THE VACCINE-AUTISM DEBATE: NEW DEVELOPMENTS

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THE VACCINE-AUTISMTHE VACCINE-AUTISM

DEBATE: DEBATE:

NEW DEVELOPMENTS NEW DEVELOPMENTS

FROM SCIENCE AND FROM SCIENCE AND POLICY POLICY

PPresentation by David Kirbyresentation by David KirbyCapitol Hill - Washington, DCCapitol Hill - Washington, DC

September 24th, 2008September 24th, 2008

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““Talking Points”Talking Points”Debate not over – Many unresolved questions.Debate not over – Many unresolved questions.

Look at kids who got sick, work backward from there: Look at kids who got sick, work backward from there: What might cause these What might cause these physicalphysical symptoms? symptoms?

Look at genetic susceptibilities: immune, metabolic, Look at genetic susceptibilities: immune, metabolic, mitochondrial, metal metabolism. What percentage of mitochondrial, metal metabolism. What percentage of the population is born “at risk?”the population is born “at risk?”

No single No single typetype of autism and no single of autism and no single causecause – Look at – Look at many different combinations of genes and many different combinations of genes and environmental “triggers.”environmental “triggers.”

Possible triggers include mercury & other heavy metals Possible triggers include mercury & other heavy metals in food, air and water, thimerosal, multiple vaccines, in food, air and water, thimerosal, multiple vaccines, pesticides, viruses, etc.pesticides, viruses, etc.

Mercury/vaccine research on at CDC, NIH, Universities, Mercury/vaccine research on at CDC, NIH, Universities, Autism Speaks Autism Speaks

Vaxed v Unvaxed study needed – Maloney Bill.Vaxed v Unvaxed study needed – Maloney Bill.

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A NEW AUTISM VOCABULARYA NEW AUTISM VOCABULARYCause, Effect & Connections of:Cause, Effect & Connections of:

Immune Immune Activation/Suppression/AutoimmunityActivation/Suppression/Autoimmunity

Oxidative StressOxidative Stress Neuro-inflammation / Rapid Neuro-inflammation / Rapid Brain Brain

GrowthGrowth Glutathione DepletionGlutathione Depletion Mitochondrial DysfunctionMitochondrial Dysfunction Metal Metabolism/Efflux Disorder Metal Metabolism/Efflux Disorder Activation of Astroglia & Activation of Astroglia &

Microglia/“Gliosis”Microglia/“Gliosis” DemyelinationDemyelination

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“Autism and the Environment”

Institute of Medicine Neuroscience.

“The environment may play a significant role in triggering autism.”

“ “Evidence points to a large genetic Evidence points to a large genetic component, but component, but genes alone cannot genes alone cannot accountaccount for its cause.” for its cause.”

Parents played a major role in this report.Parents played a major role in this report.

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Link between mercury and Link between mercury and autism?autism?

Thimerosal not out of vaccines until 2003; still in Thimerosal not out of vaccines until 2003; still in flu shot. CA: Too soon to tell? (CDC studies 8 flu shot. CA: Too soon to tell? (CDC studies 8 year olds).year olds).

Reports of drop in severe autism cases among Reports of drop in severe autism cases among youngest children. youngest children.

Today, autism rates are higher among Today, autism rates are higher among immigrants – Thimerosal is still in full use in 3immigrants – Thimerosal is still in full use in 3rdrd World.World.

Many top university studies show an association Many top university studies show an association between background mercury/thimerosal and between background mercury/thimerosal and autism.autism.

CDC continues to study mercury and autism CDC continues to study mercury and autism today.today.

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NIH: “We identified several areas of weakness that were judged to reduce the usefulness of the VSD for addressing the potential association between exposure to thimerosal and risk of ASD.”

The weaknesses of primary importance: Case ascertainment; Heterogeneity in business practices; Systematic changes over time; Estimation of total mercury burden.

Gerberding General Response: CDC CONCURS

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Thomas Burbacher at Univ. of Wash. Primate Thomas Burbacher at Univ. of Wash. Primate Center compared ethylmercury from thimerosal Center compared ethylmercury from thimerosal and methylmercury from fish. and methylmercury from fish.

Methyl stayed in blood longer, crossed blood-Methyl stayed in blood longer, crossed blood-brain barrier more.brain barrier more.

