1 ENVIRONMENTAL PATHWAYS TO AUTISM SPECTRUM DISORDERS Research Opportunities & Current US Government Studies “The Search for Causes and Cures” Presentation by David Kirby Briefing by Reps. Maloney & Smith Capitol Hill, Washington, DC- July 17, 2009

2 The Coming “Tidal Wave” U.C. M.I.N.D. Institute: % rise in CA cases since 1990: cannot be explained by changes in Dx or counting. "It's time to start looking for the environmental culprits” -- Dr. Irva Hertz-Picciotto, UC Davis. U.C. M.I.N.D. Institute: % rise in CA cases since 1990: cannot be explained by changes in Dx or counting. "It's time to start looking for the environmental culprits” -- Dr. Irva Hertz-Picciotto, UC Davis. Sacramento Bee: 6,300 CA adults get ASD services. In four years, it will almost double to 11,000. By 2018 it will triple to 19,000. “A tidal wave of ASD youngsters is moving toward adulthood.” Sacramento Bee: 6,300 CA adults get ASD services. In four years, it will almost double to 11,000. By 2018 it will triple to 19,000. “A tidal wave of ASD youngsters is moving toward adulthood.” Orange Co. Schools: “If increase is better diagnosis, both Elementary and High Schools should have similar rates. But the HS district is setting up more self-contained classrooms to accommodate the influx this coming year.” (Why so many more 9 th graders than 10 th graders?). Orange Co. Schools: “If increase is better diagnosis, both Elementary and High Schools should have similar rates. But the HS district is setting up more self-contained classrooms to accommodate the influx this coming year.” (Why so many more 9 th graders than 10 th graders?). US CDC: Autism rate among 8-year-olds in 2000: 1-in 166; In 2002: 1-in- 150; In 2004: ?? (FOIA Pending) We still do not know the rate among children born in 1996 and after. US CDC: Autism rate among 8-year-olds in 2000: 1-in 166; In 2002: 1-in- 150; In 2004: ?? (FOIA Pending) We still do not know the rate among children born in 1996 and after.

3 A NEW AUTISM VOCABULARY Cause, Effect & Connections of: Immune Hyper-activation/Suppression/Autoimmunity Immune Hyper-activation/Suppression/Autoimmunity Oxidative Stress Oxidative Stress Neuro-inflammation Neuro-inflammation Glutathione Depletion Glutathione Depletion Metal Metabolism Disorder Metal Metabolism Disorder Myelin Disorders Myelin Disorders Mitochondrial Dysfunction Mitochondrial Dysfunction Activation of Microglial cells/“Gliosis” Activation of Microglial cells/“Gliosis” Cytokine Imbalances Cytokine Imbalances Methionine Cycle Disruption/Impaired Methylation Methionine Cycle Disruption/Impaired Methylation Vitamin D Deficiency Vitamin D Deficiency Calcium Channeling Imbalances (CACNA-1G?) Calcium Channeling Imbalances (CACNA-1G?)

4 Vaccines & Autism: Asked and Answered? Only one vaccine (MMR) and one component (Thimerosal) have been studied. Only one vaccine (MMR) and one component (Thimerosal) have been studied. Almost all were epidemiological studies, many with serious flaws and limitations. Almost all were epidemiological studies, many with serious flaws and limitations. Thimerosal was reduced in – these children are not 8 years old yet; flu shot raised exposures since. Thimerosal was reduced in – these children are not 8 years old yet; flu shot raised exposures since. Early intervention can “artificially” boost ASD rates among 3-year-olds by 75% (CDC study). Early intervention can “artificially” boost ASD rates among 3-year-olds by 75% (CDC study).

5 METALS Organic Mercury Inorganic Mercury AluminumArsenic Antimony – flame retardants Lead/Tin/Cadmium etc.

6 GLUTATHIONE: Sulfur-based protein that binds with heavy metals, viruses and toxins to eliminate them from system. Very powerful fighter against oxidative stress. Critical for protecting mitochondrial membranes from permeation/damage caused by toxins. Tylenol blocks glutathione production in the liver.

