Autism and Gene Research. Who Benefits?

Managing Editor's Note: This is a thoughtful post on the heels of Eric London's departure from Autism Speaks. 

By Teresa Conrick

I am no gene expert though I did take Genetics in high school and again learned much in college and even more while getting my Masters in Science and Education.  I thought it was fascinating - recessive genes, dominant genes, punnett squares and who could forget the father of it all, Gregor Mendel?
 
Now I wonder what Gregor would think of all of this research on autism and genes and more importantly what is the purpose?  To help Gregor out, I took a Google trip backwards year by year to see what we have learned from the research, the data and the comments from researchers. Since I have a daughter with severe autism and no family members who have autism, I am interested in how the heck genes are involved and who actually benefits from. this type of research.  Fasten your seatbelts as genetic studies can be very bumpy!
 
Let's go back to the start -- but where is the start?  Using my trusty google, I put "autism gene research study" in and after much hunting, it looked like 1997 would be a good place to start.  Why then, you might ask and that would be a good question as apparently the cases were increasing and somebody or some group thought it was time to find out why, but why genes? So here in David Letterman style, let's look at those top autism gene studies over the years and see how far we have come and what we have learned:
 
1997-"Researchers discover first autism-susceptibility gene": (HERE)

"The discovery should speed the search for additional genes that increase susceptibility to autism and enhance understanding of this complex disorder. It could eventually result in more precise diagnosis and possibly better treatments." "This is just one of at least three to five genes whose interactions result in autism," says Ed Cook, MD, associate professor of psychiatry and pediatrics at the University of Chicago and lead author of the report."
 
Now why is a professor of psychiatry and pediatrics looking into genes?

So in trying to find information on Dr. Cook, I found this from 2008: (HERE)

"Dr. Cook is Professor of Psychiatry and Director of Autism and Genetics" - interesting, he changed his title and in 2008 it says he also is-"APA DSM-V Work Group Member" and from that same site, it appears that Dr. Cook is busy with many aspects of autism but this one is curious.  " Consultation Fees (include scientific advisory boards) Eli Lilly (2006). Would it be a conflict to be on Eli Lilly's scientific board and thus push gene studies rather than environmental, including vaccines, including preservatives, in vaccines?  Oh wait. There's more. What's this Dr. Cook reported in the 1997 article?:

"Dr. Cook and colleagues demonstrated that drugs, such as Prozac (fluoxetine), that inhibit serotonin transport, can reduce the repetitive behaviors exhibited by some children with autism."...and who made Prozac in '97 and currently?...why Eli Lilly of course...
 
Meanwhile, I wonder if  Dr. Cook saw this recent news piece:

"Popular autism treatment fails under study", (HERE)

"Chicago, June 2: A new government study has found that the antidepressant Celexa, widely prescribed for treating autism, does not help reduce autistic kids’ repetitive behaviors, instead it causes some of them to have nightmares. --- "Although Celexa, which belongs to the class of selective serotonin reuptake inhibitors, or SSRIs, is lesser known than similar antidepressants such as Prozac and Paxil,"..."These antidepressants are not approved for autism use and there’s little evidence that they are effective in treating the condition, still doctors prescribe $2.2 to $3.5 billion worth of these drugs to treat perhaps 30 percent of the children with this condition."
 
Obviously gene research personally benefits Dr. Cook and the company that he "consults" for, Eli Lilly. This history lesson is proving to be quite informative.  Onward we go -
 
1998- "Genetic counseling and ethical issues for autism" (HERE)

This has ominous implications - "Exciting progress is being made in the journey toward discovery of genes conferring risk for autism and autism spectrum disorders. Currently, genetic counseling for idiopathic autism rests on clinical diagnosis and empiric risk estimates. While no genetic test for risk of autism currently exists, it is possible that such a test may emerge in the near future, and that commercial availability may precede adequate understanding of test characteristics. The complexity of multifactorial conditions like autism raises a host of ethical and counseling challenges."
 
--In layman's terms, they wanted to develop a test so that parents or others could decide if they wanted to abort the pregnancy.  To this day, there is still interest in this and why, in heavan's name, can this be a benefit to anyone?
 
1999-  "The Autism Gene?" (HERE)

"The data is pretty overwhelming that autism is strongly genetic, more so than schizophrenia or diabetes." ..."We shall keep you posted when the results of this research become available."

Well, since it is 2009 and they are still hunting, I guess these researchers needed that BIG ending-  kind of like a mystery -- to keep that flow of beneficial gene money coming.
 
2000- "Autism Gene Discovered by Researchers" (HERE)

"Why don't parents who harbor the defective gene have autism themselves? Some do have very subtle symptoms, suggesting that something else, perhaps some other gene, keeps the autism-related gene in check, Rodier says."

Ouch, the parents have faulty genes and they have "symptoms" too...." Who reaps the benefits of weird parents and their bad genes? -- most likely pharmaceutical companies and more gene research people.
 
