TableofContents

TitlePage

CopyrightPage

Dedication

Introduction

Chapter1-VioxxandtheFearofScience

Chapter2-VaccinesandtheGreatDenial

Chapter3-TheOrganicFetish

Chapter4-TheEraofEchinacea

Chapter5-RaceandtheLanguageofLife

Chapter6-SurfingtheExponential

Acknowledgements

NOTES

BIBLIOGRAPHY

INDEX

ABOUTTHEAUTHOR

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Specter,Michael.Denialism:howirrationalthinkinghindersscientificprogress,harmstheplanet,

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ToEmma,whoallbyherselfisreasonenoughtorejectdenialism.

INTRODUCTION

Tenyearsago,whilewalkingthroughHarvardYard,Isawastudentwearingabuttonthatsaid“ProgressivesagainstScientism.”Ihadnoideawhatthatmeant,soIaskedhim.Scientism,heexplained, is themisguidedbelief thatscientistscansolveproblemsthatnaturecan’t.Hereeledoffaseriesoftechnologiesthatdemonstrated the destructiveness of what he called the “scientific methodapproach” to life:geneticallymodified foods,dams,nuclearpowerplants, andpharmaceuticalsallmade the list.We talkedfora fewminutes, thenI thankedhimandwalkedaway.Ididn’tunderstandhowsciencemightberesponsibleforthemany scars humanity has inflicted upon theworld, but students have oddintellectualinfatuations,andIletitslipfrommymind.

Over the next few years, while traveling in America and abroad, I keptrunningintodifferentversionsofthatstudent,peoplewhowereconvincedthat,largelyinthenameofscience,wehadtrespassedonnature’sground.Theissuesvaried,butnottheunderlyingphilosophy.Societyhadsomehowforgottenwhatwas authentic and there was only one effective antidote: embrace a simpler,more “natural” way of life. No phenomenon has illustrated those goals moreclearly than persistent opposition to genetically engineered food. “This wholeworldviewthatgeneticallymodifiedfoodistheresowehavenochoicebuttouse it is absolutely terrifying and it iswrong,” Lord PeterMelchett, a formerBritishLabourminister,toldmewhenImethimafewyearsago.

Today, LordMelchett, whose great-grandfather founded one of theworld’slargestchemicalcompanies,ispolicydirectoroftheBritishSoilAssociation,theorganic food and farming organization. The first timewe spoke, however, heservedasexecutivedirectorofGreenpeace,wherehewasinthemidstofleadinga furious campaignagainstMonsanto (whichhe referred to as “Monsatan”) toridtheworldofgeneticallyengineeredfoods.“Thereisafundamentalquestionhere,”hesaid.“Isprogressreallyjustaboutmarchingforward?Wesayno.Wesayitistimetostopassumingthatdiscoveriesonlymoveusforward.Thewaragainstnaturehastoend.Andwearegoingtostopit.”

I felt then—as I do now—that he had gotten it exactly wrong; scientistsweren’t waging a war at all, he was—against science itself. Still, I saw LordMelchett as a quaint aristocrat who found an interestingway to shrug off hisfamily’s industrial heritage. His words were hard to forget, though, and Ieventually came to realizewhy: by speaking about a “war against nature,” he

hadadoptedasystemofbeliefthatcanonlybecalleddenialism.DenialistslikeLordMelchettreplacetherigorousandopen-mindedskepticismofsciencewiththeinflexiblecertaintyofideologicalcommitment.

Wehaveallbeen indenial at somepoint inour lives; facedwith truths toopainful to accept, rejection often seems the only way to cope. Under thosecircumstances, facts, no matter how detailed or irrefutable, rarely make adifference.Denialism is denialwrit large—when an entire segment of society,oftenstrugglingwiththetraumaofchange,turnsawayfromrealityinfavorofamorecomfortablelie.

Denialism comes in many forms, and they often overlap. Denialists drawdirect relationships where none exist—between childhood vaccinations, forexample,andtherisingincidenceofdiseaseslikediabetes,asthma,andautism.They conflate similar but distinct issues and treat them as one—blending theresultsofdifferentmedicalstudiesonthesametopic,orconfusingagenerallackof trust in pharmaceutical companies with opposition to the drugs theymanufactureandeventotheveryideaofscience.

Unlessdatafitsneatlyintoanalreadyformedtheory,adenialistdoesn’treallysee it as data at all. That enables him to dismiss even the most compellingevidenceasjustanotherpointofview.Instead,denialistsinvokelogicalfallaciestobuttressunshakablebeliefs,whichiswhy,forexample,cropscreatedthroughthe use of biotechnology are “frankenfoods” and therefore unlike anything innature. “Frankenfoods” is an evocative term, and so is “genetically modifiedfood,”but thedistinctions theyseek todrawaremeaningless.All the foodweeat,everygrainofriceandearofcorn,hasbeenmanipulatedbyman;thereisnosuchthingasfoodthathasn’tbeengeneticallymodified.

Ourability tocutgenes fromoneorganismandpaste them intoanotherhastransformed agriculture. But it is a change of degree, not of type. Denialistsrefusetoacknowledgethatdistinction,inpartbecauseit’ssomuchsimplertofixblame on a company, an institution, or an idea than to grapple with a morecomplicatedtruth:thatwhilescientificprogresshasbroughthumanityimmensewealth and knowledge, it has also caused global pollution severe enough tothreaten the planet.Denialists shun nuance and fear complexity, so instead ofaskinghowsciencemighthelpresolveourproblems,theyrejectnovelstrategieseven when those strategies are supported by impressive data and powerfulconsensus.

Until I learnedaboutHolocaustdeniers, itneveroccurred tome thata large

groupcouldremainwillfullyignorantofthemosthideoustruths.Then,twenty-fiveyearsago,Ibegantowriteaboutpeoplewhorefused toacknowledge thatthehumanimmunodeficiencyviruscausedAIDS,despitewhat,eventhen,wasanoverwhelmingaccretionofevidence.HolocaustdeniersandAIDSdenialistsare intensely destructive—even homicidal—but they don’t representconventional thought and they never will. This new kind of denialism is lesssinisterbutmorepervasivethanthat.

My unusual encounter atHarvard came back tome a few years ago, and Istartedtothinkaboutwritingthisbook.Ikeptputtingitoff,though.Someofthedelaywasduesimplytoprocrastination.Buttherewasanother,moreimportantreasonformyhesitation:Ihadassumedthesenaggingglimpsesofirrationalitywereaberrations, tinypocketsofdoubt.Authoritymaybe flawed,and scienceoftenfailstofulfillitspromises.Nonetheless,Iwasconvincedthatpeoplewouldcomearoundtorealizingthatthe“scientificmethodapproach”—thedisciplinedand dispassionate search for knowledge—has been the crowning intellectualachievementofhumanity.IguessIwasinmyownkindofdenial,becauseevenasthingsgotworseIkeptassuringmyselfthatreasonwouldprevailandabooklikethiswouldnotbenecessary.

Finally, a couple of years ago, I was invited to dinner at the home of aprominent, well-read, andworldlywoman. She askedwhat I wasworking onandI toldherthatIhadbecomemystifiedbythefact thatsomanyAmericansseemedtoquestionthefundamentaltruthsofscienceandtheirvaluetosociety.Imentionedas examples anxiety about agriculturalbiotechnology,opposition tovaccinations,andthegrowingpowerofthealternativehealthmovement.

She suddenly became animated. “It’s about time somebodywrites the truthabout thesepharmaceuticalcompanies,”shecried.“Theyareevil,makingvastsumsfromlifestyledrugslikeViagraandlettingmillionsdieinsteadofhelpingthem. The government is no better; they are destroying our food supply andpoisoning our water.” Some years earlier she had been seriously ill, and sheexplainedhowsherecovered:bytakingdozensofvitaminseveryday,apracticeshe has never abandoned.With thiswoman’s blessing, her daughter,who hadjustgivenbirth,declinedtovaccinateherbaby.

Thewomandidn’tactuallysay,“It’sallaconspiracy,”butshedidn’thaveto.Denialism couldn’t existwithout the common belief that scientists are linked,oftenwiththegovernment,inanintricateweboflies.Whenevidencebecomestoo powerful to challenge, collusion provides a perfect explanation. (“Whatreasoncouldthegovernmenthaveforapprovinggeneticallymodifiedfoods,”a

formerleaderoftheSierraClubonceaskedme,“otherthantoguaranteeprofitsforMonsanto?”)

“You have a point,” I told the woman. “I really ought to write a book.” Idecided to focus on issues like food, vaccinations, and our politically correctapproach to medicine, because in each of those arenas irrational thought andfrank denialism have taken firm root. Today, anyone who defends science—particularly if he suggests that pharmaceutical companies or giant agriculturalconglomeratesmaynotbewhollyevil—willbecalledashill.

That’sdenialism,too—joinedasitofteniswithanalmostreligiouscertaintythatthereisabetter,more“natural”waytosolveourmedicalandenvironmentalproblems.Answersarerarelythatsimple, though.EveninthecaseofthedrugVioxx,whichIdescribeinthenextchapter—whereMerckwasasguiltyofmalfeasance as a company can be—it’s likely that had the drug remained on themarket, it would have been responsible for a hundred times more good thanharm.

The most blatant forms of denialism are rarely malevolent; they combinedecency,afearofchange,andthemisguideddesiretodogood—forourhealth,ourfamilies,andtheworld.Thatiswhysomanyphysiciansdismisstheideathatapatient’sracecan,andoftenshould,beusedasatoolforbetterdiagnosesandtreatment.Similarmotivations—inotherwords,wishful thinking—havehelpeddrive the growing national obsessionwith organic food.Wewant our food totastegood,butalsotobesafeandhealthy.That’snatural.Foodismorethanameal,it’sabouthistory,culture,andacommonsetofrituals.Weputfoodinthemouthsofourchildren;itisthegluethatunitesfamiliesandcommunities.Andbecausewedon’t seeour fooduntilwe eat it, any fear attached to it takesongreaterresonance.

The corrosive implications of this obsession barely register in America orEurope, where calories are cheap and food is plentiful. But in Africa, wherearablelandisscarce,scienceofferstheonlyhopeofprovidingasolutiontothegrowingproblemofhunger.Tosuggest thatorganicvegetables,whichcostfarmorethanconventionalproduce,canfeedbillionsofpeopleinpartsoftheworldwithout roads or proper irrigation may be a fantasy based on the finestintentions.Butitisacruelfantasynonetheless.

Denialistargumentsareoftenbolsteredbyaccurateinformationtakenwildlyout of context, wielded selectively, and supported by fake experts who oftendon’tseemfakeatall.Ifvastfactoryfarmsinjecthormonesandantibioticsinto

animals,which isoften trueandalwaysdeplorable, thenall industrial farmingdestroys the earth and all organic food helps sustain it. If a pricey drug likeNexium, the blockbuster “purple pill” sold so successfully to treat acid refluxdisease, offers few additional benefits to justify its staggering cost, then allpharmaceutical companies always gouge their customers and “natural”alternatives—largely unregulated and rarely tested with rigor—offer the onlyacceptablesolution.

Wenolongertrustauthorities,inpartbecauseweusedtotrustthemtoomuch.Fortunately,theyareeasilyreplacedwithexpertsofourown.Allit takesisanInternet connection. Anyone can seem impressive with a goodWeb site andsomedecentgraphics.Typetheword“vaccination”intoGoogleandoneofthefirst of the fifteen million or so listings that pops up, after the Centers forDisease Control, is the National Vaccine Information Center, an organizationthat,basedonitsname,certainlysoundslikeafederalagency.Actually,it’sjustthe opposite: the NVIC is the most powerful anti-vaccine organization inAmerica,anditsrelationshipwiththeU.S.governmentconsistsalmostentirelyofopposingfederaleffortsaimedatvaccinatingchildren.

IN2008,Americaelectedapresidentwhosupports technologicalprogressandscientific research as fully as anyonewho has held the office. BarackObamaeven stressed science in his inaugural address. “Wewill restore science to itsrightfulplaceandwieldtechnology’swonderstoraisehealthcare’squality...andloweritscosts,”hesaid.“Wewillharnessthesunandthewindsandthesoilto fuel our cars and run our factories.Andwewill transformour schools andcollegesanduniversitiestomeetthedemandsofanewage.”

Obama realizes theurgencywithwhichweneed todevelopnewsourcesofenergy. That is why he frequently compares that effort to America’s mostthrilling technological achievement: landing men on the moon. Obama hasassembled a uniformly gifted team of scientific leaders, and when he speakspubliclyaboutissueslikeswinefluorHIV,thepresidentroutinelymakesapointofsayingthathewillbeguidedbytheiradvice.

Thatisquiteadeparturefromtheattitudeofhispredecessor,who,inoneofhisfirstmajorinitiatives,announcedthathewouldprohibitfederalfundingfor

researchonnewstemcell lines.GeorgeW.Bushencouragedschools to teach“intelligent design” as an alternative to the theoryof evolution, andhe all butignored the destruction of our physical world. His most remarkable act ofdenialism,however,wastodevoteone-thirdoffederalHIV-preventionfundsto“abstinenceuntilmarriage”programs.

The Bush administration spent more than $1 billion on abstinence-onlyprograms,despitedatafromnumerousstudiesshowingthattheyrarely,ifever,accomplish their goals. Nevertheless, during the Bush administration, familyplanningorganizationsinthedevelopingworldweredeniedU.S.grantsif theysomuchasdiscussedabortionwiththeirclients.PresidentObamabeganatoncetoreversethatlegacyandrestorethefaithinprogresssomanypeoplehadlost.

IwishIcouldsaythathehashelpedturnbackthegreatertideofdenialismaswell. That would be asking toomuch. Despite the recession, sales of organicproducts have continued to grow, propelled bymillionswhomistakenly thinkthey are doing their part to protect their health and improve the planet.Supplementsandvitaminshaveneverbeenmorepopulareventhoughagrowingstack of evidence suggests that they are almost entirely worthless. Anti-vaccinationconspiracytheorists,ledbythetirelessJennyMcCarthy,continuetoflourish.

Sodoesdenialism,abettedbysomeoftheworld’smostprominentcelebrities.OprahWinfrey,forone,hasoftenprovidedaforumforMcCarthyonhershow,but she intends to do more: in early 2009, Winfrey’s production companyannouncedthatithadhiredMcCarthytohostasyndicatedtalkshowandwriteablog,providing twonewplatforms fromwhichshecanpreachhermessageofscientificilliteracyandfear.

Thisantipathytowardtheideasofprogressandscientificdiscoveryrepresentsafundamentalshiftinthewayweapproachtheworldinthetwenty-firstcentury.More than at any time since Francis Bacon invented what we have come toregardas thescientificmethod(andGalileobegantoput it touse),Americansfearscienceat leastasfullyasweembrace it. It isasentiment thathas turnedourelectrifyingageofbiologicaladventureintooneofdoubtanddenial.Therehave always been people who are afraid of the future, of course—Luddites,ignorantofthepossibilitiesoflifeonthisplanetanddeterminedtoremainthatway. No amount of data will convince climate denialists that humans havecaused the rapid, devastatingwarming of the earth.And no feat ofmoleculargenetics will make a creationist understand that our species has evolved overbillionsofyears,alongwitheveryothercreature.

Commonstrainsofdenialismareevenmore troubling, though,because theyshowwhathappenswhenunfetteredscientificachievementbumpsupagainstthelimitsofhumanimagination.Manipulatingthegenesofcowsorcornwasonlyafirststep.Today,weroutinelyintrudeoneveryaspectofhumanandnaturallife.That fact traumatizes people—and not entirely without reason. Mary Shelleycouldn’t have imagined what goes on in thousands of laboratories today.Scientists allover theworldare resurrectingviruses thathavebeenextinct formillionsofyears.Theyareconstructingorgansoutofspareparts,anditisonlyamatteroftime(andnotmuchtimeeither)beforesyntheticbiologistsdesign,thengrow, entirelynew formsof life—organisms that haveneverbefore existed inthe natural world. The speed at which all this is happening has made manypeople fear thatweareabout to losecontrol,notonlyover theworldwehavealwaysviewedasourdominion,butofhumanlifeaswell.

Nothing scares us quite as much. Controlling life is something we haveattemptedsincewedomesticatedcattleandbegan togrowfood.Thescientificrevolution helped solidify the idea that our species was in command and, asBaconput it inTheNewAtlantis, able to “establishdominionovernature andeffect all things possible.” Yet there have always been committed efforts atstoppingthemarchoftechnology.

In 1589, Queen Elizabeth refused to fund a project to make a knittingmachine,saying,“Mylord,Ihavetoomuchloveformypoorpeoplewhoobtaintheirbreadbyknittingtogivemoneythatwillforwardaninventionwhichwilltend to their ruinbydepriving themof employment.”Three centuries later, in1863,SamuelButlerbecamethefirsttowriteaboutthepossibilitythatmachinesmight evolve throughDarwinian selection.Althoughmany readers thought hewasjokinginhisessay“DarwinAmongtheMachines,”Butlerwasserious(andastonishinglyprescient):

Therearefewthingsofwhichthepresentgenerationismorejustlyproud thanof thewonderful improvementswhich are daily takingplace in all sorts of mechanical appliances. . . . Day by day,however,themachinesaregaininggrounduponus;daybydaywearebecomingmoresubservienttothem;moremenaredailybounddown as slaves to tend them, more men are daily devoting theenergiesoftheirwholelivestothedevelopmentofmechanicallife.Theupshotissimplyaquestionoftime,butthatthetimewillcomewhenthemachineswillholdtherealsupremacyovertheworldanditsinhabitantsiswhatnopersonofatrulyphilosophicmindcanfor

amomentquestion.

If anything, that fear is more pronounced today (andmore understandable)thaneverbefore.Denialismisoftenanaturalresponsetothislossofcontrol,anattempttoscaletheworldtodimensionswecancomprehend.Denialismisnotgreen or religious or anti-intellectual, nor is it confined to utopian dreamers,agrarians, or hippies. It is not right-or left-wing; it is a fear expressed asfrequentlyandwithasmuchfervorbyOxforddonsasbybusdrivers.

The fear has seeped across Britain, Europe, and the developing world. ButnowhereisitmoreevidentthanintheUnitedStates,acountrythathasalwaysdefineditselfbyitsnotionofprogressandtechnologicalprowess.Wemaybeanation of immigrants, butmore than thatwe are the nation that invents: fromrefrigerators to resistors, antibiotics, jets, and cell phones, to the computersoftwarethatgovernsmuchofourlivesandthegeneticsequencingtechnologythatwill soonbegin todoso.Whatwouldhaveseemed likesorceryacenturyago isnowregardedsimplyas fact. In1961,ArthurC.Clarkefamouslywrotethat“anysufficientlyadvancedtechnologyisindistinguishablefrommagic.”

Whocouldmakesuchastatementtoday?Whatwouldmagiclookliketous?Ithasbecomeroutinetodeliverbabiesmonthsbeforetheyareconsideredalive—nottomentiontokeeppeoplebreathinglongaftertheyare,inanymeaningfulsense, dead. My grandfather died in 1962 at the age of sixty-six. That wasexactlyhowlongmenbornattheturnofthetwentiethcenturywere“expected”to live, and while he was mourned, nobody considered his death premature.They certainly would have today, though. Just forty-six years later, a healthyfifty-year-oldmancanexpecttolivetotheageofeighty.

AtleastsincetheEnlightenment,whenscienceeffectivelyreplacedreligionasthe dominant ideology of mankind, progress has been our purpose.We havemovedfromthediscoveryofthecompass(andoursenseofwhereweareinthephysicalworld)totheinventionofgunpowder,totheastonishingabilitytotakepicturesthatseethroughhumanflesh—onlytoarriveatthedefiningeventofthetwentieth century: the splitting of the atom. As Manhattan Project scientistsgatheredinNewMexicoonJuly16,1945,toawaitresultsfromthefirsttestoftheatomicbomb,theywereanxiousandafraid.Manytookbetsonwhethertheywereabouttosettheskyablazeanddestroytheworld.

New technologies are always accompanied by new risks and at least onedeeplyunsettlingfact:onceyouinventsomethingyoucannotuninvent it.Thatsoundssimple,butsincethatdayinNewMexicomorethanhalfacenturyago

thatknowledgehas changed society, planting seedsof fear into even themostpromising discoveries. The superpowers may have averted a cold war anddismantledmany of the nuclearweapons that had threatened to annihilate us.But they didn’t uninvent them and they never could. H. G. Wells said thatcivilization is a race between education and catastrophe. He was right. Evenmorethanthat,though,civilizationisaracebetweeninnovationandcatastrophe.

That race only growsmore frantic.Global nuclearwar,while by nomeansimpossible, is a less likelyprospect than itwas twentyyears ago.But there isnothingunlikelyaboutassemblinglifefromscratch,cloningcopiesofourselves,or breeding extinct animals. InNovember 2007, for the first time, researcherssuccessfullyclonedembryosfromthesinglecellofanadultmonkey.Theworkput an end to anydebate aboutwhetherprimates—thegroup that includesnotonlymonkeys butmen—are biologically capable of being turned into clones.FaustandFrankensteinhavebeenwithusforalongtime.Butthewallbetweensciencefictionandrealityhaspracticallyvanished,andthereisevidenceofthatineventhemosttrivialplaces.

