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System Wide Dysfunction in

Autism Spectrum Disorders

Implications for Planetary Life


and Health
Barry Grushkin
Managing Director
Machine Intelligence Group
Norman W. Schwartz MD,
Medical Director The Center for Integrative Medicine
Milwaukee, Wisconsin 1
Fellow, Health Studies Collegium
Overview
 Environmental Background
 Environment and Autism
 Environment and Chronic Illness
 Organic Acids as a Window to System Wide
Dysfunction in Autism- Universality of
Metabolism
 Oxidative Stress-Cellular Dysfunction
 What We Can Do-Precautionary Principle

2
“Environmental pollution is one of the
most serious problems facing
humanity today.”
Alan McGowan, president of the Scientists’ Institute for Public
Information

3
Body Burden — The Pollution in Newborns
A benchmark investigation of industrial chemicals,
pollutants and pesticides in umbilical cord blood
Environmental Working Group, July 14, 2005
10 newborns, $10,000/baby for study

Chemicals and pollutants detected in Of the 287 chemicals


human umbilical cord blood detected in umbilical
Mercury (Hg) - tested for 1, found 1
Polyaromatic hydrocarbons (PAHs) - tested for 18, cord blood:
found 9
Polybrominated dibenzodioxins and furans • 180 cause cancer in
(PBDD/F) - tested for 12, found 7
Perfluorinated chemicals (PFCs) - tested for 12,
humans or animals
found 9
Polychlorinated dibenzodioxins and furans • 217 are toxic to the
(PBCD/F) - tested for 17, found 11
Organochlorine pesticides (OCs) - tested for 28,
brain and nervous
found 21 system
Polybrominated diphenyl ethers (PBDEs) -
tested for 46, found 32
Polychlorinated Naphthalenes (PCNs) - tested for
• 208 cause birth
70, found 50 defects or abnormal
Polychlorinated biphenyls (PCBs) - tested for
209, found 147
development in
animal tests

http://www.ewg.org/reports/bodyburden2 4
Status of Developmental Toxicity Testing
for the 2,863 Chemicals
Produced Above 1 million pounds/year
Some Data
0.4%
On Developmental 12 Tested for
Toxicity Neurodevelopmental
21.4%
Toxicity
According to EPA
No Data Guidelines
On Developmental
78.2%
Toxicity
•85,000 chemicals in
the Federal inventory
•2,000-3,000 new
chemicals introduced
each year
In Harm’s Way, www.preventingharm.org •3-5 billion tons/yr
Childhood Cancers: Ages 0-14
1971–2001
70%
All leukemia
60%
Up 32%
Acute lymphocytic 50%

leukemia
40%
Up 53%
Soft tissue cancers 30%

Up 32%
20%
Brain tumors
10%
Up 63%
Bone cancers 0%

Up 32% All leukemia Acute Soft tissue Brain tumors Bone cancers Kidney
lymphocytic cancers cancer
Kidney cancer leukemia
Up 26%

Source: National Cancer Institute,


SEER Statistics site
6
http://seer.cancer.gov/faststats/
An Old Nemesis
Photograph by Peter Essick

Lead paint chips speckle the gut of a two-year-old Cleveland girl.


Phased out decades ago, lead paint is still injuring children who
swallow it.

By David Ewing Duncan Photographs by Peter Essick

7
“Earth at the Tipping Point”

8
UN Report:
Ecosystem damage is so severe that we can no longer
be confident that the Planet Earth can support
human life for more than two generations.
Four main findings on the links between ecosystems and human
well-being: More...
10.1Over the past 50 years, humans have changed ecosystems
faster and more extensively than in any period in human
history. This has been due largely to rapidly growing
demands for food, freshwater, timber, fiber, and fuel. The
result has been a substantial and largely irreversible loss in
the diversity of life on Earth. More...
10.2 The changes made to ecosystems have contributed to
substantial gains in human well-being and economic
development, but these gains have been achieved at
growing costs. These costs include the degradation of
many ecosystem services, increased risks of abrupt
changes, and increased poverty for some groups of people.
These problems, unless addressed, will substantially
reduce the benefits that future generations get from
ecosystems. More...
10.3 This degradation of ecosystem services could get
significantly worse during the next 50 years. It is a barrier
to the achievement of the Millennium Development Goals.
More...
10.4 Reversing the degradation of ecosystems while meeting
increasing demands for their services is a challenge. This
challenge can be partially met in the future under scenarios
involving significant changes to policies, institutions, and
practices. However, these required actions will have to be
substantial when compared to the actions currently taken.