2001 - "Autism Linked to Developmental Gene" (HERE)

"Sifting through the DNA of hundreds of families, researchers have picked out a gene that may contribute to some cases of autism."

The rock, paper, scizzors approach -- again it benefits the flow of money to more gene studying.
 
2002 - "$6 million autism gene hunt" (HERE)

"A major expansion of the collaborative effort to identify genes linked to autism is about to start with a $6 million grant awarded by the US National Institute of Mental Health (NIMH)."

And this is when the gene furor becomes frothy with dollar signs.  No where in this is there any benefit to a family with a child diagnosed with autism.
 
2003 - "Gene Variant Linked to Autism" (HERE)

"In addition, autism is likely caused by anywhere from two to 10 genes.  "This is just one bit of the whole puzzle."

And voila`, the start of the additional genes and added intrigue of the "puzzle", thus more money being directed to the universities doing this fruitless research.
 
2004- "Autism gene found" (HERE)

Finally!! "Approximately 1 in 1,000 people have autism or autistic disorder. It appears to be the most highly genetic of all psychiatric disorders. If a family with one autistic child has another child the chance that this child would be autistic is 50 to 100 times more likely to than would be expected by chance."

OK, BIG false alarm. How did they get this published because from title to content, it was all bull.  And who benefited?
 
2005- "Researchers Closing In On The Genetic Structure Of Autism And Related Disorders"
(HERE)

WOW -- now it's not just autism but all related disorders.  "And in spite of the devastating disability associated with autism, it's possible that individually, some of those genes that contribute to autism might actually be beneficial."...."A person who has a genetic susceptibility factor that makes them very focused on details might be at an advantage under many circumstances and in a variety of occupations,"...So autism is cool and this then benefits the neurodiverse believers but what about children like my daughter who regressed, cannot speak and has a multitude of health issues?
 
2006- "New Autism Gene Doubles Risk

Finding Suggests Autism Is Disease of Brain and Body" (HERE)

"A single gene mutation doubles a child's susceptibility to autism, a Vanderbilt-led research team reports. It's a discovery with far-reaching implications. Why? It isn't specifically a brain gene. In fact, it affects multiple systems in the body, including immune function and gut repair."

Fantastic- finally a look at a gene(s) and the environment connecting to autism...but wait,,what's this?:

"The possibility that a MET variant might lead to immune dysfunction and gastrointestinal disturbance along with autism-spectrum disorders is an important question to pursue and one that will likely lead to some debate,"  That's because the first theory to link autism, gut problems, and immune dysfunction blamed these symptoms on childhood immunization with the measles/ mumps/rubella (MMR) vaccine. That theory has been retracted by all but one of the researchers who first proposed it. Now the MET gene findings offer new insights into the link between autism and other developmental problems."

Oh boy, talk about a sly move. These researchers seem to know how to benefit by taking facts and trying hard to make them NOT vaccine-related but instead gene related...with miniscule emphasis on "environment". Very disappointing.
 
2007- "DNA "glitches" tied to autism, researchers say" (HERE)

"Little glitches in the DNA of people with autism suggest that the disease might be caused by as many as 100 different genes, researchers reported"...."These findings certainly complicate the search for genes contributing to autism."

Unbelievable!  They've had at least 10 years of MILLIONS of dollars to tell us..it's not ONE gene but now more than a HUNDRED genes.  The benefit of this is painfully obvious and  guarantees YEARS more of genetic research dollars. Not only does this not help a current child with autism but it does not help any future, unaffected children.
 
2008- "Gene Research May Help Explain Autistic Savants" (HERE)

"Mice lacking a certain brain protein learn some tasks better but also forget faster, according to new research from MIT that may explain the phenomenon of autistic savants in humans. The work could also result in future treatments for autism and other brain development disorders."

More of the past mingled in with more promises that have never panned out and what are "future treatments"?
 
2009-"Key gene for autism identified, no effect on treatment or cure" (HERE)

"Researchers have discovered a gene that causes autism in 20% of the population who have the disorder.  The findings are interesting, but as of now, will not help in the treatment or diagnosis of autism. Still, as these studies continue, the field is narrowed as to what actually causes autism, which affects 1 in 150 individuals.  There is disagreement whether there are environmental factors or genetic predisposition factors contributing to the high incidence of children being diagnosed with the disorder.  Continued attention and studies will only serve to further the cause of research in the future helping us understand why so many are affected by autism and what we can do about it."
 