The2007filmIAmLegendwashardlyacinematicmaster-piece,butitopenswithasceneinwhichadoctorexplainstoaTVnewsanchorhowshewasableto cure cancer by mutating the measles virus and harnessing its destructivepower. She tells him that measles is like “a fast car with a madman at thewheel,”butherteambelieveditcouldbeusedforgoodif“acopweredrivingitinstead.”So theyused thevirus tocurecancer,whichwaswonderfuluntil themisprogrammed organismwiped out nearly everyone on earth. LikeGodard’sfilmLeNouveauMondeand theoriginal1954bookonwhichbothfilmswerebased, I Am Legend is pure fiction, another story of a virus gone wild. Thatdoesn’tmeanitwillbefictiontomorrow.

In early 2009, a team from the Mayo Clinic reported that certain measlesstrainscouldproveeffectiveasatreatmentforcancer.“Theseviralstrainscouldrepresent excellent candidates for clinical testing against advanced prostatecancer,”saidEvanthiaGalanis,theseniorauthorofthepaper.Theviralstrainswere inactivated, harmless, and well contained in a highly secure lab.Nonetheless,itishardnottorecoilwhenlifeimitatesartsofaithfully.

“Ofcoursethisisallpossible,”DrewEndysaidwhenIaskedhimwhetherthetheoretical threatsposedby thenewscienceofsyntheticbiologywerereal.“Ifwedon’twanttoexist,wecanstopexistingnow.”Endyisabiologicalengineerat Stanford University who is essentially attempting to turn human cells intosoftware that we can program. Instead of producing iTunes or spreadsheets,

however, this software would attack tumors, repair arteries clogged withcholesterol, and prevent diseased cells from destroying the immune system.Endyisanoptimist,buthereadilyacknowledgesthedangersassociatedwithhiswork.“Whywouldn’twebeafraid?”hesaid.“Wearespeakingaboutcreatingentirelynewformsoflife.”

FIFTYYEARSAGO,weveneratedtechnology.Atleastuntilweplacedourfeetonlunarsoil,ourculturewaslargelyoneofuncriticalreverenceforthegloriesthat science would soon deliver. The dominant image of popular Americanculturewasprogress.TVshowslikeStarTrekandTheJetsonswerebasedonakindofutopianviewofthescientificfuture.EventheFlintstonesweredescribedas a “modern”StoneAge family.Wewere entering an erawithout disease orhunger. Ifwe ran out ofwaterwewould siphon salt from the seas andmakemore; if naturewas brokenwe could fix it. If not, we could alwaysmove toanotherplanet.

Thatvisionno longerseemsquitesoenchanting.Nodoubtourexpectationswereunreasonable—forscienceandforourselves.Wealsobegan torecognizetheunintendedconsequencesofourundeniablesuccess.AboutamonthbeforeNeilArmstrongmadehislargesteponthemoon,theheavilypollutedCuyahogaRivereruptedinflamesnearCleveland,creatinganindelibleimageofindustryatwarwithnature.Afewyearslater,in1976,KarenAnnQuinlanwasremovedfromlifesupport,ignitingthefirsthorrificbattleofthemoderneraoverhowweliveanddie.TheendofthedecadewasmarkedbytheghastlyaccidentatThreeMile Island, which showed more clearly than ever that the effects of theIndustrial Revolutionwere not all benign. The thalidomide disaster,mad cowdisease,eventhedramaticandsustainedliesofBigTobaccohaveallcontributedtothesensethatifthepromiseofsciencewasn’talie,itwasn’texactlythetrutheither.

Today the image of a madman whipping up a batch of small pox, ormanufacturinganeffectiveversionofbirdfluinhiskitchen,whilenotexactlyaseasyasbakinga cake, isno longer so far-fetched. Indeed, if there is anythingmore frightening than the threat of global nuclear war, it is the certainty thathumansnotonlystandonthevergeofproducingnewlifeformsbutmaysoonbeabletotinkerwiththemasiftheywerevintageconvertiblesorbonsaitrees.

Our technical and scientific capabilitieshavebrought theworld toa turningpoint, one inwhichaccomplishments clashwith expectations.The result oftenmanifestsitselfasakindofculturalschizophrenia.Weexpectmiracles,buthavelittlefaithinthosecapableofproducingthem.Famineremainsaseriousblightonhumanity,yettheleadersofmorethanoneAfricannation,urgedonbyrichEuropeanswhohavenevermissedameal,havedecideditwouldbebettertolettheir citizens starve than to import geneticallymodified grains that could feedthem.

Foodisacompellingexampleofhowfearhastrumpedscience,butit isnottheonlyevidencethatwearewagingawaragainstprogress,ratherthan,asPeterMelchett would have it, against nature. The issues may be complex but thechoices are not:we are either going to embrace new technologies, alongwiththeirlimitationsandthreats,orslinkintoaneraofmagicalthinking.Humanityhas nearly suffocated the globewith carbon dioxide, yet nuclear power plantsthatproducenosuchemissionsaresomiredinobjectionsandobstructionthat,despiterenewedinterestoneverycontinent,itisunlikelyanotherwillbebuiltintheUnitedStates.Suchistheoppositiontoanyresearchinvolvingexperimentswithanimalsthatinscoresofthebestuniversitiesintheworld,laboratoriesareanonymous,unmarked,andsurroundedbyplatoonsofsecurityguards.

Forhundredsofyearswehada simplebut stunninglyeffectiveapproach toour interactionwith the physical world: what can be understood, and reliablyrepeated by experiment, is what nature regarded as true. Now, at the time ofmankind’sgreatestscientificadvances(andourgreatestneedforthem),thatdealis off. Snake oil salesmen may be old news in America, but today quacks—whose research isevenfundedby the federalgovernment—takeoutads in theNewYorkTimesdenouncingscientistswhorelyonevidence-basedmedicinetotreatourmostdevastatingdiseases.

Wearenowable tostaresodeeply into themolecularhistoryof thehumangenomethat,peeringonehundredmillionyearsintothepast,wecanseethatwesharedacommonancestorwiththeelephant.Scientistsaretantalizinglyclosetounderstandinghowthetrillionsofcellsinourbodiesworkandinteractwitheachother. Nonetheless, in 2007, a $27 million Creation Museum opened inKentucky, complete with bumper stickers that proclaim “We’re TakingDinosaursBack.” That’s fitting, since nomatter how you ask the question, atleast one in three American adults rejects the concept of evolution, believinginstead thathumansdescended fromheaven several thousandyears ago inourpresentform.

Scienceandreligionhavealwaysclashedandalwayswill.Einsteinputitbest:sciencewithout religion is lame, religionwithout science is blind. In the past,thatconflict,whileoftenpainful,nevermanagedtoderailprogress.Wecannolongersaythat.Ifanything,ourincreasinglyminuteknowledgeoftheoriginsofhumanityhasservedonlytofueltheintelligentdesignmovement,nottodampenit. In2005,when theAmericanMuseumofNaturalHistorymounted themostsignificant exhibition ever devoted to Charles Darwin, the leadership therecouldn’tfindasinglecorporatesponsorship,astheyalwayshadbeenabletodoin thepast.FewAmericancompanieswerewilling to riskaboycott stagedbythosewhoobjecttothetheoryofevolution.

Denialismmustbedefeated.Thereissimplytoomuchatstaketoacceptanyotheroutcome.Whodoesn’thavea familymemberwithdiabetes,Parkinson’sdisease, Alzheimer’s, or some form of cancer? When faced with genuinesolutions(notjustpromises)tosuchterriblefates,fewwillcontinuetoquestionthevalueofstemcellresearchorcloning.EvenNancyReagan,whosehusbandserved as commander-in-chief of the American war against legal abortion,becameanardentandvocalsupporterofstemcellresearchafterwatchinghimsubmittothedarkfogofAlzheimer’sdisease.

Wehaveacquiredmoreknowledgeinthepastdecadethanintheprevioustwocenturies.Evenbadnewssoonprovesitsworth.Lookatavianinfluenza:birdflumay cause a devastating epidemic. Viruses, like earthquakes and volcaniceruptions,willalwaysbepartof lifeonearth.(Not longbeforehedied,NobelPrize-winningbiologistJoshuaLederbergtoldmethatthe“singlebiggestthreattoman’scontinueddominanceonthisplanetisthevirus.”Hewasnotaloneinbelievingthat.)Nonetheless,avianinfluenzaisthefirstpotentialpandemicinthehistoryofhumanity thatcanbeunderstoodevenbefore itbecomescontagious.Researchershavemapped everygene andprotein in thevirus and arewell ontheirwaytodevelopingavaccine.

Sciencehasslowlycometodefineus.In1959,C.P.Snowdeliveredhis“TwoCultures”speechatCambridgeUniversity,inwhichheassertedthatthechasmbetween theworldsof scienceand thehumanitieswasmaking ithard tosolvethe earth’smost pressing problems.He had a point at the time.Butwe don’thave two cultures anymore, we have one. Students in many classrooms seekanswerstotheremainingintricaciescontainedwithinthehumangenome,andiftheydon’tunderstandtheirresearchtheycanalwaysturntotheInternettofindaneagertutorfromoneofadozennations.InIndiaandChina,youngengineersand biologists use Skype to conduct videoconferences with colleagues from

Boston toBerlin. It costs nothing. Two generations ago, in the unlikely eventthattheirgrandparentshadknownhowtowritealetter,theywouldneverhavebeenabletoaffordpostagestampsorfindaplacetomailit.

Ultimately, dramatic achievements have always taken us past our fears andovercome denialism—because progress offers hope and for humans nothingbeatshope.Fearmightthreatenprogress;intheend,though,itwon’tpreventit.Notlongago,afterpublishingapieceintheNewYorkeronscientistswhowerereconstructingextinctviruses, I received this letter: “Notdiscounting thegreatadvanceswehavemadewithmolecularbiologyoverthelasttwenty-fiveyears,Idaresaythequestionremains...willthisgenerationofscientistsbelabeledthegreatminds of the amazing genetic-engineering era, or themost irresponsiblescientists in thehistoryof theworld?With thepresentpostureof thescientificcommunity,mymoney,unfortunately,isonthelatter.”

Thosewordsmightaswellhavebeentornfromadenialistinstructionmanual:change isdangerous; authorities arenot tobe trusted; thepresent “posture”ofthe scientific community has to be one of collusion and conspiracy. Mostimportant, thefactsareinsideout,because“discounting”thegreatadvancesofmolecularbiologyisexactlywhattheauthorofthatletterdid.

Scientists should do a better job of explaining the nature and the potentialimpactof theirwork (andsoshould thoseofuswhowriteabout science).Weneed to have open debates—on national television and guided by people likePresidentObama—abouthowtoengagethefutureandmakesenseofboth thepossibilitiesandrisksthatlieahead.Educationwillhavetoimproveaswell.Buttocallthegroupthathasdecodedthelanguageoflife,andhasalreadybeguntouse that information to treat and prevent scores of diseases, “the mostirresponsiblescientistsinthehistoryoftheworld”isspecious.Withoutthetoolsof molecular biology, we wouldn’t have a clue how the AIDS virus works.Insteadofhavingkilledtwenty-fivemillionpeopleinthetwentiethcenturyandinfectedanevenlargernumber, thetollofsuchanunimpededepidemicwouldhavealreadynumberedinthebillions.

No achievement of modern technology, not even nuclear power, has beenmorebitterlydisputedthanourabilitytoalterthegeneticcompositionoffoodortocreateartificialproductsfromhumancells.Yetnodiscoveryismorelikelytoprovidesolutionstothegreatestthreattheearthhaseverfaced:therapidpaceofglobalwarming.Ifwedonotdevelopcleantechnologiessoon,ourspecieswon’tsurvive.

Andwearedoingjustthat.Researchersthroughoutthecountryandtheworldarefabricatingsyntheticmoleculesthatmimicthosefoundinnature.Tenyearsagotherewasn’tevenenoughbasicknowledgetoattemptthiskindofresearch.These companies are not interested inmaking fake corn or pursuing effectivewaystomanufacturefertilizerforfarmerswhoreallydon’tneedit.Instead,theyseek to fuelcarsandpower factorieswithout releasinggreenhousegases.Thatwouldnotonlykeepusfromblanketingtheearthincarbondioxide,butwouldgoalongwaytowardcounteractingthefoolishandexpedientdecisiontomakefuel fromthecorn,sugar,andsoybeans that the rapidlygrowingpopulationoftheworldsodesperatelyneedstoeat.

Toaccomplishanyofthiswewillhavetorecognizedenialismwhenweseeit.As a society and as individuals, thatmeans asking tough, skeptical questions,then demanding answers supported by compelling evidence. When thegovernment,acompany,oranyothergroupmakesaclaim,weneedtoscrutinizethat claimwith care but without passion.Most importantly, wemust learn toacceptdatathathasbeenproperlyjudgedandverified—nomatterwhatitsays,orhowmuchwemighthavewishedthatitpointedinanotherdirection.

Iwonder,astheicesheetinGreenlanddisappears,theseasrise,andoursenseof planetary foreboding grows, will denialists consider the geneticallyengineered organisms that propel our cars and sustain our factories as acontinuationofwhatLordMelchettdescribedasawaragainstnature?Orwillthey see them forwhat theyare, the latest—andgrandest—stage inourmarchtowardhumanenrichment?

1

VioxxandtheFearofScience

Thedailyworkofsciencecanberepetitiveanddreary.Eventhemosttalentedresearchers spend the bulk of their lives bathed in the fluorescent light of thelaboratory,hoveringoverabench,staringatslides,andhuntingformeaningfulpatternsinstringsofnumbers.Still,likemanyofhiscolleagues,thecardiologistEric Topol had always dreamed that one day he might have his “eureka”moment—a flash of insight that would permit him to see clearly what otherscouldn’tseeatall. In2001,Topolgothiswish—butnot inawayhehadeverimagined;therewerenoshoutsofjoy,noelationorchampagne,nothingofthekind.“Iwasjustsad,”hesaid,rememberingthemomentwhenherealizedthatoneof thenation’smostpopularnewmedicationswaskillingpeople. “Then Iwasangry,andeventuallyIbecameoutraged.”

At the time, Topol was chairman of the Cleveland Clinic’s cardiologydepartment,whichhemorethananyotherphysicianhadtransformedintooneofthefinestinAmericanmedicine.Hisresearchintohowtopreventandtreatheartattacks was highly valued and constantly cited. As perhaps the clinic’s mostvisible face, Topol was already prominent. But it was his role in helping toexpose the grave risks posed by the anti-inflammatory drugVioxx that turnedhimintooneof thecountry’sbest-knowndoctors. Italsomadehimoneof themostcontroversial, inpartbecausehe repeatedly stressedhow little regard theFoodandDrugAdministrationseemed tohave for thehundredsofmillionsofpeopleithadbeencreatedtoprotect.

Thecloakofinvincibilityhadlongbeforebeenstrippedfromanygovernmentagency, replaced by the constants of doubt and denial; politicians, scientists,doctors,andlawyersareheldinloweresteemtodaythanatanytimeindecades.Yet no previous incident—not the explosion of the space shuttleChallenger,Ford’swillingnesstodumpadeathtrapcalledthePintoontheAmericanpublic,noteventhenuclearaccidentatThreeMileIsland—demonstratesmorevividlywhythatmistrusthasbecomesopervasive.

VioxxwasintroducedbyMerckwithgreatenthusiasmin1999,oneofanewclassofdrugscalledcox-2inhibitors,whichweredesignedtointerferewithanenzyme called cyclooxygenase-2, which, among more beneficial duties,produceschemicalsthatcauseinflammation(andpain).BeforeVioxxappeared,

hundredsofthousandsofpeoplewhosufferedthedebilitatingeffectsofarthritisandotherchronicailmentsfacedanunpleasantchoiceeveryday:theycouldtakedrugs like aspirin orAdvil, or they could endure agony in order to avoid thebleedingulcersandotherseriousstomachcomplicationsthosedrugscancause.Vioxxwas referred to as “super aspirin,”which didn’t seem likemuch of anexaggeration: in early studies it offered better pain relief than any traditionalremedy,andwasfarlesslikelytodisturbthestomach.Thedrugquicklycametobeseenbythosewhoneededitmostasakindofmagicpotion,onethatonlythetools ofmodernmedicine could have produced. Driven in part by one of themost aggressive advertising campaigns in medical history, more than twentymillionAmericanstookVioxxatonetimeoranother.In2003alone,Mercksoldmorethan$2.5billionworthofthedrug.

Topol,whosufferedfromanarthriticknee,lovedVioxx.Evennowhereadilyatteststoitseffectiveness.“Nothingworkedaswellformebeforeorsince,”hesaid.“Vioxxtrulydulledthepain.”OneFebruarymorningin2001,though,henoticed a report that struck him as odd. Topol had been invited to deliver alectureaboutthefutureofcardiaccaretoagatheringattheMedicalCollegeofGeorgia inAugusta.Overbreakfastathishotel,hestarted topage through thecopyofUSATodaythathefoundonhisdoorstep.Oneparticularstoryleaptoutathim.“ItwasaboutVioxx,”hesaid,“andthisstudy,”calledVIGOR—VioxxGastrointestinal Outcomes Research—“which was intended to determinewhether Vioxx really was easier on the stomach than other, less powerfulnonsteroidalanti-inflammatorymedication.”

Between January and July 1999, researchers had followed eight thousandpatients with rheumatoid arthritis. Half took Vioxx to control their pain; theotherhalftooknaproxen,whichissoldoverthecounterasAleve.(Itwasalargeand fairly conventional randomly assigned, double-blind study—which meantthat the patients had no idea which of the two drugs they were taking, andneither did their doctors.) The first time the safety committee assigned tomonitor the study looked at the data, it found exactly what one might haveexpected: people in theVioxxgroupwere less likely to experience significantstomachdistressthanthosewhotookAleve.

Thetrialalsoshowedsomethingthathadnotbeenanticipated,andthenewstherewasdisturbing:participantswhoalreadysufferedfromheartdiseasewerefarmorelikelytohaveheartattacksiftakingVioxxthaniftheyhadbeengivenAleve.Nobodywassurewhy,andbecauseMerckhadneverexpressedconcernabout the drug’s effect on the heart, therewere no cardiologists on the safety

committee (whichwas not unusual since thatwasn’t the purpose of the trial).Scientistswonderedifthedifferencemighthavebeenduetothefactthatpeoplein the trialwere required to stop taking aspirin, since it can lower the risk ofheart attack or stroke. It was also possible that something previouslyunrecognizedaboutthechemicalcompositionofAleveitselfhelpedprotectthecardiovascularsystem.(Thatwouldhaveprovidedabenignexplanationforthediffering rate of heart attacks, andMerck endorsed the hypothesis with greatenthusiasm.)

“IwasnotadrugsafetyexpertandIneverevenhadanyinterestintheissue,”Topol said. “Myprincipal researchwas inheartdiseaseandheart attacks, andthatdatesbackmorethantwentyyears.”Topolhadmadeanameforhimselfasa postdoctoral researcher at theUniversity of California at San Francisco.HethentookajobatJohnsHopkinsUniversity,wherehebecamethefirstphysiciantotreatheartattackswiththepowerfulclot-bustingagentknownastPA;healsodirected a pivotal study that compared the efficacy of that drugwith an oldertreatment,streptokinase,insavinglives.In1991,TopolmovedtotheClevelandClinic,whereforthenextfifteenyearsheservedaschairmanofthedepartmentofcardiovascularmedicine.

What Topol saw inUSA Today thatmorning inAugustamade no sense tohim.“Whywouldanewanti-inflammatoryagentprove lessprotectiveagainstheartattacksthantheoneyoucanbuyatapharmacywithnoprescription?”hewondered.Yet,thenewspaperreportsuggestedthatpatientstakingVioxxweremorethantwiceaslikelytohaveheartattacksasthosetakingAleve.Forpeoplewith a history of heart disease, the risk was far higher. (Risk numbers don’tmeanmuchunless theyareaccompaniedby someassessmentof the statisticalprobability that those risks could occur by chance. In this study,which at thetimewasthelargesteverconductedusingVioxx,thatnumberwas.002—twoinone thousand. In other words, if the study were repeated a thousand times,resultslikethosewouldappearbychancetwice.)“Ithought,thatisinteresting,they are saying a highly touted experimental drugwasnot as good as theoneyou buy in the drugstore,” Topol said. “They weren’t saying anything aboutVioxxcausingheartattacks,justthatAleveseemedbetteratpreventingthem.”

The distinctionwas crucial because after the data wasmade public,Merckasserted,asitwouldforthefollowingthreeyears,thatVioxxposednoincreasedriskofheartattackorstroke.“Itdidseemstrange,”Topolsaid,“butIdidn’tgiveitalotofthought.Afterall,that’swhyyoudoclinicalstudies—andsoitlookedlikemaybeAlevehadsomeprotectiveeffectwedidn’tknowabout.Surprising

asthatwouldhavebeen,itcertainlywasn’tbeyondtherealmofpossibility.Still,itwasn’tmythingandIdidn’tdwellonit.”