BUT - Ethyl in brain converts to inorganic Hg BUT - Ethyl in brain converts to inorganic Hg faster than methyl. faster than methyl.

2-4 times more inorganic Hg found in brains of 2-4 times more inorganic Hg found in brains of ethyl vs methyl group.ethyl vs methyl group.

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““Changes in Changes in astrocytesastrocytes and and microgliamicroglia in primate brains after long-term in primate brains after long-term methylmercury exposure.”methylmercury exposure.”

Burbacher: Inorganic Hg, presumably from Burbacher: Inorganic Hg, presumably from methyl Hg, continued to increase throughout all methyl Hg, continued to increase throughout all exposure durations.exposure durations.

Both Both astrocyte astrocyte andand microglial microglial cells had cells had “substantially elevated” inorganic mercury “substantially elevated” inorganic mercury deposits. deposits.

““Inorganic mercury may be a toxic form Inorganic mercury may be a toxic form responsible for responsible for activation activation ofof astrocyte astrocyte andand microglia.” microglia.”

Activation of Activation of astrocyte astrocyte andand microglial microglial cells was cells was not noted for six months or more, in some cases.not noted for six months or more, in some cases.

Neurotoxicology. 1996;17:127-138.

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JOHNS HOPKINS: ‘Neurological Activation

&Neuro-Inflammation in Brain of Autism Patients Annals of Neurology - Vol 57 No 1 January 2005

Inflammation found in autopsied autistic Inflammation found in autopsied autistic brains, produced bybrains, produced by ””activation of astroglia activation of astroglia and microglia.and microglia.””

Inflammation apparently associated with Inflammation apparently associated with activation of the brainactivation of the brain’’s immune system.s immune system.

Compared with controls, autistic tissue Compared with controls, autistic tissue showed ongoing inflammation in various showed ongoing inflammation in various sections of brain.sections of brain.

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HARVARD:HARVARD:“Large Brains in Autism: The “Large Brains in Autism: The

Challenge of Pervasive Challenge of Pervasive Abnormality” Abnormality”

The NeuroscientistThe Neuroscientist, Volume 11, Number 5, 2000, Volume 11, Number 5, 2000

Neuro-inflammation, oxidative Neuro-inflammation, oxidative stress & stress & microgliamicroglia damage found in damage found in autistic brain tissue. autistic brain tissue.

“Chronic disease or external “Chronic disease or external environmental sources” (ie, heavy environmental sources” (ie, heavy metals) may be the cause. metals) may be the cause.

““Oxidative stress, brain Oxidative stress, brain inflammation, and inflammation, and microgliosismicrogliosis has has been much documented in been much documented in association with heavy metal association with heavy metal exposures.”exposures.”

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Hannah Poling - ConcessionHannah Poling - Concession

November 9, 2007November 9, 2007 Hannah met all milestones in first 18 Hannah met all milestones in first 18

months. months. At 9 monthsAt 9 months: Mimicking sounds, : Mimicking sounds, crawling, and sitting.crawling, and sitting.

At 12-monthAt 12-month pediatric visit: Saying pediatric visit: Saying “Mom” & “Dad,” pulling self up, cruising. “Mom” & “Dad,” pulling self up, cruising.

July 19, 2000 July 19, 2000 visitvisit - Hannah “spoke well” - Hannah “spoke well” was “alert and active,” with regular bowel was “alert and active,” with regular bowel movements and good sleeping habits.movements and good sleeping habits.

July 19, 2000July 19, 2000 visit – Hannah received 9 visit – Hannah received 9 vaccines: vaccines: D-T-aP, M-M-R, Hib, Varivax, and PolioD-T-aP, M-M-R, Hib, Varivax, and Polio

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Poling Concession Poling Concession July 21, 2000July 21, 2000 – Two days later: 102.3 degree fever, – Two days later: 102.3 degree fever,

“lethargic, irritable, and cried for long periods, with “lethargic, irritable, and cried for long periods, with intermittent, high-pitched screaming and a intermittent, high-pitched screaming and a decreased response to stimulidecreased response to stimuli.”.”

