Global Alert: Anthropogenic Influences on Biology and the Biota, and Connections to Autism Spectrum Disorders

8/6/2019 Global Alert: Anthropogenic Influences on Biology and the Biota, and Connections to Autism Spectrum Disorders

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RUSSEll M. JAFFE, MD,PhD, CCN, started as a skepticand became a proponent orevidence-based integrativemedicine. Dr. Jae works romfrst principles o biology toclariy the causal mechanismso health, emphasizing the endgoal o high-level unction andwell-being. Dr. Jaes clinicaland research interests ocus

on nutritional immunology, thehealing response, and treatmentprotocols or autoimmuneillness including autism. Dr. Jaehas also worked to developunctional, predictive testsand procedures to improvediagnostic precision andtreatment outcomes.

Dr. Jae received dual degrees(MD and PhD) rom BostonUniversity and carried out aresidency in Clinical Pathology

at the National Institutes oHealth in Bethesda. He is theormer director o the PrincetonBrain-Bio Center and a ormercommander in the US PublicHealth Service. His proessionalcontributions include workon clinical diagnostics andhealthcare policy, publicationo over 100 peer-reviewedarticles, and over 1000 invitedpresentations. Dr. Jae is amember o numerous scientifcassociations and the recipient o

many honors and awards.

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INTRODUCTIONAutism spectrum disorder (ASD) is one oseveral neurodevelopmental disorders thathave increased over 100-old in less than acentury, particularly in the developed world.1Over this time period, an unprecedentedtwo-way experiment between humans andthe natural world has been under way.2As human activity reaches the point whereit is aecting planetary ecosystems, thesum o local human choices has deliveredunoreseen consequences oten extending

ar beyond their source.3

The outcome o thisneither controlled nor blind experiment raisesquestions about the quality, diversity, andsustainability o lie on earth.4-28

This article rethinks conventionalunderstandings o autism rom amultidisciplinary, integrative, and unctionalperspective, drawing on the disciplines ointegrative physiology, molecular biology,environmental toxicology, and systemsdynamics. Focusing on molecular causeso autism, we lay the oundation or atypology o ASD that di erentiates between

biochemically and metabolically distinct

subgroups. This approach recognizes thatclinical expressions o ASD are diverse, andthat ASD possibly and more appropriatelymight be considered a collection o discretedisorders with some overlapping clinicalexpressions. When people with ASD arestudied as a single group (as is typicallydone), important dierences or one subgroupmay not be apparent. However, developmento better treatments or ASD depends uponaccurate diagnosis.5,6 Teasing apart possibleASD subgroups may allow or improved

diagnostic precision and, ultimately, bettertherapeutic outcomes.

mUlTIDIsCIplINARy peRspeCTIve

By seeking and blundering we learn.Johann Wolgang von Goethe (1749-1832)

In this report, we use unctional insights ophysiology7,10-15 developmental biology6-9 ,toxicology,8,28 and systems thinking9,10,15-18to develop a proposed typology o ASD.11These our disciplines combine in what can be

reerred to as integrative science.12-21

GloBal aleRT:

anThRopoGenic

influences on BioloGyand The BioTa, and

connecTions To auTism

specTRum disoRdeRs

No nation is any healthier than its children.Harry S. Truman (1884-1972, 33rd president o the United States)

By rUSSELL jAFFE, MD, PHD, CCN AND NOrMAN SCHWArZ, MD

Inegraie physiology: Includes insights omolecular biology13,14 and non-equilibriumthermodynamics15 as they describeobservable, macroscopic phenomena andbehaviors.

Molecular biology:Explores living systemsrom molecules to macro compositions ochemicals16,17seeking insights into higherorder unctions.18-25

Enironmenal oxicology: Examines the

eects o low levels o pervasive xenotoxins,with a particular ocus on times o specialvulnerability to xenotoxic eects (e.g.,gestation, early childhood development,moments o intense distress). Individualvulnerability varies based on efciency andresilience o cell systems.6-9,19

Sysem dynamics: Uses an interdisciplinaryand holistic20 perspective to look atcomponents interactions and the timing otheir interactions21 (in contrast to mechanisticand reductionist biomedical views that look a

single variables or isolated variables).20,26



NORM SChWARtz, MD, is anintegrative medicine specialistwith over 30 years experienceand an extensive background intreating complex chronic healthproblems. Formerly medicaldirector o Integrative Medicine orWheaton Franciscan Healthcarein Milwaukee, Wisconsin, he isnow in private practice, ocusingon helping individuals and

amilies who are dealing withADHD and autism spectrum andneurodevelopmental disorders. Asa Deeat Autism Now! practitioner,he approaches autism as amedical disorder that is treatable.Dr. Schwartz has a special interestin the application o ecologicalprinciples or the creation o asaer, more sustainable world orpresent and uture generations.

