highlights one of themore substantial planks of theprosecution’s case — inference: Walker-Smith’s reference to a“programme of investigation,” soundedmore like research to Rutter. Inaddition, theGMCarguedandRutterconcurredthat investigationofTheLancet 12 must have been research since LP was undertaken without aneurologisthavingseeneachchild.Rutterignoredthefactthat,aswellasbeingspecialistsingastroenterology,Walker-Smithandhiscolleaguesarehighlyexperiencedpediatricians.LPisaprocedurethatisprescribedandundertaken by pediatricians on a regular basis. Based upon the clinicalevidence available to them, they were entirely capable of making adecision on whether or not LP was appropriate in these children. Theindication forLPwasahistoryofdevelopmentalregression.Prior toLPbeing undertaken, Walker-Smith’s team had reassured themselves thattherewasahistoryofdevelopmentalregressionineachofthechildrenonwhomthisprocedurewasundertaken.

LPintheinvestigationofCDDSo what are the merits of LP in a group of children with a suspecteddiagnosisofCDD?Assetout inChapter9,“TheDevil’s in theDetail,”there is little, if any, justification formakingadistinctionbetweenCDDandautism−particularlyregressiveautism.Itisnotable,therefore,thatLP

and analysis ofCSF are advocated bymany authorities onCDD.Undercross-examination by Murch’s senior counsel at the GMC, AdrianHopkins,QC,Rutterhimselfadvocated theuseofLP insuspectedCDD:27

Q: If you are faced with a child in whom you suspect truedisintegrativedisorderasopposedtoautismwitharegressiveelementtoit,thenwouldyouregarditasreasonabletoincludelumbarpunctureinyourclinicalinvestigations?

A:Yes,Iwould.

Ina1996reviewofthemedicalliteratureandcasereportbyRussoetal.,28theauthorsdiscussthekeyfeaturesofCDDandtheoverlapwithautism.In particular, the paper refers to the physical manifestations thataccompany developmental decline in affected children. It describes theneed for thorough medical and neurological examination of childrenundergoing acute or subacute deteriorationwithCDD, includingLP andCSFanalysis formeasles antibodies to examine for evidenceofmeaslesencephalitis. The paper provided useful guidelines for how othersmightevaluateaffectedchildren.ThecasereportgoesontodescribeCDDwithonsetat3.5yearsinaboy.Thekeyfeaturesinthischild’shistorywere:

normalearlydevelopmentprogressivelossofvocalizationandlanguagedevelopmentofrestrictedinterestsrepetitivebehaviorssecondaryurinaryandfecalincontinencespontaneousinconsolablecryingepisodeslossofself-helpskills

HavingreadChapter2,“TheChildren,”theoverlapbetweenthischildand

TheLancet12isevident.Basedupontheirclinicalhistoriesandtheadviceof our colleagues in child psychiatry, there was every reason to, as inAdrian Hopkins’s query, “suspect true disintegrative disorder” in thechildrenwhopresentedtotheRoyalFree.Otherphysicians,includingHull— another prosecution witness at the GMC29 — have also describedsimilar cases and endorsed the approach undertaken by Russo and byWalker-Smith’steamattheRoyalFree.30,31Inhistextbook,Hullwrote:

For example, a girl presents at 26 months of age; herdevelopmenthasbeenquitenormaluntil20monthsofage;herparents thennoticed thatshehadbecome lessresponsiveandtendedtofallmoreoftenwhenwalking;overthenext6monthsher gait became more unsteady, she played less, her speechregressed and she became irritable. Diagnosis —developmentalregression.

Investigations…The following list containsonlyanumberofmorecommonand useful investigations … CSF… elevated protein [and]CSF:serummeaslesantibodytitreratio…

LPandautismThe role ofLP in autism ismore contentious than forCDD, and expertopinionissharplydivided.Infact,debateoverthemeritsofthisprocedurereflects, in someways, the larger debate over the priority of genetics orenvironmentinthisdisorder.Rutter,asanadvocateforthegeneticbasisofautism, sees relatively little merit in routinely investigating its possibleorganicbasisindetail,eventhoughheacknowledgestheorganicbasisofthedisorder.32,33Infact,inhisreporttotheGMClawyershewrote:

Iknowofnochildpsychiatristorchildneurologist in theUKwho would regard lumbar puncture as a justifiable routineinvestigation of children with an autism spectrum disorder.Both would be aware that periods of regression are verycommon in autism34 and are not an indication for detailedinvasiveinvestigation.

Alternatively, Christopher Gillberg, a professor of child and adolescentpsychiatry and autism expert from Sweden, advocates LP in the routineclinical investigation of children with autism, and in his hands, whenspecific hypothesis-testing studies have been performed on CSF, thesehaveconsistentlyidentifieddifferencesbetweenchildrenwithautismandnon-autism controls that support the likelihood of an underlying organicpathology.35

RutterportrayedGillberg’sexperiencesomewhatdifferently inhisGMCtestimony.When asked by Smith whether Gillberg’s published findingsadvocatedLPinautism,Rutterwasdismissive:36

AsfarasIknowhestilladvocatesdoingso,butwhatisquitestrikinginthepublishedreportsistheabsenceofanyevidencethatitisactuallyuseful.

Undercross-examinationbyHopkins,Rutterputitmorestrongly:37

TheevidencefromGillbergoranyoftheotherpeoplewhousethis approach is absolutely consistent in its negativity … SoGillberg’sownfindingsactuallyruncountertotheadvicethat

hegives.

In fact, Rutter’s antipathy towardGillbergwas a recurring theme in hisevidence,whichatonetimedescribedhimashaving

…anunenviablyhighreputationforfindingsthatcouldnotbereplicated.

Rutter’srecurringdisdainforhiscolleagueearnedhimrebukeundercross-examination.When Hopkins brought Rutter’s attention back to the factthat Gillberg’s analysis of CSF had actually led to a series of positive,publishedfindings,RutterdefaultedtoadismissalofGillberg’sscienceingeneral.

TheGMCPanelwas led to believe that the use of LPwas a peculiarlySwedish — indeed, peculiarly a Gillberg — phenomenon. DuringHopkins’s cross-examination, he pointed out to Rutter thatGillberg hadcoauthoredanauthoritative textbookwithDr.MaryColeman,apediatricneurologistfromtheUS,inwhichtheyhadwritten:38

…lumbarpunctureistheretoexcludeprogressiveencephalitisandencephalopathy…

…the evidence concerning the association, even of so calledclassicalautismcases,withawidevarietyofspecificmedicalconditions,…isnowsuchthatitmustbeconsideredclinicallyunacceptablenottoperformawork-upofthiskind.39

The challenge to Rutter from both sides of theAtlanticwas clear − his

diagnostic approach to autism was, in Gillberg and Coleman’s opinion,“unacceptable.”

This professional hostility appears to have been part of a long-standingdebate over whether or not a more thorough clinical investigation ofchildren with autism increases the yield of medical disorders and,therefore,potentialopportunitiesfortreatment.

Doesmorethoroughinvestigationofchildrenwithautismincreasetheyieldofmedicaldiagnosis?

In1996,GillbergandColeman40providedacomprehensivereviewoftheassociation between autism and medical disorders based upon sevenpopulation-basedstudies.Theywrote:

The rate of associated specific medical disorders and/ororganic conditions in autism has varied from 11 or 12% inpopulation-based studies that did not include comprehensiveneurologicalandmedicalinvestigation(Gillberg198441:Rivtoet al. 199042) to 37% in studies that did include suchinvestigation(Steffenburg199143).Inthelatterstudy,only17%wouldhavebeenshowntohaveanassociatedmedicaldisorderif the neuropsychiatric assessment had not beencomprehensive.Thusitseemsthatthemorecomprehensivethemedical examination, the greater the yield of associatedmedicaldisorders.

Intuitively, it would seem to be of fundamental importance to identifyassociatedmedical disorders, in particular, where such disorders lead tothepossibilityofeffectivetreatments;anexampleofthiswouldbeherpes

virus encephalitis. Gillberg andColemanwere critical of Rutter and hiscolleagues based upon what they consider to be a fundamental error inRutter’sanalyticalapproachtotheavailablestudies:

Someauthors(e.g.Bailey199344.Rutteretal199445)appeartobelievethattherateofassociatedmedicaldisorderscanbecomparedacrossstudiesregardlessoftherepresentativenessofthesampleorthecomprehensivenessoftheexamination.Sincealmostallautismstudies(oftenonclinicorotherwisereferredpatient groups rather than community-based samples) haveincluded only very limited medical investigation (physicalexamination plus chromosome, blood and urine screens atmost), the conclusion has been that associated medicaldisorders,althoughoccurringinaproportionofautismcases,arerelativelyrare(around10to12%accordingtoRutteretal.1994).

Inthepublishedliterature,however,theonlypopulation-basedautism sample to receive a comprehensive medical,biochemical and neurological examination was the onereported by Steffenburg (1991). TheWing and Gould (1979)studywasprobably thenextmostcomprehensivestudy in thisrespect,and theoverallprevalenceofpossiblyautism-relatedmedicaldisorderswasalmost identical.Therefore,untilotherpopulation-based samples have been subjected tocomprehensive medical examination (which is not to beequatedwitha range,howeverwide,ofbloodandurine testsonly), it remains open to speculation just how large theproportionofcaseswithassociatedmedicaldisordersis.

Theycontinued:

…regardless of whether the rate of associated medicaldisorders in autism is 11%, 24%, or 37%, there is clearly aneedforacomprehensivemedicalexamination.Severalofthemedical disorders that are now known to be sometimesassociated with autism can only be diagnosed by extensiveexamination, which should include… cerebrospinal fluidexamination (for encephalitis and progressiveencephalopathies).

Herewehavewell-recognizedauthoritiesonautismmakingastrongcasefortheroutineuseofLPinthediagnosisofmedicaldisordersassociatedwithautism.FromtheInstituteofPsychiatry,King’sCollegeLondon, in2001,anotherofRutter’sprotégés,Dr.PatrickBolton,acknowledgedbothsidesofthemedicalinvestigationsdebatewhenhewrote:

Thechoiceofappropriateteststoidentifytheseconditionshastobeguidedbythehistoryandresultsofphysicalexamination,aswellastheexpectedyieldandinvasivenessoftheprocedure.Thishasbeenthesubjectofsomedebateintheinvestigationofchildrenwithautisticspectrumdisorders,withsomecliniciansadvocatingthatanextensivemedicalworkup(e.g.brainscansand lumbar punctures) always be conducted (Gillberg andColeman,1996).Bycontrast,themajorityfavouramuchmorelimitedsetofinvestigations(Rutter1994;BartonandVolkmar1998).46,47

However,Boltonmakesnoreferencetothefactthatthediagnosticyieldofassociatedmedical conditions is substantially increased by the approachadvocatedbyGillbergandColeman.Boltoncontinued:

The likelihoodof identifyingamedicalcondition is related tothe severity of the developmental disorder and is greatest in

peoplewithsevereandprofounddegreesofhandicap

Ifthiswasintendedtoaidothersinidentifyingsubgroupsofchildren(i.e.,those with profound degrees of handicap) that should undergo moreextensivemedicalinvestigation,thenitfailstoprovideadequateguidance.Bolton also fails tomention that the likelihood of identifying amedicalcondition is directly related to the diligence with which it is sought. IncontrastwiththerathernihilisticviewofRutterandcolleagues,Dr.CherylHendryfromtheUniversityofGeorgiaadvocatesthat

ThereisalsoasignificantneedtoclarifythenatureofpossibleorganiccausesofCDD,AutisticDisorder,andotherpervasivedevelopmental disorders, as well as the mechanisms ofneurologicalinsult.48,49

Themosteffectivewaytodothisistoadoptamoreaggressive,systematicapproach to delineating the organic basis of the symptoms in each andeverychild.Rutter’s1994paper50isinstructivewhenhestates:

Gillberg has urged that the supposed strong associationwithknownmedical conditionsmeans that extensive investigationsincludinglumbarpunctureandCATscanshouldbeundertakenas routine. Federico et al (1990) have put forward similararguments… However, most reviewers have not consideredlumbar puncture or brain imaging as part of the range ofessential investigations to be undertaken in the absence ofspecificindications(Rutter1985;Bailey1994).

Rutterdoesnotprovideanexplanationofwhatthese“specificindications”mightbeuntilsomewhatlaterinthepaperwhenhestates:

It seems very dubious whether it is necessary to perform a

lumbar puncture in the absence of any clinical indications ofdeterioration.

It seems, therefore, that “deterioration” in the condition of a child is anindicationforLP.All12ofthechildrenreportedinTheLancetexhibiteddeterioration. Furthermore, under the rubric of Rutter’s “specificindications,” it has been considered routine, i.e., standard of care, toexamineCSFinchildrenwhentheirautisticregressionhasbeenassociatedwitha specific infectiousexposure.51 It seems logical toassume that thechance of identifying a causative infection is likely to be much greaterwhen developmental regression follows a documented infectious (orvaccine)exposure.Andyet,whenachild’sdeteriorationfollowsavaccine—onecontainingviruses thatarewellknown tobecapableof infectingthebrain,causinginflammation,andhavebeenassociatedwithautisminthemedicalliterature—LPisfrownedupontotheextentthatitbecomesachargeofmedicalmisconduct.

MovingonfromRutterandchildpsychiatry,whatistheopinionofexpertsin child neurology who, in contrast with many psychiatrists, are moreinvested in the organic basis of nervous system disease rather than itspossible psychological origins? The late Dr. John Menkes, professoremeritusofneurologyandpediatricsatUCLAandeditorofthedefinitivetextbookChildNeurology, was a world authority on autism and relateddisorders.ExclusionofmitochondrialcytopathybymeasurementofCSFlactate is described specifically by Dr. Menkes as an indication for theprocedureinsuchchildren.52,53Inane-mailtomeonFebruary11,2006,shortlybeforehisdeath,headded:

Itismyopinion,andwesoexpresseditinthelatesteditionofmy textbook, a CSF analysis can “assist” in the differentialdiagnosis of regressive autism. It is alsomy opinion that the

risks of a lumbar puncture in a child with autism are sominisculethatIseenocontraindicationtotheprocedure.

Dr. Marcel Kinsbourne is a pediatric neurologist and an expert inchildhood developmental disorders. He trained in medicine at OxfordUniversity and Guy’s Hospital in London and is currently an emeritusprofessorofpediatricneurologyatTuftsUniversityinBoston.Hisexpertopinionisasfollows:

Whenachildwhohashithertodevelopednormally,begins tolosementalskillsprogressively in thesecondyearof life, thisrepresents a progressive encephalopathy that requiresdiagnosis. The fact that the final outcome of the regressiontakestheformofthebehavioralsyndromeofautismisoflittlediagnostichelpas it iswell knownandgenerallyagreed thatthereareatleastdozensofdifferentcausesofsyndromesoftheautistic spectrum. Specifically such a child could have adegenerativemetabolic or a subacute inflammatory conditionof the nervous system, for instance as caused by a “slowvirus”.Ifthatwerethecase,itwouldbeimportanttoestablishthisforpurposesbothofprognosisandpotentialtreatment.

Themost direct way of determining themedical condition ofthebrain, shortofbrainbiopsy,whichwouldbe inadmissiblein most such cases, is to study the composition of thecerebrospinal fluid. Abnormal cytology and markers ofinfection suchas immuneglobulins, the infectiousagent itselforfragmentsofitsgenomecannowadaysbedetectedwithhighsensitivity. The spinal fluid is acquired through lumbarpuncture (spinal tap). In my chapter in Textbook of ChildNeurology (Menkes, Sarnat & Maria, eds, 2006), I write as

follows in the section entitled “Autism: DiagnosticEvaluation”: “A spinal tap can assist in the differentialdiagnosis of new onset seizures or autistic regression” (page1118).

Tostudyachildwhohasregressedfromnormaldevelopmentintoanautisticsyndromebylumbarpunctureisnotintheleastabusive;itisthoroughlywarrantedonclinicalgrounds.54

The UK’s experience with mad cow disease (bovine spongiformencephalopathy or BSE) has been a timely instruction in the correctapproach to neuropsychiatric syndromes of unknown cause. MartinRossor, professor of clinical neurology at the National Hospital forNeurological Diseases and St. Mary’s Hospital, London, gave thefollowingevidence to theUK’sSouthwoodBSEenquiryonOctober26,1998:55

Thedifferentialdiagnosisofpatientspresentingwithcognitivedisturbance, particularly in the young, is very wide. Suchpatientsrequirecarefulassessmentandextensiveinvestigation.

Hecontinued:

Neuro-imagingshouldbeundertakeninthemajorityofpatientspresentingwithcognitiveimpairmentanditismandatoryinallunusual casesandall youngpeople…All unusualand youngonset patients with dementia should also have thecerebrospinal fluid (CSF)examinedby lumbarpuncture.Thiswill identify inflammatory changes suggesting an infection orinflammatorydisordersuchasmultiplesclerosis.

So,youappreciate that there is, at thevery least, adivergenceof expertopinionon themerits ofLP in the investigationof autism.There is lesswhen theautism is regressiveandnodebateover theneed forLP in theinvestigationofCDD.Youmightthinkthattheappropriateforumfortheresolutionof anyoutstandingdifferenceswouldbe thepagesofmedicaljournalsratherthanfromthewitnessstandoftheGMC.

Wherearewenow?LP was abandoned in early 1997 as a routine clinical procedure in theaffected children presenting to the Royal Free. In the small number ofchildren who had this investigation, it did not reveal any evidence of amitochondrial disorder, nor were antibodies against measles and rubellapresentintheCSF.Undertheseclinicalcircumstances,Walker-Smithandhis team decided to pull this test in order to reduce the number ofproceduresthechildrenunderwent.

Mitochondrial disorders have since become a hot topic in autismwith ahigh proportion of children showing evidence of mitochondrialdysfunction56—something that theymayhavebeeneitherbornwithoracquired from an environmental stressor early in life, such as organicmercury.Nonetheless,therehavebeenadvancesindiagnostictechniques,andLPisnotnecessarilyrequiredtodetectmitochondrialdisorders.

Inhindsightwith respect to looking forapossibleviral cause, itmaybethatstoppingLPsattheRoyalFreewaspremature.WhenweundertookamoredetailedanalysisofCSFon three similarlyaffectedUSchildren incollaborationwithDr. James JeffreyBradstreet of Florida andProfessorJohnO’LearyofDublin, the sameuniqueparts ofmeaslesvirusgeneticmaterial were found in the CSF of all three children. 57 In addition,

elevated levels of measles antibody were found in two of the threechildren.NoevidenceofmeaslesviruswasfoundintheCSFofthreenon-autism control children. The laboratory techniques for measles genedetectioninO’Leary’slabhavesincebeencriticized58andvindicated.59Alargerstudyusingthesametechnologywaslaterpresentedatascientificmeeting on autism;60 submission of the full publication has awaitedresolution (successful) of the technical issues associated with measlesvirusdetection.

The Methods section of the draft paper explicitly states the clinicalindicationforundertakingtheprocedureinchildrenwithautisticdisorder:

Since AE [autistic encephalopathy] children had sufferedneurological deterioration associated with developmentalregression following a viral exposure, CSF analyses werethereforeclinicallyindicatedinthepresenceofanincompletelydiagnosedregressiveencephalopathy.

Inthisstudy,measlesvirusgeneticmaterialwaspresentinCSFfrom19of28 (68%)casesand inoneof37 (3%)non-autismcontrols.Further testsconfirmedthatwheretherewassufficientamountofsampleavailable,thegeneticmaterialwasconsistentwithhavingcomefromthevaccinevirus.

Thedraftpaperconcludesbysaying,

ThedataindicatethatvirologicalanalysisofCSFisindicatedinchildrenundergoingautisticregressionfollowingexposure61tolivevaccineviruses.

The paper’s conclusions stop well short of any claim that the MMRvaccinecausesautism.ThemostonecansayfromthefindingsofmeaslesviralgeneticmaterialinCSFisthatthereisastrongstatisticalassociationbetween the presence of this virus and the autismgroup.The finding ofmeasles antibody in CSF in the smaller study is in some ways moreinteresting since it suggests local production of an immune response tomeasles virus in the brain of some affected children. Further study isclearlyrequiredtoseeifthisfindingcanbereplicatedelsewhere.

What is the current status of genetics? Substantial – almost exclusive −investmentinageneticmodelofautismhasleadtodisappointment,tosaytheleast.Geneticstudieshavecomprehensivelyfailedtosubstantiateanybelief that for the great majority of cases autism represents a primarygenetic disorder.Rather, the prevailing consensus is that themajority ofcurrentautismcasesoccurinresponsetoavarietyofenvironmentalcausesor triggers to which there may be a genetic predisposition. But this iswhere thebiasofsomanyexperts in thefield resides.Lauding thechildpsychiatristwhofirstdescribedautism,RutterwrotethisofKanner:

In an era that has sometimes been thought of representing“epidemicenvironmentalism”,hewasastuteinsuggestingthatautismrepresentedsomekindofinbuiltdeficit.

Onecannothelpbutfeel that thisbiasinsoinfluentialabodyofexpertshasrestrictedtheirviewpointtotheextentthatprogresshasbeenimpeded.The necessary transition formany diseases from the geneticmodel to adominant environmental model is not a new one. Until the 1980s,immunodeficiencysyndromeswere relatively rare, consistingofamixedbagofgeneticanomalies thatcompromisedvariousaspectsof immunity,leading to opportunistic infections and cancer. Then they were not; anepidemicofacquiredimmunodeficiencydroppedpeopleintheirthousands

asAIDSswept theglobe.Asanother instance,Irememberonlytoowelllectures in the 1980s on the relationship between the genetics of bloodgroups and the associated risk of duodenal ulcers, stomach ulcers, andstomach cancer. An Australian doctor refocused the attention of themedical community on a helical bacterium in the stomach of ulcersufferers, treated themwith antibiotics, and cured their ulcers. Thatwastheendofanydiscussionofbloodgroupgenetics.Thisisnottosaythatitwaswrong; it justbecameredundant, irrelevant in thefaceofafarmorecompelling set of facts. Autism is currently undergoing the sametransition.

And before overfocusing on the categorical delineation of one set ofchildren from another based upon their presenting features, it should beborne inmind that themanifestationsofenvironmentally-drivendiseaseswillbedeterminedtoalargeextentbythepatternofexposuretothecausalenvironmental factor(s). Variables that matter include how old you arewhenyouget“hit,”whatdoseyougethitwith,ifyouarecoincidentallyillwithanotherdiseasewhenyougethit,whatyourgeneticpredispositionis,andbywhat routeofexposureyouarehit. In thecontextof thevaccinedebate, the nature of sequential or concurrent exposures to the likes ofmercury and aluminum that modify immune responses, and live viralvaccineswhosebehavior isdependentonthoseimmuneresponseswill, Ibelieve,beamajordeterminantofwhatanadversereactionlookslike.

Acausalexposureat6monthsofagemaycauseanautisticsyndromethatleaves a child asocial, lacking speech and language, always incontinent,and classically autistic. In contrast, the same exposure at 3 years of agemay cause the same child to lose speech and language, lose previouslyacquiredcontinence,butremainaffectionatetothoseheknowsbecausehehaslearnedtherewardsofsharedaffection;nowhisdisorderwillreceivealabel of atypical autism or CDD. In this example, the different

manifestations of the same disease process should not be artificiallydistinguished as has been advocated for autism and CDD according toRutter’smajorcriterionofage-of-onset.Todo so implies that theyhavedifferentcauses;thecluesaremissed,andthediseaseanditscause(s)endupchasing−butnevercatching−theartificiallabels.

Child psychiatry has applied itself most comprehensively to thedescription and subcategorization of autistic disorders, drawing andredrawingthelinesthatapparentlydistinguishsomeaffectedchildrenfromothers. The fifth iteration of the Diagnostic and Statistical Manual ofMentalDisorders(DSM-V)fromtheAmericanPsychiatricAssociationisinpreparation,62 redrawing these linesoncemore.Theneed todo this isdriven, in part, by the changing presentation of autistic disordersthemselves, e.g., the increasing frequency of autistic regression. Oneshould not underestimate the importance of this descriptive process, forwhich Rutter must take much of the credit. It’s simply that, from theperspective of this outsider, such a self-perpetuating processmeans thatthe actual disease (and by extension, its cause[s]) ends up chasing thedefinitionsratherthantheotherwayaround.

As a discipline, child psychiatry has been far less helpful in guidingdoctorsonhowtoinvestigateaffectedchildren.Gillbergwascandidabouttheseshortcomingswhenhewrote:

There is a very conspicuous lack of literature in the field ofautismwork-up.Guidelinesforcliniciansplanningtoworkuptheirpatientswithautismarevirtuallynonexistent.63

Finally, there is a differentway of looking at disease; one that discardscategorizationwiththeendpointdeterminationofwhetherachildfulfills

thediagnosticcriteriaforafull-blownautismdiagnosisorfallsjustshortwith a label of pervasive developmental disorder — not otherwisespecified (PDD-NOS). This alternative approach does not just startwiththeparentalnarrative−itistrulyinvestedinit,usingitasthenavigationsystemwithoutwhich thedisease iscondemnedtoforeverwander in thewilderness of psychiatric name-calling. There is no room for bias,prejudice, or recrimination in this medical model. The overspecializeddoctormust be prepared to embrace theNew, revisit themedical schoollessonsinimmunologyandbiochemistry,embraceratherthanfearchange−particularly foraconditionwheresuch ignoranceprevails,andnot runwhen parents mention vaccines as a possible trigger. There is no morecomplexadiseasethanthatseenintheautisticchildrenwhoattendedtheRoyal Free − children that the prosecuting counsel at theGMCclaimedwere not actually sick at all . . . children that some at the Royal Freeactivelyturnedaway—Godhelpthem.Butthestartingpoint iseasy—humblinginthefaceofsomuchthatisunknown;itistheparents’story.Thatdoesnotmean thatdiseasewillgiveup its secretseasily,but it’sastart.

IreturntothatfirstchildforwhomRutterdescribedimmunizationasthe“probable”causeofhisautismasIdescribedforyouinChapter9,“TheDevil’s in theDetail.”64Clearly,Rutter andhis coauthors acknowledgedthe validity of the parental narrative and documented it in strong terms.With this history of onset following vaccine exposure, what did Rutterconsider tobe themechanismofdamage that led this child into autism?Andhowwasthischildinvestigated?Havingdescribedthiscasein1994,intheearlyyearsoftheUK’sautismepidemicandwellintoitintheUS,thiswouldhaveprovidedaveryimportantinsight.WithRutter’sgravitasbehind it, who knows what impact this might have had in shapingperceptionandtheresearchagenda.Butunfortunately,asisevidentfromRutter’s testimony under cross-examination in US vaccine court 65 thechild’shistoryseemstohaveleftlittleimpressiononhim.

Q:Now,you’reactuallydiscussinginthisparagraphareviewpaper that you had published, actually a study you hadpublished back in 1993 on Systematic Investigation of 100IndividualsWithAutism.And you say here that only eight ofthese cases can be regarded as having probably a causalmedical condition, one being a child with epilepsy andtemporal lobe focus on theEEGwho had an onset followingimmunization.Doyouseethat?

A:(Nonverbalresponse.)

Q:Iassumethat thatwasacaseofregressiveautism,wasn’tit?

A: I have no memory as to whether it was or it wasn’t. I’msorry.Ican’thelpyouonthat.

Andwhat about the comorbid gastrointestinal problems in childrenwithautism; are theyneworwere they there all along, languishingwhile thecollectivedissonanceofthecognoscentidefaultedtoanattitudeof“that’sjust autism for you”? Kanner described gastrointestinal symptoms in ahighproportionofhisfirstpatients;66DohanandGoodwindescribedsuchsymptomsin1968and1971,respectively;67Walker-Smithreportedthemin1972;68GillbergandColemansought tohighlight“celiacautism”asasubtypeintheirtextbookin1985;69thereisnothingnew.

AndRutter−wheredoeshestandinallofthis?Undercross-examinationfrom Stephen Miller, QC, leading counsel for Professor Walker-Smith,Rutterwasaskedaboutgastrointestinalsymptomsinautism.

A:I think it issomethingcertainlywellworth lookingat.Thegeneralproposition,justtoreturntothatforamoment,isthatindividualswith autism frequently haveGI symptoms.That isuncontroversial and clear. It would be of potential value tounderstand what on earth that means. I agree with that.Therefore the investigation of those in more detail I wouldcertainlysupport.70

Despitethis,itwasevidentfromfurtherquestioningthatRutterhadhadnocollaborative interaction with a pediatric gastroenterologist in either aclinical or research setting. Since Rutter acknowledged that intestinalsymptomsareso“commonanduncontroversial”71inpatientswithautism,thisbegsthesimplequestion,“whynot?”

