1. 1 THE VACCINE-AUTISM DEBATE: NEW DEVELOPMENTS FROM SCIENCE AND POLICY Presentation by David Kirby Capitol Hill - Washington, DC September 24th, 2008

2. 2 “Talking Points” Debate not over – Many unresolved questions. Look at kids who got sick, work backward from there: What might cause these physical symptoms? Look at genetic susceptibilities: immune, metabolic, mitochondrial, metal metabolism. What percentage of the population is born “at risk?” No single type of autism and no single cause – Look at many different combinations of genes and environmental “triggers.” Possible triggers include mercury & other heavy metals in food, air and water, thimerosal, multiple vaccines, pesticides, viruses, etc. Mercury/vaccine research on at CDC, NIH, Universities, Autism Speaks Vaxed v Unvaxed study needed – Maloney Bill.

3. 3 A NEW AUTISM VOCABULARY Cause, Effect & Connections of: Immune Activation/Suppression/Autoimmunity Immune Activation/Suppression/Autoimmunity Oxidative Stress Oxidative Stress Neuro-inflammation / Rapid Brain Growth Neuro-inflammation / Rapid Brain Growth Glutathione Depletion Glutathione Depletion Mitochondrial Dysfunction Mitochondrial Dysfunction Metal Metabolism/Efflux Disorder Metal Metabolism/Efflux Disorder Activation of Astroglia & Microglia/“Gliosis” Activation of Astroglia & Microglia/“Gliosis” Demyelination Demyelination

4. 4 “Autism and the Environment” Institute of Medicine Neuroscience. “The environment may play a significant role in triggering autism.” “Evidence points to a large genetic component, but genes alone cannot account for its cause.” “Evidence points to a large genetic component, but genes alone cannot account for its cause.” Parents played a major role in this report. Parents played a major role in this report.

5. 5 Link between mercury and autism? Thimerosal not out of vaccines until 2003; still in flu shot. CA: Too soon to tell? (CDC studies 8 year olds). Thimerosal not out of vaccines until 2003; still in flu shot. CA: Too soon to tell? (CDC studies 8 year olds). Reports of drop in severe autism cases among youngest children. Reports of drop in severe autism cases among youngest children. Today, autism rates are higher among immigrants – Thimerosal is still in full use in 3 rd World. Today, autism rates are higher among immigrants – Thimerosal is still in full use in 3 rd World. Many top university studies show an association between background mercury/thimerosal and autism. Many top university studies show an association between background mercury/thimerosal and autism. CDC continues to study mercury and autism today. CDC continues to study mercury and autism today.

6. 6 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

7. 7 Thomas Burbacher at Univ. of Wash. Primate Center compared ethylmercury from thimerosal and methylmercury from fish. Thomas Burbacher at Univ. of Wash. Primate Center compared ethylmercury from thimerosal and methylmercury from fish. Methyl stayed in blood longer, crossed blood-brain barrier more. Methyl stayed in blood longer, crossed blood-brain barrier more. BUT - Ethyl in brain converts to inorganic Hg faster than methyl. BUT - Ethyl in brain converts to inorganic Hg faster than methyl. 2-4 times more inorganic Hg found in brains of ethyl vs methyl group. 2-4 times more inorganic Hg found in brains of ethyl vs methyl group.

8. 8 “Changes in astrocytes and microglia in primate brains after long-term methylmercury exposure.” Burbacher: Inorganic Hg, presumably from methyl Hg, continued to increase throughout all exposure durations. Both astrocyte and microglial cells had “substantially elevated” inorganic mercury deposits. “Inorganic mercury may be a toxic form responsible for activation of astrocyte and microglia.” Activation of astrocyte and microglial cells was not noted for six months or more, in some cases. Neurotoxicology. 1996;17:127-138.

9. 9 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 brains, produced by ” activation of astroglia and microglia. ” Inflammation apparently associated with activation of the brain ’ s immune system. Compared with controls, autistic tissue showed ongoing inflammation in various sections of brain. Compared with controls, autistic tissue showed ongoing inflammation in various sections of brain.

10. 10 HARVARD: “Large Brains in Autism: The Challenge of Pervasive Abnormality” The Neuroscientist, Volume 11, Number 5, 2000 Neuro-inflammation, oxidative stress & microglia damage found in autistic brain tissue. “Chronic disease or external environmental sources” (ie, heavy metals) may be the cause. “Oxidative stress, brain inflammation, and microgliosis has been much documented in association with heavy metal exposures.”

