Merck to Fund Fellowship to Groom "Vaccine Experts" At American Academy of Family Practitioners
Lee Silsby Announces HBOT Prep Formula

"We Need To Learn Where Toxins Impact Gene Expression to Find the Cause of Autism."

Brain gut By David Kirby

A new study written up in Science Daily (Mar. 2, 2009) and elsewhere says that researchers at the University of Southern California (USC) and Vanderbilt University have “identified a specific gene variant that links increased genetic risk for autism with gastrointestinal (GI) conditions.”

So far, reporting on the study, to be published in Pediatrics, has suggested that a polymorphism in the Met gene has been identified which, by itself, may explain both brain abnormalities and GI disturbances in children with autism spectrum disorder.

But there may be more to this story than that relatively simple explanation. Is it possible that these genetic variations produce susceptibilities to other environmental triggers, such as toxins? According to one of the lead authors of the paper, Patrick Levitt, PhD, autism cannot be explained by genetic factors alone.

Dr. Levitt made this comment when presenting his findings at the Neuroscience and Nervous System Disorders 2007 workshop on “Autism and the Environment - Challenges and Opportunities for Research,” of the Institute of Medicine.

(Please see: (HERE))

I hope everyone will look at these excerpts and read the full remarks (both are below) before drawing conclusions about these very significant findings.


1) Environmental factors “must” play a role in ASDs

“Gene–environment interaction is one of the unique properties of the brain. So, of course, regarding ASD, it is not genetic versus environmental, irrespective of whether you think there is a principal cause that is genetic or environmental. Because ASDs have at their core disrupted brain development, in terms of etiology, both genetic and environmental influences must play roles because this is in the basis for brain development.”

2) The Met gene is important for normal nerve and myelin development in the brain:

“It turns out that this gene is expressed in the brain during development and is important for a number of different processes, including cell migration, development of excitatory and inhibitory neurons, synapse formation, and myelination.”

3) The Met gene is also important for proper GI and immune function:

“Met is also involved in gastrointestinal repair, in immune response regulation, and some other peripheral functions that are consistent with the co-occurring medical issues that are described clinically for individuals with ASD.”

4) But manipulation of Met gene expression in animal models can change brain architecture and cause ASD behaviors

“We were studying Met in an animal model. The brain architecture changes we found when we manipulated levels of Met expression, together with long-term changes behaviorally, paralleled changes in ASD.”

5) Gene expression is controlled by transcription factors (proteins)

“Transcription factors are proteins that control how much of a gene is turned on in specific locations and at any particular time during development.”

6) Transcription factors in ASD-associated MET variants are disrupted by several toxins

It turns out that the transcription factor impacted by the ASD-associated variant in Met is SP1, which happens to be a transcription factor whose binding to DNA is disrupted by a number of environmental toxins

7) We need to learn where toxins impact gene expression in order to find the cause of autism

“Finally, if we are going to understand functional etiology of ASD, if we are trying to identify the genes that underlie risk, and we are searching for environmental factors that cause changes in brain development, we need to know where these candidate genes are expressed in the developing human brain, and where these environmental factors have their impact.”

Finally, in 2006, Dr. Levitt was quoted speaking about the same research. Noting that.
‘This variant is in the part of the gene that controls how much of the gene gets expressed…kind of like ‘volume control’ on a stereo.” He noted that people with two copies of the variant were 2.27 times more at risk for autism than the general population. People with just  one copy were also at higher risk (1.67 times). “This is a relatively common variant, seen in about 47 percent of the population,” Levitt said. “So why doesn’t everybody have autism?” Because of environmental and other genetic contributions, he said. “Genes create a vulnerability that then gets coupled with some environmental disturbance — but right now, we don’t have any idea what those factors might be.”

Challenges and Opportunities for Research
WORKSHOP PROCEEDINGS - Board on Health Sciences Policy


Dr. Patrick Levitt

Dr. Levitt: I am going to provide for you a neurobiologist perspective on where we are in terms of genetics and what some of the opportunities are in terms of genetics and designing the kinds of research we might be doing to understand gene–environment interactions. The first slide basically depicts the fact that we all understand—complex genetic disorders are complex.

Complex genetic disorders are complex and what we are trying to understand are the combination of risk alleles, variations in gene sequences or in copy number of specific genes which, in combination, end up underlying risk or, in fact, directly perturb brain development that ends up generating the three core symptoms that are diagnostic of autism spectrum disorders.

You can see in the diagram that for any disorder, a combination of risk alleles may be correct, but there may be an intermediate phenotype rather than the features of the full disorder. We know that of the three major core symptoms that are used for an autism diagnosis, dysfunction in any one of these domains can run in families. There have been large twin studies to look at heritability independent of the autism diagnosis itself.

The diagram also shows that the correct combination of risk alleles might require specific environmental factors in order for the full-blown disorder to be expressed. There also are issues of incomplete penetrance where you may have the correct combination of genetic risk, but for reasons unknown, an individual has modifier factors that reduce the impact of the risk alleles. This means that one does not express the disorder.

So, I want you to keep something in mind. I take this from Daniel Weinberger, who studies schizophrenia at the NIMH and he makes this point, I think, very well. Genes are involved in the assembly of specialized cells to perform specific functions. Thus, there are no “social behavior” or “communication” genes. If we are looking for those, you might as well stop now because they don’t exist. Genes don’t know about social behavior. They don’t know about communication. What they know about are assembling tissues and cells to perform specific functions, and when there are mutations or changes in the sequence of those genes that affect function or expression levels, or differences in the copy number of those genes, we see alterations in the assembly of cells and the specific functions that they underlie.