http://www.millenniumassessment.org

9
autism-society.org

10
11
Environment
and Autism
The autism epidemic is alerting us to the
importance of individual susceptibility to
environmental pollutants. Environmental
safeguards that protect a theoretical average
person still leave thousands at risk. Increased
understanding of susceptibility will provide the
basis of stronger health policy that truly protect
the most vulnerable.
Richard Wiles EWG

12
13
Autism and the Environment Workshop

http://www.iom.edu/CMS/3740/35684/39826/42257.aspx

14
Mercury

15
Adverse Effects of Toxic Metals on
Cell Function
 Metabolic Uncoupler
 Hapten Immunotoxins
 Enzyme Inhibitors
 Pro-oxidants
 Bioconcentrate
 Increased adverse effects with mineral
deficiencies

16
Health Place. 2006 Jun;12(2):203-9.

Findings: For every 1000 pounds of mercury


that is emitted from Texas smokestacks there
is a 61% increase in Autism rates in that state.
17
Texas autism rates,
by school districts

1990-1993 1998-2000 18
Potential association
between autism rates,
Autism rates environmental mercury other
toxins in Texas
Palmer, et al., Health and Place 2006 Jun;12(2):203-9
On average, for each 1000 lb of
environmentally released mercury,
there was a 43% increase in the rate of
special education services and a 61%
increase in the rate of autism.

All Reporting Facilities, All Chemicals TRI-(1987-2002)


Map shows 3,683 of 48,205 facilities reporting nationwide

Chemicals-TRI Total toxicity

19
POPs-Persistant organic pollutants
 Ex: Phthalates, Pesticides, Herbicides, Bisphenol A, PCB, PCBD, DDT
Used in flexible plastics, cosmetics, perfumes, food
Found in breast milk, cord blood, infants, children and adults
 Endocrine Disruptors- mimic natural hormones, alter cells signals, feeback control
 Extremely long half life up to 15 years, substances banned in 70’s still present
 Long term adipose tissues storage, difficult to detox
 No safe levels, biologic effects at pp trillion
DNA damage
Epigenetic effects by altering methylation patterns which are inheritable
Injure developing nervous system
Carcinogenic
Gender bending chemicals
Alter brain structure, neurochemistry, behavior, reproduction and
immune response in animals
Damage sperm and cause genital malformations
Precocious Puberty
Allergies, Asthma, Diabetes, Heart Disease, Thyroid disease 20
Autism increasing evidence
PUBLIC HEALTH
ASSESSMENT
BRICK TOWNSHIP
AUTISM
INVESTIGATION,OCE
AN COUNTY, NJ
EPA FACILITY ID: NJXCR
November 29, 2000
Superfund Site
Assessment Branch
Division of Health
Assessment and
Consultation
Agency for Toxic
Substances and
Disease Registry

