THE VACCINE-AUTISM DEBATE:NEWDEVELOPMENTS FROM THE UNITED STATES Presentation by David Kirby Regent Hall, London - 4 June, 2008.

THE VACCINE-AUTISMTHE VACCINE-AUTISM

DEBATE: DEBATE:

NEWNEW

DEVELOPMENTS DEVELOPMENTS

FROM THE UNITED FROM THE UNITED STATESSTATES

PPresentation by David Kirbyresentation by David KirbyRegent Hall, London - 4 June, Regent Hall, London - 4 June,

20082008

A NEW AUTISM VOCABULARYA NEW AUTISM VOCABULARYCause, Effect & Connections of:Cause, Effect & Connections of:

Immune Activation/Immune Immune Activation/Immune Suppression/AutoimmunitySuppression/Autoimmunity

Oxidative Stress/Reactive Oxidative Species (ROS)Oxidative Stress/Reactive Oxidative Species (ROS) Neuro-inflammation Neuro-inflammation Glutathione DepletionGlutathione Depletion Mitochondrial DysfunctionMitochondrial Dysfunction Impaired Oxidative PhosphorylationImpaired Oxidative Phosphorylation Metal Metabolism/Efflux Disorder Metal Metabolism/Efflux Disorder Activation of Astroglia & Microglia/“Gliosis”Activation of Astroglia & Microglia/“Gliosis” Cytokine Imbalance Cytokine Imbalance Methionine Cycle Disruption Methionine Cycle Disruption Impaired MethylationImpaired Methylation Impaired TransulfurationImpaired Transulfuration DemyelinationDemyelination

Types and Causes of Types and Causes of “Autisms?”“Autisms?” Types?Types?

““Classic”Classic” “Regressive”“Regressive” ““Inborn” Inborn” “Environmental”“Environmental”

““Genetic” Genetic” “Acquired Neuro-Immune”“Acquired Neuro-Immune”““Neurodiverse”Neurodiverse” “Mitochondrial”“Mitochondrial”

Causes?Causes?Inherited Inherited nDNA*nDNA* mutations mutations MMR MMR (UK)(UK)Inherited Inherited mtDNA*mtDNA* mutations mutations Thimerosal Thimerosal (US)(US)““Spontaneous” mutationsSpontaneous” mutations Mercury etc. in air, food, water Mercury etc. in air, food, water ““Epigenetics”Epigenetics” Multi-vaccines: over-Multi-vaccines: over-stimulation stimulation ““Geeks get lucky”Geeks get lucky” Pesticides, chemicals, jet fuelPesticides, chemicals, jet fuel

Flame retardants, solvents Flame retardants, solvents Wireless phones, TV, Wireless phones, TV,

sonogramssonograms*known causes*known causes Thalidomide*, rubella*, Thalidomide*, rubella*, terbutalineterbutaline

IS AUTISM ON IS AUTISM ON

THE THE RISERISE??

AUTISM RATES IN THE USAUTISM RATES IN THE US

0

20

40

60

80

Cases Per10,000

3 20 40 60 66

1980s 1990s 2000 2005 2008

AUTISM RATES IN THREEAUTISM RATES IN THREEEUROPEAN COUNTRIESEUROPEAN COUNTRIES

0

20

40

60

80

100

120

Rates per 10K 5 66 116 7.7 9.2 15.6

UK 1990

UK 2004

UK 2006

DK 2001

POR 2007

AZR 2007

US 2008

Reasons for Increase?Reasons for Increase? 1990’s - Expansion of criteria from DSM-IV “full 1990’s - Expansion of criteria from DSM-IV “full

blown” autism to include PDD-NOS and AS.blown” autism to include PDD-NOS and AS.

Better diagnostic tools & greater awareness.Better diagnostic tools & greater awareness.

More services & early intervention.More services & early intervention.

Diagnostic Substitution (ie, mental retardation).Diagnostic Substitution (ie, mental retardation).

Actual increase in incidence (thus not 100% Actual increase in incidence (thus not 100% genetic).genetic).

Combination of the above?Combination of the above?

California DDS – Oct ‘06: California DDS – Oct ‘06: Services Offered for DSM-IV Services Offered for DSM-IV Only Only (Note: PDD & AS (Note: PDD & AS notnot

counted)counted)

0

500

1000

1500

2000

2500

Avg per agegroup

2063 2132 1539 983 505

3 to 5 6 to 910 to

1314-17 18-21

Expected 10-21: 25,584

Actual 10-21: 12,117

“Missing” 10-21: 13,467

% “Missing” 18-21: 76%

76%

Is There a “Hidden Is There a “Hidden Horde?”Horde?”

Reported autism in US – ca1988: 3 per 10,000Reported autism in US – ca1988: 3 per 10,000 Reported autism in US – ca2008: 66 per 10,000 Reported autism in US – ca2008: 66 per 10,000

Did doctors “miss” 63 out of 66 children Did doctors “miss” 63 out of 66 children with autism, with autism, or 95% of or 95% of allall ASD cases, until recent years? ASD cases, until recent years?

Even if 60% of ASD isEven if 60% of ASD is “full blown” “full blown” DSM-IV DSM-IV autism?autism?

0

10

20

30

40

50

60

70

1988 2008

Cases per 10k95%?

60% DSM-IV

40% PDD-AS

DSM-IV

“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?

ARGUMENTS ARGUMENTS AGAINST AGAINST A VACCINE-AUTISM A VACCINE-AUTISM

LINKLINK

VSD: Generation VSD: Generation “0” “0” (FOIA)(FOIA)

VSD: Generation VSD: Generation 11(Verstraeten – 2/2000)(Verstraeten – 2/2000)

Obtained Via FOIAObtained Via FOIA

VSD: Generation VSD: Generation 22(Simpsonwood & ACIP 6/2000)(Simpsonwood & ACIP 6/2000)

VSD Generation: VSD Generation: 33(IOM Presentation 7/2001) (IOM Presentation 7/2001)

VSD: Generation VSD: Generation 44 Final Report Final Report

Vol. 112 No. 5 November Vol. 112 No. 5 November 2003,2003,

pp. 1039-1048pp. 1039-1048

“In no analyses were significant increased risks found for autismor attention-deficit disorder.”

Evidence of Harm

VSD Autism Risk Across 5 VSD Autism Risk Across 5 GenerationsGenerations1999-20031999-2003

0

2

4

6

8

Relative Risk 7.62 2.48 1.69 1.52 0

Gen 0 Gen 1 Gen 2 Gen 3 Gen 4

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

DENMARK: Autism RatesDENMARK: Autism RatesDROPDROP in 2000 and 2001in 2000 and 2001

ThiomersalThiomersal Study by Dr. Study by Dr. Elizabeth Miller - UK Public Elizabeth Miller - UK Public

Health Lab ServiceHealth Lab Service Examined medical records of 100,000 Examined medical records of 100,000

childrenchildren Those who received all three doses of DTP Those who received all three doses of DTP

were no more at risk of developmental were no more at risk of developmental disorders than those who received two, one disorders than those who received two, one or zero doses. or zero doses.

Thimerosal seemed to be “neuro-protective”:Thimerosal seemed to be “neuro-protective”: Children who received the most thimerosal were Children who received the most thimerosal were

6% 6% lessless likely to develop autism. likely to develop autism. ADD: 8% less likelyADD: 8% less likely ““Unspecified delay”: 16% less likelyUnspecified delay”: 16% less likely

CDC: CDC: MMR Studies Find No MMR Studies Find No LinkLink

Studies found no link between MMR and autism: Studies found no link between MMR and autism: UK researchers studied 498 ASD children born UK researchers studied 498 ASD children born 1979-1998.1979-1998.

Percentage of children with autism who received Percentage of children with autism who received MMR was the same as unaffected group.MMR was the same as unaffected group.

Onset of "regressive" symptoms of autism did not Onset of "regressive" symptoms of autism did not occur within 2, 4, or 6 months of receiving the occur within 2, 4, or 6 months of receiving the MMR vaccine. MMR vaccine.

IOM concluded in 2004 there is no association IOM concluded in 2004 there is no association between autism and MMR.between autism and MMR.

CDC: “There is no published scientific evidence CDC: “There is no published scientific evidence showing any benefit to separating the combination showing any benefit to separating the combination MMR vaccine.”MMR vaccine.”

2004 IOM Report: 2004 IOM Report: Preference Given to Preference Given to

Epidemiology over BiologyEpidemiology over Biology Federal Courts:Federal Courts: “Epidemiology is not “Epidemiology is not

acceptable”acceptable” to disprove causation. to disprove causation.

IOM ReportIOM Report: “We : “We cannot rule out,cannot rule out, based on the based on the epidemiology,epidemiology, the possibility that vaccines the possibility that vaccines contribute to autism in some small subset.” contribute to autism in some small subset.”

