THE VACCINEAUTISM

1

• THE VACCINE-AUTISM
• DEBATE
• NEW
• DEVELOPMENTS
• FROM THE UNITED STATES
• Presentation by David KirbyRegent Hall, London -
  4 June, 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, rubella,
  terbutaline

4

• IS AUTISM ON
• THE RISE?

5
AUTISM RATES IN THE US
6
AUTISM RATES IN THREEEUROPEAN COUNTRIES
US 2008
7
Reasons for Increase?

• 1990s - Expansion of criteria from DSM-IV full
  blown autism to include PDD-NOS and AS.
• Better diagnostic tools greater awareness.
• More services early intervention.
• Diagnostic Substitution (ie, mental retardation).
• Actual increase in incidence (thus not 100
  genetic).
• Combination of the above?

8
California DDS Oct 06 Services Offered for
DSM-IV Only (Note PDD AS not counted)
Expected 10-21 25,584Actual 10-21
12,117Missing 10-21 13,467 Missing
18-21 76
76
9
Is There a Hidden Horde?

• Reported autism in US ca1988 3 per 10,000
• Reported autism in US ca2008 66 per 10,000
  
• 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
10
NEW CDC findings 1 IN 150 - Feb 07 Average
rate was 67 per 10,000 among 8-year-olds in 2000,
and 66 per 10,000 in 2002, or about 1-in-150
children. At most sites, the range was 52 to 76
per 10,000 with a difference of almost 50
between the highest and lowest. Prevalence was
much lower (33 per 10,000) in Alabama, and higher
(106 per 1,000) in New Jersey in 2002.
Prevalence increased 10 from 2000 (1992
cohort) to 2002 (1994 cohort) in the six sites
with data for both years. Why are newest
prevalence data six years old?
11

• ARGUMENTS AGAINST A VACCINE-AUTISM LINK

12
VSD Generation 0 (FOIA)
13
VSD Generation 1(Verstraeten 2/2000)Obtained
Via FOIA
14
VSD Generation 2(Simpsonwood ACIP 6/2000)
15
VSD Generation 3(IOM Presentation 7/2001)
16
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.
17
VSD Autism Risk Across 5 Generations1999-2003

18
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
19
DENMARK Autism RatesDROP in 2000 and 2001
20
Thiomersal Study by Dr. Elizabeth Miller - UK
Public Health Lab Service

• Examined medical records of 100,000 children
• Those who received all three doses of DTP were no
  more at risk of developmental disorders than
  those who received two, one or zero doses.
• Thimerosal seemed to be neuro-protective
• Children who received the most thimerosal were 6
  less likely to develop autism.
• ADD 8 less likely
• Unspecified delay 16 less likely

21
CDC MMR Studies Find No Link

• Studies found no link between MMR and autism UK
  researchers studied 498 ASD children born
  1979-1998.
• Percentage of children with autism who received
  MMR was the same as unaffected group.
• Onset of "regressive" symptoms of autism did not
  occur within 2, 4, or 6 months of receiving the
  MMR vaccine.
• IOM concluded in 2004 there is no association
  between autism and MMR.
• CDC There is no published scientific evidence
  showing any benefit to separating the combination
  MMR vaccine.

22
2004 IOM Report Preference Given to Epidemiology
over Biology

• Federal Courts Epidemiology is not acceptable
  to disprove causation.
• 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.

23
NIH PANEL QUESTIONS CDC METHODS - 12/06

• December 2006 NIH panel identified several
  serious problems with VSD. Report was signed by
  NIH Director.
• Several weaknesses and limitations would render
  a comparative analysis "uninformative and
  potentially misleading.
• Panel was concerned about how autism diagnoses
  were made and recorded by HMO's.
• These 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).

24

• NIH MORE PROBLEMS WITH VSD STUDY DESIGN
• Many other problems 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. (Same view as
  former NIH head Dr. Healy).
• Other "serious problems - No consideration of
  immune globulin (RhoGam) and 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 between thimerosal and autism
  though they can be fixed.