See Mark Blaxill


WHAT DID THE CDC
KNOW AND WHEN
DID THEY KNOW
IT?
AGE OF AUTISM
http://www.ageofautis
m.com/2007/12/what-
21
did-the-cd.html
Appendix A: Contaminants of Concern
Acetone 1,000ppb Dioxin (2,3,7,8 TCDD) .00001ppb
Anthracene 3,000ppb Endosulfan 20ppb
Arsenic 3ppb
Ethyl benzene 700ppb
Benzene 1ppb
Flouranthene PAH) 400ppb
Benzo(b)flouranthene (PAH) 0.2ppb
Heptachlor 0.008ppb
Benzo(a)pyrene (PAH) 0.005ppb
Heptachlor epoxide 0.004ppb
Benz(a)anthracene (PAH )2,800ppb
Hexachlorocyclohexane 0.02ppb
Bis-phthalate 6,000,00 ppb alpha 0.006ppb beta0.02ppb
Bromoform 4ppb gamma0.4ppb
Butyl benzyl phthalate 2,000ppb Lead 0ppb
Cadmium 5ppb Mercury 2ppb
Carbon tetrachloride 0.3ppb MCLMethylenechloride 5ppb
Chlordane 0.6ppb Naphthalene 20ppb
Chlorobenzenes 100ppb Nickel 100ppb
Chloroform 6ppb PCB's 0.02ppb
Chromium 100ppb
Pyrene(PAH) 300ppb
Copper 100ppb
Silver 50ppb
DDT 5ppb
Tetrachloroethylene(PCE)0.7ppb
Di-n-butyl phthalate 1,000ppb
Toluene 200ppb
Dibenzo(a,h)anthracene 0.3ppb 1,1,1-Trichloroethane 200ppb
1,2-Dichlorobenzene 600ppb 1,1,2-Trichloroethane 0.6ppb
1,4-Dichlorobenzene 75ppb Trichloroethylene 20ppb
Dichloroethanes 0ppb Vinyl Chloride 0.2ppb
1,1-Dichloroethene 0.06ppb Xylene 2,000ppb
Diethylstilbestrol Zinc 3,000ppb 22
23
RESULTS: Multivariate models comparing children of mothers living within
500 m of fields with the highest quartile of organo-chlorine poundage to
mothers not living near fields- odds ratio for ASD of 6.1. (28% of moms)
ASD risk ↑with the poundage of organochlorine applied and↓ with distance
from field sites.
CONCLUSIONS: Residential proximity to organochlorine pesticide
applications during gestation and ASD among children should be further
studied. 24
Environment and
Chronic Ilness
Epidemics of
Epidemics
25
26
Bisphenol A Causes Chromosomes to Sort
Incorrectly During the Development of Egg
Cells P.A. Hunt et al, “Bisphenol A Exposure Causes Meiotic Aneuploidy in
the Female Mouse,” Current Biology 13:546-553, 2003.

27
Tests reveal high chemical levels in
kids' bodies 7:02 p.m. EDT, Mon October 22, 2007
http://www.cnn.com/2007/TECH/science/10/22/body.burden/index.html#cnnSTCText

"[Rowan's] been on this planet for 18


months, and he's loaded with a chemical
I've never heard of," Holland, 37, said. "He
had two to three times the level of flame
retardants in his body that's been known to
cause thyroid dysfunction in lab rats."
"We are the humans in a dangerous and
unnatural experiment in the United States,
and I think it's unconscionable," said Dr.
Rowan's blood had
Leo Trasande, assistant director of the
high levels of a
Center for Children's Health and the
chemical that can cause
Environment at the Mount Sinai Medical28
thyroid dysfunction in
Center in New York City.
vironmental Health Perspectives • 114:8 | August 2006

29
112: 3 |March 2004 Environmental Health Perspectives

30
115:5 | May 2007 • Environmental Health Perspectives
“This is a red flag, the impact of this class of chemicals,
whose toxicity has been under-appreciated, must be studied
in human populations, and fast.” M.M. Merzenrich

31
Perinatal Exposure to Low Level PCB’s Alters
Wiring of Primary Auditory Cortex
Kenet, T. et al. (2007) Proc. Natl. Acad. Sci. USA 104, 7646-7651

Normal Response Perninatal PCB

Perinatal PCB 32
Copyright ©2007 by the National Academy of Sciences
nature neuroscience • volume 3 no 12 • december 2000
The cause of PD is unknown, but epidemiological studies suggest an association with
pesticides and other environmental toxins, and biochemical studies implicate a
systemic defect in mitochondrial complex I. ...chronic, systemic inhibition of complex I
by the pesticide, rotenone, causes highly selective nigrostriatal dopaminergic
degeneration that is associated behaviorally with hypokinesia and rigidity.
These results indicate that chronic exposure to a common pesticide can reproduce the
anatomical, neurochemical, behavioral and neuropathological features of PD.

33
Alzheimer's disease -like pathology in aged monkeys after
infantile exposure to environmental metal lead (Pb): evidence
for a developmental origin and environmental link for for AD.

The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that
may drive AD pathogenesis; however, the triggering factors and the period of their
action are unknown. Recent studies in rodents have shown that exposure to lead (Pb)
during brain development predetermined the expression and regulation of the amyloid
precursor protein (APP) and its amyloidogenic beta-amyloid (Abeta) product in old
age. Furthermore, developmental exposure to Pb altered the levels, characteristics,
and intracellular distribution of Abeta staining and amyloid plaques in the frontal
association cortex. These latent effects were accompanied by a decrease in DNA
methyltransferase activity and higher levels of oxidative damage to DNA, indicating
that epigenetic imprinting in early life influenced the expression of AD-related genes
and promoted DNA damage and pathogenesis. These data suggest that AD
pathogenesis is influenced by early life exposures and argue for
both an environmental trigger and a developmental origin of AD.
Wu J, et. Al. J Neurosci. 2008 Jan 2;28(1):3-9.