Danish authorsDanish authors: : epidemiological expansionepidemiological expansion of of criteria (inpatient-outpatient change) “may have criteria (inpatient-outpatient change) “may have spuriously increasedspuriously increased the apparent number of the apparent number of autism cases.”autism cases.”

VerstraetenVerstraeten: “We found no evidence against an : “We found no evidence against an association, as a negative study would. Additional association, as a negative study would. Additional study is recommended, which is the conclusion to study is recommended, which is the conclusion to which a which a neutral study neutral study must come.” must come.”

NIH PANEL QUESTIONS NIH PANEL QUESTIONS CDC METHODS - CDC METHODS - 12/0612/06

December 2006 : NIH panel “identified several serious December 2006 : NIH panel “identified several serious problems” with VSD. Report was signed by NIH Director.problems” with VSD. Report was signed by NIH Director.

““Several weaknesses and limitations” would render a Several weaknesses and limitations” would render a comparative analysis "uninformative and potentially comparative analysis "uninformative and potentially misleading.”misleading.”

Panel was concerned about how autism diagnoses were Panel was concerned about how autism diagnoses were made and recorded by HMO's.made and recorded by HMO's.

These likely led to an "under-ascertainment" of cases. (CA These likely led to an "under-ascertainment" of cases. (CA rates were 3-4 per 1,000, but VSD reported just 1.1 per rates were 3-4 per 1,000, but VSD reported just 1.1 per 1,000). 1,000).

NIHNIH: MORE PROBLEMS WITH VSD STUDY : MORE PROBLEMS WITH VSD STUDY DESIGNDESIGN

Many other problems: 25% of births were excluded from Many other problems: 25% of births were excluded from the analysis. the analysis.

““A susceptible population whose removal from the A susceptible population whose removal from the analysis might unintentionally reduce the ability to analysis might unintentionally reduce the ability to detect an effect of thimerosal.“ (Same view as former detect an effect of thimerosal.“ (Same view as former NIH head NIH head Dr. HealyDr. Healy).).

Other "serious problems” - No consideration of immune Other "serious problems” - No consideration of immune globulin (RhoGam) and shots during pregnancy. globulin (RhoGam) and shots during pregnancy.

No accounting for "cumulative exposure to organic No accounting for "cumulative exposure to organic mercurials through diet or other environmental mercurials through diet or other environmental sources.”sources.”

These problems "reduce the usefulness" to prove or These problems "reduce the usefulness" to prove or disprove a link between thimerosal and autism – though disprove a link between thimerosal and autism – though they can be fixed.they can be fixed.

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

““The VSD study wasn't the last word. The VSD study wasn't the last word. Things need to be looked at again, Things need to be looked at again, perhaps with different methodology," perhaps with different methodology,"

----NIH Panel ChairNIH Panel Chair Irva Irva Hertz-Hertz- Picciotto, Picciotto, Professor of Public Professor of Public Health, UC-Davis School of Health, UC-Davis School of

Medicine. Medicine.

"Some studies are stronger than "Some studies are stronger than others. The Verstraeten study was an others. The Verstraeten study was an improvement on other studies, improvement on other studies, including the two in Denmark, both of including the two in Denmark, both of which had serious weaknesses in their which had serious weaknesses in their designs.” designs.”

--Dr. Hertz-Picciotto--Dr. Hertz-Picciotto

Vaccines for MMR in Vaccines for MMR in ChildrenChildren Cochrane Database of Cochrane Database of Systematic ReviewsSystematic Reviews 2005, Issue 4 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.”

Cochrane Review: Cochrane Review: Study Study LimitationsLimitations

Taylor 1999 - Taylor 1999 - “Demonstrates the difficulties of drawing “Demonstrates the difficulties of drawing inferences in the absence of a non-exposed population or a inferences in the absence of a non-exposed population or a clearly defined causal hypothesis.”clearly defined causal hypothesis.”

Fombonne 2001 - Fombonne 2001 - "The number and possible impact of "The number and possible impact of biases was so high that interpretation of the results is biases was so high that interpretation of the results is impossible."impossible."

Madsen 2002 - Madsen 2002 - “Interpretation is made difficult by the “Interpretation is made difficult by the unequal length of follow up and use of date of diagnosis unequal length of follow up and use of date of diagnosis rather than onset of symptoms."rather than onset of symptoms."

De Stefano 2004 – De Stefano 2004 – “Probable bias in enrollment; cases may “Probable bias in enrollment; cases may not be representative of the rest of the population of the not be representative of the rest of the population of the city."city."

Smeeth 2004 - Smeeth 2004 - 4-13% unexposed controls was deemed ok, 4-13% unexposed controls was deemed ok, but, “such a low number may indicate some bias in the but, “such a low number may indicate some bias in the selection of controls."selection of controls."

EVIDENCE TO EVIDENCE TO SUPPORTSUPPORT A THIMEROSAL-A THIMEROSAL-MERCURY LINK MERCURY LINK

Mercury in US childhood vaccines Mercury in US childhood vaccines TRIPLED TRIPLED (75mcg to 237.5mcg) (75mcg to 237.5mcg)

from 1988-1992from 1988-1992

0

50

100

150

200

250

70s-80s

1988 ~1989 1992

3 DTP = 75mcg

4 HiB=175mcg

1 DTaP=200mcg

3 HepB=237.5

UK: 75mcg _____

Hg BURDEN AND AUTISM Hg BURDEN AND AUTISM RATES IN CALIFORNIA RATES IN CALIFORNIA

1985-981985-98

SOURCE: Mark Blaxill, SAFEMINDS, 2001

Chelation results from child Chelation results from child with ASDwith ASD

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

THIOLSTHIOLS “MERCURY CAPTURERS”“MERCURY CAPTURERS”

ThiolThiol – A class of – A class of SULFUR-BASEDSULFUR-BASED proteins that proteins that bind with heavy metals and help eliminate bind with heavy metals and help eliminate them from the system.them from the system.

Thiols include – GlutaThiols include – Glutathiothione, cysteine, ne, cysteine, metallothioneine. Glutathione is also a metallothioneine. Glutathione is also a powerful antioxidant.powerful antioxidant.

Synonym for thiol - “mercaptan” from the Latin Synonym for thiol - “mercaptan” from the Latin mercurium captansmercurium captans: : “capturing mercury.”“capturing mercury.”

Chelation – Also sulfur-based; DMPS = Di-Chelation – Also sulfur-based; DMPS = Di-MercaptoMercapto-Succinic Acid-Succinic Acid

ASD kids have low or depleted levels of “thiols,” ASD kids have low or depleted levels of “thiols,” including glutathione – a powerful antioxidant.including glutathione – a powerful antioxidant.

Low thiols levels are thought to be based on genes - and Low thiols levels are thought to be based on genes - and possible mercury exposure (See: R. Deth).possible mercury exposure (See: R. Deth).

Methionine “metabolites” (methionine, cysteine, Methionine “metabolites” (methionine, cysteine, glutathione) in 20 children with autism compared vs. glutathione) in 20 children with autism compared vs. controls revealed severely abnormal profiles.controls revealed severely abnormal profiles.

Targeted nutritional intervention with Folinic acid, and Targeted nutritional intervention with Folinic acid, and Betaine resulted in significant improvement in Betaine resulted in significant improvement in methylation capacity in children with autism.methylation capacity in children with autism.

Addition of methyl B-12 to “cocktail” brought all autistic Addition of methyl B-12 to “cocktail” brought all autistic children within normal levels of methionine, cysteine children within normal levels of methionine, cysteine and glutathione. and glutathione.

METHYLATION: NEEDED FOR METHIONINE CYCLE AND TRANSULFURATION PATHWAY

Urine samples from 100s of French children yielded Urine samples from 100s of French children yielded “evidence for a link between autism and heavy “evidence for a link between autism and heavy metals.”metals.”

ASD samples had high levels of porphyrins – used to ASD samples had high levels of porphyrins – used to produce of produce of haemhaem, oxygen-carrying part of , oxygen-carrying part of haemoglobin.haemoglobin.

Heavy metals block haem, causing porphyrins to Heavy metals block haem, causing porphyrins to accumulate in urine. accumulate in urine.

Coproporphyrin was 2.6 times higher in autism vs Coproporphyrin was 2.6 times higher in autism vs controls.controls.

One author said it was “Highly likely heavy metals One author said it was “Highly likely heavy metals are responsible for childhood autism in a majority of are responsible for childhood autism in a majority of cases.”cases.”

TOXICOLOGY AND APPLIED PHARMACOLOGY - 15.3 (March, 2006)

Thimerosal and Immune Cells – UC Davis Thimerosal and Immune Cells – UC Davis M.I.N.D. Institute – March 26/06M.I.N.D. Institute – March 26/06

Tiny amounts (nanomolars) of thimerosal Tiny amounts (nanomolars) of thimerosal can:can:

1) Kill immune (dendritic) cells1) Kill immune (dendritic) cells

2) Cause cytokine imbalances2) Cause cytokine imbalances

3) Induce inflammation.3) Induce inflammation.

