THE VACCINEAUTISM

1

• THE VACCINE-AUTISM
• DEBATE
• NEW
• DEVELOPMENTS
• FROM SCIENCE AND POLICY
• Presentation by David KirbyNYU Law School, New
  York City
• June 26th, 2008

2
A NEW AUTISM VOCABULARYCause, Effect
Connections of

• Immune Activation/Immune Suppression/Autoimmunity
• Oxidative Stress/Reactive Oxidative Species (ROS)
• Neuro-inflammation
• Glutathione Depletion
• Mitochondrial Dysfunction
• Impaired Oxidative Phosphorylation
• Metal Metabolism/Efflux Disorder
• Activation of Astroglia Microglia/Gliosis
• Cytokine Imbalance
• Methionine Cycle Disruption
• Impaired Methylation
• Impaired Transulfuration
• Demyelination

3
Types and Causes of Autisms?

• Types?
• Classic Regressive
• Inborn Environmental
• Genetic Acquired Neuro-Immune
• Neurodiverse Mitochondrial
• Causes?
• Inherited nDNA mutations MMR (UK)
• Inherited mtDNA mutations Thimerosal (US)
• Spontaneous mutations Mercury etc. in air,
  food, water
• Epigenetics Multi-vaccines over-stimulation
  
• Geeks get lucky Pesticides, chemicals, jet
  fuel
• Flame retardants, solvents Wireless
  phones, TV, sonograms
• known causes Thalidomide, terbutaline,
  rubella

4

• IS AUTISM ON
• THE RISE?

5
AUTISM RATES IN THE US
6
AUTISM RATES IN THREEEUROPEAN COUNTRIES
US 2008
7
Is There a Hidden Horde?

• Reported autism in US ca1988 3 per 10,000
• Reported autism in US ca2008 66 per 10,000
  (40 per 10,000 DSM-IV)
• Did doctors miss 63 out of 66 children with
  autism,
• or 95 of all ASD cases, until recent years?
• Even if 60 of ASD is full blown DSM-IV autism?

40 PDD-AS
95?
60 DSM-IV
DSM-IV
8

• Autism and the Environment Challenges
  Opportunities for Research - Pediatrics
  20081211225
• April 2007, IOM Neuroscience workshop on most
  promising urgent scientific questions.
• The environment may play a significant role in
  triggering autism, probably through a complex
  interaction with genetic susceptibilities.
• Evidence points to a large genetic component,
  but genes alone cannot account for its etiology.
  
• Report praised involvement of parents in the
  process.

9

• ARGUMENTS AGAINST A VACCINE/ MERCURY LINK

10
VSD Generation 0 (FOIA)
11
VSD Generation 4 Final Report

• Vol. 112 No. 5 November 2003,
• pp. 1039-1048

In no analyses were significant increased risks
found for autism or attention-deficit disorder.
12
VSD Autism Risk Across 5 Generations1999-2003

13
THIMEROSAL EXPOSURE AUTISM IN DENMARK Inpatient
Only (13)1981-1994 Inpatient Outpatient
(100) 1994-2000
SOURCE Stehr-Green, et al, AMERICAN JOURNAL OF
PREVENTIVE MEDICINE, 25, no. 2 (August 2003)
101-6
14
DENMARK Autism RatesDROP in 2000 and 2001
15
2004 IOM Report Preference Given to Epidemiology
over Biology

• Federal Courts Epidemiology is not acceptable
  to disprove causation.
• 2004 IOM Report We cannot rule out, based on
  the epidemiology, the possibility that vaccines
  contribute to autism in some small subset.
• Danish authors epidemiological expansion of
  criteria (inpatient-outpatient change) may have
  spuriously increased the apparent number of
  autism cases.
• Verstraeten We found no evidence against an
  association, as a negative study would.
  Additional study is recommended, which is the
  conclusion to which a neutral study must come.