34
 Reproductive and
Developmental Toxicity
 Neurotoxicity
 Immunotoxicity
 Liver Toxicity and
Cancer
 Respiratory Toxicity and
Cancer
 Kidney Toxicity and
Cancer 35
Appendix A: Contaminants of Concern
Acetone 1,000ppb Dioxin (2,3,7,8 TCDD) .00001ppb
Anthracene 3,000ppb Endosulfan 20ppb
Arsenic 3ppb Ethyl benzene 700ppb
Benzene 1ppb Flouranthene PAH) 400ppb
Benzo(b)flouranthene (PAH) 0.2ppb Heptachlor 0.008ppb
Benzo(a)pyrene (PAH) 0.005ppb Heptachlor epoxide 0.004ppb
Benz(a)anthracene (PAH )2,800ppb Hexachlorocyclohexane 0.02ppb alpha
Bis-phthalate 6,000,00 ppb 0.006ppb beta0.02ppb
Bromoform 4ppb gamma0.4ppb
Butyl benzyl phthalate 2,000ppb Lead 0ppb
Cadmium 5ppb Mercury 2ppb
Carbon tetrachloride 0.3ppb MCLMethylenechloride 5ppb
Chlordane 0.6ppb Naphthalene 20ppb
Chlorobenzenes 100ppb Nickel 100ppb
Chloroform 6ppb PCB's 0.02ppb
Chromium 100ppb Pyrene(PAH) 300ppb
Copper 100ppb Silver 50ppb
DDT 5ppb Tetrachloroethylene(PCE)0.7ppb
Di-n-butyl phthalate 1,000ppb Toluene 200ppb
1,1,1-Trichloroethane 200ppb
Dibenzo(a,h)anthracene 0.3ppb 1,1,2-Trichloroethane 0.6ppb
1,2-Dichlorobenzene 600ppb
1,4-Dichlorobenzene 75ppb
Trichloroethylene 20ppb
Vinyl Chloride 0.2ppb
Dichloroethanes 0ppb
Xylene 2,000ppb
1,1-Dichloroethene 0.06ppb
Zinc 3,000ppb
Diethylstilbestrol
36
Trichloroethylene: Parkinsonism and
complex 1 mitochondrial neurotoxicity
OBJECTIVE: Analyze cluster of 30 industrial coworkers with Parkinson's
disease and 8-33 years exposure to trichloroethylene.
METHODS: Neurological evaluations on coworkers; animal studies were
conducted to determine whether trichloroethylene exposure is neurotoxic to
the nigrostriatal dopamine system that degenerates in Parkinson's disease;
analyze complex 1 mitochondrial neurotoxicity- a mechanism of action of
other known environmental dopaminergic neurotoxins.
RESULTS: Three workers with workstations adjacent to the trichloroethylene
(TCE) source and chronic inhalation and dermal exposure from handling
trichloroethylene-soaked metal parts had Parkinson's disease. Coworkers
more distant from the TCE source, receiving chronic respiratory
exposure, displayed many features of parkinsonism. Neurotoxic of
TCE in animal studies for 6 weeks instigated selective complex 1
mitochondrial impairment concomitant striatonigral fiber
degeneration and loss of dopamine neurons.
INTERPRETATION: Trichloroethylene, used extensively in industry and
the military and a common environmental contaminant, joins other
mitochondrial neurotoxins, MPTP (1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine) and some pesticides, as a risk factor for
parkinsonism.
37
Annals of Neurology 35: 2 204 - 210
ToxSci Advance Access published online on
March 20, 2008
Toxicological Sciences,
doi:10.1093/toxsci/kfn059 SUPPRESSION OF
HUMORAL IMMUNITY IN MICE FOLLOWING
EXPOSURE TO PERFLUOROOCTANE SULFONATE
(PFOS) Margie M.
PFOS, compounds Peden-Adams
in stain repellents, affects the
immune-system in mice at levels found in
the general human population. These levels
were much lower levels than ever reported and
were in the range seen in the Centers for Disease
Control and Prevention’s National Health and
Nutrition Examination Survey data, a snapshot of
the health, nutrition, and contaminant exposure of
the U.S. population.
The paper’s findings support the hypothesis “that
some people today could be
immunocompromised because of PFOS
exposure,” says coauthor Jennifer Keller, a
researcher with the Hollings Marine Laboratory in
Charleston, S.C. 38
http://www.iceh.org/pdfs/LDDI/LDDI
Statement.pdf