THIMEROSAL CAN CAUSE THIMEROSAL CAN CAUSE IMMUNE IMBALANCESIMMUNE IMBALANCES

AUTISM ASSOCIATED WITHAUTISM ASSOCIATED WITH IMMUNE IMBALANCES IMMUNE IMBALANCES

Presentation of UC Davis - MIND InstitutePresentation of UC Davis - MIND Institute2005 IMFAR - International Meeting for Autism Research 2005 IMFAR - International Meeting for Autism Research

Compared to typical children, those with ASD were found Compared to typical children, those with ASD were found to have:to have:

Increased autoimmunityIncreased autoimmunity

Extremely elevated levels of certain immune Extremely elevated levels of certain immune cells and cytokinescells and cytokines

Imbalances in the TH1/TH2 immune response Imbalances in the TH1/TH2 immune response

Thomas Bubacher and team at Univ. of Washington Primate Center Thomas Bubacher and team at Univ. of Washington Primate Center compared ethylmercury from thimerosal and methylmercury from compared ethylmercury from thimerosal and methylmercury from fish. fish.

Methyl Hg stayed in blood longer, crossed blood-brain barrier more.Methyl Hg stayed in blood longer, crossed blood-brain barrier more.

BUT - Ethyl Hg in brain converts to inorganic Hg faster than methyl. 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 2-4 times more inorganic Hg found in brains of ethyl vs methyl group.group.

Over half the methyl-exposed brains had Over half the methyl-exposed brains had nono detectable inorganic Hg.detectable inorganic Hg.

Half-life in brain of organic Hg: 30 days; Half-life of inorganic: 20 Half-life in brain of organic Hg: 30 days; Half-life of inorganic: 20 yearsyears

““Changes in Changes in astrocytesastrocytes and and microgliamicroglia in primate brains after long-term in primate brains after long-term methylmercury exposure.”methylmercury exposure.”

Burbacher: Inorganic Hg, presumably from Burbacher: Inorganic Hg, presumably from methyl Hg, continued to increase throughout all methyl Hg, continued to increase throughout all exposure durations.exposure durations.

Both Both astrocyte and microglialastrocyte and microglial cells had cells had “substantially elevated” inorganic mercury “substantially elevated” inorganic mercury deposits. deposits.

““Inorganic Hg in the brain may be a toxic form Inorganic Hg in the brain may be a toxic form responsible for responsible for activation of astrocyte and activation of astrocyte and microglia.” microglia.”

Activation of Activation of astrocyte and microglialastrocyte and microglial cells was cells was not noted for six months or more, in some cases.not noted for six months or more, in some cases.

Neurotoxicology. 1996;17:127-138.

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 Inflammation found in autopsied autistic brains, produced bybrains, produced by ”activation of astroglia ”activation of astroglia and microglia.”and microglia.”

Inflammation apparently associated with Inflammation apparently associated with activation of the brain’s immune system.activation of the brain’s immune system.

Compared with controls, autistic tissue Compared with controls, autistic tissue showed ongoing inflammation in various showed ongoing inflammation in various sections of brain.sections of brain.

HARVARD:HARVARD:“Large Brains in Autism: The “Large Brains in Autism: The

Challenge of Pervasive Challenge of Pervasive Abnormality” Abnormality”

The NeuroscientistThe Neuroscientist, Volume 11, Number 5, 2000, Volume 11, Number 5, 2000

Neuro-inflammation, oxidative Neuro-inflammation, oxidative stress & stress & microgliamicroglia damage found in damage found in autistic brain tissue. autistic brain tissue.

“Chronic disease or external “Chronic disease or external environmental sources” (ie, heavy environmental sources” (ie, heavy metals) may be the cause. metals) may be the cause.

““Oxidative stress, brain Oxidative stress, brain inflammation, and inflammation, and microgliosismicrogliosis has has been much documented in been much documented in association with heavy metal association with heavy metal exposures.”exposures.”

““Blood Levels of Mercury Are Related toBlood Levels of Mercury Are Related to Diagnosis of Autism: Reanalysis of an Diagnosis of Autism: Reanalysis of an Important Data SetImportant Data Set

””Journal of Child NeurologyJournal of Child Neurology, Vol. 22, No. 11, 1308-1311 (2007), Vol. 22, No. 11, 1308-1311 (2007)

““We reanalyzed the data set reported by Ip We reanalyzed the data set reported by Ip et al. and found the original et al. and found the original pp value was in value was in error.”error.”

““A significant relation A significant relation does existdoes exist between between the blood levels of mercury and diagnosis the blood levels of mercury and diagnosis of an autism spectrum disorder.”of an autism spectrum disorder.”

““Hair samples offer some support for the Hair samples offer some support for the idea that persons with autism may be less idea that persons with autism may be less efficient and more variable at eliminating efficient and more variable at eliminating mercury from the blood.” mercury from the blood.”

Study looked at Texas county levels of Study looked at Texas county levels of emissions, compared to ASD rates and special emissions, compared to ASD rates and special ed in 1,200 school districts. ed in 1,200 school districts.

Autism increased as mercury emissions rose. Autism increased as mercury emissions rose. For every thousand pounds of Hg, there was a For every thousand pounds of Hg, there was a 61 percent increase in autism rates.61 percent increase in autism rates.

One county with low mercury emissions but One county with low mercury emissions but significant autism rates was found to harbor significant autism rates was found to harbor one of the nation’s largest mercury mines. one of the nation’s largest mercury mines.

““A potentially important connection between A potentially important connection between environmental exposure to mercury and the environmental exposure to mercury and the development of autism.”development of autism.”

UNIV of TEXAS - 2005: “HIGHER RISK OF AUTISM NEAR COAL-FIRED PLANTS” - Health & Place - 12 (2006) 203-20912 (2006) 203-209

ENVIRONMENTAL HEALTH PERSPECTIVESENVIRONMENTAL HEALTH PERSPECTIVES – – Vol. 114 No. 9, September, 2006Vol. 114 No. 9, September, 2006

Funded by CDC - 284 ASD children & 657 controls, Funded by CDC - 284 ASD children & 657 controls, born in 1994 in SF Bay Area. Assigned exposure born in 1994 in SF Bay Area. Assigned exposure level by birth tract for 19 chemicals.level by birth tract for 19 chemicals.

Risks for autism were elevated by 50% in tracts Risks for autism were elevated by 50% in tracts with the highest chlorinated solvents and heavy with the highest chlorinated solvents and heavy metals.metals.

Highest risk compounds were mercury, cadmium, Highest risk compounds were mercury, cadmium, nickel, trichloroethylene, and vinyl chloride. Risk nickel, trichloroethylene, and vinyl chloride. Risk from heavy metals was almost twice as high as from heavy metals was almost twice as high as solvents.solvents.

““Our results suggest a potential association Our results suggest a potential association between autism and estimated metal between autism and estimated metal concentrations, and possibly solvents, in ambient concentrations, and possibly solvents, in ambient air around the birth residence.” air around the birth residence.”

Univ. Of TexasUniv. Of Texas – “Study links autism risk to – “Study links autism risk to distance from mercury-releasing sources” distance from mercury-releasing sources”

Health and Place – April 2008Health and Place – April 2008

Hg data from 39 coal plants and 56 industrial Hg data from 39 coal plants and 56 industrial facilities in Texas. ASD rates culled from facilities in Texas. ASD rates culled from 1,040 Texas school districts.1,040 Texas school districts.

For every 1,000 pounds of Hg, there was a For every 1,000 pounds of Hg, there was a

3.7% increase in ASD. Prevalence fell 1-2% 3.7% increase in ASD. Prevalence fell 1-2% every 10 miles from source. every 10 miles from source.

““11stst time in scientific literature that time in scientific literature that statistically significant statistically significant association between association between ASD risk and distanceASD risk and distance from Hg source was from Hg source was identified.”identified.”

““Not a definitive study, but just one more that Not a definitive study, but just one more that furthers the association.” Raymond Palmer.furthers the association.” Raymond Palmer.

WHAT ABOUTWHAT ABOUT

CALIFORNIA?CALIFORNIA?

The flu shot The flu shot maymay matter matter A pregnant woman receives 25mcg, fetus is also A pregnant woman receives 25mcg, fetus is also

exposed. Much is absorbed by fetal brain stem in exposed. Much is absorbed by fetal brain stem in rats. Human maternal/cord blood ratio is 1:2).rats. Human maternal/cord blood ratio is 1:2).

1lb fetus exposed to 25mcg is 500 times over EPA 1lb fetus exposed to 25mcg is 500 times over EPA limit. limit.