July 22–31, 2000July 22–31, 2000 - Behavior continued over next ten - Behavior continued over next ten days. Hannah also began to arch back when crying.days. Hannah also began to arch back when crying.

July 31, 2000July 31, 2000 – Hannah had 102 degree fever, – Hannah had 102 degree fever, diminished appetite, red dots on chest and diminished appetite, red dots on chest and “extremely irritable and inconsolable.”“extremely irritable and inconsolable.”

September 26, 2000September 26, 2000 - Hannah returned with 102 - Hannah returned with 102 fever, diarrhea, nasal discharge, reduced appetite, fever, diarrhea, nasal discharge, reduced appetite, and and pulling at her left earpulling at her left ear..

November 13, 2000November 13, 2000 – Hannah presented with more – Hannah presented with more diarrhea, vomiting, diminished energy, fever, and diarrhea, vomiting, diminished energy, fever, and rash on her cheek. rash on her cheek.

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Poling ConcessionPoling Concession December 14, 2000December 14, 2000 - Doctor noted Hannah had - Doctor noted Hannah had

possible possible speech delayspeech delay, was , was less responsiveless responsive to to verbal direction since July, and verbal direction since July, and lost some lost some languagelanguage..

February 8, 2001February 8, 2001 – “Encephalopathy progressed – “Encephalopathy progressed to persistent loss of previously acquired to persistent loss of previously acquired language, language, eye contacteye contact, and , and relatednessrelatedness, , following vaccinations of July, 2000. Hannah following vaccinations of July, 2000. Hannah watched the fluorescent lights repeatedlywatched the fluorescent lights repeatedly during during the examination and would not make eye the examination and would not make eye contact.”contact.”

February 8, 2001February 8, 2001 - Hannah diagnosed with - Hannah diagnosed with “regressive encephalopathy with features “regressive encephalopathy with features consistent with an autistic spectrum disorder, consistent with an autistic spectrum disorder, following normal development.”following normal development.”

May 17, 2001May 17, 2001 – Lab results “strongly indicated – Lab results “strongly indicated an underlying mitochondrial disorder.”an underlying mitochondrial disorder.”

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Poling Concession #2Poling Concession #2February 21, 2008February 21, 2008

““The cause for autistic encephalopathy The cause for autistic encephalopathy was underlying mitochondrial was underlying mitochondrial dysfunction, exacerbated by vaccine-dysfunction, exacerbated by vaccine-induced fever and immune stimulation induced fever and immune stimulation that exceeded metabolic reserves.”that exceeded metabolic reserves.”

OR: OR:

Hannah’s autism was caused by a Hannah’s autism was caused by a vaccine-induced trigger of her underlying vaccine-induced trigger of her underlying mitochondrial dysfunction.mitochondrial dysfunction.

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Dr. Gerberding on CNNDr. Gerberding on CNNMarch 29, 2008March 29, 2008

““If a child was immunized, got a fever, had If a child was immunized, got a fever, had other other complications from the vaccinescomplications from the vaccines, and , and (is) pre-disposed with the mitochondrial (is) pre-disposed with the mitochondrial disorder, it can certainly set off some disorder, it can certainly set off some damage.” damage.”

““Some of these symptoms can be symptoms Some of these symptoms can be symptoms that have characteristics of that have characteristics of autismautism." ."

““I think we have to have an I think we have to have an openopen mind mind about this.”about this.”

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Three Sources of Mito Three Sources of Mito DisordersDisorders

SourcesSources: Cleveland Clinic and UMDF: Cleveland Clinic and UMDF

1) Inherited from mother (in Mito DNA)1) Inherited from mother (in Mito DNA)

2) Inherited from both parents (in nuclear DNA)2) Inherited from both parents (in nuclear DNA)

3) “Sporadic” (acquired via medicines and 3) “Sporadic” (acquired via medicines and toxins).toxins).

““Sporadic” type estimated for 75% of all cases. Sporadic” type estimated for 75% of all cases.

Mitochondria can be damaged by mercury, Mitochondria can be damaged by mercury, aluminum, pesticides, formaldehyde, alcohol, aluminum, pesticides, formaldehyde, alcohol, even HIV meds like AZT (which delete large even HIV meds like AZT (which delete large segments of MtDNA).segments of MtDNA).