25
Quotes on the NIH Report UPI Article -December
11, 2006

• The VSD study wasn't the last word. Things need
  to be looked at again, perhaps with different
  methodology,"
• --NIH Panel Chair Irva Hertz-
  Picciotto, Professor of Public Health,
  UC-Davis School of Medicine.
• "Some studies are stronger than others. The
  Verstraeten study was an improvement on other
  studies, including the two in Denmark, both of
  which had serious weaknesses in their designs.
• --Dr. Hertz-Picciotto

26
Vaccines for MMR in Children Cochrane Database of
Systematic Reviews 2005, Issue 4
MMR associated with lower rate of upper
respiratory tract infections. MMR associated
with febrile convulsions within two weeks. MMR
unlikely associated with Crohn's disease,
ulcerative colitis, autism. BUT Studies had
several methodological difficulties Most
common Inadequate non-exposed control
groups. Meaningful inferences from individual
studies lacking a non-exposed control group are
difficult to make.

27
Cochrane Review Study Limitations

• 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 - 4-13 unexposed controls was
  deemed ok, but, such a low number may indicate
  some bias in the selection of controls."

28

• EVIDENCE TO SUPPORT A THIMEROSAL-
• MERCURY LINK

29
Mercury in US childhood vaccines TRIPLED (75mcg
to 237.5mcg) from 1988-1992
UK 75mcg _____
30
Hg BURDEN AND AUTISM RATES IN CALIFORNIA 1985-98
SOURCE Mark Blaxill, SAFEMINDS, 2001
31
Chelation results from child with ASD
32
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
33
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

34

• 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.

35
METHYLATION NEEDED FOR METHIONINE CYCLE AND
TRANSULFURATION PATHWAY
36
TOXICOLOGY AND APPLIED PHARMACOLOGY - 15.3
(March, 2006)

• Urine samples from 100s of French children
  yielded evidence for a link between autism and
  heavy metals.
• ASD samples had high levels of porphyrins used
  to produce of haem, oxygen-carrying part of
  haemoglobin.
• Heavy metals block haem, causing porphyrins to
  accumulate in urine.
• Coproporphyrin was 2.6 times higher in autism vs
  controls.
• One author said it was Highly likely heavy
  metals are responsible for childhood autism in a
  majority of cases.

37
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.

38
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

39

• 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

40
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.

41
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.

42
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.

43
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.

44
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.

45
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.

46
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.

47

• WHAT ABOUT
• CALIFORNIA?

48
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

49
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.
50

51
(No Transcript)
52

• Cremation costs rise as tooth fillings poison
  the living 8th January 2007
• Cremations cause nearly 1/6th of all UK mercury
  emissions.
• The rise in mercury pollution from crematoria is
  caused by what dentists call the "heavy metal
  generation" those who who now die with more
  teeth because of better dental care.
• Millions of Britons have two to four grams of
  mercury in their mouths. One gram can pollute a
  25-acre lake.

53
California autism increase in DDS cases by
ethnic group 2003-2007
54
Montreal School Boards PDD Highest in English
Speaking (Immigrant) District
55
PDD rates in Lester B. Pearson School Board
(LBPSB) Montreal
56
-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.

57
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

58

• THE HANNAH POLING CASE

59
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

60
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 hospitalized for 102
  degree fever Also had diminished appetite,
  small red dots on chest and was 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.

61
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.

62
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.

63
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.

64
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.

65
Hannah Poling Makes the Big Leagues in US Media

• Debate Rages Anew on Vaccine-Autism Link
• Vaccine Case An Exception Or A
  Precedent?
• Deal in Autism Case Fuels Vaccine Debate

66
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
67
The Poling Story Went Coast to
Coast
68
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

69
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.

70
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 immune stimulants
  like aluminum, Hg etc?

71
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.

72

• MITOCHONDRIAL DYSFUNCTION AND ASD REGRESSION

73
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.

74
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.
• Mito can be damaged by mercury, aluminum,
  pesticides, formaldehyde, alcohol, even HIV meds
  like AZT (which delete large segments of MtDNA).

75
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."

76
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.

77
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.

78
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 plasma 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)

79
Thimerosal Targets MitochondriaSome Results of
Recent PubMed Search

• Thimerosal induces neuronal cell apoptosis by
  causing cytochrome c and apoptosis-inducing
  factor release from mitochondria.
• - Int J Mol Med. 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 Immun. 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.
• Thimerosal a new reagent for study of
  phosphate transport in mitochondria
• - FEBS Lett. 1980 Jun 2114(2)295-8.
• Mercurial-induced hydrogen peroxide generation
  in mouse brain mitochondria
• - Chem Res Toxicol. 2007 Dec20(12)1919-26.

