Wednesday, January 16, 2008

Thank You!

Now that the series is behind us...We are making plans to shut down the blog in a few weeks. I will have a set date by Friday. I will post the shut down day on the blog.

We are going to keep the blog online, but make it inactive.

We are in the process of planning an hour long show in February. The show will feature a round table discussion and behind the scenes clips.

We will put the entire show online.
We look forward to your comments.
Thank you for participating in this blog.
We enjoyed sharing the process of the series with you and hope you enjoyed getting a first view of the series.

Thank You!

21 comments:

AutismNewsBeat said...

Ashley, you recently posted this on an Autism Speaks forum:

We have gotten thousands of responses from the series, mostly positive. The goal of the series is to raise awareness and give parents info to make their own educated decisions about vaccines. Our ombudsman service did two reports on the series here are the links. Watch this one first.

http://www.komu.com/satellite/Satell...3-36c1bccfc9d5

then this one

http://www.komu.com/satellite/Satell...1-bc25a991321d


It's laudible to empower parents with information, but only if the information is correct, and presented in its proper context. You stated several times throughout the series that there is no clear scientific evidence that links thimerosal to autism, but you never said why. Then you repeated unfounded claims as if they were true.

Will your station be correcting parts of your report, or clarifying points of fact during the February show?

Is there anything you wish you had done differently during the series?

MO BETTER said...

Great cartoon, speaking to the interface of basic science and political protectionism of clinical medicine.
http://www.ucsusa.org/scientific_integrity/science_idol/

Thanks to the Fourth Estate the countdown to Fascism has been moved back again.

Funny how titer levels aren't what is required for school children as it is REAL EVIDENCE of immunity. There are a number of kids who go through a full series of boosters and still aren't immune (maybe because their prenatal exposure to certain antigenic compounds and non-cytopathic viruses left their immune systems naive to the foreign proteins-happens, ask a research immunologist, preferably one from a Vet school so you can get a straight answer since cattle can't hire lawyers).

EFFIIIMD

ANB: Is there anyone you wish didn't participate in this blog?

The semi-fascist info-brokers who have the inability to understand the implications of basic science showing the tea-leaves of truth in medicine can't really debate the prudent approaches I have given all over this blog.

ANB said...

What's with you and run-on sentences? Is that a symptom of radiation poisoning?

Kathleen Seidel said...

"Semi-fascist info-brokers"? For heaven's sakes, effii, get a grip and whip out the Windex; there's spittle all over your monitor.

ANB said...

I didn't realize fascism was a spectrum disorder.

Edward Fogarty, MD said...

ANB and Kathleen Seidel with all of your scientific knowledge, do you have any commentary on the implications of the following abstracts:

Arch Toxicol. 2003 Jan;77(1):50-5. Epub 2002 Nov 6.
Related Articles, Links
Click here to read Click here to read Click here to read
Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes.

Westphal GA, Asgari S, Schulz TG, Bünger J, Müller M, Hallier E.

Department of Occupational Health, Georg-August-University Göttingen, Waldweg 37, 37073 Göttingen, Germany. gwestph@gwdg.de

Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.

MeSH Terms:

* Cell Division/drug effects
* Cytochalasin B/toxicity*
* Dose-Response Relationship, Drug
* Drug Antagonism
* Genotype
* Glutathione Transferase/blood
* Glutathione Transferase/classification
* Glutathione Transferase/genetics
* Humans
* Lymphocytes/drug effects*
* Lymphocytes/enzymology
* Microfilaments/drug effects
* Micronucleus Tests/methods*
* Mutagens/toxicity*
* Polymorphism, Genetic
* Preservatives, Pharmaceutical/toxicity*
* Thimerosal/toxicity*


Substances:

* Mutagens
* Preservatives, Pharmaceutical
* Cytochalasin B
* Thimerosal
* Glutathione Transferase


PMID: 12491041 [PubMed - indexed for MEDLINE]




Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.

Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.

Müller M, Westphal G, Vesper A, Bünger J, Hallier E.

Department of Occupational and Social Medicine, Georg-August-University Göttingen, D-37073 Göttingen, Germany. mmuelle3@gwdg.de

We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.

MeSH Terms:

* Anti-Infective Agents, Local/adverse effects*
* Chromatography, High Pressure Liquid
* Erythrocytes/enzymology*
* European Continental Ancestry Group/genetics
* Fluorescence
* Glutathione Transferase/drug effects*
* Glutathione Transferase/metabolism*
* Humans
* Phenotype
* Polymorphism, Genetic
* Thimerosal/adverse effects*


Substances:

* Anti-Infective Agents, Local
* Thimerosal
* glutathione S-transferase T1
* Glutathione Transferase


PMID: 11556154 [PubMed - indexed for MEDLINE]





Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141(8):947-56.

Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.

James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW.

Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. jamesjill@uams.edu

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. (c) 2006 Wiley-Liss, Inc.

Publication Types:

* Comparative Study
* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't


MeSH Terms:

* Adolescent
* Autistic Disorder/blood
* Autistic Disorder/genetics*
* Autistic Disorder/metabolism*
* Catechol O-Methyltransferase/genetics
* Child
* Child, Preschool
* DNA Primers
* Female
* Gene Frequency
* Glutathione Transferase/genetics
* Humans
* Male
* Membrane Transport Proteins/genetics
* Methionine/blood*
* Methionine/metabolism
* Methylation
* Methylenetetrahydrofolate Reductase (NADPH2)/genetics
* Oxidative Stress/genetics*
* S-Adenosylhomocysteine/blood
* S-Adenosylmethionine/blood
* Transcobalamins/genetics


Substances:

* DNA Primers
* Membrane Transport Proteins
* Transcobalamins
* reduced folate carrier
* S-Adenosylmethionine
* Methionine
* S-Adenosylhomocysteine
* Methylenetetrahydrofolate Reductase (NADPH2)
* Catechol O-Methyltransferase
* Glutathione Transferase


Grant Support:

* 1C06 RR16517-01/RR/United States NCRR
* 3C06 RR16517-01S1/RR/United States NCRR
* 5R01 HD39054-05/HD/United States NICHD


PMID: 16917939 [PubMed - indexed for MEDLINE]


Do you two know enough biochemistry to understand the implications of this work as relates to the debate here? Or do I have to keep doing the molecular math for you? Got anything better than the "windex" crap?

Thanks again for inspiring me to continually educate through this blog site-I really love this ;-)

Kathleen Seidel said...

No, Ted, I have no interest in playing a pickup game of abstract toss with you. My "windex" crack was a response to your asinine reference to people like ANB and me as "fascists."