7 ASD kids have low or depleted levels of “thiols,” including glutathione. ASD kids have low or depleted levels of “thiols,” including glutathione. Thiols are mercaptans, Latin for “capturing mercury.” Thiols are mercaptans, Latin for “capturing mercury.” Targeted nutritional intervention with Folinic acid, and Betaine resulted in significant improvement in ASD children. Targeted nutritional intervention with Folinic acid, and Betaine resulted in significant improvement in ASD children. Addition of methyl B-12 to “cocktail” brought all ASD children within normal “thiol” levels, such as glutathione. Addition of methyl B-12 to “cocktail” brought all ASD children within normal “thiol” levels, such as glutathione. Thimerosal damage to nerves was associated with glutathione depletion, protection was restored with glutathione precursors. Thimerosal damage to nerves was associated with glutathione depletion, protection was restored with glutathione precursors.

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 Hg in the brain 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:

9 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.”

10 CDC -VSD: Thimerosal and Neurodevelopmental Disorders

11 Study looked at Texas county levels of emissions, compared to ASD rates and special ed in 1,200 school districts. Study looked at Texas county levels of emissions, compared to ASD rates and special ed in 1,200 school districts. Autism increased as mercury emissions rose. For every thousand pounds of Hg, there was a 61 percent increase in autism rates. Autism increased as mercury emissions rose. For every thousand pounds of Hg, there was a 61 percent increase in autism rates. One county with low mercury emissions but significant autism rates was found to harbor one of the nation’s largest mercury mines. One county with low mercury emissions but significant autism rates was found to harbor one of the nation’s largest mercury mines. “A potentially important connection between environmental exposure to mercury and the development of autism.” “A potentially important connection between environmental exposure to mercury and the development of autism.” 12 (2006) UNIV of TEXAS : “HIGHER RISK OF AUTISM NEAR COAL-FIRED PLANTS” - Health & Place - 12 (2006)

12 Myelin: “A white fatty substance that forms a sheath around nerve fibers to provide electrical insulation”

13 The Bailey Banks Case Court ruled MMR vaccine produced acute disseminated encephalomyelitis (ADEM) – Inflammation of brain and spinal cord and damage to the myelin sheath. Court ruled MMR vaccine produced acute disseminated encephalomyelitis (ADEM) – Inflammation of brain and spinal cord and damage to the myelin sheath. ADEM can be caused by natural infections, especially measles virus. But is also a post-vaccine injury, especially rabies, pertussis, influenza, and MMR. ADEM can be caused by natural infections, especially measles virus. But is also a post-vaccine injury, especially rabies, pertussis, influenza, and MMR IOM: Biologically plausible for a vaccine to “induce...an autoimmune response...by nonspecific activation of the T cells directed against myelin proteins.” 1994 IOM: Biologically plausible for a vaccine to “induce...an autoimmune response...by nonspecific activation of the T cells directed against myelin proteins.” Symptoms: headache, delirium, lethargy, seizures, stiff neck, fever, ataxia (incoordination), nausea, vomiting, weight loss, irritability, changes in mental status. Symptoms: headache, delirium, lethargy, seizures, stiff neck, fever, ataxia (incoordination), nausea, vomiting, weight loss, irritability, changes in mental status.

14 Banks Cont’d Bailey had MRI 16 days after MMR vaccine, confirmed his diagnosis. Most given Tylenol and sent home. Bailey had MRI 16 days after MMR vaccine, confirmed his diagnosis. Most given Tylenol and sent home. Tylenol can affect glutathione, mitochondrial function and oxidative stress. Tylenol can affect glutathione, mitochondrial function and oxidative stress. A small study at UCSD showed kids given Tylenol after MMR were several times more likely to develop ASD. A small study at UCSD showed kids given Tylenol after MMR were several times more likely to develop ASD. "Tylenol and MMR was significantly associated with autistic disorder," the authors wrote. "Tylenol and MMR was significantly associated with autistic disorder," the authors wrote.