11. 11 Hannah Poling - Concession November 9, 2007 Hannah met all milestones in first 18 months. At 9 months: Mimicking sounds, crawling, and sitting. Hannah met all milestones in first 18 months. At 9 months: Mimicking sounds, crawling, and sitting. At 12-month pediatric visit: Saying “Mom” & “Dad,” pulling self up, cruising. At 12-month pediatric visit: Saying “Mom” & “Dad,” pulling self up, cruising. July 19, 2000 visit - Hannah “spoke well” was “alert and active,” with regular bowel movements and good sleeping habits. July 19, 2000 visit - Hannah “spoke well” was “alert and active,” with regular bowel movements and good sleeping habits. July 19, 2000 visit – Hannah received 9 vaccines: D-T-aP, M-M-R, Hib, Varivax, and Polio July 19, 2000 visit – Hannah received 9 vaccines: D-T-aP, M-M-R, Hib, Varivax, and Polio

12. 12 Poling Concession July 21, 2000 – Two days later: 102.3 degree fever, “lethargic, irritable, and cried for long periods, with intermittent, high- pitched screaming and a decreased response to stimuli.” July 21, 2000 – Two days later: 102.3 degree fever, “lethargic, irritable, and cried for long periods, with intermittent, high- pitched screaming and a decreased response to stimuli.” July 22–31, 2000 - Behavior continued over next ten days. Hannah also began to arch back when crying. July 22–31, 2000 - Behavior continued over next ten days. Hannah also began to arch back when crying. July 31, 2000 – Hannah had 102 degree fever, diminished appetite, red dots on chest and “extremely irritable and inconsolable.” July 31, 2000 – Hannah had 102 degree fever, diminished appetite, red dots on chest and “extremely irritable and inconsolable.” September 26, 2000 - Hannah returned with 102 fever, diarrhea, nasal discharge, reduced appetite, and pulling at her left ear. September 26, 2000 - Hannah returned with 102 fever, diarrhea, nasal discharge, reduced appetite, and pulling at her left ear. November 13, 2000 – Hannah presented with more diarrhea, vomiting, diminished energy, fever, and rash on her cheek. November 13, 2000 – Hannah presented with more diarrhea, vomiting, diminished energy, fever, and rash on her cheek.

13. 13 Poling Concession December 14, 2000 - Doctor noted Hannah had possible speech delay, was less responsive to verbal direction since July, and lost some language. December 14, 2000 - Doctor noted Hannah had possible speech delay, was less responsive to verbal direction since July, and lost some language. February 8, 2001 – “Encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness, following vaccinations of July, 2000. Hannah watched the fluorescent lights repeatedly during the examination and would not make eye contact.” February 8, 2001 – “Encephalopathy progressed to persistent loss of previously acquired language, eye contact, and relatedness, following vaccinations of July, 2000. Hannah watched the fluorescent lights repeatedly during the examination and would not make eye contact.” February 8, 2001 - Hannah diagnosed with “regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.” February 8, 2001 - Hannah diagnosed with “regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.” May 17, 2001 – Lab results “strongly indicated an underlying mitochondrial disorder.” May 17, 2001 – Lab results “strongly indicated an underlying mitochondrial disorder.”

14. 14 Poling Concession #2 February 21, 2008 “The cause for autistic encephalopathy was underlying mitochondrial dysfunction, exacerbated by vaccine-induced fever and immune stimulation that exceeded metabolic reserves.” OR: Hannah’s autism was caused by a vaccine-induced trigger of her underlying mitochondrial dysfunction.

15. 15 Dr. Gerberding on CNN March 29, 2008 “If a child was immunized, got a fever, had other complications from the vaccines, and (is) pre- disposed with the mitochondrial disorder, it can certainly set off some damage.” “Some of these symptoms can be symptoms that have characteristics of autism." “I think we have to have an open mind about this.”

16. 16 Three Sources of Mito Disorders Sources: 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 toxins). 3) “Sporadic” (acquired via medicines and toxins). “Sporadic” type estimated for 75% of all cases. “Sporadic” type estimated for 75% of all cases. Mitochondria can be damaged by mercury, aluminum, pesticides, formaldehyde, alcohol, even HIV meds like AZT (which delete large segments of MtDNA). Mitochondria can be damaged by mercury, aluminum, pesticides, formaldehyde, alcohol, even HIV meds like AZT (which delete large segments of MtDNA).