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Estimates of Mito DysfunctionEstimates of Mito Dysfunction11) ) Oliveiro et al:Oliveiro et al: Markers for Mito dysfunction found in 20% of Markers for Mito dysfunction found in 20% of ASD patients, and muscle biopsy confirmed in ASD patients, and muscle biopsy confirmed in 7.2%.7.2%.

2) 2) Kelley, Zimmerman, Natowicz:Kelley, Zimmerman, Natowicz: Mitochondrial dysfunction Mitochondrial dysfunction may account for may account for 20%20% of ASD, especially PDD-NOS with of ASD, especially PDD-NOS with language and cognitive regression in 2language and cognitive regression in 2ndnd year. Markers on year. Markers on paternal lines; early testing, “may rescue some from more paternal lines; early testing, “may rescue some from more severe brain injury and lifelong disability.” severe brain injury and lifelong disability.”

3) 3) David HoltzmanDavid Holtzman, Massachusetts General Hospital, AS Grant: , Massachusetts General Hospital, AS Grant: “Oxidative Phosphorylation in Cells from Autistic Individuals.” “Oxidative Phosphorylation in Cells from Autistic Individuals.” Mito dysfunction might be found in up to Mito dysfunction might be found in up to 30%30% of ASD cases. of ASD cases.

4) 4) Petitioners Steering CommitteePetitioners Steering Committee – VICP – Up to – VICP – Up to 50%50% of 5,000 of 5,000 cases filed in Vaccine Court show markers for mild cases filed in Vaccine Court show markers for mild dysfunction.dysfunction.

5) 5) UMDFUMDF – Mitochondrial DNA mutations in population: up to – Mitochondrial DNA mutations in population: up to 1-in-2001-in-200

6) 6) Johns HopkinsJohns Hopkins – Nuclear DNA mutations in population: up – Nuclear DNA mutations in population: up to 1-in-50to 1-in-50

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March 11, 2008March 11, 2008 CDC CDC Conference Call on Mito Conference Call on Mito

Dysfunction, Vaccines and Dysfunction, Vaccines and AutismAutism CISACISA - CDC, vaccine experts and - CDC, vaccine experts and

insurance companies – discussed 5-year insurance companies – discussed 5-year study of 30 ASD kids w/low cellular study of 30 ASD kids w/low cellular energy.energy.

All 30 had the All 30 had the samesame abnormalities as abnormalities as Hannah Poling, (who was one of them). Hannah Poling, (who was one of them). All regressed after normal development.All regressed after normal development.

Big surprise: “Inheritance pattern" found Big surprise: “Inheritance pattern" found – When 2 two cousins had autism, genetic – When 2 two cousins had autism, genetic link was always through father – clear link was always through father – clear nuclear DNA inheritance.nuclear DNA inheritance.

DNA mutation from 1-in-400 to DNA mutation from 1-in-400 to 1-in-501-in-50, , or 2%.or 2%.

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April 11, 2008April 11, 2008 – Meeting to – Meeting to Discuss Top Vaccine Safety Discuss Top Vaccine Safety

Issues in DCIssues in DCHHS convened first meeting of the national HHS convened first meeting of the national Vaccine Vaccine Safety Working GroupSafety Working Group to review CDC's to review CDC's recommended safety research agenda. SOME recommended safety research agenda. SOME Specific Questions:Specific Questions:

““Is thimerosal associated with risk for tics Is thimerosal associated with risk for tics and/or Tourettes?and/or Tourettes?

““Is pertussis vaccine associated with risk for Is pertussis vaccine associated with risk for acute neurological events?”acute neurological events?”

““Is combo MMRV vaccine associated with Is combo MMRV vaccine associated with increased febrile seizure risk?”increased febrile seizure risk?”

““Are varicella and MMRV vaccines associated Are varicella and MMRV vaccines associated with increased risk for clinically important with increased risk for clinically important events?” (2x risk of seizures)events?” (2x risk of seizures)

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April 11, 2008April 11, 2008 CDC:CDC: Clinical Outcomes To Clinical Outcomes To

StudyStudyCan vaccines cause:Can vaccines cause:

Neurodevelopmental disorders, including Neurodevelopmental disorders, including autism?autism?

Autoimmune diseases? Autoimmune diseases?