IamleftwonderinghowthosedoctorsatthePitié-Salpêtrièrewouldhaveviewedthegastrointestinalsymptomsandtheirpotentiallinktodisorderedneurology in autism. As it is, in some corner of the Cimitière deMontmartre, Paris, Charcot is likely to have turned in his grave severaltimesinthelightofwhathasbefallenthesechildren.Ultimately,ittookagroup of gastroenterologists to recognize the significance of thesesymptoms, not through some preternatural wisdom, but through thediligentapplicationof their training.Anewsyndromewasdescribedandthe findings replicated around the world .72 Erasure from the MedicalRegisterisasmallpricetopayfortheprivilegeofworkingwithaffectedfamilies.

Endnotes1 Bethlehem Psychiatric Hospital (Bedlam) in the London borough ofBromley, where Professor Sir Michael Rutter, FRS, and his colleaguesworkedintheDepartmentofChildPsychiatry.

2 GeorgesAlbertÉdouardBrutusGillesdelaTourette(1857-1904)wasa French neurologist who described what became known as Tourettesyndromeinninepatientsin1884as“maladiedestics.”Charcotgavethesyndrometheeponymoustitle“GillesdelaTourette’sillness.”

3 Joseph Jules François Félix Babinski (1857-1932) was a Polishneurologist.In1896,hedescribedwhatbecameknownasBabinski’ssign,a pathological plantar reflex (upward movement of the toes elicited bystroking the sole of the foot (“phenomène des orteils”) indicative ofcentralnervoussystem(corticospinaltract)damage.

4 PierreMarie(1853-1940)wasaFrenchneurologistwho,amongotherthings,describedadisorderofthepituitaryglandknownasacromegaly,anoverproductionofgrowthhormoneleadingto“giantism.”

5 Jean-MartinCharcot(1825-1893),“theNapoleonoftheneuroses,”wasaFrenchneurologistandprofessorofanatomicalpathology.Heisoneofthe pioneers of neurology, and his name is associated with at least 15medical eponyms, including joint manifestations of neurosyphilis,Charcot-Marie-Tooth disease, and amyotrophic lateral sclerosis (LouGehrig’sdisease).

6 SigmundFreudwenttoParisin1885tostudywithCharcot.

7 Theodore Heller, a special educator in Vienna, proposed the termdementiainfantilis in1908toaccountfortheconditionofdevelopmentalregressiondescribedin“TheDevil’sintheDetail.”

8 Kanner L. Autistic disturbances of affective contact. Nerv. Child.1943;2:217-50.

9 ThelateProfessorJohnMenkes,DepartmentofNeurology,UCLA,toAJWviae-mailofFebruary11,2006:“ItisalsomyopinionthattherisksofalumbarpunctureinachildwithautismaresominisculethatIseenocontraindicationtotheprocedure.”

10 GMCvs.Wakefield,Walker-SmithandMurch.Ruttertestimony:Tr.38.

Q.[Hopkins]LumbarpunctureforCSFanalysisisasafeandrelativelynontraumaticprocedure.Ithinkyouagreewiththatproposition?A.[Rutter]Yes.

11 The samevaccinewithdrawn asTrivirix inCanada and launched intheUKasPluserix.

12 See Chapter 4, “The Whistleblower,” and Martin Walker’s articletitled “The Urabe Farrago.” Retrieved from:http://www.wesupportandywakefield.com/documents/The%20Urabe%20Farrago.pdf

13 WeibelRE,CasertaV,BenorDE.Acuteencephalopathyfollowedbypermanentbraininjuryordeathassociatedwithfurtherattenuatedmeaslesvaccines: a review of claims submitted to the national vaccine injurycompensationprogram,Pediatrics.1998;101:383-387.DeykinEY,MacMahonB.Viralexposureandautism.AmericanJournalofEpidemiology.1979;109:628-638.RingA,BarakY,TicherA.Evidenceforaninfectiousaetiologyinautism.Pathophysiology.1997;4:1485-8.

14 Johnstone JA, Ross CAC, Dunn M. Meningitis and Encephalitis

Associated with Mumps Infection: A 10-Year Survey. Arch Dis Child1972;47:647-651.

15 Chess S. Autism in children with congenital rubella. J Autism DevDisord.1971;1:33-47.

16 DeLongRG,BeanC,BrownF.Acquiredreversibleautisticsyndromein acute encephalopathic illness in children. Child Neurology.1981;38:191-194. Gillberg C. Brief report: onset at age 14 of a typicalautisticsyndrome.Acasereportofagirlwithherpessimplexencephalitis.JAutismDevDisord.1986;16:369-375.

17 Stubbs EG, Ash E, Williams CPS. Autism and congenitalcytomegalovirus.JAutismDevDisord.1984;14:183-189.

18 ShenoyS,ArnoldS,ChatilaT.Responsetosteroidtherapyinautismsecondary to autoimmune lympho-proliferative syndrome. J Pediatrics.2000;136:682-687.

19 GMCvsWakefield,Walker-SmithandMurch.Tr.38.p.20.

20 Immune system proteins that specifically target and protect theindividualfrominvadinginfections.Antibodiesarefoundinthebloodandatthemucosalsurfacesofthebodysuchasthelungandintestine

21 VargasDL,NascimbeneC,KrishnanC,ZimmermanAW,PardoCA.Neuroglialactivationandneuroinflammationinthebrainofpatientswithautism.AnnNeurol.2005;57:67-81.

22 Department ofNeurology, theChicagoMedical School ofRosalindFranklinUniversity;theSutterNeuroscienceInstituteinSacramento;andthe Department of Educational Psychology at Illinois State University.See:M.Chez,T.Dowling,P.Patel,P.Khanna,M.Kominsky.Elevationof Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of AutisticChildren.PediatricNeurology, 2007;36:361-365. “The current procedure

[LP]was elective andwas done to exclude a degenerative process. Thepatients had routine clinical cerebrospinal fluid studies performedincludingcellcountforredandwhitebloodcells,totalproteinandglucoselevels.”

23 GMCvsWakefield,Walker-Smith,andMurch.AttendancenotefromunusedmaterialRuttertoFieldFisherWaterhouse.September7,2006.

24 AJWlettertoPegg.February3,1997.

25 GMCvsWakefield,Walker-SmithandMurch.RutterTestimonyTr.35.p.56.

26 Emphasisadded.

27 GMCvsWakefield,Walker-SmithandMurch.RutterTestimonyTr.38.p.25.

28 RussoM,PerryR,KolodnyE,GillbergC.Hellersyndromeinapre-schoolboy.Proposedmedical evaluationandhypothesizedpathogenesis.EuropeanChildandAdolescentPsychiatry.1996;5:172-177.

29 Hull D and Milner AD. Hospital Paediatrics. London. ChurchillLivingston,1984.

30 Mouridsen SE et al. A comparative study of genetic andneurobiological findings in disintegrative psychosis and infantile autism.PsychiatryandClinicalNeurosciences.2000;54:441-445.

31 MalhotraSandGuptaN.JAutismDevDisord.1999;29:491-498.

32 Rutter et al. Autism and known medical conditions: myth andsubstance.J.ChildPsychol.Psychiat.1994;35:311-322.

33 RutterreporttoFieldFisherWaterhouse.May7,2007.

34 Emphasisadded.

35 Gillberg C, Terenius L, Hagberg B,Witt-Engerstrom I, Eriksson I.CSFbetaendorphins in childhood neuropsychiatric disorders.BrainDev.1990;12:88-92.AhlsenG,RosengrenL,BelfrageM,PalmA,HaglidK,Hamberger A, Gillberg C. Glial fibrillary acidic protein in thecerebrospinal fluid of children with autism and other neuropsychiatricdisorders.BiolPsychiatry.1993;15:734-43.GillbergC,SvennerholmL.CSFmonoamines in autistic syndromesandother pervasive developmental disorders of early childhood. Br JPsychiatry. 1987;151:89-94. Gillberg C. Not less likely than before thatmeanCSFHVAmaybehighinautism.BiolPsychiatry.1993;15;34:746-7.NordinV,LekmanA,JohanssonM,FredmanP,GillbergC.Gangliosidesincerebrospinalfluidinchildrenwithautismspectrumdisorders.DevMedChildNeurol.1998;40:587-94.Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA.Neuroglialactivationandneuroinflammationinthebrainofpatientswithautism.AnnNeurol.2005;57:67-81.

36 GMCvsWakefield,Walker-SmithandMurch.RutterTestimony.Tr.35.p.23

37 GMCvsWakefield,Walker-SmithandMurch.RutterTestimony.Tr.38.p.22

38 GMCvsWakefield,Walker-SmithandMurch.RutterTestimony.Tr.35.p.22

39 Emphasisadded

40 GillbergCandColemanM.Autismandmedicaldisorders:areviewoftheliterature.DevMedandChildNeurol.1996;38:191-202.

41 Gillberg et al. Infantile autism and other childhood psychoses in aSwedishurbanarea.JChildPsychandPsychiat.1984;25:35-43.

42 Ritvoetal.TheUCLA-UniversityofUtahepidemiologicsurveyofautism:theetiologicroleofrarediseases.Am.JPsychiat.1990;147:1614-21.

43 SteffenburgS.Neuropsychiatricassessmentofchildrenwithautism:apopulationbasedstudy.DevMedChildNeurol.1991;33:495-551.

44 BaileyA,etal.PrevalenceofFragileXanomalyamongautistictwinsandsingletons.JChildPsychiat.1993;34:673-688.

45 Rutter M, et al. Autism and known medical conditions: myth andsubstance.JChildPsychol.Psychiat.1994;35:311-322.

46 Emphasisadded.

47 Bolton P. Developmental Assessment. Advances in PsychiatricTreatment.2001;7:32-42.

48 GillbergCandColemanM.Autismandmedicaldisorders:areviewoftheliterature.DevMedandChildNeurol.1996;38:191-202.

49 Hendry CN. Childhood disintegrative disorder: Should it beconsideredadistinctdiagnosis?ClinicalPsychologyReview.2000;20:77-90.

50 Rutter M, et al. Autism and known medical conditions: myth andsubstance.JChildPsycholandPsychiat.1994;35:311-322.

51 DeLongRG,BeanC,BrownF.Acquiredreversibleautisticsyndromein acute encephalopathic illness in children. Child Neurology.1981;38:191-194.

52 Menkes JH and Sarnat HB. Child Neurology. 6th Edition.Philadelphia:Lippincott,WilliamsandWilkins,2000.

53 Menkes JH and Sarnat HB. Child Neurology. 6th Edition.Philadelphia:Lippincott,WilliamsandWilkins,2000.

54 Kinsbourne to Wakefield and Radcliffes Lebrasseur. E-mail. July2006.

55 http://62.189.42.105/report/volume1/toc.htm.(nolongeravailable).

56 Oliveira G, Diogo L, GarciaMP,Miguel ACT, Borges L, VicenteAM,OliveiraCRMitochondrialdysfunctioninautismspectrumdisorders:a population-based study.Developmental Medicine & Child Neurology.2005;47:185-189.WeissmanJ,KelleyRI,BaumanM,CohenBH,MurrayKF,MitchellRL,Kern RL. Natowicz MR. Mitochondrial disease in autism spectrumdisorder patients: a cohort analysis. PLoS ONE. 2008;3(11):e3815.Doi:101371/journal.pone.0003815 Autism Speaks. (2010) Mitochondriaand Autism: Energizing the Study of Energetics. Retrieved fromhttp://www.autismspeaks.org/science/science_news/mitochondria_autism_energetics.php

57 Bradstreet JJ, El Dahr J, Anthony A, Kartzinel JJ, Wakefield AJ.Detection of Measles Virus Genomic RNA in Cerebrospinal Fluid ofThreeChildrenwithRegressiveAutism:aReportofThreeCases.Journalof American Physicians and Surgeons. 2004; 9:38-45 [All children hadreceivedMMRandnonehadahistoryofmeasles.]

58 StatementandreportofProfessorS.BustininUKMMRlitigation.

59 HornigM,BrieseT,BuieT,BaumanML,LauwersG,SiemetzkiU,HummelK,RotaPA,BelliniBJ,O’LearyJJ,SheilsO,AldenE,PickeringL, LipkinWI. Lack ofAssociation betweenMeaslesVirusVaccine andAutism with Enteropathy: A Case-Control Study. PLoS ONE. 2008;

3(9):e3140.

60 Bradstreet JJ, El Dahr J,Montgomery SM,Wakefield AJ. TaqManRT-PCR Detection of Measles Virus Genomic RNA in CerebrospinalFluidinChildrenwithRegressiveAutism.PaperpresentedatInternationalMeetingforAutismResearch;Sacramento,California;2004.[AllchildrenhadreceivedMMRandnonehadahistoryofmeasles.]

61 Emphasisadded.

62 American Psychiatric Association. (2009, December 10). DSM-5Publication DateMoved toMay 2013. [News Release]. Retrieved fromhttp://www.dsm5.org/Newsroom/Documents/09-65%20DSM%20Timeline.pdf

63 GillbergC.MedicalWork-UpinChildrenwithAutismandAspergerSyndrome.BrainDysfunction.1990;3:249-260.

64 Rutter M, et al. Autism and known medical conditions: myth andsubstance.JChildPsycholandPsychiat.1994;35:311-322.

65 United States Court of Federal Claims.King vsHealth andHumanServices.Case1:03-vv-00584-UNJDocument80Filed07/01/2008.

66 Kanner L. Autistic disturbances of affective contact. Nerv Child.1943;2:217-250.

67 DohanFC.Schizophrenia:Possible relationship to cereal grains andceliac disease. In: Sankar S, ed. Schizophrenia: Current Concepts andResearch.Hicksville,NY:PJDPublications,1968Goodwin MS, Cowen MA, Goodwin TC., Malabsorption and cerebraldysfunction: amultivariate and comparative study of autistic children, JAutChildSchizophr1971;1:48-62

68 Walker-SmithJ,AndrewsJ.Alpha-1-antitrypsin,autism,andcoeliac

disease.TheLancet.1972;2:883-884.

69 GillbergCandColemanM.TheBiology of theAutistic Syndromes.NewYork:PraegerPublications,1985.

70 GMCvsWakefield,Walker-SmithandMurch.RutterTestimonyTr.38p.47.

71 GMCvsWakefield,Walker-SmithandMurch.RutterTestimonyTr.38,p.53.

72 KrigsmanA,BorisM,GoldblattA,StottC.ClinicalPresentationandHistologicFindingsatIleocolonoscopyinChildrenwithAutisticSpectrumDisorder and Chronic Gastrointestinal Symptoms. Autism Insights.2009;1:1-11.Horvath K, Perman JA. Autistic disorder and gastrointestinal disease.CurrentOpinioninPediatrics.2002;14:583-587.Melmed RD, Schneider C, Fabes RA, et al. Metabolic markers andgastrointestinalsymptomsinchildrenwithautismandrelateddisorders.JPediatrGastroenterolNutr.2000;31:S31-S32.Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT.Gastrointestinalabnormalitiesinchildrenwithautisticdisorder.JPediatr.1999;135:559-63.BalzolaF,DanielaC,RepiciA,BarbonA,SapinoA,BarberaC,CalvoPL, Gandione M, Rigardetto R, Rizzetto M. Autistic enterocolitis:confirmationofanewinflammatoryboweldiseaseinanItaliancohortofpatients.Gastroenterology.2005:128(Suppl2);A-303.

Gonzalez L, Lopez K, Martınez M et al. Endoscopic and histologicalcharacteristics of the digestive mucosa in autistic children withgastrointestinal symptoms.Arch. Venezolanos Puericultura Y Pediatria.2006;69;19-25.

CHAPTERELEVEN

DisclosureI have been accused and ultimately found guilty of professionalmisconduct for not disclosing inThe Lancet paper that Iwas amedicalexpert involved in assessing the merits of litigation against themanufacturersofMMRonbehalfofplaintiff childrenpossiblydamagedbythisvaccine.Notwithstandingthefactthat−longbeforepublication−detailsofmyinvolvementasanexpertinthelitigationhadbeenprovidedtomyseniorcoauthors,1thedeanofthemedicalschool,2andtheeditorofTheLancet,3itisamatteroffactthatitwasnotdisclosedinthepublishedpaper.

TheLancetdisclosurerulesin1997werewrittenintheactivevoice.Theyasked that the author(s) determine what they considered to constitute aconflictandtodiscloseornotaccordingly(subjectiveduty).Atthetimeoftheir referral to the Royal Free, not one of the children reported inTheLancet was involved in litigation. Each one of those 12 children wasreferredtoWalker-Smithpurelyforinvestigationoftheirsymptoms.ThematteroflitigationhadnobearingonTheLancetpaper.

Moreover,suchadisclosuremighthaveconveyedthewrongimpression,i.e., that the children’s parents were involved in and motivated bylitigation,which,totheextentthatIcanbecertain,wasnotthecase.Onthebasisof thesefacts, Imade thedetermination thatnosuchdisclosurewasrequired.Notably,Hortonwroteaneditorialin1997indefenseofhisownfailuretodiscloseanauthor’sfinancialconflict,citingthedangersof

becomingobsessedwithdisclosureandthepotentialforthisobsessiontoharmfreediscussioninscience.4ThecautionheexpressedisparticularlyrelevantincircumstanceswheresuchdisclosuremightcreateamisleadingimpressionasitmighthavedonewithTheLancetpaper.Hisapparentpleainmitigationdidnot,itseems,extendfarbeyondhisownredemption.

Since the early part of the 21st century, disclosure rules have changed.They are now written almost exclusively in the passive voice — whatothers reviewing or reading the particular paper might perceive as anauthor’spossibleoractualconflict(s)ofinterest(objectiveduty).Thisisanentirely different ball game.The author is required to put himself in thecollective shoes of all potential readers and to disclose anything that hebelieves theymightpossiblyconsider tobeaconflict. In the interestsoftransparency this is commendable, but it is a very different situation ascomparedwiththerulesthatguidedauthorsin1998.

What have been the practical consequences for this move to stricterdisclosurerequirementsfrom1998to2007forTheLancet?Forthemorethan 1000 consecutive contributions written by 3567 authors in volume351(January1throughMay31,1998),thereweredeclarationsofconflictsof interest from only five authors, and these were confined to just twoletters.Incontrast,performingthissameexerciseonjusttwoissuesofthejournal from2007 (volume369,number9579, andvolume370,number9584),althoughthesecontainonly61consecutivecontributionswrittenby203authors,therearedisclosuresofconflictsofinterestfrom40authorsin13articles.Withthestricterrulesinplace,between1998and2007therateof disclosures perLancet articlewent fromone in two hundred tomorethanoneintwoarticles.5

Interestingly,whileIfollowedthedisclosurerulesin1997whenthepaperwassubmitted toTheLancet,at theGMCIwas judgedaccording to thecurrentrules.Themainreasonsforthisweretwofold,beingtheevidenceofTheLanceteditor(coveredinChapter8,“Horton’sEvidence”)andtheopinionoftheprosecution’sexpertwitnessProfessorSirMichaelRutter.ItisuponthelatterthatIwishtodwellfortheremainderofthisessay.

Rutter’s résumé is impressive, boasting membership on editorial andadvisory boards of no fewer than 21 medical journals and over 400publications in thefieldofchildpsychiatry.Asanexpertwitness for theprosecution−paidby theGMC−Rutterenlightened theGMCPanelonthefactthathehadbeenamemberofhishospital’sethicscommittee“fora long time,”and, therefore,wasan“expert” inconflictsdisclosure.6Healso explained that he was an expert witness on behalf of the vaccineindustryintheUKMMRlitigationandthathehadexaminedtwoofTheLancet 12 children.7 His opinion on the matter of disclosure inevitablycarried considerableweight in the panel’s determination ofmy guilt forlackofdisclosureinTheLancet.

Inhis report to theGMCon thismatterprior to thehearing,hedeclaredthatfailuretodiscloseinTheLancetwas“quiteunsatisfactory.”8Whenitcametothehearing,hewasconsiderablymoreforthright.Itisunsettling,therefore,thatinhisauthoritativeevidencetotheGMChemisrepresentedTheLancet’sstandardatthematerialtime.

Smith [Prosecution Counsel]: … In 1996 if you were aresearch doctor formulating a research project andsubsequently when you submit it for publication, would anypossible conflict of interest and I underline we are in 1996would it be a subject to which you would have given

consideration?

Rutter: Yes, it would be routine to have done so and it is interms not of the individual investigator’s actual conflict ofinterest as they think but ofperceptions.9There are umpteendocumentsonethical issuesand theyallmakeclear that it isperceivedconflicts9whichare important,and that in1996aswellasnowthatwouldhavetobeseenaspotentiallyrelevantinthatitwouldhavetobemadeexplicit.

DespiteTheLancet’ssubjectivestandardat thematerial time,Rutterwasof the opinion that, then and now, a researcher had an objective duty todiscloseconflictinginterests.Hisreasonforthedisclosureobligationwassothat

…thereaderofthepublishedresearchcouldjudgeforhimselfwhether the quality of the reported science outweighs thepotentialfortheconflicttobiastheinterpretation.10

Whilethisislaudable,itwasnotTheLancetstandardatthematerialtime.At theGMC,Rutterwasasked toexpandupon the reasoningbehindhisopinion.

Smith: I know this is a huge subject but you say itwould besomething in 1996 that shouldhavebeengiven considerationto.Just inbroadtermsfirst,what is itsrelevance toscientificresearch, why is it regarded as something that should beconsideredanddeclaredifthereisapossibleperception?

Rutter:Becausethereisactuallya[vast]substantialresearchliteraturewhichshowsthateverybody,thatisallofusaswellas the rest of theworld outside,whetherwe like it or not, isinfluenced in our judgments by what we think might be thecase, so if there is a reason for favouring one interpretationthananotheryouhavetoassumethatalthoughyoumaynotbeconsciousofit,itwilldoso.Thatisthereasonwhythesethingshave to bemade transparent,made overt, so that people canjudge for themselves is the science of such high quality thatreally theperceived11possible conflict of interest canbe castaside because the evidence is so strong or is this open to avariety of interpretationswhere the fact that one answerwilllead toonesortofoutcomeandanother toadifferentsortofoutcomemayinfluencejudgment.

Onceagain,RuttercitesanobjectivestandardwhileTheLancetpolicyondisclosure in1998wasverynarrowandbasedentirelyon the subjectivestateofmindoftheauthor.Thedisclosureobligationwassubsequently−andappropriately−mademuchbroaderandbasedonanobjectivethird-party standard of what a reasonable person would perceive to be aconflicting interest at The Lancet and throughout scientific andmedicalpublishing.However,RutterfaultedmeforviolatingthestricterobjectivestandardwellbeforeitwasimplementedatTheLancet.12SmiththenaskedRutterwhether,intheory,hewouldhavedisclosedhisinvolvementintheMMRlitigationunderthethen-applicablestandard:

Smith:…Iwanttoaskyouthis;puttingyourselfintheshoesofareasonablyresponsibleandexperiencedsubmittertomedicaljournalswouldyouregardthattestastriggeringdisclosureinrelationtoDrWakefield’sinvolvementinthelitigation?

Rutter:Yes,Iwould,forthereasonsIhavealreadygiven.

Smith:Wouldyouregarditasamatteraboutwhichadoctorshouldhaveanyhesitation?

Rutter:NohesitationIwouldhavethought.

Rutter’sroleinvaccinelitigationAs referred to above,Rutterwas a paid expert in at least three separatelitigation projects on behalf of the vaccine manufacturers and USgovernment; in these projects, he was to offer an expert opinion thatthimerosal-containingvaccinesandMMRdonotcauseautismandthatthedramatic increase in the incidence of autism is unlikely to be real13 butsimply the result of better ascertainment and a broadening of thediagnosticcriteria.

Rutterservedasadefendants’expertinUSlitigationwheretheplaintiffsalleged that mercury (thimerosal) in vaccines caused autism. He alsoserved as a defendants’ expert in the UK MMR litigation which,coincidentally,includedtwoofthechildrendescribedinTheLancetcaseseries. Finally, he was an expert for the US government (in a specialvaccine court created by statute in 1986) in the Omnibus AutismProceeding.Hewas paid in each of these litigations on the basis of hisopinionthatvaccines(that is,MMRand/ormercury-containingvaccines)donotcauseautism.14,15

Rutteroffered a similaropinion in an expert report he filedonFebruary

18,2008,intheUSOmnibusAutismProceeding.Hisexpertopinion,forwhich he was being well paid, was based in part on his publishedresearch.16 He went on to explain his past and present involvement inlitigation.17

Rutter was hired to offer his interpretation of the epidemiological datarelatingtoMMRandautism−currentlyamatterofextensivecontroversy,debate, and extensive calls for further investigations. Thus, it could bearguedthathehadandcontinuestohaveafinancialinterestinpreservingtheabsenceofevidenceinthepublishedmedicalliterature−includinghisown, much of which he cites in references and footnotes in his expertreports. It is, therefore, the potential, if not the reality, of his ability toprofit substantially from an absence of evidence of causal association intheliteraturethattriggershisobligationtodisclosehisroleasanindustryexpertinthepapershepublishes.

DoasIsay,notasIdoButdoesRutterdoasRuttersays−andnotinthelaxer,subjectiveeraofthe late1990s,but in thepious, objective eraof2005andbeyondwhenmuch stricter rules have applied? Between 2005 and 2008, Rutterpublishedatleastfivepapersinpeer-reviewedmedicaljournalsthathadadirectbearingontheissueofMMRvaccineandautism;forexample,thesepapersincludethefollowingstatements:

ThesignificanceofthisfindingisthatMRvaccinationismostunlikelytobeamaincauseofautism.18

However, the epidemiological evidence on the main

hypothesized environmental explanation, namely themeasles-mumps-rubellavaccine,isconsistentlynegative.19

ThereisnosupportforthehypothesisforaroleofeitherMMRorthimerosalincausation[ofautism],buttheevidenceforthelatterismorelimited.20

Themeasles-mumps-rubella vaccinewas postulated as a riskfactor but the epidemiological evidence has been consistentlynegative.21

With undisguised contempt for those continuing to investigate thepotentialroleofvaccinesinautism,thisarticleconcludes:

Thereisnodisgraceinbeingwrong,butthereisadisgraceinpersistingwithatheorywhenempirical findingshavemadeitapparentthatthehypothesisorclaimwasmistaken.21

Theclaimsthattheso-called“epidemic”ofautismwasduetoeithermeasles-mumps-rubella(MMR)vaccineorthemercury-containing preservative thimerosal that used to be present inmanyvaccinesarenotsupportedbytheevidence.22

NowhereinanyofthesepapersisadisclosureofthefactthatRutterwasinthepayofthevaccinemanufacturersandtheUSgovernmenttodefendtheirpositioninvaccine-autismlitigationnoristhereanydisclosureofhisroleasapaidexpertat theGMC.The lackofdisclosure in thesepapersmayhaveoccurredforoneof tworeasons:eitherRutterfailedto tell the

journals’editors,orhediddiscloseandtheeditorsdeemeditunnecessaryto avail their readers of this important information, preventing thosereadersfrombeingable,asRutterstresses,to“judgeforthemselves.”Onlyoneofthejournalsmakesanymentionofdisclosure,sheddingsomelightonwhichofthesetwoalternativesislikelytobecorrect.AtthebottomofRutter’s2009article20itstates:

Conflictsofinterest:Nonedeclared.Theimportanceofthismattergoesfarbeyondasimplefailuretodisclose.In2005,Rutterwasactuallyontheeditorialboardofoneoftherelevantjournals,theJournalofChildPsychologyandPsychiatry,whosepositionon disclosure— presumably endorsed byRutter in his editorial role—wasveryclear.23

In psychology, as in other scientific disciplines, professionalcommunications are presumed to be based on objectiveinterpretationofevidenceandunbiasedinterpretationsoffact.Anauthor’seconomicandcommercialinterestsinproductsorservices used or discussed in their papers may color suchobjectivity. Although such relationships do not necessarilyconstitute a conflict of interest, the integrity of the fieldrequires disclosure of the possibility of such potentiallydistorting influenceswhere theymay exist. The reader24maythenjudgeand,ifnecessary,makeallowancefortheimpactofthebiasontheinformationbeingreported.In general, the safest and most open course is to discloseactivities and relationships that, if known to others,might beviewedasaconflictofinterest,evenifyoudonotbelievethatanyconflictorbiasexists.