17. 17 Estimates of Mito Dysfunction 1 ) Oliveiro et al: Markers for Mito dysfunction found in 20% of ASD patients, and muscle biopsy confirmed in 7.2%. 2) Kelley, Zimmerman, Natowicz: Mitochondrial dysfunction may account for 20% of ASD, especially PDD-NOS with language and cognitive regression in 2 nd year. Markers on paternal lines; early testing, “may rescue some from more severe brain injury and lifelong disability.” 3) David Holtzman, Massachusetts General Hospital, AS Grant: “Oxidative Phosphorylation in Cells from Autistic Individuals.” Mito dysfunction might be found in up to 30% of ASD cases. 4) Petitioners Steering Committee – VICP – Up to 50% of 5,000 cases filed in Vaccine Court show markers for mild dysfunction. 5) UMDF – Mitochondrial DNA mutations in population: up to 1-in-200 6) Johns Hopkins – Nuclear DNA mutations in population: up to 1-in-50 6) Johns Hopkins – Nuclear DNA mutations in population: up to 1-in-50

18. 18 March 11, 2008 CDC Conference Call on Mito Dysfunction, Vaccines and Autism CISA - CDC, vaccine experts and insurance companies – discussed 5-year study of 30 ASD kids w/low cellular energy. CISA - CDC, vaccine experts and insurance companies – discussed 5-year study of 30 ASD kids w/low cellular energy. All 30 had the same abnormalities as Hannah Poling, (who was one of them). All regressed after normal development. All 30 had the same abnormalities as Hannah Poling, (who was one of them). All regressed after normal development. Big surprise: “Inheritance pattern" found – When 2 two cousins had autism, genetic link was always through father – clear nuclear DNA inheritance. Big surprise: “Inheritance pattern" found – When 2 two cousins had autism, genetic link was always through father – clear nuclear DNA inheritance. DNA mutation from 1-in-400 to 1-in-50, or 2%. DNA mutation from 1-in-400 to 1-in-50, or 2%.

19. 19 April 11, 2008 – Meeting to Discuss Top Vaccine Safety Issues in DC HHS convened first meeting of the national Vaccine Safety Working Group to review CDC's recommended safety research agenda. SOME Specific Questions: “Is thimerosal associated with risk for tics and/or Tourettes? “Is thimerosal associated with risk for tics and/or Tourettes? “Is pertussis vaccine associated with risk for acute neurological events?” “Is pertussis vaccine associated with risk for acute neurological events?” “Is combo MMRV vaccine associated with increased febrile seizure risk?” “Is combo MMRV vaccine associated with increased febrile seizure risk?” “Are varicella and MMRV vaccines associated with increased risk for clinically important events?” (2x risk of seizures) “Are varicella and MMRV vaccines associated with increased risk for clinically important events?” (2x risk of seizures)

20. 20 April 11, 2008 CDC: Clinical Outcomes To Study Can vaccines cause: Neurodevelopmental disorders, including autism? Autoimmune diseases? Nervous system demyelinating disorders? Encephalitis/encephalopathy? Outcomes associated with post- immunization fever?

21. 21 April 11, 2008 CDC Also Proposes Mito Research: Q: “Is immunization associated with increased risk for neurological deterioration in children with mitochondrial dysfunction?” Q: “Is immunization associated with increased risk for neurological deterioration in children with mitochondrial dysfunction?” “CISA has formed a working group to study methods related to mitochondrial disorders and immunization, in collaboration with partners.” “CISA has formed a working group to study methods related to mitochondrial disorders and immunization, in collaboration with partners.”

22. 22 “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, 2008 Autism 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.

23. 23 Barack Obama: April, 2008 “We've seen just a skyrocketing autism rate. Some people are suspicious that it's connected to the vaccines. The science right now is inconclusive, but we have to research it.” “We've seen just a skyrocketing autism rate. Some people are suspicious that it's connected to the vaccines. The science right now is inconclusive, but we have to research it.” John McCain: March, 2008 “It's indisputable that autism is on the rise amongst children, the question is what's causing it. And we go back and forth, and there's strong evidence that indicates that it's got to do with a preservative in vaccines.”

24. 24 Dr. Bernadine Healy on CBS News May, 2008 “Officials have been too quick to dismiss the hypothesis as 'irrational,' without sufficient studies of causation, without studying the population that got sick.” “Officials have been too quick to dismiss the hypothesis as 'irrational,' without sufficient studies of causation, without studying the population that got sick.” “Never turn your back on any scientific hypothesis because you are afraid of what it might show."

25. 25 Since the beginning of 2008, we have heard from: 1) Both Presidential Candidates 2) Director of the CDC (and her "open mind") 3) Former head of the NIH and American Red Cross 4) Chair of the House Science Subcommittee on Investigations 5) Dr. Jon Poling, respected Pediatric Neurologist 6) HHS Vaccine Safety Working Group 7) CDC Vaccine Safety Research Agenda 8) Medical personnel at HHS Vaccine Injury Compensation Program 9) Strategic Planning Workgroup of the IAC Committee 10) Clinical Immunization Safety Assessment Network - CISA 11) Autism researchers at Johns Hopkins University Medical School 12) America's health insurance companies 13) Autism Speaks They have all advocated, or at least considered, exploring the possible links between vaccines and autism.