In addition to his medicaldegree and residency training,

Dr. Schwartz has receivedpostgraduate training andeducation rom the AmericanAcademy o EnvironmentalMedicine, the Santa Fe Institute orComplex Studies, the FunctionalMedicine Institute, the InternationalCollege o Integrative Medicine,and the American Academy or theAdvancement o Medicine. He is aounding member o the AmericanSociety o Integrative MedicalPractice and a Fellow o the HealthStudies Collegium, a health policy

and clinical outcomes researchoundation.

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When collectve le on eath and n the bosphee s appecated as a supe ogansm thatcontnuall eacts and ebalances tsel, t becomes appaent that how ogansms nteact and

nuence the envonment afects the health and the ofspngs sustanablt.

INTeRDepeNDeNCe wITh All lIfe

Survival of a complex system (cell)is constrained by the least available

essential item.Russell Jae (1947- ), biotechnologist

(based on Justus von Leibig, 1803-1873)

People are to the environment as fsh areto water, which is to say, interdependent.Physiologic systems are also remarkablyresilient, as complexity theory,22 systemsdynamics,23 and inormatics24 has helpedunderstand. Cooperation occurs at multipleinterconnected levels to ensure rapid

responses to internal and external stressorsto maintain homeostasis.25-47Whereverwe look in detail, myriad interconnectionsbetween living systems and the biosphere areobserved.26-36 For example:

1. The water we drink has been recycledand purifed or eons inside earthaquiers.32

2. The air we breathe is exchanged globallywith all other respiring organisms.27,35,43

3. The essential nutrients within us arerecycled through soil with remarkableefciency and lack o waste.10,14,42

4. Conserved biochemistry across allcellular lie includes metabolic controlpoints that show special vulnerability totoxins at certain times.34

Lie is sel-organizing, exhibiting propertieso complex adaptive systems that operate arrom thermodynamic equilibrium. Organismsmust maintain local coherent autonomy

and global connectivity over 16 orders omagnitude in space and time to achieve ahealthy, dynamically stable state. From abiomolecular standpoint, these propertieso biological systems oten emerge onlyat quaternary or architectural levels oorganization.28-34 This means that unctionsand properties in complex systems25,29

are unpredictable rom understandinglower levels o organization.30 Complexunctions include the exquisitely balancedneuroimmunohormonal, reproductive,catabolic recycling, and anabolic rebuilding

processes upon which lie depends. A

common energy source and structure thatdistinguishes lie rom inert matter drives these

processes.19,32-34The extent to which ecosystems and

organisms are able to maintain stability andhomeostasis is intimately related to the qualityo the environment. We now know that theftness o the planet to support lie is not astable state but is actively maintained arrom equilibrium by interdependent lie ormssharing the same atmosphere, hydrosphere,and lithosphere.16-31 This interdependenceo biota (the total collection o organisms)means that harm in one locale can havewide-ranging consequences elsewhere. I we

view biology as a grand synthesis, regulatedby interdependent sel-sustaining mechanisms,it is clear that study o isolated parts can yieldonly limited inormation. Systems approachesthat use holistic tools will yield more useulinormation and, in this instance, can provideinsights into the causes and management opervasive developmental disorders (PDDs),including ASD.32

beyOND pReDICTAble lImITsBiology builds elegant complexity romsimple undamental building blocks.32

Myriad agents interact over multiplelevels o organization, and a uniyingtheoretical understanding to elucidate basicprinciples is still emerging. Until the lastew decades, the biological and medicalsciences were largely phenomenologicalin approach, based on observation andexperiments leading to description andcategorization. A very small percentageo this medical science, observational atbest, has passed rigorous scientifc scrutiny.In act, the US Congressional Ofce oTechnology Assessment ound that 87% o

general medical practice is validated onlyby consensus, and not by peer-reviewedevidence.33 Lewis Thomas, in his essays onThe youngest science as well as Sir WilliamOsler a century beore in hisAequanimitasessays tackle the same theme.34,35

Science proceeds by describing andexplaining, leading to testable predictions.Although the past several decades haveproduced a large body o data describingthe state o our biosphere, how oneassesses the ftness o the environment iscentral to how one shapes a response.