So, what do we know from a genetics perspective? Well, there have been three approaches used: (1) linkage studies that look for excess sharing of genomic regions on chromosomes that track with the disease; (2) allelic association studies, where we look for excess sharing of alleles; this is accomplished by studying single nucleotide polymerphisms (SNPs), in which a single nucleotide is changed, or differences in microsatellite sequences at a single locus; and (3) a defined copy number variation (CNV), where we look for submicroscopic changes (thousands of bases, rather than macroscopically identified millions). CNVs thus are not obvious changes, such as chromosomal rearrangements, but submicroscopic changes that alter chromosome structure, which could be either deletions or duplications. Keep in mind that most of the chromosome is not occupied by sequences of bases that encode the transcript that will be translated into protein, but rather encode regions whose functions we really don’t understand, but we think may be involved in regulation of gene expression.

I want to mention here some of the previous and current caveats to what we know in terms of ASD and genetics. You need to keep these in mind as you read genetic studies to determine the degree to which you can rely on the findings and conclusions. First, there may and are likely ascertainment biases. This means that the subject population that has
been studied genetically may not necessarily be broadly representative, or perhaps they are broadly represented, but they represent one small domain of the spectrum. Second, until recently the sample sizes used in studies typically were small and underpowered.

Why is this a problem? Well, as my friend, Ted Slotkin, tells me, if you do enough comparisons, you will find something. For genetics, this means that if you try to find an association between many different SNPs and a disorder, eventually you will identify some relationship statistically—but one needs to correct for what we call Type 1 error, that is, false-positive results. There are debates regarding the best ways to correct, and many earlier studies may not have corrected at all, leaving us with nonreplicable findings.

Third, the accuracy and completeness of the diagnosis and characterization of the phenotypes are essential to understand who you are studying in terms of a cohort to be used in a genetic study. If this is not done at a high standard, an already heterogeneous disorder like autism becomes even more difficult to study genetically because the study population may be diluted with poorly defined subjects. Fourth, in the past there have been issues with technical quality control; that is, the quality of the assays used to identify SNPs and other changes. This is becoming a nonissue as technology advances.

 Finally, and perhaps most important, there is for the most part a lack of assigned gene/variant function, in which the polymorphism does something to gene expression or gene function. Keep in mind that this concern comes from a biologist. One may identify a variant associated with autism, but if it is not a coding variation that would clearly change the coding of an amino acid, what does it do? You are stuck with that finding in terms of translating that to a biological substrate for the brain changes that may underlie the disorder.

So, what do we know about linkage? Well, the most recent autism genome project consortium identified a modest signal on chromosome 11p, and this is being followed up. In addition, by doing some data filtering, a few other loci seen in previous studies were seen, including regions on 2q and 7q. From previous work, there are in the literature dozens of other reports of linkage, but the bottom line is that with disease heterogeneity, as we have seen in schizophrenia, for example, and other disorders, the linkage signals are generally relatively small and there may be difficulty in replication from study to study. This is telling us something about the disorder, that there is locus heterogeneity. Thus, there are likely to be many different genes or combinations of risk alleles
 that may underlie ASD.

Regarding CNV, there has been a lot of discussion over the last month about two studies, the AGP (Autism Genome Project) study and a study out of the Cold Spring Harbor group, essentially identifying somewhere between 8 and 10 percent of the individuals in their study having CNVs. The findings are exciting, as CNVs have been implicated in other disorders (e.g., certain cancers), but the findings are not without issues. There is no overlap in terms of chromosomal sites, as far as I could tell, between what was found in the Cold Spring Harbor study and in the AGP study and one does not know the biological significance yet. We are going to talk about that later perhaps, I think, in terms of what CNV might contribute to this disorder.

Regarding rare mutations, we know that there are loss of function mutations that have been identified in a single individual that was part of a genetic study, or even in individual families in which there is an autism diagnosis. I have listed some of those genes up there. The reason I list those is because it turns out that a number of those mutations are found in genes that at least biologically have some things in common; they are involved in synapse formation and function. Keep in mind, however, that rare mutations generally do not translate into genetic variations across large segments of the affected population. They are important in trying to understand the genetic contribution to the neurobiological disruptions.

Genetic syndromes with co-occurring ASD diagnosis have often been overlooked in the past. My friend Art Beaudet talks about these all the time. Disorders such as Fragile X, Rett, Angelman, and Timothy have a relatively high prevalence of co-occurring autism diagnosis. In addition, there are some common themes in terms of the neurobiological changes known to occur in each of these disorders, related to the changes in neural development. Keep in mind that genetically the causes are quite distinct from each other, but the high co-occurrence suggests that there may be many genetic routes to impact negatively the three core functions used to diagnose ASD.

The literature is also replete with reports of association of common risk alleles with ASD; that is, gene variants have been identified from standard association studies that give us some clues regarding the impact of common variants on genetic risk. I have listed some of those on this slide: (1) nonfunctional risk alleles, meaning that there has been a change in the sequence of the gene, but we don’t know what that sequence change means. I have listed some of those genes up there. The neurexins, the GABA beta 3 subunits and Gral-2 and some risk alleles that have been identified, but not necessarily replicated in every study; and (2) functional risk alleles, that is, variants that have been identified that either change the function of the gene product or change how much of the gene product is actually produced. The promoter region of the reelin gene is one example, and I have placed a red circle around Met, a finding from my laboratory that I will tell you about in a moment.

I have posed some questions related to the influence of genetics on autism expression that might also be retitled “Gaps in Knowledge” (1) How much of genetic risk is due to direct impact of mutations on brain development? (2) How much of what we are talking about in terms of genetic influence is actually the combination of genetic mutations changing the trajectory or course of neural development in wiring the brain up? (3) How much of the risk is due to direct impact of mutations on peripheral functions, that is, other organ systems that influence brain development? I raise this as a possibility because we know that peripheral organ development and brain development are linked physiologically. (4) How much of the risk is due to genetically established sensitivities to environmental perturbations? We know this exists experimentally, but we really don’t understand it in the clinical population. (5) How much of the phenotypic heterogeneity of individuals with ASD are influenced combinatorially through genetic and environmental factors? That can be viewed as my red herring question.