Topol delivered his address and returned to Cleveland, where DebabrataMukherjee—“one of my fellows and a brilliant scientist”—had also seen thereportwhichshowedthatpeopleusingVioxxwerefarmorelikelytosufferfromheart attacks than those taking over-the-counter pain medication. Mukherjeebecameintenselycuriousaboutthereasonsforsuchsurprisingresults.Hedoveinto the data that Merck had been required to provide the FDA, and soonrealized that the initial report failed to include all the essential information atMerck’sdisposal. (Nor couldhe find any scientific support for the company’ssuggestionthattheresultsreflectedAleve’spreviouslyunrecognizedprotectivepowersratherthanthedangersofVioxx.)

“DebhadgoneontotheFDAWebsitetolookatallthedatapresentedintheadvisorycommitteemeetings—something,by theway, that Ihadneverdone,”Topolsaid,shakinghisheadwithawansmileofadmirationforthediligenceofhis young colleague. Vioxx was not the only cox-2 inhibitor on the market;Celebrex,madebyPfizer,was introduced that sameyear, andBextrahadalsorecently been approved by the FDA. But each drug functioned in a slightlydifferentway and the numbers forVioxxweremore disturbing than those foreitherof theothers.Mukherjee toldTopol that therewasa“realproblemwithVioxxinparticular,”herecalled.“IhadmanyotherthingsonmymindsoIsaid,‘Nahhh, it’snot thatbigadeal.Wehavedifferentworktodo.Let’snotwasteourtimeonthis.’Debwouldn’thaveit.HeinsistedthatIlookatthedatawithhim,absolutelyinsisted.SoIdid.”

Once Topol had the statistics in front of him, he saw whyMukherjee hadbecome so agitated. “The evidence was right there,” he said. “I still cannotbelieve that nobody else had seen it. That’swhen I began to understandwhatwasreallygoingon in thatUSAToday story. It justclicked: thecompanywasattributing these miraculous functions to Aleve instead of investigating thepotentialdangersoftheirnewdrug.Theywereplayinggames:whattheysaidatthetimedidn’tseemtobeanoutrightlie,butitalsowasn’tthetruththatpeopleneededtoknow.Isaidlet’swritethisup.Afterall,thesedatamattered.Itwasn’teven a heart study, itwas supposed to assess stomach complications, but youcan’t just shy away from information like that. Therewere toomany lives atstake.”

TopolandMukherjeequicklyputapapertogether,alongwithStevenNissen,another prominent cardiologist at the Cleveland Clinic, who had attended the

advisory meeting where Vioxx was approved. “Deb drove the research and Igaveitaframework,”Topolsaid.Thepaperwasthefirst independentanalysistoincludeallthedatatheFDAhadobtainedfromtheVIGORstudy,anditcastserious doubt on the supposition that naproxen offered special cardiovascularprotection. The study was published in the Journal of the American MedicalAssociation later thatyear.Thethreestoppedshortofcallingforamoratoriumon theuseofVioxx—thedataat theirdisposalwerenotconclusiveenough towarrantsuchasuggestion.However,theydidwarndoctorstotakespecialcarewhen prescribing the drug to people with heart disease. In their review, theauthorsstressed thatVioxxandothercox-2 inhibitorscouldcauseserioussideeffects, and that a broader examination of their impact would be essential.“Given the remarkable exposure and popularity of this new class ofmedications,” they wrote, “we believe that it is mandatory to conduct a trialspecificallyassessingcardiovascularriskandbenefitoftheseagents.Untilthen,weurgecautioninprescribingtheseagentstopatientsatriskforcardiovascularmorbidity.”

ERICTOPOLISTANNEDand trim,aganglyman inhis fiftieswithanovalface,grayinghairthathasbeguntothin,andthetypeofrelaxedaffectthatonlysomeonewhomovesfromaclimatelikeCleveland’stobalmySanDiegocouldcultivate. Today, Topol has an entirely new kind of job: he is professor ofgenomics and the director of the Scripps Translational Science Institute in LaJolla.Scripps,oneof thenation’s largestbiomedical researchorganizations, iseager to apply the emerging science of genomics—the information containedwithin our genes—to clinical medicine. Topol believes genetics will soonprovidetheknowledgeweneedtomakesubstantialreductionsintheincidenceof heart disease. And that knowledge, of genetic predispositions and theirimplicationsforindividuals,isincreasingrapidly.Naturally,anyreductionintherateofheartdisease,whichkillsatleastamillionAmericanseveryyear,wouldhaveaprofoundimpactonpublichealth.Thefieldisyoung,andithasn’tbeenlongsinceScrippsdecidedtoinvestheavilyinit.WhenIvisitedLaJollainthespringof2008,theinstitute’sbuildingwasonlypartiallyfinished.Severalfloorsconsisted of little more than concrete shells and plastic sheeting. The setting,though, was spectacular: Topol’s office looks out onto the Torrey Pines GolfCourse, and beyond that, the Pacific Ocean. As I watched from his office

window,dozensofpeoplefloatedbyonparasailsbeforegentlysettingdownintheshimmeringgreensea.

IfTopol’slifeseemsenviable,ithasn’tbeenthatwayforlong.HispersistentcriticismofMerck and, by implication, of theFDA, lasted threeyears, duringwhichtimeVioxxkilledthousandsofpeople.Topolfoundhimselfanoutcastinhis own profession, shunned for his warnings and eventually driven from thedepartment he made famous. “There were years of sleepless nights, ofbitterness,” he said, speaking almost as if he were describing the ordeal ofanotherperson.“YearsduringwhichIallowedmyselftowonderwhatonearthwerewedoingtopeopleinthenameofscience.”HecametorealizethatMerckpossesseddatathatshouldhaveledthecompanytoquestionVioxx’ssafetylongbeforeitwasapproved.

Research published in the Britishmedical journal theLancet has estimatedthat88,000Americanshadheartattacksafter takingVioxx,andthat38,000ofthemdied.IntestimonybeforeCongress,DavidGraham,theFDA’sseniordrugsafety researcher, said the death toll may have reached as high as 55,000—almostexactlythenumberofAmericansoldierskilledintheVietnamWar.(Wewillneverknowforsure; thereisnoprecisewaytoaccountforthenumberofdeathscausedbyadruglikeVioxx,whichwastakenbymillionsofpeople.It’seasy tonoticean increasedrateofheartattacks ina largegroup.Provingwithcertaintythespecificcauseofanyoneofthemisnearlyimpossible.)

“ThiswasoneofthemostremarkablebreachesoftrustinAmericanscientifichistory,”Topolsaid.Hestoodupandpouredcoffee.“Ithasbeenyearsnowandeven todaynothing fundamentalhasoccurred toensure that thiswon’thappenagain.Thatiswhatamazesme.Itisasifwetooknothingfromthistragedybutfearandasensethatthosescientistswereliars.Oneofthemostimportantdrugsof our time was released without the proper safety checks, and after thecompany’s own scientists wondered in writing whether it would kill people.When Americans say they are skittish about the drug system and aboutconventionalmedicineitself,cananyonereallybesurprised?”

TherehavebeenaraftofstudiesreleasedaboutVioxx—fromtheGovernmentAccountabilityOffice,theInstituteofMedicine,andmanyprivateorganizations;eventually both the Senate Finance Committee and the House Committee onGovernment Reform held hearings. Every report, andmuch of the testimony,described the FDA’s bureaucratic inefficiencies, its reluctance to takecontroversial positions, and Merck’s willingness to exploit those weaknesses.“The FDA set up an internal safety auditing group for drugs going onto the

market,”Topolsaid.“Theyhaverespondedbyapprovingfewernewdrugsthanatanytimeintheirhistory.Theorganizationisjustparalyzed.”

By the end of themillennium, Americans had come to assume that a drugapproved by the federal government was a drug they could swallow withoutwondering whether it would kill them. Vioxx changed all that. Thousands oflawsuits later, in2007, the companyplacednearly$5billion into a settlementfund. That deposit permittedMerck to avoid nearly fifty thousand lawsuits. Italsobroughtanendtohundredsofclass-actioncasesfiledonbehalfofdeadorinjuredVioxxusers,which,hadtheysucceeded,couldwellhaveputMerckoutof business. The settlement was the largest ever made by a pharmaceuticalcompany.Aspartofthedeal,Merckwasneverforcedtoadmitfaultinasingleoneofthosedeaths.

The Vioxx episode wove strands of fear and uncertainty together with aninchoatesense,sharedbylargeswathsofAmericansociety,thatwearecedingcontrolofourlivestotechnology,particularlytohighlysophisticatedtechnologywe can barely understand, and that we are doing so at a speed that seems toaccelerateeveryyear.Denialismisatleastpartlyadefenseagainstthatsenseofhelplessness.Whatperson,afterwatchingVioxxkillherhusband,wouldn’tsaynotothenextwonderdrug?Thestoryline—apredatorydrugcompanylustingforprofits—isnot entirelynew.Thenotionof technologyas a force thatdoesmore harm than good, and of scientists toyingwith human life, dates back atleast to Shelley and Goethe. Rousseau, the first Romantic, longed for theinnocence and supposed simplicity of nature. He was convinced that sciencewouldhaveaperniciouseffectonsociety,promisingmorethanitcouldpossiblydeliver.G.K.Chesterton,inhisbookEugenicsandOtherEvils,wasevenmoredirect,referringtoorganizedscienceas“governmenttyranny.”

Itwouldbehardtofindmanyexamplesinthepastfourcenturiesofscientistsacting together to threaten humanity. Only a few are necessary, though, andtherehavebeenenoughdarkmomentsalongtheremarkablemarchofprogressto generate anxiety and feed denial. Most of those moments were caused byerror,not evil.Yes, in1970 theFordMotorCompany,probably thedefinitiveindustrialsymboloftwentieth-centuryAmerica,introducedacar,thePinto,thatits engineers knew was likely to kill passengers. (Before the Pinto wasintroduced, in what may well stand out as the most remarkable memo in thehistoryofengineering,Fordstatisticiansarguedthatthe$11costoffixingeachcar addedup tomore than twice the amountofmoney—at$200,000perburndeathand$67,000foreachseriousinjury—thattheywouldhavehadtopayin

lawsuitsorsettlements.)

Moreoften,therearesimplerreasonstoquestiontheprimacyofscienceandtechnology.Inthenameofimprovingourlives,someofthesmartestpeopleonearthhavemanagedtoruinquiteafewofthem.DES,ordiethylstilbestrol,wasthefirstsyntheticestrogen.Itwascheap,easytoproduce,andunusuallypotent.First prescribed in 1938, DES was given to women who had experiencedmiscarriagesorprematuredeliveries.Despitemixedresultsinthelaboratory,thedrug was considered safe and effective both for a pregnant woman and herdevelopingfetus.Itwasn’t.IntheUnitedStates,asmanyastenmillionpeoplewere exposed to DES by 1971, when it was pulled from the market. “DESDaughters,”astheycametobeknown,areatincreasedriskforseveraltypesofcancer, as well as structural abnormalities of the reproductive tract,complicationswithpregnancy,andinfertility.

Fearbuilds farmoreeasily than itdissipates.RonaldReaganonce famouslyclaimed that the“ninemost terrifyingwords in theEnglish languageare: ‘I’mfrom thegovernment and I’mhere tohelp.’ ” If anyoneneededa reminderofhowfarourfaithinsciencehadfallenbytheendofthetwentiethcentury,Vioxxdemonstrated that fiveotherwords couldprove just as frightening: “Trustme,I’mascientist.”Itwasquiteacrash.PharmaceuticalcompanieswereamongthemosthighlyvaluedinstitutionsinAmericaafterWorldWarII,andit’snothardto seewhy.They introduced the corevaluesof consumer culture toAmericanmedicine.DrugsbecamelikeeverythingelseMadeinAmerica:productsmeanttoeaselifeandsolveproblems.

The flood of new antibiotics and the rapid development of vaccinations foreverythingfromdiphtheriatopoliohelpeddefinethespiritofthecountrywithasingle word: optimism. America was a can-do nation and it possessedtechnology thatwould solve theworld’s problems. From infectious disease tocancer,andfrompollutiontohunger,wewouldovercomeitall.Nylon,Lycra,Teflon, Kevlar, and Mylar, for example—all made by DuPont—were alltriumphs of ease and modernity. We could fix whatever was broken, curewhateverailedus,andmake lifeeasier foreveryonealong theway.Today thewords“DuPont,”“Merck,”and“Monsanto”areoftenusedasepithets,andtheycompete with tobacco companies for the role of the most loathed Americancorporations. Conventional medicine and technology itself, despite their clearratesofsuccess,seemtomanypeopleaslikelytocausedangerastoenhanceourlives.

InaHarrispollofattitudestowardcorporateAmericapublishedin2008,just

27 percent of respondents said they “somewhat or strongly” trusted thepharmaceutical industry. More than half described their views as firmlynegative, which places Big Pharma slightly below Big Oil, and a bit abovetobaccocompanies, intheesteemoftheaverageAmerican.ThefiguresfortheFDAwereonlymarginallyhigher.Whatwaswrittenwithsincerityonlyafewdecadesago isnowplayedstrictly for laughs: in2006, the satiricalnewspaperthe Onion ran a story in its “Science and Technology” section under thisheadline: “Wonder Drug Inspires Deep, Unwavering Love of PharmaceuticalCompanies.” The year before, a film version of John le Carré’s novel TheConstant Gardener was released. Like the book, it portrayed an internationalpharmaceuticalconglomerateasavariciousandcartoonishlyevil.Theplotwasludicrousandappealedtotheworstpossiblestereotypesofmindlesscapitalism.Butpeopleateitup.

Vioxx and other preventable catastrophes ensured that they would.Corporations,wrapping themselves in themantle of progress but all too oftenpropelledbygreed,havedonemore than religionor evenLuddism to inflamedenialists and raise doubts about the objectivity of science. In 2008, reportssurfaced that formore than a year,Merck and Schering-Plough concealed thefactthattheirjointlymarketedcholesteroldrug,Vytorin,wasnomoreeffectivethangenericstatinscostinglessthanhalfasmuch.Nonetheless, thecompaniesstillspentmorethan$100millionduringthattimetoadvertisethedrug’sspecialqualities.

News like that has become routine. In early 2009, the British companyAstraZenecawasfoundtohavesomehowmislaidunfavorablestudiesabout itsantipsychotic drug Seroquel. At about the same time,more than one hundredstudents at theHarvardMedicalSchool publicly questioned the ethics of theirprofessors, some of whom are frequently paid as consultants by thepharmaceutical companies whose products they are supposed to judge. Thesituation got so bad that the Institute ofMedicine, the branch of theNationalAcademy of Sciences charged with providing advice on critical issues ofmedical research, denounced physicians who accepted money from drugcompanies. “It is time for medical schools to end a number of long-acceptedrelationshipsandpracticesthatcreateconflictsofinterest,threatentheintegrityof their missions and their reputations, and put public trust in jeopardy,” theIOM concluded in a report. Just two weeks later, the Scientist revealed thatMerckhadpublishedajournalfilledwithfavorablearticlesaboutmorethanoneofthecompany’sdrugs,withouteverbotheringtodisclosethatthepublication,the Australasian Journal of Bone and Joint Medicine, was sponsored by the

companyitself.“Tothejaundicedeye,[thejournal]mightbedetectedforwhatitis:marketing,” PublicCitizen’s PeterLurie said. “Many doctorswould fail toidentifythatandmightbeinfluencedbywhattheyread.”

If all that wasn’t sufficiently damning, the Baystate Medical Center inSpringfield,Massachusetts, revealedthatScottS.Reuben, itshighlyinfluentialformerphysicianinchargeofacutepaintreatment,fabricateddatafromtwenty-onemedicalstudies thatclaimedtoshowthebenefitsofpainkillers likeVioxxandCelebrex.“Thepharmasareinbigtroubleintermsofcredibility,”saidRobFrankel, a brand consultant who focuses on medical industries. “They’re justaboveCongressandused-carsalesmen.”

THIRTY YEARS AGO NOBODY discussed the principal motive behindscientificresearch:nobodyneededto.Itwasaquestforknowledge.Today,thedefault assumption is that moneymatters most of all, and people tend to seescience through the prismof commerce.At least untilViagrawas introduced,andendorsedontelevisionbyBobDole,aformercandidateforthepresidency,nodrughadbeenmarketedmoresuccessfullythanVioxx.In2000,theyearafterit first appeared, Merck spent $160 million advertising their painkiller. Theywere able todo that thanks to the advent, just threeyearsbefore, of direct-to-consumeradvertising.Onlytwocountriesallowedpharmaceuticalcompaniestoadvertiseprescriptiondrugsdirectlytoconsumers:NewZealandandtheUnitedStates.

InAmerica,suchadsvirtuallyalwaysconsistofglossypromotionalmaterialsused to announce major medical advances. (The federal government requiresthat they include tiny print “information” presented in medical jargon, themeaning of which, for most consumers, is nearly impossible to understand.)These advertisements are not really intended to educate patients, nor to helpthem become more sophisticated about their own health. They are purely anattempt to get doctors to fillmore prescriptions, and theyworkwith stunningregularity.“Blockbuster”drugslikeVioxx,Viagra,andthecholesterolmedicineLipitorcanbecomeamultinationalcorporation’scentralsourceofincome.

Our regulatory system encourages companies to invest inmarketing, not inresearch: in theUnitedStates, a newdrug typically takes a decade to develop

and costs hundreds ofmillions of dollars.With stakes that high, and lawsuitswaiting foranycompany thatcommitseven the smallest error,pharmaceuticalfirms are far more likely to profit from aggressive sales of products that arealready available than from introducing anything new. One reason the adssucceedisthatitisnearlyimpossibletospendadaywithoutseeingoneormoremajordrugs advertisedon television. (Another reason is the amountofmoneycompanies spend. The marketing budget for AstraZeneca’s heartburn pillNexium, a sure moneymaker, is bigger than the comparable budget forBudweiserbeer.)

RheumatoidarthritisafflictsmorethantwomillionAmericans,anditcanbedevastating. Many of those people were overjoyed when advertisements forVioxxbeganblanketingtheairwavesin1999.Suddenly,menwhocouldn’tbendoverweretyingtheirshoesagain,walkingdogs,andregaininglivesthatslowlyhadbeenconsumedbypain.DorothyHamillskatedacrossmillionsoftelevisionscreens on behalf ofVioxx, overcoming arthritis andmovingwith the nimblecertaintyofateenagerattheOlympics.“Peopledancinginthestreets,twirlingtheirpartnersinjoy,”Topolsaid.“That’sallanybodyeversaw.”GotalktoyourdoctoraboutVioxx,theadwouldsay.Andpeopledid,bythemillions.In1996,American pharmaceutical companies spent $11.4 billion on directadvertisements; by 2005 the figure was more than $29 billion. Doctors wereoverwhelmed with requests, and for the most part were only too happy tocomply, writing nearly one hundred million prescriptions for Vioxx alonebetween1999and2004.

The words “ask your doctor” have become code for “change yourprescription.”Often,whatpeopleendedupwithwasnobetterthanthecheaperandmorereadilyavailabledrugstheyweretakinginthefirstplace.Andjustasoften,thedrugsforsaleweresonewtothemarketthattheirsafetywashardtogauge. “Americansmust face an inconvenient truth about drug safety,”HenryWaxman, theveteranCaliforniacongressman,saidwhenaskedhispositiononthe impact of these advertisements. Waxman is perhaps the most astutecongressionalobserverofAmericanmedicine,andsincetheelectionofBarackObama, in his new role as chairman of the House Energy and CommerceCommittee,hemayalsobethemostpowerful.“Thetruthisthatweinevitablyallowdrugson themarketwhose risksarenot fullyknown,”hesaid. In2006,the Institute ofMedicine suggested amoratorium on such advertising, a briefpausebeforepermittingcompanieslikeMercktohawkpowerfulchemicalsasiftheywereCheeriosorvacuumcleaners.ThatwouldcertainlyhavesavedmanyoftheliveslosttoVioxx.

People tendtoseewhat theyare lookingfor,however,andtomillions,painrelief was all that mattered. When it comes to getting a message across, theSuperBowl,whereadsfordrugs likeVioxxandViagrahavebeenubiquitous,will always matter more than theNew England Journal of Medicine. In thisatmosphere, Eric Topol was largely on his own, and he became the target ofMerck’sfullestfury.“Merckwentaftermewithalltheyhad,”hetoldme.TopolhadcollaboratedwithMerckoften—at the timeofhisclashwith thecompanyoverVioxx hewas actually running one of its trials, for the anti-platelet drugAggrastat. Like most people in his profession, Topol considered Merck aremarkable place. During one stretch beginning in 1987, it was named byFortunemagazine for seven straight years as themost admired corporation inAmerica,arecordthatremainsunmatched.Merckseemedtoprovethatprofitsand decency were not incompatible. “I was in no way predisposed to havenegativefeelingstowardMerck,”Topolsaid.“Infactitwasquitethecontrary.”None of that mattered, though, because they came after him with a cleaver.“Theysaidmyfirstpaperwas‘datadredging,’”bywhichtheymeantapedanticreportfullofnumbersthatprovednothing.“Theytoldanyonewhowouldlistenthat Ihadbeena fine researcheruntil theday thatpaperwaspublished,butatthatmomentIhadsuddenlylost it.Andat thetimeallIhadsaidwas,‘Waitaminute,thereneedstobesomemorestudyhere.’”