Whereas traditional environmental models

use genetically determined, reductionistreproductive success as the criterion

or determining ftness, systems biologyunderstands that organisms alter ecosystemotherthan through simple genetic inheritancknown as epigenetics.36 When collective lon earth and in the biosphere is appreciateas a super organism that continually reactsand rebalances itsel, it becomes apparentthat how organisms interact and inuencethe environment aects their health and theosprings sustainability.37-47 Living systemsresilience and capacity or homeostaticsel-regulation can successully handleenvironmental toxins only up to a fnite

limit.32,40,38

As human activity pushes ecological and

biological boundaries beyond predictablelimits,39 clinical40 and epidemiologicobservations are documenting some o theconsequences. For example, as environmenttoxins disperse and interact in waterways,soil and air, ecosystem disruptions result.41-51

These disruptions have proved challengingto calculate and accurately model; howeverconservative estimates include an 8.8 yearaverage reduction in lie span due to toxicminerals and related toxins alone, without

taking into consideration other xenotoxins. Tincremental medical cost rom toxic mineralscalculated to exceed $100 billion annually Sanawane, personal communication, 2006

GlObAl AleRT

A new consciousness is developingthat sees the earth as a single

organism, and recognizes that anorganism at war with itself is doomed

Carl Sagan (1934-1996)

Healthy systems are resourceul,interdependent, variable, and resilient.When these complex systems becomedistressed, their responses become fxed orrigid, increasing the risk o system overload,collapse or ailure.42 In 1998, an internationteam o Earth scientists defned nineundamental planetary biophysical systems,and also defned boundaries within whichthe systems could unction successully andbeyond which progressive harm to livingsystems would occur.43 They also made clethat transgression o one boundary adverse

aects resilience in other lie orms.



For three o the nine systems delineated bythat team o scientists, boundary conditionshave already been exceeded.44 Theconsequence o concurrently transgressingmultiple boundaries enrolls living systems in theunprecedented experiment described in theintroduction. The three aected systems include:

1. Bioogica diversiy: The planet isexperiencing a dramatic increase (by two to

three orders o magnitude) in species loss,with rates between one hundred and onethousand species lost per million species peryear (versus the natural background rate oone loss per million species per year).45

2. Nirogen cyce: There is a greater than100% deviation in the nitrogen cycle romhistorical levels.46

3. Cimae cange:Carbon dioxideconcentrations are approaching the dangerzone o 400 ppm, resulting in climate

change that makes it possible to kayak at theNorth Poll in January (as was done by MITastrophysicist Sara Seager in 2008).47

explORING The eTIOlOGy OfAUTIsm

That a disease is complex ormultifactorial does not imply that

simple solutions cannot be found orthat clinical advances following insight

cannot be swift.JA Rees (Science, 2002;296 : 698-701)

Reproductive, neurodevelopmental andlearning disabilities have rapidly increasedover the past century.48 One in fve childrenentering kindergarten currently carries amental health diagnosis,49 representing atenold increase within one generation. Asshown in Figure 1, the rate o increase inautism has steadily risen since 1992. Overthe most recent 2-year period, the Centersor Disease Control and Prevention (CDC)documented an increase rom 1 in 15 to 1 in10 students diagnosed with attention-defcithyperactivity disorders (ADD/ADHD), andan increase in ASD rom 1 in 150 to 1 in 110children (Figure 2).46-50 Autism is also growingaster than other developmental disabilities(Figure 3, next page).

Where ASD is concerned, evidencecontinues to accumulate that environmentalactors play an important and potentiallycausal role in its etiology.50 This article oersa straightorward set o interdisciplinaryconcepts and relationships that associatethe rising epidemic o neurodevelopmentaldisorders51 to exposure to multiple toxins atvulnerable times.52,53

Whee ASD s concened, evdence contnues toaccumulate that envonmental actos pla an mpotant

and potentall causal ole n ts etolog.