Now if that doesn't confirm all of the bullshit that we have read:
 
- The findings will not help in the diagnosis of autism.
- The findings will not help in the treatment of autism.
- There is disagreement whether there are environmental factors or genetic predisposition factors contributing to the high incidence of children being diagnosed.
and this is THE lie, the vortex of perpetual deception :
 
"Continued attention and studies will only serve to further the cause of research in the future helping us understand why so many are affected by autism" -
 
BUT it is not to understand or help these children like Megan Conrick. It is to find elusive genes, dramatic titles, false promises and MONEY. It is also a way to dodge the vaccine issue that many want to deny. The reality of "serve to further the cause of research" really means to be tricked into a belief that has exceeded its time and a trust that has been lost.  It is time to investigate the true factors that started and regressed our children into an autism diagnosis: vaccines, their ingredients and the connection to our children's immune, gastrointestinal, mitochondrial and brain dysfunctions.  
 
Teresa Conrick has two beautiful daughters. When she is not teaching, she is researching the biomedical implications of autism, both past and present.
 
 
 

Comments

[Mark Blaxill]

"Genes do nothing."

It all depends on what work the word "do" does.

It's certainly possible to pick a fight on this one but almost entirely a waste of energy.

Seems to me "apple bottom genes" was eloquent and clear in his point. That's why his comment was selected as the comment of the week. I suggest we move on.

[genes make the apple]

you missed my point

my only problem is with your premise of "genes do nothing" and then you reasoning behind that - genes DO do something.

First

you seem to have made the assumption that e I must somehow be implying that autism is genetic. I never said that. This is a frequent misnomer going around our community. Someone hears/sees the word "gene" or "genetic" and then jumps to conclusion that any such person mentioning it must be supporting genetics alone. I watched a presenter at A1 get attacked when he dared mention GxE interactions (which really is part of the theories presented in the vaccine court and by other researchers noted here).

All that really had nothing to do with my point but seemed to be what was thought was my point.

Second

I am a plant breeder. I know genetics and molecular biology well.

But my point was and still stands that stating genes making those proteins (or gene products) is "nothing" is not correct.

Again, if you think "genes do nothing" try removing them from a living organism and expect the proteins to do all that work on their own. Proteins don't form until the genes direct them how to form - you eluded to that yourself. Is not that direction "something"?

If genes do nothing then what gets passed on generation to generation? How were the suspected ties between family histories of autoimmune problems and vaccine injuries that Wakefield and others have mentioned passed on?

Back to the group think about mentioning "genes" and assuming someone means genes only...

I support the possibilities of genes AND the environment interacting which have been supported by researchers like Hornig and James. Such interactions are possible explanations to the subsets of variants seen. It doesnt mean "genes alone did..." it simply means genes had a role and we must consider that role.

I have also taught others. Some have a very hard time with understanding genetics. To blanket tell people who do not have an understanding, "genes do nothing", is misleading and wrong.

[Natasa]

Following the Agousti mice gene story below, this one for Keith:

a workshop on University of Utah website will teach you how to influence the mRNA transcripts (expressed proteins in short) of your genes:

http://teach.genetics.utah.edu/content/epigenetics/

It will teach you for example that "The genome dynamically interacts with the environment as chemical switches that regulate gene expression receive cues from stress, diet, behavior, toxins and other factors..."

[Natasa]

A great illustration on genes and what they "do" (or don't do):
Biologists have long known that having a particular gene is no guarantee you will express the associated trait, any more than having a collection of CDs will fill your home with music. Like CDs, genes are silent unless they are activated. Because activating and silencing doesn't alter the sequence of the gene, such changes are called epigenetic...

full story here http://www.biotech-info.net/moms_diet.html

[apple bottom genes]

Thanks for the non sequitor Keith, but you've completely missed my point. It is lazy to use "genetics" as a shorthand for discussing conditions such as autism. You can talk about anything in terms of genetics since all animals are made up of genes, but that usually doesn't tell you much, and most often it derails you from seeing or understanding what is important. Like I've said before, autism is genetic in the same way that mumps is genetic. If you want to know why humans but not monkeys get mumps, the answer is in the genetic differences between the two species. If you want to know why humans get mumps at all, you better take a good hard look at the environmental etiological agent: the mumps virus. Talking about mumps as a genetic disease tells you nothing important about the disease.

Genes do nothing. If you want to understand the molecular biology of autism you need to talk about proteins (and more importantly, how environmental factors act on them). Everywhere you see the word "gene", substitute the word "gene product" and see if what you're reading still makes sense. It's a good way to separate the wheat from the chaff.

Some conditions are certainly caused by genetic mutation. All that means is that there is a change in the genetic code that causes a different protein to be made - nevertheless, it's still the protein that does the dirty work. But if you think ONLY in terms of genes then you miss all the types of conditions that are caused by too much or too little of the "right" gene products. Or the "right" gene products getting into the wrong places. And those types of problems far outweigh problems stemming from genetic mutation. The pace of genetic change in human populations is too slow to account for significant increases or decreases in disease. Once you know that a disease has increased or decreased significantly you can put to bed "genetics" as an important etiological agent.

[Benedetta Stilwell]

What apple bottom jeans said:
Example would be what farmers call a free martin. Twin calves- one female and one male. The famale calf will never ever bear offspring because of her close contact with her brother's testerone while in the womb. Congraduations on having the best statement. You stated it very well.