By theendof2001,however,Topolhadmovedon.Hehadbegun to focusprimarilyongenomicsandhis researchswitched from treatingheartattacks topreventingthem.OtherswerestudyingwhetherVioxxincreasedtheriskofheartattacks,andhe felthehaddoneallhecould toaddress the issue.At the time,TopolhadnoideahowdivisiveVioxxhadbecomeatMerckitself.Itturnedoutthatscientiststherehadworriedasearlyas1996abouttheeffectthedrugwouldhaveonthecardiovascularsystem.Thereasonforthatconcernwasclear.Vioxxaltered the ratio of two crucial substances, the hormone prostacyclin and amolecule called thromboxane,which together help balance blood flow and itsabilitytoclotproperly.Suppressingprostacyclinreducesinflammationandpain,and that made Vioxx work. Suppress it too powerfully, however, andthromboxanecancauseincreasedbloodpressureandtoomuchclotting,eitherofwhichcanleadtoheartattacks.By2002,Merckdecidedtoembarkonamajorstudy of the cardiovascular risks caused by Vioxx—just as Topol and hiscolleagues had suggested. The trial would have produced useful data fairlyrapidly,butjustbeforeitbegan,thecompanyabruptlyscuttledtheproject.Intheend,Mercknevermade any significant effort to assess the cardiovascular riskposedbyitsmostsuccessfulproduct.

Instead,thecompanyissueda“CardiovascularCard”tosalesrepresentatives.More than three thousandmembers of the sales forcewere instructed to referdoctors with questions to the card, which claimed—falsely—that Vioxx waseighttoeleventimessaferthanothersimilarpainkillers.Thesalesrepsweretoldtoproducethecardonlywhenallelsehadfailed,tohelp“physiciansinresponseto their questions regarding the cardiovascular effects of Vioxx.” The FDA,realizingthatdoctorsneededtounderstandthegravityofthefindingsfromtheVIGOR trial, issued a strongly worded letter instructingMerck to correct therecord. “Your claim in the press release that Vioxx has a ‘favorablecardiovascular safety profile,’” the letter read in part, “is simplyincomprehensible, given the rate of heart attack and serious cardiovascularevents compared to naproxen.” The company reacted swiftly: “Do not initiatediscussionsoftheFDAarthritiscommittee...ortheresultsofthe...VIGORstudy,” the sales force was told. If doctors proved too querulous, the Merckrepresentativeswereinstructedtorespondbysaying,“Icannotdiscussthestudywithyou.”

In the summer of 2004, the Lancet asked Topol and the gastroenterologistGaryW.Falk,acolleagueofTopol’sfromtheClevelandClinic,tosumupthestate of knowledge about Vioxx and similar drugs known, as a class, by thenamecoxibs.TheireditorialwaspublishedthatAugustunderthetitle“ACoxibaDayWon’tKeeptheDoctorAway.Topolwastakenabackwhenherealizedhow little had changed. “Itwas amazing to see that nothinghadbeendone inthree years,” he recalled. “It was not even clear that Vioxx protected thestomach.Itcostfourdollarsadayforthesedarnpills.”OnSeptember29ofthatyear,TopolhappenedtodinewithRoyVagelos,Merck’smuch-admiredformerchiefexecutive,whohadbeenretiredfornearlyadecade.TopolwasvisitingaNew York-based biopharmaceutical company called Regeneron whose boardVagelos chairs. There were few people in medicine for whom Topol had asmuchrespect.“WestartedtalkingaboutVioxx,”hesaid.“ItwasthefirsttimeIeverspoketoRoyaboutit.Irememberthatconversationwell:itwasatRuth’sChris SteakHouse inWestchester. Roywent on for awhile.Hewas entirelyopposedtotheMerckapproachtoVioxx.Andhedidn’tmincewords.”

The followingmorning aMerck cardiologist called Topol and told him thecompanywas removingVioxx from themarket.Another trial had shown thatpatients taking thedrugwereat increased riskofheart attackand stroke.Thatstudy, APPROVe, began in 2000 as an attempt to discover whether Vioxxhelpedpreventtherecurrenceofcolonpolyps.Itdidn’t.“Iwasshocked,”Topolsaid.“ButIthoughtthatitwasresponsibleforthemtopullit.AndSteveNissen

camedowntomyoffice,alsoverypleased,andsaid,‘Isn’tthatgreat?Theyarepullingthedrug.’Weboththoughtitwastherightthingtodo.”

ForTopol,thatcouldwellhavebeenhowthestoryended.ButMerckbegantomountapressoffensive.Themessagenevervaried:Merckputpatientsfirst.“EverythingtheyhadeverdoneinthecourseofVioxxwasputtingpatientsfirst.All thedatawasout there,”Topolsaid, still stunnedby thebrazenpublic lies.“This just wasn’t true. It wasn’t right. I called and tried to speak to RayGilmartin”—Merck’schiefexecutive.“Neitherhenoranyoneelsereturnedmycalls.”(Thatitselfwassignificant:afterall,Topolranoneofthemostimportantcardiologydepartmentsinthecountry;hewasalsothedirectorofaMerckdrugtrial.) “This was a breach of trust that really rocked the faith people have ininstitutions like those,” Topol said. “We are talking about thousands of heartattacks. There were simply gross discrepancies in what they presented to theFDAandwhatwaspublishedinjournals.Itookthemon.Ihadto.”

Thatweek,Topolwroteanop-edpiecefortheNewYorkTimes.Hecalledit“Vioxx Vanished.” The Times had a better idea: “Good Riddance to a BadDrug.”NotingthatVioxxincreasedtheriskofheartattacksandstrokes,Topolwrote that “our twomost common deadly diseases should not be caused by adrug.”He also published a column in theNewEngland Journal ofMedicine,called “Failing the Public Health”: “The senior executives at Merck and theleadership at the FDA,” he wrote, “share responsibility for not having takenappropriateactionandnot recognizing that theyareaccountable for thepublichealth.”

OnDecember3,2005,inavideotapeddepositionpresentedundersubpeonaatoneof themany trials following the recall,Topol argued thatVioxxposed an“extraordinary risk.” A colleague from the Cleveland Clinic, Richard Rudick,told him that Gilmartin, the Merck CEO, had become infuriated by Topol’spublicattacksandhadcomplainedbitterlytotheclinic’sboardaboutthearticlesintheTimesandtheNewEnglandJournalofMedicine.“WhathasMerckeverdonetotheclinictowarrantthis?”Gilmartinasked.

Twodaysafterthattestimony,Topolreceivedanearlycalltellinghimnottoattend an 8 a.m. meeting of the board of governors. “My position—chiefacademic officer—had been abolished. I was also removed as provost of themedicalschoolIfounded.”TheclinicreleasedastatementsayingthattherewasnoconnectionbetweenTopol’sVioxxtestimonyandhissuddendemotion,afterfifteenyears,fromoneofmedicine’smostprominentpositions.Aspokeswomanforthecliniccalleditasimplereorganization.Thetiming,sheassuredreporters,

wasacoincidence.

DID THE RECALL of Vioxx, or any other single event, cause millions ofAmericans to question the value of science as reflexively as they had onceembracedit?Ofcoursenot.Overthedecades,asourknowledgeofthephysicalworldhasgrown,wehavealsoenduredthesteadydripofdoubt—aboutboththedefinitionofprogressandwhetherthepursuitofsciencewillalwaysdriveusinthe direction we want to go. A market disaster like Vioxx, whether throughmalice,greed,orsimplyerror,presenteddenialistswitharareopportunity:theirclaimsofconspiracyactuallycametrue.Morethanthat,inpursuitofprofits,itseemedasifamuch-admiredcorporationhadcompletelyignoredtheinterestsofitscustomers.

Itisalsotrue,however,thatspectaculartechnologycanbackfirespectacularly—and science doesn’t always live up to its expectations. When we seesomethingfailthatwehadassumedwouldwork,whetherit’sa“miracle”drugorapowerfulmachine,werespondwithfearandanger.Peopleoftenpointtotheatomic bomb as the most telling evidence of that phenomenon. That’s notentirelyfair:howevermuchwemayregretit,thebombdidwhatitwasinventedtodo.

That wasn’t the case in 1984, when a Union Carbide pesticide factory inBhopal, India, released forty-two tons of toxicmethyl isocyanate gas into theatmosphere, exposing more than half a million people to deadly fumes. Theimmediate death tollwas 2,259;within twoweeks that number grew tomorethaneightthousand.Norwasittruetwoyearslater,whenanexplosionatUnit4of theV. I.LeninAtomicPowerStation transformedaplacecalledChernobylinto a synonym for technological disaster. They were the worst industrialaccidents in history—one inflicting immense casualties and the other aworldwide sense of dread. The message was hard to misinterpret: “Our livesdepend on decisions made by other people; we have no control over thesedecisionsandusuallywedonotevenknowthepeoplewhomakethem,”wroteTedKaczynski,betterknownastheUnabomber,inhisessay“IndustrialSocietyand Its Future”—the Unabomber Manifesto. “Our lives depend on whethersafetystandardsatanuclearpowerplantareproperlymaintained;onhowmuchpesticideisallowedtogetintoourfoodorhowmuchpollutionintoourair;on

how skillful (or incompetent) our doctor is. . . . The individual’s search forsecurityisthereforefrustrated,whichleadstoasenseofpowerlessness.”

Kaczynski’sactionswereviolent,inexcusable,andantitheticaltothespiritofhumanityheprofessedtorevere.Butwhohasn’tfeltthatsenseofpowerlessnessorfrustration?Reapingthebenefitsoftechnologyoftenmeansgivingupcontrol.Thatonlymatters,ofcourse,whensomethinggoeswrong.Fewofusknowhowtofixourcarburetors,orunderstandthemechanismthatpermitstelephonecallstobounceinstantlyoffsatellitesorbitingtwenty-eightthousandmilesabovetheearthonlytolandasplitsecondlaterinsomebodyelse’sphoneontheothersideoftheworld.

That’sokay;wedon’tneed toknowhow they function, as longas theydo.Two hundred or even fifty years ago, most people understood their materialpossessions—inmanycasestheycreatedthem.Thatisnolongerthecase.Whocan explain how their computer receives its constant stream of data from theInternet?Or understands the fundamental physics of amicrowave?When youswallowantibiotics, or give them toyour children, doyouhave any ideahowtheywork?Or howpreservatives aremixed intomanyof the foodswe eat orwhy?Theproportionofoursurroundings thatanyordinarypersoncanexplaintodayisminute—anditkeepsgettingsmaller.

Thisgrowinggapbetweenwhatwedoeverydayandwhatweknowhowtodoonlymakesusmoredesperate to findaneasyexplanationwhensomethinggoeswrong.DenialismprovidesawaytocopewithmedicalmistakeslikeVioxxand to explain the technological errors of Chernobyl or Bhopal. There are noreassuringsafetystatisticsduringdisastersandnobodywants tohearabout thetens of thousands of factories that function flawlessly, because triumphs areexpected, whereas calamities are unforgettable. That’s why anyone alive onJanuary28,1986, is likely to remember thatclear,coldday incentralFlorida,when the space shuttleChallenger lifted off from theKennedy SpaceCenter,only to explode seventy-three seconds later, thendisintegrate in a densewhiteplume over the Atlantic. It would be hard to overstate the impact of thataccident. The space program was the signature accomplishment of Americantechnology: it took us to themoon, helped hold back theRussians, andmademillions believe there was nothing we couldn’t accomplish. Even our mostcompelling disaster—theApollo 13mission—was a successful failure, endingwiththetriumphoftechnologicalmasteryneededtobringtheastronautssafelybacktoearth.

By1986,Americahadbecomesoconfidentinitsabilitytocontroltherockets

weroutinelysentintospacethatonthatparticularJanuarymorning,alongwithits regular crew, NASA strapped a thirty-seven-year-old high school teachernamedChristaMcAuliffefromConcord,NewHampshire,ontowhatessentiallywas a giant bomb. She was the first participant in the new Teacher in Spaceprogram.Andthelast.

Thecatastrophewasexaminedinmercilessdetailatmanynationallytelevisedhearings. During themost remarkable of them, Richard Feynman stunned thenationwithasimpledisplayofshow-and-tell.Feynman,ano-nonsensemanandoneofthetwentiethcentury’sgreatestphysicists,droppedarubberO-ringintoaglassoficewater,whereitquicklylostresilienceandcracked.Thering,usedasa flexible buffer, couldn’t take the stress of the cold, and it turnedout neithercould one just like it on the shuttle booster rocket that unusually icy day inJanuary. Like somany of our technological catastrophes, thiswas notwhollyunforeseen. “MyGod,Thiokol,whendoyouwantme to launch,nextApril?”Lawrence Mulloy, manager of the Solid Rocket Booster Project at NASA’sMarshallSpaceFlightCenter,complainedtothemanufacturer,MortonThiokol,whenengineersfromthecompanywarnedhimthetemperaturewastoolowtoguaranteetheirproductwouldfunctionproperly.

SCIENTISTS HAVE NEVER BEEN good about explaining what they do orhow they do it. Like all human beings, though, they make mistakes, andsometimes abuse their power. The most cited of those abuses are the twinsstudiesandotheratrocitiescarriedoutbyNazidoctorsunderthesupervisionofJosefMengele.Whilenotaspurelyevil(becausealmostnothingcouldbe),themostnotoriousevent inAmericanmedicalhistoryoccurrednot longago:from1932to1972,inwhatbecameknownastheTuskegeeExperiment,U.S.PublicHealth Service researchers refused to treat hundreds of poor, mostly illiterateAfrican American share-croppers for syphilis in order to get a betterunderstanding of the natural progression of their disease. Acts of purposefulmalevolencelikethosehavebeenrare;themoresubtlescientifictyrannyoftheelitehasnotbeen.

In1883,CharlesDarwin’scousinFrancisGaltoncoinedtheterm“eugenics,”which would turn out to be one of the most heavily freighted words in thehistoryofscience.TakenfromaGreekwordmeaning“goodinbirth,”eugenics,

as Galton defined it, simply meant improving the stock of humanity throughbreeding.Galtonwasconvincedthatpositivecharacteristicslikeintelligenceandbeauty,aswellaslessdesirableattributeslikecriminalityandfeeblemindedness,were wholly inherited and that a society could breed for them (or get rid ofthem)astheywould,say,aLipizzanerstallionoratangerine.Theideawasthatwithproperselectionofmateswecoulddispensewithmanyoftheillsthatkillus—high blood pressure, for instance, or obesity, as well as many types ofcancer.

Galtonsawthisasnaturalselectionwithatwist,andfeltitwouldprovide“themore suitable races or strains of blood a better chance of prevailing speedilyoverthelesssuitable.”Galtonposedthefundementalquestioninhis1869book,HereditaryGenius:woulditnotbe“quitepracticabletoproduceahighlygiftedrace of men by judicious marriages during consecutive generations?” As theYale historianDaniel J. Kevles points out in his definitive 1985 study In theNameofEugenics,geneticistslovedtheideaandeagerlyattemptedtoputitintoaction.EugenicsfoundparticularfavorintheUnitedStates.

In 1936, the American Neurological Association published a thick volumetitledEugenicalSterilization,areportissuedbymanyoftheleadingdoctorsintheUnitedStatesandfundedbytheCarnegieFoundation.Therewerechaptersonwhoshouldbesterilizedandwhoshouldn’t,anditwaschockfullofchartsandscientificdata—aboutwhoenteredtheNewYorkCityhospitalsystem,forexample,atwhatageand forwhatpurpose.Theboardof theANAnoted inapreface that “the report was presented to and approved by the AmericanNeurological Association at its annual meeting in 1935. It had such anenthusiasticreceptionthatitwasfeltadvisabletopublishitinamorepermanentformandmakeitavailabletothegeneralpublic.”

Had their first recommendation appeared in a novel, no reader would havetakenitseriously:“Ourknowledgeofhumangeneticshasnottheprecisionnoramplitudewhichwouldwarrant the sterilizationof peoplewho themselves arenormal [italics in the original] in order to prevent the appearance, in theirdescendants, of manic-depressive psychosis, dementia praecox,feeblemindedness,epilepsy,criminalconductoranyoftheconditionswhichwehave had under consideration. An exception may exist in the case of normalparentsofoneormorechildrensufferingfromcertainfamilialdiseases,suchasTay-Sachs’ amaurotic idiocy.”Of course, for peoplewhowerenot considerednormal, eugenics had already arrived. Between 1907 and 1928, nearly tenthousand Americans were sterilized on the general grounds that they were

feebleminded.Somelawmakerseventried tomakewelfareandunemploymentreliefcontingentuponsterilization.

Today,ourknowledgeofgeneticshasboththeprecisionandtheamplitudeitlacked seventy years ago. The Nazis helped us bury thoughts of eugenics, atleast for awhile.The subject remains hard to contemplate—but eventually, intheworldofgenomics,impossibletoignore.Nobodylikestodwellonevil.Yettherehasneverbeenaworsetimeformyopiaorforgetfulness.ByforgettingtheVioxxes,Vytorins, thenuclearaccidents, andconstant flirtationwitheugenics,and instead speaking only of science as a vehicle formiracles,we dismiss animportant aspect of who we are. We need to remember both sides of anyequationorweriskactingasifnomistakesarepossible,nogrievancesjust.Thisisanaspectofdenialismsharedbroadlythroughoutsociety;wetendtoconsideronly what matters to us now, and we create expectations for all kinds oftechnologythataresimplyimpossible tomeet.Thatalwaysmakesiteasierforpeople, already skittish about their place in a complex world, to questionwhethervaccineswork,orAIDS iscausedbyHIV,orwhy theyought to takeprescribedpainmedicationinsteadofchondroitinorsomeotheruselessremedyrecommendedwholeheartedlybyalternativehealersthroughoutthenation.

IFYOULIVEDwithintractablepain,wouldyouriskaheartattacktostopit?What chanceswouldbe acceptable?One in ten?One in ten thousand?“Thesequestions are impossible to answer completely,” Eric Topol told me when IaskedhimaboutitonedayaswewalkedalongthebeachinCalifornia.“Mercksold Vioxx in an unacceptable and unethical way. But I would be perfectlyhappyifitwasbackonthemarket.”

Huh?Eric Topol endorsingVioxx seemed tomake asmuch sense asAliceWaterscampaigningforMonsantoandgeneticallymodifiedfood.“Ican’tstressstrongly enough howdeplorable this catastrophe has been,” he said. “But youhave to judgeriskproperlyandalmostnobodydoes.Forone thing,yourarelyseeadiscussionoftheeffectofnothavingdrugsavailable.”Riskalwayshasanumeratorandadenominator.Peopletendtolookatonlyoneofthosenumbers,though,andtheyarefarmorelikelytorememberthebadthanthegood.That’swhywecan fear flyingalthough it ishundredsof times safer thanalmost anyotherformoftransportation.Whenaplanecrashesweseeit.Nobodycomeson

television to announce the tens of thousands of safe landings that occurthroughouttheworldeachday.

Wemakesimilarmistakeswhenjudgingourrisksofillness.Diseaserisksarealmostinvariablypresentedasstatistics,andwhatdoesitmeantohavealifetimeheart attack risk 1.75 times greater than average? Or four times the risk ofdeveloping a certain kind of cancer? That depends: four times the risk ofdevelopingacancer thataffects1percentof thepopulationisn’t terriblenews.Ontheotherhand,aheartattackrisk75percentgreaterthanaverage,inanationwhereheartattacksareepidemic,presentsarealproblem.Fewpeople,however,see graphic reality in numbers. We are simply not good at processingprobabilisticinformation.Evensomethingasstraightforwardastherelationshipbetweencigarette smokingandcancer isn’t all that straightforward.Whenyoutell a smoker he has a 25 percent chance of dying from cancer, the naturalresponseistowonder,“Fromthiscigarette?Andhowlikelyisthatreally?”Itisgenuinely hard to know, so all too often we let emotion take over, both asindividualsandasaculture.

Theweekin2003thatSARSswept throughHongKong, theterritory’svastnew airport was deserted, and so were the city’s usually impassable streets.Terrifiedmerchantssoldfacemasksandhandsanitizertoanyonefoolishenoughtogooutinpublic.SARSwasaseriousdisease,thefirsteasilytransmittedvirustoemerge in thenewmillennium.Still, itkilledfewer thana thousandpeople,according to World Health Organization statistics. Nevertheless, “it has beencalculated that the SARS panic cost more than $37 billion globally,” LarsSvendsenwrote inAPhilosophyofFear.“Forsuchasumoneprobablycouldhave eradicated tuberculosis, which costs several million people’s lives everyyear.”

Harmisn’tsimplyaphilosophicalconcept;itcanbequantified.WhenMerck,oranyanothercompany,withholdsinformationthatwouldhaveexplainedwhyadrugmight“fail,”peoplehavea right to theiranger.Nonetheless, thebiggerproblemhaslittletodowithanyparticularproductorindustry,butwiththewaywe look at risk.America takes theHollywood approach, going to extremes toavoid the rare but dramatic risk—the chance thatminute residues of pesticideappliedtoourfoodwillkillus,orthatwewilldieinaplanecrash.(Thereisnobigger scam than those insurance machines near airport gates, which urgepassengers to buy a policy just in case theworst happens.A traveler ismorelikely towin the lottery thandie inanairplane.AccordingtoFederalAviationAdministration statistics, scheduled American flights spent nearly nineteen

millionhoursintheairin2008.Therewasn’tonefatality.)