16
2005 - IOM SPECIAL REPORT QUESTIONS CDC METHODS

• IOM panel said CDCs handling of VSD data
  suffered from a lack of transparency.
• Original datasets were removed from hard drive,
  copied to disc, sent to Atlanta and lost.
• Datasets were not archived in a standard manner
  are not available for reanalysis.
• IOM panel said CDC vaccine officials should seek
  legal advice about Federal Data Quality Act.
• Felony to lose or destroy taxpayer funded records
  Possible jail time for violators.

17
2006 - NIEHS PANEL QUESTIONS VSD FOR FUTURE USE

• December 2006 - NIH panel identified several
  serious problems with VSD. Panel Report was
  signed by NIH Director.
• Several weaknesses and limitations would render
  a an ecological analysis "uninformative and
  potentially misleading.
• Concern over diagnoses recorded by HMO's, which
  likely led to an "under-ascertainment" of cases.
  (CA rates were 3-4 per 1,000, but VSD reported
  just 1.1 per 1,000).
• 25 of births were excluded from the analysis. A
  susceptible population whose removal from the
  analysis might unintentionally reduce the ability
  to detect an effect of thimerosal.

18

• 2006 - NIEHS MORE PROBLEMS WITH VSD
• Other "serious problems - No consideration of
  immune globulin (RhoGam) and flu shots during
  pregnancy.
• No accounting for "cumulative exposure to organic
  mercurials through diet or other environmental
  sources.
• These problems "reduce the usefulness" to prove
  or disprove a link to thimerosal going into the
  future - though they can be fixed.
• The VSD wasn't the last word. It was an
  improvement on other studies, including the two
  in Denmark, both of which had serious weaknesses
  in their designs.
• Dr. Irva Hertz-Picciotto, NIH Panel Chair, Prof
  of Public Health, UC-Davis Med School

19
2008 CDC Responds to NIEHS Critiques

20
CDC - Detailed Response to Weaknesses
Finding ASD Diagnostic Criteria Too Narrow
Finding Variations in Business Practices
21
CDC More Responses
FINDING No Accounting for Background Mercury
FINDING Low Case Ascertainment
CDC No studies were ecological Chart reviews,
neuro-psychological exams, and parent interviews
were done (though not in Verstraeten)
22
2006 Cochrane Review MMR

• Taylor 1999 - Demonstrates the difficulties of
  drawing inferences in the absence of a
  non-exposed population or a clearly defined
  causal hypothesis.
• Fombonne 2001 - "The number and possible impact
  of biases was so high that interpretation of the
  results is impossible."
• Madsen 2002 - Interpretation is made difficult
  by the unequal length of follow up and use of
  date of diagnosis rather than onset of symptoms."
• De Stefano 2004 Probable bias in enrollment
  cases may not be representative of the rest of
  the population of the city."
• Smeeth 2004 Only 4-13 unexposed controls -
  Such a low number may indicate some bias in the
  selection of controls."

23
Other Studies (for QA)

• Miller UK Hg protects kids against neuro
  disorders (some parents demand Hg in shots).
• Fombonne Canada PDD rates rise in Montreal
  after removal of Hg (immigrant rate is twice as
  high).
• Pichichero US/Argentina Ethylmercury clears
  from blood quickly (but not necessarily from
  body)
• NEJM No neuropsych effects from thimerosal
  (except for a more than double risk for tics)
• California Thimerosal came out but ASD still
  rising (Confounding factors?)

24

• EVIDENCE TO SUPPORT A THIMEROSAL-
• MERCURY LINK

25
Mercury in US childhood vaccines TRIPLED (75mcg
to 237.5mcg) from 1988-1992
26
Hg BURDEN AND AUTISM RATES IN CALIFORNIA 1985-98
SOURCE IOM Immunization Safety Report, 2001
27
TYPICAL FLU SHOT INGREDIENT
25 micrograms Hg EPA Limit 0.1mcg/Kg/day
110 lb woman 5 times over EPA daily limit 14
lb infant 17 times over limit 1.1 lb fetus 50
times over EPA daily limit
28
Chelation results from child with ASD
29
THIOLS MERCURY CAPTURERS