Nervous system demyelinating disorders?Nervous system demyelinating disorders?

Encephalitis/encephalopathy?Encephalitis/encephalopathy?

Outcomes associated with post- Outcomes associated with post- immunization fever?immunization fever?

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April 11, 2008April 11, 2008CDC Also Proposes CDC Also Proposes Mito Mito

Research:Research: Q: “Is immunization associated Q: “Is immunization associated

with increased risk for neurological with increased risk for neurological deterioration in children with deterioration in children with mitochondrial dysfunction?”mitochondrial dysfunction?”

““CISA has formed a working group CISA has formed a working group to study methods related to to study methods related to mitochondrial disorders and mitochondrial disorders and immunization, in collaboration with immunization, in collaboration with partners.”partners.”

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“Bridging from Cells to Cognition in Autism: Pathways to Defective Brain

Function and Plasticity”Dr. Martha Herbert, Harvard – Am. Journ. Biochem. & Biotech

4 (2): 167-176, 2008Autism may begin when early environmental, infectious, seizure, or autoimmune insult triggers an immune response that increases oxidative stress in the brain.

Oxidative stress leads to DNA damage (nuclear and mitochondrial) and metabolic (glutathione) enzyme blockage.

Inflammatory and oxidative stressors persist beyond early development, producing ongoing functional consequences.

Continued use of damaged mitochondria and impaired metabolic function generates additional oxidative stress.

Mito dysfunction in autism would activate astroglia and microglia.

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Barack Obama: Barack Obama: April, 2008April, 2008

“ “We've seen just a skyrocketing autism We've seen just a skyrocketing autism rate. Some people are suspicious that rate. Some people are suspicious that it's connected to the vaccines. The it's connected to the vaccines. The science right now is inconclusive, but we science right now is inconclusive, but we have to research it.” have to research it.”

John McCain: John McCain: March, 2008March, 2008

““It's indisputable that autism is on the It's indisputable that autism is on the rise amongst children, the question is rise amongst children, the question is what's causing it. And we go back and what's causing it. And we go back and forth, and there's strong evidence that forth, and there's strong evidence that indicates that it's got to do with a indicates that it's got to do with a preservative in vaccines.”preservative in vaccines.”

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Dr. Bernadine Healy on Dr. Bernadine Healy on CBS NewsCBS NewsMay, 2008May, 2008

““Officials have been too quick to Officials have been too quick to dismiss the hypothesis as 'irrational,' dismiss the hypothesis as 'irrational,' without sufficient studies of without sufficient studies of causation, causation, without studying the without studying the population that got sick.”population that got sick.”

““Never turn your back on any Never turn your back on any scientific hypothesis because you are scientific hypothesis because you are afraid of what it might show." afraid of what it might show."

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Since the beginning of 2008, we have heard Since the beginning of 2008, we have heard from:from:

1) Both Presidential Candidates1) Both Presidential Candidates2) Director of the CDC (and her "open mind")2) Director of the CDC (and her "open mind")3) Former head of the NIH and American Red Cross3) Former head of the NIH and American Red Cross4) Chair of the House Science Subcommittee on 4) Chair of the House Science Subcommittee on InvestigationsInvestigations5) Dr. Jon Poling, respected Pediatric Neurologist5) Dr. Jon Poling, respected Pediatric Neurologist6) HHS Vaccine Safety Working Group6) HHS Vaccine Safety Working Group7) CDC Vaccine Safety Research Agenda7) CDC Vaccine Safety Research Agenda8) Medical personnel at HHS Vaccine Injury Compensation 8) Medical personnel at HHS Vaccine Injury Compensation ProgramProgram9) Strategic Planning Workgroup of the IAC Committee9) Strategic Planning Workgroup of the IAC Committee10) Clinical Immunization Safety Assessment Network - 10) Clinical Immunization Safety Assessment Network - CISACISA11) Autism researchers at Johns Hopkins University 11) Autism researchers at Johns Hopkins University Medical SchoolMedical School12) America's health insurance companies12) America's health insurance companies13) Autism Speaks13) Autism Speaks

They have all advocated, or at least considered, exploring They have all advocated, or at least considered, exploring the possible links between vaccines and autism.the possible links between vaccines and autism.