80
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.

81
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!)

82
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.

83
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.

84

• A FEW MORE RECENT STUDIES 2007-2008

85
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.

86
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.

87
VACCINE INJURY IN PRIMATES IMFAR Meeting
London May, 2008

• Macaques given routine US vaccine schedule.
  Dosage reduced to match body weight. Followed for
  5 years/
• 13 vaccinated animals showed increased
  aggression, impaired cognitive skills,
  developmental delay and autistic like behavior.
  Also poor reflexes, insular and aggressive
  behavior, and less interest in surroundings.
• Three unvaccinated animals developed normally.
• MRIs showed vaxed animals had abnormal brain
  activity, including opioid receptors, inked to
  sleeplessness, hallucinations, poor social
  skills.
• Damage also to amygdala, which regulates emotions.

88
Oxidative Stress and Mercury Deposits in
Autistic BrainsAm. Journal of Biochemistry and
Biotech 4(2) 73-84, 2008

• Harvard researchers showed a potential link
  between mercury and autopsied brains of young
  people w/ASD.
• Marker for oxidative stress was 68.9 higher in
  autistic brain issue than controls.
• Mercury levels were 68.2 higher (not
  significant, probably due to small sample size).
• Elevated Hg levels were significantly associated
  with OS.
• Data suggest a need for more extensive studies
  of oxidative stress, its relationship to the
  environmental factors and its possible
  attenuation by antioxidants in autism.

89
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.

90
Being Born Small, Early Raises Autism RiskCDC
study found link was most pronounced for
low-birth-weight US NEWS WORLD REPORT - June
2, 2008

• Low birth weight had twofold increase in autism
  risk, higher among girls.
• Could be a marker for an impaired fetus with a
  neurological problem which is retarding its
  growth. OR, being small may be related to harm to
  the neurological development of the fetus, such
  as infection during pregnancy.
• These findings support the idea that there are
  different kinds of autism and different
  mechanisms underlying those cases.
• Mercury exposure at birth (12.5mcg) _at_8.8lbs
  31xEPA
• _at_4.4lbs 62xEPA
• Mercury exposure at 2 mos (62.5mcg) _at_13.2lbs
• _at_6.6lbs 208xEPA

91

• RECENT DEVELOPMENTS IN U.S. POLICY AND POLITICS
• (Almost Done No Yawning!)

92
June 07 -1st Autism Case in Vaccine Court Is
MMR a Cause?

• Case of Michelle Cedillo of Arizona.
• Had severe brain damage after MMR.
• Govt said she had autism before shot.
• Govt argued that OLeary lab was unreliable
  had UK documents.
• New data may refute that.
• CW Michelle will be compensated for injury, but
  maybe not ASD.

93
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.

94
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.

95
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.

96
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).

97
Three-Step, Two-Trigger Path Jon Poling
(Not a Square Dance from Texas)

• 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

98
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?

99
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?

100
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.

101
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.

102
Federal Register 5-23-08 (Vol. 73 No. 101)DEPT
OF HEALTH HUMAN SERVICES/CDC

• June 12, 2008 - 12-2PM
• Teleconference Meeting on HHS Grants for Vaccine
  Injury Prevention Studies
• CLOSED TO THE PUBLIC
• Topic Associations of Vaccine Adverse Events
  and Human Genetic Variations Request for Proposal

103
Bill Clinton on AutismCampaign Trail, Oregon
May, 2008

• You do not want to bring your children into
  the world where we go on with the number of
  children who are born with autism tripling every
  20 years, and nobody knows why,"

104
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.

105
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.

106
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.

107
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."

108
Dr. Healy on CBS News

• We have the opportunity to understand whether
  or not there are susceptible children -- perhaps
  medically, perhaps from a metabolic issue, or
  mitochondrial disorder -- that makes them more
  susceptible to vaccines.

109
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."

110
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.

111
THE END Remember the kids!
112
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.

113
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.

114
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.