• Thiol A class of SULFUR-BASED proteins that
  bind with heavy metals and help eliminate them
  from the system.
• Thiols include Glutathione, cysteine,
  metallothioneine. Glutathione is also a powerful
  antioxidant.
• Synonym for thiol - mercaptan from the Latin
  mercurium captans capturing mercury.
• Chelation Also sulfur-based DMPS
  Di-Mercapto-Succinic Acid

30

• ASD kids have low or depleted levels of thiols,
  including glutathione a powerful antioxidant.
• Low thiols levels are thought to be based on
  genes - and possible mercury exposure (See R.
  Deth).
• Methionine metabolites (methionine, cysteine,
  glutathione) in 20 children with autism compared
  vs. controls revealed severely abnormal profiles.
• Targeted nutritional intervention with Folinic
  acid, and Betaine resulted in significant
  improvement in methylation capacity in children
  with autism.
• Addition of methyl B-12 to cocktail brought all
  autistic children within normal levels of
  methionine, cysteine and glutathione.

31
METHYLATION NEEDED FOR METHIONINE CYCLE AND
TRANSULFURATION PATHWAY
32
THIMEROSAL CAN CAUSE IMMUNE IMBALANCES

• Thimerosal and Immune Cells UC Davis M.I.N.D.
  Institute March 26/06
• Tiny amounts (nanomolars) of thimerosal can
• 1) Kill immune (dendritic) cells
• 2) Cause cytokine imbalances
• 3) Induce inflammation.

33
AUTISM ASSOCIATED WITH IMMUNE IMBALANCES

• Presentation of UC Davis - MIND Institute
• 2005 IMFAR - International Meeting for Autism
  Research
• Compared to typical children, those with ASD were
  found to have
• Increased autoimmunity
• Extremely elevated levels of certain immune cells
  and cytokines
• Imbalances in the TH1/TH2 immune response

34

• Thomas Bubacher and team at Univ. of Washington
  Primate Center compared ethylmercury from
  thimerosal and methylmercury from fish.
• Methyl Hg stayed in blood longer, crossed
  blood-brain barrier more.
• BUT - Ethyl Hg in brain converts to inorganic Hg
  faster than methyl.
• 2-4 times more inorganic Hg found in brains of
  ethyl vs methyl group.
• Over half the methyl-exposed brains had no
  detectable inorganic Hg.
• Half-life in brain of organic Hg 30 days
  Half-life of inorganic 20 years

35
Changes in astrocytes and microglia in primate
brains after long-term methylmercury exposure.
Neurotoxicology. 199617127-138.

• 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.

36
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 brains immune system.
• Compared with controls, autistic tissue showed
  ongoing inflammation in various sections of
  brain.

37
HARVARDLarge 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.

38
Blood Levels of Mercury Are Related to Diagnosis
of Autism Reanalysis of an Important Data
SetJournal of Child Neurology, Vol. 22, No. 11,
1308-1311 (2007)

• We reanalyzed the data set reported by Ip et al.
  and found the original p value was in error.
• A significant relation does exist between the
  blood levels of mercury and diagnosis of an
  autism spectrum disorder.
• Hair samples offer some support for the idea
  that persons with autism may be less efficient
  and more variable at eliminating mercury from the
  blood.

39
UNIV of TEXAS - 2005 HIGHER RISK OF AUTISM NEAR
COAL-FIRED PLANTS - Health Place - 12 (2006)
203-209

• 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.
• One county with low mercury emissions but
  significant autism rates was found to harbor one
  of the nations largest mercury mines.
• A potentially important connection between
  environmental exposure to mercury and the
  development of autism.

40
ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 114 No.
9, September, 2006

• Funded by CDC - 284 ASD children 657 controls,
  born in 1994 in SF Bay Area. Assigned exposure
  level by birth tract for 19 chemicals.
• Risks for autism were elevated by 50 in tracts
  with the highest chlorinated solvents and heavy
  metals.
• Highest risk compounds were mercury, cadmium,
  nickel, trichloroethylene, and vinyl chloride.
  Risk from heavy metals was almost twice as high
  as solvents.
• Our results suggest a potential association
  between autism and estimated metal
  concentrations, and possibly solvents, in ambient
  air around the birth residence.