At 6 months, a 7kg baby receives 12.5mcg – or 17 At 6 months, a 7kg baby receives 12.5mcg – or 17 times over limit. At 7 months, baby receives 12.5mcg.times over limit. At 7 months, baby receives 12.5mcg.

At 18 months, a 10kg infant receives 25mcg – or 25 At 18 months, a 10kg infant receives 25mcg – or 25 times overtimes over

Other shots contain 5+ mcg in residual Hg.Other shots contain 5+ mcg in residual Hg.

Total by 18 mos: Total by 18 mos: 80 mcg 80 mcg UK exposure until 2004: UK exposure until 2004: 75 75 mcg mcg

THE SHANGHAI PLUMETHE SHANGHAI PLUME(Moves up and down Pacific Coast)(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.

“ “Cremation costs rise as tooth Cremation costs rise as tooth fillings poison the living” fillings poison the living” 8th 8th

January 2007January 2007

Cremations cause nearly 1/6Cremations cause nearly 1/6thth of all of all UK mercury emissions. UK mercury emissions.

The The rise in mercury pollutionrise in mercury pollution from from crematoria is caused by what dentists crematoria is caused by what dentists call the "heavy metal generation" – call the "heavy metal generation" – those who who now die with more those who who now die with more teeth because of better dental care.teeth because of better dental care.

Millions of Britons have two to four Millions of Britons have two to four grams of mercury in their mouths. grams of mercury in their mouths. One gram can pollute a 25-acre lake. One gram can pollute a 25-acre lake.

California autism: increase California autism: increase in DDS cases by ethnic in DDS cases by ethnic

group: group: 2003-20072003-2007

30

40

50

60

70

80

90

"Other"

White

Black

AVERAGE

Asian

Filipino

Hispanic

Montreal School Boards: PDD Highest in English Speaking

(Immigrant) District

PDD rates in Lester B. PDD rates in Lester B. Pearson School Board Pearson School Board

(LBPSB) Montreal(LBPSB) Montreal

-June 6, 2007- -June 6, 2007- Canadian Broadcasting Canadian Broadcasting

NewsNews

““Autism rates Autism rates higherhigher in immigrant families”in immigrant families” “ “Health-care specialists in Montreal Health-care specialists in Montreal

are trying to understand why such a are trying to understand why such a high number of autistic children high number of autistic children come from immigrant families, a come from immigrant families, a phenomenon seen in major cities phenomenon seen in major cities across North America.”across North America.”

What About Al?What About Al?

Al – is a known neuro-Al – is a known neuro-toxintoxin Al – is Al – is synergisticsynergistic with Hg with Hg Al – is an immune Al – is an immune stimulantstimulant Al – is damaging to Al – is damaging to mitochondriamitochondria Al – is found in Al – is found in more shotsmore shots today, today,

maybe in higher concentrations, maybe in higher concentrations, (to offset Hg removal?)(to offset Hg removal?)

Al – is Al – is notnot your friend your friend

THE HANNAH THE HANNAH POLINGPOLING CASECASE

Poling Concession #1Poling Concession #1 November 9, 2007November 9, 2007

Hannah met all milestones in first 18 months. Hannah met all milestones in first 18 months.

At 9 monthsAt 9 months: Mimicking sounds, crawling, and : Mimicking sounds, crawling, and sitting.sitting.

At 12-monthAt 12-month pediatric visit: Saying “Mom” & pediatric visit: Saying “Mom” & “Dad,” pulling self up, cruising. “Dad,” pulling self up, cruising.

July 19, 2000 July 19, 2000 visitvisit - Hannah “spoke well” was - Hannah “spoke well” was “alert and active,” with regular bowel “alert and active,” with regular bowel movements and good sleeping habits.movements and good sleeping habits.

July 19, 2000July 19, 2000 visit – Hannah received 9 vaccines: visit – Hannah received 9 vaccines:

D-T-aP, M-M-R, Hib, Varivax, and PolioD-T-aP, M-M-R, Hib, Varivax, and Polio

Poling Concession #1Poling Concession #1 July 21, 2000July 21, 2000 – Two days later: 102.3 degree fever, – Two days later: 102.3 degree fever,

“lethargic, irritable, and cried for long periods, with “lethargic, irritable, and cried for long periods, with intermittent, high-pitched screaming and a intermittent, high-pitched screaming and a decreased decreased response to stimuliresponse to stimuli.”.”

July 22–31, 2000July 22–31, 2000 - Behavior continued over next ten - Behavior continued over next ten days. Hannah also began to arch back when crying.days. Hannah also began to arch back when crying.

July 31, 2000July 31, 2000 – Hannah hospitalized for 102 degree – Hannah hospitalized for 102 degree fever – Also had diminished appetite, small red dots on fever – Also had diminished appetite, small red dots on chest and was “extremely irritable and inconsolable.”chest and was “extremely irritable and inconsolable.”

September 26, 2000September 26, 2000 - Hannah returned to hospital - Hannah returned to hospital with 102 degree fever, diarrhea, nasal discharge, with 102 degree fever, diarrhea, nasal discharge, reduced appetite, and reduced appetite, and pulling at her left earpulling at her left ear..

November 13, 2000November 13, 2000 – Hannah presented with more – Hannah presented with more diarrhea, vomiting, diminished energy, fever, and rash diarrhea, vomiting, diminished energy, fever, and rash on her cheek. on her cheek.

Poling Concession #1Poling Concession #1 December 14, 2000December 14, 2000 - Doctor noted Hannah had - Doctor noted Hannah had

possible possible speech delayspeech delay, was , was less responsiveless responsive to to verbal direction since July, and verbal direction since July, and lost some lost some languagelanguage..

February 8, 2001February 8, 2001 – “Encephalopathy progressed – “Encephalopathy progressed to persistent loss of previously acquired to persistent loss of previously acquired language, language, eye contacteye contact, and , and relatednessrelatedness, , following vaccinations of July, 2000. Hannah following vaccinations of July, 2000. Hannah watched the fluorescent lights repeatedlywatched the fluorescent lights repeatedly during during the examination and would not make eye the examination and would not make eye contact.”contact.”

February 8, 2001February 8, 2001 - Hannah diagnosed with - Hannah diagnosed with “regressive encephalopathy with features “regressive encephalopathy with features consistent with an autistic spectrum disorder, consistent with an autistic spectrum disorder, following normal development.”following normal development.”

May 17, 2001May 17, 2001 – Lab results “strongly indicated – Lab results “strongly indicated an underlying mitochondrial disorder.”an underlying mitochondrial disorder.”

Poling Concession #1Poling Concession #1

October 4, 2001October 4, 2001 – Hannah found with – Hannah found with lactate-to-pyruvate ratio of 28:1, often seen lactate-to-pyruvate ratio of 28:1, often seen in disorders of mitochondrial oxidative in disorders of mitochondrial oxidative phosphorylation. (Reference ratio is 20:1) phosphorylation. (Reference ratio is 20:1) Confirmed with muscle biopsy.Confirmed with muscle biopsy.

February 2004February 2004 - Mitochondrial DNA analysis - Mitochondrial DNA analysis revealed single nucleotide change in the 16S revealed single nucleotide change in the 16S ribosomal RNA gene (T2387C).ribosomal RNA gene (T2387C).

April 14, 2006April 14, 2006 - Hannah brought by - Hannah brought by ambulance to Athens Regional Hospital and ambulance to Athens Regional Hospital and developed tonic seizure. Diagnosed with developed tonic seizure. Diagnosed with complex partial seizure disorder. This complex partial seizure disorder. This epilepsy was NOT related to vaccinations.epilepsy was NOT related to vaccinations.

Poling Concession #1 Poling Concession #1 ConclusionConclusion

Nov 9, 2007Nov 9, 2007

““Medical personnel at the Division of Vaccine Medical personnel at the Division of Vaccine Injury Compensation of HHS have conducted a Injury Compensation of HHS have conducted a thorough review and concluded that thorough review and concluded that compensation is appropriate.”compensation is appropriate.”

“ “The vaccinations Hannah received The vaccinations Hannah received significantly aggravated an underlying significantly aggravated an underlying mitochondrial disorder, which predisposed her mitochondrial disorder, which predisposed her to deficits in cellular energy metabolism, and to deficits in cellular energy metabolism, and manifested as a regressive encephalopathy manifested as a regressive encephalopathy with features of autism spectrum disorder.”with features of autism spectrum disorder.”

Poling Concession #2Poling Concession #2February 21, 2008February 21, 2008

Amended report from Dr. Zimmerman:Amended report from Dr. Zimmerman:

““The The causecause for regressive encephalopathy at for regressive encephalopathy at age 19 months was underlying age 19 months was underlying mitochondrial dysfunction, exacerbated by mitochondrial dysfunction, exacerbated by vaccine-induced fever and immune vaccine-induced fever and immune stimulation that exceeded metabolic stimulation that exceeded metabolic reserves.” reserves.”