Ontheotherhand,weconstantlyexposeourselvestothelikelyrisksofdailylife, ridingbicycles (and evenmotorcycles)without helmets, for example.Wethink nothing of exceeding the speed limit, and rarelyworry about the safetyfeaturesofthecarswedrive.Thedramaticrarities,likeplanecrashes,don’tkillus.Thebanalitiesofeverydaylifedo.

Wecertainlyknowhowtocountthenumberofpeoplewhodiedwhiletakinga particularmedication, but we also ought tomeasure the deaths and injuriescausedwhencertaindrugsarenotbrought tomarket; that figurewouldalmostalways dwarf the harm caused by the drugswe actually use. That’s even truewithVioxx.Aspirin,ibuprofen,andsimilarmedications,whenusedregularlyforchronicpain,causegastrointestinalbleedingthatcontributestothedeathofmorethan fifteen thousand people in theUnited States each year. Another hundredthousand are hospitalized. The injuries—including heart attacks and strokes—causedbyVioxxdonotcompareinvolume.Inonestudyoftwenty-sixhundredpatients,Vioxx,when taken regularly for longer than eighteenmonths, causedfifteenheartattacksorstrokespereveryonethousandpatients.Thecomparablefigure for those who received a placebo was seven and a half per thousand.TherewasnoincreasedcardiovascularriskreportedforpeoplewhotookVioxxforlessthaneighteenmonths.Inotherwords,Vioxxincreasedtheriskofhavingastrokeorheartattackbylessthan1percent.Thoseareoddsthatmanypeoplemightwellhavebeenhappytotake.

“AllMerckhad todowasacknowledge therisk,and theyfought that to theend,”Topolsaid.“AfterfifteenmonthsofhagglingwiththeFDAtheyputatinylabelonthepackagethatyouwouldneedamicroscopetofind.Iftheyhaddoneitproperlyandprominently,Vioxxwouldstillbeonthemarket.Butdoctorsandpatientswouldknowthatiftheyhadheartissuestheyshouldn’ttakeit.”

Mosthumanbeingsdon’twalkoutthedoortryingtohurtotherpeople.Soifyouarenotdeliberatelytryingtodoharm,whataretherulesforusingmedicinesupposed to be?What level of riskwould be unacceptable?A better questionmight be, Is any risk acceptable? Unfortunately, we have permitted thedevelopment of unrealistic standards that are almost impossible to attain. Thepharmaceutical industry, in part through its own greed (but only in part), hasplaceditselfinapositionwherethepublicexpectsitnevertocauseharm.Yet,drugsarechemicalsweputintoourbody,andthatentailsrisks.Nomatterhowwelltheywork,however,ifonepersoninfivethousandisinjured,hecouldsueand have no trouble finding dozens of lawyers eager to represent him. People

nevermeasuretheriskofkeepingthedrugoffthemarket,though,andthatistheproblem.IfyouappliedFDAphaseIorIIorIIIcriteria—allrequiredfordrugapproval—todrivinganautomobileinnearlyanyAmericancity,nobodywouldbeallowedtoenterone.WhenwecomparetheriskoftakingVioxxtotheriskofgettingbehindthewheelofacar,it’snotatallclearwhichismoredangerous.

5

RaceandtheLanguageofLife

Inthespringof1998,ateamofresearchersfromtheCentersforDiseaseControltraveledtoameetingoftheAmericanThoracicSocietyinChicago,wheretheypresentedareportontheseverityofasthmaamongHispanics.Minoritieslivingin America’s largest cities visit the emergency roommore often, spendmoretimeinthehospital,anddieinfargreaternumbersfromasthmathantherestofthe population; they are also farmore likely to develop pneumonia and otherpulmonarydiseases.Noneof thatwasnews tomostof thosewhoattended themeeting,buttheCDCstudywasthefirsttofocusspecificallyontheprevalenceof asthma in Hispanics. During the course of his presentation, the pulmonaryspecialistDavidHomapointedoutthatheandhiscolleagueshadrunacrossoneparticularlysurprisingresultintheirresearch:HispanicslivingintheNortheastof the United States were three times more likely to develop asthma thanHispanicsintheSouth,Southwest,orWest.

Many people in the audience found that odd; differences in the rates ofpulmonarydiseaseareoftenaresultofsocialconditions, theenvironment,anddisparities in the quality of health care. Poor people rarely receive the bestpossibletreatmentsandconsequentlytheydon’tdoaswellasricherpatients—withasthmaorwithmostotherillnesses.Thestudywasdesignedtoaccountforthosefacts.Evenso,aHispanicmaninNewYorkwasmorelikelytogetsickthan one in Los Angeles or Chicago. Some participants shook their heads insurprisewhentheysawthedata,butEstebanGonzálezBurchardwasnotamongthem.Burchard,atthetimeatwenty-eight-year-oldinternalmedicineresidentatBoston’sBrighamandWomen’sHospital,hadknownforyearsthathewantedto specialize in pulmonary disease, largely because of its punishing effect onminorities.Hesat rivetedbyHoma’spresentation,andparticularlyby thedatathatsuggestedtheillnessseemedsomuchworseontheEastCoastthaninotherpartsoftheUnitedStates.

“IjumpedwhenIheardhimsaythat,”BurchardtoldmewhenwefirstmetinhisofficeattheUniversityofCaliforniaatSanFrancisco,whereheisassistantprofessorinthedepartmentsofbiopharmaceuticalsciencesandmedicine.“IamHispanicandIhavelivedonbothcoastsandIknewthattheobviousdifferencethere had to be between Puerto Ricans”—who reside principally in the East—“and Mexicans”—who are more likely to live in the West. At the time,

Burchard was working in the laboratory of Jeffrey Drazen, a professor at theHarvardSchool ofPublicHealth,whowas soon to become editor of theNewEngland Journal ofMedicine. In his lab,Drazen had identified a genetic riskfactor that would explain the differences in asthma severity between AfricanAmericansandCaucasians.BothheandBurchardthoughttheCDCdatamighthelpexplaingeneticdifferenceswithintheHispaniccommunityaswell.

“ItalkedtoDavidHomaandsuggestedthatthisdatacouldverypossiblybetheresultofgenetics,”Burchardsaid.“Idon’tknowifhethoughtIwasalittlecrazyorwhat.”Afterall,geneticsseemedunlikelytoprovideanexplanationforsuch a striking disparity among people with a common ethnic heritage. TheprevailingviewsincetheearlydaysoftheHumanGenomeProjecthasbeenthatsuch differences no longer seem worth thinking about, and many notableresearchers have argued that focusing on race in this way is not onlyscientificallyunsoundbutsociallydangerous.Yetsomethinghadtoaccountforthewidegap,soBurchardpersuadedHomathattheCDCoughttotakeacloserlook at the data. Two years later, the CDC study, now focusing on thedifferencesamongHispanicsofCuban,PuertoRican,andMexicandescent,waspublished. It showed that the prevalence, morbidity, and mortality rates ofpeoplewithasthmavariedsignificantlywithinthosegroupsandconcludedthatgeneticsseemedtobeatleastpartlyresponsible.

Burchard, like most physicians, believes that social and economicdisadvantages explain much about why minorities in the United States sufferdisproportionately fromsomanydiseases—eight times the rateof tuberculosisaswhites,forexample,tentimestherateofkidneyfailure,andmorethantwicethe rate of prostate cancer. Tuberculosis has served for generations as thesignature disease of urban crowding, homelessness, and poverty, and manypeople who die of AIDS do so because the virus makes them susceptible toinfections that cause pneumonia. But Burchard asked himself whethereconomics and environment alone could explain why one group of Latinos(PuertoRicans)hadamongthehighestratesofasthmaintheUnitedStateswhileanothergroup(Mexicans)hadvirtuallythelowest.Thatmadenosense.“Iwasconvincedthen,andamevenmoreconvincednow,”hetoldme,that“therearespecific ethnic, genetic, and environmental risk factors in play here.” For thepastdecade,Burchardhasworkedwithoneprincipalgoalinmind:tounderstandthemeaningofsuchgeneticdifferencesbetweenracialgroups. Ithasnotbeeneasy,norhas theresearchalwaysbeenparticularlywelcome.Grantmoneyhasoftenbeenhardtofind,andskepticismfromcolleaguespalpable.ButBurchardpersisted.

In2001,withthehelpofseniorscientistsfrommedicalcentersintheUnitedStates,Mexico,andPuertoRico,heembarkedonanexhaustiveattempttobetterunderstand the clinical, genetic, and environmental differences in severityamongMexican and Puerto Rican asthmatics. The investigative study, calledGALA—Genetics of Asthma in Latino Americans—has not only revealedgenetic differences within Hispanic populations. Perhaps more importantly, ithasdemonstratedthatdespitehavingmoresevereasthma,PuertoRicansrespondlesswelltothestandardtreatmentstheyaremostlikelytoreceive.Albuterol,forexample,isthemostcommonlyprescribedasthmamedicationintheworld,andfrequently the soledrugpeople receive (orneed) to treat their asthma.Yet formany Hispanics it can prove useless. Nonetheless, albuterol is often the onlyasthmadrugprescribedforPuertoRicansorMexicansintheUnitedStates.

“The idea has become fashionable that we are all one species and thatethnicity and race do not play defining roles in determining the causes ofdisease,”Burchardsaid.“Butlookatthedata.Theone-size-fits-allapproachtomedicineandtodrugtherapydoesnotwork.Weseethatoverandoveragain.Ican’t think of anything more important in medicine right now than trying toteaseoutthecausesofthesedifferences.Butbelieveme,therearemanypeoplewhothinkIamwrong.”Hesatback,shookhishead,andsmileddarkly.“Thereareseriousscientistswhosayweshouldnotevendothiskindofresearch,thatracesshouldbetreatedasoneandthatthegeneticsofhumanityarenotdiverseenoughtoplaythiskindofroleindiseases.Youcan’tlookatthedataandmakethose assumptions,” Burchard said. “But if reality upsets people, they willsimplylookinanotherdirection.Peopledenywhatmakesthemuncomfortable,andmany—eveninmybusiness—sayweshouldn’tusetheword‘race’atall.”

It has never been easy to invoke the subject of race in America.Discriminationhaslongbeenasobviousinmedicineasinotherareasofsociety.In the era of personalizedmedicine,where relevant new information seems toappeardaily, the issuehasbecomemorevolatile thanever.Atmanymeetingswhereraceandgeneticsarediscussed,researchersspendasmuchtimedebatingsemanticsastheydodiscussingscientificresults.(In2008,oneparticipantataNational InstitutesofHealth conferenceongenomics and race argued that notonlyistheterm“race”unacceptable,butsoistheterm“Caucasian,”becauseitimpliesracialratherthangeographicancestry.)

“Howmuchofafactordoesgeneticsplayintheseresearchresults?”Burchardcontinued.“Iwilltellyouhonestly,Idon’tknow—butneitherdoesanyoneelse.I amHispanic and Iwant people to get the treatment that serves thembest. I

want every tool atmy disposal and every tool at the disposal ofmy patients.Genetics isoneof themostpowerfulweaponswehave.Yes,wearestrikinglysimilarinmany—evenmost—ways.Butgeneticsalsomakesusdifferent.Thatscaressomepeople,butitisafact.

“Wearefinallycomingtoaperiodinscientifichistorywherepeoplemaybeable to benefit from those differences.Where they can actually help treat andcurediseases.Youwouldthinkthat issomethingthatscientistswouldsupport.Buttoooftenitisnot.Let’sfaceit,inthiscountrytherehavebeenmajorefforts,guided by endless waves of political correctness, to close the door to thepossibilitythattherecouldbeimportantracialdifferencesamonghumanbeings.AtfirstIfounditsurprising.Idon’tanymore.Butbehonest:whocanpossiblybenefitfromthisapproachtomedicine?”

ON JUNE 26, 2000, surely one of the most notable days in the history ofscience,PresidentBillClintonannouncedthecompletionofthefirstdraftoftheHumanGenomeProject.HespokeintheEastRoomoftheWhiteHouse,whereThomas Jefferson andMeriwetherLewis hadpresented themapofLewis andClark’s historic expedition to the public. The symbolism was impossible toignore, as were the parallels between what Clinton described as Clark’s“courageousexpeditionacross theAmericanfrontier” twocenturiesearlierandtheHumanGenome Project’s exploration of the contours and complexities ofthe human cell. Many of the scientists who had struggled to compile thatblueprintofhumanDNA—thestringofthreebillionpairsofchemical“letters”thatmakeupourgeneticcode—stoodbythepresident’sside.“Withoutadoubt,this is themost important,mostwondrousmapeverproducedbyhumankind,”Clintonsaid.“WearelearningthelanguageinwhichGodcreatedlife.”Britishprime minister Tony Blair, joined the conference by satellite, along withresearcherswhohadcontributedtotheworkinEngland.Science,Clintonsaid,wasonthevergeofgainingimmensepowertoheal,powerthatuntilrecentlywecouldnothaveimagined.Henotedthattheinformationpackedintothestructureofourgenomewassovaluable,andthepotentialbenefitsofunderstandingitsogreat, that itwas conceivable that “our children’s childrenwill know the termcanceronlyasaconstellationofstars.”

That’s unlikely, but Clinton’s optimism hardly seemed misplaced, and it

seemsevenlesssonow.Byassemblingacompletemapofthehumangenome,and then refining it literally every day, geneticists have already transformedfieldsasdiverseasanthropology,history,molecularbiology,andvirology.

An entire industry, genomics, has emerged to study the structures andfunctions of genes and how they interact with each other. The hereditaryinformation contained within our genes, our DNA, is written in a four-letterlanguage that, if printed out,would fillmore than a thousandNewYorkCitytelephonebooks.(Eachlettercorrespondstooneoffournucleotidebases:Aforadenine, T for thymine,C for cytosine, andG for guanine.) These sequences,arrangedinmillionsofthreadlikehelixesandpassedfromonegenerationtothenext,carrywithinthemtheinstructionsrequiredtoassemblealllivingthings—asetofinstructionswhichgenomicscientistsareworkingfeverishlytodecode.

The resemblance among humans is startling: compare one person with anyother,chosenrandomlyfromanytwoplacesonearth,andgeneticallytheywillbemorethan99percentidentical.Itdoesn’tmatterwhetheroneofthosepeopleis from Sweden and the other from Zambia, or whether they are twins, or ofdifferentgenders.Yet,therearestillmillionsofplacesinourgenomewherethatrecipevariesamongindividualsbyjustasinglegeneticletter.Thoseplacesarecalled single-nucleotide polymorphisms, or SNPs (pronounced “snips”). SNPsareusefulmarkersfordifferentversionsofgenes,andtheyhelpemphasizethedifferencesthatscientistsaretrying—withincreasingsuccess—toassociatewithvariousdiseases.Overthepastdecade,researchershavebeenabletousethesesurrogates asmolecular guideposts to identify scores of genes that playmajorroles in diseases ranging from prostate cancer to age-related maculardegeneration.

The Human Genome Project launched a modern Klondike, and billions ofdollars have been invested in an attempt to understand the exact structure ofvirtuallyeverygene in thehumanbodyand then translate thatknowledge intoeffectivedrugs.Weareintheearlieststagesofthisvasteffortatsiftingthroughthe rawdata thatcontains the languageof life.Eventually,however,genomicswillalmostcertainlyprovidetheinformationnecessarytohelpanswermanyofthemostfundamentalquestionswecanaskaboutourselvesandaboutbiology.Towhatextentaregenes responsible forhowwegrow, think,evolve,becomesick, and die? Are traits that pass through generations in a communitygenetically determined, or are they the expression of cultures that have beensharedforthousandsofyears?Isitevenpossibletoquantifyhowmuchofwhatwearecomesfromgenesandhowmuchfromthecircumstancesofourlives?

The last question is the most important because when we understand howhumansareputtogetherwewillhaveamuchbettergraspofthegeneticbasisofmajor diseases—what causes them and what causes people to vary sodramatically in their ability to respond to particular medicines. As everyphysicianknows,drugsthatworkwellforonepersondon’tnecessarilyworkforothers.Some,likealbuterol,areeffectiveonwhitesbutnotonmanyHispanics.For AfricanAmericans, who suffer from congestive heart failure at twice therate ofwhites, there isBiDil—acombinationof twoolder drugs,whichwhentakeninconcertturnouttoworkfarbetterforblacksthanforwhites.(Thedrug,whenusedinthisfashion,becamethefirstrace-basedmedicineapprovedbytheFDA,specifically to treatblacks.Theactioncaused intensecontroversy,but italsoofferedanewformofrelieftoAfricanAmericanswithheartfailure.)

While vital clues to causes of various afflictions emerge in a torrent, theyrarelyprovidedefinitiveanswers.Buttheinitialmapdidproveconclusivelythatallhumansshareanearlyidenticalgeneticheritage.Manyresearchershaveevenargued that relying on race as a way to define and connect large groups ofseeminglysimilarpeoplenolongermakessense,exceptasawaytodiscriminateagainstthem.

PresidentClintonmadeapointtostressthatathisnewsconference.Afterall,what could be more exciting to a liberal politician raised in the South thanunshakable evidence that racism was based on a series of socially createdmisconceptionsabouthumanevolution?AsEricLander,agenomicpioneerandthedirectorof theBroad Institute, the research collaborationbetweenHarvardandMIT,putit,“Racialandethnicdifferencesareallindeedonlyskindeep.”

J.CraigVenter,whoatthetimewaspresidentofCeleraGenomics,theprivatecompany that dueled with the government to complete the project first, alsoattended the ceremony. There is nomore compelling or astute scientist in theworldofgenomicsthanVenter,whoin1992foundedtheInstituteforGenomicResearch.Acommenthemadethatday,that“theconceptofracehasnogeneticor scientific basis,” has been repeated often. So have the remarks of hismaincompetitor,FrancisS.Collins,therenownedgeneticistwholedthefederalefforttomapthegenome,pointedoutthatthedatashowedtherewereprobablymoresignificantgeneticdifferenceswithinracialgroupsthanbetweenthem.(In2009,Collinswas named byBarackObama as director of theNational Institutes ofHealth.)Allthosecommentsprovidesupportforthecomfortingideaofafamilyofman,evenasocietywithoutrace.

Nor should such findings be surprising; we are a young species, one that

migrated out of Africa and throughout the world only about one hundredthousand years ago—relatively recently in evolutionary terms.Many scientistsalready understood this well. In fact, during the first decade of the HumanGenome Project some participants were so convinced of the homogeneity ofhumanitythattheyinsistedthatthegenomicsequenceofanyonepersoncouldbeusedasabasicreferencetemplateforeveryoneelseonearth.

Therewasawidelysharedfeeling,accordingtoM.AnneSpence,whowasontheGenomeProject’s ethics committee, that the sequenceswouldbe the sameandthatgenderoughtnottomatter.Spenceandseveralothersinsistedthatsuchthinkingmadenosense.Foronething,mencarryaYchromosomeandwomentwoXs. That would have to account for some differences. Nonetheless, mostdrug research in America has been carried out on middle-aged white men.People often have radically different responses to the same medicines—andwomen,inparticular,reactinwaysthatmendonot.Spencepointedthatoutandalsoargued that sequencing thegenomewasnot simplya scientificenterprise,butonewithlastingimplicationsforourpolitical,social,andculturallives.

Shemay have beenmore right than she knew. In its early days, instead ofsettlingdebatesaboutraceandmedicine,theGenomeProjectinflamedthem.Bythetimethegenomewaspublished,nearlyayearafterClinton’sannouncement,twodistinctcampshadformed:thosewhobelievedracenolongerexistedasabiological entity, and those who argued that race and ethnic backgroundcontinued toprovidecrucial informationformedical research.Debateseruptedinscientificjournals,atacademicconferences,onuniversitycampuses,andevenwithinthefederalgovernment’sscientificestablishment.Consideringtheterm’sorigins,theanxietyisnothardtounderstand.Classifyingpeoplebyracehashadaprofoundlydisturbinghistory,leavingalegacyofhatredthroughouttheworld.Naturally, then, many scientists rushed to embrace our remarkable geneticsimilarities as a way to dismiss race entirely. As Robert Schwartz of TuftsUniversity argued in awidely circulated article published in theNewEnglandJournalofMedicine,“Raceisasocialconstructnotascientificclassification.”

Hewenton topointout that racial identificationplays itsmost important—anddestructive—role insettingsocialpolicies. Inonewayoranother racehasbeen used to justify much of the abuse humans have inflicted on each otherthroughout history. Putting race together with medicine has been particularlyexplosive.Onehasonly to thinkof theTuskegeeExperiment tosee that.Racehasbeenused to justifyeugenics,andmore thanonce to justifygenocide.Thefactsofthehumangenomesuggestedthatitmightbepossibletomovebeyond

suchdivisivewaysofthinkingaboutourspecies.“Sadly,”Schwartzwrote,“theideaofraceremainsingrainedinclinicalmedicine.Onwardroundsitisroutineto refer to a patient as black,white, orHispanic yet these vague epithets lackmedicalrelevance.”