And no, I am no repository of scientific knowledge and have never claimed to be one. Like you, I am a parent of a kid with an ASD diagnosis. Like you, I am well-educated in a field that has nothing to do with autism. I make every effort to be an intelligent consumer of scientific information, and to be judicious about the information sources in which I place my trust. Although it is well-established that immunization (like all medical interventions) is occasionally followed by adverse health effects in both autistic and neurologically typical individuals, I have never had any reason or personal inclination to attribute autism to vaccine injury, either before or after reading many of the studies and arguments presented by those who support a causal connection. And your hostile, egotistical, arrogant, bombastic, spluttering bursts of outraged chest-pounding, arm-waving, finger-pointing and name-calling haven't brought me an inch closer to conversion.

ANB said...

After the Gates Foundation and WHO depopulate the Earth with vaccines, demand for your TiterMeter® should skyrocket!

Fogarty said...

ANB and Kathleen you guys are my foils for the debate, your personal attacks are fun and enliven the debate bringing out some interesting commentary here.

I am in a field that has increasingly to do with autism-IMAGING. I am a physician who understands heavy metal chemistry. I know loads more science than you two who are not physicians or research PhDs. Therefore you ought pay some more attention to what I am trying to tell the people in this debate, but if you don't care thats fine. The attention you are paying it is actually hurting your own cause for arguing against the potential for neurobehavioral dysfunction increasing in children with increasing vaccine schedules.

Again, not trying to convince you of anything; it is the spark of understanding in some top flight people at the great universities of Missouri that you are helping me reach through your foil. You are also galvanizing those in the Missouri legislature who stood up against the continued use of thimerosal in this state to stick to their guns by simply following my voice on this blog.

Forgive me, my passion in this debate has to do with improving the culture of medicine to look beyond the institutional denial of need to avoid heavy metal exposures in the at risk populations (such we see with gadolinium, iodine, thorotrast and other heavy metal agents used quite heavily in radiology with recurrent scientific expose of the harm these elements cause). Seems a bit inconsistent that medically used aluminum and mercury in vaccines given parentarally keep getting a pass in the at-risk population. Other less toxic metals keep getting identified in my field as harmful for selected populations-again seems to be quite inconsistent as to how the FDA, CDC and others are dealing with these issues.


Read Simpsonwood-smart guys see what has happened in there.

Got any grammar lessons for me now?

ANB said...

Coherent self expression is the least of your problems.

Fogarty said...

There you go again-can't debate so you make a personal attack. Nice.

MBq said...

But Ted, what about all of that Tin that goes along for the ride when you do a scintigraphy study? Stannous Chloride must inhibit GSTM1 quite a bit. Maybe you're causing the autism epidemic in your area. Injecting those pharma metals in to people.

Come to think of it, TC conjugated to GSH doesn't stick around very long even in the worst case scenarios. You must have a pretty good grasp of glutathione:metal excretion patterns. What makes Hg so unique?

ANB said...

That's a great question, mbq! Can't wait for Dr. Fogarty to "debate" you.

Fogarty said...

Well if you read this . . .


1: Congenit Anom (Kyoto). 2006 Mar;46(1):34-8.

In vitro embryotoxicity testing of metals for dental use by differentiation of
embryonic stem cell test.

Imai K, Nakamura M.

Department of Biomaterials, Osaka Dental University, Hirakata-city, Osaka, Japan.
imai@cc.osaka-dent.ac.jp

We examined embryotoxicity using the embryonic stem cell test (EST) protocol.
Tests were conducted using standard reagents for the atomic absorption
measurement of 11 metal ions, silver, cobalt, chromium, copper, mercury, nickel,
palladium, antimony, tin, vanadium, and zinc from among metals comprising dental
alloys. In addition, for four metals like silver, cobalt, chromium, and nickel,
the tests were also conducted using a test solution extracted from powder in the
cell culture medium. The embryotoxic potential was obtained from a
biostatistics-based prediction model, which was calculated from three endpoints,
the ID50, IC50ES and IC(50)3T3. Data with the standard reagents showed that
chromium and mercury ions corresponded to class 3, that is, having a strong
embryotoxicity, while antimony, tin, and vanadium ions exhibited a weak
embryotoxicity. The other metal ions demonstrated no embryotoxicity. On the other
hand, when extracts of metal powder in cell culture solutions were used, silver
exhibited a weak embryotoxicity while all other metals exhibited no
embryotoxicity. In the future, it will be important to clarify the embryotoxicity
of the many dental materials that are in use today. In addition, it is necessary
to develop substances to ensure they have no toxicity before use in dental
applications.

Publication Types:
Research Support, Non-U.S. Gov't

Mesh Terms:
Animals
BALB 3T3 Cells
Cell Differentiation*
Dental Materials/chemistry
Dental Materials/toxicity*
Embryo, Mammalian/drug effects*
Metals/toxicity*
Mice
Stem Cells/cytology*
Toxicity Tests

Substances:
Dental Materials
Metals

PMID: 16643597 [PubMed - indexed for MEDLINE]

IT SEEMS TIN IS A DISTANT SECOND TO MERCURY . . .

but really my whole point across this blog has a nuance on genetics that seems to keep getting ignored on both sides of the debate at some level . . . it is the subpopulation of children in this country that can't handle heavy metals due to genetic polymorphism that are unique.

So yes, I will be the first to admit that there are problems with all heavy metals, tin included in the select at-risk population. Maybe you need to read up on some of my older posts on the molecular genetics here. I have also stated in several threads that in the at-risk population can't handle many other exposures.

Again, those trying to defend the use of a heavy metal in a subpopulation that can't handle it have nothing on me in this debate. The point is to quantify who these kids are and perform an act of environmental hygeine-protect them from all heavy metal exposures (primarily) and be cautious with many other exposures including radiation. I will soon be writing up a case report advocating extreme caution with the use of gadolinium contrast agents in any child with autism as the detoxification kinetics would parallel the same concerns for the use of gadolinium in renal and hepatically impaired adult patients.

MBQ another point against you is that none of my procedures in children are done particularly frequently or as a universal mandate. So though you have valid concerns as relates to less dangerous heavy metals in imaging which I am beginning to educate others on and address, the widespread exposure to vaccine related heavy metals in this population completely dwarfs the population exposure from my specialty.

TO BE FAIR, HERE IS A PIECE THAT SHOULD CORROBORATE THE CONCERNS YOU HAVE:
Thanks for educating me on the loack of perception of risk that I previously had regarding scintigraphy in those who are poor metal excreters.

1: Nucl Med Biol. 2006 Oct;33(7):915-21.

Cytotoxic and genotoxic effects induced by stannous chloride associated to
nuclear medicine kits.

Guedes AP, Cardoso VN, De Mattos JC, Dantas FJ, Matos VC, Silva JC, Bezerra RJ,
Caldeira-de-Araujo A.