41
Univ. Of Texas Study links autism risk to
distance from mercury-releasing sources Health
and Place April 2008

• Hg data from 39 coal plants and 56 industrial
  facilities in Texas. ASD rates culled from 1,040
  Texas school districts.
• For every 1,000 pounds of Hg, there was a 3.7
  increase in ASD. Prevalence fell 1-2 every 10
  miles from source.
• 1st time in scientific literature that
  statistically significant association between ASD
  risk and distance from Hg source was identified.
• Not a definitive study, but just one more that
  furthers the association. Raymond Palmer.

42
THE SHANGHAI PLUME(Moves up and down Pacific
Coast)
Lower urban mercury plume. 10-day traverse from
South China Sea, ending May 5, 2002. Trajectory
calculations by N.O.A.A.
43

44
(No Transcript)
45
Annals of the School of Medicine, Universidad
Nacional San Marcos, Lima An Fac Med Lima 2007
68(3)

• Neurotoxic Effects of Thimerosal, At Vaccine
  Doses, on the Encephalon and the Development
• of Hamsters at 7 Days After Birth
• Thimerosal was associated with low body weight,
  low encephalon weight and smaller stature in
  hamsters.
• Neurotoxic effects also produced in hippocampus,
  cerebral cortex and cerebellum.
• Decrease in neuronal density found in exposed
  group.
• Neuronal necrosis, demyelination and gliosis also
  found.
• Risk in thimerosal group was high and
  statistically significant.

46
What About Al?

• Al is a known neuro-toxin
• Al is synergistic with Hg
• Al is an immune stimulant
• Al is damaging to mitochondria
• Al is found in more shots today, maybe in
  higher concentrations, (to offset Hg removal?)
• Al is not your friend

47

• THE HANNAH POLING CASE

48
Poling Concession 1 November 9, 2007

• 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.
• 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

49
Poling Concession 1

• 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 2231, 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.
• September 26, 2000 - Hannah returned to hospital
  with 102 degree 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.

50
Poling Concession 1

• 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 - 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.

51
Poling Concession 1

• October 4, 2001 Hannah found with
  lactate-to-pyruvate ratio of 281, often seen in
  disorders of mitochondrial oxidative
  phosphorylation. (Reference ratio is 201)
  Confirmed with muscle biopsy.
• February 2004 - Mitochondrial DNA analysis
  revealed single nucleotide change in the 16S
  ribosomal RNA gene (T2387C).
• April 14, 2006 - Hannah brought by ambulance to
  Athens Regional Hospital and developed tonic
  seizure. Diagnosed with complex partial seizure
  disorder. This epilepsy was NOT related to
  vaccinations.

52
Poling Concession 1 ConclusionNov 9, 2007

• Medical personnel at the Division of Vaccine
  Injury Compensation of HHS have conducted a
  thorough review and concluded that compensation
  is appropriate.
• The vaccinations Hannah received significantly
  aggravated an underlying mitochondrial disorder,
  which predisposed her to deficits in cellular
  energy metabolism, and manifested as a regressive
  encephalopathy with features of autism spectrum
  disorder.

53
Poling Concession 2February 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 Hannahs autism was caused by a
  vaccine-induced exacerbation of her underlying
  mitochondrial dysfunction.

54
CNN Worldwide Coverage Vaccine case draws new
attention to autism debate
March 6th - March 6th - CNN - Live 30
Minute April 2nd - CNN Larry CNN International
Press Conference from Atlanta King Live - and
Interview Courthouse with Polings All Day
Coverage
55
CDC Director Gerberding ReactsCause or
Precipitator?