[Benedetta Stilwell]

To the blog --- sorry guys --- the lesson continues. Gee Wiz Teresa! You have to be dedicated to go through all that! I remember when I was in school majoring in microbiology, and we had to read all these endless bunch of research papers, and even had to write research reports that sounded just like this. (scientific jargon)! No english professor would have let them get by with. It took a little time for me to figure out they were trying to do was hide the fact that what they studied was really simple, and they were saying it in the most confusing way possible. Toxin induced injury is a good sum up, but they have to already know unless they are really really dense.

[Keith]

Apple bottom genes

If you think genes do "nothing" then one should be able to take them away and still be able to create an organism OR remove them from an existing one and still have that function.

Genes are the blueprint which direct those proteins how to form and when.

[Teresa Conrick]

Sorry guys - the lesson continues...

Anyway, I saw this in the news this week:

ADHD Genes Found; Known to Play Roles in Neurodevelopment

-- Missing DNA Segments May Suggest Future Drug Targets -- (repeat, FUTURE DRUG TREATMENTS!!)

PHILADELPHIA, June 23 /PRNewswire-USNewswire/ -- Pediatric researchers have identified hundreds of gene variations that occur more frequently in children with attention-deficit hyperactivity disorder (ADHD) than in children without ADHD. Many of those genes were already known to be important for learning, behavior, brain function and neurodevelopment, but had not been previously associated with ADHD.

"Because the gene alterations we found are involved in the development of the nervous system, they may eventually guide researchers to better targets in designing early intervention ( for children with ADHD," said lead author Josephine Elia, M.D., a psychiatrist and ADHD expert at The Children's Hospital of Philadelphia.

The study appeared online today in the journal Molecular Psychiatry.

Unlike changes to single DNA bases, called SNPs or "snips," the alterations examined in the current study are broader changes in structure. Called copy number variations (CNVs), they are missing or repeated stretches of DNA. CNVs have recently been found to play significant roles in many diseases, including autism and schizophrenia Everyone has CNVs in their DNA, but not all of the variations occur in locations that affect the function of a gene. The current study is the first to investigate the role of CNVs in ADHD.

Individually, each CNV may be rare, but taken together, a combination of changes in crucial regions may interact to raise an individual's risk for a specific disease. "When we began this study in 2003, we expected to find a handful of genes that predispose a child to ADHD," said study co-leader Peter S. White, Ph.D., a molecular geneticist and director of the Center for Biomedical Informatics at Children's Hospital. "Instead, there may be hundreds of genes involved, only some of which are changed in each person. But if those genes act on similar pathways, you may end up with a similar result -- ADHD. This may also help to explain why children with ADHD often present clinically with slightly different symptoms."

ADHD is the most common neuropsychiatric disorder in children, affecting an estimated 1 in 20 children worldwide. It may include hyperactive behavior, impulsivity and inattentive symptoms, with impaired skills in planning, organizing, and maintaining focus. Its cause is unknown, but it is known from family studies to be strongly influenced by genetics.

Drawing on DNA samples from the Children's Hospital pediatric network, the researchers analyzed genomes from 335 ADHD patients and their families, compared to more than 2,000 unrelated healthy children. The team used highly automated gene-analyzing technology at the Center for Applied Genomics at Children's Hospital, directed by Hakon Hakonarson, M.D., Ph.D., a co-leader of this study.

The study team found a similar quantity of CNVs in both groups. However, distinct patterns emerged. Among 222 inherited CNVs found in ADHD families but not in healthy subjects, a significant number were in genes previously identified in other neurodevelopmental disorders, including autism, schizophrenia and Tourette syndrome. The CNVs found in ADHD families also altered genes important in psychological and neurological functions such as learning, behavior, synaptic transmission and nervous system development.

"We took a systems biology approach, grouping genes into groups with common functions," said White. "We found that the sets of genes more likely to be changed in ADHD patients and families affected functions that made sense biologically." For instance, said White, the team found four deletions of DNA in a gene recently linked to restless legs syndrome, a type of sleep disorder common in adults with ADHD.

Another deletion occurred in a gene for a glutamate receptor. Glutamate is a neurotransmitter, a protein that carries signals in the brain. While ADHD medications act on dopamine and serotonin, which are also neurotransmitters, this new finding may suggest an important role for glutamate as well, at least for some ADHD patients.

"As we delve into the genetics of very complex diseases such as ADHD, we find many contributing genes, often differing from one family to another," added White. "Studying the functions of different genes allows us to identify biological pathways that may be involved in this neuropsychiatric disorder."

Some of the biological pathways involved in ADHD may also be common to other neurological conditions, say the researchers. Likewise, there is some overlap among the CNVs found in ADHD that also occur in autism, schizophrenia and other neurological disorders. This overlap was not surprising, said Elia, because ADHD patients frequently also have one of more of these disorders. However, as researchers learn more about specific genes in neurological conditions, the hope is that researchers might in the future personalize treatments to a patient's own genetic profile, to achieve more targeted, specific therapies.