39
Scientific Consensus Statement on Environmental Agents
Associated with Neurodevelopmental Disorders

40
Scientific Consensus Statement on Environmental Agents
Associated with Neurodevelopmental Disorders

High-confidence Conclusions
Alcohol
Lead
Mercury
PCBs
PBDEs ManganeseArsenicSolvents
PAHs
Pesticides
Endocrine disruptors
Fluoride
Food additives
Nicotine environmental tobacco smoke
41
Scientific Consensus Statement on Environmental Agents
Associated with Neurodevelopmental Disorders

42
Ultrasound Disrupts Neuronal Migration

43
44
45
46
Women Lead Environmental
Health Movement
There is an Ethiopian proverb that when
spider webs unite they can tie up a lion.
The lion of globally destructive production
patterns and consumption may one day be
ensnared and ultimately domesticated by the
gossamer webs of human consciousness and
community action.

Biosphere destruction mortally wounds all…


we come to understand their wounds are so
often intimately related to the wounds of the
earth. 47
What happens when we realize that her
breast cancer,
husband's lymphoma,
brother's melanoma,
son's learning disability,
best's friend's attention deficit disorder,
daughter's endometriosis,
niece's cleft palate,
cousin's chronic anxiety and panic disorder,
best friend's severe chemical sensitivity, best
friend's daughter's asthma,
uncle's infertility,
neighbor's son's testicular cancer, and
sister's daughter's childhood leukemia,
are found to have common causes?
48
What happens when we begin to understand that
these new human pandemics may be profoundly
connected to what is happening to the fish in the
sea, the birds in the sky, and the animals of the
earth… the web of life?

Perhaps we will understand that cancers &


infertility of the fish, disappearance of the frogs,
cleft palates of the mice, shifts in gender
orientation of the birds, susceptibility to viruses
and infections of the seals, disappearance of the
songbirds… that all this and much, much more may
be telling us a story that is our story.

49
The story that the birds and the fish and the
mice are telling us is the story of Inter-Being
-- the story that all life on earth is truly,
breathtakingly, concretely connected right
now; what we do to the mice of the field and
the birds of the forest, we also ultimately do
also to ourselves and our families.
This is among the great stories of our time.

Michael Lerner, President, Commonweal, Bolinas, CA

http://www.commonweal.org/extinctenvhealth.html
The Age of Extinction and The Emerging Environmental Health Movement

50
Organic Acids as a
Window to System Wide
Dysfunction in Autism

Universality of Metabolism

51
Biochemical Abnormalities in ASD
 Oxidative Stress  Lipids
 Folate cycle  Phospholipids
 Methylation  Fungal metabolites
 Sulfation  Bacterial metabolites
 Citric acid cycle  Neurotransmitters
 Amino acids  Ammonia
 Fatty Acids  Ketosis
 Carbohydrate  Neopterin/biopterin
 Carnitine  Nutrient Deficiencies
 Creatine  Taurine
 Porphyrins  Histidine
52
Organic Acids in Autism
Autism is complex and multifactorial. Organic acids
can help identify interface of genes, nutrients and
environment.
Glycolysis
Methylation, Folic Acid
Tricarboxcylic Acid (Krebs) Cycle
Functional Nutrient Deficiency- depletion or enz ↓
Excessive gut bacterial or fungal growth
Excessive toxic load
Neurotransmitter metabolism
CHO, FA metabolism
Glutathione metabolism
Mitochondrial function 53
Organic Acids in Autism
Measures essential metabolites in 1st AM urine…
simple & non-invasive specimen into underlying
causes of symptoms & provide information about
functional needs to guide treatment in complex
chronic problems. Most frequent abnls:
Folic acid cycle
Methylation cycle
Dysbiosis
Krebs energy cycle
Glutathione synthesis
Neurotransmitter metabolites.