So, in the interests of transparency, the journal appears to publishdisclosuresandletthereaderdecide,indicatingthatinthisinstanceitwasRutter who failed to disclose. As a paid expert witness for the vaccineindustry,Rutter’sobligation todisclosewassetevenhigher in2001inacommentary25publishedbyseveraleditors,includingHorton,because,asthey explained, such relationships carry a great risk for inappropriateinfluenceandbias.

Financial relationships (such as employment, consultancies,stockownership,honoraria,paidexperttestimony26,27)arethemosteasilyidentifiableconflictsofinterestandthemostlikelytounderminethecredibilityofthejournal,theauthors,andofscienceitself…Disclosureoftheserelationshipsisparticularlyimportant in connection with editorials and review articles,because bias can be more difficult to detect in thosepublicationsthaninreportsoforiginalresearch.

Four of Rutter’s articles that are cited above fall under the category of“Reviews.”

In terms of the significance of Rutter’s testimony, his critical role indefining the GMC’s position on disclosure and my “dishonesty” wasdrivenhomebySmith—erroneouslyonmany levels—onDay138ofthehearingasshedemandedtheerasureofmymedicallicense.

ThechildrendescribedintheLancetpaperwere…admittedforresearch purposes under a programme of investigations forProject172-96.Thepurposeof theprojectwas to investigatethepostulatednewsyndromefollowingvaccination.Whentheywere subsequently described in the Lancet paper… DrWakefield failed to state that this was the case and that his

failurewasdishonest,i.e.,thatheintendedtodoitanditwasirresponsible,andthatitresultedinamisleadingdescriptionofthe patient population, a matter which you will recall isfundamentaltoanyscientificpaper.

Professor Rutter described it, you will remember, as“absolutelycrucial”(Day37-44E-G).Itisfundamentaltothereadership’s understanding of amatter which, in the case ofthis paper (the Lancet paper) DrWakefield knew, as he hasadmitted,hadmajorpublichealth implicationswithregardtothe public attitude to vaccination, and which he knew wouldreceive a media coverage that would result in nation-wideconcern.Itissubmitted,again,thatthisisplainlyaverygravematter.

RutterandtheGMCTheGMC’sethicalguidance fordoctors in this case,which ispostedas“ActingAsAnExpertWitness—GuidanceforDoctors,”requiresthatanexpertwitnessgivehonesttestimony:28

If you are asked to give evidence or act as a witness inlitigation or formal inquiries, youmust be honest in all yourspokenandwrittenstatements.Youmustmakeclearthelimitsofyourknowledgeorcompetence.

The ethical guidance amplifies on this requirement by requiring that theexpertbe“notmisleading”andthathe“notdeliberatelyleaveoutrelevantinformation.”Finally,theethicalguidancerequiresthatanexpert“mustbehonest,trustworthy,objective,andimpartial.”

James Moody, Esq., an attorney acting pro bono on behalf of severalautism organizations, haswritten to Rutter, bringing to his attention thefact that these instances of lackof disclosure are to beput in thepublicdomainandofferinghimtherightofreply.Thee-mailwassentonMarch6,2010,andaresponsewasrequestedbyMarch12,2010.Therespectivejournaleditorshavealsobeencontacted.Atthetimeofgoingtopress—April28,2010—noreplyhasbeenreceived.

RutterisalsothesubjectofacomplainttotheGMCclaimingthathegavedishonestandmisleadingexperttestimonyinviolationoftheabove-citedGMCguidance.Asnotedabove,RutterhasbeenapaidexpertforindustryinatleastthreelitigationprojectsintheUKandUS,yetheroutinelyfailstodisclose thisconflicting interest inhispublishedpapers.Thus,puttinghimself “in the shoes of a reasonably responsible and experiencedsubmitter to medical journals,” as Smith instructed, Rutter could nothonestlyand ingoodfaith testify that Ishouldhavemadedisclosures—evenunder the current broader objective standard—because he fails tomake theverysamedisclosures inhisownpublishingactivities.29 In thelight of these facts, the question now is whether hewill bring this newevidencetotheattentionoftheGMC.

Based upon the documentary evidence, one is entitled to believe thatRutter uses his position of prominence in the scientific community topublisharticlesdenyinganyvaccine-autismconnectionwithoutdisclosinghisconflictinginterestthathewaspaidbyindustrylawyersandbytheUSgovernment (in a statutory program to defend industry in vaccine court)for thatvery sameopinion.WhileProfessorRuttermaywellbelievehispublished opinions are independent and honest, the objective standardsapplicable since approximately2002 todisclosable conflictsof interest30

imposedadutytodiscloseinpublishedresearchpapersthathewasbeingemployed by industry and government to support their position inlitigation.

The purpose of this chapter is not to mitigate my lack of disclosure in1998.Ifollowedtherulesandnotoncedidmyco-defendants,myboss,orthedeanofthemedicalschool—allofwhomwereawareofmyroleasanexpert in theMMRlitigation—ever suggestduring thepreparationandsubmissionofTheLancetpaperthatdisclosurewouldbeappropriate.Themeritsof thispositionondisclosurearedebatableand thisdebate -onamatter of opinion—would have beenmore appropriately held betweenscientists rather than in the adversarial and punitive arena of a GMChearing. Rather, this essay is about what amounts to, in my opinion,hypocrisy, double-standards, and professional retribution dressed insanctimoniouspiety.

Endnotes1 CorrespondencebetweenAJW,John-WalkerSmithandSimonMurch.February1997.

2 CorrespondencebetweenAJWandArieZuckerman1996-97.

3 CorrespondencebetweenRichardBarrandRichardHorton.April-July1997[seeChapter8,Horton’sEvidence].

4 Horton R. Conflicts of interest in clinical research: opprobrium orobsession.TheLancet.1997;349:426.

5 Literature reviewcourtesyofRichardBarrandKirstenLimb.August2007.

6 GMCvsWakefield,Walker-SmithandMurch.Tr.35-2C

7 GMCvsWakefield,Walker-SmithandMurch.Tr.35-5B.

8 GMCvsWakefield,Walker-SmithReportofProfessorRuttertoGMC.p.32.May15,2007.

9 Emphasisadded.

10 GMCvsWakefield,Walker-SmithandMurch.Tr.37-55D.

11 Emphasisadded.

12 GMCvsWakefield,Walker-Smith andMurch.Tr. 37-57C (Ex. 60)(emphasisadded)

13 Arealincreasewouldbesuggestiveofanenvironmentalcause(non-genetic),e.g.,vaccines.

14 Rutter’sexpertreportshavenotbeenmadepublic,buthedidtestifyinUSvaccinecourtonMay27,2008,inthetestcases(MeadandKing)InRe:ClaimsforVaccineInjuriesResulting inAutismSpectrumDisordersoraSimilarDevelopmentalDisorder.

15 InoneexpertreportintheUKMMRlitigation,forexample,ProfessorRutteroffered theopinion inanexpert reportdatedJune23,2003:“Theepidemiological findings show no systematic connection between thetimingoftheintroductionofMMRandthetimingoftheriseintherateofautism and other pervasive developmental disorders. Accordingly, theepidemiologicalfindingsprovidenogroundsforconcludingthat[Child’s]disorderislikelytohavebeenassociatedwithMMR.”

16 “With respect to the possibility that toxins may contribute to thecausationofmentaldisorders,Ihavereviewedtheevidenceontheeffectsof environmental lead5,6, and have done the same for the effects of themeasles-mumps-rubellavaccine7.Ihavepublishedextensivelyongeneticsofmentaldisorders(Rutter,20068)andespeciallyontheinterplaybetweengenetic and environmental factors (Rutter, 20079; Rutter, in press10)…WithrespecttotheVaccineCourthearings,Ihaveparticularexpertiseinthestepsneededtoidentifyenvironmentalcausesofdisease(AcademyofMedicalSciences11,Rutter,200712)…Ibasemyopinionsontheavailablescientific evidence and, in the body of the report, I note the scientificpapersthatarerelevantinrelationtoindividualpoints.Inaddition,Ialsomakeuseofmyextensiveclinicalexperienceoverthelastfourdecadesindiagnosingautismspectrumdisordersandtreatingchildrenandadultswiththesedisorders.”[Internalfootnotesinoriginal.]

17 “WithrespecttotheissuesbeingconsideredbytheVaccineCourt,Iwish tomake explicit that some four years ago I agreed to serve as anexpert witness with respect to Thimerosal vaccine litigation. In thatconnection, I partially drafted a report that, in the event, was neversubmittedbecause the litigationwasputonhold.Similarly,aboutayear

beforethat,thesamesituationarosewithrespecttolitigationoverMMR.Oncemore, thedraftreportwasneverfinalizedandwasneversubmittedbecausethelitigationwasdropped.Finally,lastyearIservedasanexpertin relation to the British General Medical Council’s case against 3pediatricians involved in AndrewWakefield’s research into autism andMMR.Theissuesinvolvedtheredidnotconcernthescientificcaseatallbut,rather,wereinvolvedstrictlywiththeethicalconductoftheresearchundertaken… Regarding potential conflicts of interest, I declare thatthroughoutthewholeofmycareerIhaveneverreceivedanyfundingformy research from pharmaceutical companies or any other commercialorganization.IagreedtoserveasanexpertwitnessinlitigationintheUKregardingthemumps—measles—rubellavaccineandreceivedstandardfees for the time spent inpreparing for this role, but the litigationneverresultedinacourthearing.”

18 HondaH,ShimizuY,RutterM.NoeffectofMMRwithdrawalontheincidenceofautism:atotalpopulationstudy.JournalofChildPsychologyandPsychiatry.2005;46:572-579

19 RutterM.Aetiology ofAutism: Findings andQuestions. J IntellectDisabilRes.2005;49(Pt4):2318.

20 RutterM.Incidenceofautismspectrumdisorders:changesovertimeandtheirmeaning.ActaPaediatrica.2005;94:2-15.

21 RutterM.Autismresearch:lessonsfromthepastandprospectsforthefuture.JAutismDevDisord.2005;35:241-257.

22 RutterM.Commentary:factandartifactinthesecularincreaseintherateofautism.Int.J.Epidemiol.2009;38:1238-1239.

23 JournalofChildPsychologyandPsychiatry.Notes for contributors.AllauthorssubmittingapapermustcompleteaFullDisclosureofInterestsform.www.apa.org/journals.

24 Emphasisadded.

25 DavidoffM,etal.Sponsorship,Authorship,andAccountability.TheLancet.2001;358:8546.Thisstandardwassubsequentlyincorporatedintothe ICMJE Uniform Requirements for Manuscripts Submitted toBiomedicalJournals:EthicalConsiderationsintheConductandReportingof Research: Conflicts of Interest. See:http://www.icmje.org/ethical_4conflicts.html.

26 Emphasisadded.

27 GMCvsWakefield,Walker-Smith,andMurch.Tr.138

28 GoodMedicalPractice:WritingreportsandCVs,givingevidenceandsigning documents. Retrieved from: http://www.gmc-uk.org/guidance/good_medical_practice/probity_reports_and_cvs.asp

29 GMCvsWakefield,Walker-SmithandMurch.Tr.37-57D.

30 Actingasanexpertwitness—guidancefordoctors.Retrievedfrom:http://www.gmcukorg/guidance/ethical_guidance/expert_witness_guidance.as.

CHAPTERTWELVE

Deer

Relations between BD [Brian Deer] and the Sunday Timesare at the best of times volatile and therewasn’t a storywepublished in the Sunday Times which wasn’t heavilyrewrittenorcutback.1

ItmaysurprisereaderswhohaveenduredsofarthatIdon’twishtospendany more time than is absolutely necessary on Brian Deer. Despite mywish, this chapter is heavy going. Other chapters deal directly andindirectlywiththemajorityofhisoriginalallegations.However, inorderto put his journalistic style andquirkyperceptionof events at theRoyalFree intocontext, Iwillprovidea factual analysisof anarticlehewrotemore recently, in fact, at the conclusion of the evidence in the GMChearing.Thearticleisparticularlymisleading;clearlyajudgmenthasbeenmade that I represent zero risk as far as defamation goes. When thathappens, people can get careless. My sense is that Deer’s article waswritten in some desperation, following a lackluster performance by theprosecution andwhat appeared tobe—at least tomanyof those in thechamber–ademolitionoftheGMC’scase.

On February 8, 2009,Deer’s byline accompanied two related articles inTheSundayTimes,thefirstofwhichwastitled

“MMRdoctorAndrewWakefieldfixeddataonautism.”

BlockedexcerptsofDeer’sarticlesareprovidedwithagraybackground.His articles contained allegations that I committed scientific fraudinasmuchthat,apparently,Ihad“changedandmisreportedresultsin[my]research”2 inThe Lancet paper, with the clear implication that this wasintended to create the appearance of a possible link between MMRvaccinationandautism−andthatIdiditformoney.

Since Deer sat through the majority of the GMC hearing where thesematters had been aired in considerable detail, he knew or should haveknown that these allegations were false, misleading, or based onincompleterecordsand,attheveryleast,opentoquestion.

ThedoctorwhosparkedthescareoverthesafetyoftheMMRvaccine for children changed and misreported results in hisresearch, creating the appearance of a possible link withautism,aSundayTimesinvestigationhasfound…Confidentialmedical documents and interviews with witnesses haveestablishedthatAndrewWakefieldmanipulatedpatients’data,which triggered fears that theMMR triple vaccine to protectagainst measles, mumps and rubella was linked to thecondition.

False: There is no basis in fact for any suggestion that I “manipulatedpatients’ data” at any time. At the GMC, no charge of manipulation orfalsification of patient data was brought against me, and none of theevidencepresentedduringtheGMChearingovertheyearandahalfthatittooksupportsanyallegationofmanipulationofdatabymeoranyoftheother12coauthorsonthepaper.Thespecificsofthisallegationaredealtwithbelow.

TheresearchwaspublishedinFebruary1998inanarticlein

TheLancetmedicaljournal.Itclaimedthatthefamiliesofeightoutof12childrenattendingaroutineclinicatthehospitalhadblamedMMRfortheirautism,andsaidthatproblemscameonwithindaysofthejab.

Whatthisclinicalpaperactuallystatesisthat

Onsetofbehaviouralsymptomswasassociated,bytheparentswithmeasles,mumps,andrubellavaccinationineightofthe12children…

Theteamalsoclaimedtohavediscoveredanewinflammatoryboweldiseaseunderlyingthechildren’sconditions.

False:nowhereinTheLancetpaperissuchaclaimmade.

However,ourinvestigation,confirmedbyevidencepresentedtotheGeneralMedicalCouncil (GMC), reveals that: Inmostofthe12cases,thechildren’sailmentsasdescribedinTheLancetweredifferentfromtheirhospitalandGPrecords.

ThedocumentsrelevanttotheevidencepresentedinTheLancetpaperareclearlyidentifiedinitandincludedtheRoyalFreeHospital(RFH)recordsand, where available, the developmental records from parents, healthvisitors[UKregisterednurseswhovisitthehome]andGPs.Therefore,asstated in the paper, the team relied on the totality of the informationavailabletous.Thisisentirelynormalpractice.

In contrast, the records that were available to the GMC included a

complete setof thechildren’s localhospital records, a full setof theGPrecordsincludingallGPswhohadbeeninvolvedineachchild’scare,theRFH records, and any other records relating to each child (e.g. schoolmedicalrecords).

Therefore, reliance by Deer upon any differences between these datasources (i.e., thosereliedonbyTheLancet authorsvis-a-vis those relieduponbyDeerinhisallegations)isdisingenuousandmisleadingsincethemajorityofthelatterrecordswerenotavailabletotheRoyalFreedoctorsatthematerialtime.

Thatisnottosay,however,thatDeer’sinterpretationofanydifferencesisaccurate. Rather he appears to have cherry-picked differences betweenthesedocumentswithaviewtounderminingthecredibilityofTheLancetpaper.Specificinstancesofthisareprovidedbelow.

Although the research paper claimed that problems came onwithin days of the jab, in only one case didmedical recordssuggest this was true, and in many of the cases medicalconcernshadbeenraisedbeforethechildrenwerevaccinated.

Labeling our clinical case series as a “research paper” is intended toconvey the impression that the childrenwere investigated purely for thepurposes of experimentation, an allegation that formed a central part ofDeer’s original complaint to the GMC3,4 (see the Afterword, “Ethics,EvidenceandtheDeathofMedicine”).Incontrast,thepaperreportedonthe findings in clinically referred childrenwhowere investigated on thebasisoftheirpresentingsymptoms.

…thatproblemscameonwithindaysof the jab, inonlyone

casedidmedicalrecordssuggestthiswastrue.Inmanyofthecases medical concerns had been raised before the childrenwerevaccinated.

False:Deerdisingenuouslyconflates“problems”with“medicalconcerns.”With respect to “problems,” The Lancet paper was quite specific inreferring to the timing of onset of “behavioural problems” in relation toMMRexposure.Nowhereinthepaperwasanyreferencewasmadetotheonset of “medical concerns.” The latter is an entirely nonspecificexpressionthatmightrelatetoanythingthatcausedachildtopresenttoadoctor.TheuseofthistermtoreflectwhathadbeensaidinTheLancetisentirelymisleading.

The paper described parental reports of the onset of “behaviouralproblems” coming on within an average (mean) of 6.5 days after thevaccine.Aswill be shownbelow,Deer’s implication that these childrenwereexhibitingsignsofautismbeforevaccinationis,onceagain,falseormisleading.

Hospitalpathologists,lookingforinflammatoryboweldisease,reportedinthemajorityofcasesthatthegutwasnormal.Thiswas then reviewed and the Lancet paper showed them asabnormal.

Thisallegationillustrateshowrigorousclinicalandscientificinvestigationisvulnerabletomisrepresentationasafalsificationofdata.Asanexampleof the fallacyof thisallegation,adetailedexplanation isprovidedof theprocessbywhichthepathologyintissuebiopsiesfromthesechildrenwasdiagnosedandreported.Firstly,Iplayednopartinthediagnosticprocessatall.Secondly,thefactthatareviewofthesamplestookplaceisclearlyspelledoutforalltoreadinTheLancetpaperitself(seebelow).Therewas

nosinisterattempttohideanyinitialassessmentsasDeerimplied.

Biopsies were initially reviewed by duty pathologists who often had nospecialist expertise in gastrointestinal disease, particularly in children.Walker-Smith, the senior clinician, who has unparalleled experience ofassessing the appearances of bowel disease in children, reviewed allbiopsies at a weekly clinicopathological meeting of his team. This wasundertakenwiththeassistanceofhistopathologistDr.SueDavies.Atthesemeetings,Walker-Smithpointedout the fact that inflammationhadbeenoverlookedinsomeoftheautismcases.

Itwasdecidedthat,inordertostandardizetheanalysisofthebiopsies,thesenior histopathologist with the most expertise in intestinal disease, Dr.Paul Dhillon, should review all biopsies from autistic children. In turn,Dhillon decided that pathology should be graded on a reporting formdesignedbyhim5 to document the presence and severity ofmicroscopicdamage.Thereafter,aregularreviewofbiopsiestookplaceinvolvingDrs.Dhillon and Anthony, a trainee pathologist. I was also in attendance.Dhillon’sdiagnosisformedthebasisforwhatwasreportedinTheLancet.This process has, in fact, been described in the relevant medicalliterature1,6 (see below) and was also presented in evidence by me inDeer’spresenceattheGMChearing(seebelow).OncethepaperhadbeenwrittenindraftformbymetoincludeDhillonandAnthony’sfindings,itwas circulated to all authors for their modification and approval. Deershouldhavebeenawareof thesefactsbeforehepublishedhisclaims;hesat through the evidence, and the details are set out in the publishedliterature.

DocumentedbelowandavailabletoDeeratthetimeofwritinghisarticle

are the specific references to this diagnostic process,which appeared inTheLancet1998paperandtwosubsequentpublishedpapersin2000and2004.

Ileal lymphoidnodularhyperplasia,non-specific colitis, andpervasivedevelopmentaldisorderinchildren7

Formalin-fixed biopsy samples from ileum and colon wereassessed and reported by a pathologist (SED).8 Fiveileocolonic biopsy series from age-matched and site-matchedcontrols whose reports showed histologically normal mucosawere obtained for comparison. All tissues were assessed bythree other clinical and experimental pathologists (APD, AA,AJW).9

This process was reported in greater detail in follow-up studies thatincludedthe12Lancetchildren.10TheResultssectionofthissamepaperdocumentedahighdegreeofagreementbetweenindependentpathologistsinanobserver-blindedanalysis(i.e.,wherethepersonscoringthebiopsywas unaware of the diagnosis in the individual from whom the biopsycameandthescoregiventothesamebiopsybyotherobservers).11

Afurtherpublicationprovidedadetailedreviewofthediagnosticprocess,specificallyreferringtotherolesofDhillonandAnthony.Italsoreferredto theclinicopathologicalmeetingand the fact thatpathological findingswere frequently modified as a consequence of this expert and thoroughreviewprocess.12Thedetailsofthediagnosticprocesswerealsodescribedby me during evidence (Days 49 and 50) at the GMC with Deer inattendance.13

Dhillon’sroleinthediagnosticprocessisalsoconfirmedinastatementheprovidedtotheGMCandthatwassignedbyhimonJuly28,2006.14Thiskey document confirms his role in making the diagnosis in The Lancetchildren in themoststringentway, i.e.,byablindedreviewasdescribedabove.

Thereshouldhavebeennodoubtinanyone’smindattheGMChearingasto the extraordinary diligence with which the diagnostic process wascarriedoutandthefactthatIwasnotinanywayresponsibleforthefinaltissuediagnosisinTheLancetchildren.BacktoDeer…

Throughhislawyers,Wakefieldthisweekenddeniedtheissuesraisedbyourinvestigation,butdeclinedtocommentfurther.

Unfortunately, Deer’s allegations were only provided to me on themorningofFriday,February6,2009.IwasgivenadeadlineofSaturday,February7,middayLondontime,i.e.,6:00A.M.CentralStandardTimeinTexas,leavingnoadequatetimeformeormylegalteamtodealwiththematter.

The following section deals with the accompanying story on the insidepages that appeared in The Sunday Times of February 8, 2009. It isconcernedwithspecificallegationswithrespecttoindividualchildren.

HiddenrecordsshowMMRtruthASundayTimesinvestigationhasfoundthataltereddatawasbehindthedecade-longscareovervaccination.

ItsresearchcausedoneofthebiggeststirsinmodernmedicalhistorywhenitsresultswerepublishedinTheLancetmedicaljournal.Thefive-pagepapersuggestedapotentiallinkbetweenMMRandwhatthedoctorscalleda“syndrome”ofautismandinflammatoryboweldisease.

The childrenwere not named in the tables of results. Elevenboysandonegirl,agedbetween2½and9½,weresaid,forthemost part, to have a diagnosis of regressive autism, wherechildren appear to develop quite normally, but then,terrifyingly, lose their languageskills.Theboweldiseasewasdescribedasnonspecificcolitis,asevereformofinflammation.

ThedynamiteinTheLancetwastheclaimthattheirconditionscouldbelinkedtotheMMRvaccine,whichhadbeengiventoall12children.

False: The Lancet paper did not “claim that their conditions could belinkedtotheMMRvaccine.”Nosuchclaimwasevermadeinthepaper;onthecontrary,itwasexplicitlystatedinthatpaperthatnoassociation—letaloneacausalassociation—hadbeenprovedbetweenMMRandthesyndrome described. It reported only that the parents said onset ofsymptomsstartedafterMMRvaccinationin8of12cases.

According to the paper, publishedonFebruary 28, 1998, theparentsofeightofthechildrensaidtheir“previouslynormal”child developed “behavioural symptoms” within days ofreceivingthejab.

“Intheseeightchildrentheaverageintervalfromexposuretofirstbehaviouralsymptomswas6.3days,”saidthepaper.

At face value, these findingsweremore than grounds for thepanic that took off over MMR. If such startling results wereobtained from twothirds of a group of previously normalchildren turning up at one clinic at just one hospital, whatmightbehappening,unreported,allovertheworld?Thismightbethefirstsnapshotofahiddencatastrophe,asecretepidemicofvaccinedamage.

Tolaunchthefindings,theRoyalFreeheldapressconference,and issuedavideonewsrelease.Theresearchers’ leader,DrAndrewWakefield, then41,wasemphatic inhiscomments totheassembledmedia.

“It’s a moral issue for me,” he said. “I can’t support thecontinued use of these three vaccines, given in combination,untilthisissuehasbeenresolved.”

Elevenyearslater,thefalloutcontinuesaroundtheworld.Thepapertriggeredapublichealthcrisis.InBritain,immunisationrates collapsed from 92% before the Lancet paper waspublished,to80%atthepeakofBritain’salarm.Measleshasreturnedasofficially“endemic”.

With less than95%of the population vaccinated,Britain haslost itsherdimmunityagainst thedisease.In1998therewere56 cases reported; last year there were 1,348, according tofiguresreleasedlastweekthatshoweda36%increasein2007.TwoBritishchildrenhavediedfrommeasles,andothersputonventilators, while many parents of autistic children torturethemselves for having let a son or daughter receive theinjection.

“There’s not a day go by I don’t cry because of whathappened,”saidthemotherofaseverelydisabled12-year-oldgirl.“Ishouldn’thavetookher[fortheMMR],andyouknoweveryone will say, ‘Don’t blame yourself’, but I do. I blamemyself.”

Yet thescienceremainsaproblem.Noresearchershavebeenable to replicate the results produced byWakefield’s team intheLancetstudy.

False:Itwasnottruetosaytherehadbeennoreplicationoftheworkasstated above; three independent groups have reported on intestinalinflammation (ileitis and colitis) in childrenwith autism since the initial1998publicationinTheLancet.15Similarfindingsofboweldiseasehavesincebeenpublishedbythreegroups.16

Some used statistics to see if autism took off in 1988, whenMMRwasintroduced.Itdidnot.

False:Althoughecologicaldataprovidelittlemorethancorrelations,intheUKautismdidtakeoffwhenMMRvaccinewasintroduced.ApaperfromTaylor et al.17 showed this correlation when crucial factors such as theinclusionofolder childrenwhohadbeenpartof acatchup campaign−omittedfromtheoriginalpaper−weretakenintoconsideration.18

Others used virology to see ifMMR caused bowel disease, acoresuggestioninthepaper.Itdidnot.

Thisclaimismisleadingandbetraysignorance,anattempttomislead,orboth.Virologyhasbeenusedforthedetectionofmeaslesvirusandotherviruses in the intestinal tissuesofchildrenwithautism.Whethermeaslesvirus is present or not, “virology” tests, as used, cannot “see if MMRcausedtheboweldisease,”itcanonlydeterminepresenceorabsenceofaparticularvirusand,atmost,indicateapossibleassociation.

Yet more replicated the exact Wakefield tests. They showednothinglikewhathesaid.

False:Firstly,thetestsreportedinTheLancetpaperarenotinanymanner“Wakefield tests,”butclinical investigations thatweredeemednecessarybytheappropriateclinicians.NodetailsareprovidedinsupportofDeer’sclaim nor are the assertions attributed to any expert. As shown above,thosestudies thathave lookedforboweldisease inautisticchildrenwithgastrointestinalsymptomshavefoundit.15,16

Wakefieldhimself,however,standsbyhisresults,insistingthata linkbetweenMMRandautismmerits inquiry.The12otherdoctorswhosenameswereattachedtotheLancetpaper,whichwaswrittenbyWakefield,werenot involved inpreparing thedataused.

False:Theotherauthorsgeneratedand, indeed,preparedall thedata thatwasreportedinTheLancet.Imerelyputtheircompleteddataintablesandnarrative formfor thepurposeofsubmission forpublication.Allauthorswereprovidedwithdraftsof thepaper for thepurposeof checking theirdataandmakingamendmentsasnecessarypriortosubmission.

“This study created a sensation among the public that wasimpossible to counter, despite overwhelming evidence to thecontrary,” says Professor Gary Freed, director of the childhealth research unit at the University of Michigan, who haswatchedthescaretakeoffinAmerica.

“Overwhelming biologic and epidemiologic evidence hasdemonstratedconclusivelythatthereisnoassociationbetweenthe MMR vaccine and autism, and yet this thing goes on.”Aspects of the project are now before the General MedicalCouncil(GMC),thedoctors’disciplinarybody.

Wakefield and two professors, John Walker-Smith, 72, andSimonMurch,52,arechargedwithcarryingoutunauthorisedresearchonthe12children.Thecharges,whichtheystronglydeny,relatetotheethicsofthetreatmentofthe12children,nottheresultsoftheresearch.

InevidencepresentedtotheGMC,however,therehasemergedpotentialexplanationsofhowWakefieldwasabletoobtaintheresults he did. This evidence, combined with unprecedentedaccess to medical records, a mass of confidential documentsand cooperation from parents during an investigation by this

newspaper, has shown the selective reportingand changes tofindings that allowed a link betweenMMR and autism to beasserted.