Mostscientiststhinkitwillbeyears,possiblydecades,beforewereapthefullintellectualharvestof theHumanGenomeProject.Aftercomprehensivestudy,wecanexplainasmallpercentageofgeneticlinkstocommondisease.Butthereismuchmorewedon’tunderstand—includinghowsomegenesworktoprotectusfromillnessesthatothergenescause.Meanwhile, that99percentfigurehasbeenpublishedeverywhereandisusedasthebasisofapropagandawarbybothsidesin theracedebate.Thereisnodisputingourhomogeneity.It isalsotrue,however,thatweshare98.4percentofourgeneswithchimpanzees.Fewpeoplewould argue that makes us nearly identical to them. Even drosophila—thecommon fruit fly—has a genetic structure that shares almost two-thirds of itsDNAwithhumans.Does thatmeanwe aremostly like fruit flies?The simpleand largelyunansweredquestion remains:what canwe learn from theother 1percent(orless)ofourgenomethatsetsusapartfromeveryoneelse?

“WHATWEAREgoingtofindispreciselythattheotherpercentplaysarolein determining why one person gets schizophrenia or diabetes while anotherdoesn’t,whyonepersonrespondswelltoadrugwhileanothercan’ttolerateit,”NeilRischsaid.Risch,whoisLamondDistinguishedProfessoranddirectorofthe Institute for Human Genetics at the University of California at SanFrancisco,arguesthattheconceptofraceremainshighlyvaluableinmedicine,and that people only pretend otherwise out of a misguided sense of decency.“It’scrazytobanishracejustbecauseitmakespeopleuncomfortable,”hesaid.“It’sagenuinelyniceideaandIunderstandthereasonsforit.Butscientificallyitjustmakesnosense.

“These are imperfect but valuableways to describe a group,” he continued.“Youcantalkaboutageinthesameway.Rarelywouldaperson’schronologicalage correspond exactly with his biological age—for both environmental andgeneticreasons.Usingabirthyearisnotnecessarilyaprecisewaytomeasureit.Weallknowthereisageisminsociety.Doesthatmeanasphysiciansweshouldignore a person’s date of birth? Of course not. It’s an important tool in ourarsenal.”

Risch is one of the most prominent and highly respected geneticists in the

UnitedStates,andwhenitcomestothisissue,oneofthemostcontroversial.Heisalsoantsy;whenwemetinhisofficehewouldsitquietlyforafewmoments,then burst into speech and then abruptly stop. “Here’s the deal,” he said,“especiallyforcomplexmajordiseases.Youseedifferencesinhealthratesandisyour firstconclusiongoing tobe that theyarebasedongenetics?Ofcoursenot.Inevitably,theenvironmentisplayingsomeroleandtheinteractionbetweenenvironmentandgeneticsisincrediblycomplex.

“If you go to morbidity and mortality statistics, what do you find?” hecontinued. “You find that African Americans generally have higher rates ofdiseaseanddeathacrosstheboardforeverything;allcancers,heartdisease,justabout everything.This just doesn’tmake sensegenetically.Thedifferentiationbetweenracialgroupsisnotbigenoughforonegrouptohaveallthegenesfordisease.Soofcourseit’senvironmental.”Hesmiled,pausingforemphasis.“Butwhen you eliminate the environmental differences you are still left with asignificantdisparitybetweenraces,andthereiswheregeneticfactorsmayplaymoreofarole.”

Rischrattledoffalistofdiseasesinwhichgeneticvariationsbetweenethnicgroups had been observed: Crohn’s disease is more common in people ofEuropeanheritage,andRisch’steamidentifiedaSNPthatconfersamuchhigherrisk on Europeans than on any other geographical group. “This is clear andunequivocal,”hesaid.“ThoseSNPsdon’texistinAsiansorinAfricans.Thereare others. Hemochromatosis”—a condition in which the body produces andstores too much iron. “Between 8 and 10 percent of Europeans have thismutation.Intherestoftheworld,though,itisalmostnonexistent.”Perhapsthemost interesting example is of a particular protein used by theAIDS virus todockwithcells and infect them.TheDelta32mutationon theCCR5 receptorprevents that; theviruscan’t findaconvenientway to lockonand infectcellsthat carry this mutation, which is present in as many as 25 percent of whitepeople,particularly innorthernEurope.Themutationhasneverbeen found inAfricansorAsians.

“There are real, powerful, and useful implications to all this,” Risch said.“Interferon is a treatment used for hepatitis C. Forty percent of Caucasiansrespondwelltoitandactuallyclearthevirusoutoftheirsystem.Africansdon’trespond at all. Not at all. This matters immensely. It’s not socio-cultural oreconomic. It seems to be genetic. Andwe need to know this, because givingblacksinterferonwhentheyhavehepatitisCisnotgoingtohelpthem.Wehavetocomeupwithothertreatments.”

Latein2008,theNationalHumanGenomeResearchInstituteheldaforumatwhich genetic researchers discussed with ethicists how best to present theirdiscoveries to the public. Studies that underscore racial differences are almostalways in dispute. In 2005, the geneticist Bruce Lahn and colleagues at theUniversity ofChicagopublished twopapers that described their investigationsinto theevolutionof thehumanbrain.Lahnfoundthatmutations in twogenesthat regulate brain development were more common in Eurasians than inAfricans. That implies that those variants conferred a survival or reproductivebenefit,andthattheyemergedafterhumansleftAfrica.

Nobodyknowswhatthosegenesdo,andtherewasnoevidencetoshowthattheyhadactedon intelligence.Nonetheless,putting thewords“gene,”“brain,”and“race”togetherinasentenceisboundtocausetrouble.Peopleonbothsidesof the political divide leapt to conclusions; Lahn, a lifelong liberal, wasembraced by the right and denounced as a sensationalist even by some of hiscolleagues.Hehadstressedthat thestudyhadnoracialcomponentperse,andthatgenesotherthanthoseinthebraincouldhavecausedtheirselection.Norisitclearwhat,ifanything,thosemutationsrepresent.Butbecausetheywerelesscommon among sub-Saharan Africans than in other populations, the workcausedasensation.Still,Lahnhaswonderedforyearswhethertheremightbeagenetic element to variations in social status. “You can’t deny that people aredifferentattheleveloftheirgenes,”hesaidatthetime,citingtheexamplesofskincolorandphysicalappearance.“Thisisnottodenytheroleofculture,buttheremaybeabiologicalbasisfordifferencesaboveandbeyondculture.”

That kind of talk infuriated his colleagues, and it still does. At the NIHworkshop, Celeste Condit, a professor of speech communication at theUniversity of Georgia, spoke about the way she thought Lahn’s study wasframed.“Thepaperscouldbeseenashavingapoliticalmessage,”Condit toldSciencemagazine: in otherwords, the researchmight have implied that thosegenescontribute todifferences inIQ.Lahn,whohassinceshifted thefocusofhisworktostemcellresearchinpartbecauseofthecontroversy,hasrepeatedlystatedhehadnotmeanttosuggestthat.

During the bicentennial celebration of Darwin’s birth, in 2008, the journalNatureinviteddistinguishedscientiststodebatewhetherthesubjectofraceandIQ was even worthy of study. The dispute was lively. “When scientists aresilencedbycolleagues,administrators,editorsandfunderswhothinkthatsimplyaskingcertainquestionsisinappropriate,theprocessbeginstoresemblereligionrather than science,” Stephen Ceci and Wendy M. Williams, geneticists at

CornellUniversity,wrote.“Undersucharegime,werisklosingagenerationofdesperatelyneededresearch.”TheBritishneuroscientistStevenRosedisagreedfunde mentally, calling the study of the relationship between race and IQ“ideologymasqueradingasscience.”

Despitethesubject’svolatility,andthefactthatmostpeoplewouldprefertodeny its implications, neither the federal government nor the pharmaceuticalindustry is quite ready to abandon the concept of race. In March 2008, theNational Institutes of Health announced the establishment of the Center forGenomics and Health Disparities. (If there were no genomic disparities, whyestablishsuchacenter?)Afewmonthsearlier,thePharmaceuticalResearchandManufacturersofAmericahadreleasedalengthyreportdescribingnearlysevenhundred new drugs that were under development to treat diseases thatdisproportionately affect African Americans. (There was more than a littlemarketingbehindthereport;manyofthosedrugs,shouldtheymakeitthroughtheFDAapprovalprocess,wouldalsoprovebeneficialforotherethnicgroups.)

Someof thegenetic factors involved indrug responsehavebeenknownfordecades and can be attributed to proteins called drug metabolizing enzymes.Differences in the genes that encode thesemolecules are responsible for howquickly the enzymes process and eliminate drugs from our bodies, as well ashowtheyarebrokendownintheblood.Ifadrugismetabolizedtooquickly,itmaynotreachahighenoughconcentrationtoworkproperly.Ifitismetabolizedtooslowly,however,enoughofthatdrugcouldaccumulatetoreachatoxiclevelinthebody.Ineithercase,thepatientwouldsuffer,butnoneofthatisnewstophysicianswithethnicallydiversepatientpopulations.

“Almost every day at the Washington drug clinic where I work as apsychiatrist, race plays a useful diagnostic role,”SallySatelwrote in amuch-debated 2002 New York Times article entitled “I Am a Racially ProfilingDoctor.”Shehaswrittenoftenaboutthesubject.“WhenIprescribeProzactoapatient who is African-American, I start at a lower dose, 5 or 10 milligramsinsteadof theusual 10-to-20milligramdose. I do this inpart because clinicalexperience and pharmacological research show that blacks metabolizeantidepressantsmoreslowly thanCaucasiansandAsians.Asa result, levelsofthemedicationcanbuildupandmakesideeffectsmorelikely.Tobesure,notevery African-American is a slow metabolizer of antidepressants; only 40percent are. But the risk of provoking side effects like nausea, insomnia orfuzzy-headednessinadepressedperson—someonealreadyterriblydemoralizedwhomayhavebeenreluctanttotakemedicationinthefirstplace—istoworsen

thepatient’sdistressand increase thechances thathewill flush thepillsdownthetoilet.SoIstartallblackpatientswithalowerdose,thentakeitfromthere.”

Themainargumentagainstrelyingonraceinthiswayissimplebutpowerful:differentracesreceivedecidedlydifferentstandardsofhealthcareintheUnitedStates,andthatisunacceptable.ThedisparityexplainswhyAfricanAmericansandHispanicshavemorechronicillnessesthanwhites,andwhytheytakelongerto recover from them.Genetics is only one piece of a puzzle; ifwe place toomuch emphasis on it we will invariably continue to neglect more significantreasonsforthegulfthatseparatesthehealthofblackandwhiteAmericans.Youdon’t have to be an astute student of the United States, or the history of themodernworld,totakesuchconcernsseriously.

Even so, respect for other ethnic groups cannot alter biological reality.Everyoneknowshowdifferentweallarefromeachother.Someofusaredarkandsomearelight,sometallandothersshort.It’sgenetic;weinheritthosetraitsfromourparents.Infact,entireindustriescatertodifferenceslikethese:nobodywouldexpecttoseeBarackObamawearingthesamesizesuitasKobeBryant.

“Many of my colleagues argue that we should banish the word ‘race’completely,”NeilRischtoldme.“Theysaylet’susedifferentwords.Insteadofrace we should talk about geographic distribution of ancestors. And that’scompletelyfinewithme;wecancall itGOAD.Now, thinkabout that for twominutes, and then tell me: if we described people that way, do you actuallybelievetherewouldbeno‘goadists’?”

ICELANDMIGHTSEEMlikeanoddplace tosearchforanswers tocomplexquestions about race and genetics. The country has three hundred thousandresidents, all of whom are so genetically similar that telephone numbers areorganized by first names in the Reykjavik phone book. A thousand years ofvolcanic eruptions and other catastrophes have had the effect Darwin wouldhaveanticipated: thoseplaguesandnaturaldisastersprunedthepopulationandcutbacksharplyonthegeneticdiversityoftheisland.Asaresult,thehereditaryinstructionsoftheentirenationhavepassedthroughasmallgenepoolforfiftygenerations.

Therearethousandsofillnesses—likecysticfibrosis,sickle-cellanemia,and

Huntington’s chorea—whose cause can be traced directly to themutation in asinglegene.Theyusually followsimpleMendelianpatternsof inheritanceandrun in families.Mostmajor diseases, on the other hand, including cancer andcardiovascularillnesses,whichkillmillionsofpeopleeveryyear,aretheresultofacomplexcombinationofenvironmentalhistory,behavioralpatterns,andtheinteraction of hundreds of genesworking together in ways that even nowweonlydimlyunderstand.

Themostdirectapproachtofindingtheoriginsofthosediseasesistocomparethe DNA of people who are sick to the DNA of their healthy relatives (andancestors). When a group is almost identical, their differences become muchmore apparent. Those kinds of studies are hard to conduct in a racially andethnicallydiversecountryliketheUnitedStates,whereancestorscanrarelybetraced for more than a few generations. If one group’s cultural heritage,environment, and habits differ from another’s then so almost certainly are thecauses of its illnesses. That’s not a problem in Iceland. Despite centuries ofseclusiononaremoteislandintheNorthAtlantic,peopletheredevelopseriousdiseases at roughly the same rate as people in other industrialized countries.There is no place more ideally suited for research into the genetics of majordiseases.

“What do race and genetics have to do with common diseases?” bellowedKariStefanssonwhenIaskedtodiscussthesubjectwithhim.Helookedasifhiseyeswerereadytoburst.“Everything,obviously.Howcanyoubestupidenoughtoask thatquestion?”Wewerestanding inhisofficeatdeCODEgenetics, thecompany he founded in 1996 to mine the genetic heritage of the Icelandicpeople. Stefansson is six feet five inches tall, dresses almost exclusively inblack, and is famously imperious.When he hovers over you and calls you anidiot itmakes an impression that doesn’t fade quickly.The first timewemet,nearly a decade ago, I couldn’t believe that Stefansson could be socondescending.SincethenIhavecometoregardhisconversationalmannerasapersonaltrait,likefrecklesoratwitch.Throughoutthattime,Stefansson’sself-confidencehasneverwavered—andthat’snotwhollywithoutreason.

Perhaps more than any scientific institution other than the U.S. NationalInstitutes of Health, which is funded by the federal government, deCODE isresponsible for producing a stream of genetic information that promises tochange medicine in ways that even a decade ago would not have seemedpossible. Almost no day passes without some revelation describing how ourgenesinfluencethewaywelive,behave,getsick,anddie.DeCODEhasisolated

genes that are associated with type 2 diabetes, prostate cancer, heart attack,obesity,andschizophrenia,tonamejustafew.Thecompanyhasevenunearthedtentativehintsattherelationshipbetweenfertilityandlongevity.AllbyhominginondifferencesintheDNAofpeoplewhoareasalikeasanygrouponearth.

“Differencesmatter,”Stefansson said, striding into his officewith a proteindrink in eachhand. “Theymatter enough to cure diseases and savemillionoflives.Race.Geographicalancestry.Callitwhatyouwant.Ifourworkhasshownus anything, it ought to be that the even smallest of goddamn differencesmatter.” Stefansson spent more than a decade at the University of Chicago,where he became a tenured professor of neurology. He returned to Icelandbriefly in the early 1990s to run the Institute of Pathology, then the country’smostdistinguishedscientificresearchorganization.Hewasrestless,though,andforfiveyearsmovedbacktotheUnitedStatesasaprofessorofneurologyandpathologyattheHarvardMedicalSchool.Itwasthen,duringabriefvisithometoconductresearchonhisspecialty,multiplesclerosis,thatStefanssonrealizedIcelandwasageneticjackpot.

ThedeCODEbuilding,justabriefwalkfromthecenterofoldReykjavik,iscraftedfromthestarkschoolofNordicrealism,allplateglassandangularbitsofsteel. It is eerily clean and quiet and the mood seems surreal: perhaps that’sbecause I have only visited in themiddle ofwinter,when the sun sets beforenoon, and at the height of summer,when people play chess in the courtyardsuntilfoura.m.Despiteitsunparalleledresearchsuccess,thecompanyhasbeenbadly hurt by Iceland’s economic shipwreck, not to mention some unluckyinvestmentdecisionsanditsownoutsizedambitions.DeCODEneversawitselfsolely as a research center. It intended to become amajor biotechnology andpharmaceuticalcompany,butthoseplanshavelargelyremainedunfulfilled.

Nonetheless, deCODE helped start a revolution. Fueled by the almostunimaginably rapid growth in sequencing power, genomics is beginning totransformthewaywethinkaboutmedicine,andabouttherestofourlives.Thebenefits, particularly drug treatments tailored to individual needs, have beenoverlyhyped,asnewtechnologiesalwaysare.Inthepast,itoftentooktwenty-fiveyearstoturnascientificdiscoveryintoacommontherapy.(Orlonger.TheGerman chemist Adolf Windaus won the Nobel Prize in 1928 for work thathelped determine the chemical composition of cholesterol. It took almost acentury until that discoverymade itsway into a class of drugs—statins—nowtaken by millions of people every day.) Powerful computers and genesequencingtechnologyarechangingallthat,supplyingthevocabularynecessary

tomakesenseofthedigital informationcontainedwithineachofourbodies—andeachofourcells.

SNPS PROVIDE A useful way to calculate a person’s genetic risks ofdeveloping scores of diseases. Yet they are a half-measure, an imperfectsubstitute for the information that comes from scanning an entire genome—which still costs $100,000. The price won’t stay high for long. (In fact, onecompany, Complete Genomics, claims it will be able to sequence an entirehuman genome for $5,000 by 2010.) The cost of combing through billions ofbitsofDNAhas fallenbya factorofmore thanonehundred thousand in lessthan two decades. In 1990, as the Human Genome Project got under way,scientistsestimatedthatsequencingasinglegenomewouldcost$3billion.Thefinal bill is hard to calculate, because the figures include the cost of manyscientificactivitiesrelatingtogenomicscarriedoutduringthethirteen-year-longproject.Butthetotalwasfarlessthantheoriginalestimate,andwhentheprojectendedin2001,theteamsaidthattheycoulddoitagainfor$50million.

Five years later, the molecular geneticist George Church said he couldsequenceagenomeforabout$2million.Thefollowingyear,ittooktwomonthsand less than $1million to sequence the complete genome of JamesWatson,whoin1953discoveredthestructureofDNAalongwithFrancisCrick.Adropin cost from $3 billion to $100,000 in twenty years is impressive. Time is aneven more useful measuring stick: what took thirteen years in 1988 and twomonthsin2007willalmostcertainlytakelessthanfiveminuteswithinthenexttwo or three years. Church, who is director of the Lipper Center forComputationalGeneticsatHarvardMedicalSchool,andholdsdualpositionsatHarvardandMIT,expectstoseesteeperpricedeclinesandthefastersequencingratesthatcomewiththem,soon.Churchhelpeddeveloptheearliestsequencingmethods, nearly twenty-five years ago,whileworking in the lab of theNobelPrize-winningchemistWalterGilbert.

“Idon’tknowwhetherwecansqueezeitdownbyafactorofonehundredinthenextyearorso—it’shardtoevenguesswhatthecostwillbeinfiveyears.Butitwillbelow,”hesaid.“Youjustdon’tgetthatkindofchangeinanyotherindustry.” In 2007, Church embarked on his most audacious undertaking, thePersonalGenomeProject.Heintends tosequencethegenomesofonehundredthousandvolunteers—hehas already sequenced andpublished the genomes ofthefirstten.Theeventualdatabasewillproveinvaluableincorrelatinggenomicinformation with physical characteristics. Researchers will have access to the

database at no cost. Naturally, without the rapid evolution of sequencingtechnologytheprojectwouldnothavebeenpossible.

“In1984, thirtybasepairs”—thirty rungson thehelical ladderof sixbillionnucleotides thatmakeupourDNA—“wasagoodmonth’swork,”Church toldme.“Nowittakeslessthanasecond.”CraigVenter,whoknowsasmuchabouthow to sequenceagenomeasanyone, agrees. “I spent tenyears searching forjustonegene,”hesaid.“Todayanyonecandoitinfifteenseconds.”Indeed,theXPrizeFoundationhasoffered$10milliontothefirstgroupthatcansequenceonehundredhumangenomesintendaysatacostof$10,000orlesspergenome.Asmanyastwodozenteamsareexpectedtocompete.

In 2007, seizing on the cascade of genetic information that had suddenlybecome acessible, deCODE and two California companies, 23andme andNavigenics,begantosellgene-testingservicesdirectlytoconsumers.Thetestsanalyzeup toonemillionof themost commonSNPs—asmall fractionofourgenome—focusing on the most powerfully documented relationships betweenthoseSNPsandcommondiseases.Foreachdiseaseorcondition,thecompaniesestimatetheriskofahealthypersondevelopingthatillness.BothdeCODEand23andmesold their first testsfor justunder$1,000,butpriceskeepfalling.Bytheendof2008,a23andmetestcost$400.Navigenicscharges$2,500foritsfullregimen, which includes the services of genetics counselors; deCODE offerspackagesatvariousprices.