So, here is my concept of where we are with understanding autism brain pathophysiology. I am being facetious, but that is a thimble in case you didn’t recognize that blurry image. In essence, we know very little about the changes in brain development and brain organization that underlie ASD. That is a real problem in trying to understand the causes. Genes, environment, or both? How can you answer any of the questions I posed without knowing what exactly is disrupted in terms of brain architecture and development? Part of the problem, in my opinion, has been that the gene–environment debate has been held in isolated silos, that is, separated disciplines in which there is rare exchange of ideas. The silos, or disciplines, need to interconnect. This harkens back, and we talked about it on the conference call among presenters, to when developmental neurobiologists spent an enormous amount of time trashing each others’ work because one was either in the “nature school” or the “nurture school” regarding brain development. Of course, that was silly because we know that the brain is built through a genetic blueprint that takes information from the outside world and utilizes it to direct the developmental course to wire up circuits. This gene–environment interaction is one of the unique properties of the brain. So, of course, regarding ASD, it is not genetic versus environmental, irrespective of whether you think there is a principal cause that is genetic or environmental. Because ASDs have at their core disrupted brain development, in terms of etiology, both genetic and environmental influences must play roles because this is in the basis for brain development.

So, here is a concept regarding what we might do to address mechanisms: Translational approaches that incorporate multiple technical strategies. There are a number of different strategies in which we are trying to link these domains experimentally. One approach is to focus on neurodevelopmental genes that have been characterized for altering the assembly of circuits that are likely to be disrupted in individuals who develop autism; it does allow investigators to move freely between animal models in which the biological functions of the genes are studied, and going back and working with human geneticists to try to determine whether there are meaningful relationships that would make sense in terms of variations of that gene that might underlie partial risk for ASD.

One also can begin from human genetic research data and develop model systems that probe biological functions, trying to make sense in terms of what has been identified as a variant associated with the disorder that carries genetic risk. I would suggest that it doesn’t necessarily help to knock out a gene in a mouse if the variant that has been identified in the human genetic research is not a complete null, but rather a variant that alters protein function or levels of gene expression. Genetic knockout studies may generate some very interesting biological findings, but these may not necessarily be relevant to the pathophysiology of ASD. Of course, with model systems, such as genetically engineered mice, you can do experiments. You can manipulate the system both genetically and environmentally at different developmental ages. I have diagrammed an example, in which one can expose genetically manipulated mice to different environmental factors that we know change the course of trajectory and development. The impact of exposure may be influenced by genetic variation and you can design experiments to do this in developing model systems.

So, I just want to highlight for the last minute or two what we have done in our laboratory. There is only one data slide, and it summarizes work published in 2006 in the Proceedings of the National Academy of Sciences.

We took the approach of studying the role of a gene in brain development and then extending these to human genetic studies for several reasons. We were examining the role of a tyrosine receptor, Met, in cerebral cortical development. Met actually has been the focus of thousands of scientific studies because its dysregulation is implicated in certain kinds of cancers. It turns out that this gene is expressed in the brain during development and is important for a number of different processes, including cell migration, development of excitatory and inhibitory neurons, synapse formation, and myelination. We were studying Met in an animal model. The brain architecture changes we found when we manipulated levels of Met expression, together with long-term changes behaviorally, paralleled changes in ASD. We also realized the Met is located under a linkage peak on chromosome 7 in humans, a region implicated multiple times in studies of ASD.

The major finding is that we identified an SNP in the 5′ region of the gene that controls how much of the gene is expressed. We showed experimentally that it reduced how much of the Met gene is expressed, and we believe the mechanism for this is due to the 5′ SNP It turns out that the transcription factor impacted by the ASD-associated variant in Met is SP1, which happens to be a transcription factor whose binding to DNA is disrupted by a number of environmental toxins

Thus, the Met variant that is strongly associated with ASD actually had a functional outcome. It changed how much of the gene was actually produced. Met is involved in brain development, but we also thought more broadly about this when we were debating about doing the human genetics studies. Met is also involved in gastrointestinal repair, in immune response regulation, and some other peripheral functions that are consistent with the co-occurring medical issues that are described clinically for individuals with ASD.
We spent a lot of time with clinicians to talk to them about whether this made sense because it is not a small number of children who have co-occurring medical conditions. Though still unsettled, it may be a relatively large number. These detailed delineations of the population are telling us about disorder etiology and perhaps even the biology as well.

It turns out that the transcription factor impacted by the ASD-associated variant in Met is SP1, which happens to be a transcription factor whose binding to DNA is disrupted by a number of environmental toxins. So, here one can see that the possibility of combining environmental toxin work with this variant in a humanized mouse model, for example, or introducing the humanized mutations in cells, opens up the possibility of studies that examine combined genetic and environmental influences.

So, for one example, we have actually shown that if you expose cells that have either the G or C (ASD-associated) variants of this gene to BaP, which is a common environmental toxin, levels of gene expression are reduced quite dramatically for both the common and ASD-associated variants. Keep in mind that the common SNP (G) results in more than double the amount of gene transcription in the cells than the ASD-associated variant. I’ve added here a hypothetical threshold for when a disorder is expressed. If the toxin reduces levels of Met expression for both the G and C variants, but the C variant starts out lower, the environmental exposure will result in even lower levels of expression that reduce below the threshold. In this example, even with BaP exposure, expression of the gene with the G allele still does not drop below disorder threshold. Thus, BaP does not directly cause the disorder, but has differential effects due to genetic variation.

So, what do we need to do in the future? I’ve listed some suggestions here. We need to increase subject ascertainment, characterizing populations in great detail, which will allow geneticists, psychologists, and neuroscientists to stratify groups more accurately to determine if certain phenotypes are associated with specific genetic variants, including SNPs, CNVs, and other genetic changes. Given that we all agree that we need to be very careful about how we phenotype in doing the genetic studies, it simply doesn’t make sense to start out with a cohort of 1,000, because by the time you stratify based in different characteristics of ASD, or even life history, the study will be underpowered.
Deep sequencing to identify more functional variants will be important to pursue. If we are going to translate the genetics to more than just associations or statistical arguments, we have to translate the findings to biologically relevant changes. Thus, functional characterization of the variants is a very high priority.