Epilepsy was “part of the same pathogenesis Epilepsy was “part of the same pathogenesis that led to that led to autistic encephalopathyautistic encephalopathy.”.”

Hannah Poling Makes the Hannah Poling Makes the Big Leagues in US MediaBig Leagues in US Media

””Debate Rages Anew on Vaccine-Debate Rages Anew on Vaccine-

Autism Link”Autism Link”

““Vaccine Case: An Exception Or A Vaccine Case: An Exception Or A Precedent?”Precedent?”

““Deal in Autism Case Fuels Vaccine Deal in Autism Case Fuels Vaccine Debate”Debate”

CNN Worldwide Coverage: CNN Worldwide Coverage: “Vaccine “Vaccine case draws new case draws new

attention to autism debate”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

The Poling The Poling Story Story Went Went

Coast to CoastCoast to Coast

CDC Director Gerberding CDC Director Gerberding Reacts:Reacts:

“Cause” or “Precipitator?”“Cause” or “Precipitator?”““The government has made absolutely no The government has made absolutely no statement about indicating that vaccines are a statement about indicating that vaccines are a causecause of autism. That is a complete of autism. That is a complete mischaracterization of the findings of the mischaracterization of the findings of the case.” – case.” – Conference Call, March 5Conference Call, March 5

““The court (government) apparently made the The court (government) apparently made the decision that it is fair to say that vaccinations decision that it is fair to say that vaccinations may have been one of the may have been one of the precipitatorsprecipitators.”.”

– – Press Conference, Press Conference, March 6March 6

Dr. Gerberding on CNNDr. Gerberding on CNNMarch 29, 2008March 29, 2008

““If a child was immunized, got a fever, had If a child was immunized, got a fever, had other other complications from the vaccinescomplications from the vaccines, and , and (is) pre-disposed with the mitochondrial (is) pre-disposed with the mitochondrial disorder, it can certainly set off some disorder, it can certainly set off some damage.” damage.”

““Some of these symptoms can be symptoms Some of these symptoms can be symptoms that have characteristics of that have characteristics of autismautism." ."

““I think we have to have an I think we have to have an open mindopen mind about this.”about this.”

CDC Multiple Vaccine CDC Multiple Vaccine Q&AQ&ASource: Source: www.cdc.govwww.cdc.gov

Q: Is simultaneous vaccination with multiple vaccines Q: Is simultaneous vaccination with multiple vaccines safe? Wouldn't it be safer to separate combination safe? Wouldn't it be safer to separate combination vaccines?vaccines?

A: “The A: “The availableavailable scientific data show that simultaneous scientific data show that simultaneous vaccination with multiple vaccines has no adverse effect on vaccination with multiple vaccines has no adverse effect on the the normalnormal childhood immune system.” childhood immune system.”

Q: Can so many vaccines, given so early in life, Q: Can so many vaccines, given so early in life, overwhelm a child's immune system, suppressing it so overwhelm a child's immune system, suppressing it so it does not function correctly?it does not function correctly?

A: “No evidence suggests that the recommended childhood A: “No evidence suggests that the recommended childhood vaccines can ‘overload’ the immune system. Babies are vaccines can ‘overload’ the immune system. Babies are exposed to numerous bacteria and viruses on a daily basis.”exposed to numerous bacteria and viruses on a daily basis.”

Q: But are they injected with immune stimulants like Q: But are they injected with immune stimulants like aluminum, Hg etc?aluminum, Hg etc?

““Commentary: A view from Commentary: A view from the CDC”the CDC”

CNN - April 3, 2008CNN - April 3, 2008

““Some may call it a ‘one size fits all’ Some may call it a ‘one size fits all’ approach, but the recommended approach, but the recommended vaccine schedule is vaccine schedule is flexibleflexible… parents … parents shouldn't be reluctant to have such shouldn't be reluctant to have such discussions with the child’s doctor.”discussions with the child’s doctor.”

““We're currently conducting the We're currently conducting the largest study to investigate the largest study to investigate the potential causes of autism, looking potential causes of autism, looking at genetic, environmental and at genetic, environmental and hormonal factors, as well as selected hormonal factors, as well as selected mercury exposuresmercury exposures.” .”

MITOCHONDRIALMITOCHONDRIAL DYSFUNCTION AND DYSFUNCTION AND ASD REGRESSIONASD REGRESSION

““Mighty Mito” FactsMighty Mito” Facts

MITO - MITO - “disease”“disease” in classic form is very rare: 2- in classic form is very rare: 2-per-10K (0.02%) in general population. per-10K (0.02%) in general population.

MITO - MITO - “dysfunction”“dysfunction” in ASD is more prevalent. in ASD is more prevalent. Some studies show 10%-20 %, maybe more Some studies show 10%-20 %, maybe more among regressive cases: among regressive cases: 1000 times more 1000 times more common?common?

MITO - dysfunction can be very mild - many are MITO - dysfunction can be very mild - many are unaware. Severe forms usually inherited, can be unaware. Severe forms usually inherited, can be fatal in youth.fatal in youth.

MITO - disease 1MITO - disease 1stst noted in 1940s: Same decade noted in 1940s: Same decade as autism.as autism.

MITO - dysfunction can cause weak muscle tone, MITO - dysfunction can cause weak muscle tone, fatigue, poor digestion, other ASD signs. Mito fatigue, poor digestion, other ASD signs. Mito treatments used in ASDtreatments used in ASD..

Three Sources of Mito Three Sources of Mito DisordersDisorders

SourcesSources: Cleveland Clinic and UMDF: Cleveland Clinic and UMDF

1) Inherited from mother (in Mito DNA)1) Inherited from mother (in Mito DNA)

2) Inherited from both parents (in nuclear DNA)2) Inherited from both parents (in nuclear DNA)

3) “Sporadic” (acquired via medicines and 3) “Sporadic” (acquired via medicines and toxins).toxins).

““Sporadic” type estimated for 75% of all cases. Sporadic” type estimated for 75% of all cases.

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

““Developmental regression and Developmental regression and mitochondrial mitochondrial

dysfunction in a child with autism”dysfunction in a child with autism”Journal of Child Neurology.Journal of Child Neurology. 2006 Feb;21(2):170-2 2006 Feb;21(2):170-2

Poling, Frye, Shoffner, Zimmerman - Johns Hopkins Hospital, Poling, Frye, Shoffner, Zimmerman - Johns Hopkins Hospital, Baltimore, MDBaltimore, MD

Described “oxidative phosphorylation disorder” in 19-Described “oxidative phosphorylation disorder” in 19-month-old. Subtle abnormalities in some enzymes and month-old. Subtle abnormalities in some enzymes and amino acids.amino acids.

Authors looked at records of 159 patients with autism Authors looked at records of 159 patients with autism (DSM-IV) and 94 controls with other neurologic (DSM-IV) and 94 controls with other neurologic disorders.disorders.

Aspartate aminotransferase was elevated in 38% of Aspartate aminotransferase was elevated in 38% of

patients with autism compared with 15% of controls.patients with autism compared with 15% of controls. Serum creatine kinase level also was abnormally Serum creatine kinase level also was abnormally

elevated in 22 of 47 patients (47%) with autism. elevated in 22 of 47 patients (47%) with autism.

““Metabolic evaluation is indicated in autistic patients Metabolic evaluation is indicated in autistic patients and defects of oxidative phosphorylation might be and defects of oxidative phosphorylation might be prevalent."prevalent."

““Evidence of Mitochondrial Evidence of Mitochondrial Dysfunction in Autism”Dysfunction in Autism”

American Journal of Biochemistry and BiotechnologyAmerican Journal of Biochemistry and Biotechnology 4 (2): 4 (2): 208-217, 2008208-217, 2008

““Many cases of autism show evidence of Many cases of autism show evidence of mitochondrial dysfunction (MtD) mitochondrial dysfunction (MtD) withoutwithout classic features associated with mitochondrial classic features associated with mitochondrial disease.”disease.”

““MtD appears to be more common in autism MtD appears to be more common in autism

and presents with less severe signs and and presents with less severe signs and symptoms.”symptoms.”

““Exposure to environmental toxins is the likely Exposure to environmental toxins is the likely etiology for mitochondrial dysfunction in etiology for mitochondrial dysfunction in autism.” autism.”

““This dysfunction then contributes to a number This dysfunction then contributes to a number of diagnostic symptoms observed in autism.”of diagnostic symptoms observed in autism.”

Estimates of Mito Dysfunction Estimates of Mito Dysfunction inin ASDASD

11) ) Oliveiro et al:Oliveiro et al: Markers for Mito dysfunction found Markers for Mito dysfunction found in 20% of ASD patients, and muscle biopsy confirmed in 20% of ASD patients, and muscle biopsy confirmed in in 7.2%.7.2%.

