The Biological Plausibility of a Relationship between Vaccines and Autism Spectrum Disorders. A presentation to the Florida Governor's Task Force on Autism Spectrum Disorders

1. The Biological Plausibility of a Relationship between Vaccines and Autism Spectrum Disorders David Berger, MD Medical Director Wholistic Pediatrics Tampa, FL (813) 960-3415 www.wholisticpeds.com A PRESENTATION TO THE FLORIDA GOVERNOR’S TASK FORCE ON AUTISM SPECTRUM DISORDERS

2. Discover Magazine, 3/14/07

5. Mercury levels in Certain Fish Species (PPM) (EPA 2006; http://www.cfsan.fda.gov/~frf/sea-mehg.html) MACKEREL KING 0.730 SHARK 0.988 SWORDFISH 0.976 TILEFISH (Gulf of Mexico) 1.450 BASS (SALTWATER, BLACK, STRIPED) 3 0.219 BASS CHILEAN 0.386 BLUEFISH 0.337 CARP 0.14 GROUPER (ALL SPECIES) 0.465 HALIBUT 0.252 LOBSTER (NORTHERN/AMERICAN) 0.310 MACKEREL SPANISH (Gulf of Mexico) 0.454 MARLIN * 0.485 ORANGE ROUGHY 0.554 SNAPPER 0.189 TUNA (CANNED, ALBACORE) 0.353 TUNA(FRESH/FROZEN, ALL) 0.383 TUNA (FRESH/FROZEN,ALBACORE) 0.357 TUNA (FRESH/FROZEN, BIGEYE) 0.639 TUNA (FRESH/FROZEN, SKIPJACK) 0.205 TUNA (FRESH/FROZEN, YELLOWFIN) 0.325 TUNA (FRESH/FROZEN, Species Unknown) 0.414

6. On average, for each 1000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. Palmer et al. Health & Place 12 (2006) 203–209 Total toxicity Autism rates Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Palmer et al. Health & Place 2008

9. SAM SAH MTase SAHH Homocysteine B6 THF MS CBS B12 Protein synthesis BHMT Choline Betaine Effect of Oxidative Stress on Methionine Transsulfuration THF: tetrahydrofolate 5-CH 3 THF Methylation of DNA, RNA, proteins, membrane phospholipids, creatine, neurotransmittors Cystathionine Cysteine GSH GSSG Methionine Adenosine ( AK and/or ADA) MAT B6

10. Neurotoxicity of Thimerosal in Human Brain Cells is Associated with Glutathione Depletion: Protective Effect of Cysteine or Glutathione Supplementation Neurotoxicology. 2005 Jan;26(1):1-8 S. Jill James, William Slikker, Elizabeth New, Stefanie Jernigan, Stepan Melnyk Department of Pediatrics University of Arkansas for Medical Sciences Little Rock, AR

11. 0 2.5 5 10 20 VIABILITY OF GLIOBLASTOMA AND NEUROBLASTOMA CELLS WITH INCREASING DOSE OF THIMEROSAL Viability (MTT OD) Glioblastoma Cells Neuroblastoma Cells ( 48 hr Exposure ) ( 3 hr Exposure ) 0 2.5 5 10 20 0 2.5 5 10 20  M Thimerosal  M Thimerosal

12. Control Thimerosal +GSH + Cystine +NAC + Methionine O.D. (Viability) Viability of Glioblastoma cells exposed to 15  M Thimerasol in the presence of GSH-ester, Cystine, N-acetylcysteine (NAC), or Methionine

13. Control Thimerosal +GSH + Cystine +NAC + Methionine O.D. (Viability) Viability of Neuroblastoma cells exposed to 15  M Thimerosal Pretreated with 100  M GSH-ester, Cystine, N-acetylcysteine (NAC), or Methionine

15. Jill James, 2004 Assessment of Single Nucleotide Polymorphins in Children with Autism vs. Controls

17. The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health ….. Mercury in all of its forms is toxic to the fetus and children, and efforts should be made to reduce exposure to the extent possible to pregnant women and children as well as the general population . _______________________________________________________________ Vaccine inserts would typically say “0.01% thimerosal as a preservative”, which to anyone would sound like an extremely small amount. When called to testify in front of the Institute of Medicine, an independent group formed by our government to monitor safety issues, Dr. Neil Halsey of Johns Hopkins University, and head of the vaccine recommendation committee that reports to the CDC, went on record as saying “No one ever did the math…. No one knows what dose of mercury, if any, from vaccines is safe. We can say there is no evidence of harm but the truth is no one has looked” MERCURY Statement: Pediatrics 2001 Jul, American Academy of Pediatrics: Committee on Environmental Health.

22. Some Children with Autism Do Not Clear Mercury Mercury in first-cut baby hair of children with autism versus typically-developing children J. B. Adams; J. Romdalvik; K. E. Levine; Lin-Wen Hu (Arizona State University) Toxicological & Environmental Chemistry , May 2, 2008 Children with autism were examined to determine amounts of mercury (Hg) in their baby hair and the factors that might affect Hg body burden. US children with autism ( n = 78) and matched controls ( n = 31) born between 1988 and 1999 were studied. Hg in first-cut baby hair was determined using cold vapor atomic fluorescence spectrometry (CVAFS). Twenty samples were split and also measured with Neutron Activation Analysis (NAA). Logistic regression analysis showed that compared to children with higher levels of mercury (above 0.55 mcg g-1), children with lower levels of mercury in their hair (below 0.55 mcg g-1) were 2.5-fold more likely to manifest with autism . Children with autism had similar mercury exposure as controls from maternal seafood and maternal dental amalgams. Children with autism also had 2.5-fold higher incidence of oral antibiotic use during their first 18 months of life. Their mothers were possibly more likely to use oral antibiotics during pregnancy or nursing. The amount of Hg in the baby hair of children with autism showed a significant correlation with the number of maternal dental amalgams. The lower level of Hg in the baby hair of children with autism indicates an altered metabolism of Hg, and may be due to a decreased ability to excrete Hg. This is consistent with usage of higher amounts of oral antibiotics, which are known to inhibit Hg excretion in rats due to alteration of gut flora, and may exert a similar effect in humans. Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems seen in individuals with autism.

25. Mitochondrial Dysfunction and Autism Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment Daniel A. Rossignol, J. Jeffrey Bradstreet, International Child Development Resource Center Abstract: Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD) without the classic features associated with mitochondrial disease . MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environmental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress . MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions . Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT) represent supported and rationale approaches . The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

28. Vaccine Induced Autoimmunity (Cohen&Shoenfeld, Tel Aviv University, Journal of Autoimmunity , 1996)

38. Antonio (7 y/o) on first chelation challenge with DMSA

39. Antonio, after 4 cycles of DMSA

40. Antonio, after 8 cycles of DMSA

41. Antonio After Chelation with DMSA Has bad gas during the DMSA days, and is moody, then this goes away when the DMSA is finished. Doing better and better in speech therapy If he does not want to do things he cries. Teachers are reporting improvements seen on a month-to-month basis More hand gesturing In a more advanced class. The mimicry behavior has stopped. After finishing chelation, language is the major barrier, but behaviors and stemming are under control

42. Baseline

43. DMPS/Glutathione-IV

44. DMPS/Glutathione-Rectal

45. We Need More Research! The Bottom Line: ----The Bottom Line----The Bottom Line----The Bottom Line----The Bottom Line---