Cumulative Growth o Number o Cases(U.S. School Years 1992 - 2008)

2011 www.thoughtulhouse.org

PercentCumulativeGrowth(%)

2200

2000

1800

1600

1400

1200

1000

800

600

400

200

0

2200

2000

1800

1600

1400

1200

1000

800

600

400

200

092 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09

U.S. and Outlying Areas, Autism, Ages 6 -22

22% 45%87%

121%173%

247%

324%

411%

533%

662%

805%

971%

1145%

1342%

1558%

1779%

2039%

figur 1: Autis irease 1992 - 2009 (%)Note: Cumulative growth in autism cases by percent (%)

suggests that rate o increase continues to rise.

figur 2: chage i autis requey over tie

1 in every110

1 in every150

1 in every166

1 in every250

1 in every500

1 in every1,000

1 in every10,000 1970s 1995 1999 20 01 2005 2007 2009

Particularly implicated are substancesknown as xenotoxins, which causeoxidative damage54 to vulnerable cellcomponents through ree radical generationand concomitant depletion o protectiveantioxidants such as tocopherols,55ascorbate,56 glutathione,57and coenzyme

Q10.58 Xenotoxin exposures are particularlypernicious when the aected organismis also experiencing a defcit o essentialnutrients.25-31

In addition to xenotoxins, a number oother environmental inuences aect growthactors59and development. These include:


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repair, digestion,105 detoxifcation, immune106and neurohormone unctions, and synthesis

o elective protective products.107

All theseprocesses are sacrifced when the cell energydrops, as marked by a reduction in the ATP/ADP ratio o less than 100. Whereas healthycells have an abundance o potential energystored in ATP to apply to any cell need, a losso this reserve potential shits cells into survivalmode until cell energy is rebuilt.

b. Enzyme inhibiion. Inhibition o enzymesby toxins disrupts cell equilibrium that dependsupon enzyme catalysts. Metabolic controlsystems, digestion, nutrient assimilation,

detoxifcation, and neurohormonal regulation allbecome disintermediated.108

C. Oxidaie damage. Depletion oprotective antioxidant deenses109 such asascorbate leads to an unhealthy increase in thecell reduction-oxidation (or redox) potential,which, in turn, leads to an increase in the risko oxidative damage. This also means that theproton gradient between the cell cytoplasmand the mitochondrial110 battery is reduced,111

causing urther declines in ATP energyproduction.112 This then increases the risk o

a shit to surv ival mode away rom healthyelective synthesis.113 Studies o exposure levelsto chemically diverse toxicants common inindustrial societies also confrm that increasedoxidative stress results in essential nutrientdefcits and disruptions in critical cell signalingpathways.114

D. Cumulaie repair defcis. Inammation115(or cumulative repair defcits) means thatexposure to xenotoxins is occurring abovelevels that can be detoxifed. Cumulativerepair defcits and defcits in needed nutrients

are sufcient to cause disability rom repairdeects. In the etus or developing child, thisinammation may contribute to ASD116 and PDDrisk.117

e. Bioconcenraion. As detoxifcation abilityalls, bioconcentration o toxic matter rises.Whereas cell systems usually have hal- livesor turnover measureable rom ractions o a

second to days, toxins o concern have hal-livesor turnover in the environment rom months to

millennia.118

f. Auoimmuniy. When toxins bind to cellproteins, their conormation and unction arealtered. This can render them oreign to thebody, provoking autoimmune responses.119Autoimmunity contributes to chronic anddegenerative illness. Aspects o ASD and PDDmay be autoimmune120 expressions duringgestation and childhood development.121 Losso homeostasis during gestation and early liecan also disrupt core immune communicationsystems, as observed in some cases o ASD and

PDD.122

(In the elderly, loss o homeostasis canmaniest as hypertension and hypercoagulationsyndromes, with an increase in heart attack andstroke, accelerated aging, and loss o innateanti-cancer surveillance.)

ChIlDReN ARe NOT lITTle ADUlTs

Childrens exposure to chemicals atcritical stages in their physical and

cognitive development may have severelong-term consequences or health.