54
55
56
Altered in Autism
abnormal abnormal

abnormal abnormal

abnormal
abnormal

abnormal abnormal

abnormal

abnormal abnormal

abnormal abnormal

abnormal 57
abnormal
Universality of Metabolism
The network of biochemical reactions inside cells
are some some of the most complex in nature.
These pathways can be displayed on a single
chart that applies to all life forms on the planet,
reflecting biology’s unity within diversity.
Central to almost every step in metabolism is ATP-
life’s energy currency.
At the center of anabolism (synthesizing) and
catabolism (breaking down) in all cells is citric
acid cycle
Citric acid cycle is the source of energetic electrons
that generate 90% of ATP in cells
58
“Citric acid cycle, core
of biosynthesis and all cellular biology, the
creative and generative center of all life. It
has persisted for four billion years and
remains the central metabolic essence of
biology from cellular biology to global
ecology. It survived the oxygen catastrophe,
remaining the center of biosynthesis. It is the
basic aspect of our search for laws of life.

Harold Morowitz
59
Energy for Life- Expensive

Adenosine-5'-triphosphate- ATP Adenosine 5'-(Tetrahydrogen


Triphosphate); C10H16N5O13P3 F.W. 507.21 CAS: 56-655

1 gram cost = $682.00


Consume ~ body weight in ATP/day
70K g x $682/gm = $47,740,000 1 day ATP
Lifetime ATP Cost = $1,193,500,000,000
> One trillion dollars lifetime
cost if you had to buy your ATP 60
Mitochondria Fundementals

 Contain Citric Acid cycle- supplies energetic


electrons to Electron Transport Chain (ETC)
tp produce 90% of cell’s ATP
 Each mitochondria has approximately 17,000
ETCs, a whopping ~ 600 amps current at rest
for an adult
 Mitochondria deliver energy for life and
maintain order and structure in body

61
Mitochondrial Fundamentals
 Surface area inside mitochondria energy
producing cristae cover 10,000 m2 (300, 000
ft2); ~ two football fields (if spread on surface)
 At rest, 600 amps current;
95% body’s ATP comes from mitochondria;
body weight of ATP produced each day
 Couples OxPhos to respiration to detox
 ~100 to ~1000/cell; <100 in sperm
 Inner & outer membrane unique structures
 Embedded proteins selectively active
62
Mitochondria Fundamentals
 Mitochondria produce ~90% of ATP in health
 Other functions besides Krebs’ cycle:
Urea generation,
Heme synthesis
Fatty acid oxidation,
Apotosis signaling,
Ca, Fe, Cu storage
 Contain ~ 1000 proteins many involved in ETP,
function like semi-conductor; ~ 98% efficient of
O2 taken up utilized by cyt c to form water
63
Mitochondria: Genetics
 Only organelle with DNA (apart from nucleus)
 mtDNA: compact, circular, easily damaged,
only 13 proteins encoded,
 Dicotomy: mtDNA & nuclear gene mutations;
129 nuclear, 30 mtDNA currently known
 Clinical links: Diabetes, Parkinsonism,
Alzheimer’s, cancer, aging, apoptosis
 Antibiotic related mitochondrial inhibition

64
Mitochondria summary…
…are tiny organelles inside cells that generate almost all
ATP for cell work.
~ 300-400 per cell, i.e. ten million billion in human
body. Look like bacteria…appearances not deceptive:
Once free living organisms that adapted to life inside
larger cells ~ two billion years ago. Their unique DNA
is a badge of former independence. Their tortuous
relations with their host cells have shaped the whole
fabric of life, from energy, sex, and fertility, to cell
suicide, ageing, and death.

Nick Lane Power, Sex, Suicide Mitochondria and the meaning of life,
Oxford University Press, 2005
65
Mitochondrial Oxidative Stress
 MtDNA comes from mother
 More sensitive to damage; less repair
mechanisms
 90% of body oxygen consumed by mitochondria
 4 to 5% of all oxygen processed in mitochondria
generates reactive oxygen species (ROS):
Superoxide
Hydrogen peroxide
Hydroxyl radical
These are rapidly stopped and soaked up by 66
dismutases, catalases, etc.
Journal of Child Neurology. 21:2, February
2006 Developmental Med & Child Neurology 2007, 49: 726–73