Elia and White stressed that much further work must be done before genetic findings lead to ADHD treatments.

The National Institutes of Health provided grant support for the study, as did the University of Pennsylvania, the Pennsylvania Department of Health, the Cotswold Foundation and the ADHD: Climbing to a Cure Foundation. Elia, White and Hakonarson all are faculty members of the University of Pennsylvania School of Medicine (Penn). Xiaowu Gai, Ph.D., of the Center for Biomedical Informatics at Children's Hospital, was a co-first author with Elia. Other collaborators were from Children's Hospital and Penn.

Elia et al, "Rare Structural Variants Found in Attention-Deficit Hyperactivity Disorder Are Preferentially Associated with Neurodevelopmental Genes," Molecular Psychiatry, published online, June 23, 2009.

About The Children's Hospital of Philadelphia

The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

OK-

key terms to know:

-FUTURE DRUG TREATMENTS!!)
-Children's Hospital of Philadelphia
-adhd, autism, schizophrenia and Tourette syndrome

Looking at this part:

"Called copy number variations (CNVs), they are missing or repeated stretches of DNA. CNVs have recently been found to play significant roles in many diseases, including autism and schizophrenia. Everyone has CNVs in their DNA, but not all of the variations occur in locations that affect the function of a gene."

and this then is where "gene research" would be interesting--what can cause these CNV issues?

Here's a good example-

http://www.citypaper.com/news/story.asp?id=13317

Mercury Rising
A Possible Link Between Chemical Exposure And Autism May Have Been Overlooked In The Very Earliest Cases At Johns Hopkins

Mr.Dan Olmsted certainly did his homework:

" the idea of parental exposure leading to autism in a child "can not be dismissed, because of the theoretical possibility that chemical toxins could effect genetic material prior to conception."

"Dozens of studies have implicated mercury in genetic damage, including chromosomes breaks, point mutations, and partial and complete deletions. One study on hamsters (it is unethical to test toxic substances on humans) found mercury produced more point mutations than lead, a widely recognized threat to children's mental development."

an example of mercury:

Mutagenesis. 2000 Nov;15(6):525-30.
Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins.
Schurz F, Sabater-Vilar M, Fink-Gremmels J.

Department of Analytical and Molecular Pharmacology, TNO Pharma Zeist, Utrecht, The Netherlands.

The mechanisms of toxicity and, particularly, the potential carcinogenicity of inorganic mercury are still under debate. Results of mutagenicity and genotoxicity testing with mercury have been inconsistent: mercury induces DNA single-strand breaks at low concentrations in mammalian cells but has not proved mutagenic in several bacterial mutagenicity assays. We investigated the mutagenicity of subtoxic concentrations of inorganic mercury and the role of metal-binding proteins and free radicals in this process. A mutagenicity assay using NIH 3T3 cells, transfected with a vector containing lacZ' as a reporter for mutational events, was applied. In this model, inorganic mercury significantly increased the mutation frequency in the lacZ gene, even at the lowest concentration tested. The mutation frequency was greatest at an Hg(2+) concentration of 0.5 microM. To identify the mechanisms involved, different cellular responses to non-cytotoxic concentrations of HgCl(2) were measured. Hg(2+) increased the intracellular amount of reactive oxygen species. This induction of oxidative stress was observed, although the intracellular glutathione (GSH) and metallothionein (MT) concentrations were increased significantly. Mercury-induced MT expression was even more pronounced after GSH depletion. Correspondingly, radical formation was more evident in the presence of the GSH-depleting agent L-buthioneine-[S:,R:]-sulfoximine. These findings suggest that the observed mutations might be a consequence of oxidative processes, rather than due to a direct interaction of mercury with nuclear DNA. The results also indicate that the auto-induction of MT by Hg(2+) fails to prevent these mutational events.

And so it is very possible that mercury AND thimerosal can cause these CNV issues.

and here is thimerosal:

Toxicol Sci. 2003 Aug;74(2):361-8.
Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts.
Baskin DS, Ngo H, Didenko VV.