2) 2) Kelley, Zimmerman, Natowicz:Kelley, Zimmerman, Natowicz: Mitochondrial Mitochondrial dysfunction may account for dysfunction may account for 20%20% of ASD, especially of ASD, especially PDD-NOS with language and cognitive regression in PDD-NOS with language and cognitive regression in 22ndnd year. Markers on paternal lines; early testing, “may year. Markers on paternal lines; early testing, “may rescue some from more severe brain injury and rescue some from more severe brain injury and lifelong disability.” lifelong disability.”

3) 3) David HoltzmanDavid Holtzman, Massachusetts General Hospital, , Massachusetts General Hospital, AS Grant: “Oxidative Phosphorylation in Cells from AS Grant: “Oxidative Phosphorylation in Cells from Autistic Individuals.” Mito dysfunction might be found Autistic Individuals.” Mito dysfunction might be found in up to in up to 30%30% of ASD cases. of ASD cases.

4) 4) Petitioners Steering CommitteePetitioners Steering Committee – VICP – Up to – VICP – Up to 50%50% of 5,000 cases filed in Vaccine Court show markers for of 5,000 cases filed in Vaccine Court show markers for mild dysfunction.mild dysfunction.

Some Markers for Mito Some Markers for Mito DysfunctionDysfunction

And Reported Rates in ASD And Reported Rates in ASD KidsKids 47% (elevated serum creatine kinase, Poling et 47% (elevated serum creatine kinase, Poling et

al) al) 38% (elevated aspartate aminotransferase, 38% (elevated aspartate aminotransferase,

Poling)Poling) 28% (elevated plasma lactate/pyruvate ratio, 28% (elevated plasma lactate/pyruvate ratio,

(Correia et al)(Correia et al) 20% (elevated plasma lactate, Oliveiro et al)20% (elevated plasma lactate, Oliveiro et al) 17% (elevate plasma lactate, Correia et al)17% (elevate plasma lactate, Correia et al) 13-16% (two hyperlactidemia markers, Oliveiro 13-16% (two hyperlactidemia markers, Oliveiro

et al)et al) 65% - Shoffner (certain biomarkers)65% - Shoffner (certain biomarkers)

Thimerosal Targets Thimerosal Targets MitochondriaMitochondria

SomeSome Results of Recent PubMed Results of Recent PubMed SearchSearch““ThimerosalThimerosal induces neuronal cell apoptosis by causing cytochrome c induces neuronal cell apoptosis by causing cytochrome c

and apoptosis-inducing factor release from and apoptosis-inducing factor release from mitochondriamitochondria.” .” - - Int J Mol Med. 2005 Dec;16(6):971-7.Int J Mol Med. 2005 Dec;16(6):971-7.

““MitochondrialMitochondrial mediated mediated thimerosalthimerosal-induced apoptosis in a human -induced apoptosis in a human neuroblastoma cell line”neuroblastoma cell line” - - Neurotoxicology. 2005 Jun;26(3):407-16. Neurotoxicology. 2005 Jun;26(3):407-16.

““Biochemical and molecular basis of Biochemical and molecular basis of thimerosalthimerosal-induced apoptosis in -induced apoptosis in T cells: a major role of T cells: a major role of mitochondrialmitochondrial pathway” pathway” - - Genes Immun. 2002 Aug;3(5):270-8.Genes Immun. 2002 Aug;3(5):270-8.

““Inhibition of malate transport and activation of phosphate Inhibition of malate transport and activation of phosphate transport in transport in mitochondria mitochondria by by thimerosalthimerosal” ” - - FEBS Lett. 1980 Aug 11;117(1):149-51.FEBS Lett. 1980 Aug 11;117(1):149-51.

““ThimerosalThimerosal: a new reagent for study of phosphate transport in : a new reagent for study of phosphate transport in mitochondriamitochondria””- - FEBS Lett. 1980 Jun 2;114(2):295-8.FEBS Lett. 1980 Jun 2;114(2):295-8.

““MercurialMercurial-induced hydrogen peroxide generation in mouse brain -induced hydrogen peroxide generation in mouse brain mitochondriamitochondria” ” - - Chem Res Toxicol. 2007 Dec;20(12):1919-26. Chem Res Toxicol. 2007 Dec;20(12):1919-26.

““Heavy-Metal Toxicity: Emphasis on Heavy-Metal Toxicity: Emphasis on Mercury”Mercury”

Integrative Medicine Integrative Medicine • Vol. 6, No. 2 • Apr/May • Vol. 6, No. 2 • Apr/May 20072007

Neustadt MD & Pieczenik MDNeustadt MD & Pieczenik MD

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

Formaldehyde Causes Mito Damage, Formaldehyde Causes Mito Damage, Oxidative Stress and Glutathione Oxidative Stress and Glutathione

Depletion Depletion Chem Biol InteractChem Biol Interact. 2001 Jan 30;130-132(1-3):285-96. . 2001 Jan 30;130-132(1-3):285-96.

Low dose formaldehyde caused “marked Low dose formaldehyde caused “marked decrease in decrease in mitochondrialmitochondrial potential and inhibition of mitochondrial potential and inhibition of mitochondrial respiration,” as well as respiration,” as well as oxidative stressoxidative stress in cells. in cells.

GlutathioneGlutathione was also depleted in a dose-dependent was also depleted in a dose-dependent manner. manner.

““Antioxidants & iron Antioxidants & iron chelatorschelators protected against cell protected against cell toxicity.” toxicity.”

““Toxicity was prevented with cyclosporine orToxicity was prevented with cyclosporine or carnitine carnitine to to prevent opening ofprevent opening of mitochondrial mitochondrial permeability pore. permeability pore.

““This suggests formaldehyde targets This suggests formaldehyde targets mitochondriamitochondria.” .”

(NOTE: CDC repressed evidence of formaldehyde off-(NOTE: CDC repressed evidence of formaldehyde off-gassing in gassing in Hurricane KatrinaHurricane Katrina refugee trailers!) refugee trailers!)

“Bridging from Cells to Cognition in Autism: Pathways to Defective Brain

Function and Plasticity”Dr. Martha Herbert, Harvard – Am. Journ. Biochem. & Biotech

4 (2): 167-176, 2008

Autism may begin when 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.

“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.

A FEW MORE RECENT A FEW MORE RECENT STUDIES: STUDIES: 2007-20082007-2008

““Maternal Residence Near Agricultural Maternal Residence Near Agricultural Pesticide Applications & ASD in Pesticide Applications & ASD in

California’s Central Valley”California’s Central Valley”Environmental Health PerspectivesEnvironmental Health Perspectives

Volume 115, Number 10, October 2007 Volume 115, Number 10, October 2007 Calif. women living near farms with organo-Calif. women living near farms with organo-

chlorine pesticides may be more at risk for chlorine pesticides may be more at risk for children with autism.children with autism.

Autism rates near fields was extremely high - Autism rates near fields was extremely high - 28% of mothers had children with autism, six 28% of mothers had children with autism, six times higher than those who did not live nearby.times higher than those who did not live nearby.

7% of ASD in Central Valley might have been 7% of ASD in Central Valley might have been connected to insecticides from fields. connected to insecticides from fields.

Italian scientists in 2005: Pesticides “could Italian scientists in 2005: Pesticides “could cause neurological changes that lead to cause neurological changes that lead to autism.”autism.”

ASD & PET SHAMPOO PESTICIDE?ASD & PET SHAMPOO PESTICIDE?IMFAR Meeting – IMFAR Meeting – London – May, 2008London – May, 2008

■ ■ Chemicals included insecticides, pet Chemicals included insecticides, pet shampoos, and weed killers, 3 months before shampoos, and weed killers, 3 months before conception until first birthday.conception until first birthday. ■ ■ Mothers of ASD kids were twice as likely Mothers of ASD kids were twice as likely to report using pet shampoos with pyrethrins to report using pet shampoos with pyrethrins vs. controls. Used for flea control, pyrethrins vs. controls. Used for flea control, pyrethrins affect pests' central nervous system. affect pests' central nervous system. ■ ■ Strongest association was in Strongest association was in secondsecond trimester, when ASD mothers were 2.6 times trimester, when ASD mothers were 2.6 times more likely to have been exposed to the more likely to have been exposed to the chemical. chemical.

■ ■ In lab, pyrethrins have also been found to In lab, pyrethrins have also been found to affect a part of the brain that protects it from affect a part of the brain that protects it from chemicals within the blood. chemicals within the blood.