Departamento de Biofísica e Biometria, Universidade do Estado do Rio de Janeiro,
Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro 20551-030, Brazil.
anderson-guedes@ig.com.br

At present, more than 75% of routine nuclear medicine diagnostic procedures use
technetium-99m (99mTc). The binding between 99mTc and the drug to obtain the
radiopharmaceutical needs a reducing agent, with stannous chloride (SnCl2) being
one of the most used. There are controversies about the cytotoxic, genotoxic and
mutagenic effects of SnCl2 in the literature. Thus, the approaches below were
used to better understand the biological effects of this salt and its association
in nuclear medicine kits [methylenediphosphonate (MDP) bone scintigraphy and
diethylenetriaminepentaacetic acid (DTPA) kidney and brain scintigraphy]: (i)
bacterial inactivation experiments; (ii) agarose gel electrophoresis of
supercoiled and linear plasmid DNA and (iii) bacterial transformation assay. The
Escherichia coli strains used here were AB1157 (wild type) and BW9091 (xthA
mutant). Data obtained showed that both MDP and SnCl2 presented a high toxicity,
but this was not observed when they were assayed together in the kit, thereby
displaying a mutual protect effect. DTPA salt showed a moderate toxicity, and
once more, the DTPA kit provided protection, compared to the SnCl2 effect alone.
The results suggest a possible complex formation, either MDP-SnCl2 or DTPA-SnCl2,
originating an atoxic compound. On the other hand, SnCl2-induced cell
inactivation and the decrease in bacterial transformation generated by DTPA found
in XthA mutant strain suggest that the lack of this enzyme could be responsible
for the effects observed, being necessary to induce DNA damage repair.

Publication Types:
Research Support, Non-U.S. Gov't

Mesh Terms:
Cell Survival/drug effects
DNA, Bacterial/drug effects*
Dose-Response Relationship, Drug
Escherichia coli/cytology*
Escherichia coli/drug effects*
Escherichia coli/genetics
Mutagenicity Tests
Mutation
Nuclear Medicine/instrumentation*
Reagent Kits, Diagnostic*
Tin Compounds/administration & dosage*

Substances:
DNA, Bacterial
Reagent Kits, Diagnostic
Tin Compounds
stannous chloride

PMID: 17045172 [PubMed - indexed for MEDLINE]




Back to the primary issues of what the role of public policy makers should be and where research needs to go . . . our "safety" experts at the CDC and the FDA are too far down the road here to change course without major heads rolling so of course no one wants to pursue my advocated points of scientific safety on the issue of vaccine-related heavy metal exposures (or any other heavy metal exposures for that matter).
As more and more science is showing, these kids are unable to handle such exposures, it is clear we need A BIOCHEMICAL TEST THAT IS USED AS AN ENVIRONMENTAL EXPOSURE RISK STRATIFIER IN NEONATES TO IMPROVE POPULATION NEURODEVELOPMENT. Urinary porphyrins may be the answer, some "bone-fide" researchers should be fast-tracking that approach to decreasing the rate of neurobehavioral dysfunction in US children as relates to heavy metal exposures. Screening these kids need only the monies of a week in Iraq and the best and brightest working on the issue. Again, problem is here - if you read the tea leaves once we get there, its gonna make a lot of industry look bad (not just vaccines either, mine too; we will understand in the future that scinitigraphy delivered Tin, MR delivered gadolinium and many other innocuous exposures in the neurotypical at similar dose levels are harmful in these metabolically challenged kids.


Heres another tea leaf for you guys . . .

1: J Toxicol Environ Health A. 2007 Jun;70(12):1046-51.

Mercury, lead, and zinc in baby teeth of children with autism versus controls.

Adams JB, Romdalvik J, Ramanujam VM, Legator MS.

Chemical and Materials Engineering, Arizona State University, Tempe, Arizona,
USA.

This study determined the level of mercury, lead, and zinc in baby teeth of
children with autism spectrum disorder (n = 15, age 6.1 +/- 2.2 yr) and typically
developing children (n = 11, age = 7 +/- 1.7 yr). Children with autism had
significantly (2.1-fold) higher levels of mercury but similar levels of lead and
similar levels of zinc. Children with autism also had significantly higher usage
of oral antibiotics during their first 12 mo of life, and possibly higher usage
of oral antibiotics during their first 36 mo of life. Baby teeth are a good
measure of cumulative exposure to toxic metals during fetal development and early
infancy, so this study suggests that children with autism had a higher body
burden of mercury during fetal/infant development. Antibiotic use is known to
almost completely inhibit excretion of mercury in rats due to alteration of gut
flora. Thus, higher use of oral antibiotics in the children with autism may have
reduced their ability to excrete mercury, and hence may partially explain the
higher level in baby teeth. Higher usage of oral antibiotics in infancy may also
partially explain the high incidence of chronic gastrointestinal problems in
individuals with autism.

Publication Types:
Research Support, Non-U.S. Gov't

Mesh Terms:
Administration, Oral
Anti-Bacterial Agents/administration & dosage
Anti-Bacterial Agents/therapeutic use
Autistic Disorder*
Body Burden
Case-Control Studies
Child
Child, Preschool
Humans
Lead/analysis*
Lead/pharmacokinetics
Mercury/analysis*
Mercury/pharmacokinetics
Tooth, Deciduous/chemistry*
Zinc/analysis*
Zinc/pharmacokinetics

Substances:
Anti-Bacterial Agents
Lead
Mercury
Zinc

PMID: 17497416 [PubMed - indexed for MEDLINE]


MBQ-Good questions-and again, I am not defending the use of heavy metals exposures in any medical or non-medical sense in any autistic child or soon-to-be identifiable at risk children. Two years ago I would have thought much differently about gadolinium and 5 years ago I would be on your side of this debate.


EFFIIIMD

PS: We could pre-treat some of these exposures by thinking about the approach opined in this piece:

1: Neurotoxicology. 2005 Jan;26(1):1-8.

Thimerosal neurotoxicity is associated with glutathione depletion: protection
with glutathione precursors.

James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S.