Department of Neurosurgery, Baylor College of Medicine, 6560 Fannin Suite 944, Houston, Texas 77030, USA. dbaskin@tmh.tmc.edu

Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. Little is known about the reactions of human neuronal and skin cells to its micro- and nanomolar concentrations, which can occur after using thimerosal-containing products. A useful combination of fluorescent techniques for the assessment of thimerosal toxicity is introduced. Short-term thimerosal toxicity was investigated in cultured human cerebral cortical neurons and in normal human fibroblasts. Cells were incubated with 125-nM to 250-microM concentrations of thimerosal for 45 min to 24 h. A 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) dye exclusion test was used to identify nonviable cells and terminal transferase-based nick-end labeling (TUNEL) to label DNA damage. Detection of active caspase-3 was performed in live cell cultures using a cell-permeable fluorescent caspase inhibitor. The morphology of fluorescently labeled nuclei was analyzed. After 6 h of incubation, the thimerosal toxicity was observed at 2 microM based on the manual detection of the fluorescent attached cells and at a 1-microM level with the more sensitive GENios Plus Multi-Detection Microplate Reader with Enhanced Fluorescence. The lower limit did not change after 24 h of incubation. Cortical neurons demonstrated higher sensitivity to thimerosal compared to fibroblasts. The first sign of toxicity was an increase in membrane permeability to DAPI after 2 h of incubation with 250 microM thimerosal. A 6-h incubation resulted in failure to exclude DAPI, generation of DNA breaks, caspase-3 activation, and development of morphological signs of apoptosis. We demonstrate that thimerosal in micromolar concentrations rapidly induce membrane and DNA damage and initiate caspase-3-dependent apoptosis in human neurons and fibroblasts. We conclude that a proposed combination of fluorescent techniques can be useful in analyzing the toxicity of thimerosal.

and pre-autism epidemic research on it:

Chromosomal Aberrations Induced by Thimerosal Exposure

Analysis of nine known or suspected spindle poisons for mitotic
chromosome malsegregation using Saccharomyces cerevisiae D61.M. Albertini S
(1990). Mutagenesis 6:65-70. (2263203)
Effects of 10 known or suspected spindle poisons in the in vitro
porcine brain tubulin assembly assay. Brunner et al., (1991). Mutagenesis
6:65-70. (2038274)
In vitro studies with nine known or suspected spindle poisons:
results in tests for chromosome malsegregation in Aspergillus
nidulans.Crebelli et al., (1991). Mutagenesis 6:131-136. (2056914)
The detection and assessment of the aneugenic potential of
environmental chemicals: the European Community Aneuploidy Project. Parry
and Sors. (1993).Mutat Res 287:3-15. (7683383)
Effects of potential anueploidy inducing agents on microtubule
assembly in vitro. Wallin and Hartley-Asp (1993). Mutat. Res. 287:17-22.
(7683380)
An evaluation of the use of in vitro tubulin polymerization,
fungal and wheat assays to detect the activity of potential chemical
aneugens. Parry (1993). Mutat. Res. 287:23-28. (7683381)
A comparison of two in vitro mammalian cell cytogenetic assays
for the detection of mitotic aneuploidy using 10 known or suspected
aneugens. Warr et al., (1993). Mutat. Res. 287:29-46. (7683382)
Induction of mitotic aneuploidy using Chinese hamster primary
embryonic cells. Test results of 10 chemicals. Natarajan et al., (1993).
Mutat. Res. 287:47-56. (7683384)
C-mitosis and numerical chromosome aberration analyses in human
lymphocytes: 10 known or suspected spindle poisons. Sbrana et al., (1993).
Mutat. Res. 287:57-70. (7683385)
The cytochalasin-B micronucleus/kinetochore assay in vitro.:
studies with 10 suspected aneugens. Lynch and Parry (1993). Mutat. Res.
287:71-86. (7683386)
An overview of the results of testing of known or suspected
aneugens using mammalian cells in vivo. Natarajan (1993).Mutat. Res.
287:113-118. (7683377)
In vivo studies on chemically induced anueploidy in mouse somatic
and germinal cells. Leopardi et al., (1993). Mutat. Res. 287:119-130.
(7683378)
Synopsis of the in vivo results obtained with the 10 known or
suspected aneugens tested in the CEC collaborative study. Adler (1993).
Mutat. Res. 287:131-137. (7683379)
Micronucleus test and metaphase analyses in mice exposed to known
and suspected spindle poisons. Marrazzini et al., (1994). Mutagenesis
9:505-515. (7854141)

Then this from the study:

"Another deletion occurred in a gene for a glutamate receptor. Glutamate is a neurotransmitter, a protein that carries signals in the brain."

and then this:

Neurotoxicology. 2007 May;28(3):587-93. Epub 2006 Dec 27.Click here to read Links
Decreased N-methyl-D-aspartic acid (NMDA) receptor levels are associated with mercury exposure in wild and captive mink.
Basu N, Scheuhammer AM, Rouvinen-Watt K, Grochowina N, Evans RD, O'Brien M, Chan HM.