Deer’sstatementisclearlyintendedtoconveytheimpressionthatitwasIwho “obtain[ed] the results” and that these resultswere obtained bymy“selectivereportingandchanges,”with theclear implicationofscientificfraudonmypart,forthepurposeofallowing“alinkbetweenMMRandautismtobeasserted.”

False:Ididnotobtaintheresultsinthesensethatisintended.Theresultswereobtainedbythecliniciansinvestigatingthesechildren.Ihadnorolein obtaining these results other than to collate them for publication.Theprocess by which the clinicians obtained the results is apparent in TheLancetpaperandhadbeendescribedingreatdetailtotheGMChearing.

The only thing that “allowed a link between MMR and autism” to besuggested was the parental history. This was faithfully reported in TheLancet.

…attheheartofWakefield’sfindingsTheSundayTimesfoundmorediscrepancies,inconsistenciesandchanges.

Much of the anonymized information which follows comes from themedical recordsofdisabledchildren−confidential recordsheldbyDeerbut intended solely for use by clinicians involved in the children’s care.Deer’s allegations address two aspects: these are the history of therelationship ofMMR to the pattern of onset of the children’s symptomsandthemicroscopicexaminationofthechildren’sintestinaltissues.

ItisessentialtonotethatTheLancetpaperclearlystatedthatthehistoryofthe onset of behavioral symptoms was associated by the parents withMMR in 8 of the 12 children, and it is the initial behavioral symptomsdescribedbytheparentsthatwereported.WithrespecttothetimingoftheMMR and the onset of symptoms, Deer relies upon evidence in thechildrenidentifiedas1,2,6,7and8ofTheLancet12.

Child1

Thefirst, in theLancet tables,concernedthe firstchild in thepaper:ChildOne,fromCottesmore,Leicestershire.Hewas3½yearsoldandthesonofanairforcepilot.InNovember1995,hisparentshadbeendevastatedafterreceivingadiagnosisofautism.

“Mr andMrs [One]’s most recent concern is that theMMRvaccinationgiven to their sonmaybe responsible,” theirGPtoldthehospitalinaletter.

Inthepaperthisclaimwouldbeadopted,withWakefieldandhisteamreportingthatChildOne’sparentssaid“behaviouralsymptoms”started“oneweek”afterhereceivedtheMMR.

Child 1 was reported as suffering “fever and delirium.” This deliriumstarted1weekafterMMRvaccinationandlastedfor3days19anddenoteshis firstbehavioral symptomasspecificallystated inTheLancet.20With

respecttohissubsequentclinicalcourse,Walker-Smith,inhislettertotheGPstated,

Between the age of 1 year and 18 months his developmentslowedandthendeteriorated.21

EvidencefromChild1’sGPattheGMChearingconfirmedthatMrs.1’sviewwas that her child had developed normally until he had hisMMRvaccine.Thiswasdocumentedinthemedicalrecordsandformedthebasisof the information contained inTheLancet paper. The facts are entirelyaccurateasreported.

Theboy’smedical recordsrevealasubtlydifferent story,onefamiliartomothersandfathersofautisticchildren.Attheageof9½months,10weeksbeforehisjab,hismotherhadbecomeworriedthathedidnothearproperly:theclassicfirstsymptompresented by sufferers of autism. Child One was among theeightreportedwiththeapparentsuddenonsetofthecondition.

A review of the additional GP records (not available to the Royal FreeteamatthetimeofwritingTheLancetpaper)showsthat,withrespect tohis claim aboutChild 1’s hearing,Deer fails tomention the crucial factthat in the entry documenting his mother’s concerns about Child 1’shearing,heradditionalconcernwasaboutadischargefromChild1’sleftear.22 This concern is not suggestive of an incipient developmentaldisorderbutofanearinfection.ThiswouldhavebeensufficientreasonforhismothertoexpresspossibleconcernsaboutChild1’shearing.HerewehaveanexampleofDeer’shighlyselectivereportingofresults thatwerenot available to the authors of The Lancet paper at the material time.Throughouthisreporting,Deerappearstorelyselectivelyonsuch“facts”thatsupporthispremisethatIhaveperpetratedafraud.

Child1’sRoyalFreeHospitalrecordscontainnoreferencewhatsoevertoanyhearingdifficulties.Theserecordsincludethereferral letterfromtheGPtoProfessorWalker-Smith.TheonlyreferencetoChild1’shearingisintheRoyalFreeHospitalrecordofJanuary21,1996,wherehishearingisreportedasbeing“normal.”23

Thehealthvisitorrecords24wereavailabletotheRoyalFreeteamandaredescribedbelow.

“11.3.93Hearinganddevelopmentnormal.”25

“12.8.93Hearinganddevelopmentnormal.”26

Child2

Sowas thenextchild tobeadmitted.ThiswasChildTwo,aneight-year-old boy from Peterborough, Cambridgeshire,diagnosed with regressive autism, which, according to theLancetpaper,started“twoweeks”afterhisjab.

However, this child’s medical records, backed by numerousspecialist assessments, said his problems began three to fivemonthslater.

The Lancet paper described the onset of Child 2’s first behavioralsymptomsashavingoccurred2weeksafterMMRvaccination.The firstreferencetoonsetofhisbehavioralsymptoms,ascorrectlyreportedinTheLancet, is found in the assessment of Child 2 by consultant childpsychiatristDr.MarkBerelowitzinChild2’sRoyalFreeHospitalrecordsasdescribedinalettertoDr.SimonMurch:27

[Child2’s]milestonesinthe1styearwerenormal.Attheageof13monthsshe[Child2’smother]saidhehad25words,buthegradually losthiswordsover thenext7 to8months.…hisFragile X was negative his brain scan is normal as is hisEEG…[his mother] reiterated that [Child 2] started headbanging about 2 weeks after the MMR and hasn’t lookedrightsince.28I thought that thehistoryandpresentationwereverytypicalofautismorarelateddisorder…

ThisisconfirmedintheRoyalFreerecordsinthedischargesummary:

Until 20months of age…normal developmental progress.…Mum does recount that at 13 months of age he had had hisMMRimmunisationand2weeksfollowingthishadstartedwithheadbangingbehaviourand screaming throughout thenight.Hesubsequentlyseemedgenerallysickly.29

The problem became progressively more severe with loss of language,incoordination, and other features of developmental regression, but thefirstbehavioralsymptomwascorrectlystatedas

…headbangingabout2weeksaftertheMMR.

ThereareadditionalreferencesintheRoyalFreeHospitalrecordsfromthe

senior medical authors of the paper to his subsequent developmentaldeterioration. These include an outpatient note from Walker-Smith thatsaid“hadMMRat15months[ThisisanerrorbyJWSthatshouldread‘13months’],wentdownhilleversince.”30AndaletterfromBerelowitzdatedSeptember30,1996,said“had25wordsat13monthswhichhethenlost,begantogetabitclumsyat15months.”31

Thedifferencebetween14daysandafewmonthsissignificant,accordingtoexperts.Autismusuallyrevealsitselfinthesecondyearoflife,whenthevaccineisroutinelygiven.Iftherewasnosudden onset after the MMR injection, as claimed for the“syndrome”,theconditioncouldbeascribedtoaconventionalpattern.

The sudden onset of Child 2’s behavioral symptoms means that hiscondition could not be ascribed to “a conventional pattern.” In fact,elsewhere in his records, not referenced by Deer, experts describe hisregressive pattern of autism as “unusual.”32 Deer failed to include thisinformation.

Child6andChild7

More apparent anomalies lurked among the following 10children, as they arrived at the Royal Free hospital betweenSeptember1996andFebruary1997.

ChildSix,aged5,andChildSeven,aged3,weresaidtohavebeen diagnosed with regressive autism, with an onset ofsymptoms “one week” and “24 hours” after the jab

respectively.

But medical records show that neither boy was “previouslynormal”,as theLancetarticledescribedall thechildren,andthat both had already been hospitalised with brain problemsbeforetheirMMR.

False:TheLancetarticledescribed these twochildrenashaving“normaldevelopmentfollowedbylossofacquiredskills.”Itdidnotsaythattheywere “previously normal” which is a nonspecific term, potentiallycovering all aspects of their health. The paper did not state that thesechildrenhadbeendiagnosedwith“regressiveautism”asDeerreported.Infact, at the time that paper was written, “regressive autism” was not arecognized diagnosis. Over the years, theywere diagnosedwith variousbehaviorallabelswithintheautisticspectrumincludingautism,Asperger’ssyndrome,andPDD.Theclinicalhistoryandthemedicalrecordsconfirmthat they underwent developmental regression, having been previouslydevelopmentallynormal.

Child6

ChildSixreceivedhisvaccineattheageof14months,buthadtwicepreviouslybeenadmittedwithfits.

WhetherornotChild6sufferedfrom“fits,”thispointisirrelevanttothefactthathisearlydevelopmentpriortoMMRwasconsiderednormal.Hisfit was a febrile convulsion33 which is not uncommon in children withfever and is certainly not indicative of an underlying brain problem orincipientautism.

Child 6’s early development prior to MMR was normal according todocumentssuppliedtotheRoyalFree.34

ItisnotablethatheshouldnothavereceivedMMRvaccineinviewofhishistoryofseizures.InalettertotheconsultantcommunitypediatricianonMay19,1997,Child6’sdoctorwrotethisfromtheRFH:

Mum gave a history in [Child 6] of changes in socialinteraction following on immediately from his MMRvaccination.35

Consistent with the changes in social interaction, Child 6’s initialbehavioral symptomwas confirmed by hismother andwas described inThe Lancet as “gaze avoidance.”36 Thus, Child 6’s initial behavioralsymptomwasaccuratelyreportedinTheLancet.

Child7

ChildSevenwasgivenhisMMRat theageof20monthsbut,again,problemsalreadyshowed.

“Hedevelopedwell,hadsocialsmilingandwasresponsivetohismother,”apsychiatristwrote.“Buthebegantohavepaleepisodes and [sic] petit mal [convulsions], and had an EEG[anelectroencephalogram,acommontestforepilepsy]doneat15months,whichwasabnormal.”

Onceagain,TheLancetpaperspecifically reportedon thedevelopmentalstatus of children, andChild 7was developmentally normal prior to hisMMR.Itisalsonotablethatinviewofhishistoryoffits,heshouldneverhavereceivedanMMRvaccine.

HealthvisitorrecordsareavailablefromDecember21,1994,at10monthsof age showing his development as entirely normal with no concernswhatsoever.37

ThereisanentryinhisGP’srecordsonSeptember27,1995,at19monthsofagethatstates“happybaby.”38

Inspiteofhishistoryofseizures,hisdevelopmentaltrajectorywasentirelynormal as evidenced by an entry in his GP’s records when he was justunder20monthsofage:“Developmentnormal.”39

Child7receivedhisMMRat21monthsofageonNovember24,1995.40InMay1996,hisGPrecordstates:

…bowel problems, constipation and bleeding. MMR Nov 95,quieter since, never happy, does not laugh. Cry or whine allday,falling,unsteady.41

He continued to deteriorate, and on January 29, 1996, his local hospitalrecordsread:

Significant change in behaviour past 2 weeks. He becameaggressiveandincontinent.42

The change following MMR vaccination is described in a letter datedJanuary21,1997,fromWalker-SmithtoChild7’sGPinresponsetohisreferral:

Many thanks for referring [Child 7]. I was very interested tohearthehistoryofthischildinwhichtheredoesseemtobeaclearrelationshipbetweensymptomatologyandtheMMR.Hehad theMMR rather later than the usual at 21 months. Hismother tells me that 24 hours afterwards he had a fit-likeepisodeandsleptpoorlythereafterandsheattributeschangesinhisbehaviourtothisevent.

Let’sreturntoDeer:

Meanwhile,neither [Child6norChild7]wasdiagnosedwithregressive autism, or even nonregressive classical autism.Three of the children had been diagnosed with Asperger’sdisorder, in which language is not lost, and which is notregressive:nothinglikewhatafflictedOneandTwo.ThiswasalsothediagnosisforChildTwelveintheseries,asix-year-oldboyfromBurgessHill,WestSussex.

Child6

False:Based upon this child’s records he received various diagnoses onthe autistic spectrum over the years, including autism43 and autistic

spectrum disorder.44 Evidence of Child 6’s regression can be found atvarious places in his records.45 Child 6’s GP confirmed the mother’sperceptionoftherelationshipofChild6’sautismtoMMRinhisevidencetotheGMConJuly20,2007:

Q:As far as you understood,Doctor, did this child’smotherhavebeliefsastothereasonwhyChild6wasautistic?

A:Yes.

Q:Canyoutelluswhat theywereand, ifyoucanremember,whenshefirstmadethemcleartoyou?

A:Iamnotsurewhenshefirstmadethemclear,probablyfroman early stage. Shewas convinced that it was to dowith theMMRvaccination.Shesaidhewasfinebeforethen.

And Seven would be diagnosed with an odd behaviouralcondition called “pathological demand avoidance syndrome”[PDA].Thisusuallymanifestsassocialmanipulativeness,andisnothinglikethe“syndrome”beingclaimed.It issometimesmarkedbyachildputtinghishandsonhisears,whilesinging“lah-lah-lah,can’thearyou”.

Child 7’s records confirm that he was developmentally normal prior toMMR.46 In contrast with the claim that Child 7’s clinical course was“nothing like the syndrome being claimed,” his history is captured in

Walker-Smith’sletterofJanuary21,1997,tothereferringGPasdescribedabove. There are many references to Child 7’s behavioral anddevelopmental regression in the records.47 And in contrast with Deer’sclaimthatChild7didnothaveanautismdiagnosis,hisrecordsshowthat,as with other children, Child 7’s diagnosis changed over time as hiscondition developed and included not just PDA, butwas documented as“autism,”and“autisticspectrumdisorder.”48

Child8

Only onewas a girl, ChildEight, aged 3, fromWhitleyBay,Tyne & Wear. She was reported in the journal as havingsufferedabraininjury“twoweeks”afterMMR.

Her medical records did not support this. Before she wasadmitted, shehadbeen seenby local specialists, andherGPtold the Royal Free of “significant concerns” about herdevelopmentsomemonthsbeforeshehadherMMR.Mrs 8 expressed concerns about 8’s health and developmentfromanearlystage.

False:Child8wasreportedinTheLancetasfollows:

The only girl (child number 8) was noted to be a slowdeveloper compared with her older sister.49 She wassubsequently found to have coarctation of the aorta. Aftersurgical repair of the aorta at 14 months, she progressedrapidly,andlearnttotalk.Speechwaslostlater.

Based upon the diagnosis of Berelowitz, the Royal Free’s childpsychiatrist, she is reported in The Lancet as having a possible post-vaccine encephalitis (brain inflammation). In contrast with Deer’s falseassertion, her medical records confirm exactly the history that wasreported inThe Lancet. This report is supported by her records ofwhatBerelowitzinterpretedasalikelyencephaliticepisode.

Within 2 weeks of MMR at 19 months developed rash andfebrile convulsions… followed by behavioural deterioration,lossofwordsandvocalisation,screaming,hyperacusis,ataxiaandnocturnalmyoclonicjerks.50

Berelowitzcontinued:

MMR Jan 95, grand mal convulsion Feb 95 2 weeks afterMMR,neverthesameagain.51

The description of Child 8 in The Lancet is an entirely accuraterepresentation of her history as documented in her clinical record anddescribedbelow.Inparticular,Deeromitsthecriticalfactthatbecauseofthe concerns of developmental delay, she was assessed twice prior toMMRbya localdevelopmentalpediatricianwho reportedheconsideredher to bewithin the normal range for development on both occasions.52Theseassessmentstookplaceattheagesof10.5months(May20,1994)and17months(December16,1994).InDecember1994,herdevelopmentwasconsideredageappropriate.

Child8sufferedfromcoarctationoftheaorta.Thiswouldreadilyaccountfor her mother’s concerns about her slow development. The mother’sconcerns about Child 8’s development were with reference to herdevelopmentrelativetohersister53asreportedinTheLancet.

Of note is her GP’s comment in her referral letter to the Royal FreeHospitalofOctober3,1996:

[Child8’s]developmentdidappeartogetworsefollowingtheMMR.54

Child8’sGPcommentsinherstatementmadetotheGMC55thatChild8received her MMR on January 27, 1995, and that since then Mrs. 8“perceivedadefinitereversal”inChild8’sdevelopment.

What is striking is that inFebruary 1995 (Child 8 seenonFebruary17;letterdictatedMarch2,1995),amatterofweeksafterherMMR,shewasonce again reviewed by the same developmental pediatrician (Dr.Houslby) who now determined that she was “globally developmentallydelayedfunctioningatabouttheoneyearlevel.”56

Thus, within the space of just 1 month, Child 8 had deterioratedconsiderably.Ratherthanprogressingdevelopmentally,shehadgonefromfunctioning at around the 18-month level down to the 1-year level in 1month.Verylittle,ifany,attentionseemstohavebeenpaidtothis.Child8’s reaction to the MMR vaccine, although acknowledged, received nofurtherconsiderationandnoappropriateinvestigation.

ThereisagreatdealofevidenceofregressioninChild8’smedicalhistoryandaclearpapertrailofhermother’sassociationofherproblemswiththeMMR, long before any contactwith doctors at theRoyal FreeHospital.

ThisiscorroboratedbymultiplereferencesinChild8’srecords:57

DuringtheGMChearing,Child8’sGPgavethefollowingevidence:58

Q:Whatwas themotherofChild8’sperceptionofChild8’sreactiontothevaccine?

A: I felt that the mother was concerned fairly soon after thevaccine–IthinkIsawherathomeonahomevisitshortlyafterthevaccination–shehadhadakindoffeverishreactiontoit.There obviously was no suggestion of delay at that point.Severalmonths laterhermumsaidshehadbeenlookingatavideo when Child 8 had a little bit of speech before thevaccinationandshefeltthatthathadreducedpost-vaccination.

Q:Theincidentyoudescribeofthevideowassometimelater,wasit?

A:Yes.

Q:Intermsofthemoreimmediatereactiontothevaccine,yousaythatmumreportedafever.

A:Yes.IrememberseeingherathomeandthenIthinkshewas

admittedwithafebrileconvulsionshortlyafterwards.

AletterfromDr.Bushby,thegeneticist,toaGP,Dr.Tapsfield,providedfurtherconfirmationofChild8’sreactiontoMMR.59

In summary, the reporting of Child 8’s behavioral and developmentalhistory in The Lancet paper was entirely accurate. In contrast, Deer’sallegationthathermedicalrecordsdidnotsupportherdescriptioninTheLancetisfalse.

Allegations of changinghistopathological60 findings in the children’sbiopsiesThemeticulous process by which the pathology in tissue biopsies fromThe Lancet 12 was diagnosed and reported has already been described.Withregardtotheallegedmisrepresentationofthepathology,Deerreliesonevidencerelatedtochildren3,8,9,and10.

WhenthechildrenfirstarrivedattheRoyalFree,inadditiontoautism,theywerealsoreportedwithconstipation,diarrhoeaorothercommonbowelcomplaints.Thiswasthereasongivenforthemtravellingbetween60and5,000milestoLondontoenterthecareofWakefield’steam.

TheLancet12allhadgastrointestinalsymptomsincludingabdominalpain,diarrhea, laxative-dependent constipation, bloating, and, in some cases,foodintolerance.

It is misleading to suggest that they entered the care of “Wakefield’s

team.”Deeriswellawarethatallofthesechildrenwereundertheclinicalcare of JohnWalker-Smith’s team of pediatric gastroenterologists at theRoyalFree.Atnotimeweretheyunderthecareof“Wakefield’steam”−therewasnosuchteamofferingcaretochildren.

Wakefield,now52,aformergutsurgeon,wasatthetimedoingacademic research in the Royal Free’s medical school onCrohn’sdisease,anulcerating inflammation. In1995,hehaddeveloped a theory that this condition was caused by themeasles virus, which is found live in MMR. The theory hassincebeendiscounted.

False:Thetheoryhasnotbeendiscounted.

Thisworkwasthebedrockonwhichhebasedhisnewclaims.Yet this tooappearsproblematic.Thechildrenweresupposedto have a new inflammatory bowel disease, written up in theLancet paper as “consistent gastrointestinal findings”involving “nonspecific colitis”. Wakefield said that thisinflammationof the colon caused the gut to become“leaky”,allowingfood-derivedpoisonstopassintothebloodstreamandthebrain.

False: Any new claim was that these children had bowel disease; anyrelationshipbetweenmeaslesvirusandCrohn’sdiseasehadnobearingonthis,letaloneformingits“bedrock.”

False:TheLancetpaperdidnotclaimthat thechildrenweresupposedtohaveanewinflammatoryboweldisease.

False:Ididnotsaythat“thisinflammationofthecoloncausedtheguttobecome ‘leaky’, allowing food-derived poisons to pass into thebloodstream and the brain.” This was merely a hypothesis that waspresentedassuchintheDiscussionsectionofthepaper.

“Theuniformityoftheintestinalpathologicalchangesandthefact that previous studies have found intestinal dysfunction inchildren with autisticspectrum disorders, suggests that theconnection is realandreflectsauniquediseaseprocess,” theLancetPaperexplainedofthe“syndrome”.

Yetpathologyrecordsofsamplestakenfromthechildrenshowapparent problems with this evidence. The hospital’sconsultants who took biopsies from the children’s colonsconcluded that they were not uniform but varied andunexceptional.

Letmereviewforyoutheclaimsandwhatthereportsactuallysaid.

Child8

ForChildEight, the pathology report said: “Noabnormalitydetected”,while theLancetpapersaid:“Nonspecificcolitis”.Thispatternwasrepeatedfortwo[Child9andChild10]oftheotherchildren.”

Child 8’s routine report, undertaken by a neuropathologist (an expert inbrain pathology), in fact described “minimal inflammatory changes.”61

Thiswas confirmed in a letter fromDr.DavidCassonofNovember27,1997, noting that “All pieces of colonic tissue demonstrated minimalinflammatorychanges.”62

When the biopsies were reviewed and scored by experts in bowelpathology, namely Dhillon and Anthony, these doctors determined thattherewasmildinflammationinthececum,ascendingcolon,andrectum.63Thiswascorrectlyreportedas“nonspecificcolitis”inTheLancet.

Child9

Child 9’s clinical histopathology was reported in the routine pathologylaboratory as showing “no histological abnormality.”64 Walker-Smithreviewed Child 9’s biopsies directly with Dhillon. Both agreed that thebiopsies, in fact, showed inflammation consistent with an indeterminatecolitis.65,66 In addition, the research scoring by Dhillon and Anthonyrecordedthis:

Increase in chronic inflammatory cells, cryptitis, reactivefollicular hyperplasia, and increase in intraepitheliallymphocytes.67

A revised diagnosis of “indeterminate colitis” was made, which wascommunicatedtothechild’sdoctorbyWalker-Smith.ThisdiagnosiswasreportedinTheLancet.

Child10

Child 10’s routine histopathology report was provided by an expert ingynecologicalpathology.Itsaidthefollowing:

Nosignificanthistologicalabnormality68

When reviewedbyWalker-Smith’s clinical team, itwas evident to themthat the biopsies showed abnormality, and a supplementary report wasrequestedwhichdescribedmildchronicinflammation.69ThebiopsieswerereviewedbyDhillonandAnthonywhoreported

Mild chronic inflammation in the caecum, ascending,transverse,andsigmoidcolon,andrectum.70

ThiswascorrectlyreportedinTheLancet.

Child3

The most striking change of opinion came71 in the case ofChildThree,asix-year-old fromHuyton,Merseyside.Hewasreported in the journal tobesuffering fromregressiveautismandboweldisease:specifically“acuteandchronicnonspecificcolitis”.Theboy’shospitaldischargesummary,however,saidtherewasnothinguntowardinhisbiopsy.

False: Child 10’s initial routine histopathology report, provided byDhillon,wasabnormal.Itread:

Smallbowelmucosashowsanincreaseinintra-epithelialsmall

lymphocytes;and,Mild inflammatoryandreactivechanges inthesmallbowelsamples.72

Followinghisreview,Walker-Smithnoted:

Marked increase in IEL’s [intra-epithelial lymphocytes] inileum with chronic inflammatory cells. Increase ininflammatorycellsincolonandIEL’sincreased.73

ThebiopsieswerereviewedbyDhillonandAnthonywhoreported:

Mildchronic inflammation in thecaecum,andascendingandsigmoid colon, and rectum, with mild-to-moderateinflammationinthetransversecolon.74

These findingswerecommunicatedby theclinical team toChild3’sGPDr. Shantha75 in a letter of April 10, 1996, from Dr. David Casson (alecturerinpediatricgastroenterology).

Small bowel mucosa showed an increase in intra-epitheliallymphocytesbuttherewas[sic]noarchitecturalabnormalities.Histology of the terminal ileum showed prominent lymphoidfollicles.Colonichistologywasall reportedaswithinnormalhistologicallimits.Overallthereappearedtobethereforemildinflammatoryreactivechangesinthesmallbowelsamples.

In other words, his records show a blatant contradiction between whatDeer reported and what is clearly and consistently stated in the clinicalrecords.

OncethebiopsieshadbeenreviewedbyWalker-Smith’sclinicalteam,thehistological findingswere revised, and a letterwas sent toChild3’sGPinforming him of this change and the resulting treatmentrecommendations.InaletterofDecember31,1996,Walker-SmithwrotetoDr.Shantha:

Yourememberyoukindlyreferred[Child3]tomeandwesenta discharge summary to you on the 4th of October, 1996.Further critical analysis of histology results have led to anamendment to the discharge summary which I am nowenclosing. Our final diagnosis is of indeterminate ileocolitiswith lymphonodular hyperplasia. In the light of thesehistological findings and if gastrointestinal symptoms persist,treatment with a drug such as Asacol might be of sometherapeuticvalue…76

ThedischargesummarywasrevisedbyhandbyaDr.Hepsteadtoreadasfollows:

Diagnosis: indeterminate ileo-colitis and lymphoid nodularhyperplasia.77,78

Underthehistologysection,therevisionreads:

Ilealmucosashowsanincreaseinintra-epitheliallymphocytesbut therearenoarchitecturalabnormalities.Histologyof theterminal ileum showed prominent lymphoid follicles. Colonichistologyrevealedanincreaseofchronicinflammatorycells.

MotivatedbyLitigation?

Further questions arise about the motivations of Wakefield.Fiveyearsagothismonth,TheSundayTimesreportedthatheworkedforlawyers,andthatmanyof thefamilieswereeitherlitigants or were part of networks through which they wouldsue.Farfromroutinereferrals,astheyappeared,manyofthemhadmadecontactwithoneanother.

The clear inference fromDeer’s statement is that the children’s referralwasmotivatedby the fact that theywere litigants. In fact, at the timeoftheirreferraltotheRoyalFreeHospitalnoneofthechildrenwerelitigants.Only one child (Child 12) received a legal aid certificate in the intervalbetweenhisreferraltoWalker-SmithandhisfirstattendanceattheRoyalFree.ThiswascapturedinmyevidenceonDay53oftheGMChearing.79

Child6andChild7

Child Six and Child Seven were brothers from East Sussex;ChildFour,a9½-year-old fromNorthShields,Tyneside,wasregisteredwith the sameGPasChildEight. In short, the12,none of whom came from London, fetched up far-from-routinelyatthehospital.

As stated in The Lancet, children were referred by their GPs orpediatriciansasisroutinepracticeintheNationalHealthService.Thiswasagroupofchildrenreferredtoanexpert teaminatertiaryreferralcenterwithaparticularexpertiseinchildhoodboweldiseaseforinvestigationoftheirintestinalsymptoms.Theirreferralhadabsolutelynothingtodowithlitigation,80 and there has been no evidence produced in support of thisclaim.InhisevidenceonDay73ofthehearing,Walker-Smithconfirmedtheclinicalbasisofthechildren’sinvestigations.81Laterthatsamedayhe

wasaskedwhetherthechildrenweregenuinelyill:

Q:Did it prove to be the case, that they were seriously sickchildren?

A:Theywere.Theywereinsomewaysreallyquiteshocking,inthesensethattheparentshadhadachildwhichwasperfectlywellandthen,quitedramatically,overashortperiodoftime,major behavioural problems and bowel problems hadappeared. There was video evidence and photographicevidenceofthechildrenbeforeandafterinsomecases.

TherewasnosuchsenseofempathyfromDeerinTheSundayTimes.