15 Banks “Bailey’s ADEM was severe enough to cause lasting, residual damage, and retarded his developmental progress, which fits under the generalized heading of PDD-(NOS).” “Bailey would not have suffered this delay but for the administration of MMR. “A proximate sequence of cause and effect leading inexorably from vaccination to PDD.”

16 HepB, Myelin and MS Vaccine Court – 65 HepB-Demyelinating Cases. Vaccine Court – 65 HepB-Demyelinating Cases. Sample case: Court ruled adult female contracted a demyelinating disease and MS, and eventually died, after receiving the Hepatitis B vaccine series. Sample case: Court ruled adult female contracted a demyelinating disease and MS, and eventually died, after receiving the Hepatitis B vaccine series. Just the most recent case in a rash of rulings on HepB and “demyelinating diseases such as transverse myelitis (TM), Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating disease (CIDP), and multiple sclerosis (MS).” Just the most recent case in a rash of rulings on HepB and “demyelinating diseases such as transverse myelitis (TM), Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating disease (CIDP), and multiple sclerosis (MS).”

17 HepB and Myelin in Infants Oct issue of Neurology - Hep B vaccine in infants associated with a 50% increased risk for CNS inflammatory demyelination. Oct issue of Neurology - Hep B vaccine in infants associated with a 50% increased risk for CNS inflammatory demyelination. Especially true for GSK’s Engerix B vaccine - Risk was 74%. Among ASD children with MS it increased 177% Especially true for GSK’s Engerix B vaccine - Risk was 74%. Among ASD children with MS it increased 177% “The Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term. “The Engerix B vaccine appears to increase this risk, particularly for confirmed multiple sclerosis, in the longer term.

18 Mitochondria: “Powerhouse of the cell that converts food and oxygen into energy” Mitochondrial Dysfunction: Low cellular energy caused by genes or environmental factors such as metals and drugs, including antidepressants and Tylenol

19 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 Followed by fevers, rashes, and descent into ASD. Followed by fevers, rashes, and descent into ASD.

20 Poling Concession #2 February 21, 2008 Amended report from Dr. Zimmerman: “The cause for regressive encephalopathy at age 19 months was underlying mitochondrial dysfunction, exacerbated by vaccine-induced fever and immune stimulation that exceeded metabolic reserves.” Epilepsy was “part of the same pathogenesis that led to autistic encephalopathy.” SHORT VERSION: Hannah’s autism was caused by a vaccine-induced exacerbation of her underlying mitochondrial dysfunction.

21 “Bridging from Cells to Cognition in Autism: Pathways to Defective Brain Function and Plasticity” Dr. Martha Herbert, Harvard – Am. Journ. Biochem. & Biotech 4 (2): , 2008 Autism may begin when an early environmental, infectious, seizure, or autoimmune insult triggers an immune response. This response 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.

22 “Bridging from Cells to Cognition in Autism: Pathways to Defective Brain Function and Plasticity” In the central nervous system, continued use of damaged mitochondria and impaired metabolic function may generate additional oxidative stress. This oxidative stress causes further activation of the immune system, leading to even more oxidative stress. Such a mechanism would self-sustain and possibly progressively worsen. Mitochondrial dysfunction found in autism would activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum pro-inflammatory gene response.