There needs to be continued wise investments in model systems that will allow us to pursue gene–environment influences more rigorously than can be done in human populations.
Finally, if we are going to understand functional etiology of ASD, if we are trying to identify the genes that underlie risk, and we are searching for environmental factors that cause changes in brain development, we need to know where these candidate genes are expressed in the developing human brain, and where these environmental factors have their impact. There is a difference between mouse and human brains, and it is essential to keep in mind that one cannot always extrapolate findings between species because of fundamental differences, particularly related to brain areas that simply are not represented in the mouse, but which may be at the heart of ASD. For this type of information, there is an enormous gap in terms of understanding where key genes might be playing a role in neurodevelopment, and how their perturbation may impact the core features of ASD

David Kirby is author of Evidence of Harm, a founding contributor to Huffington Post and a contributor to Age of Autism. His next book, “ANIMAL FACTORY” – about the impact of industrial livestock production on our health and the environment – will be released within the year.


Mary McK

My theory is simple. These kids have a genetic component, but also have an environmental component in the form of an insult. That insult is to the immune system through multiple immunzations in one day. You give a 6 month old 5 vaccinations in one day, yes his immune system crashes. You are asking a baby's body to fight 5 deadly diseases in one day. Some babies do ok, others don't. Those with the compromised immune system through the genetic component can develop autism. Babies 50 years ago did not get 5 vaccines in one day, hence the rise in autism.


What about the chemical substances in the vaccines, ie. 2-Phenoxyethanol(2-PE), which is a preservative in several vaccines (an alternative to thimerosal). Classed as "Very Toxic Material". Also, 2-PE contains Phenol, which has the ability to disable the immune system's primary response mechanism. Effects include behavioral disorders, etc. Phenol is well aborbed from the gastrointestinal tract and through the skin. There should be more research on this preservative(2-PE) to see if there is a link.


"Vaccine safety is not just about better vaccines; it’s also about protecting those who are most likely to poorly react to them. It is not possible to have a good public health policy for disease prevention that fails to take this fact into account."

Absolutely - when one dares to venture beyond the statistical aspect alone, it becomes clear that from a moral perspective, there is no such thing as an "insignificant minority".

It's beyond shameful when "science" is held up as an excuse for ongoing injury.

Kathy Blanco

Thought this was interesting and goes along with my thinking that set up to autism is inflammation in utero, aka, brought to you by the diet of mother, thyroid function, toxins, infections, etc etc..

If a child is already acutely inflamed then the NF-kappaB pump has already been primed and the risk for vaccine injury is greater. Acute inflammation is caused by illness, injury, surgery, poor diet, and stress at home. This problem is magnified if the child had a history of inflammation while in the womb, was born prematurely, or had health struggles during the first few years of life. Even a previous round of vaccines can prime the inflammatory NF-kappaB pump. Environmental toxicity is another factor that cannot be ignored, as is the health of the mother prior to and during pregnancy. A mother’s obesity and eating habits have a significant effect on the nerve health of her child.

The main point to understand is that if the NF-kappaB system is already on the edge of overheating due to other factors, then the intentional pushing of this system with vaccines poses a serious risk to the child. Multiple vaccines given at one time, with multiple pro-inflammatory adjuvants, obviously increase the risk. Any person objectively reviewing the science on this issue could reach no other conclusion.

The issue of NF-kappaB is so important that the next generation of vaccines will utilize it in an attempt to make less toxic vaccines (the laser-guided approach rather than the shotgun). While NF-kappaB-targeted vaccines will be less blatantly toxic, making them free of adverse side effects is another story altogether. Manipulating NF-kappaB is playing with the essence of the life force of a cell. At any given time there are numerous ons and offs relating to how NF-kappaB is naturally working to maintain health. The new vaccines will turn on the inflammatory aspect of NF-kappaB – which could easily upset the applecart in some other needed aspect of health.

No matter how good research scientists are at developing new vaccines, there will always be a percentage of at-risk-already-inflamed children who are likely to respond in a poor manner. Vaccine safety is not just about better vaccines; it’s also about protecting those who are most likely to poorly react to them. It is not possible to have a good public health policy for disease prevention that fails to take this fact into account.


To Sorsha: Previously I had written, "...not the 'quirky' kind, but that which involves chronic physical illness and debilitating mental disability." My child could merit the "quirky" category, so unkindness was not my intention.

Surely you realize that some people don't acknowledge the biomedical ailments we frequently write about here. To them, "autism" is defined merely as non-neurotypical wiring. I felt the distinction needed to be made between inconvenience and incapacitation.

Tim Kasemodel

Dr. Patrick Levitt:

“Genes create a vulnerability that then gets coupled with some environmental disturbance — but right now, we don’t have any idea what those factors might be.”


Evidence That Supports Mutagenic Effects of Thimerosal:

Statement from the "emergency Overview" section on the Eli Lilly MSDS for thimerosal:

Primary Physical and Health Hazards: Skin Permeable. Toxic. MUTAGEN Irritant (eyes).
Allergen. Nervous System and Reproductive Effects.
Caution Statement: Thimerosal may enter the body through the skin, is toxic, ALTERS GENETIC MATERIAL, may be irritating to the eyes, and causes allergic reactions. Effects of exposure may include numbness
of extremities, fetal changes, decreased offspring survival, and lung tissue changes.

Definition of Mutagen, from Wikipedia, the free encyclopedia

In biology, a mutagen (Latin, literally origin of change) is an agent that CHANGES THE GENETIC INFORMATION (usually DNA) of an organism and thus increases the number of mutations above the natural background level.


1) The mutagenic effect of the mercury fungicide Ceresan M in Drosophila melanogaster.
Mathew C, Al-Doori Z.