International Program on Chemical Saety,

WHO, ILO, UNEP (2011)

The exquisitely poised and fnely tunedprocess o brain development is continuousrom embryonic development through thelie span.123 Under usual circumstances,neurodevelopmental unctions operate so wellthat their adaptive and sel- correcting natureis easily overlooked or taken or granted.However, the complexity, sensitivity,124connectivity, plasticity,125 and development othe human nervous system are vulnerable todysunction and intererence at each stage o

development.126

In addition, the developingor remodeling brain is more vulnerable thanthe stable brain. Childrens metabolic anddetoxifcation systems have less reserve thanthose o adults, when corrected or weightdierences, increasing childrens vulnerability tomultiple, intermittent toxic exposures. For betterand or worse, childhood behaviors interact withand are more exposed to the environment.127

through mental and physical exercises, saeand adequate nutrition,100 and supportive

amily structures.101

More specifcally, apositive cycle should include sufciencyo essential nutrients reected in predictivemarkers, thus recognizing biochemicalindividuality. This cycle would also includemental and physical activities sufcient toprovide stress resilience. The fnal element othis positive cycle is relationship to others andthe environment that includes stewardshipand meaningul work, providing the basis orresilient sel-esteem, optimism today, and hopeor tomorrow. This can be synthesized as theAlkaline Way or sustainable living.

fURTheR lINKs TO AsD

The persistence o and interaction among newlysynthesized chemicals with toxic eects raisesseveral concerns. First, there is an alarmingabsence o adequae deelopmenalneurooxiciy esing. In general, chemicalsintroduced into the environment have beenassumed to be sae unless or until harm isestablished with a high level o scientifcconsensus. This approach has proven costlyto both lie orms and social structures. Subtleyet proound eects rom modest levels o

persisting toxins are increasingly ound,102

which supports a precautionary principleapproach. The burden o demonstrating saetyshould be placed on that which is novel, ratherthan assuming innocence or the latest andgreatest.

Second, the inabiliy o adequaelymonior polluans, when the levels that causeharm are below the detection limits o generallyavailable equipment, is a serious shortcoming.In this area as well, it would be more sensible toadopt a precautionary approach, placing theburden o establishing saety on the source o

novel compounds with regard to long-term orsystemic eects.103Third, it is clear that xenotoxic tMs, vOCs,

POPs, EMFs, and radioisoopes disrupbiological processes in multiple, synergisticways, and deplete essential protectiveantioxidants and buering minerals. Xenotoxinscan also result in the ollowing negativeoutcomes:

A. Decreased AtP and decreased productiono other high-energy compounds in themitochondria.104 This results in reduced energyor key elective cellular processes such as

it s clea that xenotoxc TMs, VOCs, POPs, EMFs, and radioisotopesdisrupt biological processes n multple, snegstc was, and deplete essental

potectve antoxdants and bufeng mneals.

Te developng o emodelng ban

s moe vulneable than the stable ban.



eleGANT fUNCTIONAl COmplexITy

Our task must be to ree ourselves bywidening our circle o compassion toembrace all living creatures and the

whole o nature and its beauty.Albert Einstein (1879-1955), Nobel laureate in Physics

The human brain has an average o 1021molecules, and perorms an estimated 1016

operations per second. This more recent andprecise measurement is two orders o magnitudeaster than previous estimates. The adult brainuses about 10 watts o energy, which represents6.7 x 10 -5 times less energy than a comparablesuper computer. (The 120,000 processors inthe super computer Blue Gene achieved acomparable speed in 2008128 while consuming1.5 megawatts o power.) The incredibleefciency o the human brain is achieved throughmassive parallel processing resulting rom theinterconnections o nerves and the catalyticpower o enzymes. Additional processing

capacity may come rom discrete piezoelectriccollagen fbrils, insulated by glycosaminoglycansthat wrap around each fbril.

This astounding neural connectivity requires anintricate process o successul sequencing andsynchronization in the seven ollowing areas:

1. Diereniaion o stem cells intoprogressively more specialized nervecells,129

2. Prolieraion to replace unneeded or worn-out cells by apoptosis (programmed cell

death),130

3. Migraion to go where needed or wherethe milieu is more avorable,131

4. Axonal extension to connect and reachout,132

5. Synapogenesis to allow nerves to connectand interconnect,133

6. Gliogenesis to protect and repair nerves,134and

7. Myelinaion to insulate nerves and acilitateinormation ow.135

These delicate processes enable the humannervous system to respond isually to a singlephoton in both the retina and the enterocyte;respond audiorily at near quantum molecularvibration thresholds in the ear and with similarsensitivity to neurochemical oscillaions inthe gut-associated lymphoid tissue (GALT);136distinguish the smell137or ase138 o asubstance based on a handul o molecules;

sense minute pressure changes in the skin and

in the tentorium covering the brain;139,140 andperceive sound inerals as brie as a milliontho a second between let and right ears.76 Sincethe introduction o xenotoxins, intererence withthese systems has been inadequately studied,particularly as regards interactions amongdierent toxic agents. The rising rates o ASDand PDD raise questions or which there areas yet too ew answers. The increase in ASDhas outpaced best eorts to increase available

resources to understand and treat theseconditions more eectively.