Department of Pediatrics, University of Arkansas for Medical Sciences and
Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
jamesjill@uams.edu

Thimerosol is an antiseptic containing 49.5% ethyl mercury that has been used for
years as a preservative in many infant vaccines and in flu vaccines.
Environmental methyl mercury has been shown to be highly neurotoxic, especially
to the developing brain. Because mercury has a high affinity for thiol
(sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH),
provides the major intracellular defense against mercury-induced neurotoxicity.
Cultured neuroblastoma cells were found to have lower levels of GSH and increased
sensitivity to thimerosol toxicity compared to glioblastoma cells that have
higher basal levels of intracellular GSH. Thimerosal-induced cytotoxicity was
associated with depletion of intracellular GSH in both cell lines. Pretreatment
with 100 microM glutathione ethyl ester or N-acetylcysteine (NAC), but not
methionine, resulted in a significant increase in intracellular GSH in both cell
types. Further, pretreatment of the cells with glutathione ethyl ester or NAC
prevented cytotoxicity with exposure to 15 microM Thimerosal. Although Thimerosal
has been recently removed from most children's vaccines, it is still present in
flu vaccines given to pregnant women, the elderly, and to children in developing
countries. The potential protective effect of GSH or NAC against mercury toxicity
warrants further research as possible adjunct therapy to individuals still
receiving Thimerosal-containing vaccinations.

Mesh Terms:
Acetylcysteine/pharmacology
Anti-Infective Agents, Local/antagonists & inhibitors
Anti-Infective Agents, Local/toxicity*
Astrocytes/drug effects
Cell Line, Tumor
Cell Survival/drug effects
Cells, Cultured
Chromatography, High Pressure Liquid
Culture Media
Cystine/pharmacology
Dose-Response Relationship, Drug
Electrochemistry
Glutathione/analogs & derivatives*
Glutathione/metabolism*
Glutathione/pharmacology*
Humans
Neurons/drug effects
Thimerosal/antagonists & inhibitors
Thimerosal/toxicity*

Substances:
Anti-Infective Agents, Local
Culture Media
S-ethyl glutathione
Thimerosal
Cystine
Acetylcysteine
Glutathione

PMID: 15527868 [PubMed - indexed for MEDLINE]

Again-free speech is running this situation into an improvement at least in THOUGHT for US children. We can do much better if we just pay attention to the science rather than the politics.

MBq said...

"it is the subpopulation of children in this country that can't handle heavy metals due to genetic polymorphism that are unique"

The nuances haven't been ignored, your assertions are nothing more than assertions. I'm sure you can find a study or two from J.James and Marvin Boris to add substance to your claim but as of this moment, autistic children are not known to possess combinations of SNPs associated with an inability to handle heavy metals.

As intriguing as that James et al. study may appear, the full article contains a key passage that speaks to a fundemantal concept of toxicology. Biological effects are dependent on dosage, be it genes mercury, tin, or X-rays.
------------------------------
Acute high dose exposures to
Thimerosal (mmol/L) in cultured cells were used to
study mechanistic aspects of Thimerosal toxicity and
not intended to mimic exposures of developing brain
cells in vivo to Thimerosal in vaccines (nmol/kg).

AutismNewsBeat said...

But aren't assertions important at the dawn of a new paradigm? How else to fight evidence-based fascism, if not with speculation and alternative inference?

GENXRAD said...

"Sigh"
You are missing the point again, toxicologic biological effects are only dependent on dosage in a genetically identical population. Simple nomenclature in toxicology even reveals that there is variability in toxicity calculations, that is the concept of LD. An LD 50 means the dose only killed 50% of the population-what's protecting the other 50% . . . BETTER GENES.

TOXICOLOGIC EFFECTS OF HEAVY METALS ARE WIDELY VARIABLE IN A GENETICALLY HETEROGENOUS POPULATION, HUMANS HAVE MUCH WIDER GENETIC VARIABILITY THAN LAB RATS.

TOXICOLOGIC EFFECTS ARE ALSO VARIABLE ACROSS THE DEVELOPMENTAL SPECTRUM-HERES ONE FOR XRAYS:

Biological effects of X-rays in BRCA carriers who recieve x-rays at a point of CRITICAL DEVELOPMENT:

1: J Clin Oncol. 2006 Jul 20;24(21):3361-6. Epub 2006 Jun 26.

Comment in:
J Clin Oncol. 2006 Jul 20;24(21):3328-30.

Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation
carriers in the international BRCA1/2 carrier cohort study: a report from the
EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators' Group.

Epidemiological Study of BRCA1 and BRCA2 Mutation Carriers (EMBRACE); Gene Etude
Prospective Sein Ovaire (GENEPSO); Gen en Omgeving studie van de werkgroep
Hereditiair Borstkanker Onderzoek Nederland (GEO-HEBON); International BRCA1/2
Carrier Cohort Study (IBCCS) Collaborators' Group, Andrieu N, Easton DF,
Chang-Claude J, Rookus MA, Brohet R, Cardis E, Antoniou AC, Wagner T, Simard J,
Evans G, Peock S, Fricker JP, Nogues C, Van't Veer L, Van Leeuwen FE, Goldgar DE.

Institut National de la Santé et de la Recherche Médicale Emi00-06, Paris,
France.

PURPOSE: Women who carry germline mutations in the BRCA1 and BRCA2 genes are at
greatly increased risk of breast cancer (BC). Numerous studies have shown that
moderate to high doses of ionizing radiation are a risk factor for BC. Because of
the role of the BRCA proteins in DNA repair, we hypothesized that BRCA carriers
might be more sensitive to ionizing radiation than women in the general
population. PATIENTS AND METHODS: A retrospective cohort study of 1,601 female
BRCA1/2 carriers was performed. Risk of breast cancer from exposure to chest
x-rays, as assessed by questionnaire data, was analyzed using a weighted Cox
proportional hazards model. RESULTS: In this cohort, any reported exposure to
chest x-rays was associated with an increased risk of BC (hazard ratio [HR] =
1.54; P = .007). This risk was increased in carrier women aged 40 years and
younger (HR = 1.97; P < .001) and in women born after 1949 (HR = 2.56; P < .001),
particularly those exposed only before the age of 20 years (HR = 4.64; P < .001).
CONCLUSION: In our series of BRCA carriers, we detected a relatively large effect
on BC risk with a level of radiation exposure that is at least an order of
magnitude lower than in previously studied medical radiation-exposed cohorts.
Although part of this increase may be attributable to recall bias, the observed
patterns of risk in terms of age at exposure and attained age are consistent with
those found in previous studies. If confirmed, the results have important
implications for the use of x-ray imaging in young BRCA1/2 carriers.

Publication Types:
Multicenter Study
Research Support, Non-U.S. Gov't

Mesh Terms:
Adult
Breast Neoplasms/etiology*
Breast Neoplasms/genetics
Breast Neoplasms/prevention & control
Breast Neoplasms/radiography
Cohort Studies
Europe
Female
Genes, BRCA1*
Genes, BRCA2*
Genetic Predisposition to Disease
Germ-Line Mutation*
Heterozygote
Humans
Mammography/adverse effects*
Mass Screening/adverse effects*
Middle Aged
Proportional Hazards Models
Questionnaires
Retrospective Studies
Risk Assessment
Risk Factors
PMID: 16801631 [PubMed - indexed for MEDLINE]


Go back to previous posts of mine, a lot of the MANY PHYSICIANS and SCIENTISTS who are looking into this from the outside of the conditioned culture of denial in pediatrics know that getting the scientific hard evidence of these effects in humans becomes an ethical tight rope in some instances and frankly unethical in many other faster scientific approaches to prove this point. As I have addressed before . . . thimerosal is too dangerous to get past an IRB for re-entry into the vaccine schedule and yet there is this major inconsistency that it keeps showing up in flushots dosed to 6 months olds.