• The government has made absolutely no statement
  about indicating that vaccines are a cause of
  autism. That is a complete mischaracterization of
  the findings of the case. Conference Call,
  March 5
• The court (government) apparently made the
  decision that it is fair to say that vaccinations
  may have been one of the precipitators.
  Press Conference, March 6

56
Dr. Gerberding on CNNMarch 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.

57
CDC Multiple Vaccine QASource www.cdc.gov

• Q Is simultaneous vaccination with multiple
  vaccines safe? Wouldn't it be safer to separate
  combination vaccines?
• A The available scientific data show that
  simultaneous vaccination with multiple vaccines
  has no adverse effect on the normal childhood
  immune system.
• Q Can so many vaccines, given so early in life,
  overwhelm a child's immune system, suppressing it
  so it does not function correctly?
• A No evidence suggests that the recommended
  childhood vaccines can overload the immune
  system. Babies are exposed to numerous bacteria
  and viruses on a daily basis.
• Q But are they injected with stimulants like
  aluminum, Hg etc?

58
Commentary A view from the CDC CNN - April 3,
2008

• Some may call it a one size fits all
  approach, but the recommended vaccine schedule is
  flexible parents shouldn't be reluctant to have
  such discussions with the childs doctor.
• We're currently conducting the largest study to
  investigate the potential causes of autism,
  looking at genetic, environmental and hormonal
  factors, as well as selected mercury exposures.

59

• MITOCHONDRIAL DYSFUNCTION AND ASD REGRESSION

60
Mighty Mito Facts

• MITO - disease in classic form is very rare
  2-per-10K (0.02) in general population.
• MITO - dysfunction in ASD is more prevalent.
  Some studies show 10-20 , maybe more among
  regressive cases 1000 times more common?
• MITO - dysfunction can be very mild - many are
  unaware. Severe forms usually inherited, can be
  fatal in youth.
• MITO - disease 1st noted in 1940s Same decade as
  autism.
• MITO - dysfunction can cause weak muscle tone,
  fatigue, poor digestion, other ASD signs. Mito
  treatments used in ASD.

61
Three Sources of Mito DisordersSources
Cleveland Clinic and UMDF

• 1) Inherited from mother (in Mito DNA)
• 2) Inherited from both parents (in nuclear DNA)
• 3) Sporadic (acquired via medicines and
  toxins).
• 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).

62
Developmental regression and mitochondrial
dysfunction in a child with autismJournal of
Child Neurology. 2006 Feb21(2)170-2Poling,
Frye, Shoffner, Zimmerman - Johns Hopkins
Hospital, Baltimore, MD

• Described oxidative phosphorylation disorder in
  19-month-old. Subtle abnormalities in some
  enzymes and amino acids.
• Authors looked at records of 159 patients with
  autism (DSM-IV) and 94 controls with other
  neurologic disorders.
• Aspartate aminotransferase was elevated in 38 of
  patients with autism compared with 15 of
  controls.
• Serum creatine kinase level also was abnormally
  elevated in 22 of 47 patients (47) with autism.
• Metabolic evaluation is indicated in autistic
  patients and defects of oxidative phosphorylation
  might be prevalent."

63
Evidence of Mitochondrial Dysfunction in
AutismAmerican Journal of Biochemistry and
Biotechnology 4 (2) 208-217, 2008

• Many cases of autism show evidence of
  mitochondrial dysfunction (MtD) without classic
  features associated with mitochondrial disease.
• MtD appears to be more common in autism and
  presents with less severe signs and symptoms.
• Exposure to environmental toxins is the likely
  etiology for mitochondrial dysfunction in
  autism.
• This dysfunction then contributes to a number of
  diagnostic symptoms observed in autism.

64
Heavy-Metal Toxicity Emphasis on
MercuryIntegrative Medicine Vol. 6, No. 2
Apr/May 2007Neustadt MD Pieczenik MD

• Metal toxicity creates multi-system
  dysfunction, which appears to be mediated
  primarily through mitochondrial damage from
  glutathione depletion.

65
Estimates of Mito Dysfunction in ASD

• 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 2nd 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.

