The Biochemical Basis of

Autistic Disorders :
The Mercury, Androgen (Testosterone), &
Glutathione Connection

Mark R. Geier, MD, PhD, FABMG, FACE

President
The Genetic Centers of America
Phone: (301)989-0548
Email: mgeier@comcast.net

David A. Geier
Vice-President
The Institute of Chronic Illnesses, Inc.

Copyright 2008
 Mercury Exposure

Background Information
Thimerosal & Vaccines:
 Thimerosal is an organic mercury compound
(50% mercury be weight) that is metabolized to
ethylmercury and thiosalicylate and has been
present since the 1930s as a preservative in
some vaccines and pharmaceutical products to
prevent bacterial and fungal contamination.

 The FDA in 1999, under the recommended

childhood immunization schedule, determined
infants might be exposed to cumulative doses of
ethylmercury that exceed some federal safety
guidelines established for exposure to
methylmercury, another form of organic
mercury.
 Thimerosal: The Early History
Source:
Geier DA, Sykes LK, Geier MR.
A Review of Thimerosal (Merthiolate) and its Ethylmercury Breakdown
Product: Specific Historical Considerations Regarding Safety & Effectivness.
Journal of Toxicology & Environmental Health: Part B Critical Reviews
2007;10:575-96.
 Smithburn KC, Kempf GF, Zerfas LG, Gilman LH.
Meningococcic Meningitis: A Clinical Study of 144 Epidemic Cases.*
Journal of the American Medical Association 1930

“TREATMENT
The treatment has remained essentially the same throughout
the epidemic. The routine adopted included, on admission, a
skin sensitization test, rhacehicentesis and intratheceal serum
intramuscular serum and (especially during the second month
of the epidemic) serum intravenously. Intravenous
administration of an antiseptic solution was tried and found
wanting despite the in vitro activity of the agent.”

* From the Lilly Laboratories for Clinical Research, Indianapolis City Hospital

The bacteriologic and serologic studies were made by H. M. Powell, A.B., Sc.D., and F. G.
Jones, of the biologic department of the Lilly Research Laboratories.
 Powell HM, Jamieson WA. Merthiolate as a Germicide.*
American Journal of Hygiene 1931

“Toxicity in Man. Merthiolate has been injected intravenously into 22 persons

in doses upt to 50 cubic centimeters of 1 per cent solution. As many as five
intravenous doses, or a total of 180 cubic centimeters of 1 per cent
Merthiolate, have been given to one individual (see table 7). These large doses
did not produce any anaphylacotid or shock symptoms. Neither did these
quantities in the repeated doses bring about any demonstrable later toxic
effects. The toleration of such intravenous doses indicates a very low order of
toxicity of Merthiolate for man. This information has been supplied through
the kindness of Dr K. C. Smithburn of Indianapolis who has had occasion to
use Merthiolate in a clinical way. Dr. Smithburn state that in these cases
‘beneficial effect of the drug was not definitely proven. It did not appear
however to have any deleterious action when used in rather large doses
intravenously when all the drug entered the vein.’”

* From the Research Laboratories, Eli Lilly Company, Indianapolis, Indiana.

We wish to express our thanks to Dr. G. H.A. Cloves; Director of Research of the Eli Lilly
Company, for assistance and suggestions in the course of this investigation.
Letter from the Director of Biological Laboratories
of Pitman-Moore Company to W. A. Jamieson,
Director of Biological Division, Eli Lilly & Company
(July 22, 1935)

“We have obtained marked local reaction in about 50

percent of the dogs injected with serum containing
dilutions of Merthiolate varying from 1 in 40,000 to 1
in 5,000…no connection between the lot of serum and
the reaction. In other words, Merthiolate is
unsatistifactory as a preservative for serum intended
for use on dogs…”
 Engley FB. Mercurials as Disinfectants: Evaluation of Mercurial
Antimicrobic Action & Comparative Toxicity for Skin Tissue Cells.
Presented May 21, 1956 at 42nd Midyear Meeting of the Chemical
Specialties Manufacturers Association, Chicago, IL.
 The Dose, Makes the Poison:
Late 1980s to Early 2000s:
• Rh-negative mothers were routinely administered Thimerosal
containing Rho(D)-immune globulins at 28 weeks gestation (10.5 to
in some instances more than 40 µg mercury per dose).
• Infants may have been exposed a total of 237.5 µg mercury during
the first 18-24 months of life, if all Thimerosal-containing vaccines
were administered.