Anyone of any scientific grit who looks into all these inconsistencies on their own, as I have-not relying on the media spin the pharma-induced conditioning of MDs sees the inconsistencies and you have to question them.

Our society cannot trust the PHaRMA influenced weak science of epidemiology. It is a HORRIBLE NEGATIVE PREDICTOR OF HARM IN SMALL SUBSETS OF GENETICALLY AT-RISK INDIVIDUALS. They won't be found to protect the hand that feeds the researchers, that is the ART of EPIDEMIOLOGY. Some ethical pathways to showing the rate of all iatrogenesis related to vaccines are listed on some of my other posts here-simple prospective and fairly large protocol comparisons. This will actually give us an idea of how many people should be through vaccine court now and every year as fallen soldiers in the war on disease-its not just kids either. Look at the MS-Hep B connection which French Courts have recognized.

Read Simpsonwood, and do a "Show Me" state favor, publish on this blog who you are what you do.

Of course you could remain anonymous as nearly everyone else has and continue to ask good questions that reveal your bias and allow me to continue to educate Missouri State legislators, journalists, parents and many others on this issue which is the most complex issue facing medicine-a big part of why we all haven't figured this out for so long. (I KNOW ANB A RUN_ON SENTENCE, STARING THE THROW THEM IN THERE FOR YOUR PETTY GLEE).


Back to some genetic-toxin interactions, see below . . . notice the MESH headings the concordance of toxin-induced effects in a genetic subpopulation that can't handle them . . . see the sulfation pathway again in the at risk population of a terrible chronic disease that I might add seems to be more prevalent, just better diagnosis?

1: Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144(7):885-90.
Genetic susceptibility to environmental toxicants in ALS.
Morahan JM, Yu B, Trent RJ, Pamphlett R.
The Stacey MND Laboratory, Department of Pathology, The University of Sydney,
Sydney, New South Wales 2006, Australia.
Environmental toxicants such as heavy metals, pesticides, and chemicals appear to
be risk factors for sporadic amyotrophic lateral sclerosis (SALS). An impaired
ability to break down these toxicants because of differences in detoxification
genes could underlie some cases of this disease. We therefore examined the
frequencies of single nucleotide polymorphisms (SNPs) in 186 SALS patients and
186 controls at the allele, genotype, and haplotype levels for the
metallothionein (MT) family of genes, metal transcription factor-1 (MTF-1), and
glutathione synthetase (GSS). Exposure to heavy metals, solvents/chemicals, and
pesticides/herbicides was assessed by questionnaire, and gene-toxicant
interactions were analyzed. An intronic SNP upstream of MT-Ie differed in SALS
patients and controls at the allele and genotype levels. Haplotypes covering MT-I
isoforms also differed between the two groups. Alleles and genotypes of one MTF-1
SNP differed in female SALS patients. One GSS haplotype interacted with both
metals and solvents/chemicals to increase the risk of the disease. Differences in
genes involved in handling toxicants, and interactions between toxicants and
these genes, appear to be present in some patients with SALS. This suggests that
impaired detoxification mechanisms play a role in SALS. (c) 2007 Wiley-Liss, Inc.
Publication Types:
Research Support, Non-U.S. Gov't
Mesh Terms:
Aged
Alleles
Amyotrophic Lateral Sclerosis/genetics*
Case-Control Studies
DNA-Binding Proteins/genetics
Female
Genetic Predisposition to Disease*
Genotype
Glutathione Synthase/genetics
Haplotypes
Hazardous Substances/toxicity*
Humans
Male
Metallothionein/genetics
Middle Aged
Polymorphism, Single Nucleotide
Protein Isoforms/genetics
Risk Factors
Transcription Factors/genetics
Substances:
DNA-Binding Proteins
Hazardous Substances
Protein Isoforms
Transcription Factors
transcription factor MTF-1
Metallothionein
Glutathione Synthase
PMID: 17503480 [PubMed - indexed for MEDLINE]


ENVIRONMENTAL DISEASE IS HUSHED IN US MEDICINE FOR CORPORATE PROTECTION, NOW WE ARE DEALING WITH THE LAST GREAT AMERICAN INDUSTRY AND ITS ENVIRONMENTAL ACHILLES HEEL-AUTISM.

EFFIIIMD

MBq said...

GENXRAD said..."You are missing the point again, toxicologic biological effects are only dependent on dosage in a genetically identical population....."

That's true but LD50 values are meant as a median. I think we might agree that there has to be a dose that is never lethal and there is also a dose that would always be lethal to 100% of the animals.

To apply your logic, there would have to be a dose of thimerosal that would never cause autism, just as there would have to be a dose that would cause anyone to become autistic. Would you agree?

"TOXICOLOGIC EFFECTS ARE ALSO VARIABLE ACROSS THE DEVELOPMENTAL SPECTRUM-HERES ONE FOR XRAYS"

Right again. Since many women undergo routine mammograms, does that mean screening for breast cancer is actually causing it in some cases and why should I trust this instance of PHaRMA influenced weak science of epidemiology.

GENXRAD said...

MBQ:
Right again, breast cancer screening is causing genetic errors in women who are BRCA carriers (BRCA genes encode for DNA repair) and 20 years of fairly unhelpful mammograms in very dense tissued women are associated with increased rates of breast cancer in this population. But again no one in radiology and inparticular the ivory towers of breast imaging is gonna admit that. But its clear in many correlations of basic science-genetics and clinical medicine/radiology correlations with epidemiology. This is what visionary thinkers in medicine understand before the epidemiology is done or gets avoided for political and economic reasons.

SEE ABSTRACT:
1: N Engl J Med. 2007 Jan 18;356(3):227-36.

Comment in:
N Engl J Med. 2007 Jan 18;356(3):297-300. N Engl J Med. 2007 May 3;356(18):1885-7; author reply 1885-7. N Engl J Med. 2007 May 3;356(18):1885-7; author reply 1885-7. N Engl J Med. 2007 May 3;356(18):1885-7; author reply 1885-7. N Engl J Med. 2007 May 3;356(18):1885-7; author reply 1885-7.

Mammographic density and the risk and detection of breast cancer.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G,
Chiarelli A, Minkin S, Yaffe MJ.