After the 1972 mercury poisoning in Iraq, there was widespread concern over the
use of mercury fungicides in seed dressing. The ethyl mercury fungicide Ceresan
M, claimed to be responsible for the two earlier outbreaks of poisoning in 1956
and 1960 in Iraq, was tested in Drosophila to study its mutagenic
potentialities. Of the two concentrations used, namely 30 and 40 mg of the
chemical in 100 cc of the food medium, the latter treatment resulted in a
significant increase in the frequency of sex-linked recessive lethals.

2) Lead and mercury mutagenesis: type of mutation dependent upon metal concentration. Ariza ME, Williams MV.

Department of Medical Microbiology, Comprehensive Cancer Center, The Ohio State
University, Columbus 43210, USA.

Lead and mercury are toxic metals that are widely distributed in the
atmosphere, soil, and groundwater. It is estimated that 2-4 x 10(4) tons of
these metals are released annually into the environment by natural and
industrial processes. Therefore, human exposure to low relatively nontoxic
concentrations of these metals is unavoidable. However, the possible health
effects of such exposure remain controversial. We have previously reported that
LOW, SUBTHRESHOLD CONCENTRATIONS (0.1-1 microM) of these metals ARE MUTAGENIC in the transgenic Chinese hamster ovary cell line AS52. The purpose of the
present study is to determine the types of MUTATIONS INDUCED IN THE GPT GENE in AS52 cells. Using multiplex polymerase chain reaction and southern blot
analyses, we characterized the 138 lead-induced, 192 mercury-induced, 29
reactive oxygen radical-induced, and 20 spontaneously arising mutants for point
and deletion mutations in the gpt gene. Similar levels of point mutations were
observed in the lead- and mercury-induced populations (47.8 and 53.6,
respectively), which was significantly less than that occurring in the
spontaneously arising and reactive oxygen intermediate-induced mutants.
However, further examination of the data revealed that at concentrations of the
metals of equal to or less than 0.4 microM, the majority of the mutations in
the gpt gene were point mutations, while at higher concentrations, DELETIONS(partial and complete) WERE THE PROMINENT TYPE OF MUTATION.*** These results are consistent with the hypothesis that lead and mercury induce mutations in
eukaryotic cells by at least two distinct mechanisms.

PMID: 9890195 [PubMed - indexed for MEDLINE]

NOTE: Lets all keep in mind that fetus' and infants in the U.S. all around the world are still getting thimerosal containing vaccines, never mind the rest have background exposure as well.


Excellent point Sorsha. My son is further down the spectrum than yours, but I would never presume that Asperger's folks are just "quirky" and that's it. In SOME ways I think they have it harder because more is expected from Aspies and HFAs in terms of being in the world since they present so well, yet they are not always equipped to meet those expectations social skills wise. This can make for a very hard life. Those of us with A.D.D./A.D.H.D experience, but not nearly to the degree as Aspies.


to the poster who talked 'quirky' autism as some lesser disease - please use a little more kindness here. My son has recovered to the level many would consider 'quirky' (meaning his gut issues have stabalized) - but he still cannot form relationships, doesn't have a single friend and his adult prospects for meaningful work seem like a distant dream - I try to maintain hope, but as karenatlanta said, he still has 'hardware damage', even though he's experienced some healing. my son is no less a victim than any other child with this senseless, preventable disability.

michael framson

"We Need To Learn Where Toxins Impact Gene Expression to Find the Cause of Autism."

Why not cut to the chase "Learn Where Toxins Cause Autism" or better yet, "Toxins cause Autism." I'm of the opinion that we aren't improving our genetics, but simultaneously polluting our body and genetics with the usual suspects of environmental toxins.

Will we continue to build a genetics research industry at the same time we add another 80,000+ chemicals and drugs to our environment when we have no idea of their long term impact?

So which route will pay dividends sooner. Clean up the environmental toxins(the trigger)or research what loads the gun?

I really don't know.


Folks, forget about the imaginary wing deal, this is shell shock all over again. Would to God above the future doctors at Harvard medical school would dig deep and entrench themselves in the history of just a century ago.

During the Great War they executed shell shock victims. Shell shock, of course, is most likely heavily dotted with cases of macromercurialism. Adult on-set Autism Spectrum Disorder.

The trenches got so bad, the troops wee wee'd on their hankies and tied them around their faces hoping the available cysteine in their urine would work as a shield against mercury toxicity. Troops routinely wore gas masks to protect themselves, not from an enemy chemical attack, but from mercury residue present in the fumes generated by their weapons.

Even the blasted Treaties of Armaments, the official weapons book of the British empire, over several decades, shifts the focus of instruction away from concerns for gentle handling to avoid accidental discharge of the fulminate of mercury, to extreme caution due to its' "very poisonous" characteristics.

Essentially, the troops who became the victims of mercury-poisoning were left to defend themselves against charges of malingering and cowardice in the face of the enemy. Their fifteen minutes of fame was spent attempting to gather their scattered thoughts, calm their quivering bodies, and clear the brain fog in a last futile effort to present something, anything to reverse the guilty until proven innocent prejudice consistent with overwhelming ignorance and total lack of compassion.

Just maybe Private Harry Farr is OUR unfinished business. When America is forced to face the horror and injustice dealt by the governments beckoning to the real 'merchants of death' it won't be so hard for them to finally see the full scale of what's been done to our children?