Early 2000s – Present:

• All pregnant women to receive flu vaccine anytime during
pregnancy (25 µg mercury / dose).
• Infants to receive 3 flu vaccines during first 18-24 months of life
(12.5 µg mercury / dose) = 37.5 µg mercury.
• Children from 3 years-old through 18 years-old are to receive
yearly flu vaccines (25 µg mercury / dose) = 375 µg mercury.
● US Hot Spots Have Mercury Levels in Excess of US Government Regulations
Source: Commission for Environmental Cooperation, 2008.
 Thimerosal (Mercury) Doses** Infants Received:
Source: Bigham M, Copes R. “Thiomersal in vaccines: balancing the risk of adverse effects with the
risk of vaccine-preventable disease,” Drug Saf, 2005;28:89-101.

__________________________

** Assuming an infant receiving 187.5 μg of mercury from Thimerosal-

containing vaccines during the first 6 months of life from the routine
childhood vaccination schedule, in combination with environmental
exposure from mercury in breast milk (164 μg of mercury).
1
• “Learning and developmental disabilities (LDDs) include but are
not limited to deficits in learning and memory, reduced IQ, attention
deficit hyperactivity disorder (ADHD), autism spectrum disorder,
conduct disorders and developmental delays.”

• “There is no doubt that mercury exposure causes learning and

developmental disorders”
Increased Mercury
Exposure in
Autistic Disorders
The Centers For Disease Control & Prevention
(CDC)

Vaccine Safety Datalink (VSD)

Thimerosal Dose-Response Studies

 Simpsonwood Meeting (7-8 June
2000) in Norcross, GA where the
findings of the Vaccine Safety
Datalink (VSD) analysis showing a link
between Thimerosal-containing
vaccines and neurodevelopmental
outcomes were discussed in a closed
meeting by employees from the CDC,
FDA, & the vaccine manufacturers.
Dr. B renier: Page 113: “We hav e as ked you t o keep t his inf ormat ion
confident ial…”

Dr. Johnston: Page 198: “F orgi ve this personal comm ent, but I got
cal led out a eight o’c lock emergency call and m y daught er-in-law
delivered a son by C-Secti on. Our f irs t male in the line of the next
generat ion, and I do not want t hat grands on to get a thimerosal
containing vacc ine”

Dr. W eil: Page 207: “The num ber of dos e related relat ions hi ps are li near
and stat isti cally signif ic ant . You can play with thi s all you want. They
are linear. They are stat is tically s ignifi cant . The pos it ive relat ions hi ps
are thos e that one might expec t f rom the Faeroe I slands studi es . They
are als o relat ed t o t hos e dat a we do hav e on experim ental animal dat a
and simi lar to the neurodev el opment al t ox data on other substances , so
that I think you can’t ac cept that this is out of the ordinary. It is n’t out of
the ordinary. ”

Dr. B rent: Page 229: “…w e are in a bad pos it ion from t he standpoi nt of
def ending l aw sui ts if they were i ni tiat ed and I am conc erned. ”
Dr. Clem ents: Page 247: “I am really conc erned that we have tak en
of f like a boat going dow n one arm of the mangrove sw am p at high
speed, when in f ac t there was not enough disc uss ion really early on
about whic h way t he boat should go at all. And I reall y do want to risk
of fending ev eryone i n t he room by say ing that perhaps thi s study
should not have been done at all, becaus e the out com e of it could
have t o some ex tent, been predicted, and w e have all reached t his
point now where we are lef t hanging…”
“… But nonet heles s, we know f rom many experienc es in history t hat
the pure scienti st has done res earch becaus e of pure scienc e. But
that pure sc ience has result ed in splitt ing the at om or some other
proces s which is com pletely beyond t he pow er of the s cient is ts who
did the res earch t o cont rol i t. And what we hav e here is peopl e who
have, for ev ery best reas on in the worl d, purs ued a di rec ti on of
researc h. But t here i s now the point at which t he researc h res ult s
have t o be handled, and ev en if t his c om mit tee decides that there is
no as sociat ion and that inf ormat ion gets out , the work t hat has been
done and t hrough t he freedom of inform ation that wil l be tak en by
ot hers and will be us ed i n way s bey ond the control of t his group. An I
am very conc erned about that as I suspec t i t is already t oo l ate to do
anything regardles s of any profess ional body and what t hey say. My
mandat e as I sit here i n t his group is to make sure at t he end of the
day t hat 100,000, 000 are im munized wit h DT P, Hepatit is B and i f
poss ible Hib, this year, next year and f or many years t o come, and
A Prospective Assessment of the Association between Thimerosal-
Containing Rho(D)-Immune Globulin and Autistic Disorders
By Geier DA, Geier MR
Journal of Maternal, Fetal, & Neonatal Medicine 2007;20:385-90
________________________________
 Increased Mercury
Body-Burden in
Autistic Disorders:

A Clinical Perspective
 Conclusions:
** There was a significant increase in the brain
concentration of the Hg / Se ratio in autistics vs
controls.

** There was a significant increased in brain

oxidative stress markers in autistics vs controls.

** There was a significant correlation between

brain mercury concentrations and oxidative stress
markers in autistics vs controls.
Low Glutathione in
Autistic Disorders
 Methionine Cycle & Transsulfuration Pathway
Source: James SJ, et al**. Metabolic biomarkers of increased oxidative stress and impaired
methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.

________
 ** Mercury Excretion is Directly Related to Glutathione Secretion

Source: Clarkson TW, Nordberg GF, Sager PR. Reproductive and developmental toxicity of metals. Scan J Work Environ
Health 1985;11:145-54.
 Biochemical Markers in Autistics:
Sourece: James SJ, et al. Metabolic biomarkers of increased oxidative stress and impaired
methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.

___________________
___________________
Visual Evidence of Thimerosal

Induced

Human Neuron Damage

 ↑ ↑

Human Neuroblastoma Cells

Human Neuroblastoma Cells
24 Hrs Incubation
24 Hrs Incubation
100 nM Thimerosal
No Thimerosal
[20 ppb Mercury]
 ↑ ↑

Human Fetal Cells

Human Fetal Cells
24 Hrs Incubation
24 Hrs Incubation
10 nM Thimerosal
No Thimerosal
[2 ppb Mercury]
Mercury & Testosterone

Toxicity
** Observed that female hormones afforded total protection against Thimerosal toxicity.
** Observed testosterone at 1.0 µM levels that by itself did not significantly increase neuron death,
within 3 hours when added with 50 nM Thimerosal caused 100% neuron death [50 nM Thimerosal at
this time point did not significantly cause any cell death].
Geier MR, Geier DA. The potential
importance of steroids in the
treatment of autistic spectrum
disorders and other disorders
involving mercury toxicity. Med
Hypotheses 2005;64:946-54.
 Mannin g J T, Baro n-Cohen S, Wheel wri ght S, Sand ers G. T he 2nd t o 4t h digit rat io
and a ut ism. D ev Med Chi ld Neurol 200 1;43:16 0-4 .

The aut hor s ex am ined 7 2 chi ldre n wi th aut ism , inc lu ding 2 3 chi ldren wi th Asp erg er
sy nd ro me, 3 4 si bli ng s, 88 fat hers, 8 8 mot hers, and sex and a ge-mat ched cont ro ls.
The aut ho rs dem onst rat ed that the m ore se verel y a ffec ted t he chi ld ren were t he
hi gher the lev els of prenat al test ost erone.

Low er Testo ste ro ne/

Hig he r E stro gen

Hig her Tes tostero ne /

Low er Es troge n

AS = As perg er Syn dro me

 Stero ido gen ic P ath wa y:

Cholesterol DHEA-S

ê Progestogens éâ Androgens
17-hydroxy-
Pregnenolone è è DHEA èß Androstenediol
pregnenolone

ê ê ê ê

è 17 hydroxy èß
Progesterone è Androstenedione Testosterone
-progesterone

ê ê ê ê

11 deoxy- èß
corticosterone 11-deoxycortisol Estrone Estradiol

ê ê ê ê

Corticosterone Cortisol Estriol

Estrogens
ê Corticoids
→

←
→

→
Hydroxysteroid Sulfotransferase

→ →

→
→

→
→ →
→

→
→
___________________________________________
 Elevated Testosterone
(Androgens) in Children with
Neurodevelopmental
Disorders:

Potential Insights into Levels

&

Potential Adverse Effects

 Developmental Medicine & Child Neurology
1999;41:392–395
Studies on precocious puberty have primarily focused on
children with typical patterns of growth and cognitive
development. This study reviewed diagnostic data from the
records of 15,719 patients with neurodevelopmental
disabilities for diagnoses associated with premature sexual
development/precocious puberty. Thirty-two individuals
with premature sexual development were identified…
Discussion
The US Department of Health and Human
Services and the National Institute of
Child Health and Development (NICHD)
of the National Institutes of Health (NIH)
estimate the incidence of precocious
puberty in the general population to be
approximately one in 10,000 children (US
Department of Health and Human
Services 1997). The incidence of
precocious puberty has been estimated to
be higher in children with
neurodevelopmental disabilities than in
children without neurodevelopmental
disabilities.
Our retrospective review of this
population with neurodevelopmental
disabilities suggested that a child with a
neurodevelopmental disability was at least
20 times more likely to experience early
pubertal changes.
 Am J Psychiatry 1997;154:1626-7

• In 4 of 12 prepubertal autistic children (6–10 years old) in our inpatient child

psychiatry department, we have observed precocious secondary sexual
characteristics (growth of pubic hair, increase of testis volume) that suggest high
androgenic activity in infantile autism.

• To test our hypothesis of a hyperandrogeny and autism association, we

measured plasma testosterone and adrenal androgen in nine drug-free inpatients
with DSM-IV autism and 62 normal subjects of same age, sex, weight (within 2
kg), and stage of puberty.

• Results showed that three of the nine autistic subjects had an abnormally high
plasma testosterone concentration (over two standard deviations above the mean
for the comparison subjects), with values above that of the highest in the
comparison subjects.
 Other Effects of Elevated
Testosterone (Androgens) in
ASDs
• Testosterone levels are positively correlated with a number of autistic
traits and inversely correlated with social development and empathy.

• A medical questionnaire was completed by n=54 women with ASDs,

n=74 mothers of children with ASDs, and n=183 mothers of typically
developing children.

• Compared to controls, significantly more women with ASDs reported

(a) hirsutism, (b) bisexuality or asexuality, (c) irregular menstrual cycle,
(d) dysmenorrhea, (e) polycystic ovary syndrome, (f) severe acne, (g)
epilepsy, (h) tomboyism, and (i) family history of ovarian, uterine, and
prostate cancers, tumors, or growths.

• Compared to controls, significantly more mothers of ASD children

reported (a) severe acne, (b) breast and uterine cancers, tumors, or
growths, and (c) family history of ovarian and uterine cancers, tumors,
or growths.

• These results suggest current hormone abnormalities in women with

ASC and their mothers.
A summary of the interaction between the transsulfuration and androgen pathways in
autistic spectrum disorders

PAPS = 3’-phosphoadenosine 5’-phophosulfate CBS = Cystathionine β-Synthase

BHMT = Betaine Homocysteine Methyltransferase
MS = Methionine Synthase
SAM = S-adenosylmethionine
MTase = Methyltransferase
SAH = S-adenosylhomocysteine
THF = Tetrohydrofolate
5-MTHF = 5-Methyltetrahydrofolate
5, 10-MTHF = 5, 10-Methyltetrahydrofolate
SAHH = SAH Hydrolase
DHEA-S = Dehydroepiandrosterone-sulfate
DHEA = Dehydroepiandrosterone
Treatment Overview:

The Protocol
• Furthermore, in our own clinical experience we have
observed that leuprolide acetate (LUPRON®) administration
to nearly 200 patients diagnosed with ASDs significantly
lowered androgen levels and has resulted in very
significant overall clinical improvements in socialization,
sensory/cognitive awareness, and health/physical/behavior
skills, with few non-responders and minimal adverse
clinical effects to the therapy.

• The following are some specific areas of significant clinical

ameliorations in frequent symptoms that occur in patients
diagnosed with ASDs observed:

• hyperactivity/impulsivity
• stereotypy
• aggression
• self-injury
• abnormal sexual behaviors
• irritability behaviors