Campbell Family Institute for Breast Cancer Research, Toronto, ON, Canada.
boyd@uhnres.utoronto.ca

BACKGROUND: Extensive mammographic density is associated with an increased risk
of breast cancer and makes the detection of cancer by mammography difficult, but
the influence of density on risk according to method of cancer detection is
unknown. METHODS: We carried out three nested case-control studies in screened
populations with 1112 matched case-control pairs. We examined the association of
the measured percentage of density in the baseline mammogram with risk of breast
cancer, according to method of cancer detection, time since the initiation of
screening, and age. RESULTS: As compared with women with density in less than 10%
of the mammogram, women with density in 75% or more had an increased risk of
breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4),
whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than
12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8
to 65.9). Increased risk of breast cancer, whether detected by screening or other
means, persisted for at least 8 years after study entry and was greater in
younger than in older women. For women younger than the median age of 56 years,
26% of all breast cancers and 50% of cancers detected less than 12 months after a
negative screening test were attributable to density in 50% or more of the
mammogram. CONCLUSIONS: Extensive mammographic density is strongly associated
with the risk of breast cancer detected by screening or between screening tests.
A substantial fraction of breast cancers can be attributed to this risk factor.
Copyright 2007 Massachusetts Medical Society.

Publication Types:
Research Support, Non-U.S. Gov't

Mesh Terms:
Adult
Aged
Breast/pathology
Breast Neoplasms/epidemiology
Breast Neoplasms/pathology
Breast Neoplasms/radiography*
Case-Control Studies
Female
Humans
Image Processing, Computer-Assisted
Mammography*
Middle Aged
Risk

PMID: 17229950 [PubMed - indexed for MEDLINE]

The dense-mammogram-BRCA population of women needs to have the ALARA principle adovacted towards screening which is the principle of the lowest dose to gather the greatest diagnostic information (non-inoizing radiation or a lower dose radiation imging technique). The problem here is also one of economics at a cross roads with public policy and individual care decisions. So I would strongly encourage any BRCA carriers to investigate with their primary care physicians the utility of less harmful modalities for screening. Breast MRI in high risk women is already getting a screening consensus push from major medical societies and policy people but the cost is prohibitive for the insurance industry, so it is resisted. Also, we must include the other radiation insults to the breasts as a consideration of the rate of radiation induced cancer in this selected population-just like Dr. Miles should have considered all thimerosal exposures through childhood instead of just the pre-natal dose associated with rhogam before coming to the false conclusion that her small study was really exonerating the realtionship between vaccines and autism (again another leap of logic-she didn't look at all vaccines exposures).

As for the LD50 discussion you are also dealing with lab rats that don't have other concurrent heavy metal exposures from fish, lead paint, etc which are pre-loading these kids for a fall with injected metals (the act of injection bypassing some of the potential gut barrier protections on metal absorption as well as metabolism through the liver before entering the bloodstream.

We had a case last year of a 9 year old girl who had a flushot contianing thimerosal and had a siezure within a minute of the dose. I then got paid to read her $1500 MIR and she had a neuorlogy consult and then an EEG so how much was that dose? Simple thing would have been to just giver her some flumist and avoid the mercury exposure or any other exposure that may have related to an injectable substance. Immunizing the mucosal surfaces of the upper respiratory system directly sure seems like a much better idea. Now that young child has the fear and documentation of a seizure event for life. The pediatrician who is agreat friend of mine, has started to change his practice and thinking because of all I have educated him. Flumist is a simple alternative for those patients who want to use their capital forces in avoiding injectable thimerosal for flu coverage-why is the culture so afraid to change on that idea? CONDITIONING.

Apparently you haven't read enough of my posts, as the growing number of people reading this debate may already see that my logic would not apply to the idea that there is an absolute safe dose of thimerosal for 100% of the populace. It is rather the reverse; that is, a population of superconjugators of mercury exists in large numbers for which high doses of thimerosal are completely fine (go back to the paper on thimerosal and GST kinetics-did you actually read the abstract even?). Lets look again:

Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.
Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.
Müller M, Westphal G, Vesper A, Bünger J, Hallier E.
Department of Occupational and Social Medicine, Georg-August-University Göttingen, D-37073 Göttingen, Germany. mmuelle3@gwdg.de

We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.


Though this paper actually insinuates that even super conjugators may have a developing problem with successive doses, I won't lean on for this arguement as there are clearly other detoxification systems that will help in the super-detoxifiers and the even poor detoxifiers in this pathway among our children that exist in a an increasingly metal polluted world by simple Darwinian selection.

So it is the pre-loading of toxins by many other industries even that is intensifying the effect of adjuvants (aluminum in addition to mercury) in vaccines in kids who are slow metal detoxifiers. Again-maybe we should have vaccine manufactures start helping the field of envrionmental medicine in understanding the risks of complication of vaccinations in those children pre-loaded at birth with higher metlas levels than would be present in past gereations on this planet; have the CDC go after the poluters in Brick Township and other autism hotspots to defend their vaccine program (oh but they failed us on that too now haven't they). The bioaccumulation of heavy metals in other species over time is clearly documented and this syndrome is a product of industrialization with punctuated effects delivered by vaccines which in the case of many like my son who also has significant environmental lead exposures get unequal scrutiny to other expusres because they are coming at the hand of physicians rather than coal miners.

Before you go asking about my son and his lead issues and trying to deflect the vaccine debate here you would need to know that he has a female twin who has had virtually all of the sme envrionmental exposures. So I know you are going to say see-its genetic. It is rather the most complex epigenetic-gender influenced developmentally impacted problem ever, and the smartest in medcine know whats going on or can figure it out just by paying attention to the works of many now who are figuring this out all over the place outside of the last wall of defenders in the establishment who won't say "forgive" us because we didn't have enough understanding 10 years ago on this to see what was really happening AND WE DON'T WANT A LITIGATION CRISIS that leads us to no line of defense for a bioterrror strike (I actually agree that these are critical counters, but as I have posted all of this blog there is a better way to do all of this, come on BB King can check his glucose with a tiny finger prick and the brainiacs in immunology can't get a titer check done easier than a ful lab draw?). I realize its probably 'cause no one else ever thought of it. Its one of those "duh" ideas that comes out of the Plains states all the time. In the meantime we in North Dakota wil be pursuing some research on titer checks for the concerned parents who would rather subject their kids to a blood draw and have been screened as coming from families at higher risk for autoimmune disease and neuropsychiatric problems. Now that I think about it, maybe it is such a terrible thing to start an IV for nuclear scinitigraphy studies that this risk far outweighs the Tin dose so we should avoid DMSA-Renal scans for that sole reason, wonder what BILLINMIDMO and Kathleen Siedel think? I don't hear screaming too often because we have great nurses in ND who are grosssly underpaid by comparison to Missouri and the rest of the nation.