National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, 1125 Colonel By Drive (Raven Road), Ottawa, Ontario, Canada. nbasu@uottawa.ca

Mercury (Hg) impairs glutamate homeostasis but little is known about its effects on the N-methyl-d-aspartic acid (NMDA) receptor. Here, we investigated NMDA receptor levels, as determined by [(3)H]-MK801 binding, in both wild and captive mink (Mustela vison) that experienced different levels of methylmercury (MeHg) exposure. Competitive in vitro binding experiments showed that inorganic Hg (HgCl(2); IC(50)=1.5-20.7 microM), but not MeHg (MeHgCl; IC(50)>320 microM), inhibited binding to the NMDA receptor in several brain regions of mink. In a survey of trapped wild mink, NMDA receptor levels in the brain were negatively correlated (p<0.005) with concentrations of total Hg (R=-0.618) and MeHg (R=-0.714). These findings were supported by a laboratory feeding study in which captive mink were exposed to dietary MeHg (0-2 ppm) for 89 days. Concentration-dependent decreases in NMDA receptor levels were found in the basal ganglia, cerebellum, brain stem and occipital cortex. These findings are of physiological and ecological concern because they demonstrate that Hg, at dietary concentrations as low as 0.1 ppm, can significantly reduce NMDA receptor levels.

and then thimerosal:

Mol Psychiatry. 2004 Sep;9(9):833-45.Click here to read Links
Neurotoxic effects of postnatal thimerosal are mouse strain dependent.
Hornig M, Chian D, Lipkin WI.

Jerome L and Dawn Greene Infectious Disease Laboratory, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. mady.hornig@columbia.edu

The developing brain is uniquely susceptible to the neurotoxic hazard posed by mercurials. Host differences in maturation, metabolism, nutrition, sex, and autoimmunity influence outcomes. How population-based variability affects the safety of the ethylmercury-containing vaccine preservative, thimerosal, is unknown. Reported increases in the prevalence of autism, a highly heritable neuropsychiatric condition, are intensifying public focus on environmental exposures such as thimerosal. Immune profiles and family history in autism are frequently consistent with autoimmunity. We hypothesized that autoimmune propensity influences outcomes in mice following thimerosal challenges that mimic routine childhood immunizations. Autoimmune disease-sensitive SJL/J mice showed growth delay; reduced locomotion; exaggerated response to novelty; and densely packed, hyperchromic hippocampal neurons with altered glutamate receptors and transporters. Strains resistant to autoimmunity, C57BL/6J and BALB/cJ, were not susceptible. These findings implicate genetic influences and provide a model for investigating thimerosal-related neurotoxicity.

This then is the big issue they are missing--they said:

"Studying the functions of different genes allows us to identify biological pathways that may be involved in this neuropsychiatric disorder."

but they are not looking into the exposure or.... what is causing the gene dysfunction. Yes, it could be mercury and/ or thimerosal and maybe others but they sure are NOT looking. Again, money for the gene research and money to market pills later for it.

Our job then is to change "neuropsychiatric disorder" to "toxin-induced illness".

Class is over.... :)

[Allison Chapman]

Great Post Teresa!! The "We found the Autism Gene" title parade has gotten silly. The public gets more confused everytime because they saw another report just months ago saying the same thing. They are wondering...why are they still looking if they've found it (them)?

At 1st whenever there was a report like this I would get several phone messages and e-mails saying "did you see? they found the gene(s)!!" Now it's stopped because anyone with a brain realizes they haven't found a thing.

I just decided to do the whole gene study on my son, my husband and I. If we find anything that just relates to my son's case maybe I could supplement around it or it would give something tangible in it's outcome. But I know that so far, nothing related to any of the previous "autism" possible tiny precentages of gene(s) found, have turned up for him yet, nada. I find it fascinating that insurance will pay for this kind of $$$$ hunt instead of the physical/biological environmental toxicity per child hunt, and the correlating treatments for it. The only thing this gene hunt does is protect denial of involvement of vaccination. An awful lot of money is being spent to seemigly avoid the answers. Our children deserve so much more. Thanks Teresa!!

[Teresa Conrick]

Thanks Tim and everyone who thought this was helpful.

I just wanted to also add that seeing millions of dollars wasted on frequent, bogus, gene studies is frustrating. Case studies on families with more than one child need to be be switched from "what gene?" to "what exposure?"....meaning,what do they all have in common?

[Tanners Dad]

Teresa You were added to my list of heroes at AutismOne. I am glad we got to meet. You continue to amaze me with your intelligence, wit, determination, and guts. I am just thankful you are on our side. Your thoughts & research will continue to light our path out of the darkness of Autism. Thank You again!

[apple bottom genes]

Maybe the problem is that genes are a shortcut for discussing molecular biology in detail. The fact of the matter is that genes do nothing - absolutely nothing. They are a string of nucleotide base pairs that sit there and do zilch. Ribosomes have to come along and translate that string of nucleotides into a linear strand of amino acids. When that line of amino acids folds up into a three-dimensional form, well then you've got something - a protein. Proteins do everything. Genes do nothing.

If you're a girl, is it because you have XX chromosomes? No. You're a girl if you had early exposure to XX gene products AND you lacked exposure to other proteins (namely the Y gene products). As proof (and this experiment has been done) if you take an XX mammalian zygote and allow it to develop in the presence of testosterone, the embryo becomes a boy. You can't tell the XX zygote is a boy by looking at its DNA. You also can't determine how it became a boy by looking at its DNA. You'd have to understand the environmental factors to know what happened and why (i.e. that someone added testosterone to the developing embryo).