67
Autism and Mito Dysfunction
 Unknown how many children at risk may as high as
1 in 50.
 Thimerosal, mercury, aluminum, pollution,
pesticides, medicines and prenatal alcohol exposure
have all been shown to damage mitochondria.
 1 in 20 children with autism may have underlying
mitochondrial dysfunction.
 The CDC is beginning to wake up and address
national vaccine schedule.
 The genetic susceptibility for mitochondrial
dysfunction is not rare and how environmental
triggers interact is still largely unknown.
 Children with mitochondrial dysfunction are more
susceptible to regressive autism following viral
infections and/or a vaccine reaction. 68
Hannah Poling and mitochondrial
dysfunction-a wake up call
To understand Hannah's case, it is important to understand mitochondria, which
act like batteries in our cells to produce energy critical for normal function.
Because the government's concession hinged on the presence of Hannah's
underlying medical condition, mitochondrial dysfunction, some claim the
decision is relevant to very few other children with autism. As a neurologist,
scientist and father, I disagree.
Emerging evidence suggests that mitochondrial dysfunction may not be rare at
all among children with autism. In the only population-based study of its kind,
Portuguese researchers confirmed that at least 7.2 percent, and perhaps as
many as 20 percent, of autistic children exhibit mitochondrial dysfunction.
While we do not yet know a precise U.S. rate, 7.2 percent to 20 percent of
children does not qualify as "rare." In fact, mitochondrial dysfunction may be
the most common medical condition associated with autism.
Although unlikely, if the Portuguese studies are incorrect and mitochondrial
dysfunction were found to be a rarity occurring in less than 1 percent of all
autism, it would still impact up to 10,000 children (250,000 worldwide), based
on current estimates that 1 million people in the U.S. (25 million worldwide)
have autism. If, on the other hand, the research showing that 7.2 percent to 20
percent of children with autism have mitochondrial dysfunction is correct,
then the implications are both staggering and urgent.
Jon Poling MD,PhD
69
Oxidative Stress
Cellular Dysfunction

70
Metabolic Adaptations to an Oxygen Environment
Are Closely linked to Evolution (and survival)

71
From: Dr. Paul Falkowski, Science 311 1724 (2006)
72
73
74
Increased excretion of a lipid
peroxidation biomarker in autism.
Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC.
Department of Neurosciences, UMDNJ-New Jersey Medical School,
Newark, 07103, USA.
Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):379-84.

75
Oxidative stress results in injury
to macromolecules

Reactive oxygen species/Free Radicals

Detoxifying
Nucleic acid damage,
enzyme systems
mutation, carcinogenesis

Membrane damage Polysaccharide damage


Lipid peroxidation hyaluronic acid, arthritis
Protein damage
enzymes, receptors
transporters
76
February 2007. 5:2 e35

We have discovered a previously unrecognized regulatory


pathway on which chemically diverse toxicants converge,
at environmentally relevant exposure levels, to disrupt
the function of progenitor cells of the developing central
nervous system.
The remarkable sensitivity of progenitor cells to low levels of
toxicant exposure, and the discovery of a mechanism by
which small increases in oxidative status can markedly
alter cell function, provide a novel and specific means by
which exposure to chemically diverse toxicants might
perturb normal development.
77
Mark Nobel, University of Rochester Medical Center Used with permission
78
Many environmental toxicants
are potent pro-oxidants
Environmentally relevant levels of toxicants make cells more
oxidized in precisely the range that alters the response to the
environmental signals, with variable consequences:
• Cell division is suppressed
• Cells are made more vulnerable to inducers of cell death
 Cell regulation is altered

Mark Noble, University of Rochester Medical Center Used with Permission


79
Oxidative stress- fine tuning of cell response
Quiescence Proliferation Apoptosis Necrosis

Transformed C Oxidative stress induces:


• A - terminally differentiated
cells to die by apoptosis or
necrosis
B
• B - mitotically competent
Growth

cells to proliferate, but at


higher oxidative stress, cells
Mitotic Stimulus will die by apoptosis or
competent necrosis
A
Differentiated • C - highly proliferative
tumor or transformed cells to
die by apoptosis or necrosis
Redox status Aw (1999) Am J. Clin Nutr 70:559
Reductants Oxidants 80
What We Can Do
Precautionary Principle
“When an activity raises threats of harm to
human health or the environment,
precautionary measures should be take
even if some cause and effect relationships
are not fully established scientifically.”

Wingspread Conference, 1998.