But, alas I digress. Sure there is a dose of thimerosal that would never cause autism in superconjugators, and WE JUST DON'T KNOW WHO CAN'T HANDLE EVEN THE TINIEST AMOUNT OF THIS SUBSTANCE BECAUSE TESTING THE THEORY ON HUMANS IS A REPETITION OF TUSKEEGEE!!!
Maybe Adam Weinmaster is the unique genetic individual who can even handle microgram.

(Although I have this so wrapped up I could clearly prove thimerosal induced autism by a sacrifice of a few 100 unfortunate kids to autism and hope Bryan Jepson, MD can pull them out or those guys ot at SUNY Buffalo in PEDIATRICS who are chelating kids.)

Genetic variation at some level is completely infinite outside of identical twins and even identical twins can be spurred to epigenetic difference with the right exposures (cancer is an epigenetic disease that affects identical twins differently). So again one person's dose of a tiny exposure may cause disease that another can handle 10 times greater quantity.


BIG PICTURE HERE MBQ-WE CAN COVER ALOT MORE KIDS ON VACCINES BY IMPROVING THE FAILING CONFIDENCE BY FOLLOWING ME LEAD ALL OVER THIS BLOG AND BY VACCINATING SMARTER, AVOIDING THIMEROSAL AND SELECTING OUT THE WEAK CONJUGATORS BY ADVANCING THE SCIENCE TOWARDS THESE GOALS ASAP.

By the way, what is your name-what do you do for a living and why are you so interested in this debate that ANB says no one is paying attention to anymore?

Fogarty

MBq said...

GENXRAD says..."But, alas I digress. Sure there is a dose of thimerosal that would never cause autism in superconjugators, and WE JUST DON'T KNOW WHO CAN'T HANDLE EVEN THE TINIEST AMOUNT OF THIS SUBSTANCE BECAUSE TESTING THE THEORY ON HUMANS IS A REPETITION OF TUSKEEGEE!!!"

It probably isn't necessary to invoke Tuskegee here, but at least we are getting somewhere on the issue of toxic thresholds. OK, so you may not know the dose that would never cause autism, but let's assume, for the purposes of discussion, that it is somewhere between a single molecule and the levels found in a vaccine.

If we are to assume that thimerosal can ever cause autism then we must also assume that there are upper and lower limits to exposure, true?

So taking in to account genetic variability in a heterogeneous population, would it be reasonable to assume that a less genetically prone individual would become autistic at some exposure below a lethal dose?

In humans of any age or genetic makeup, mercury will reliably cause the symptoms of mercury poisoning if exposure is high enough. It stands to reason that the same would apply if mercury can ever induce autism. Would you expect that level to be 2x, 5x, 10x, 100x the level where autism first appears?

FOGARTY said...

MBQ: Those are some excellent points purely toxicologically speaking, and from a single variable point of view without real consideration of genetics and the real world of course.

I'll forgive you for failing to really address multiple points on this thread and allow you to walk around the issues you don't want to address-because they clearly indicate a problem. Lets hope KOMU keeps it up for years so as to show your anonymous and less credible role in this debate. People with real character and grit in life reveal much more in this type of forum, so I encourage you to do so in order for all those reading now and in the future to have a better idea of the background you have, as clearly your questions are not "lay" public in nature.

It probably isn't necessary to invoke Tuskegee here, but at least we are getting somewhere on the issue of toxic thresholds. OK, so you may not know the dose that would never cause autism, but let's assume, for the purposes of discussion, that it is somewhere between a single molecule and the levels found in a vaccine.
Sounds reasonable.

So taking in to account genetic variability in a heterogeneous population, would it be reasonable to assume that a less genetically prone individual would become autistic at some exposure below a lethal dose?
Of course, but I am clarifying the interpretation of your point here-a less genetically prone individual would mean the type of child that would not be likely to become autistic at current or 1990's levels of thimerosal administration. Therefore I assume you are saying lets take the NT kid and guess how much mercury it would take to make him autistic.

Few more points of clarity here, please realize regressive autism is really a three armed beast with a hundred criss-crossing fingers/pathways in to the autistic syndrome so, there are other cases that have less to do with thimerosal but rather autoimmune induction by other components of vaccines or viruses such as those in vaccines which in the past also caused autism in a much more severe form and non-vaccine related viruses as impacting this are not getting enough attention whose checking on West Nile or some new as of yet undiscovered virus that may be causative in say 20-30%? You should check out my post on the history of vet vaccines in mucousal disease which is caused by a viral agent from the same family as rubella and is clearly an interesting observation from veternary science on the persistence of non-cytopathic viruses from vaccines in a population and the resulting problems in subsequent generations of the vaccinated populace). Remember too that the whole CDC schedule is a metavariable that keeps changing which needs controlled prospective studies to really track the rates of all iatrogenesis related to it for Vaccine Court to really understand how many fallen soldiers on the war against disease should be getting their CDC pension as per the implicit social contract for vaccination that never gets honored in the individual walking wounded as the Weinmasters have experienced. Also, vaccines are not just problematic in children as the French Courts have ruled Hep B as causative in MS in quite a few.

Back to your questions:
In humans of any age or genetic makeup, mercury will reliably cause the symptoms of mercury poisoning if exposure is high enough. It stands to reason that the same would apply if mercury can ever induce autism. Would you expect that level to be 2x, 5x, 10x, 100x the level where autism first appears?
This is an unclear question at some level since there is no indication of indexing toxicologic effects as relates to age, developmental sensitivities can change across very short time periods at the start of life in particular. For example from medical imaging, you really don't want to risk iodinated contrast in a fetus developing its thyroid unless a mother might die of trauma if you don't do an enhanced CT. When you are dealing with implicit half-life considerations that we can't really ethically get at in humans on metal retention you start to lose the understanding of the logrithmic scale here. In super detoxifiers who have a half life of thimerosal that is 7-8 days versus a a variable population of kids where it could range from 50 to 500 days things are not linear. Remember also that thimerosal in this population is likely driving an endophenotypic worsening of the population kinetics just by looking at the abstracts I have pasted into this thread above (did you really read those yet?). So the answer to your question is this, since autism is a childhood developmental syndrome that is based on metal toxicities which are even variable in kids with normal detoxification kinetics as a variable of weight we would have to substratify the dose-risk to multiple ages; in utero, at day one, at one month, at 3 months etc. So the math is getting too complex to actually allow me to comitt to a one point index of 2x or 4x or 8x etc. This is calculus not arithmetic MBQ and the only way to protect the at risk is to find them and cover them with an environmental hygeine protocol that includes a heavy metal "sterile" environment. That still won't prevent some of the cases of non-cytopathic viral origin but empirical pharmacologic therapy of anti-vrials could clear those cases.