VACCINE INJURY IN PRIMATES VACCINE INJURY IN PRIMATES IMFAR Meeting – London – May, 2008IMFAR Meeting – London – May, 2008

Macaques given routine US vaccine schedule. Dosage Macaques given routine US vaccine schedule. Dosage reduced to match body weight. Followed for 5 years/reduced to match body weight. Followed for 5 years/

13 vaccinated animals showed increased aggression, 13 vaccinated animals showed increased aggression, impaired cognitive skills, developmental delay and impaired cognitive skills, developmental delay and autistic like behavior. Also poor reflexes, insular and autistic like behavior. Also poor reflexes, insular and aggressive behavior, and less interest in surroundings.aggressive behavior, and less interest in surroundings.

Three unvaccinated animals developed normally.Three unvaccinated animals developed normally. MRI’s showed vaxed animals had abnormal brain MRI’s showed vaxed animals had abnormal brain

activity, including opioid receptors, inked to activity, including opioid receptors, inked to sleeplessness, hallucinations, poor social skills.sleeplessness, hallucinations, poor social skills.

Damage also to amygdala, which regulates emotions.Damage also to amygdala, which regulates emotions.

Oxidative Stress and Mercury Deposits in Autistic Brains

Am. Journal of Biochemistry and BiotechAm. Journal of Biochemistry and Biotech 4(2) 4(2) 73-84, 200873-84, 2008

Harvard researchers showed a potential link Harvard researchers showed a potential link between mercury and autopsied brains of young between mercury and autopsied brains of young people w/ASD.people w/ASD.

Marker for oxidative stress was 68.9% higher in Marker for oxidative stress was 68.9% higher in

autistic brain issue than controls.autistic brain issue than controls.

Mercury levels were 68.2% higher (not significant, Mercury levels were 68.2% higher (not significant, probably due to small sample size).probably due to small sample size).

Elevated Hg levels were significantly associated with Elevated Hg levels were significantly associated with OS.OS.

““Data suggest a need for more extensive studies of Data suggest a need for more extensive studies of oxidative stress, its relationship to the oxidative stress, its relationship to the environmental factors and its possible attenuation environmental factors and its possible attenuation by antioxidants in autism.”by antioxidants in autism.”

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 Thimerosal was associated with low body weight, low encephalon weight and smaller stature in hamsters. encephalon weight and smaller stature in hamsters.

Neurotoxic effects also produced in hippocampus, Neurotoxic effects also produced in hippocampus, cerebral cortex and cerebellum.cerebral cortex and cerebellum.

Decrease in neuronal density found in exposed group.Decrease in neuronal density found in exposed group. Neuronal necrosis, demyelination and gliosis also Neuronal necrosis, demyelination and gliosis also

found. found. Risk in thimerosal group was high and statistically Risk in thimerosal group was high and statistically

significant. significant.

““Being Born Small, Early Raises Autism RiskBeing Born Small, Early Raises Autism RiskCDC study found link was most pronounced for CDC study found link was most pronounced for

low-birth-weight” low-birth-weight” US NEWS & WORLD REPORTUS NEWS & WORLD REPORT - - June 2, 2008June 2, 2008

Low birth weight had twofold increase in autism risk, higher Low birth weight had twofold increase in autism risk, higher among girls. among girls.

““Could be a marker for an impaired fetus with a neurological Could be a marker for an impaired fetus with a neurological problem which is retarding its growth. OR, being small may problem which is retarding its growth. OR, being small may be related to harm to the neurological development of the be related to harm to the neurological development of the fetus, such as infection during pregnancy.“fetus, such as infection during pregnancy.“

““These findings support the idea that there are different kinds These findings support the idea that there are different kinds of autism and different mechanisms underlying those cases.”of autism and different mechanisms underlying those cases.”

Mercury exposure at birth (12.5mcg): Mercury exposure at birth (12.5mcg): @8.8lbs = [email protected] = 31xEPA

@4.4lbs = [email protected] = 62xEPA

Mercury exposure at 2 mos (62.5mcg): Mercury exposure at 2 mos (62.5mcg): @13.2lbs = @13.2lbs =

@6.6lbs = [email protected] = 208xEPA

RECENT RECENT DEVELOPMENTS IN U.S. DEVELOPMENTS IN U.S. POLICY AND POLICY AND POLITICSPOLITICS

(Almost Done – No Yawning!)(Almost Done – No Yawning!)

June ‘07 -1June ‘07 -1stst Autism Case in Autism Case in Vaccine Court:Vaccine Court: Is MMR a Is MMR a

Cause?Cause? Case of Michelle Cedillo of Arizona.Case of Michelle Cedillo of Arizona. Had severe brain damage after MMR.Had severe brain damage after MMR. Gov’t said she had autism before shot.Gov’t said she had autism before shot. Gov’t argued that O’Leary lab was Gov’t argued that O’Leary lab was

unreliable – had UK documents.unreliable – had UK documents. New data may refute that.New data may refute that. CW: Michelle will be compensated for CW: Michelle will be compensated for

injury, but maybe not ASD.injury, but maybe not ASD.

The The NEXTNEXT Hannah Poling Hannah Poling

Case chosen to replace Hannah as 1Case chosen to replace Hannah as 1stst thimerosal test case had SAME mito thimerosal test case had SAME mito markers, and was also pulled as test markers, and was also pulled as test case.case.

This case will be re-filed outside of This case will be re-filed outside of Autism Omnibus Proceedings with Autism Omnibus Proceedings with new theory of causation: Autism can new theory of causation: Autism can be caused by aggravated be caused by aggravated mitochondrial dysfunction.mitochondrial dysfunction.

2008 - CDC Studies on 2008 - CDC Studies on MMRMMR

www.cdc.gov/ncbddd/autism/documents/vaccine_stwww.cdc.gov/ncbddd/autism/documents/vaccine_studies.pdfudies.pdf

““The Autism and Biopsy Study” The Autism and Biopsy Study” Can MMR cause autism through persistent Can MMR cause autism through persistent measles infection in the intestine? Examination measles infection in the intestine? Examination of intestinal tissue of children with autism for the of intestinal tissue of children with autism for the presence of measles virus. presence of measles virus.

““Immunizations & Possible Immunizations & Possible Developmental Regression” Developmental Regression” CDC & NIH study of whether the MMR vaccine CDC & NIH study of whether the MMR vaccine is linked with developmental regression, which is linked with developmental regression, which occurs in a subset of children with autism. occurs in a subset of children with autism.

March 11 -March 11 - CDC Conference CDC Conference Call on Mito Dysfunction, Call on Mito Dysfunction,

Vaccines and AutismVaccines and Autism CISA - CDC, vaccine experts and insurance CISA - CDC, vaccine experts and insurance

companies – discussed 5-year study of 30 ASD kids companies – discussed 5-year study of 30 ASD kids w/low cellular energy.w/low cellular energy.

All 30 had the All 30 had the samesame abnormalities as Hannah abnormalities as Hannah Poling, (who was one of them). All regressed after Poling, (who was one of them). All regressed after normal development.normal development.

Big surprise: “Inheritance pattern" found – When 2 Big surprise: “Inheritance pattern" found – When 2 two cousins had autism, genetic link was always two cousins had autism, genetic link was always through father – clear nuclear DNA inheritance.through father – clear nuclear DNA inheritance.

DNA mutation may range from 1-in-400 to DNA mutation may range from 1-in-400 to 1-in-501-in-50, , or 2%.or 2%.

DNA mapping underaway – paternal grandparents DNA mapping underaway – paternal grandparents tested.tested.

CDC-CISA Conference Call – CDC-CISA Conference Call – Cont’dCont’d

BUT – is DNA mutation enough to confer MtD? BUT – is DNA mutation enough to confer MtD? Or is an environmental trigger needed? And what Or is an environmental trigger needed? And what triggers "metabolic decomposition" anyway?triggers "metabolic decomposition" anyway?

In only 2 of the 30 cases, (6%) regression linked In only 2 of the 30 cases, (6%) regression linked to shots (Hannha was one).to shots (Hannha was one).

In other 28 cases, traced to fever-inducing In other 28 cases, traced to fever-inducing infection.infection.

But if fever causes 94% of mito reggression, But if fever causes 94% of mito reggression,

shouldn’t there be less today - and less in shouldn’t there be less today - and less in wealthier countries? wealthier countries?

(Hannah spoke at 9 months, but had several (Hannah spoke at 9 months, but had several fevers after that without regression. Now, fevers fevers after that without regression. Now, fevers improve symptoms - reported in Pediatrics).improve symptoms - reported in Pediatrics).

““Three-Step, Two-Trigger” Path – Three-Step, Two-Trigger” Path – Jon PolingJon Poling

((NotNot a Square Dance from Texas) a Square Dance from Texas) STEP ONESTEP ONE: Child is born with DNA mutation for : Child is born with DNA mutation for

mito susceptibility.mito susceptibility.