Jim Moody

Ah ha! So, Wakefield was right after all! It was that groundbreaking article in The Lancet 2/28/98 that was the first to report on the new syndrome, later named autistic enterocolitis. Now, Levitt and colleagues propose a gene defect in MET that may be the susceptibility gene. But this occurs in about half the population. So, it must be something else, genes + an environmental trigger = ASD. Oh, now that's a novel thought. The article says: "The etiology of ASD is currently unknown, but genetic vulnerability and gene-environment nteractions contribute to ASD risk." There are huge implications for this finding. Once it fiannly sinks in to CDC and the leadership at IACC that there IS in fact an environmental trigger, possibly vaccines, research $$ and projects can be aggressively focussed on finding this. It's elimination from a child's environment can bring an end to the epidemic of new cases. The strategic plan required by the Combating Autism Act provides the mechanism to get this research done with all deliberate speed, but because of CDC hostility to the notion of an epidemic (= environmental cause) and the possibility that vaccines might be implicated, vaccine research was first included and then clensed from the plan, and there is only a tiny dolup of money for 3-5 environmental studies over five years. Unacceptable! The article also says: "The current data set is consistent with the hypothesis that the genetic risk that underlies disruption of a single cell signaling system, the MET signaling system, can lead to independently generated brain-based and systemic dysfunctions that ultimately interact to influence long-term pathophysiological processes." Translation: gut-brain connection. This research might even help Special Master Hastings realize that Michelle Cedillo does, in fact, have inflamatory bowel disease, and that this IS realted to her autism. This should be a clarion call for more focussed research $$ on both the precise mechanism of damage and the environmental trigger.

Kathy Blanco

Gatagorra (what a name, I love it, it sounds trekee)...anyways, I will voice it again, your so eloquent, I would buy any book you wrote on this subject-wishing I was your publisher. And you hit it on the head..the feel sorry for us public is trying to distance themselves, why saying SHEESH, glad it's not me and my if to push us away into some dark corner and forget us all. What I think is pinning them down is they are starting to wonder what is increasing autism, and that it cannot be explained by our bad genes alone. It must be something that "we" have been talking about for some time, vaccines, toxins, etc. This makes it more "at the doors" of everyone's conscience, and may turn the tide, by sorrow in numbers. In my facebook profile today, I published one of the most devastating videos of autism I have seen...and it was so real...that after it was shown at the congressional hearing with Dan Burton, moms and dads were crying. I don't know why in the HELL it is not published on all television commercials and AS public service announcements. Afterall, we all sit through those commercials of starving children in all parts of the world to gather fear and our sympathy. Maybe we haven't touched peoples hearts yet? Maybe we haven't pinned the actual emotions of our everyday lives? I would be happy to contribute the before and after 8mm choppy videos (very artsy, can use them for some artsy fartsy types in ad camapaigns), and then see what happens when you trust authorities that things are safe. I guess maybe the bell curve of concern on the public level has not been reached. Maybe do as the lyme commmunity has with their film called UNDER YOUR SKIN, in which it shows the suffering of the undiagnosed, and undertreated. I think this must be done. The money may be a lot, but I think it should be an independent film of high quality. With the real story, not the the higher functioning can get along in society autism, I mean the low level, gut wrenching, organ dysfunction kind.


Thank you for this, David. It's all a lot to think about. I have no idea if this has any bearing on this discovery, but I found a study in which it seems that something about the Met gent relates to intelligence in girls in China:

My question about it is, why was anyone studying the relationship between intelligence and a Met polymorphism? I also found it curious that if you google MET receptor tyrosine kinase on chromosome 7q31, mostly what comes up (aside from this new study on autism) are studies on colon and other gastrointestinal cancers and cancer metastasis.

One thing that struck me about Dr. Leavitt (no relation of Michael Leavitt, I take it?) is what a skilled diplomat he must be present the environmental argument in front of such an assembly.

Another thing that stood out in my mind as a maybe a bit of a stretch was the idea of heterogeniety in the "genetics" of schizophrenia. That seems like a very diplomatic way of saying they ain't found nothin'. I would hardly trust any of the past genetic studies of the condition because it's always been the hotbed for research fraud. The drug companies rely on perceptions of schizophrenia's genetic etiology in order to drag all "mental disorders" by association into genetic diagnostic territory, mostly to justify drugs for all these conditions (if there's no method of prevention and no cure, drug risks seem "acceptable"; if there's a known environmental cause that can be prevented and related recovery strategies, then drug risks become unacceptable).

Wasn't Cold Spring Harbor once some kind of eugenic "research" facility?

As long as these ideas are being built on actual solid science, then I think they may serve us. But the questions are still unanswered-- what are these toxins doing to gene expression? Were these children actually born with these mutations or were they induced, etc.?


I just finished listening to audio presentation by Bruce H. Lipton, Ph.D. on the Wisdom or your Cells. Every parent of a child with any type of gene mutation or who was not born with a birth defect but a regressive developmental delay should listen to this tape. It will clarify a lot and explain how you can change the way your genes are expressing. Excellent, just excellent and light years ahead of the mainstream......


To John Kurtin,

I agree that we're all in this together and that we need one another. I'm glad you feel this way though it's unfortunate that any of us have to be in this boat in the first place. You would understand that six-fold.

I would like to add, though, that research into cause is what's lead to my twin's quality of life being improved. Wakefield's research into the gut-brain connection lead to a diet which means that our household actually sleeps at night without the "help" of psychiatric drugs and their side effects.

Also, the research and reports on the role of heavy metals in autism mean that my son's development has been kick started at long last. Unlike some children, my son has an immediate, lasting response to chelation that been enormously positive. Research into the role of mitochondrial damage via hypervaccination lead to my twins being treated for mitochondrial dysfunction, also with positive results. Then there's inflammation, information on intestinal damage and malabsorbtion of certain minerals and on and on-- all information which has directly fed into the treatments which have improved my kids' lives.

I agree with Nancy that stemming the tide of the epidemic, which would require establishing cause, is as great a priority as helping the children already effected for moral reasons and for reasons of cost. As the economy tanks and threats to the environment lead to resource shortages in the future, how is humanity going to shoulder the cost of an ever increasing epidemic of disabled children? The fact is, even with every form of help and intervention that exists, whether it's behavioral or medical, many children with autism will never be independent and will require support from public coffers. The system is already overwhelmed and the children of the early part of the epidemic are only beginning to come of age. Things are going to get worse.