ThemothersofChildTwoandChildThreetoldmewhatotherssaid inmedicalrecords: theyhadheardofWakefield throughtheMMRvaccinecampaign,Jabs.(sic)

Thus,when theyarrivedonMalcolmward,andproduced the“finding”aboutMMR,82itwasbynomeansarandomsampleofcases.

TheLancetpaperdescribedthefindingsofwhatwasclearlydescribedasa“self-referredgroup”ofpatients.Ithasneverbeensuggestedbyanyoftheauthorsthatthiswasa“randomsampleofcases.”

What parents did not know was that, two years before,Wakefield had been hired by Jabs’s83 [sic] lawyer, RichardBarr,ahigh-streetsolicitorinKing’sLynn,Norfolk.Barrhad

obtained legalaid toprobeMMRforanyevidence thatcouldbeusedagainstthemanufacturers.

False:Deerhasnoknowledgeoftheparents’stateofmind.MyroleintheMMRlitigationwaspublicknowledgefromanearlystage.Forexample,TheIndependentnewspapercarriedastoryonNovember27,1996,called“Law:AshotintheDark.”84Thesecondparagraphopenedwith:

Williamisoneof10childrentakingpartinapilotstudyattheRoyalFreeHospitalinLondon,whichisinvestigatingpossiblelinks between the measles vaccine with the bowel disorderCrohn’sdisease,andwithautism.

Deerwrote:

…ThereisnosuggestiontheotherdoctorsknewofWakefield’sinvolvementwithBarr.

False:Mycolleagues’stateofknowledgeisclearlydocumentedinpapersthat were in Deer’s possession and adduced in evidence to the GMC.Specifically, I firstwrote toWalker-Smith about a patient inNovember1996 informing him that this child had been awarded funding from theLABthatwould,ifnecessary,coverthecostsofhisinvestigation.85ThisisclarifiedinmyevidenceonDay53oftheGMChearing:

Q:CanInowleavethatbackgroundmaterial,andmovebacktotheRoyalFreerecords,page76.On6NovemberyouwrotetoProfessorWalker-Smithaboutthispatient,intheseterms:

“ThisisachildthatIwouldliketobeincludedinourstudyif

you consider him suitable. His community paediatrician, DrMills, was initially enthusiastic about referring him. He nowseems to have gone cold on this. Nonetheless, JS has beenawardedLegalAid,whowillpayfortheinvestigations86andthisisinhand…”

Intheevent,thisfundingsourcewasnotnecessarysincehisinvestigationswere paid for by the NHS. The clinical records of Child JS show thatWalker-Smithknewthatat leastonechildwas in receiptof legalaid forthepurposeoffundinghisinvestigationinNovember1996.

IthenhadameetingonJanuary21,1997,withtheclinicalteamaspartofajointTuesdayinterdepartmentalmeetingattendedbyWalker-SmithandMurch,whereIinformedthemthatIhadagreedtoactasanexpertintheMMRlitigation.

ThiswasfollowedupbyaletterfrommetoWalker-SmithonFebruary3,1997, reiterating my position with respect to acting as an expert anddescribingmyreasonsforagreeingtoactinthiscapacity.ThisletterwasreadintotheevidencebymeattheGMChearingwithDeerinattendance.Theevidencewasasfollows:

Coonan: …was the question of you acting as an expert inlitigationeverraisedwithyourclinicalcolleagues?

A: We had a meeting in January 1997 where the issue wasdiscussed. My clinical colleagues were, in fairness, veryreluctant to become involved in litigation in any form. Iperfectlyappreciatedthat.

Q:Whowaspresentatthemeeting?

A: My memory is that Professor Walker-Smith and SimonMurchwere there. Iwillbeadvisedorcorrectedbut Idonotrememberspecificallywhoelsewasthere.Ibelieveothersmayhavebeenthere…

Q: I am going to ask you to produce an exchange ofcorrespondencerelating to thisdiscussion…Wouldyoubesokindastoreadthisout?Itisyourletter.

A:Certainly.

“DearJohn

re:Enterocolitisandregressiveautism

Further to our meeting on Tuesday 21 January, I thought itimportanttowritetoyoutoclarifymyroleinthelegalissues.Ifullyappreciateyourdesirenottobecomeinvolvedinthelegalaspectof thesecases,but I feel that it is important toexpressthereasonsthatIdofeelobligedtobecomeinvolved.

The future for thechildrenwithwhomwearedealing is verybleak indeed. Not only are the provisions for these childrenwithinthecommunityinadequateatpresent,butlookingaheadtothefuture,therewillcomeatimewhentheparentsofthesechildren die, and the patients, as chronically disabled adults,lefttofendforthemselvesinanextremelyhostileworld.Werethereanylong-terminstitutionsleftforsuchchildren,thenthatis where they would end up. Since these hospitals are beingclosed on an almost weekly basis around the country, thesehopeless individuals will be left to ‘care in the community’.Onedoesnot like to imaginehow itwillallend.Maybe theironlyhopeisinpeopletakingthepossibleorganicbasisoftheirdisease seriously enough to investigate it and institute theappropriatetherapieswherepossible.

Vaccinationisdesignedtoprotectthemajority,anditdoessoat theexpenseofaminorityof individualswhosufferadverseconsequences. Although the case against MMR is far fromproven, it isone thatweareobliged to investigate inviewofthe consistent history given by these patients’ parents and bythe observationsmade in theUnited States. If this disease iscaused by theMMR vaccination, then these children are thefew unfortunates that have been sacrificed to protect themajority of children in this country. If this is the case, oursocietyhasanabsoluteobligationtocompensateandcareforthosewhohavebeendamagedby the vaccine for thegreatergood. This is an inescapable moral imperative and is theprincipal reason that I have decided to become involved inhelping these children pursue their claims. I have consideredthis issue ingreatdepthand,whilst itmaynotbe thewishof

others within the group to become involved, it falls tome tomake sure that their legal cases are presented in the bestpossiblelight.Fortunately, thisisentirelyconsistentwithbestclinicalpracticewhich, Ibelieve, youareproviding for thesechildren. I felt it important, however, to let you know of myfeelings on this, and the position that I feel I am obliged toadopttosupport thesechildren.Withoutourhelp,Igenuinelybelievethatthemedicalprofessionwouldotherwiseputthemtooneside,asitappearstohavedoneinmanycasesalready.Mypresentfearsforthesechildrenaremuchlessthanthehorribleimaginings if theydonot receive theappropriate help that isdue to them at this stage. However, I am an optimist, and Ibelieve that this project will turn out to be both enlighteningandrewardingforallthosewhohavebeeninvolved,andIammostgratefulforyourhelpandencouragement.

Kindestregards&bestwishes,

Yourssincerely”

Q: Did Professor Walker-Smith reply to your letter on 20February1997,withacopytoDrMurch?

A:Yes.

Q:DrWakefield,Ithinkyoumayhavedealtwiththisalready,

butsothatthePanelhasyourresponseintheroundinthelightofyouranswers,wasthereanywayinwhichyourinvolvementwiththeLegalAidBoardwaskeptsecret?

A:No.

ButagainwithDeer…

Whathasnotbeenreportedisthatthenatureoftheprojecthadbeenvisualisedbeforeanyof thechildrenwereevenadmittedtotheRoyalFree.

In June 1996— themonth beforeChildOne’s arrival at thehospital—Wakefield andBarr filed a confidential documentwith thegovernment’sLegalAidBoard,appearingalready toknowofa“newsyndrome”.

The document to which Deer refers87 describes a research proposal fordetecting measles virus in biopsy tissues. It involved the analysis ofbiopsies from five childrenwithCrohn’s disease,where there is awell-establishedintestinaldisease,andfivechildrenwithautisticregressionandintestinal symptoms.Thiswasacompletely separatepieceofwork fromTheLancetpaper.

Thedocumentstatesthefollowinginparagraph3,page1:

Briefly these conditions consist of Crohn’s disease (andinflammatoryboweldisease);therearealsopersistentreports

ofchildrensufferingsymptomsakin toautism(heredescribedas disintegrative disorder) coupled with inflammatory boweldisease.

Thedocumentonlymakesreferencetoreportsofsymptomsandmakesnoclaim to theexistenceof thesyndrome thatwasdescribed inTheLancetpaper, i.e.,“ileocolonic lymphoidnodularhyperplasia,nonspecificcolitisandpervasivedevelopmentaldisorderinchildren.”

The document makes it clear in paragraph 3, page 2, that whatdistinguishesthechildrenwithCrohn’sdiseaseandthosewiththeputativeenteritis/disintegrativedisordersyndromeisthepresenceof“aprimafaciegastrointestinal pathology” in the children with Crohn’s disease. Deer’sclaimseekstoconveytheimpressionthatIwas“aware”ofthesyndromeeventuallydescribedinTheLancetpaperbeforechildrenwiththepossiblesyndromewere ever investigated and, hence, I hadpredetermined that itwouldbepresent.

Referring to inflammatory bowel disease, and then bowelproblemswithautism,WakefieldandBarrwrotetotheboard,successfullyseekingmoney.

“Theobjective,”theywrote,“istoseekevidencewhichwillbeacceptable in a court of law of the causative connectionbetweeneitherthemumps,measlesandrubellavaccineorthemeasles/rubella vaccine and certain conditions which havebeenreportedwithconsiderablefrequencybyfamilieswhoareseekingcompensation.”

ItwasmadeclearduringtheGMChearing88thatBarrwasresponsiblefor

describingthelegalaspectsofthissubmissiontotheLegalAidBoardand,accordingly,itwashewhowrotetheparagraphabove.

Twentymonthslater,theRoyalFreeteamdeliveredthepaperthathadfounda“newsyndrome”.

The“newsyndrome” thatDeer refers tocouldonlyhavebeendescribedafter the children had been investigated and could not have beenanticipated in June 1996. At that stage (June 1996) the evidence for apossible syndrome was the symptoms, i.e., autistic regression andinflammatoryboweldisease.Thesyndromethatwasultimatelydescribedisthecombinationofautisticregressionandintestinalinflammation.Deerconflates the former with latter. In doing so, he leads the reader intobelievingthatIhadalreadymadeupmymindaboutthefinalsyndromeasearlyasJune1996,beforethechildrenhadeverbeeninvestigated.

Today,the12childrenaremostlyteenagers.Atleastthreearebloggers, two in support of Wakefield, while others havelimitedskills.Thewrongfulstigmaofdisabilityhangsheavyonmost,andheaviestonthefamilieswiththemisguidedburdenofguiltthatthevaccinescarehasvisitedonthem.

Wakefield has left Britain to live in Austin, Texas, where herunsaclinicofferingcolonoscopies toAmericanchildren.Hetours the country, giving lectures and speeches against thevaccine,andattractingaloyalfollowingofyoungmothers.

InWakefield’sview,theLancetpaperwasaccurate,includingreasonable reassessmentof findings.Otherdoctors, includinganexperiencedpathologistconcurredwithhisjudgmentonthe

revisedreportsofnonspecificcolitis,hehassaid.

False: In fact it is I who have concurredwith the judgment of others –qualified histopathologists who generated the revised reports— not theotherwayaroundasDeer’sarticlereports.

Behaviouraldiagnoses,meanwhile,involvedaconfusingarrayof technicalnames,andhe trustedwhat theparents toldhim.The fact that they said the problems followed MMR impliedthatregressionwasinvolved.

False: I was not responsible for making a clinical diagnosis of thebehavioral disorder, on the one hand, nor on the other, determining,whetherregressionhadoccurredand,ifso,whetherMMRwasthetrigger.The Lancet paper documents the basis for making the developmentaldiagnoses:thisrequiredafullclinicalhistory,referencetorecordsofearlydevelopment, and in the majority of children, review by a childpsychiatrist.

Many of the parents of the original 12 children continue tosupporthimandcampaignvigorouslyonhisbehalf.Butotherswhose children took part in the Lancet project are tooburdenedandtraumatisedforcampaigning.

Atleastinthis,Deeriscorrect.

TheSourceWhat gave Deer the unqualified gall, the verbal swagger, to challengeexpertsinthefieldofpathologyandpediatricboweldiseaseinthepopularpress?Partof theanswer,at least, isanother expert inboweldisease—

ProfessorTomMacDonald fromSt.Bartholemew’s.MacDonald isnotaclinician,notapathologist,butascientist.WorkingpreviouslyaspartofWalker-Smith’steam,hedidnotmakethejourneytotheRoyalFreewhenhisprofessor’steamtransferredin1995.IntheMMRlitigation,bothintheUSandtheUK,heactedasanexpertforthedefendants.

DTheGMCvettedMacDonaldasapotentialwitnessagainstmeandhiserstwhile colleagues. The attendance note of his meeting with GMClawyersin2005reads:

He [MacDonald] believes Wakefield is a charlatan, who hasbeenpursuinghisownagendasince1995,thisbeingtowintheNobel Prize. He believes Wakefield’s alleged link betweenmeaslesvaccineandCrohn’swasentirely fabricated inordertoobtainpublicityforthisreason.92

Withrespecttotheautismquestion,itismysincerebeliefthat,asasourcefor Deer, MacDonald’s contempt for me and for the notion of boweldiseaseinchildrenwithautismiscapturedinthefollowingmemotoDeer.Thememo itself refers to a colonoscopyvideo, presumably fromoneofTheLancet12:

Of course, when this [video] was made, Wakefield alreadythoughthehadtheNobelprizeinhisgraspbecausehethoughthe saw measles virus in the big lymphoid follicles in theileum…Howeverwhenyouseethevideo,youcanseethatitisvirtually impossible to biopsy the ileum without biopsying alymphoid follicle. If you then decide that on histology tissuesection [down the microscope], the presence of a follicle ispathology,thenyouendupwithhowWakefieldcanclaimthat88.5%89of thechildrenhad ilealpathology.It isadeliberatedeception.90

OtherthanapreoccupationwiththeNobelPrize,MacDonald—ifitishe— fails to explain to Deer why biopsies from the ileum of non-autisticchildren (in which it would be equally “virtually impossible” to miss alymphoid follicle) did not show the same changes as the children withautism. He may also have failed to disclose conflicting agendas, onescientific (asabove)andonepersonal;as related tomebyJohnWalker-Smith,whenMacDonald declined the invitation to transfer to theRoyalFreewithWalker-Smith,hehad reportedlyvowed tohisboss todestroymycareer.91Deerhasbeenusefultohiminthatrespect.

PostscriptA complaint has beenmade to theUK’s Press Complaints Commission(PCC)aboutDeer’sreportage.Intheirresponsetothiscomplaint,lawyersactingforTheSundayTimesconsideredthatafullresponsetothedetailsofthecomplaintwouldbetooonerousat thisstage.Despitethefact thatthematterscoveredinthecomplaintdidnotformpartoftheGMC’scase(andfindings)againstme,thePCCdeferredactiononthecomplaintuntilafter the GMC process was complete. The PCC did require that Deer’sarticles be removed fromThe Sunday Times website. In defiance of thePCC, the articles were reinstated when a press release was issued thathighlighted the PCC’s directive. The PCC’s failure to enforce theirdirectiveisnotreassuring.

Endnotes1 E-mail fromAlistairBrett, in-house lawyer forTheSundayTimes, toAbelHaddenofBell-Pottinger.June18,2004.

2 WakefieldAJ,MurchSH,AnthonyA,LinnellJ,CassonDM,MalikM,BerelowitzM,DhillonAP,ThomsonMA,HarveyP,ValentineA,DaviesSE, Walker-Smith JA. Ileal lymphoid nodular hyperplasia, non-specificcolitis and pervasive developmental disorder in children. The Lancet.1998;351:637-641.[retracted]

3 Deer’s allegation to the GMC regarding unethical experimentation:Letter of Deer to TimCox-Brown February 25, 2004, p. 3. “Therefore,therewas,inmyview,neitherethicalapproval,norclinicalindicationfortheinvasiveinvestigationofsomechildren.”

4 Walker-SmithJA.Statement.TheLancet.2004;363:822-823.

5 SeestatementofDr.Dhillonbelow,footnote16.

6 Wakefield AJ. Autistic enterocolitis: is it a histological entity?Histopathology.2006;50:380-384.

7 WakefieldAJ,MurchSH,AnthonyA,LinnellJ,CassonDM,MalikM,BerelowitzM,DhillonAP,ThomsonMA,HarveyP,ValentineA,DaviesSE, Walker-Smith JA. Ileal lymphoid nodular hyperplasia, non-specificcolitis and pervasive developmental disorder in children. The Lancet.1998;351:637-641.[retracted]

8 Dr.SueDavies,consultanthistopathologist,RoyalFreeHospital.

9 AmarP.Dhillon,AndrewAnthony,AndrewWakefield.

10 WakefieldAJ,AnthonyA,MurchSH.Enterocolitis inchildrenwithdevelopmental disorders. American Journal of Gastroenterology. 2000;

95;2285-2295.EnterocolitisinChildrenWithDevelopmentalDisorders

Mucosalbiopsiesweretakenfromtheileum,cecum/ascendingcolon, transverse colon, descending/sigmoid colon, andrectum. Hematoxylin and eosin-stained histological sectionsfrom all biopsies were reviewed in the routine pathologylaboratory,followedbyindependentreviewandscoringonastandard proforma (Table 1)10. In those cases where therewas disagreement between these two reports, sections wereexamined and reported by a third senior pathologist,whosearbitrationprovided the final score. In an identicalmanner,histological sections from the ileum and colon of childrenwithoutdevelopmentaldisorderwerescored(medianage11.5years; range 2-13). These included 22 consecutiveileocolonoscopic biopsy series that had been reported asnormal after routinehistopathologyassessment.All childreninthisnon-IBDcontrolgrouphadundergoneileocolonoscopyfor investigation of intestinal symptoms and are included inthe 37 endoscopic controls, as described above. To validatefurther the evaluation and scoring, 10 coded ileocolonicbiopsy series (five affected children and five non-IBDcontrols) were reviewed at another institution by a seniorpathologist in an observer-blinded fashion.Data from theseindependentassessmentswerecompared.

11 Results.Tenileocolonicbiopsyserieswerereviewedandscoredinanobserver-blindedfashionatanindependentinstitution.Noindicationwasgivenofhowmanysamplescamefromeachpatientgroup.Cases[autisticchildren’sbiopsies]wereclearlydistinguishedfromcontrols[non-autisticchildren’sbiopsies]bytheblindedreviewer11.Outofapossibletotalof15points,independentscoreswereidenticalforthesamecriterioninfourof

10cases(40%),withinonepointofeachotherinfiveof10cases(50%),andwithintwopointsofeachotherinoneof10cases(10%)(Spearmanrank correlation 0.79; p < 0.006). No reviewer scored systematicallyhigherorlowerthantheother.

12 Wakefield AJ. Autistic enterocolitis: is it a histological entity?Histopathology.2006;50:380-384.Thiswasaninvitedresponsetoapaperby MacDonald and Domizio that questioned the validity of the boweldisorderinautisticchildren.[Histopathology;samevolumeasabove.]Autisticenterocolitis:isitahistopathologicalentity?

Forthepurposeofclarification,childrenwithdevelopmentaldisorder were seen in the Department of PaediatricGastroenterology at the Royal Free for evaluation of theirgastrointestinal symptoms. Definitive and appropriateassessment included ileocolonoscopy, upper gastrointestinalendoscopy and histopathology. Biopsy specimens weresubjected to routine assessment by the duty pathologist andsubsequentdetailedreviewwithscoringonasemiquantitativescale as illustrated in the manuscript of MacDonald andDomizio.TheproformawasdesignedbyProfessorA.DhillonoftheDepartmentofHistopathology,whowithDrA.Anthonyevaluated the sections for thepurposesofcompletionof thisproforma. The interobserver variation using thehistopathologyproformawashighandisdescribedindetail.1Bothpathologistshaveanextensive,publishedtrackrecordinmucosal histopathology. In addition, all diagnoses wereroutinely reviewed at a weekly clinicopathological meetinginvolvingcliniciansandpathologists,andfrequentlymodifiedasaconsequence.

13 GMC vs Wakefield, Walker-Smith, and Murch. Dr. Wakefield’sevidence.Tr.49

Coonan:Iwanttocomeonnowtowhatyou,inanticipation,describe as “Research tests”, and we see that under theheadingof“intestinalbiopsy research” thereare referencesintheright-handcolumnonpage221tohistology,andweseethaton the firstpageof thisdocument, in the fourthcolumndown, there was also a reference to histology. Why ishistology captured under this heading of “Research tests”withthesourcereferenceatpage221?Whatisthedifferencebetweenthetwo?Wakefield:Standardroutinehistopathology is involved in theclinicaldiagnosisofdiseaseinthesechildren.DrPaulDhillonaspartofhiscontributiontothisdecidedatarelativelyearlystagethat, inlightofthefindingsinthesechildren,inlightoftheapparentnoveltyandsubtletyofsomeofthechanges,aproformadrivenanalysiswouldbenecessaryinordertoprovideasemi quantitative estimate of what was going on in theirintestine, and to this end he designed a histology pro formawhich could be scored as, for example, zero for noinflammation; one for mild inflammation; two for moderateinflammation,and three for severe inflammation,andhe tookthevariouscategoriesofchangesintheintestineandsetthemoutunder thosenumbers,normal,mild,moderateandsevere.AndthatwasusedinadetailedhistopathologicalreviewbyDrDhillon and Dr Anthony, principally, with me looking overtheir shoulders to learn, and that formed the basis of theresearchhistopathology.Coonan: Sowe have, is this right,DrWakefield, a strata ofclinical histopathology but also a strata of researchhistopathology?Wakefield:Correct.

AndonDay50:

Coonan:Ihavetwoothershortmatterstodealwith.WhenitcametothedraftingofTheLancetpaper,canwejustidentifytogether the materials that you would have had available?Firstofall,wouldyouhavehadthereferralletters?Wakefield:Yes.Coonan:Would youhavehad the clinical notesgeneratedatthe Royal Free, including correspondence to and from theRoyalFree?Wakefield:Yes.Coonan: Would you have had the clinical histopathologydocumentationgeneratedbythehistopathologistincludingDrDavis?Wakefield:Yes…Coonan: Would you have had the product of any Fridayafternoonamendmentsinthenotes?Wakefield:Yes.Coonan:WehaveheardabouttheroleofDrDhillon.DidyouhavetheproductofDrDhillon in relation to this child prior to the drafting of TheLancetpaper?Wakefield: Yes, indeed; Dr Dhillon’s detailed research,overview, in the pro forma driven format that I have talkedabout last week was available and in fact was the finaldeterminantofthediagnosisinthesechildren.Coonan:Justforcompleteness,wouldyoutakevolume7ofthePanelbundles,and lookat tab16? In general terms,what istab16?Wakefield:Sometimeduringthecourseoftheinvestigationofthese children it became clear that therewas a possible newsyndrome emerging, that bowel disease was indeed beingfound,immunologicalabnormalitieswerebeingfound.Bywayof our training in academic medicine, which is largely proforma driven and database driven, it was felt appropriate todevelopa system, albeit rather primitive at the time, tomake

surethatalltherelevantinformationwasbeingcaptured.Thisisnotnecessarilyaresearchexercise,althoughitcanbe;itisaway of making sure that you have ticked the boxes, that youhave captured the relevant information in a consistent wayacrossagroupofpatients.Sothisisaproformaorthesearedraftproformasinvariousstatesofpreparationthedesignofwhich was mine. What I have attempted to do in this is tocapture the salient features of his child’s history, thedemographic information, their infancy, their childhooddevelopment, their infectious and vaccine exposure, theirhistologyandsoonandsoforth.Coonan:DiditincludetheproductfromDrDhillon?Wakefield: Yes. If you turn to page 243, you will see anexample of the histology pro forma that I mentioned to you.Nowthisisasummaryproforma.Eachindividualbiopsy,andthere may be seven or eight of them from the colon of aparticular child, has one page like this. You will see thedesignationdownthelefthandcolumnof:acuteinflammation,chronicinflammation,epithelialorlaminarpropriachanges,etcetera. These are just histological matters of interest. Thenacross the top, if therewerenoneof these featuresof interestpresent,therewasazeroscore.Iftheywerepresentandmild,thenascoreof1,moderate2,severe3,andthenatotalscoregiven.ThisisDrDhillon’scontributiontothiswork.ThiswasdoneincooperationwithDrAndrewAnthony.

14 SignedstatementofDr.A.P.DhillontotheGMC.

17. In quite a different way [to routine diagnostichistopathology],whenahistopathologistprovides systematicobservations for research purposes, it is best practice to beunbiasedandnottoseetheclinicaldetailsofthepatientwho

hasprovidedthesample.Inthecontextofinflammatoryboweldisease, the histopathologist might put more order into hisobservations and may say whether there is acuteinflammation, chronic inflammation, ulceration, orarchitecturalchanges.He/shewillalsocommentontheextentto which these things can be seen on the slide.Histopathologists sometimes record their observations as a“score” ranging 0-III, where ‘0’ could represent noinflammation, ‘I’ could represent mild inflammation, ‘II’could represent moderate inflammation, and ‘III’ couldrepresent severe inflammation. 18. I often use this type ofscoring system when I am asked to undertake a systematicreview forresearchpurposes. Iwill lookateachslidedownthemicroscopeandrecordtherelevantfeaturesforeachslidein a table. I may record a score for some of the relevantmicroscopicalfeaturesinthetableaswell.19. The different scores of 0-III representing for example,different degrees of inflammation, are not necessarilyreproduced in a published research paper unless a specificrefereerequestsit.20. My appointment in the Medical School requires me toundertakeresearchactivities.Around1997,IwasaskedbyDrWakefield to review a series of slides of gut biopsies frompatients from the paediatric gastroenterology department.…Biopsieswouldhavebeentakenfromdifferentpartsofthegutfromeachpatient,andIwouldhavelookedatthewholeseriesofbiopsiesforeachpatient.21. For my research review of slides, I was not given anyclinical details about the children who had provided thesamples. I made microscopical observations and recordedthese observations using the system described above. TheobservationsweregiventoDrWakefield.22.WhenIwasaskedtodothisreviewofslides,Ididnotknowwhatsymptomsthechildrenhad.Thereviewoftheslideswas

straightforwardandwasamatterofsayingwhethertherewasinflammation or not as well as other relevant microscopicalobservations.23.The idea topublish theseriesofchildrendescribedin the1998 Lancet paper had arisen probably in 1997. It was thenthat I learned more about the clinical syndrome which thechildren (included in the slide series which I had reviewed)apparentlyhad.Myclinicalcolleaguestoldmethatthiswasagroupofchildrenwithasyndromethatincludedgutproblems,endoscopicchangesandaparticularhistologicalappearance.These children had delayed or regressed development. Thesyndromebecamemorecoherent tomewhenIsawadraftofthepaper.24. The paper contained histology paragraphs and a tablewhichincludesacolumnwherethehistologicalfindingsforthe12childrenhavebeenwrittenup.Ididnotwritethehistologysection of the paper and I cannot remember whether I madeany amendments to the draft paper which would have beencirculated to all of the authors. I do not know if any otherhistopathologistsundertook thesamereviewexercisewith theslidesasme,andIdidnotseetheirobservations.25.The personwhowrote the histological findingsmayhavelookedat theobservationswhich I provided toDrWakefield.ThepersonwritingtheresearchpapermayhavetranslatedtheRomannumeralscoreswhichImayhaveusedintosomethingreadable. For example, the term “lymphoid nodularhyperplasia” is synonymous with “increased or enlargedlymphoidfollicles”,andthisinaspectofchronicinflammation.26.Thepaperwaspublished in theLancet inFebruary1998and was entitled “Ileal-lymphoid nodular hyperplasia, non-specific colitis, and pervasive developmental disorder inchildren” (“the Lancet paper”). I was named as one of theauthors on this paper because of the blinded review of theseriesofslideswhichIundertookinaresearchcapacity.

15 GonzalezL,etal.EndoscopicandHistologicalCharacteristicsoftheDigestiveMucosa inAutistic Childrenwith gastro-Intestinal Symptoms.Arch Venez Pueric Pediatr, 2005;69:19-25. Balzola F, et al. PanentericIBD-like disease in a patient with regressive autism shown for the firsttimebywirelesscapsuleenteroscopy:Anotherpieceinthejig-sawofthegut-brain syndrome? American Journal of Gastroenterology, 2005.100(4):979-981.Krigsman A, et al.http://www.cevs.ucdavis.edu/Cofred/Public/Aca/WebSeccfm?confid=238&webid=1245.(lastaccessedJune2007)[nolongeravailable;fullpapernowpublishedbelowasfootnote16].BalzolaF,etal.Autisticenterocolitis: confirmation of a new inflammatory bowel disease in anItaliancohortofpatients.Gastroenterology2005;128(Suppl.2);A-303.