Much of deCODE’s research relies on its own formidable database, while23andme, whose slogan is “Genetics just got personal,” has emphasizedgenealogy and intellectual adventure, not just medicine, and encouragescustomerstosharedata,participateinresearchstudies,andformsocialnetworksonitsWebsite.In2008,Timemagazinenamedthe23andmetestasitsinventionof the year, but critics have described the company’s approach as frivolousbecauseitnotonlyprovidesdiseaseinformationbutalsohelpscustomerslearnaboutlessuseful—butperhapsmoreamusing—traitslikewhethertheyhavedryearwaxorcantastebitterfoods.Nobodydisputesthequalityofthecompany’sscience,however,oritsstandards.(Ishouldstateclearly,andfortherecord,thatthefoundersof23andmeareclosefriendsofmine,andhavebeenforyears.)

The testingprocess is similar at eachcompany.After spitting intoa tubeorswabbing their cheeks for saliva, customers submit samples of their DNA.Withinweeks,theyreceiveane-mailinformingthemthattheycanretrievetheirinformation from a secureWeb site. These are not diagnostic tests and theirpredictivevalueissubjecttomuchdebate.Manydiseasesinvolvetheinteraction

ofscoresorevenhundredsofgenes.ASNPthatshowsaheightenedriskforaparticularconditionalmostalwaysonlytellspartofthestory,andsomepeopleworrythatsincethedataisrarelydefinitivecustomersmightbemisled.“Wearestill too early in the cycleof discovery formost tests that arebasedonnewlydiscovered associations to provide stable estimates of genetic risk for manydiseases,” wrote Peter Kraft andDavid J. Hunter, both epidemiologists at theHarvardSchoolofPublicHealth,inanarticletitled“GeneticRiskPrediction—AreWeThereYet?”intheApril16,2009,issueoftheNewEnglandJournalofMedicine.Theythoughtnot.“Althoughthemajorfindingsarehighlyunlikelytobe false positives, the identified variants do not contributemore than a smallfractionoftheinheritedpredisposition.”

None of the services pretend that genetic tests alone can explain complexhealth problems. On its Web site, 23andme states that “in order to make adiagnosis,yourdoctorconsidersnotonlyyourgeneticinformation,butalsoyourparticular personal and family history and your physical condition, aswell asany symptoms you are experiencing. Your genotype is only part of theequation.” Making a similar point, deCODE suggests that you explore yourgenetic risk factors and keep a vigilant eye on your prospects for prolongedhealth. Even Navigenics, the most clinically oriented of the three, tellsprospectivecustomersthat therearenocertainanswersin theinformationtheyprovide:“Thislevelofpersonalizationmayhelpyoutakeactiontodetecthealthconditionsearly,reducetheireffectsorpreventthementirely.”

Evenknowledgeableconsumerscanstruggletoputpartialgenomicdataintoperspective, particularly if a report indicates that they are at greatly increasedriskofdevelopingaseriousillness.Thatinformationisbasedonwhatisknown—which in most cases is only a fraction of what there is to learn. Threeprominenthealthofficials, including theeditorof theNewEnglandJournalofMedicineandthedirectorof theNationalOfficeofPublicHealthGenomicsattheCentersforDiseaseControl,havesuggested thatuntilbetterdata iswidelyavailable,apersonwoulddomore to improvehishealthoutlookby“spendingtheirmoneyonagymmembershiporapersonaltrainer.”

Caveatsandcautionarenecessarybecauseriskisrelativeandfewpeopledealwithabstractprobabilitiesrationally.If,forinstance,apersonhasfourtimesthenormal risk of developing a particular disease, should he worry? That is anextremelyelevatedfigure.Withoutcontext,however,anumbermeansnothing.Take thedigestivedisorderceliacdisease; fewer thanone inahundredpeopledevelopceliacdisease in theUnitedStates, soa relative risk figure four times

theaveragewouldmeanthatyoustandaslightlygreaterthan96percentchanceofavoidingitcompletely.

That doesn’tmeangenomic tests aren’t useful.They can change (and save)your life. Jeff Gulcher, deCODE’s forty-eight-year-old chief scientific officer,wasn’taroundthelasttimeIwasinReykjavik.Stefanssonandhehaveworkedtogether formore than two decades, since the day that, as a graduate student,GulcherwalkedintoStefansson’slaboratoryattheUniversityofChicago.

WhenGulchertookhisdeCODEmetest,amonthbeforeIarrived,helearnedthathisrelativeriskofdevelopingprostatecancerwas1.88.Thatmeanthewasalmost twice as likely as the average person to get the disease. Gulcher tookthoseresultstohisphysician,whoorderedaprostate-specificantigentest.PSAisaproteinproducedbycellsoftheprostategland.Theresultsfluctuate,butingeneral the higher they are, themore likely aman is to have prostate cancer.Gulcher’s test showed that he had 2.4 nanograms of PSA per millimeter ofblood,wellwithinthenormalrange.Thosetestsareroutinelyrecommendedformen fiftyyearsof age andolder.ButbecauseGulcherwasnotyet fifty,mostdoctorswouldneverhavegivenhisresultsasecondthought.

WithGulcher’sgeneticprofile inhand,however,hisphysicianscheduledanultrasound,justtobesure.Thefilmsrevealedanaggressivetumor,thoughithadnotyetspreadbeyondtheprostate.“JeffwassoyoungthatnobodywouldhavemadeanythingofthatkindofPSAscorefortenyears,”Stefanssonsaid,staringintoGulcher’s empty office. “Bywhich time hewould surely have been longdead.” Gulcher had surgery, quickly recovered, and returned to work. Hisprognosisisexcellent.

Gulchermakeshis livingpondering themeaningof risk.Mostpeopledon’t.Critics of the tests say they are still too complex for an average consumer tofully understand. Kari Stefansson disagrees. “That is such bullshit,” hescreeched. “We are actually criticized for revealing valuable information tounsuspectingcitizensattheirrequest,peoplewhopaidforexactlythatservice.Ifsomebodydoesnotwanttoknowthisinformationheshouldnothavethetestdone.It’snotrequired.Butitisextraordinarilypatronizingtotellapersonthatheisnotmatureenoughtolearnabouthimself.

“By theway,”hecontinued,“inmostAmericanstates,youcanget inacaranduseyourdriver’slicenseasidentificationtobuyagun.Thenyoucandrivetoaliquorstore.Youcanhavethebottle,thegun,andthecar.That’sfine.Butforheaven’ssakedon’tlearnanythingimportantaboutyourselforyourfamily.

Forsomediseasesthereisnotreatmentornousefulresponseyet.Butyouhavetorememberthatourabilitytotreatdiseaseswasalwaysprecededbyourabilitytodiagnosethem.Soourabilitytopreventdiseaseswillsurelybeprecededbyourabilitytoassessrisk.”

Thatfact iseasier tohandleintheorythaninpractice,however.ThroughouttheearlyyearsoftheAIDSepidemicmanypeoplewhohadreasontofeartheymightbe infectedneverthelessdidn’twant toknow.At the time, therewasnotreatmentorcure.Apositivetestwasadeathsentencewithnoreprieve.“Thesedecisionsarenevereasytomake,”saidArthurCaplan,thedirectoroftheCenterforBioethics at theUniversity ofPennsylvania. “That lag betweenknowledgeand application can be excruciating. Maybe personal genomics will lookdifferentintenyears,butrightnowit’saworldoffortune-tellingandbadnews.”

That depends on what you learn. If, for example, you discover that youpossessagreatly increased riskofdeveloping type2diabetesorheartdisease,there are changes in diet and lifestyle that can help. There are also numerousmedications. Will they help enough? Nobody will know until more geneticinformationisavailable.Thetestshavealreadyproventheirvalueinotherways,though.Genome-wideassociation testshaverevealedhowabnormalcontrolofinflammation lies behind one of the principal causes of age-related maculardegeneration,whichisaleadingcauseofvisionlossinAmericanssixtyyearsofageandolder.Morethanonepromisingdrugisalreadyunderdevelopment.Thetests have also discovered genes that reveal pathways of inflammation criticalforthedevelopmentofinflammatoryboweldisease,aswellasgeneticpathwaysforheartdisease,diabetes,andobesity.

Aprincipal goal of this research is toprovidedoctorswith information thatwill take the guesswork out of writing prescriptions. In the case of the bloodthinnerwarfarinthathasalreadybeguntohappen.WarfarinisprescribedtotwomillionpeopleeachyearintheUnitedStates.Theproperdosecanbedifficulttodetermine,anduntilrecentlydoctorssimplyhadtomakeaneducatedguess.Toomuchofthedrugwillputapatientathighriskforbleeding;toolittlecancauseblood clots that lead to heart attacks. The dose can depend on age, gender,weight,andmedicalhistory.Butitalsodependsongenetics.TwoversionsoftheCYP2C9genecanretardthebody’sabilitytobreakdownwarfarin.Thiscausesthe drug’s concentration in the bloodstream to decrease more slowly, whichmeansthepatientwouldneedalowerdose.Armedwiththatkindofinformation—whichthesetestsnowprovide—aphysicianisfarmorelikelytogetthedoserightthefirsttime.

Thatistheessenceofpharmacogenetics.Ifthreepeopleoutofathousanddieduringaclinicaltrialduetoadrugreaction,thatdrugwillnevermakeittothemarket in the United States, even though it would have worked withoutcomplicationsformorethan99percentofpatients.Ifweknewwhothosethreepeoplewere likely tobe, however, noneof thatwouldmatter.Obviously, thatkindof knowledgewouldhave saved thousandsof lives lost toVioxx.And itwouldhavepermittedmillionswhowerenotatriskofheartattackorstroketocontinuetotakeadrugthathadhelpedthemimmensely.

“Wearejuststartingallthis,”GeorgeChurchsaid.Inadditiontohisacademicandentrepreneurialcommitments,Churchadvisesseveralgenomicscompanies,including 23andme. “But there is already great value to these tests. If youhappentohaveaSNPthat leads toadisease thatchangingbehaviorwillhelp,then it’smagnificent.So if youhaveapropensity todiabetes, you’regoing towanttoexercise,don’teatcertainthings,etcetera.Ifyouhaveapropensitytoacertaintypeofheartdisease,etcetera,etcetera.IfyouhaveapropensitytowardsAlzheimer’s,youmightwanttostartonastatinearly,youknow?”

AFTERWALKINGOUTofChurch’slaboratoryatHarvard,Itookacabtotheairport and flew home. It wasn’t a pleasant flight because I couldn’t stopthinking about the terrifying phrase “propensity toward Alzheimer’s.” Whowouldn’tfearadiseasethatstartsbymakingusforgetmuchofwhatwewouldchoosetorememberandendsinferaldespair?Ihavespecialreasontoworry.Afewyearsagomyfatherbegantodisappearintoacloudofdementia.Hisillnesstook thenormalpattern—first forgettingkeys (aswealldo), thennames, thensimpledirections,andeventuallywhateveryouhadtoldhimfiveminutesbefore.Inevitably,hebecameincapableoffendingforhimself.Icanthinkofnoworsefate.

Formostcommondiseases,therelativerisksposedtoindividualsbyspecificgeneticmutationsremainunclear.Therearejusttoomanymovingpartswehaveyet to analyze. Alzheimer’s is an exception. Genomic studies have providedcompelling evidence that a variant of at least one protein, called APOE andfound on chromosome 19, dramatically increases the risk of developing thedisease. APOE contains the instructions necessary to make a protein calledapolipoprotein, which plays a complicated role in moderating cholesterol and

clearingfatsfromtheblood.Therearethreecommonforms,oralleles—APOE2,3,and4.APOE4isthetimebomb.

Peoplewith twocopiesofAPOE4have fifteen times the riskofdevelopingAlzheimer’s than a typical person of similar ethnic heritage. They are also atgreatriskoflosingtheirmemoryfarmorerapidlythanpeoplewithoutthisallele,or those who have just one copy. The correlation between APOE4 andAlzheimer’sdiseaseissodramaticthatwhenJamesWatsonbecamethesecondperson (CraigVenterwas the first) to publish his entire genomic sequence in2007,hechose,ofallthebillionsofnucleotidesthatcomprisehisDNA,toblockonlythatdata.ThereisAlzheimer’sinWatson’sfamily,anddespitehisage—hewasseventy-nineatthetime—Watsonsaidhedidn’twishtoknowthestatusofsuchadebilitatingdiseaseforwhichthereisnocure.

Many, perhaps most, people would make the same decision, choosing tosubscribe to thatwell-worn aphorism fromEcclesias tes: “Withmuchwisdomcomesmuch sorrow; themore knowledge themore grief.”Others adhere to amoreradical,denialistvision:“Ignorance isbliss.” Iprefer tosee fate thewayLawrence of Arabia saw it after he managed to cross the Nefud desert.“Remember,”hesaidtoastunnedAli,whohadwarnedthatthetripwouldkillLawrence,thecamels,andallhismen.“Nothingiswrittenunlessyouwriteit.”It’snotasifIbelievedthatknowledgewouldpermitmetoaltermyprospectsofdevelopingAlzheimer’s,butitwouldsurelypermitmetoaltereverythingelseinmylife.

“There’s almost nothing that you can’t act on in some way or another,”Churchhad toldmeatHarvard.“It’sprobabilistic just likeeverydecisionyoumakeinyourlife.Whatcaryou’vegot,whethertojogornot.Youcanalways—ifthere’snocure,youcanmakeacure.YoucanbeAugustoOdone.YoucandothenextLorenzo’sOil.Youmaynotbesuccessful,butatleastitwillkeepyoubusywhileyou’redying,orsomebodyinyourfamilyisdying.

“AndIwoulddefinitelyprefertobebusythantobeignorant,”hecontinued.“Inotherwords,‘Gee,Idon’tknowifIhavetheHuntington’sgene,soIdon’tknowifIshouldgooutandraisemoneyandgeteducated.’Ithinkanincreasingnumberofpeoplearegoingtobealtruistic—orselfish,dependinguponhowyoulookatit—andsay,‘Iwanttoknow,soIcanspendamaximumamountoftimewithmylovedones,fixingthefamilydisease.’”

I had already signed up for the tests offered by Navigenics, deCODE, and23andme.MyAPOEstatuswasincludedonmyNavigenicsreport,anditnever

occurredtomenottolook.

Afewdayslater,Ipouredmyselfacupofcoffee,satdown,andsignedintotheWebsite,wheremydatawaswaiting.Liketheothercompanies,Navigenicsissues a detailed guide,which it calls yourHealth Compass, that assesses therisksassociatedwithmanyoftheSNPsinyourprofile.(AtthetimeitwastheonlycompanytoprovidecustomerswiththeirAPOEstatus,althoughatfirst ithad done so by a complicated and misleading route that involved testing adifferentgene,onethatisofteninheritedwithAPOE.)

Idownloadedthe40,000-wordreportonmypersonalhealth.Eachconditionwas described in three ways: as a percentile, which showed where my risksranked compared to the sample population; as the likelihood that I woulddevelop a given condition over my lifetime; and compared to the averageperson’srisk. Iheldmybreathand turned topagesix,whereIdiscovered thatmy lifetimeriskofdevelopingAlzheimer’s—4.4percent—washalf thatof theaverage man with my ethnic background. I don’t have either APOE4 allele,whichisagreatrelief.“Youdodgedabullet,”myextremelywisephysiciansaidwhen I told him the news. “But don’t forget they might be coming out of amachinegun.”

Hewas absolutely right.As is the casewithheart disease, diabetes, autism,andmanyotherconditions,therewillalmostcertainlyprovetobemanycausesofAlzheimer’s.One theory holds, for example, that in some cases cholesterolmayplayasignificantrole;peoplewithAlzheimer’softenaccumulatetoomuchofasubstancecalledamyloidprecursorprotein(APP).WeallproduceAPP,butin peoplewithAlzheimer’s disease the protein gives rise to a toxic substancecalledbetaamyloidthatbuildsupandeventuallycausesplaquesthatkillbraincells. There remainsmuch to be learned about this process, but some doctorsrecommendthatpeoplewithafamilyhistoryofAlzheimer’sdiseasetakestatins,which help to reduce cholesterol levels even when the results from standardcholesteroltestsarenormal.

ThisiswhenIrealizedthatbecominganearlyadopterofpersonalgenomicsisn’tlikebuyingoneofthefirstiPodsorsomeothercooltechnologicalgadget;thereisalotmoreatstake.MytestsshowedthatIhaveasignificantlyincreasedriskofheartattack,diabetes,andatrialfibrillation.Thesearenotsolelydiseasesinfluencedbygenetics,andeffectivemeasuresexisttoaddressatleastsomeofthoserisks—dietandexercise,for instance.That’s thegoodnews.AddingthatdatatomyfamilyhistoryofAlzheimer’sdiseasesuggeststhatitwouldprobablymake sense for me to begin taking a statin drug to lower cholesterol (even

thoughmineisnothigh).

Butcomplexasthosevariablesare,it’sstillnotthatsimple.Aboutonepersonintenthousandwhotakestatinsexperiencesaconditionknownasmyopathy—muscle pain and weakness. (And since millions of Americans take the drug,those numbers are not as insignificant as theymight seem.) It turns out that IhaveoneCalleleatSNPrs414056,whichislocatedintheSLCO1B1gene.Thatmeans I have nearly five times the chance of an adverse reaction to statins aspeoplewhohavenoCsonthatgene.(Itcouldbeworse;twoCsandyouroddsclimbtoseventeentimestheaverage.)Now,whatdoesthatmeanexactly?Well,ifthestudyiscorrectIstillhavefarlessthana1percentchanceofexperiencingmyopathy.I’ll takethoseodds.As23andmepointsout initsdescriptionof thestatin response,“Pleasenote thatmyopathy isavery rare sideeffectof statinseven among thosewith genotypes that increase their odds of experiencing it.”Therisksofheartdisease,however,and,inmyfamily,Alzheimer’sdisease,arenotrare.

CRUISING THROUGH ONE’S genomic data is not for the faint of heart.Thanks to23andme, Inowknow that I am left-eyedandcan tastebitter food.Cool.But I am also a slow caffeinemetabolizer. That’s a shame, because forpeoplelikemecoffeeincreasestheriskofheartattack,andIalreadyhaveplentyofthoserisks.Theinformation,though,helpsexplainamysteryofmyyouth.Idrankalotofcoffee,andperiodicallyIwouldseestudiesthatsuggestedcoffeeincreasedtheriskofheartdisease.Thenotherreportswouldquicklycontradictthem.With thisnewgenetic information thosedifferencesstart tomakesense;somepeople react badly to a lot of coffee andothers do not. I endedupwithgeneticbadluckonthecaffeinefrontandhavenochoicebuttodrinklessofit.

I’mnotresistanttoHIVormalariabutIamresistant,unusuallyenough,tothenorovirus(whichisthemostcommoncauseofwhatpeoplethinkisstomachflu;actually,it’snotfluatall).MymaternalancestorscamefromsomewhereintheUrals—but I alsohave abit ofBerber inmebecause at somepoint seventeenthousandyearsago,afterthelastIceAge,mypaternallineseemstohavemadeitswayintonorthernAfrica.

Ifthecalculationsprovidedbythesetestsfailtosatiateyourcuriosity,youcan

alwaysanalyzethemillionlinesofrawdatathatspellyourDNA(oratleastasmuchofitasthesecompaniescurrentlyprocess).YoucandownloadthedatainaZipfileasifitwereasongfromiTunesorsomefamilyphotos.Thensimplyplug that information into a free program called Promethease that annotatesthousandsofgenotypesandspitsbackunimaginablydetailedinformationaboutwhateverisknownabouteverySNP.Prometheaseisnotforeveryone,orreallyforverymanypeople.It’ssocomprehensivethatitisdifficulttointerpret—sortof like getting all the hits from aGoogle search dumped in your lap (and formostpeople,inalanguagetheydon’tspeak).

Thesearestillearlydaysingenomics,but itwon’tbelonguntilpeoplewillcarry their entire genome on their cell phone—along with an application thathelpsmakesenseofitall.Whenyoupickupthosedozeneggsatthestoreyourphonewillremindyouthatnotonlydoyouhavehighcholesterolbutyouhavealreadyboughteggsthisweek.Itwillwarnadiabeticagainstafoodwithsugar,and a vegan to skip the soup because itwasmade frommeat stock. Itwouldensurethatnobodywithhemochromatosisslippedupandboughtspinach,andinmycase,whenIbuycoffeebeans,itwouldnagmetorememberthattheyhadbetterbedecaf.

Someday—andnotsolongfromnow—medicinereallywillbepersonal.Theneveryone will be a member of his own race. When that happens one has towonder,Willdiscrimination finallydisappear,orwill it just findanewvoice?That’s up to us. In literature, scientific future is often heartless and grim.The1997 filmGattaca was a work of science fiction about aman burdenedwithDNAhe inherited fromhis parents, rather thanhavinghad it selected for himbeforeconception.Mostpeopleweremadetoorder.Butnotthemaincharacter,Vincent. He was a member of “a new genetic underclass that does notdiscriminatebyrace.”Avictimofgenoism.Ashepointsoutinthefilm,“Whatbegan as a means to rid society of inheritable diseases has become a way todesign your offspring—the line between health and enhancement blurredforever. Eyes can always be brighter, a voice purer, a mind sharper, a bodystronger,alifelonger.”