Pure toxicologic discussion here is missing the point and we can all quibble about association versus causation for legal reasons (and the problems with Daubert as relates to science law which is something else I will address on this blog). Maybe we should also start to discuss the impact of aluminum on the toxicology of mercury as dosed in vaccines and as relates to autism (some others have alluded to this in other posts).

In a grayscale world of many concurrent exposures in a population that cannot handle multiple exposures of various agents from organics to metals because of this very critical deficit of central detoxification pathways, we can not look at the problem top down as you are but must approach it bottom up as I am. So starting with the fact that the history of medicine has failed to until now to really take into account that there is a keystone symphonic orchestration of pathways needed for appropriate detoxification of metals and organics that is corrupted or slowed in variable fashion in a small population, all bets go off from the traditional approach to toxicology. Again, as illustrated all over this blog I have put the problem into the appropriate perspective-a continued approach to finding more and more genes associated with environmental disease will continue to show these biochemical pathways meandering across this neuropsychiatric syndrome. We must FUNCTIONALLY screen and protect rather than just sit on our hands saying we can't figure this out-I mean hey, I am just some dummy in the middle of nowhere that has figured this out right? If one is a committed physician paying attention to and investigating all nuances of this it is possible to eventually get this, even some of those at Mayo or Harvard will get this eventually. Further if the MDs that keep denying this can't stand up to little old Dr. Engley or Dr. Haley or those both inside and outside of pediatrics who know what is going in a public forum for an honest debate the you know they are just hiding behind weak epidemiology to protect their turf, pride, sense of medical righteousness or whatever you want to call it. Debate is nowhere more abhorred in all professional societies than medicine, its a very authoritarian, close-minded culture that mimics the military. Surgeon General can't debate a little rogue captain out on the plains about educating the public of the adverse events rate of the entire current CDC schedule because there are no prospective studies of protocol iatrogenesis rates in vaccine science. Simple fall back to 1970's protocol comparison in a state like ND which has great vaccination rates within a small subset of the population that by family history would be at risk will take time for statistical significance (I can wait) but would be really easy to do and now that this little prairie state has the proximity of collegiality working for me, people are starting to think the freaky geek Fogarty might just be on to something here.

As a physician, if you begin to identify that there is a population of people that are showing up with a range outside of the norm of increased heavy metal half-lives you then move to find those people (children in this instance) and help them avoid the exposure which is what happens in medicine reluctantly in all sorts of areas. Malignant hyperthermia is a great example, heard of it? Do you know toxicologically speaking why millions of doses of anesthetic can be given without any problems but have a wicked consequence in the at risk population? Further, if the best way to really treat that issue is not mainstream because pharmaceuticals don't general bypass bottle neck but create them, then you start to drop your pride as an MD for all the bad mouthing of the complementary approaches and start to advocate it.

MBQ go back and study some more genetics, because the problem with some of your questions is that they are the ones that should have been asked about thimerosal in the 1930's and then in the 1940's and then in the 1950's and then in the 1960's and in the 70's and in the dermatologic literature in the 1980's this was addressed and in the ophthalmologic literature the advocacy to take it out was further addressed late but in the 1990's and then in 1999 the AAP said get it out of vaccines but the slippery slope keeps getting wetter now doesn't it?

Back to how vaccines, not just thimerosal are creating problems as we look at the aluminum effect:

1: Neuromolecular Med. 2007;9(1):83-100.

Aluminum adjuvant linked to gulf war illness induces motor neuron death in mice.

Petrik MS, Wong MC, Tabata RC, Garry RF, Shaw CA.

Department of Ophthalmology and Program in Neuroscience, University of British
Columbia, Vancouver, British Columbia, Canada.

Gulf War illness (GWI) affects a significant percentage of veterans of the 1991
conflict, but its origin remains unknown. Associated with some cases of GWI are
increased incidences of amyotrophic lateral sclerosis and other neurological
disorders. Whereas many environmental factors have been linked to GWI, the role
of the anthrax vaccine has come under increasing scrutiny. Among the vaccine's
potentially toxic components are the adjuvants aluminum hydroxide and squalene.
To examine whether these compounds might contribute to neuronal deficits
associated with GWI, an animal model for examining the potential neurological
impact of aluminum hydroxide, squalene, or aluminum hydroxide combined with
squalene was developed. Young, male colony CD-1 mice were injected with the
adjuvants at doses equivalent to those given to US military service personnel.
All mice were subjected to a battery of motor and cognitive-behavioral tests over
a 6-mo period postinjections. Following sacrifice, central nervous system tissues
were examined using immunohistochemistry for evidence of inflammation and cell
death. Behavioral testing showed motor deficits in the aluminum treatment group
that expressed as a progressive decrease in strength measured by the wire-mesh
hang test (final deficit at 24 wk; about 50%). Significant cognitive deficits in
water-maze learning were observed in the combined aluminum and squalene group
(4.3 errors per trial) compared with the controls (0.2 errors per trial) after 20
wk. Apoptotic neurons were identified in aluminum-injected animals that showed
significantly increased activated caspase-3 labeling in lumbar spinal cord (255%)
and primary motor cortex (192%) compared with the controls. Aluminum-treated
groups also showed significant motor neuron loss (35%) and increased numbers of
astrocytes (350%) in the lumbar spinal cord. The findings suggest a possible role
for the aluminum adjuvant in some neurological features associated with GWI and
possibly an additional role for the combination of adjuvants.

PMID: 17114826 [PubMed - in process]

Really love that one since this much of this crisis has been brokered on policies relating to biological terrorism and the real need for legal protectionism-why can't people just admit we have a double edged sword in vaccines which have great benefits and also severe consequences for the unfortunate few who's genetics or autoimmune friendly-fire events are impacting their reactions to them?

PS: Did you read that abstract from Adams at ASU? Seems that baby teeth are the biomarkers of heavy metal half-life elevation that you seem to have tried to discount, recall your statement>>>

MBQ said:
The nuances haven't been ignored, your assertions are nothing more than assertions. I'm sure you can find a study or two from J.James and Marvin Boris to add substance to your claim but as of this moment, autistic children are not known to possess combinations of SNPs associated with an inability to handle heavy metals.
In fact that Adams-ASU CHEMISTRY DEPARTMENT one is down right damning against autistic children having a particularly specific problem with mercury handling as reflected in the concentrations in their collected baby teeth. So, although much Hg may be from non-vaccine sources how can anyone advocate continued mercurials in this population.
YOU CAN'T UNLESS YOU ARE AN IDIOT OR YOUR JOB DEPENDS ON IT.