16 GaliatsatosP,GologanA,LamoureuxE.Autisticenterocolitis:factorfiction.CanadianJournalofGastroenterology.2009;23:95-98.Krigsman A, Boris M, Goldblatt A, Stott C. Clinical Presentation andHistologicFindingsatIleocolonoscopyinChildrenwithAutisticSpectrumDisorder and Chronic Gastrointestinal Symptoms. Autism Insights.2009;1:1-11.ChenB,GirgisS,El-MataryW.Childhoodautismandeosinophiliccolitis.Digestion.2010;81:127-9.Epub2010Jan9.

17 TaylorB,MillerE,FarringtonCP,PetropoulosMC,Favot-MayaudI,Li J,Waight PA.Autism andmeasles,mumps, and rubella vaccine:Noepidemiological evidence for a causal association. The Lancet.1999;353:2026-9.

18 Wakefield AJ. MMR vaccination and autism. The Lancet,1999;354:949-950.

19 Clinic note of Professor Walker-Smith, June 20, 1996. Royal Free

Hospitalrecords.

20 WakefieldAJ,MurchSH,AnthonyA,LinnellJ,CassonDM,MalikM, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A,Davies SE,Walker-Smith JA. Ileal lymphoid nodular hyperplasia, non-specific colitis and pervasive developmental disorder in children. TheLancet1998;351:637-641.[retracted]

21 Generalpracticerecords,p.54.

22 Generalpracticerecords,p.6.

23 “Hearing”followedbyahorizontalarrowwhichdesignates“normal”inmedicalclerking.

24 Generalpracticerecords,p.14.

25 [Age2months]Healthvisitorrecord.

26 [Age7months]Healthvisitorrecord.

27 Dr.MarkBerelowitzlettertoDr.SimonMurch.September30,1996.RoyalFreeHospitalrecords,pp.143-144.

28 Emphasisadded.

29 RoyalFreeHospitalrecords,p.145.

30 RoyalFreeHospitalrecords,p.25.

31 RoyalFreeHospitalrecords,p.143.

32 LetterfromDr.RobertSurtees,pediatricneurologistatGreatOrmondStreet Hospital, to Dr. Hilary Cass at Harper House. August 23, 1996.Generalpractitionerrecords,p.146.

33 East Suffolk Health Authority discharge note. March 16, 1993:“febrileconvulsion”

34 HealthVisitorRecords.p.3.

35 LetterfromDr.CassontoDr.Bennett,communitypediatrician.May19,1997.RoyalFreeHospitalRecords,p.80.

36 Lackofeyecontactisacardinalfeatureofautism.

37 Healthvisitorrecords,December21,1994.

38 Generalpracticerecordsp.23.

39 General practice records p. 24. “DevelopmentN” (circled) standingfor“normal.”

40 Generalpracticerecordsp.296.

41 Generalpracticerecordsp.296.

42 Localhospitalrecordspp.111-112.

43 Generalpracticerecords,p.28—“autism”.FileRFH17—diagnosedwithautismatage3yearsbyBennett(communitypediatrician).

44 CorrespondencefromJWStoDr.NalletambysummarizingChild6aswithin the autistic spectrum and having chronic bowel symptoms.February10,1996.

45 Generalpractice records,p.244—reference to regressivenatureofthe problem.General practice records, p. 309— sequence of regressiondescribedindetail.

46 General practice records, p. 218 — no concern about early

developmentalmilestones.

47 General practice records p. 86 — at 21 months saying 3-4 wordsentences, followingMMR speech stopped— “flat effect,” “completelybabyish.”Generalpractice recordsp.219—regression in language skills at about2.5years(seealsoGPR220).Generalpracticerecordsp.357—ProfessorNeville:behaviouraproblemat20months,afterMMR.“Stoppedspeakingandlostbowelcontrol.”General practice records p. 279— letter from ProfessorWalker-Smith:mothergiveshistoryoffitfollowingMMRandchangesinbehavior.

48 General practice recordsp. 222—September1998:diagnosedwith“Pathological Demand Avoidance in the autistic spectrum” (see alsoGPR230).General practice records p. 276 — February 1997 -GP thinks he has“autism/autisticspectrum.”Generalpracticerecordsp.239—“diagnosisofautisticspectrumdisordersomewherebetweenhighfunctioningautismandAsperger’s.”Generalpracticerecordsp.59—“autisticspectrum”diagnosis.Generalpracticerecordsp.417—“pervasivedevelopmentaldisorder.”Generalpracticerecordsp.353—“pervasivedevelopmentaldisorder.”General practice recordsp. 222—“pervasivedevelopmental disorder intheautisticspectrum.”General practice records pp. 135, 141, 163, 169, 189, 239, 276, 357.General consensus by early 1997 that Child 7 has autism spectrumdisorder.

49 Confirmed in letter fromDr. Houlsby to Dr. Tapsfield, attached tostatementofDr.Jelly.

50 RoyalFreeHospitaldischargesummary,January27,1997,attachedtostatementofDr.Jelly.

51 Generalpracticerecords,p.25.

52 Confirmed in letter fromDr. Houlsby to Dr. Tapsfield, attached tostatement of Dr. Jelly and letter to Dr. Hunter from Dr. Houlsby,December23,1994:“feltthatherabilitiesalthoughdelayedontheaverageageofattainmentwerenotoutsidetherangeofnormal.”

53 RoyalFreeHospitalrecords,p.7.January19,1996.

54 RoyalFreeHospitalrecords,p.21.

55 Dr.JellystatementtoGMC,Day29.

56 Generalpracticerecords,p.94.

57 General practice records p. 25 — “MMR Jan 95, grand malconvulsionFeb952weeksafterMMR,neverthesameagain.”General practice records, p. 76—discharge letter fromRFH: “dramaticdeterioration”from18months.General practice records, p. 83—GP letter: some developmental delaybeforeMMRbut“motheradamantthatshelostherspeechafterMMR.”Generalpracticerecords,p.94—at17monthsshewaswithinthelowerrangeofnormal,at20monthsshewasgloballydevelopmentallydelayedfunctioningatabouta“oneyearlevel.”Generalpracticerecords,p.111—letterfromGP:“regressionafterMMR.”Generalpracticerecords,p.120—lossofspeechshownonvideo.General practice records, p. 121—clear evidenceof regressionprior toadmission.Generalpracticerecords,p.127—concernoverlackofspeech(althoughcontinuedtosayafewwords).General practice records, p. 130 — mother associates “setback” withMMR.Generalpractice records,p.131— letter frompediatrician: “atoneyearlevelonDenverDevelopmentalAssessment.”

General practice records, p. 133— letter frompediatric cardiologist: nospeechwhereaspreviouslysaidsinglewords.Generalpracticerecords,p.136—evidenceofregression.Generalpracticerecords,p.139-evidenceofregression.Generalpracticerecords,p.142—herspeechhasregressed.Royal Free Hospital records, p. 7 — admitted with history ofdevelopmentaldelayfollowingdramaticdeterioration.Royal Free Hospital records, p. 17 — letter to AW from Dr. Berney:appearstoacceptabruptpostMMRregression.Royal Free Hospital records, p. 18 — mother reports “catastrophicdeterioration”postMMR.“Becameadifferentperson.”RoyalFreeHospitalrecords,p.20—historyofdramaticdeteriorationinreferraltoBerelowitz.RoyalFreeHospitalrecords,p.49—goodevidenceofregression.Local hospital records, p. 20 — accepts that there were concerns redevelopment prior to MMR but then makes clear that there was asubsequentdeterioration.Localhospitalrecords,p.45—furtherevidenceofregression.

58 GMCvsWakefield,Walker-Smith,andMurch.EvidenceofDrJelley.Tr.29.

59 GMCvsWakefield,Walker-Smith,andMurch.Tr.29:

[Child 8’s] mother came to the Genetics clinic recentlywithout[Child8].Unfortunatelywearestillunabletoreachafirm diagnosis to explain [Child 8’s] developmental delay,coarctationoftheaortaandslightlyunusualface.Hermotherreportsthatsheisstillwithoutspeech.Much of our discussion recently centered around [Child 8’s]mother’sconcerns thatherproblemsstemmedfromherMMRvaccinationat19months.She tellsmethatacoupleofweeksaftertheinjectionshedevelopedameaslesrashandwasvery

poorly with it. She subsequently fitted and was admitted tohospital where she was found to be dehydrated. [Child’s 8]mother is aware that there may be an underlying cause for[Child 8’s] problems but is obviously also anxious that theMMR injection either caused her developmental delay orexacerbatedit.ShehasbeenintouchwithanorganisationJabs[sic]and is incontactwithamotherofachildwhosimilarlyfeels that her child’s problems date from the MMRimmunisation. Interestingly [Child 8’s] mother feels verystronglythat[Child8’s]speechwascomingonwellbeforeshehadher immunisationand that shehad severalwordsat thatstagewhichshesubsequentlylost.

60 Histopathology is theprocessofmakingamicroscopicdiagnosisontissuestakenfromapatient.

61 RoyalFreeHospitalrecords,p.61.

62 RoyalFreeHospitalrecords,p.15.

63 ProformareportofChild8.

64 RoyalFreeHospitalrecords,p.48.

65 Inhisevidence to theGMConDay81,page12,Walker-Smithwasquestioned:

StephenMillerQC:We have got up to 11December 1996.You have told thePanel in general terms and in relation toindividual children about the review of histologywhich youcarriedoutwithDrDhillon?Walker-Smith:Yes.Miller:InDecember1996,sointheperiodwithwhichweare

now concerned, in which we are looking at this child’sinvestigation. Was this child one of the children whosehistologyyoureviewedwithDrDhillonafterhedidhisblindedassessmentoftheslides?Walker-Smith:Yes.Miller: Ifwe lookat thepenultimatepage in theclip thatwehave,D14.Professor,justunderhalfwaydowninthatnoteofthewayyoudealwithabriefsummaryofthehistory,thentheblood results. Then, under “Endoscopy,” what have youwritten?Walker-Smith:Ihavewritten:“Lymphoidnodularhyperplasiaterminalileum.”Miller:Then“Histology”underneaththat?Walker-Smith:Ihavewritten:“ProminentlymphoidfolliclesDhillon — moderate to mild increase in intra epitheliallymphocytes. Increase in chronic inflammatory cells throughthecolon—superficialmacrophagesnotquitegranuloma”.Thenmyoverallclinicalopinion:“Indeterminatecolitis.”

66 GMCvsWakefield,Walker-SmithandMurchTr.81,p.13.

Miller: “Histologically there was an increase in chronicinflammatory cells throughout the colon with a moderateincreaseinintra-epitheliallymphocytes.”Walker-Smith:Yes.Miller:Again,puttingthatalongsidewhatyouhavesaidinthishandwritten note atD14, is that taken from that handwrittennote?Walker-Smith:Itis.Miller:Becauseyouhavesaid:

“Moderatetomarkedincreaseinintra-epitheliallymphocytes.Increaseinchronicinflammatorycellsthroughoutthecolon.”

67 Child9draftproformareport.

68 RoyalFreeHospitalrecords,Vol.2,p.47.

69 GMCvsWakefield,Walker-SmithandMurch.Tr.81.

Miller:Ifwelookat59Aitsetsoutwhattheoriginalfindingwas of Dr Jarmulowicz. Then microscopic descriptionsupplementaryreportatthebottomofthepage.Walker-Smith:Yes.Miller: These biopsies have been reviewed following aclinicopathologicalmeeting. The ileal biopsy shows confluentlymphoid aggregates within otherwise unremarkable smallintestine. The large bowel biopsies show a very subtlescattering of chronic inflammatory cells within the laminapropria.Thesuperficiallaminapropriacontainsfocalnucleardebrisandthesurfaceepitheliumappearsslightlydegenerate.Noactiveinflammationisseen.Morelevelshavebeencutandno granulomas have been identified. Comment: Minorabnormalities.?Significance.”And that is countersigned on this occasion by Dr Davies aswellasbyDrJarmulowicz.Walker-Smith:Yes.Miller:What, ifanything, is thedifferencebetween those twosetsoffindings?Walker-Smith: The principal difference really is in the largebowelreport–averysubtlescatteringofchronicinflammatorycellswithinthelaminapropriaisaclearindicationofchronicinflammation.Andtheso-calledfocalnucleardebris,thattellsus that there has been some damage in the past; and the

surface epithelium said tobe slightlydegeneratealso tells usthat therehasbeensomedamage,but there isnoevidenceofactive inflammation.Curiously, thisreportactually leavesoutan important observationwhichDr Jarmulowiczmade in thefirst report, saying that the lymphoid tissue shows reactivechanges,whichIregardasratherimportant.Miller:Theconclusionfromthesecondreport,theamendedorupdatedreportis:“Minorabnormalities?Significance.”Whomakesthedecisionastotheinterpretationoveralloftheabnormalities,ifthereareabnormalities,ontheslides?Walker-Smith:Theclinician.Miller: How does that work? You have a report from ahistopathologistinwhichhesetsoutindetailwhatthefindingsare for individual sections, or groups of sections, and thencomestohisconclusion;butintermsofthemanagementofthepatienthowdoesthedecisiongetmade?Walker-Smith: The histology report gives the objectiveevidence of things that are seen down the microscope in adescriptiveterm.Thehistopathologistsdooffertheiropinionasto possible significance, but the clinician is the personresponsibleforputtingtogethertheclinical features—that isthesignsandthesymptoms—theendoscopicfeaturesandtheobservedhistopathologicalfeatures.Miller:IfwelookatDrCasson’snoteatpage17involume2.Wehaveseenthetophalfofthisnotebefore,whichiswrittenon the printed form for endoscopy — it is under histology.“Colonic biopsies — normal crypt architecture; very milddistribution of chronic inflammatory cells. Decreased gobletcells. Focal abnormalities of epithelium, i.e. tufting. Nucleardebrisinsub-epitheliumdeposits.”Walker-Smith:Yes.Miller:Thatisagainaslightlydifferentdescription.Walker-Smith:Yes.

Miller: But in what circumstances would that have beenwritten?Walker-Smith:PresumablythatwaswrittenbyDavidCassonat thetimeof thehistopathologicalmeetingasarecordashesawit.Miller:Thenatthelastlinehedoesthosearrowsleadingfromonethingtoanother,sothereisanarrowandthen:“Enough chronic inflammation to merit treatment withsulphasalazine.”Walker-Smith:Ithinkthismightbeaquotationfrommyself.Miller:Perhapsyoucouldexplainhowitcomesabout?Walker-Smith: Usually I and my two consultant colleagueswould come to a view as to the clinical significance of thefindingswhichweobservedattheclinicopathologicalmeetingbecauseoneofthejuniordoctorsdidinfactpresentthehistoryand findings. Then the relevant consultant endoscopistwouldtell us about the endoscopic findings; then we would see infrontofusonthescreenwhatthehistopathologywas.Thenthecliniciansandindeedthejuniordoctorswoulddiscusstogetherwhat was the way forward because the parents are usuallywaitinginthewardafterthemeeting,andDrCassonwouldgoand speak to them. I believed on the total picture that itwasappropriate to use sulphasalazine and, although it is notwritten there, I was obviously making a diagnosis ofindeterminatecolitis.

70 ProformareportofChild10.

71 Emphasisadded.

72 RoyalFreeHospitalrecords,pp.86and87.

73 JWSpresentationtoWellcomeTrustmeeting,December1996.

74 ProformareportofChild3.

75 RoyalFreeHospitalrecords,p.27.

76 Generalpracticerecords,p.99.

77 RoyalFreeHospitalrecords,p.35.

78 RoyalFreeHospitalrecords,pp.35and36.

79 GMCvsWakefield,Walker-Smith,andMurch.Tr.53.

Coonan: Thank you very much. Can I turn from medicalmatters and research matters to the question of legal aid?ThereisareferencetolegalaidthatIwouldlikeyoutolookatinvolume1ofthePanelbundleatpage242.ThisisalegalaidcertificateforChild12andformypurposestheonlythingIneedfromthisisthedate,atthebottomright-handcorner,9October1996.Didyouevergettoknowthatthischildhadalegalaidcertificate?Wakefield:Yes.Q:Whendidyougettoknowthat?A:No, I cannot remember,butas it turnsout this is theonlychild who was, to our knowledge involved in litigation —subsequent knowledge. It turns out that this is the only childwho had a legal aid certificate prior to [errata: after] theirreferralandinvestigationattheRoyalFreeHospital.Q: But at the time of the referral or about the time of thereferralandinvestigationdidyouknowthenthathehadalegalaidcertificate?A:Ihavenomemoryofit.Q:DidthischildbecomeoneoftheLegalAidBoardchildren?A:Yes,Ithinkhedid.Q: Did you have any understanding or appreciation of any

litigation motivation by the mother at or about the time ofreferral.A:No,themother’smotivationisevidentinthelettersthatshehas written to Professor Walker-Smith and that is thegastrointestinal symptoms and problems that she felt werepresentinherchild.

80 Letterfrom8ofthe12parents.December22,2008.OnelivesintheUSand2couldnotbecontacted.Thethirdremainingparentsentane-mailofsupportbutwishedtoremainanonymous.

AnOpenLetter:ToWhomItMayConcernWearewritingtoyouasparentsofthechildrenwho,becauseof their symptoms of inflammatory bowel disease andassociated autism, were seen at the Royal Free HospitalPaediatric Gastroenterology Unit by Professor Walker-Smithand Dr Simon Murch with the involvement of Dr AndrewWakefield on the research side of their investigations. Ourchildren became the subjects of a paper published in TheLancet in 1998. We know these three doctors are beinginvestigated by the General Medical Council (GMC) on thebasis of allegations made to them by a freelance reporter.Amongthemanyallegationsmadearethesuggestionsthatthedoctorsacted inappropriatelyregardingourchildren, thatDrWakefield“solicitedthemforresearchpurposes”andthatourchildrenhadnotbeen referred in theusualwayby theirownGPs. It is also claimed that our children were givenunnecessary and invasive investigations for the purpose ofresearch,andnotintheirinterest.Weknowthiswasnotso.AllofourchildrenwerereferredtoProfessorWalker-Smithintheproper way in order that their severe, long-standing anddistressing gastroenterological symptoms could be fully

investigated and treated by the foremost paediatricgastroenterologistsintheUK.ManyofushadbeentoseveralotherdoctorsinourquesttogethelpforourchildrenbutnotuntilwesawProfessorWalker-Smithandhiscolleagueswerefullinvestigationsundertaken.Wewerealltreatedwithutmostprofessionalism and respect by all three of these doctors.Throughoutourchildren’scareattheRoyalFreeHospitalwewerekeptfullyinformedabouttheinvestigationsrecommendedandthetreatmentplanswhichevolved.Alloftheinvestigationswere carried out without distress to our children, many ofwhommade great improvements on treatment so that for thefirsttimeinyearstheywerefinallypain-free.WehavebeenfollowingtheGMChearingswithdistressaswe,theparents,havehadnoopportunitytorefutetheallegations.Forthemostpartwehavebeenexcludedfromgivingevidencetosupportthesedoctorswhomweallholdinveryhighregard.It is for this reason we are writing to the GMC and to allconcerned to be absolutely clear that the complaint that isbeing brought against these three caring and compassionatephysicians does not in any way reflect our perception of thetreatmentofferedtooursickchildrenattheRoyalFree.Weareappalled that these doctors have been the subject of thisprotracted enquiry in the absence of any complaint from anyparent about any of the children who were reported in theLancetpaper.

81 GMCvsWakefield,Walker-SmithandMurch.Tr.73.Q: As far as you were concerned and your colleagues, Dr Murch, DrThomson and the junior doctors involved in your department, whatwasyourrolegoingtobe?A: Our role was a purely clinical role, inasmuch as we would see thechildrenanditwouldbemeinthisparticularcase,Iwouldseeallofthechildrenwherepossiblemyselfintheout-patientclinic.Iwouldthenmake

a decision as to whether I thought the children had any kind of bowelinflammation,whetherCrohn’sdiseaseorotherbowel inflammation. If Ithoughtclinicallythatthechildrequiredinvestigationonclinicalgrounds,I would then recommend ileocolonoscopy. Then I would also movetowards considering other investigations which may be undertaken. Wehadformedtheimpressionthatneurologicaldisease,whichpresentedinamannersimilartoautism,hadtobeexcludedinthesechildren.Therehadbeenquite a lot of discussionabout this, particularly involvingDrMikeThomson, who in our discussions had discussed this with us. Theseinvestigations were obviously clinically drawn, but we had not actuallyfinalisedpreciselywhatwasgoingtobethewayforwardatthattime.

82 Emphasisadded.

83 Jabs is the acronym for Justice and Awareness Basic Support.www.jabs.org.uk.

84 Langdon-DownG.(1996,November27).“Law:AshotintheDark.”TheIndependent.Page25.

85 ChildJS,RoyalFreeHospitalrecords,p.76.

86 Emphasisadded.

87 ProposedProtocolandCostingProposalsfortestingaselectednumberofMRandMMRvaccinatedchildren.‘LABprotocol”.

88 GMCvsWakefield,Walker-SmithandMurch.Tr.73.

Coonan:Isthatacorrectwayofapproachingmatters?Thatusing thatprotocol itwillbepossible toestablish thecausallink between the administration of the vaccine and theconditions outlined in this proposed protocol and costingproposals?

Wakefield:Yes.Thisishisdocumentandthesearehiswords,and theyare crafted ina legalway. Inotherwords, theyarenot necessarily what a scientist might say. For example, itwould be possible to establish “the causal link”. Now, it ismoreaccuratetosaythat itwouldbepossible toestablishanassociation,forexample,orapossiblecausalassociation,thatwouldbe scientificallymoreaccurate, but thedifferencewiththis document is that one was dealing with a balance ofprobabilityargument,whichisalegalargumentandsomethingwithwhich I had no familiarity at all. I was used to dealingwith scientific levels of proof and not balance of evidencearguments,so,asIsay,thesearehiswords,hisinterpretation,and it is framed in a way that would be understandable to,presumably,colleaguesattheLegalAidBoard.

89 WakefieldAJ,AnthonyA,MurchSH,ThomsonM,MontgomerySM,DavisS,etal.Enterocolitisinchildrenwithdevelopmentaldisorders.Am.J.Gastroenterol.2000;95:2285-2295.

Histologically, reactive follicularhyperplasiawaspresent in46of52(88.5%)ilealbiopsiesfromaffectedchildrenandinfourof14(29%)withUC,butnot innon-IBDcontrols(p<0.01).

90 Emphasisadded.

91 DisclosedbyWalker-SmithtoAJW;personalcommunication.

92 GMC vsWakefield,Walker-Smith, andMurch.Attendance note ofmeetingbetweenMacDonaldandGMClawyers.March23,2005.

CHAPTERTHIRTEEN

PoisoningYoungMindsLikeitornot,thereisanunrelentingdebateaboutwhethervaccineshavepoisoned the minds of some children. That vaccines may do so isacknowledged1 (by, among others, autism expert Professor Sir MichaelRutter2)andisnotactuallythedebateathand;therealquestionsarewhichchildren and how many? The base of the tsunami that is the autismepidemic—onesustainedhithertobycompetingargumentsfortherisingnumberofdiagnosesandthoseinvestedinnon-environmentalcauses-isno longer able to support its top.3 In accordance with simple wavemechanics, the tsunami’s slope is too great and breaking is inevitable.Breaking, for the purpose of this metaphor, extends to the shoreline’shorizon, from the child to the family, to schools, to the state budget, topublicconfidenceinhealthcareinfrastructure,andbeyond.

But another form of poison has been insinuated into the collectiveconscious of young, ableminds that threatens like an aftershock on theseabed.Although the tendrils of this poison are deeply embedded in thehistoryofhumanconflict,itsmainrootsaretobefoundinthepropagandaofemergentNaziGermanycirca1935.Asanexample,amathquestiontoGerman children in schools where Jewish children were limited to 1.5percentby1935andbannedfromeducationaltogetherby1939,readsasfollows:

The Jews are aliens in Germany — in 1933 there were66,060,000inhabitantsintheGermanReich,ofwhom499,682wereJews.Whatisthepercentofaliens?4

Itwasdeemedimportant,indeednecessary,tosowtheseedofanti-Semiticpropaganda early into young, fertileAryanminds.Clearly, thiswas justthebeginning.

Recently I was providedwith the text of another exam paper, this timefrom the UK’s January 2008 national General Certificate of SchoolEducation(GCSE)biologyexam(highertier),whichstudentsweregivenaspartoftheirpreparationforthe2009exams.Itreadasfollows:

TheMMRvaccineisusedtoprotectchildrenagainstmeasles,mumpsand,rubella.a. Explain, as fully as you can, how the MMR vaccineprotectschildrenfromthesediseases.

b. Readthepassage.

Autism is a brain disorder that can result in behaviouralproblems.In1998,DrAndrewWakefieldpublishedareportina medical journal. Dr Wakefield and his colleagues hadcarriedouttestson12autisticchildren.DrWakefieldandhiscolleagues claimed tohave foundapossible linkbetween theMMRvaccineandautism.DrWakefieldwrotethattheparentsof eight of the twelve children blamed theMMR vaccine forautism. He said that symptoms of autism had started withindaysofvaccination.Somenewspapersusedpartsofthereportin scare stories about the MMR vaccine. As a result, manyparents refused to have their children vaccinated. DrWakefield’s researchwas being funded through solicitors forthe twelve children. The lawyers wanted evidence to useagainstvaccinemanufacturers.Use information from the passage on the opposite page to

answerthesequestions.(i) Was Dr Wakefield’s report based on reliable scientificevidence?

Explainthereasonsforyouranswer.

(ii)MightDrWakefield’sreporthavebeenbiased?

Givethereasonforyouranswer.

Let us pause there in order to reflect upon the question. While severalquanta removed from the implications of the Reich’s insidiousmathematicstest, thecoercivesubtextis thesame.Itwasset,apparently,byteacherstrainedinscience.Itwassetforchildrenwhosefuturesdependupon providing answers that will allow them to pass the exam, i.e., byexpressingviewsconsistentwiththoseoftheState.Itisintendedtoembedopinion.

First,Iwilldeconstructthepassagethatthestudentsaregiventoread.

Autism is a brain disorder that can result in behaviouralproblems.

Actually, rather than being a brain disorder, autism is a disorder thataffectsthebrain.5Agrowingbodyofpublishedevidenceindicatesthatformanychildren,autismisasystemicdisorderaffectingtheimmunesystem,theintestine,andvariousmetabolicprocessessuchasthoseresponsiblefordetoxification. Similarly, Pediatric Autoimmune Neuropsychiatric

Disorders Associated with Streptococcal Infections (PANDAS) is asystemic disorder associatedwith adverse neurologic (e.g., tic disorders)and behavioral consequences (e.g., obsessive compulsive disorder)followingstreptococcal infectionsof, forexample, the tonsils rather thanthebrainsofsusceptiblechildren.

In1998,DrAndrewWakefieldpublishedareportinamedicaljournal.DrWakefieldandhiscolleagueshadcarriedouttestson12autisticchildren.

I, and 12 other well-respected physicians and scientists, published thereport that described the results of clinical tests carried out on 12 sickchildrenwhowereadmittedtotheRoyalFreeHospitalunderthecareofasenior pediatric gastroenterologist for investigation of their clinicalsymptoms. An apparently novel inflammatory bowel disease wasdiscoveredandhassincebeenconfirmedinfivedifferentcountries.6Thepaperwasacaseseries(ratherthanananalyticstudy,e.g.,acase-controlstudy); this was clearly stated in the paper. It is a typical and well-establishedmodeofpresentingmedicalcaseswithsimilarfeatures.Itisahypothesis-generatingstudythatisaprecursortoanalyticstudiesinwhichinclusionofcontrolsisappropriate.

Dr Wakefield and his colleagues claimed to have found apossiblelinkbetweentheMMRvaccineandautism.

We specifically stated in the paper that the findings did not prove anassociation—letaloneacausalassociation—betweenMMRvaccineandthesyndromethatwasdescribed.

Dr Wakefield wrote that the parents of eight of the twelvechildrenblamedtheMMRvaccineforautism.

Appropriately and accurately, we reported the parental histories ofdevelopmental regression following MMR vaccination in eight of thetwelve children. No one would have suggested censoring, for example,parental reportsofnaturalchickenpox if this iswhathadpreceded theirchild’sregression.

He said that symptoms of autism had started within days ofvaccination.

Wedidnotsaythis;weprovidedanaccountoftheparentalreportsofthe“onsetoffirstbehavioralsymptoms,”whichhadoftenstartedwithindaysofreceivingtheMMRvaccine.