CONNeCTING The DOTs

I we can grasp that we are theworld we depend on, then we will fnd

where we truly belong and geton with seeking a way to live in harmony

within a r ich, vibrant community oliving things.

David Suzuki (1936- ) and Amanda McConnell

(1970- ), The Sacred Balance, 2007

Based on the preceding discussion, we proposesix ASD subgroups and six correspondingavenues o possible intervention. I confrmed,these subcategories would acilitate moreaccurate diagnosis through use o validatedunctional tests, and would enhance thelikelihood o meaningul therapeutic outcomes.Each o the proposed subtypes has a distinctinternal biochemical and external environmentalmilieu.

1. Redox increase.This reects low cell vitality

as a unction o antioxidant electron carriers thatare depleted and unable to prevent oxidativestress and ree radical damage to systemsthat are perorming development or repairunctions.141

2. Digesie compeence. This includes theability to break down, assimilate, and eliminatewhat is taken in, and requires examining theentire digestive system, rom prebiotics toprobiotics, rom mucins to secretory IgA, rommetallothionein to bile acids, and rom stomachacid to pancreatic digestive enzymes.

3. Anabolic/caabolic balance. This reectsrepair competences or their defcit, includingneural and systemic unresolved inammation.142

4. Deoxifcaion. This pertains to the abilityto saely convert toxins into more easily excretedand less harmul substances beore delicatecontrol systems are damaged.

5. Somaosenory inormaion processingand analysis.Limited reserves can lead tosystem overload and entrainment o inormationprocessing.143

6. Neuroimmunohormonal eedbackinegraion.144 Neurotransmitter, immuneand hormonal systems unction as a single,integrated control system with cytokines asmessengers.145 (Jae has called attentionto the complete parallel with GoverningVessel as described in traditional Orientalmedicine.146)

CONClUsION

The problem lies not in the intentionnor in the dedication o individuals,

but as so oten in the history o sciencrom a limitation in the prevailing

paradigm or model that governs andlimits thinking in any given era.

Thomas Kuhn, PhD (1922-1996), Proessor,

Philosophy o Science

Autism spectrum disorders are a complex groo neurodevelopmental disorders near or atepidemic levels, particularly in the developed

world. The causes remain unknown, and theclinical expressions diverse. The increase in 7years rom less than 1 in 10,000 to around 1100 children (2010 estimate) is not explainabthrough genetics.

Because ASD typically aects multiple bodsystems, with altered unction spanning virtuaevery level o biology and behavior, it can bechallenging to deliver therapies that accuratematch an individuals biological state. Bycomprehensively synthesizing physiology,molecular biology, integrative toxicology andsystems dynamics, it is possible to come to a

more unctional understanding o ASD. Withthe goal o improving diagnostic precision antherapeutic outcomes, we propose six likelysubgroups with distinct biochemical proflesand implications or best outcomes therapies.This proposed classifcation requires urtherexploration.

Autism research, to date, has been guidedprimarily by a reductionist, linear model thatocuses on genetics, and considers single-variable, placebo-controlled experimentaldesigns as the gold standard. This approachas limited ability to capture epigeneticchanges, and also implicitly presumes thatASD is a single condition with a spectrum osymptomatic expressions. When data averagor whole groups are taken, the distinctivecharacteristics o subgroups cannot be easilyobserved.

As stewards or the generations to come, aas physicians concerned about the sueringthat ASD and PDD entail, we believe it is timeto devote sufcient resources to test the validio possible discrete ASD subgroups. In a utuarticle, we will model an integrative approacand propose predictive markers or eachsubgroup.



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Global Alert: Anthropogenic Influences on Biology and the Biota, and Connections to Autism Spectrum Disorders