What's more, public perceptions of cause will impact how individuals with autism are treated in general, not just medically, and this goes directly to your concerns. Right now, Florida and other states are seeing a crisis of abuse of autistic children in public schools and private institutions. From what I learned in sociology, it's the unknown etiology of autism-- a disorder which has risen rampantly and threatens to effect even higher rates of children-- that could theoretically be driving a certain denial mechanism which in turn feeds abusive rationales. It's a mechanism which arises specifically in response to mysterious and pervasive threat. Unknown etiology means "could happen to anyone, anytime" and drives a regrettable human need to distance themselves from misfortune by castigating and generating negative attitudes towards the unfortunate. That doesn't just lead to individuals in the private sector and in government being tight with funds, it can lead to the system turning the other way when a school aide or instructor severely injures or kills a child through mishandling, which is happening more and more frequently these days. There have been studies on the phenomenon and it matters what the public perceives and it especially matters whether the public knows the truth in terms of how children with disabilities are impacted.

All pretty complex and I'm sure there's diagreements over theories. My point is that the hunt for cause could kill a few birds on the way, one of which is forging more public empathy for effected families which can lead to support for improved services and supports, the other "birds" are to stop the epidemic so that we can pay for the children already here and already in need and then, of course, to potentially figure out how to get more kids back to health.

Maurine Meleck

For John Kirton,
Proper research that will make a difference and more services for those already on the spectrum must go hand in hand. If we don't stop the epidemic, we're looking at less money and fewer resources for our children
every day.


Studying the Somali population is a great idea... how about a vaxed vs. unvaxed study on that population on the Somalis.


"We Need To Learn Where Toxins Impact Gene Expression to Find the Cause of Autism."

Could they possibly do some of this research on the Somali community of Minneapolis where the incidence of (severe) autism is reported to be 1 in 28?


To John Kirton: If I had 6 kids on the autism spectrum, I'd be asking to prioritize day-to-day support, too. But consider the consequences if society doesn't stop making more children who develop autism -- not the "quirky" kind, but that which involves chronic physical illness and debilitating mental disability. When the bathtub is flooding, you try to shut off the faucet before you grab the towels.

Thousands upon thousands of parents are reporting their children's mental and physical regressions shortly after vaccine administration, but sadly it's not being properly investigated because of a huge mental blind spot by the "health care professionals" who promote the shots.

It's tragic that causality and physical needs are requiring such huge energy and funding, but don't minimize the needs of one focus in order to benefit the other. Like much in life, these efforts must be made concurrently. Yes, the evolving science is daunting, but we must continue contributing.

Kathy Blanco


I am going to print out your comment for my giant session with mitochondrial specialists at OHSU. I truly feel there are some predispositions to autism...but one wonders about why the genes become fragile in the first place, and you hit the nail on the head...toxins. What has increased the last four decades? Also, I really do feel there is an awful lot of autism moms and dads out ther who are going on undiagnosed with celiac...which changes genes expression, damages myelin etc. It also damages the thyroid function in mother, which would damage the baby in utero (they say just three days of transient thyroid dysfunction in rats). Also, what mothers eat can change methylation factors. Infections, can damage ATP co factors and kreb cycle pathways. Many moms I know have CFS-Fibro-Arthritis-borderline Diabetes or Metabolic Syndrome/Thyroid/MS/Diagnosed and undiagnosed autoimmune disorders. A mother with anti microsomal antibodies...can damage the baby. Moms moms I know who have a child with autism have that problem. They also have inflammation, again, another factor we can blame on the food supply, infections and toxins (and or if you are obese). This is why I started my list on yahoo, because I figured out that those three prong things are the cause to autism...kind of a no brainer ( ). Much of those same moms and dads are positive symptomatic or asymptomatic lyme disease/mycoplasma. They have numerous L form bacteria/no cell walled with damaged D3 pathways, they have Klebsiealla, Gamma Strep, Heompholis, Staph, Parasites, etc. Most test positive for simean virus 40 from their polio vaccines, and most have viral, bacterial and fungal processes. Some have mold histories or exposures.

These must, in all their combination, along with factors such as damaged immune function/cholesterol function (remmber, cholesterol is a function of repair of damaged vessels, and what damages blood vessels? BACTERIA + Toxins).

Why aren't we testing for all these things while mom is pregnant, better yet, before pregnancy? It would save a lot of kids. Of course, not vaccinating too.

My two NT daughters live near a refinery in UTAH. I hate the location...

My grandchildren have no signs of autism, however, one of the children has hypertonia...scary, could be like CP, but no signs. However, I looked up if it could be mercury/uranium (high in Utah) that can cause that, and whala...although the mom does not have amalgams, never vaccinated her children, she was vaccinated, and got my lion share (babies chelate their mothers), and of course, it doesn't help matter to live near a refinary (within five miles). So yes, I can see how hardwiring can occur, and I can also see when the brain is maturating and pruning around the age of two, the signs of autism may emerge even without a vaccine. Some infections take time to damage the brain, this is true with congenital lyme disease. It is also true of children who were cord clamped too soon (read why at ). One of my autistic chidlren, while pregnant with him, I had either a lyme flare or the actual EBV mono virus (tested positive). I looked and looked for a resarcher who could tell me what EBV could do. OF recent, the MS society has stated, it is a myelin eater. So, I go there to think, my child's myelin was already in jeopardy, then I vaccinate...not good. My next autistic child, I had STREP while pregnant. Got an IM BICCILLIN shot. Changing flora right before birth, great idea, not. Again, STrep, is a myelin eater as well. So there may be set ups to autism. Giving tylenol during pregnancy or birth or vaccine fever, another hit ( ). IN the treating autism book, where I am also in, I noticed a trend, all the mothers used tylenol!!!

When one of my daughters visited her ND, who was pro liking the fact she is not vaccinating, he gently reminded her there are other causes of autism, such as mothers putting babies on rugs that have formaldehyde in them, plastics, fluoride, MSG/GMO, CORN (in syrup, and actual corn) mold, mercury in other sources or other heavy metals, dioxins, endocrine disruptors, etc. These also have increased in our everyday products, with the procedures at birth at the same time the vaccine schedule went up. It's no wonder we have children with lower IQ, inability to cope, mental and emotional distress, Autism, ADHD, Bi polar, and the like?