Some newspapers used parts of the report in scare storiesabout theMMRvaccine.Asaresult,manyparentsrefused tohavetheirchildrenvaccinated.

This is misleading and without any evidential basis. Asked whatvaccinationstrategyIwouldrecommend,Isuggestedin1998(andnow)areturn to single-spaced vaccines. This recommendation was based uponextensive research by me into the safety studies of measles-containingvaccines,compiledintoareportthatwasseveralhundredpageslong.TheconclusionsofthisreportwithrespecttotheinadequacyofMMRvaccinesafety studies have since been endorsed by the gold-standard scientificreviewbytheCochraneCollaboration.7However,whileafallinuptakeofMMRwas reported following our publication, figures for the reciprocaluptake in single vaccineswere not. I have contacted privateUK clinicsprovidingsinglevaccines,andIaminformedthattheyhaveadministeredtens, if not hundreds, of thousands of doses, none of which aredocumentedintheofficialstatistics.Bizarrely,whenthedemandforsinglevaccineswas at its highest, theUK government revoked the license forimportationofsinglevaccinesinAugust1998,6monthsafterIhadmade

my recommendation. Parents with genuine safety concerns aboutMMRweredeniedachoiceofhowtoprotecttheirchildren:theUKgovernmenthad decided to put protection of policy before protection of children.Beyond this point, vaccine uptakemaygenuinely have fallen, forwhichthe government with its “our-way-or-no-way” policy must takeresponsibility.

DrWakefield’s researchwas being funded through solicitorsfor the twelve children. The lawyers wanted evidence to useagainstvaccinemanufacturers.

Thisisfalse.TheallegationthatTheLancetpaperwasfundedbytheLABthrough lawyers looking to sue vaccine manufacturers was made by afreelancejournalistwhosimplygotitwrongandwhoseclaimshavenowbeendiscreditedbytheevidence(seeChapter12,“Deer”).NotonesinglecentofLABfundingwasspentonTheLancetreport.Infact,thefundingfortheLABstudy(aseparateviraldetectionstudy)wasnotevenavailabletobespentuntil9monthsafterthechildreninTheLancetstudyhadbeeninvestigated,theirresultsanalyzed,andthepaperwrittenandsubmittedtoTheLancetforpossiblepublication.Thesearemattersoffact.

In other words, the students’ required reading is substantially false ormisleading.And yet in order to gainmarks, the students,whatever theirunderstandingofthetruestateofaffairs,arerequiredtoendorsetheerrorsof their examiners or fail on the question. The examiners provide abreakdownoftheirmarkingscheme:

Answer (i) Was Dr Wakefield’s report based on reliablescientificevidence?

A.No (any two from sample size small [only 12], conclusionbasedonhearsayfromparents,only8parentslinkedautismtoMMR,nocontrolused(2marks))

First,thequestionisconfusing;areportprovidesfacts,anditsconclusions(ifany)arebaseduponevidence.Theoptionsgivenforacorrectanswercompletelyfailtounderstandthenatureandpurposeofacaseseries(suchas Kanner’s original description of autism in 11 children), which isessentially an uncontrolled report of the children’s history backed up,where available in our case, by contemporaneous developmental recordsandGP reports, andclinical findings includingadetailedanalysisof thechildren’sdiseasedintestinaltissues.

Answer(b)(ii)(yes)beingpaidbyparents/lawyers(1mark)

As stated above,TheLancet 1998 paperwas not funded in anyway bylawyers.AndrewardingtheanswerthatIwasbeingpaidby“parents” isextraordinary;itnotonlybearsnoresemblancetothetruth,butthereisnomentionofparentspayingintheparagraphuponwhichtheexaminersbasetheirquestion(see“Postscript”laterinthischapter).

Finally, to part (a) of the exam question: “can we explain how MMRvaccine protects children from these diseases.” A simple answer − onepleasing to the examiners −would be:by the induction of specific, life-long antibody and cellular immunity that produces high herd immunityand interrupts chains of virus transmission.While this may get a goodmark, itwould be false. In truth, there ismuch that is not known aboutvaccine-induced immunity.The legacyofmumpsvaccination– a policyforced on reluctant public health systems in theUS andUK, essentiallythrough commercial pressures — has simply made mumps a moredangerousdisease.Mumpsisatrivialdiseaseinchildrenbutsubstantially

more dangerous in adolescents and adults. The vaccine does not protectenoughchildren,andwhatprotection itdoesconferdoesnot last−evenwith boosters. The effect has been to leave pubertal and post-pubertalindividuals susceptible tomumpsand its complications.Measlesvaccinecomes considerably closer to the examiner’s preferred answer, althoughwaningimmunityisalsoaproblemthatmaynotbeovercomebyboosterdoses,apracticethathasyettobestudiedadequatelyforsafety.Thelong-termconsequenceofwaningimmunityat thepopulationlevelisanissueofgenuineconcern.

Iwouldscorepreciselyzeroformyresponse.Butwhatofthosewhofacethe question in the future or who have already taken the test? Theexaminingboardwas sent a seriesof searchingquestionsbya journalistabout this issue. Immediately, the exampaperwas takendown from thewebsite.Whathappensnow?Willthestudentswhohavealreadyansweredthe question pass if their answers conform to the dictate of the publichealthapparatchiks,orwilltheyfailbecausetheiranswersarewrong?Andthesciencegraduateswhosetthequestion—onwhatdidtheybasetheirposition? From their response to the journalist’s questions, the answerwouldappeartobetheintegrityofTheSundayTimes—somuchforduescientific process. Where does that leave the prospects for tomorrow’smedicalscience?

Consider the recent revelation during the course of Vioxx class actionhearings:thepublishinghouseElsevier(ownerofTheLancetandover500other medical and scientific titles) created six fake journals that weredressedup to look like scientific journals, fundedbyMerckwithout anydisclosure,andstronglyfavorabletoMerckintheircontent.8AndMerckitself circulated an internal memo that suggested corporate policy onVioxxincludedseekingoutdissentingdoctorsanddestroyingthemwhere

they live.9 Parents of theworld’s remaining neurotypical childrenmightwishtoconsiderthiswhendiscussingcareerchoices.

“Corporate government” is heavily invested in propaganda,many of thetechniques of which are a legacy of the Third Reich. It is difficult tobelieve that it was not influential in setting the UK school’s biologycurriculum.Fortheirefforts,JuliusStreicher,10 theReich’sapothecaryofyoungAryanmindpoisoning,wouldhavegiventheGCSEexaminersandwhoeverwaspullingtheirstringsnomorethanasixoutoftenanda“seemeafterclass.”StreicherwastriedandsentencedtodeathatNuremberg.Whoknowswherehemightotherwisehaveendedup?

PostscriptSometime after this chapter originally appeared as an article in Age ofAutism, an angrymother sent me the page of her son’s AQA11 sciencetextbook. AQA may have been instructed that their exam-questionpropaganda was not damning enough, for this time they had throwncautiontothewindandhadwritteninreferencetoTheLancetpaper:

ControllingInfectiousDisease

TheMMRDilemma12

…Itturnedoutthattheresearchhasbeendoneonatinygroupoftwelvechildren.Thescientisthadbeenpaid£55,000bytheparentsofsomeofthechildrentoprepareevidenceagainstthevaccine for a court case. What’s more, Dr Wakefield had

developedsomemeaslestreatmentswhichwouldnothavebeenusedifparentswereconfidentinMMR.Nooneknewthiswhenhepublishedhisresults.

AQA has excelled itself: this is such utter garbage that one wonderswhether Julius Streicher actually survived the hangman’s noose inNuremberg with little more than whiplash, only to return as a grayingbiologyteacherneedingtomakealittlemoneyontheside.Andbywayofself-assessmentindystopianscience,youcanalwaysgotoDeer’swebsitewhereyouwillfindthefollowing:

Astaughtinschools:In2008,Deerscoredaprofessionalfirstwhenfindingsfromhisinvestigationbecamethesubjectforanexam question for British teenagers,13 set by the UKAssessmentandQualificationsAlliance.Seequestion5at thislink,and,ifyoufeelyouneedto,goheretoseehowyouwouldhavescoredonthisGCSEtopic.

Endnotes1 WeibelRE,etal.Acuteencephalopathyfollowedbypermanentbraininjury or death associated with further attenuated measles vaccines: areviewofclaimssubmittedtotheNationalVaccineInjuryCompensationProgramme.Pediatrics.1998;101:383-387.AgeofAutism.(2009,February27)WhyistheMediaIgnoringtheBaileyBanks Autism Vaccine Decision? Posted athttp://www.ageofautism.com/2009/02/why-is-the-mediaignoring-the-bailey-banks-autism-vaccine-decisionhtml.

2 Rutter M, Bailey A, Bolton P, et al. Autism and known medicalconditions: myth and substance. Journal of Child Psychology andPsychiatry,1994;35(2):311-22.

3 Hertz-Picciotto, IandDelwiche,L.Therise inautismand theroleofage at diagnosis. Epidemiology, 2009; 20:84-90; andhttp://www.dds.ca.gov/Autism/docs/AutismReport_2007.pdf

4 Corelli M. (2002, May-June). Poisoning young minds in NaziGermany: children and propaganda in the Third Reich. Retrieved fromhttp://findarticles.com/p/articles/mi_hb6541/is_4_66/ai_n28923014/.Herbert Hirsch, Genocide and the Politics of Memory. Chapel Hill:UniversityofNorthCarolinaPress,1995,p.119.

5 Herbert M. Autism: A brain disorder, or a disorder that affects thebrain?ClinicalNeuropsychiatry.2005;2:354-379.

6 WakefieldAJ,AnthonyA,Murch SH. Enterocolitis in childrenwithdevelopmental disorders. American Journal of Gastroenterology 2000;95;2285-2295.Gonzalez L, et al. Endoscopic and Histological Characteristics of theDigestiveMucosa inAutisticChildrenwithGastro-IntestinalSymptoms.ArchVenezPuericPediatr,2005;69:19-25.

BalzolaF, et al.Panenteric IBD-likedisease in apatientwith regressiveautismshownforthefirst timebywirelesscapsuleenteroscopy:Anotherpiece in the jig-saw of the gut-brain syndrome? American Journal ofGastroenterology,2005.100(4):979-981.Krigsman A, Boris M, Goldblatt A, Stott C. Clinical Presentation andHistologicFindingsatIleocolonoscopyinChildrenwithAutisticSpectrumDisorderandChronicGastrointestinalSymptoms.AutismInsights2009:11-11.BalzolaF,etal.Autisticenterocolitis:confirmationofanewinflammatorybowel disease in an Italian cohort of patients. Gastroenterology.2005;128(Suppl.2);A-303.GaliatsatosP,etal.Autisticenterocolitis:factorfiction.CanadianJournalofGastroenterology.2009;23:95-98.

7 Demicheli V, Jefferson T, Rivetti A, et al. Vaccines for measles,mumps and rubella in children.Cochrane Database Systematic Review,2005(4):CD004407. “The Cochrane Collaboration is an international,independent,not-for-profitorganisationofover27,000contributors frommore than 100 countries, dedicated to making up-to-date, accurateinformationabouttheeffectsofhealthcarereadilyavailableworldwide.”www.cochrane.org/

8 The allegations, reported in theScientist.com (http://www.the-scientist.com/blog/display/55679/) involve the Australasian Journal ofBone and Joint Medicine, a publication paid for by pharmaceuticalcompanyMerck that amounted to a compendium of reprinted scientificarticlesandone-sourcereviews,mostofwhichpresenteddatafavorabletoMerck’sproducts.TheScientistobtainedtwo2003issuesofthejournal−whichboretheimprintofElsevier’sExcerptaMedica−neitherofwhichcarriedastatementobviatingMerck’ssponsorshipofthepublication.

9 RoutM.(2009,April1).VioxxmakerMerckandCodrewupdoctorhit list. Retrieved fromhttp://aftermathnews.wordpress.com/2009/04/27/vioxx-maker-merck-and-

co-drew-updoctor-hit-list/

10 Streicher ran the Sturmerverlag (Storm Trooper Publishing House).Streicher alsopublishedan introduction to the teacher’smanualbyFritzFink,Die Judenfrage imUnterricht [The JewishQuestion in ClassroomInstruction] (Nuremberg: Sturmerverlag, 1937). Excerpts from thisteacher’s manual can be found at:www.calvin.edu/academic/cas/gpa/fink.htm

11 TheAssessmentandQualificationsAllianceisthelargestofthethreeEnglishexamboards.

12 AQAScience(GCSE)2006.NelsonThornes(Publishers),p.74.

13 Emphasisadded.

AFTERWORD

Ethics,EvidenceandtheDeathofMedicineCo-writtenwithJamesMoody,Esq.*FirstappearedinTheAutismFile

magazineinApril2010.

DocumentsProveInvestigationsofTheLancetChildrenWereEthical

Acting on at least two false premises, the General MedicalCouncil found *Dr. Wakefield and his colleagues guilty ofperformingresearchonchildrenwithoutethicscommittee(EC)approval.

Falsepremise1.

TheGMCconfuseddiagnosticclinicaltestswithresearch.

Falsepremise2.The GMC claimed there was no current EC approval thatcoveredtheresearchaspectsofTheLancetpaper.Therewas—theprosecutionhadfailedintheirdutytoidentifyit.

The core finding by theGeneralMedicalCouncil againstDr.Wakefield

andProfessorsWalker-SmithandMurch(TheLancetdoctors)isthattheyperformedunethicalresearchonautisticchildren—childreninwhomtheydiscoveredanewboweldisease.Nottominimizetheimportanceofethicsinmedicine,thefindingisofa“technical”violationbecausetherewasnofinding that any child was harmed, only that for some children thediagnostic tests were not yet approved by the Royal Free’s ethicscommittee.However,asshownindetailbelow,thedocumentaryevidencedemonstratesbeyondallreasonabledoubtthatthediagnostictestsonTheLancet children were performed according to clinical need, that theresearch portion of the case series was approved by the EC, and thatresponsibleofficialsattheRoyalFreewerewellawareofthescopeoftherelevantapprovalsat the timeandmadenoobjection.At the same time,the GMC improperly reclassified routine clinical care as research andignored pre-existing EC approval for research on bowel biopsies. ThelegacyofthistrialthreatensfarmorethanTheLancetdoctors,notonlybydenying autistic children the diagnostic tests and treatments they sodesperately need but also by terrorizing doctors into depriving theirpatients of the innovative diagnostic and therapeutic interventions theydeserveinfavoroftherelativesafetyofmediocrityinmedicine.

SettingtheStageProfessor SirMichaelRutter, the “dean” ofUK autism experts,was thefirsttodescribeacaseofvaccine-causedautisminthescientificliteraturein1994.TheUKDepartmentofHealthwaslargelyresponsibleforfuelingpublic doubt about MMR safety by introducing in 1988, and abruptlywithdrawing in 1992, two MMR vaccines containing the Urabe AM-9strain ofmumps known to causemeningitis that had beenwithdrawn inCanada before its introduction in the UK. As a matter of fact, the USvaccine court began compensating for cases of vaccine-caused autismstartingin1991,9andtheUSDepartmentofHealthandHumanServiceshasbeensecretlysettlingcasesofvaccine-causedautismwithoutahearing

alsosince1991.10Clearly,vaccinescancauseautism.Whatremainstoberesolved is the body count, appropriate treatments, and reform of thevaccine schedule to prevent autism and other vaccine-caused chronicdisorders.Nobodyknowshowmuchautism,orotherchronicdisorders,iscausedbyvaccinesbecausenocomprehensivescientificstudieshaveeverbeen done comparing the health of unvaccinated children to those fullyvaccinated.Someareoftheopinionthatbecausetheyfearaccountabilityand liability, public health authorities are now actively opposing suchresearch.However,thisresearchisabsolutelynecessarytopreventdiseaseandmaintainpublicconfidenceinvaccines.

Why then does Dr. Wakefield get all the attention, blame, or credit(depending on your perspective) for simply posing the hypothesis of apossible association between MMR and autism and calling for furtherresearch? Unlike others who ran for cover, he continues to undertake aprogram of careful scientific research designed to determine howmanychildrenhavebeenaffected.Heislookingfortheprecisemechanismsandmarkers for this type of vaccine injury because his goals are preventingavoidable vaccine injury, treating those already injured, and of restoredpublic trust.ThemostvisibleofDr.Wakefield’searlyworkwasapaperpublishedintheFebruary1998issueofTheLancetreportingacaseseriesof 12 children who developed autism and bowel disease, the majorityfollowingMMRvaccination.Thepapercautiouslywarnedthatnocausalassociationwas shown and called for further research. This commencedthe politicalwar to suppress vaccine safety science and to cover up thedenialofappropriatetreatmenttoautisticchildrenwhomightbevictimsofvaccine injury. TheGMC investigation ofTheLancet doctors, begun in2004 and extending into the year 2010, is just the most recent field ofbattle in this titanic struggle.The initialGMCfindings, releasedJanuary28, 2010, were predictably followed by Lancet editor Horton’s formalwithdrawal of the case series, citing ethical concerns. Horton haddescribedthepaperinhisGMCtestimonyas“importantnewinformation

that would be of interest to a general medical readership.” But now,becausehe’sattheeyeofthispoliticalstormovervaccinesafety,hehascommitted “editorial genocide,” attempting to erase the contribution ofthese12children.

Researchvs.ClinicalPracticeApprovalbyanyhospital’sethicscommitteeis,ofcourse,aprerequisitetoconducting research on patients, but no such oversight or approval isrequired for ordinary clinical practice. EC approval was an obvious,routine,andclearlyunderstoodprocedure,especiallyatteachinghospitalsliketheRoyalFree,longbeforethemid-1990s.Sincetheconsequencesofdoingunapproved researchonpatients canobviouslybe serious, doctorsmust have an easyway to determinewhere diagnostic and clinical careendsandresearchbegins.Diagnostictestingandclinicalcareareprimarilyfor the benefit of the particular patient; research, on the other hand, is asystematic investigation, an “experimental study,”designed to contributeto generalizable knowledge. GMC ethics guidance specifically exempts“innovative therapeutic interventions designed to benefit individualpatients”from“research”requiringECapproval.

The authoritativeBelmontReport recognized that theprecise boundariesbetween clinical practice and research (requiring ethics oversight for theprotection of human subjects) are “blurred” because—in practice theyoftenoccurtogether.Theterm“practice”refers to“interventionsthataredesignedsolelytoenhancethewell-beingofanindividualpatientorclientandthathaveareasonableexpectationofsuccess.Thepurposeofmedicalor behavioral practice is to provide diagnosis, preventive treatment, ortherapy to particular individuals.” The fact that some forms of practicehave elements other than immediate benefit to the individual, however,shouldnotconfuse thegeneraldistinctionbetweenresearchandpractice.

Evenwhenaprocedureappliedinpracticemaybenefitsomeotherperson,it remains an intervention designed to enhance the well-being of aparticular individual or groups of individuals; thus, it is clinical practiceandneednotbereviewedasresearch.Theguidingprincipleinthepracticeof medicine is the primacy of patient care. In the service of thisoverarching goal, the defining characteristic of clinical diagnosis is thedefinition of the disease entity, even when no immediate treatment ispossible. TheBelmontReport continues: “When a clinician departs in asignificant way from standard or accepted practice, the innovation doesnot, in and of itself, constitute research. The fact that a procedure is‘experimental,’ in the sense of new, untested or different, does notautomatically place it in the category of research. Radically newprocedures of this description should, however, be made the object offormal research at an early stage in order to determinewhether they aresafe and effective.” In otherwords, introducing innovative interventionsfortheclinicalpurposeofbenefitingthespecificchildrenbeingevaluatedis not research, even if data about the intervention is collected frommedical records for research purposes in a retrospective or prospectivemanner.

DiagnosticTestsAppropriatetoClinicalNeedThe children reported inThe Lancet were all sick. All had a history ofnormal or near normal development followed by loss of acquired skills(regression).Allhadgutissues,whichwaswhytheywerereferredtotheworld leader in the field of pediatric gastroenterology, Professor JohnWalker-Smith. At that time, each child’s local National Health ServiceTrust had to pay for care, so the “extra-contractual referral” had to belocallyapprovedandjustifiedbytheclinicalneedsofeachchildtobeseenat a tertiary care facility such as theRoyal Free.Diagnostic testingwasjustified by each child’s medical history and clinical presentation. Suchdiagnostic investigations, indicated by clinical need, did not require ECapproval because they were undertaken in the patient’s interest for the

purpose of establishing a diagnosis and directing treatment. Thesediagnostic investigations includedcolonoscopies to lookat thechildren’sbowel for treatable inflammation, while some had lumbar punctures tolook at the cerebrospinal fluid, principally for evidenceofmitochondrialdysfunction.1 Both are routine tests for children with unexplainedsymptoms of intestinal and/or neurological dysfunction. The clinicalimperativeforinvestigationssuchascolonoscopyandlumbarpunctureintheautisticchildrenwasstatedexplicitlybyallthreedoctorsinevidenceatthe GMC hearing, and it was contained in a succession ofcontemporaneousdocuments from1996onwards,examplesofwhichareprovidedbelow.

ECApprovalforBiopsyResearchOnSeptember5, 1995,ProfessorWalker-SmithwasgrantedgenericECapproval for biopsy research on children undergoing diagnosticcolonoscopy for bowel symptoms (designatedby theECas project 162-95).2Theconsentformfortwoextrabiopsiessignedbyparentsexplainedthat “chronic inflammatory bowel diseases are still little understood andtheir cause is unknown. It is therefore of great value for laboratoryresearchtohavesuchbiopsiesavailabletostudyhowinflammationintheboweldevelopsandisinfluencedbytreatment…Whetherornotyouagreetothiswillinnowayinfluenceyourassessmentortreatment.”

Children with a pervasive developmental disorder and severe boweldiseasestartedcomingtotheRoyalFreeHospitalforclinicalinvestigationbeginning in mid-1996. The first 12 of these consecutively referredchildren were reported as The Lancet case series. The only aspect of“research” involving these children was the collection of the twoadditional biopsies and the later biopsy analysis in the laboratory,approved as EC 162-95. All the children had the EC-approved research

consentformincludedintheirfiles,aswellasconsentsforotherclinicalprocedures.

Based upon common features reported in this initial group of children(termeda“pilotstudy”),theRoyalFreeteamdevelopedadetailedclinicaland research protocol that included research aspects in addition to thepreviouslyapprovedbiopsiessuchasgenetictestingandmarkersofbraininflammation.Themajority of these additional research testswere to beundertakenonsamplesleftoverfromthediagnostictests.Theapplicationto the EC was submitted on September 16, 1996, designated as project172-96,andapprovedonDecember18,1996.ECapproval required thatchildrenenrolledinthisresearchstudybegivenaninformationsheetandthatasignedaconsentformbeplacedineachchild’sfile.

NoneofTheLancetChildrenWerePart of theEC172-96ResearchProjectTheEC172-96 handout to parents beganwith the title of the study, “ANew Paediatric Syndrome: Enteritis and Disintegrative DisorderFollowing Measles/Rubella Vaccination,” and explained that the RoyalFree team “have formulated the hypothesis that in certain (perhapsgenetically susceptible) children, live-virus vaccines may produce long-term inflammation of the intestine and failure to absorb, in particular,vitamin B12…We would like to carry out a series of tests which, webelieve,willhelpustoestablishthefeaturesofthispossibledisease.Ouraimistocharacterizetheproblemsothat,forthefuture,wemaybeabletotreat affected children and improve their wellbeing.” The consent formstated:“Ihavereadandunderstoodtheaimsandnatureofthisstudy,andhave discussed in detail, the implications of the study with the Doctorsconcerned.Iherebyagreetoletmychild________takepartinthestudy.Iunderstand that I can withdraw my child from the study at any stage

withoutprejudicinghis/hermanagementor treatment in anyway.”NoneofTheLancetchildrenhadthesepapersintheirfile.

ThefactthatthefilesofTheLancetchildrenallcontainedthe162-96ECconsent for research biopsies and neither the EC-approved informationsheetforthe172-96researchstudynortheassociatedconsentformmakesconfusion impossible. The GMC allegation and finding thatThe Lancetchildrenwereenrolled inECproject172-95 isobjectively impossibleasshownbytheconsentformsineachchild’srecord.

The EC Knew The Lancet Children Were Being Seen for ClinicalNeed,NotResearchCrucially, the application submitted to theEC for 172-96 explained thatthediagnostictestswereforclinicalpurposes.TheECapplicationasked:“Would the procedure(s) or sample(s) be taken especially for thisinvestigationoraspartofnormalpatientcare?”Ouranswerwas:

Yes: in view of the symptoms and signs manifested by thesepatients,alloftheproceduresandthemajorityofthesamplesareclinically indicated8 [i.e.,normalpatientcare].Additionalintestinal biopsies (5 per patient) will be taken for viralanalysis.DNAforgenotypingwillusebloodcellsisolatedfromthe routine blood sample and will not require an additionalsample.

The EC obviously contemplated a situation such as this where the testsincludedintheinvestigativeprotocolincludedboththoseforclinicalandresearchpurposes.IftheECbelievedthatthediagnostictestingdescribedin theapplicationwasnotappropriate for thechildrenwith the indicatedsymptoms, then surely a question would have been raised. So, the

followingquestion arises:Why isn’t theGMCprosecutingEC chairDr.Pegg and the other members of the EC for approving such supposedlyriskyandrecklessprocedures?

Children with bowel disease and PDD kept being referred to the RoyalFreewhiletheformalprotocolwaspendingbeforetheEC.Theycontinuedto receive diagnostic tests and clinical care appropriate to childrenexhibitingsymptomsofboweldiseaseandlossofacquireddevelopmentalskills.However,straightforwardclinicalandethicsissueshadbythistimealready become hotly “political” because the topic of the proposedresearchincludedpossiblevaccinedamageandwerethusreceivingcarefulscrutiny.Inresponsetoaninquiryaboutthetestingdoneonthesechildren,ProfessorWalker-Smith explained in aNovember11,1996, letter toECchairmanPeggthat

These children suffer from a disease with a “hopelessprognosis”inrelationtotheircerebraldisintegrativedisorder.They have often not had the level of investigation which wewould regard as adequate for a child presentingwith such adevastating condition. In relation to their gastrointestinalsymptoms which will be present in all the children weinvestigate,thesehaveoftenbeenunder-investigated.3

Heexplained thateachchildalreadybeing treatedwascertain to receive“reasonable benefit,” the key requirement distinguishing clinical practicefromresearch,by

a. Establishing a diagnosis and excluding metabolic andothercauses

b. Commencingonatherapeuticregime.

The clinical benefit to each ofThe Lancet children clearly distinguishesthatcaseseriesfromresearch.ProfessorWalker-Smithconfirmed,beyonddoubt,thatchildrenhadalreadybeeninvestigatedwellbeforeECapprovalforproject172-96wasgiven:

Wehavesofarinvestigated5suchchildrenonaclinicalneedbasis,8 all in fact have proved to have evidence of chronicbowelinflammation.…Icanconfirmthatchildrenwouldhavetheseinvestigationsevenif therewerenotrial.Imustmakeitclear that we would not be investigating children withoutgastrointestinalsymptoms.

It would have been unethical, if not appalling, to have refused careand turned these children away while the EC was reviewing theprospectiveresearchprotocol.

Dr.WakefieldagainnotifiedtheEConFebruary3,1997, thatadditionalchildrenhadbeen seen in theclinicprior to starting the176-96 researchproject.HewrotetoamendtheproposedprotocolbydeletingtheMRIandEEG in light of the fact that neurological studies had not revealed anyhelpful clinical information, and adding an intestinal permeability test.4Deletion of the MRI and EEG was purely a clinical decision taken byWalker-Smith in the children’s best interests, i.e., not research, butwasmentioned since Pegg wished to be informed of “any” changes. In thisletterWakefieldconfirmedthat,inadditiontothe5childrenreferredtobyWalker-Smith in his November 11 letter, a further 4 children had beeninvestigated, and now a total of 8 children had evidence of intestinalinflammation.ThustheECknewinFebruary1997that9children—9ofthe12whowentontobereportedinTheLancet—hadalreadybeenseenand evaluated in the clinic, but those children had nothing to do withproject172-96.ItshouldhavebeenevidenttoDr.Peggthatthisprotocol

wasstillbeingrevisedbasedonwhatwaslearnedfromthepilotstudy.

Ultimatelyand ironically,project172-96wasneverundertaken.Fundingfor the additional research elements contained in this proposal was notforthcoming,anditwasnotpursuedfurther.TheLancetdoctors,therefore,didnotviolatetheECapprovalfor172-96byenrollingchildrenwhodidnot meet the inclusion criteria and did not perform “research” on thesechildren before the project’s start date—because research project 172-96wasneverstarted.