66
Some Markers for Mito DysfunctionAnd Reported
Rates in ASD Kids

• 47 (elevated serum creatine kinase, Poling et
  al)
• 38 (elevated aspartate aminotransferase, Poling)
• 28 (elevated lactate/pyruvate ratio, (Correia et
  al)
• 20 (elevated plasma lactate, Oliveiro et al)
• 17 (elevate plasma lactate, Correia et al)
• 13-16 (two hyperlactidemia markers, Oliveiro et
  al)
• 65 - Shoffner (certain biomarkers)

67
Thimerosal Targets Mitochondria

• Thimerosal induces neuronal cell apoptosis by
  causing cytochrome c and apoptosis-inducing
  factor release from mitochondria.
• - Intl Journal of Molecular Medicine. 2005
  Dec16(6)971-7.
• Mitochondrial mediated thimerosal-induced
  apoptosis in a human neuroblastoma cell line
• - Neurotoxicology. 2005 Jun26(3)407-16.
• Biochemical and molecular basis of
  thimerosal-induced apoptosis in T cells a major
  role of mitochondrial pathway
• - Genes Immunology. 2002 Aug3(5)270-8.
• Inhibition of malate transport and activation
  of phosphate transport in mitochondria by
  thimerosal - FEBS Lett. 1980 Aug
  11117(1)149-51.
• Mercurial-induced hydrogen peroxide generation
  in mouse brain mitochondria - Chem Res Toxicol.
  2007 Dec20(12)1919-26.

68
Bridging from Cells to Cognition in Autism
Pathways to Defective Brain Function and
PlasticityDr. Martha Herbert, Harvard Am.
Journ. Biochem. Biotech 4 (2) 167-176, 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.

69
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.

70
Formaldehyde Causes Mito Damage, Oxidative Stress
and Glutathione Depletion Chem Biol Interact.
2001 Jan 30130-132(1-3)285-96.

• Low dose formaldehyde caused marked decrease in
  mitochondrial potential and inhibition of
  mitochondrial respiration, as well as oxidative
  stress in cells.
• Glutathione was also depleted in a dose-dependent
  manner.
• Antioxidants iron chelators protected against
  cell toxicity.
• Toxicity was prevented with cyclosporine or
  carnitine to prevent opening of mitochondrial
  permeability pore.
• This suggests formaldehyde targets
  mitochondria.
• (NOTE CDC repressed evidence of formaldehyde
  off-gassing in Hurricane Katrina refugee
  trailers!)

71
Maternal Residence Near Agricultural Pesticide
Applications ASD in Californias Central
ValleyEnvironmental Health Perspectives Volume
115, Number 10, October 2007

• Calif. women living near farms with
  organo-chlorine pesticides may be more at risk
  for children with autism.
• Autism rates near fields was extremely high - 28
  of mothers had children with autism, six times
  higher than those who did not live nearby.
• 7 of ASD in Central Valley might have been
  connected to insecticides from fields.
• Italian scientists in 2005 Pesticides could
  cause neurological changes that lead to autism.

72
ASD PET SHAMPOO PESTICIDE?IMFAR Meeting
London May, 2008

• Chemicals included insecticides, pet shampoos,
  and weed killers, 3 months before conception
  until first birthday.
• Mothers of ASD kids were twice as likely to
  report using pet shampoos with pyrethrins vs.
  controls. Used for flea control, pyrethrins
  affect pests' central nervous system.
• Strongest association was in second trimester,
  when ASD mothers were 2.6 times more likely to
  have been exposed to the chemical.
• In lab, pyrethrins have also been found to
  affect a part of the brain that protects it from
  chemicals within the blood.

73

• RECENT DEVELOPMENTS IN U.S. POLICY AND POLITICS

74
The NEXT Hannah Poling

• Case chosen to replace Hannah as 1st thimerosal
  test case had SAME mito markers, and was also
  pulled as test case.
• This case will be re-filed outside of Autism
  Omnibus Proceedings with new theory of causation
  Autism can be caused by aggravated mitochondrial
  dysfunction.

75
Email from HHS to CBS

• Here are the numbers of compensable cases for
  encephalitis / encephalopathy and seizures in our
  database from October 1, 1988 to March 4, 2008.
• Encephalitis/Encephalopathy 611
• Seizure Disorders 711
• Total
  1,322
• There's not much difference in the medical
  history and outcomes for children that were
  compensated for "encephalopathy" versus
  "seizures."
• Those compensated for encephalopathy often had
  seizures as part of their clinical picture, and
  vice versa.