TRIGGER ONE:TRIGGER ONE: Child encounters pre- or neo-natal Child encounters pre- or neo-natal environmental trigger.environmental trigger.

STEP TWO:STEP TWO: Child develops mild, asymptomatic Child develops mild, asymptomatic mito dysfunction.mito dysfunction.

TRIGGER TWOTRIGGER TWO: Fever and/or immune : Fever and/or immune overstimulation from infection of vaccines overstimulation from infection of vaccines “exceeds metabolic reserves.”“exceeds metabolic reserves.”

STEP THREE:STEP THREE: Encephalopathy, illness, regression, Encephalopathy, illness, regression, autismautism

Questions Raised On and Questions Raised On and From From

CDC – CISA Confernce CallCDC – CISA Confernce Call Do we vaccinate children with known MtD sooner? Do we vaccinate children with known MtD sooner?

More slowly?More slowly? Do we develop an efficient test for MtD Do we develop an efficient test for MtD beforebefore

vaccination begins?vaccination begins?

Do we alter schedule somehow, to lower risk of Do we alter schedule somehow, to lower risk of immune over-stimulation in susceptible children?immune over-stimulation in susceptible children?

Do we set a maximum number of vaccine exposures on Do we set a maximum number of vaccine exposures on any one day?any one day?

Do we allow MMR to be separated out, on request of Do we allow MMR to be separated out, on request of parents?parents?

Do we separate MMR from Varicella on same day? Do we separate MMR from Varicella on same day? CDC stoped recommending Pro-Quad (MMR+V) CDC stoped recommending Pro-Quad (MMR+V) because it because it doubleddoubled seizure risk. seizure risk.

Do we set new limits on kids playing “catch up?”Do we set new limits on kids playing “catch up?”

April 11, 2008April 11, 2008 – Meeting to – Meeting to Discuss Top Vaccine Safety Discuss Top Vaccine Safety

Issues in DCIssues in DCHHS convened first meeting of the national HHS convened first meeting of the national Vaccine Safety Vaccine Safety Working GroupWorking Group to review CDC's recommended safety to review CDC's recommended safety research agenda. research agenda. SOME Specific Questions:SOME Specific Questions:

Is thimerosal associated with risk for tics Is thimerosal associated with risk for tics and/or Tourettes?and/or Tourettes?

Is acellular pertussis vaccine associated with Is acellular pertussis vaccine associated with risk for acute neurological events?risk for acute neurological events?

Is combo MMRV vaccine associated with Is combo MMRV vaccine associated with increased febrile seizure risk?increased febrile seizure risk?

Are varicella and MMRV vaccines associated Are varicella and MMRV vaccines associated with increased risk for clinically important with increased risk for clinically important events related to virus reactivation?events related to virus reactivation?

CDC Also Proposes CDC Also Proposes Mito Mito Research:Research:

Q: “Is immunization associated Q: “Is immunization associated with increased risk for neurological with increased risk for neurological deterioration in children with deterioration in children with mitochondrial dysfunction?”mitochondrial dysfunction?”

““CISA has formed a working group CISA has formed a working group to study methods related to to study methods related to mitochondrial disorders and mitochondrial disorders and immunization, in collaboration with immunization, in collaboration with partners.”partners.”

CDC:CDC: Clinical Outcomes To Clinical Outcomes To StudyStudy

Autoimmune diseases Autoimmune diseases

Nervous system demyelinating Nervous system demyelinating disordersdisorders

Encephalitis/ encephalopathyEncephalitis/ encephalopathy

Neurodevelopmental disorders, Neurodevelopmental disorders, including autism spectrum disorder including autism spectrum disorder (ASD)(ASD)

Clinically important outcomes Clinically important outcomes associated with post-immunization associated with post-immunization fever.fever.

Federal RegisterFederal Register: 5-23-08 (Vol. 73 No. : 5-23-08 (Vol. 73 No. 101)101)

DEPT OF HEALTH & HUMAN DEPT OF HEALTH & HUMAN SERVICES/CDCSERVICES/CDC

June 12, 2008 - 12-2PMJune 12, 2008 - 12-2PMTeleconference Meeting on HHS Teleconference Meeting on HHS

Grants for Vaccine Injury Grants for Vaccine Injury Prevention StudiesPrevention Studies

CLOSEDCLOSED TO THE PUBLIC TO THE PUBLIC

Topic: “Associations of Vaccine Topic: “Associations of Vaccine Adverse Events and Human Genetic Adverse Events and Human Genetic

Variations” Request for ProposalVariations” Request for Proposal

Bill Clinton on Autism:Bill Clinton on Autism:Campaign Trail, Oregon Campaign Trail, Oregon

May, 2008May, 2008

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

Hillary Clinton on Autism:Hillary Clinton on Autism:Campaign QuestionnaireCampaign Questionnaire

Feb. 2008Feb. 2008

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

Barack Obama on Autism:Barack Obama on Autism:Campaign Trail, Campaign Trail, Pennsylvania Pennsylvania

April, 2008April, 2008

““We've seen just a skyrocketing We've seen just a skyrocketing autism rate. Some people are autism rate. Some people are suspicious that it's connected to suspicious that it's connected to the vaccines. The science right now the vaccines. The science right now is inconclusive, but we have to is inconclusive, but we have to research it.” research it.”

John McCain on Autism:John McCain on Autism:Campaign Trail, Texas Campaign Trail, Texas

March, 2008March, 2008

““It's indisputable that autism is It's indisputable that autism is on the rise amongst children, the on the rise amongst children, the question is what's causing it. And question is what's causing it. And we go back and forth, and there's we go back and forth, and there's strong evidence that indicates strong evidence that indicates that it's got to do with a that it's got to do with a preservative in vaccines.”preservative in vaccines.”

Dr. Bernadine Healy on Dr. Bernadine Healy on CBS NewsCBS NewsMay, 2008May, 2008

““Officials have been too quick to Officials have been too quick to dismiss the hypothesis as 'irrational,' dismiss the hypothesis as 'irrational,' without sufficient studies of without sufficient studies of causation, causation, without studying the without studying the population that got sick.”population that got sick.”

““Never turn your back on any Never turn your back on any scientific hypothesis because you are scientific hypothesis because you are afraid of what it might show." afraid of what it might show."

Dr. Healy on CBS NewsDr. Healy on CBS News

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

Healy on CBS NewsHealy on CBS News

The IOM concluded there is no link The IOM concluded there is no link based mostly on population studies. based mostly on population studies. But, “Populations do not test But, “Populations do not test causality they test associations.”causality they test associations.”

““I am a member of the IOM. I love the I am a member of the IOM. I love the IOM. But a report from 2004 basically IOM. But a report from 2004 basically said, 'Don’t pursue susceptibility said, 'Don’t pursue susceptibility groups. Don't look for those children groups. Don't look for those children who may be vulnerable.' I really take who may be vulnerable.' I really take issue with that conclusion."issue with that conclusion."

Dr. Healy on Don Imus Dr. Healy on Don Imus Radio ShowRadio ShowMay, 2008May, 2008

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

THE END: Remember the THE END: Remember the kidskids!!

Evidence of Harm – Evidence of Harm – IntroductionIntroduction

First Words in Book:First Words in Book:

““Does mercury in vaccines cause autism Does mercury in vaccines cause autism in children? A definitive answer has in children? A definitive answer has proven elusive, and it remains so to this proven elusive, and it remains so to this day.”day.”

““No one can say with certainty that No one can say with certainty that thimerosal helped fuel the explosion in thimerosal helped fuel the explosion in cases of autism, attention deficit cases of autism, attention deficit disorder, speech delay and other disorder, speech delay and other disorders over the past decade.” disorders over the past decade.”

EOH – IntroductionEOH – Introduction““Several potential culprits beside thimerosal have Several potential culprits beside thimerosal have been mentioned, though there is no hard evidence been mentioned, though there is no hard evidence to link any of them to autism. Possible to link any of them to autism. Possible environmental “triggers” include: mercury in fish, environmental “triggers” include: mercury in fish, pesticides, PCB’s, flame retardants, jet fuel, live pesticides, PCB’s, flame retardants, jet fuel, live viruses in vaccines or some as-yet unidentified viruses in vaccines or some as-yet unidentified virus, and even rampant cell phone use. It is virus, and even rampant cell phone use. It is plausible that any combination of the above, with plausible that any combination of the above, with or without thimerosal exposure added into the or without thimerosal exposure added into the mix, might cause harm to some fetuses and infant mix, might cause harm to some fetuses and infant children.”children.”

““At the very least, the thimerosal debate has At the very least, the thimerosal debate has compelled the scientific community, however compelled the scientific community, however reluctantly, to consider an environmental reluctantly, to consider an environmental component to the disorder, rather than looking component to the disorder, rather than looking for a purely genetic explanation.”for a purely genetic explanation.”

EOH IntroductionEOH Introduction

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