When we did Genetic SNPS my kids are the type where a chemical may come into their bodies and stay. Detox pathways, are screwed. I do believe this is due to the fact I have the same problem, and harbored these same chemicals and toxins while pregnant with them. I was even exposed to malathion helicopter campaigns over silicon valley at the time of both of those pregnancies. (malathione contains mercury salts).

I often wonder that mothers who may be taking in giant levels of selenium/glutathione are the ones that go unscathed? Fruits, some proteins and vegees are necessary in the diet to build glutathione. Some infections cause glutathione block, like lyme disease. (CFS society recent report).

We may be looking at a multi faceted syndrome caused by mankind, and greed and averice for the average joe and who care for you? This is why we all have to be wise as serpents in this day and age, and try to protect our children from these sources of damage. Unfortunately, the last person we look at is our ownselves. This is a thing I have pushed for a long time, why can't we prevent autism?

John Kirton

All of this is very interesting, however... The bad thing about research is for every 'study' that supports one set of views, there are three others that support an opposite conclusion. Autism? It's the water, bad parenting, vaccinations, genetics, heavy metals, pollution, preservatives, etc.. etc., etc...

As the Dad of six children with Autism I'm more concerned with research that can help the Autistic person to have a more full life. Research to uncover the best in education, social training, nutrition and treatments. Some funding spent on 'why' is acceptable, but the bulk needs to be addressing the here and now and plan for the future.

Funding for Autism research is good, funding to help with day to day living, is better.

Autism is a spectrum disorder, caused by a spectrum of reasons, needing a spectrum of treatments and a spectrum of funding. (Spectrum: A broad sequence or range of related qualities, ideas, or activities).

Our country must get moving to discover what can be done improve this situation. If every parent of Autism will be an advocate we can make a HUGE difference for our children. So make calls, write, search and read. Do what you can when you can. We are all in this together and we need each one of us.


I agree with Karenatlanta that our kids have hardware damage.

Consider the findings of this gene study:
They found that children with Autism had several mutations that effect dopamine production including ATP7B. However, the parent sample ONLY had mutations in the ATP7B gene.

So wouldn't that mean the children could not have inherited the other mutations, and something would had to have caused the mutations?

I hope these researchers will also consider investigating the ATP7B gene as another genetic risk factor since it relates to metal metabolism and certain studies have already linked autism to environmental pollution (including mercury from power plants.)

Additionally, mutations to ATP7B have been linked to excessive aluminum storage (and we all know that Al is in vaccines, Al damages the blood brain barrier, and Al toxicity causes mitochondrial dysfunction.)

And furthermore, mitochondrial dysfunction results in higher levels of ROS, and "When mtDNA residues are oxidized, they become more difficult for the mitochondrial polymerase to copy accurately, resulting in deletions, rearrangements, and other mutations."

Children with autism have high levels of oxidative stress, and low levels of available glutathione. So could the high ROS levels be causing their genetic mutations?

Links to the studies and claims mentioned in this comment can all be found at:

The Met gene

"So far, reporting on the study, to be published in Pediatrics, has suggested that a polymorphism in the Met gene has been identified which, by itself, may explain both brain abnormalities and GI disturbances in children with autism spectrum disorder."

Given that the ND folk declare that there is nothing wrong with their GI tracts (they don't seem to understand why we have problems with our kids' health) would it be safe to assume that it is indeed the environmental insult, i.e., the vaccines that are messing up the Met gene in our kids. Can they add the MMR vaccine to this Met gene in the lab or in a rat and see if it indeed screws it up?


I second Natasa's post! In fact she's been saying this for years and the study from last summer on post mortem children with autism and controls confirms an underlying calcium channeling dysfunction. Why more people are not discussing this is baffling to me. Thimerosal, per UC Davis Mind Institure affects calcium channeling, so do some viruse, etc. If anyone hasn't done it yet they should read the paper Natasa put together on this a few years ago.


"In essence, we know very little about the changes in brain development and brain organization that underlie ASD. That is a real problem in trying to understand the causes. Genes, environment, or both?"

As the parents have been saying for years now - "something happened to my child after I vaccinated him." We are born with our genes given to us by our parents, its our destiny. What we can do, is control our environment. We can change the present and in doing so, can hope for a better future for our kids.

The bottomline is, we do not know enough about the brain and the immune system and how they interact. Perhaps we will never know. What we can do and should do, is stop giving the insult. Injecting mercury and aluminum, and pathogens, in massive doses in bodies ill-equipped to deal with them does not make for common sense. Its time the pediatricians stopped deluding themselves, and the people whose health they are supposed to be safeguarding.


My son had several polymorphisms relating to clearing toxins. It's interesting to study how the gene defects relate to even life giving hormonal, adrenal, and inflammatory response. The cleaner we get him the better he does. While not expressing all the gene defects, some like the VDR (Vit D defect)also show up on testing as lacking.
Quite a web of destruction we have to navigate through as parents.
Starting diet and metal removal is only the tip of the iceberg. Amy Yasko has quietly been saying this for years.
Our kids have hardware damage.
Perhaps this is why some pediatricians skip all the investigative metabolic work and prescribe drugs.


Many environmental toxins (including toxins/proteins produced by infectious agents) that are implicated in autism are capable of influencing gene expression through at least one direct mechanism, that of plasma membrane calcium channels. These ion channels on the outside 'borders' of the cell have a "direct phone line" to cell nucleus and gene regulation:
"...One of the ways in which calcium channels influence neuronal and many other activities is via signaling pathways that control gene expression. This involves regulation of various transcription factors, including CREB. ... Through its stimulation of CREB nuclear calcium may modulate the expression of numerous genes including neurotransmitter receptors ... with the involvement of most having been implicated in autism"

imo there are many etiologies/underlying causes of autism, but they would all share common pathways like this one. The functioning of calcium channels is negatively affected by various environmental toxins, and so these various epigentic factors would produce the same/similar end result, i.e. autism.

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