On the other hand, the biopsy research covered by 162-95 proved to beextremely informative, and this is where Dr.Wakefield’s and ProfessorMurch’sresearchfocused.ProfessorWalker-SmithwroteagaintoPeggonJuly15,1998:

Furthertoouroriginalstudy[TheLancetcaseseries],wearenow continuing to see such children by clinical need andperformingileocolonoscopyandlimitedbloodtestsinordertodecide whether to give such children Mesalazine [anti-inflammatorymedication for inflammatoryboweldisease].AsDr.Wakefieldiscarefullyanalyzingourresultsandsomeofthebiopsiesbeing takenarebeingused for research (wealreadyhaveresearchpermissionfortakingextrabiopsiesinchildrenwhowecolonoscope).IwouldlikeformallytorequestEthicalCommitteeapprovalforourclinicalresearchanalysisofthesechildrenwhowearecontinuingtoseebyclinicalneed.5

He requested only continued permission to analyze the results of theclinical data for the purposes of publication and this was granted. Thewholematterwas reviewedby thedeanof themedical school,Professor

Zuckerman,onJuly15,1998,whoseannotatedapprovalread:

All the necessary steps with Ethical Committee and othermatters.

High-LevelOversightWithoutObjectiontotheClinicalCareFurtherevidenceofthelevelofintensescrutinygiventotheappropriatenessoftheclinicalcareofTheLancetchildrencomesfromaJuly6,1998,letterfromProfessor Sir David Hull ex-chairman of the Joint Committee onVaccinationandImmunization—clearlyawarethatvaccinesafetyresearchwas underway and concerned about potential government liability—toDeanZuckermanseekinghishelp“onamatterofpersonalconcern.”Hullwasconcerned that“manymorechildrenhadbeensimilarly investigatedand still more were on the waiting list.” Referencing the Hull letter,ProfessorWalker-Smithagain reassuredDeanZuckerman inhis July14,1998, letter that “[t]hese subsequent children are being seen by clinicalneedtodecideuponatreatmentandhelpthesechildren.”

AlsoinresponsetotheHullletter,ProfessorWalker-SmithwrotetoRoyalFreeCEOMartinElseexplaining:

Thechildrenwithautismwhohavegastrointestinalsymptoms,from the verybeginning, havebeen investigatedaccording toclinicalneed.ThishasbeenapprovedbytheEthicsCommittee.Also it is routine for us to have ethical approval to takeendoscopic biopsies for research purposes with parentalconsent for all childrenwho are endoscoped.We have nevermoved outside any frame that has not been approved by theEthics Committee or indeed that is outside the bounds ofethical behaviour in the widest sense. We have the clearestevidence both published and unpublished that these children

have a form of chronic inflammatory bowel disease… Thechildren that we are seeing with autism and gastrointestinalsymptoms deserve the kind of investigation that we areperforming.

Again referencing theHull letter, Peggwrote toZuckerman on July 24,1998,explaining:

We approved data collection from clinically indicatedinvestigations. It is not, at present, the role of an ethicscommitteetoquestionclinicians’judgmentastowhatareandwhat are not clinically indicated investigations.However,wedonotjusttakethewordoftheinvestigator,ratherweaskforindependentexpertreviewofallapplications.InthiscaseDr.Owen Epstein provided a review of the project and I have aletterfromhim“stronglysupporting”thestudy.

DeanZuckermanwrotebacktoSirDavidHullonJuly28,1998,assuringhimthatallof thechildrenwereseenaccording toclinicalneedand thatoversightbytheECwasappropriate.Withallthisscrutiny,atthehighestlevels, where was the objection by anybody that the diagnostic testsperformedonTheLancetchildrenweresomehowunethical?

TheGMCImproperlyReclassifiedClinicalCareasResearchThere were no ethical violations in relation to the investigation andreportingofTheLancet12.Nochildwassubjectedtoanyinvasivetestforthe purpose of research. TheGMC prosecution rested on the claim thatThe Lancet children were part of research project 172-96. It appears tohaveconcealedEC162-95researchapprovalforbiopsies,and,forthefirsttime,attemptedtosecond-guessthejudgmentofeminentcliniciansaboutwhat investigations were clinically indicated to diagnose and treat

desperatelyillchildren.

TheGMCdidnotfindProfessorWalker-Smith,theseniorclinician,guiltyofdishonesty.Thepanelmusthaveaccepted the integrityofhispositionontheclinicalmeritsofthesetestsbothin1996andnow.Thedocumentsconfirm not only this doctor’s position on the clinical need forinvestigation and the inadequacy of previous investigations on thesechildren,butmakeitclearthattheRoyalFreeEC,thedean,theCEO,andeven Sir David Hull knew all along that autistic children with boweldisease were being seen and investigated according to clinical need. In1996-98 senior medical staff knew what was being done and whatapprovalwasinplace.

GMC Complainant Brian Deer Knew the Biopsy Research WasApprovedbytheEthicsCommitteeDocuments recently released under the Freedom of Information Act(FOIA) reveal that thecomplainant, journalistBrianDeer,knew in2004that the research biopsies had EC approval as part of 162-95. This wasdisclosedtohiminJanuary2004throughhisFOIArequesttotheStrategicHealthAuthoritythathasresponsibilityfortheRoyalFreeHospital.6

Youmaythinkitstrangethatalthoughthisdocumentwasclearlyrelevanttotheconductofresearchonbiopsiestakenfromchildrenunderthecareof Professor Walker-Smith, the GMC appeared to know nothing of it.Presumably Deer disclosed this document to the GMC, otherwise hewould have risked exposure as a fraud for withholding key evidencefollowing any serious initial investigation by GMC staff. It was notincludedinthedocumentsuponwhichtheGMCreliedinformulatingtheiroriginal chargesagainst thedoctors thathadbeen suppliedbyDeerwith

hiscomplaint.NorwasiteverdisclosedinthedocumentssuppliedtothedefendantsbytheGMC,includingalloftheunusedmaterialthattheGMCisobligedtodisclose.Infact,theGMC’sfindingsexplicitlystated:

The research studywascarriedoutonChild“x”without theapproval of theEthicsCommittee in that itwas not researchcovered by anyEthicsCommittee application other than thatforProject172-96.

Deer either concealed this information from the prosecution, or theprosecution concealed it from the doctors. In the light of theEC’s priorapprovalofbiopsyresearchin162-95,Deer’s2004allegationofunethicalresearchwould have been rendered palpably false.Whether or notDeerdisclosed this key document, a competent investigation by the GMCshouldhaverevealedit.Sincetheapprovaldocumentsfor162-95wereinthe possession of the Royal Free’s ethics committee, they should havebeen obtained by the GMC’s lawyers and volunteered byDr. Pegg, thecommittee’schairman,duringtheprocessoftakinghiswitnessstatement.ThereisnoevidenceinanyoftheGMCmaterialthatthiseverhappened,whichmustraiseaseriousquestionoverprosecutorialcompetence,ifnotmisconduct. Moreover, EC chairman Pegg made no mention of thisapprovalinhisstatementorevidence,implicatinghimaswell.

Theprosecutionproceededon thebasisofapreconceivedassumptionofguiltratherthanconductingafairandthoroughinvestigation.Perhapsthiswhole GMC case has not been an honest effort to protect patients butpolitically motivated scapegoating after all? As Lancet editor Hortonboastedinhis2004bookMMR:ScienceandFiction,

The GMC seemed nonplussed by Reid’s (the then HealthSecretary) intervention urging the GMC to investigate

Wakefieldasamatterofurgency.Intruththeyhadnotacluewhere tobegin.Atadinner Iattendedon23February2004,onemedicalregulatorandIdiscussedtheWakefieldcase.HeseemedunsureofhowtheCouncilcouldplayausefulpart inresolving any confusion. As we talked over coffee while theother dinner guests were departing, he scribbled down somepossible lines of investigation and passed me his card,suggestingthatIcontacthimdirectlyifanythingelsecametomind. He seemed keen to pursue Wakefield, especially givenministerial interest.Herewasprofessionally led regulationofdoctors in action--notes exchanged over liqueurs in abeautifully wood-paneled room of one of medicine’s mostvenerableinstitutions.

Perhapsthisisjustonepartofanongoingcampaigntostopresearchintothe safety ofMMR and vaccines on the one hand, and on the other toconcealtheappallingrefusaloftheNHStoprovidepropercareforautisticchildrenwithsevereGIproblems,whichisitselfanegregiousviolationofbasicmedicalethics.

SoitwasthatTheLancetcaseserieshadtheappropriateethicalapprovalforthebiopsyresearchandthisethicalapprovalwasstatedinthepaperaspublished. IfDeerprovided theGMCwith evidenceof 162-95, then theprosecutionwithheldthedetailsofthisECapprovalfromthepanel.

WhileDr.Wakefield’sresearchhadoperatedunder162-95,thedocumentswere not in his possession but that of the ethics committee. During hisevidence Dr. Wakefield stressed the importance of relying, not onmemory, but on the original documents,many ofwhich—like 162-95—onlybelatedlycametolightduringtheoralevidence.Whereverpossible,

he had avoided speculation during the preparation of the defense on thebasisthatreconstructionoftheeventsof9yearsearlier,intheabsenceofthecontemporaneousdocuments,was fraughtwithhazard.Hewas right.TheGMC’sfailuretoeitherobtainordisclosecrucialdocumentssuchas162-95had,ironically,damnedthedefendants’chanceofafairtrial.TheGMClawyersmayclaiminmitigationthat,inapplyingthewrongethicalapprovaltoTheLancetstudy,theyhadrelieduponanerroneousstatementmade by Professor Murch in 2004, a statement prepared hastily, undergreatduress,andcrucially,intheabsenceoftherelevantdocuments.Thispoint wasmade repeatedly by the defense during the hearing; it fell ondeafears.

The GMC Panel’s comment on the crucial matter of prior valid ethicalapproval was as dismissive as it was insipid, and utterly bereft of anyanalysis:

ThePanelhasheardthatethicalapprovalhadbeensoughtandgranted forother trialsand ithasbeenspecifically suggestedthatProject172-96wasneverundertakenandthatinfact,TheLancet 12 children’s investigations were clinically indicatedand the research parts of those clinically justifiedinvestigationswerecoveredbyProject162-95. In the lightofalltheavailableevidence,thePanelrejectedthisproposition.7

DireImplicationsTheGMC findings have dire consequences for the practice ofmedicinegenerally,necessarytreatmentsfordesperatelyillautisticchildren,andforthefutureoftheGMCinitsroleofprotectingpatients.January28,2010,maygodownasthedaythatinnovativeclinicalcarediedintheUK,killedoff by the post hoc reclassification of such care as unethical research.Imaginebringingyourdesperatelyillchildtoaclinic,onlybetoldbythe

mosteminentdoctorsinthefieldthattheirhandsaretied,andtheycandonothing because the condition and treatments have not yet been welldescribed in themedical literature, and theyhave to design a “research”protocol, submit it to a committee, and wait months for approval.Preposterous?Ofcourse,butthisiswhatwillhappeniftheGMCfindingslead to any sort of punitive action.Doctors justwon’t take the risk of aprotracted investigation that may be for collateral purposes such as thesettlingofscores,muchlessoflosingtheirlicense,andwillsettleintothesafemediocrityofdolingoutmedicine“bythebooks.”Medicinewillnolonger be a learned profession but just a series of rote steps performedmechanically and utterly without inspiration. Patients’ care will suffer,whichisexactlytheoppositeofGMC’ssupposedmission.Althoughallofmedicinewill suffer, the impactwill bemost immediately borne by themost severely ill autistic children. They will continue to be denied thediagnosisandcare that is theirbasichumanandethical right.TheGMChas become complicit in this phase of the overall battle to get at thescientific truth about vaccines and autism, and other chronic disorders,sacrificing thesechildrenonanaltarmadeofdeliberate ignoranceof thepreventableharmfromvaccinesandindifferencetotheirmedicalneeds.Ifwearetoretainthebenefitsofvaccines,wemustfulfillourdutytothesechildrenandtothedoctorsbraveenoughtocometotheiraid.

Doctors beware: prepare to be second-guessed bymedical regulators onyourclinicaljudgmentandspecificallyonwhether—despiteyourtraining,expertise,anddocumentaryevidence—testsyouundertakeon thesickestofyourpatientsareclinicallyindicatedorforthepurposeofresearch.

Endnotes1 Based on the clinical protocol for children undergoing neurologicaldeteriorationformBirminghamChildren’sHospital.

2 Ethical Practices Committee approval for taking of research biopsiesduringcolonoscopyEPC162-95.

3 Letter,JohnWalker-SmithtoDr.MichaelPegg,Nov.11,1996.

4 Letter,Dr.WakefieldtoDr.Pegg,Feb.3,1997.

5 Letter, JWS to Dr. Pegg, July 15, 1998. Copies to Zuckerman andannotatedJuly17,1998.

6 LetterfromJohnWalker-SmithtoMs.CarrolloftheRoyalFreeEthicalPracticesCommitteeFeb.27,1997.

7 Fitness to Practise Panel applying the General Medical Council’sPreliminaryProceedingsCommitteeandProfessionalConductCommittee(Procedure)Rules1988.Findingonfacts.Jan.28,2010.

8 Emphasisadded.

9 Age ofAutism. (2009, February 27).Why is theMedia Ignoring theBailey Banks Autism Vaccine Decision? Retrieved fromhttp://www.ageofautism.com/2009/02/whyis-the-mediaignoring-the-bailey-banks-autism-vaccine-decision.html.See alsoBaileyBanks, by his fatherKennethBanks v. Secretary of theDepartmentofHealthandHumanServices.UnitedStatesCourtofFederalClaims. 20 July 2007. Retrieved fromhttp://www.uscfc.uscourts.gov/sites/default/files/Abell.BANKS.02-0738Vpdf.

10 AttkissonS.(2008,June19).VaccineWatch.CBSNewsInvestigates:

Primary Source. Retrieved from http://www.cbsnews.com/8301-501263_162-4194102-501263.html.

Epilogue

There ismore to come—muchmore: the journeys of fellow travelers,anotherwhistleblower,misconduct inCongress, and an over-the-counternutritional supplement called transfer factor, a naturally occurringsubstance, intendedasan immune-enhancingagent tohelpchildrenclearmeasles infection but branded falsely as anMMRvaccine “competitor.”Despite a lack of evidence, it has been alleged that I started a child ontransfer factor. In fact, the parents chose to use this non-prescriptionsupplementfortheirchild.Itwasneverusedbymeormycolleaguesasan“experimentaldrug,”andtheissueofpediatricqualificationswasentirelyirrelevant.Andsoon…

AsIsharesomefinalthoughts,rumorsofapossible$2Mfraud(andCDCcollusion) by Dr. Paul Thorsen (a senior investigator on the famously“negative”MadsenDanish studies that claimed,wrongly, to exonerate aroleforthimerosalandMMRinautism1)abound.Furtherrumorsindicatethatanothergovernmentwitness inUSvaccinecourtand reputedautismexpert isunder investigation forethicalviolations inCanada. In theUK,Rutter, Horton, Zuckerman, Pegg, and Salisbury are the subjects ofcomplaints to theGMC.Oh, yes, and another several thousand childrenhavegonetothewallwhilethis“TheatreoftheAbsurd”hasbeenplayingout.Deaths,2deportation,3 imprisonment,4andsuicide5—will these tooturnouttobeavoidableadversevaccinereactions?

Stop for a moment. Politicians, regulators, manufacturers, attorneys,bloggers,andhangers-on:Actnowtoprotectchildren.Actnowtoprotectthe benefits of the vaccine program. Put safety first above any other

consideration.Insistonthis,Mr.andMrs.Gates.

Thereisnoplaceforindulgingfutiledisplacementactivity,sanctimoniousposturing,andself-protectionism.Inthebattlefortheheartsandmindsofthepublic, youhave already lost…Why?Because theparents are right;theirstoriesaretrue;theirchildren’sbrainsaredamaged;thereisamajor,major problem. In the US, increasingly coercive vaccine mandates andfear-mongering advertising campaigns are a measure of your failure -vaccine uptake is not a reflection of public confidence, but of thesecoercivemeasures,andwithoutpublicconfidence,youhavenothing.

Withtheissueofvaccinesafetyinmind, in2001Igot togetherwithDr.LauraHewitson,anoutstanding researcher,at that timeat theUniversityofPittsburgh.Withcolleagues,wedesignedastudythatshouldhavebeendone many years before. We set out to examine the safety of the USvaccineschedule—startingwiththehepatitisBvaccine(HBV)givenondayoneoflifethroughtopre-schoolboosters.Thefirstpaper—thefirstofmany-reporteddelayedacquisitionofsurvivalreflexes(e.g.,feeding)in infant monkeys after the day one HBV shot (containing mercurypreservative). Following rigorous peer-review and online publication inNeurotoxicology, the paper was withdrawn, not apparently, on theinstructions of the scientific editor, but by the publishing companyElsevier.6 The links between this company and the pharmaceuticalindustryhavebeenreportedbyMarkBlaxillinoneofhisexcellentpiecesforAge of Autism.6 Science, it would seem, is available to the highestbidder.

EmperorNerodidnotfiddlewhileRomeburned,buthedidblamethefireonothers— theChristians—whomheput to the sword toappease the

angrymob.Governments,incontrastwithNero,areguiltyofboth—theyhavefiddledandappeased.Itwillbelefttofuturegenerationstorepairandrebuild.

Therewillbevictoryofasort.Anditwillbeavictoryfromthebottomup;inthetruespiritof theAmericanConstitution, thepeoplewillhavetheirsay. Itwillnot come from the topdownbecauseaphalanxof lobbyists,“experts,”andtruebelieversstandsbetweenthePresidentandthepeopleheissworntoserve.

Sinking slow, out over Crystal Mountain, the Texan sun still hurts theland.Thecedarsdrawonparchedearth.Andthesunisgone.Starscreepinto thenight skyand the forestbegins tomove.Mychildrenareasleepandmybeeriscold.FromthelipsofWillieNelson,theballadofBobbyMcGee fallswitha saltymelancholy:“I’d tradeallmy tomorrows forasingleyesterday.”AndforamomentIamthere,onthecold,wetprecipiceofHoundsGhyllviaduct,180feetaboveoblivionasthesmallboylooksquestioninglyintomyface,slipsmyhand,andisgone.

Endnotes1 WakefieldAJ,BlaxillM,StottC.MMRandAutisminPerspective:theDenmark Story. Journal of American Physicians and Surgeons.2004;9(3):89-91.

2 MarikarS,ChildsD,ChitaleR. (2009, January5).DeathCertificate:John Travolta’s Son Died of a Seizure. Retrieved fromhttp://abcnews.go.com/Entertainment/MindMoodNews/story?id=6576215&page=1.

3 Campsie A. (2009, July 16). Deportation of Hacker to US for trialwould be ‘disastrous’. The Herald. Retrieved fromhttp://www.heraldscotland.com/deportation-ofhacker-to-us-for-trial-would-be-disastrous-1914708.

4 Information for criminal justice professionals (n.d.) Retrived fromhttp://www.nas.orguk/nas/jsp/polopoly.jsp?d=471.

5 NationalsuicidepreventionstrategyforEngland.(n.d.)Retrievedfromhttp://www.nas.org.uk/nas/jsp/polopoly.jsp?d=2520&a=2371.

6 BlaxillM.(2010,March2).JoanCranmer’sFatefulDecisionsandtheSuppression of Autism Science. Age of Autism. Retrieved fromhttp://www.ageofautism.com/2010/03/joan-cranmers-fateful-decisions-and-the-suppression-of-autism-science.html#more.

Postscript

byJamesMoody,Esq.

We read in Sir Graham Wilson’s classic book The Hazards ofImmunization:1“Itisforusandforthosewhocomeafterustoseethatthesword which vaccines and antisera have put into our hands is neverallowed to tarnish through overconfidence, negligence, carelessness, orwant of foresight.” In Callous Disregard, Dr. Andy Wakefield hasrevealedthedetailsofhisongoingmissiontoheedthiswarning.

Although improvements in sanitation, nutrition, and clinical care in ouradvanced post-industrial civilization had reducedmuch of the burden ofinfectiousdisease,vaccinescontinuedtobepromotedasthe“weapon”ofchoiceinthewaragainstdisease.

Aswithanywar,therearecasualties(beginningwiththetruth),andthisisalsothecaseinthewaragainstinfection.Asmallnumberofcasualtiesareinevitable−andsomearguethisisjustifiableduetothepurportedoverallbenefits to society. But we have a moral, ethical, and legal duty tominimize the collateral damage and to take good care of the innocentvictims (includingprovidingcompensation) in thiswaragainst infection.The“communitarian”wingofpublichealthhasdecidedthat thegoodofthemanysupplantstheethicalobligationsowedtoeachchild.Somepublichealth officials have accepted an unknown burden of chronic disease −

especiallyautismbutalsootherimmune,autoimmune,anddevelopmentaldisorders − as a fair trade for the prevention of acute morbidity andmortalityfrominfection.Epidemicratesofautism,2compellinganecdotalevidence of lower autism rates in unvaccinated populations (e.g., non-vaccinatingAmish families3) and a lack of baseline data comparing thehealthhistoriesofvaccinatedversusunvaccinatedchildren,togethersignalan urgent need to reassess the acceptability of a “greater good” vaccinepolicy.Acrucialgapinourvaccinesafetysciencewasrecentlyrecognizedby theUSNationalVaccineAdvisoryCommittee.4And theCenters forDisease Control (CDC) guards its Vaccine Safety Datalink databasestatisticsseeminglyas tightlyasourmilitary leadersguardourcountry’snuclearsecrets.

Without transparency and data, it is simply impossible to conclude howmuchchronicillness,includingautism,iscausedbyvaccines.

Theterribletragedyofepicproportionisthatmostoftheautismepidemic(and other chronic adverse reactions) could have been prevented bychangesinthevaccineschedule,formulationandscreening,aswellasanongoing program of comparative baseline research in humans andprimates. I speculate that the motive for the cover-up and the ongoinggovernment policy of “deliberate ignorance” ismost likely the fear thathonesty about chronic vaccine adverse events would increasingly temptparents toforegotherisksandrelyuponthepurportedherdimmunityofothers. (Herd immunity itself is in question because there have beendiseaseoutbreakseveninhighlyvaccinatedpopulations.)Withouthonestinvestigation, transparency and disclosure, can there truly be informedconsent?

Asyouhavereadinthisbook,theUSvaccinecourtbegancompensatingand the US Department of Health and Human Services began secretlysettling cases of vaccine caused autism since 1991, including the quietconcession of liability in the case of Hannah Poling,5 one of the “test”casesintheOmnibusAutismProceeding.TherealsowasasettlementforMMR-caused autism in the 2002 Hiatt case ($5.1 million)6 and mostrecently the Bailey Banks case.7 The precedent for the admission ofvaccine-inducedautismis there;whatremains toberesolvedis thebodycount, appropriate treatments, and reform of the vaccine schedule topreventautismandothervaccinecausedchronicdisorders.

With a history including the clandestinemeeting betweenUS regulatorsand industry at the Simpsonwood Retreat Center in Norcross, GA, in2000;8 highly biased and ineffectual Institute of Medicine “reviews” ofvaccinesafetyin2001and2004;andadeeplyflawedstringof“studies”reminiscentofthejunkepidemiologyonceusedtodefendtobaccosafety,all as water under the bridge, the CDC eventually admitted that itsepidemiologywasflawed9and,inaleakedmediastrategydocument,thatit did not have the science to dispel safety questions of “anti-vaccine”challengers.10

Dr. Wakefield has been attacked in an orchestrated campaign to“discredit” him and his research, an attack which included the longestrunning“showtrial”inthehistoryoftheUK’slicensingbody,theGeneralMedical Council (GMC). Sadly, this “kangaroo court” was an orgy ofprosecutorial misconduct, false testimony, and mischaracterization ofappropriate clinical care of desperately sick children spun as “unethical”research. In one of the more bizarre incidents of this skirmish, theannouncementoftheretractionofTheLancetpaperfollowingtheJanuary28,2010,GMCfindingswasproclaimedattheFebruary4,2010,meeting

oftheNationalVaccineAdvisoryCommittee(whichadvisestheSecretaryofHealthandHumanServicesonvaccinepolicy).Thiswasgreetedwithcheers and “high fives” from the federal and public health elite inattendance.MypubliccommentattheendofthemeetingsimplypointedoutthatthisOrwellianefforttoerasehistoryandthecontributionsmadetosciencebythese12childrenwillnotsucceed.

Dr.Wakefieldisthe“RalphNaderofvaccinesafety.”Heisthelatestinalong line of scientists who use the power of the scientific method tochallenge establishment orthodoxy. Thanks to Galileo, Semmelweiss,Needleman,andMcBride,wenowtakeitforgrantedthattheEarthisnotthecenterof theUniverse, thatdoctorsmustwashtheirhandstopreventthe spread of infection, that lead impairs neurological development inchildren,andthatthalidomidecausesbirthdefects.Andnow,thankstoDr.Wakefield,wewillonedayhavesafervaccinesandbetter treatmentsforautism.

Endnotes1 WilsonG.TheHazardsofImmunization.London:TheAthlonePress,1967.

2 http://www.cdc.gov/ncbddd/autism/addm.html.

3 BlaxillM.(2008,May14).Olmsted,theAmishandAutism.PartOne.Retrieved from http://www.ageofautism.com/2008/05/olsted-the-amis.html.BlaxillM. (2008,May 15).Olmsted, theAmish andAutism. Part Two.Retrieved from http://www.ageofautism.com/2008/05/olsted-the-am-1.html

4 NVAC.(2009,June2).“RecommendationsontheCentersforDiseaseControl and Prevention Immunization Safety Office Draft 5-YearScientificAgenda.(seeinparticularrecommendation#7).Retrievedfromhttp://www.hhs.gov/nvpo/nvac/NVACRecommendationsISOScientificAgendaFinal.pdf

5 Kirby D. (2008, February 26). The Vaccine Court Document EveryAmerican Should Read. Huffington Post. Retrieved fromhttp://www.huffingtonpost.com/david-kirby/thevaccineautism-court-_b_88558.html.CBS News. Retrieved fromhttp://www.cbsnews.com/sections/primarysource/main501263.shtml?contributor=41919.

6 Taylor G. (2008, March 9). Phil and Misty Hiatt: We WereCompensated Too. Adventures in Autism. Retrieved fromhttp://adventuresinautism.blogspot.

7 Kennedy R, Kirby D. (2009, February 24). Vaccine Court: AutismDebate Continues. Huffington Post. Retrieved fromhttp://www.huffingtonpost.com/robert-f-kennedy-jr-anddavid-

kirby/vaccine-court-autism-deba_b_169673.html.

8 See http://www.safeminds.org/government-affairs/foia/simpsonwood.html.

9 KirbyD.(2008,June21).CDC:VaccineStudyUsedFlawedMethods.Huffington Post. Retrieved from http://www.huffingtonpost.com/david-kirby/cdc-vaccine-study-usedfl_b_108462.html.

10 Moody J. (2009,August 5).CDCMediaPlanShocker−WeDon’tHavetheScience−Someclaimsagainstvaccinecannotbedisproved.Ageof Autism. Retrieved from http://www.ageofautism.com/2009/08/cdc-media-plan-shocker-we-don’t-have-thescience-some-claims-against-vaccine-cannot-be-disproved-.html

BIOGRAPHY

Photocredit:VibekeDahl

Andrew Wakefield, MB, BS, FRCS, FRCPath, is an academicgastroenterologist. He received his medical degree from St. Mary’sHospitalMedicalSchool(partof theUniversityofLondon)in1981,oneof the third generation of his family to have studied medicine at thatteaching hospital.He pursued a career in gastrointestinal surgerywith aparticular interest in inflammatoryboweldisease.HequalifiedasFellowof the Royal College of Surgeons in 1985 and in 1996 was awarded aWellcome Trust Traveling Fellowship to study small intestinaltransplantation inToronto,Canada.Hewasmade aFellowof theRoyalCollege of Pathologists in 2001. He has published over 130 originalscientificarticles,bookchapters,andinvitedscientificcommentaries.

In the pursuit of possible links between childhood vaccines, intestinalinflammation,andneurologicinjuryinchildren,Dr.Wakefieldlosthisjobin the Department of Medicine at London’s Royal Free Hospital, hiscountry,hiscareer,andhismedicallicense.

He ismarried toCarmel, a physician and a classical radiopresenter.Hehas four children, James,Sam, Imogen, andCorin, and a blackmongrelcalledBella.

a GeneralMedicalCouncilvs.Wakefield,Walker-Smith,andMurch