23 Seven Studies to Watch 1) Unanimous endorsement by the National Vaccine Advisory Committee to look at the feasibility of a large vaccinated-unvaccinated study, with autism as an outcome. 1) Unanimous endorsement by the National Vaccine Advisory Committee to look at the feasibility of a large vaccinated-unvaccinated study, with autism as an outcome. 2) NVAC endorsement of vaccine-autism investigations into children with mitochondrial dysfunction. 2) NVAC endorsement of vaccine-autism investigations into children with mitochondrial dysfunction. 3) NVAC endorsement of vaccine-autism investigations into children with regressive form of ASD (15-55%). 3) NVAC endorsement of vaccine-autism investigations into children with regressive form of ASD (15-55%). 4) NVAC endorsement of investigations into vaccine injuries such as encephalitis, seizure disorders and demyelinating diseases at risk factors for ASD. 4) NVAC endorsement of investigations into vaccine injuries such as encephalitis, seizure disorders and demyelinating diseases at risk factors for ASD. 5) NIH Early Autism Risk Longitudinal Investigations EARLI study which will follow 1,200 pregnant mothers with one ASD child, looking at all environmental triggers, including metals, thimerosal and vaccines. 5) NIH Early Autism Risk Longitudinal Investigations EARLI study which will follow 1,200 pregnant mothers with one ASD child, looking at all environmental triggers, including metals, thimerosal and vaccines. 6) HHS/EPA National Children’s Study, which will follow 100,000 children and look at all environmental factors and outcomes, including metals, vaccines and ASD. 6) HHS/EPA National Children’s Study, which will follow 100,000 children and look at all environmental factors and outcomes, including metals, vaccines and ASD. 7) CDCs Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network, to study, "mercury exposures, including any vaccine use by the mother during pregnancy and the child's vaccine exposures.” 7) CDCs Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network, to study, "mercury exposures, including any vaccine use by the mother during pregnancy and the child's vaccine exposures.”

24 ASD and Mitochondria – PloS Online – 12/08 Scientists at Cleveland Clinic, Harvard and Johns Hopkins: "There might be no difference between the inflammatory or catabolic stress of vaccinations and that of common childhood diseases.” Scientists at Cleveland Clinic, Harvard and Johns Hopkins: "There might be no difference between the inflammatory or catabolic stress of vaccinations and that of common childhood diseases.” "Large, population-based studies will be needed to identify a possible relationship of vaccination with autistic regression in persons with mitochondrial cytopathies." "Large, population-based studies will be needed to identify a possible relationship of vaccination with autistic regression in persons with mitochondrial cytopathies."

25 Dr. Duane Alexander - NICHD “Important to ask if some children are more susceptible to some vaccine characteristic or component, and may develop an ASD in response.” There may be "subpopulations unable to remove mercury from the body as fast as others, or some adverse or cross-reacting response to a vaccine component, or a mitochondrial disorder increasing the adverse response to vaccine- associated fever.”

26 Dr. Anthony Fauci - NIAID "If we can show that individuals of a certain genetic profile have a greater propensity for developing adverse events, we may want to screen everyone prior to vaccination."

27 The “1322 Project” Announced at Autism One - Expert legal review of previous Vaccine Court decisions to determine ASD prevalence. Announced at Autism One - Expert legal review of previous Vaccine Court decisions to determine ASD prevalence. Preliminary results show ASD rate many times higher than 1-in Final results to be announced soon. Preliminary results show ASD rate many times higher than 1-in Final results to be announced soon. CBS Evening News: At least 1322 cases paid out for vaccine- induced brain damage, encephalopathy and/or seizure disorders. CBS Evening News: At least 1322 cases paid out for vaccine- induced brain damage, encephalopathy and/or seizure disorders. “There may be cases involving autistic-like disorders which manifested following a Vaccine Injury Table injury. Any residual effects thereof would be presumed to be vaccine-caused. Autism cases involving Table Injuries have been compensated.” “There may be cases involving autistic-like disorders which manifested following a Vaccine Injury Table injury. Any residual effects thereof would be presumed to be vaccine-caused. Autism cases involving Table Injuries have been compensated.” – Gary J. Golkiewicz, Vaccine Court Chief Special Master – Gary J. Golkiewicz, Vaccine Court Chief Special Master