76
2008 - CDC Studies on MMR www.cdc.gov/ncbddd/autis
m/documents/vaccine_studies.pdf

• The Autism and Biopsy Study
• Can MMR cause autism through persistent measles
  infection in the intestine? Examination of
  intestinal tissue of children with autism for the
  presence of measles virus.
• Immunizations Possible Developmental
  Regression
• CDC NIH study of whether the MMR vaccine is
  linked with developmental regression, which
  occurs in a subset of children with autism.

77
March 11 - 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.
• 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.
• DNA mutation may range from 1-in-400 to 1-in-50,
  or 2.
• DNA mapping underaway paternal grandparents
  tested.

78
CDC-CISA Conference Call Contd

• BUT is DNA mutation enough to confer MtD? Or is
  an environmental trigger needed? And what
  triggers "metabolic decomposition" anyway?
• In only 2 of the 30 cases, (6) regression linked
  to shots (Hannha was one).
• In other 28 cases, traced to fever-inducing
  infection.
• But if fever causes 94 of mito reggression,
  shouldnt there be less today - and less in
  wealthier countries?
• (Hannah spoke at 9 months, but had several fevers
  after that without regression. Now, fevers
  improve symptoms - reported in Pediatrics).

79
Three-Step, Two-Trigger Path

• STEP ONE Child is born with DNA mutation for
  mito susceptibility.
• TRIGGER ONE Child encounters pre- or neo-natal
  environmental trigger.
• STEP TWO Child develops mild, asymptomatic mito
  dysfunction.
• TRIGGER TWO Fever and/or immune overstimulation
  from infection of vaccines exceeds metabolic
  reserves.
• STEP THREE Encephalopathy, illness, regression,
  autism

80
Questions Raised On and From CDC CISA
Confernce Call

• Do we vaccinate children with known MtD sooner?
  More slowly?
• Do we develop an efficient test for MtD before
  vaccination begins?
• Do we alter schedule somehow, to lower risk of
  immune over-stimulation in susceptible children?
• Do we set a maximum number of vaccine exposures
  on any one day?
• Do we allow MMR to be separated out, on request
  of parents?
• Do we separate MMR from Varicella on same day?
  CDC stoped recommending Pro-Quad (MMRV) because
  it doubled seizure risk.
• Do we set new limits on kids playing catch up?

81
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 acellular pertussis vaccine associated with
  risk for acute neurological events?
• Is combo MMRV vaccine associated with increased
  febrile seizure risk?
• Are varicella and MMRV vaccines associated with
  increased risk for clinically important events
  related to virus reactivation?

82
CDC Clinical Outcomes To Study

• Autoimmune diseases
• Nervous system demyelinating disorders
• Encephalitis/encephalopathy
• Neurodevelopmental disorders, including autism
  spectrum disorder (ASD)
• Clinically important outcomes associated with
  post-immunization fever.

83
CDC Also Proposes Mito Research

• 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.

84

• Workshop Mitochondrial Disorders of
  Childhood Testing, Potential Relationships to
  Autism Spectrum Disorders, and Triggers for
  Neurological Deterioration
• June 29, 2008 Indianapolis
• Sponsored by HHS, CDC, FDA, NIH agencies and
  timed around United Mitochondrial Disease
  Foundation Meeting.
• HHS Goals and Objectives - Convene 11 experts
  in mitochondrial disorders or autism to discuss
  how the neurology of mitochondrial disorders
  might inform autism research.
• UMDF Address neurological features of
  mitochondrial disorders, exacerbating factors,
  and testing and diagnosis.

85
6/19/08 -Should I vaccinate my baby?

• 1. Delaying the first hepatitis B shot
• 2. Not doing some shots at all
• 3. Checking for 'titers' before giving booster
  shots
• 4. Spreading the vaccines out over a longer
  period of time
• 5. Splitting up combined shots

                       /health
86
Hillary Clinton on AutismCampaign
QuestionnaireFeb. 2008

• Yes, (autism is epidemic). I am committed to
  make investments to find the causes of autism,
  including possible environmental causes like
  vaccines.