81
In this study the average elemental concentration in
organic foods on a fresh weight basis was found to be
about twice that of commercial foods.

Altern Complement
Med, 2001;7(2): 161-173

82
“an organic diet provides a dramatic and immediate protective
effect against exposures to organophosphorus pesticides... Within
eight to 36 hours after switching to organic versions, the pesticides in
the urine disappeared and remained nondectable untill
conventional diets were reintroduced ”

“dietary intake of OP pesticides represents the major 83


source of exposure in young children.”
Canada first to label bisphenol A as officially dangerous
Would pave way for a federal ban ENVIRONMENT REPORTER
April 15,2008

84
Goals: Limit Toxins
Clean Water, Whole Food
 Chlorine free, clean water
 Perfume free, natural, biodegradable detergents, soaps, shampoos
 Cotton, free of flame retardants
 Avoid fluoride, arsenic treated wood
 Minimize all plastics
 Aluminum free cookware, deodorants, baking soda; avoid aluminum cans, foil
 Herbicide, pesticide free inside and outside of home
 As much as possible organic produce, free ranging, humanly raised animal
consumption
 Detox Foods- cruciferous veggies, ginger, garlic, onions,egg

85
Average Decline in Sperm Density Across
North America and Europe in the 20th
Century

Shanna H. Swan, E.P. Elkin, and L. Fenster, “The Question of Declining


Sperm Density Revisited: An Analysis of 101 Studies Published 1934-
1996,” Environmental Health Perspectives 108:961-966, 2000. 86
The Truth About First It Was Bees, Now
Honeybees Provide Clues It's Bats That Are
to Their Disappearance Dying

Natural News January 24, 2008 by: Laura


Natural News April 11, 2008 by: Heidi
Weldon
Stevenson 87
All Things are Bound Together
Other species are our kin. This statement is literally true in
evolutionary time. All higher eukaryotic organisms, from flowering
plants to insects and humanity itself, are thought to have descended
from a single ancestral population that lived about 1.8 billion years
ago…All this distant kinship is stamped by a common genetic code
and elementary features of cell structure.”
Edward O. Wilson

Humankind has not woven the web of life. We are but one thread
within it. Whatever we do to the web, we do to ourselves. All things
are bound together. All things connect.
Chief Seattle

88
Autism as a Wake-up Call
The rise in autism diagnoses, along with the rise in other
immune and chronic illnesses, is really a wake-up call. Put
alongside the warnings about the ecological instability of our
planet, it shows that our situation is serious. It calls for pulling
out all the stops and throwing our best intelligence, resources
and organization into getting a grip.
Autistic individuals may not be “different” from the rest of us
but simply “more sensitive” to environmental injury—they may
be the “canaries in the coal mine” warning us of impending
greater disaster. If the level of environmental insults continues to
rise, more children and more adults—and more of life on earth
will experience harm.
Martha Herbert
89
Additional Sources of
Information
 Changing the Course of Autism, Bryan Jepson MD
 Healing the New Childhood Epidemics, Ken Bock MD
 Children with Starving Brains, Jaquelyn McCandless MD
 Special Diets for Special Kids, Lisa Lewis
 Evidence of Harm, David Kirby
 Websites
– www.autism.com
– www.safeminds.org
– www.autismone.org
– www.generationrescue.org
– www.vaccineawareness.com
– www.ddr.org
90
Environmental Groups
 Save our kids, heal our planet. www.sokhop.com
 Collaborative on Health and the Environment: www.cheforhealth.org
 Institute for Children’s Environmental Health: www.iceh.org
 Environmental Health News: http://www.environmentalhealthnews.org/
 Our Stolen Future: www.ourstolenfuture.org
 Pesticide Action Network: http://www.panna.org/
 Coming Clean: www.chemicalbodyburden.org
 Natural Resources Defense Council: www.nrdc.org/health
 Beyond Pesticides: www.beyondpesticides.org
 Greenpeace Chemical Kitchen: www.greenpeace.org
 Alliance for a Healthy Tomorrow http://www.healthytomorrow.org/

91
If you want to go fast go alone.
If you want to go far, go together.
African Proverb

Together, we know enough…to mitigate,


remediate, and prevent the epidemics of
autism, chronic illness and lack of wellness.
If not now, when?
Thank you

Barry Grushkin bgrushkin3@cs.com


Norm Schwartz 92