Hey we could go one further and break this thing down to the level of quarks, and somebody will undoubtedly chime in to point out that any information gained by the particle accelerator will be useful in putting together the puzzle of autism. I disagree.

Thinking about autism on the level of genetic variance is a trap. You will never be far enough away from the trees to see the forest. The pace of genetic change within populations is slow; excluding major bottlenecks, it occurs on the order of millenia. Any condition that increases or decreases significantly in a population within a shorter timeframe is de facto NOT genetic.

If the rate of autism has truly increased then it is indeed a waste of resources to target genetic changes as important etiological factors of disease.

[michael framson]

Teresa, I so appreciate the continuing effort you make to enlighten what at times can be a very,very dark world.

In my romantic notion of wisdom and justice, it would be the writers, readers, and commentators on AoA who would direct research, mandate the studies, and sit as majority members on every advisory board that deals with why there are so many sick and injured children.

Then "The Riddle" of Autism as Dr. Karp refers to it, would be less of a riddle and more of action at stopping industry's rampage on our children's health whether vaccines or ubiquitous environmental toxic chemicals.

Its clear that AoA is part of the solution and the rest, disappointingly and self-evident, are part of the problem.

[Jimsomnia]

Angela,
Darryn Sikkora DOESN'T know what autism is and is getting plenty of research money to demonstrate her ignorance.

My son was also evaluated by her and Dr. Robert Nickel, who told us that his condition was "incurable and untreatable" and that we should "accept the diagnosis and let go of him."

Biomed treatments have made him the smart, affectionate, empathetic young man he is today. No miracle cures, but he's getting better despite OHSU and CDRC's ignorance and total lack of help.

Sikkora recently was on public radio telling folks that biomed treatments are "possibly dangerous" but CDRC would never tell a parent not to use "alternative" treatments if they work.

That is a LIE. She told us exactly that, but it was ten years ago and no one believes me.

So when OPB wants to talk to an "autism expert," guess who they call?

[Heidi R]

Thanks for reminding me how aggrivating the genetic versus environmental stance really is. Good job Red!

[Natasa]

To Keith: indeed some of the genetic studies out there are useful and on the good track. The ones dealing with detox and immune/inflammatory pathways. Those that could be put to good use when finding the triggers, causes and susceptibility factors, and could lead to more treatments.

But unfortunately those potentially useful genetic studies are so few and far between and they get buried deep beneath the pile of useless rubbish that makes up the rest of gene 'studies'.

One small example is the MIF gene polymorphisms and expression in autism. I'm dying to find out more, eagerly waiting for detailed follow up studies, that could lead to treatment trials. Waiting and waiting....

[Angela Warner]

This is a terrific article Theresa! Thank you for digging all of this out and sharing with us.

I'll second the nomination of the OHSU study, although I'm surprised that Darryn Sikkora even knows what the hell autism is. Nathan was evaluted at The Autism Clinic at the CDRC. Darryn Sikkora was the principal evaluator, and the ultimate diagnosis was (if you can believe this one) Adjustment Disorder. Nathan was diagnosed with PDD-NOS shortly after that. CDRC recommended 6 to 8 weeks of therapy and said he should be fine. We did six months and he was not fine.

My son did not develop empathy and go on to recover because all of a sudden a gene turned on or he developed one. My son developed empathy and recovered from autism through bio-medical interventions and appropriate therapy and social interventions.

Darryn Sikkora is a dufas.

[Lisa@TACA]

Nice history lesson Teresa. A really well done article.

Why is that others in mainstream media and medicine refuse to look at all the clues and the hundreds of thousands of kids?

I feel like a scene from: And the band played on....
"Just tell me the number and we will go away until then. Until we have a large enough number of those affected we will not cause any alarm."

Too bad we don't even have the luxury of a number. Wonder when our kids will matter?

[Bob Moffitt]

Thank you, Theresa, for taking the time and making the effort to expose the charlatons who have fashioned themselves a financially lucrative career....seeking the ever illusive "autism gene".

In many respects, these charlatons remind me of O.J. Simpson's "Dream Team" of lawyers...who devoted so much time and effort casting spurious allegations against everyone and everything that incriminated their client in the murder of his wife and Mark Goldman. The Dream Team accused police officers of planting evidence, criminalists of contaminating evidence .. allowing a sympathetic jury to delude themselves into believing that somehow...the contaminated evidence...morphed into O.J. Simpson's DNA.

O.J.'s promise to spend the rest of his life looking for the "real" killers of his wife has the same credibility as the "gene" researchers who pretend they are seriously pursuing the "real" cause of autism.

To this day I don't know how the members of O.J.'s "Dream Team" sleep at night..and..I feel exactly the same about the "gene" charlatons.