87
Barack Obama on AutismCampaign Trail,
Pennsylvania 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.

88
John McCain on AutismCampaign Trail, Texas
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.

89
Dr. Bernadine Healy on CBS NewsMay, 2008

• 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."

90
Healy on CBS News

• The IOM concluded there is no link based mostly
  on population studies. But, Populations do not
  test causality they test associations.
• I am a member of the IOM. I love the IOM. But a
  report from 2004 basically said, 'Dont pursue
  susceptibility groups. Don't look for those
  children who may be vulnerable.' I really take
  issue with that conclusion."

91
Dr. Healy on Don Imus Radio ShowMay, 2008

• The issue is really almost one of ideology or
  religion, more than it is of science. It is the
  sense that vaccines are critically important.

92
THE END Remember the kids!
93
6/19/08 -Should I vaccinate my baby?

• Story Highlights
• Parents have concerns about possible vaccine and
  autism link
• Doctors from CDC say vaccine schedule is
  flexible
• Sears Schedule recommends spreading vaccines out
  over time
• Looking at family history can give clues as to
  whether your child is at risk

94
Evidence of Harm IntroductionFirst Words in
Book

• Does mercury in vaccines cause autism in
  children? A definitive answer has proven elusive,
  and it remains so to this day.
• No one can say with certainty that thimerosal
  helped fuel the explosion in cases of autism,
  attention deficit disorder, speech delay and
  other disorders over the past decade.

95
EOH Introduction

• Several potential culprits beside thimerosal
  have been mentioned, though there is no hard
  evidence to link any of them to autism. Possible
  environmental triggers include mercury in
  fish, pesticides, PCBs, flame retardants, jet
  fuel, live viruses in vaccines or some as-yet
  unidentified virus, and even rampant cell phone
  use. It is plausible that any combination of the
  above, with or without thimerosal exposure added
  into the mix, might cause harm to some fetuses
  and infant children.
• At the very least, the thimerosal debate has
  compelled the scientific community, however
  reluctantly, to consider an environmental
  component to the disorder, rather than looking
  for a purely genetic explanation.

96
EOH Introduction

• Some parents, fearing harmful effects, have
  been tempted not to vaccinate their children.
  Most people would agree that this is foolhardy
  and dangerous. Few of us are old enough to
  remember the great epidemics of influenza,
  pertussis, smallpox, polio, diphtheria and
  measles that once swept entire populations -
  until the advent of vaccines reduced those
  maladies to abstract, unthreatening concepts, at
  least in America. These diseases, all of them
  preventable, can kill children. When vaccination
  rates fall, disease rates rise.

97

• WHAT ABOUT
• CALIFORNIA?

98
Possible Confounding Factors

• Hg in vaccines and Rho-Gam until 2003.
• Flu shot for infants and pregnant women.
• Early intervention More 3-5 y/o counted.
• Rising aluminum exposures.
• Rising Hg levels in air and soil.
• Immigration from countries that still use Hg.
• Expanding criteria in 2008?

99
The flu shot may matter

• A pregnant woman receives 25mcg, fetus is also
  exposed. Much is absorbed by fetal brain stem in
  rats. Human maternal/cord blood ratio is 12).
• 1lb fetus exposed to 25mcg is 500 times over EPA
  limit.
• At 6 months, a 7kg baby receives 12.5mcg or 17
  times over limit. At 7 months, baby receives
  12.5mcg.
• At 18 months, a 10kg infant receives 25mcg or
  25 times over
• Other shots contain 5 mcg in residual Hg.
• Total by 18 mos 80 mcg UK exposure until 2004
  75 mcg

100
California autism increase in DDS cases by
ethnic group 2003-2007
101
Montreal School Boards PDD Highest in English
Speaking (Immigrant) District
102
PDD rates in Lester B. Pearson School Board
(LBPSB) Montreal
103
-June 6, 2007- Canadian Broadcasting News

• Autism rates higher
• in immigrant families
• Health-care specialists in Montreal are trying
  to understand why such a high number of autistic
  children come from immigrant families, a
  phenomenon seen in major cities across North
  America.