Somepeoplewatchedthatmovieandshuddered.Iwasn’tamongthem.Therearemanyworrisomepossibilitiesaboutthefuture,questionsofprivacy,equity,and personal choice not least among them. Even the most ethically complexissuescanbeframedpositively,though,providedwearewillingtodiscussthem.Thereisnoreasonwhythepasthastobecomethefuture.

“Terrible crimes have been committed in the nameof eugenics.Yet I am a

eugenicist,”theBritishdevelopmentalscientistLewisWolperthaswritten.“Forit nowhas another, verypositive, side.Modern eugenics aims tobothpreventand cure those with genetic disabilities. Recent advances in genetics andmolecularbiologyofferthepossibilityofprenataldiagnosisandsoparentscanchoosewhether to terminateapregnancy.Thereare thosewhoabhorabortion,but that is an issue that should be kept quite separate from discussions aboutgenetics. In Cyprus, the Greek Orthodox Church has cooperated with clinicalgeneticiststoreducedramaticallythenumberofchildrenbornwiththecripplingblooddiseasethalassemia.Thismustbeaprogrammethatweshouldallapplaudandsupport.Ifindithardtothinkofasensiblereasonwhyanybodyshouldbeagainst curing those with genetic diseases likemuscular dystrophy and cysticfibrosis.”

Youdon’thavetobeDr.Frankensteintoagreewithhim.Weneedtoaddressthese issues and otherswe have yet to envision. Therewill bemanyways toabusegenomics.Thesametechnologiesthatsaveandprolongmillionsoflivescanalsobeusedtoharmpeopleanddiscriminateagainst them.Buthasn’t thatalwaysbeentrue?Thestakesarehighernow,but theopportunitiesaregreater.Wearestill incontrolofourfate,althoughdenialistsactas ifwearenot.Theworstonlyhappenswhenweletithappen.

ACKNOWLEDGMENTS

I have been luckywith editors throughoutmy career, but nevermore so thanduringmydecadeattheNewYorker.FormuchofthattimeIhaveworkedwithJohnBennet,who, likeallof thegreatones,combinesdeft literary talentwithunique psychiatric skills. I could not have made my way toward this bookwithout his guidance. Among the many people at the magazine (past andpresent)whohavealsohelpedmeIwanttothank:DorothyWickenden,HenryFinder, Jeff Frank, Ann Goldstein, Elizabeth Pearson-Griffiths, ElizabethKolbert, Pam McCarthy, Sarah Larson, Julia Ioffe, Ame lia Lester, LaurenPorcaroandAlexaCassanos.

Severalfriendsandcolleaguesreadearlyportionsofthebook,andafewevenwadedthroughallofit.Naturally,mysins(andevenmyopinions)arenottheirs;butthebookwouldhavebeenimmeasurablyweakerwithoutthem.Inparticular,Iwould like to thankDanielZalewskiandMeghanO’Rourke.Somehow, theyeachfoundtimetoreadchapters,andthenprovidedetailedsuggestionsforhowtomakethembetter.MyfriendRichardBrodyreadthebookasIwroteit,withgreat enthusiasm but a stern eye for faulty logic and broken sentences. SuzyHansenservednotonlyasanablefactchecker,butalsoasademandingreader.Any mistakes that survived her attention—or anyone else’s—are my faultcompletely.

At thePenguinPress,AnnGodoff andVanessaMobleyembraced thebookfromthemomentIspoketothemaboutit.Myeditor,EamonDolan,joinedtheprocessafteritbegan—butsomehowseemedtounderstandwhatIwastryingtodobetterthanIdid.Hereadthoughtfully,rapidly,anddeeply.Idon’tknowwhatmore a writer could ask. I am also indebted to Nicole Hughes, Tracy Locke,CarolineGarner,andLeighButler,whodoublesasalongtimefriend.

Many friends have heard me drone on about this subject for years—encouragingme all the while. (And also arguing—which I tend to see as thesamething.)FortheirsupportandgoodcheerIwouldliketothankGaryKalkut,Esther Fein, Gerry Krovatin, Sarah Lyall, Robert McCrum, Anne McNally,Richard Cohen, John Kalish, Jacob Weisberg, Deborah Needleman, JacobLewis,SergeyBrin,AnneWojcickiandAlessandraStanley.

WhenIwasachilditoftenannoyedmethatmyparents,HowardandEileenSpecter, acted as if I could do anything. As I age, however, I have come to

realize there isaroleforblinddevotion in thisworld—andI thankthemfor itprofusely. My brother, Jeffrey, and his wife Yaelle, shouldered much familyresponsibilitywhile Ihidbehindmy laptop,andwithout thathelp therewouldhavebeennobook.

Over the years, I have interviewedmany peoplewho have helpedme formandrefinetheideasinDenialism.Itwouldbeimpossibletothankthemall—andby trying I would only fail. Others, quite sensibly, preferred to remainanonymous.IwasaidedgreatlyearlyintheprojectbyalengthydiscussionwithJuanEnriquez—amanwhoknowsdenialismwhenheseesitandhasrejecteditwith singular eloquence. I would also like to thank: Linda Avey, EstebanGonzalezBurchard,ArtCaplan,RobCarlson,JoeCerrell,GeorgeChurch,JuneCohen, JohnElkington,DrewEndy,EdFarmer,TonyFauci, JayKeasling,C.EverettKoop,MarieMcCormick,BrianNaughton,MarionNestle, PaulOffit,NeilRisch,PaulSaffo,RobertShapiro,EricTopol,KariStefanssonandEckardWimmer.

Thousands of words of thanks have already been written on behalf of myfriend and agent, Amanda Urban. They are insufficient. She combinesintelligence,tenacity,vigorandloyalty-nottomentiontheoccasionaltouchoffury—inabundleunlikeanyotheron theplanet.AnnaQuindlenhasbeenmyfriend since newspapers used hot type—fortunately for me the friendshipoutlastedit.Anna,too,readearlydraftsandprovidedmewithmanynotes—forwhichIammoregratefulthanshecouldknow.

OnmyfirstdayofworkattheWashingtonPost,nearlytwenty-fiveyearsago,I noticed a tall man wandering aimlessly in the aisles, looking a bit like hebelongedinanotherplace.ThatplaceturnedouttobetheofficeoftheeditoroftheNewYorker.DavidRemnick’sleadershipofthemagazinehasbeenpraisedbymanyothers—andIcanonlyaddtothechorus.NearlyeveryMonday,proofofhisgift turnsuponnewsstandsand inhundredsof thousandsofmailboxes.David is a remarkable editor—but an even better friend. Our conversation—often separatedbycontinents—has lastedmanyyears.Hewas the earliest andmost consistent proponent of this book—and I thank him for that and foreverythingelse.Denialismisdedicatedtomydaughter,Emma,whoattheripeoldageofsixteenmanagestoteachmesomethingneweveryday.

NOTES

Mostoftheinformationcontainedinthisbookcomeseitherfrominterviewsorfromthelargeandconstantlygrowingbodyofscientificresearchthataddressesthe subjects of each chapter. I will put footnotes on my Web site,www.michaelspecter.com.

IthoughtitmightbeusefulheretopointoutatleastsomeofthesourcesIfoundparticularly compelling. Traditional journalists (a category that includes me)tend toderideblogsassomuchuneditedandcontradictorynoise.That’softentrue;butsomeofthemostinsightfulsciencewritinginAmericacanbefoundonblogs these days—and I was lucky to have them at my disposal. Five inparticular stand out as well-written, factually precise, and remarkablycomprehensive:Aetiology,which focuses on evolution, epidemiology, and theimplications of disease (http://scienceblogs.com/aetiology/); RespectfulInsolence, amedical blog that explains itself at theoutsetwith the thoroughlyaccurate comment “A statement of fact cannot be insolent”(http://scienceblogs.com/insolence/); ScienceBased Medicine(http://www.sciencebasedmedicine.org); Neurodiversity, which is almostcertainly the most complete archive of documents related to autism on theInternet (http://www.neurodiversity.com/main.html); and Denialism(http://scienceblogs.com/denialism/).Forsomereason,Ididn’tstumbleuponthelastofthemuntillateintheprocessofwritingthisbook—butit’sexcellent.

1.VioxxandtheFearofScience

For a book that addresses the causes of our growing sense of disillusionmentwith the American medical establishment, I would suggest John Abramson’sOverdosed America: The Broken Promise of American Medicine(HarperPerennial, rev. ed., 2008). There were two congressional hearings onVioxx.Documents pertaining to the first, held onNovember 19, 2004, by theSenate Finance Committee, are available athttp://finance.senate.gov/sitepages/hearing111804.htm.RepresentativeHenryA.Waxman convened hearings in theHouse onMay 5, 2005,which focused onhow drugs are marketed in the United States. All testimony and supportingmaterial is available at http://waxman.house.gov/News/DocumentSingle.aspx?DocumentID=122906.Inretrospect,theinitial2001studybyEricTopolandhiscolleagues,whichappearedintheJournaloftheAmericanMedicalAssociation,standsoutas restrained,well-reasoned,andprescient.UnlessyouareanAMA

member, though, you will have to buy it (http://jama.ama-assn.org/cgi/content/full/286/22/2808).“WhatHaveWeLearntfromVioxx?”byHarlan M. Krumholz and several colleagues examines the episode and itsimpact. The article, published by the British Medical Journal, appeared inJanuary2007(www.bmj.com/cgi/content/full/334/7585/120).

Fortwoparticularlyusefuldiscussionsofeugenics,IwouldrecommendDanielJ.Kevles,IntheNameofEugenics:GeneticsandtheUsesofHumanHeredity(HarvardUniversityPress,1995).Toget a senseofhowa thoughtful scientistcan follow reason and logic out the window (and take large segments of theworld with him), there is no better place to go than to Francis Galton’sHereditaryGenius(PrometheusBooks,1869).

2.VaccinesandtheGreatDenial

For adeeply insightful primeronvaccines, theplace to turn isArthurAllen’sVaccine: The Controversial Story of Medicine’s Greatest Lifesaver (Norton,2007). Paul Offit not only invents vaccines, he writes about them with greatauthority.Iamdeeplyindebtedtohis2008bookAutism’sFalseProphets:BadScience, Risky Medicine, and the Search for a Cure (Columbia UniversityPress). TheNationalAcademy of Sciences, through the Institute ofMedicine,has released two exhaustive reports on the safety of vaccines: ImmunizationSafety Review: Measles-Mumps-Rubella Vaccine and Autism (2001), andImmunization Safety Review: Vaccines and Autism (2004). Both are availablethroughtheNASWebsite(.http://wwwnationalacademies.org).

Itwouldbehypocriticalofme,inthisbookaboveall,toignorethosewhorejectthescientificconsensus.Twoplacestobegin:theNationalVaccineInformationCenter (http://www.nvic.org), and David Kirby’s book Evidence of Harm:Mercury in Vaccines and the Autism Epidemic: A Medical Controversy (St.Martin’s Press, 2005). Kirby also maintains a robust collection of articles,testimony,andtranscriptsathttp://www.evidenceofharm.com/index.htm.

3.TheOrganicFetish

ThebestbookIhaveeverreadaboutthewaysinwhichgeneticallyengineeredandorganicfoodrelatetoeachotherandtosocietyisbythehusband-and-wifeteam Pamela Ronald and Raoul Adamchak, Tomorrow’s Table: OrganicFarming, Genetics, and the Future of Food (Oxford University Press, 2008).

AdamchakisanorganicfarmerandRonaldaplantgeneticist.Theirknowledge,sophistication, and priorities ought to provide at least some evidence thatseeminglyirreconcilabledifferencesarenotimpossibletoresolve.(Ronaldalsomaintains a fascinating blog by the same name,http://pamelaronald.blogspot.com.) Everything Marion Nestle writes is worthreading(usuallymorethanonce).IparticularlyrecommendFoodPolitics:Howthe Food Industry Influences Nutrition and Health (University of CaliforniaPress,2002)andWhattoEat(NorthPointPress,2006).DeniseCarusorunstheHybridVigorInstitute.Hercalltoexcesscautionseemsunwarrantedtome,butnobody makes the argument better or more thoroughly: Intervention:ConfrontingtheRealRisksofGeneticEngineeringandLifeonaBiotechPlanet(HybridVigorPress,2006).

Fordataonagriculturalproduction,hunger,ordevelopmentinAfrica,Isuggestthat any interested reader look at theWorldBank’s2008WorldDevelopmentReport: Agriculture for Development. (The URL for this report is almostcomically long. It would be far easier to go to the bank’s general site,www.worldbank.org,andtype“2008worlddevelopmentreport”intothesearchbox.) Among the other studies I have found useful: the PewCharitable Trust2008 reportPuttingMeaton theTable: IndustrialFarmAnimalProduction inAmerica (http://www.ncifap.org/)and theRockefellerFoundation’s2006studyAfrica’s Turn: A New Green Revolution for the 21st Century(www.rockfound.org/library/africas_turn.pdf). The annual report of the Foodand Agriculture Organization of the United Nations always addresses theseissues,butnevermoredirectlythanthe2004studyAgriculturalBiotechnology:Meeting the Needs of the Poor? (www.fao.org/es/esa/pdf/sofa_flyer_04_en.pdf).Finally,LouiseO.Frescohaswrittenoftenandrevealinglyaboutissuesoffoodsecurityinthedevelopingworld.Seeparticularlyherreport,lastupdatedin2007,Biomass,Food&Sustainability:IsThere a Dilemma?(www.rabobank.com/content/images/Biomass_food_and_sustainability_tcm43-38549.pdf).

Therearemanydiscussionsof the“precautionaryprinciple,”fear,andthe ideaof risk. Four stand out to me: Cass Sunstein’s Laws of Fear: Beyond thePrecautionaryPrinciple(CambridgeUniversityPress,2005);LarsSvendsen’sAPhilosophy of Fear (Reaktion Books, 2008); Peter L. Bernstein’sAgainst theGods: TheRemarkable Story ofRisk (Wiley, 1996); andLeonardMlodinow’sTheDrunkard’sWalk:HowRandomnessRulesOurLives(Pantheon,2008).

4.TheEraofEchinacea

The Cochrane Collaboration (www.cochrane.org), through its Database ofSystematic Reviews, comes as close as possible to providing authoritativeinformation in a field that needs it badly. In addition, theNationalCenter forComplementary Medicine, the Harvard School of Public Health, and theMemorialSloan-KetteringCancerCentereachofferinformationonvitaminsandsupplements at http://nccam.nih.gov, http://www.hsph.harvard.edu, andhttp://www.mskcc.org/mskcc/html/1979.cfmrespectively,asofcoursedomanyotherinstitutions.

The twobest recent treatments of alternative health haveboth beenwritten oredited by Ernst Edzard, who is professor of complementary medicine at theuniversities of Exeter and Plymouth. The first, written with Simon Singh, isTrickorTreatment:TheUndeniableFactsaboutAlternativeMedicine(Norton,2008). Edzard also edited Healing, Hype or Harm? A Critical Analysis ofComplementaryorAlternativeMedicine (Societas,2008).For theothersideofthe story,AndrewWeil is theman to see.He is prolific, but onemight beginwithHealthyAging:ALifelongGuidetoYourPhysicalandSpiritualWell-Being(Knopf,2005).

Foradisciplinedandopinion-freehistoryofvitaminregulationinAmerica,seethe 1988 Surgeon General’s Report on Nutrition and Health. The managingeditorwasMarionNestle,andthe750-pagereportisavailableatherWebsite,among other places (www.foodpolitics.com/wp-content/uploads/surgeon-general.pdf).

I try toremainopen-mindedonallscientific issues,but thereare limits.ThoseeagertoexplorethephenomenonofAIDSdenialismareontheirown.Anyoneseekingtounderstandtheactualrootsofthedisease,oritsnaturalprogression,however,canstartatwww.aidstruth.org—whichlivesuptoitsname.

5.RaceandtheLanguageofLife

Forageneralargumenton the issueof raceandethnicbackground inmedicaltreatment,thereisthe2003piecebyBurchardandRischetal.,“TheImportanceofRaceandEthnicBackgroundinBiomedicalResearchandClinicalPractice.”For an abstract and an extensive list of subsequent papers on the topic go tohttp://content.nejm.org/cgi/content/short/348/12/1170; Sandra Soo-Jin Lee’s

essay“RacializingDrugDesign:ImplicationsofPharmacogenomicsforHealthDisparities,” in the December 2005 issue of the American Journal of PublicHealth, is a smart discussion of race and genomics(www.ajph.org/cgi/reprint/AJPH.2005.068676v2.pdf). The New YorkUniversitysociologistTroyDusterhaswrittenwidelyonthe topicaswell;seeBackdoor to Eugenics (Routledge, 2003), among many other publications.RobertS.Schwartzargues thatgenomicshas turned theconceptof race intoadangerous anachronism in his “Racial Profiling in Medical Research,” NewEngland Journal of Medicine 344, no. 18 (2001). It can be purchased at thejournal’sWebsite(http://content.nejm.org).

Thebest short explanatorybook Ihaveever readon the subjectofgenetics isAdrianWoolfson’sAnIntelligentPerson’sGuide toGenetics (OverlookPress,2004).Twootherbookshaveprovenvaluabletome:JamesSchwartz,InPursuitoftheGene:FromDarwintoDNA(HarvardUniversityPress,2008),andBarryBarnes and JohnDupré,Genomes andWhat toMake of Them (University ofChicagoPress,2008).

6.SurfingtheExponential

As I note in the book, the phrase “surfing the exponential” comes fromDrewEndy of Stanford University. The best study on the topic is New Life, OldBottles:RegulatingFirst-GenerationProductsofSyntheticBiologybyMichaelRodemeyer,a formerdirectorof thePewCharitableTrust’s InitiativeonFoodandBiotechnology.Thisreport,issuedinMarch2009undertheauspicesoftheWoodrowWilson International Center for Scholars, can be obtained from theSynthetic Biology Project(http://www.synbioproject.org/library/publications/archive/synbio2/).

TheETCGroup(ActionGrouponErosion,TechnologyandConcentration)hastakentheleadincallingforstricteroversightofthisnewdiscipline.Thegroupposes thoughtful questions that demand thoughtful answers. On December 8,2008,StewardBrand’sLongNowFoundationsponsoredanunusuallyamicabledebate between ETC’s Jim Thomas and Endy. The conversation provides athoroughairingoftheissuesandcanbepurchasedonDVDatAmazon.com(thepodcast is also available at no charge:http://fora.tv/media/rss/Long_Now_Podcasts/podcast-2008-11-17-synth-bio-debate.mp3).

ETC has released many studies, all of which can be found on the group’s

homepage (http://www.etcgroup.org/en/issues/synthetic_biology.html). Themost important and comprehensive of them,Extreme Genetic Engineering, ishere(http://www.etcgroup.org/en/issues/synthetic_biology.html).

Scientistsareoftenaccusedofignoringtheethicalimplicationsoftheirwork.Itisworthnothing, then, thatCraigVenter—thegenomicworld’sbrashestbrandname—embarked on a yearlong study of the ethical and scientific issues insyntheticbiologybefore stepping into the lab.SyntheticGenomics:OptionsofGovernance, by Michele S. Garfinkel, Drew Endy, Gerald L. Epstein, andRobertM.Friedman,isavailableatwww.jcvi.org/cms/research/projects/syngen-options/overview/, and the technical reports that were commissioned for thestudycanbefoundathttp://dspace.mit.edu/handle/1721.1/39658.

Thescientific rootsof syntheticbiologyareexplored inPhilipJ.Pauly’sbookControlling Life: Jacques Loeb and theEngineering Ideal in Biology (OxfordUniversity Press, 1987). It’s expensive and hard to find; but it is out there. Iwould also recommend Michael Rogers’s book about the early days ofrecombinantDNA technology,Biohazard (Knopf,1979).That, too, isdifficulttofind.ForanyoneinclinedtowonderwhyEckardWimmercreatedasyntheticpoliovirus,Isuggestreadinghis2006articleontheimplicationsoftheresearch,publishedintheJournaloftheEuropeanMolecularBiologyOrganization,“TheTest-TubeSynthesisofaChemicalCalledPoliovirus.”Afree,full-textversionof the article can be found athttp://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16819446.

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ABOUTTHEAUTHOR

MichaelSpecterwritesabout science, technology, andglobalpublichealth fortheNewYorker,wherehehasbeenastaffwritersince1998.SpecterpreviouslyworkedfortheNewYorkTimesasarovingcorrespondentbasedinRome,andbefore that as the Times’s Moscow bureau chief. He also served as nationalsciencereporterfortheWashingtonPostaswellastheNewYorkbureauchief.HehastwicereceivedtheGlobalHealthCouncil’sExcellenceinMediaAward,firstforhis2001articleaboutAIDS,“India’sPlague,”andsecondlyforhis2004article “The Devastation,” about the health crisis in Russia and the country’sdrasticdemographicdecline. In2002,Specter received theScience JournalismAwardfromtheAmericanAssociationfortheAdvancementofScience,forhisarticle “Rethinking theBrain,” about the scientific basis of howwe learn.Hiswork has been included in numerous editions of The Best American ScienceWriting.