Another Nail in the Coffin...
Although I have begun to despair that the "mercury-causes-autism" hypothesis can ever be killed, a recent study by Zhao et al has driven another nail into its coffin.
In their study - "A unified genetic theory for sporadic and inherited autism." - the authors describe exactly how spontaneous mutations could cause both sporadic autism (autism in families without a family history of autism) and familial or inherited autism.
You see, this has been the real mystery in autism (not the faux myteries of "poor excretion" and "mercury poisoning") - how families with inherited autism can show the same mutation in all affected members yet not have the same mutation as other families with inherited autism (for example, see here, here, here, here and here).
The answer, it appears, is that females with mutations associated with autism may be resistant to developing autism. Why this is so is not yet clear, but it has been shown pretty conclusively. These women may have one of the many mutations that cause autism but they do not develop the disorder themselves.
However, even those who don't develop autism are still carriers of that genetic mutation and (on average) 50% of their sons will receive that the mutation. Of the sons receiving the mutation, a high percentage of will develop autism. Additionally, about 50% of their daughters will also get the mutation, although only a few will develop autism (all who receive the mutation will be carriers).
This, of course, is not the entire story, but it is a reasonable lay summary of the article.
For those people who will immediately say, "Aha! It's those nasty chemicals/viruses/cell phones that are causing mutations in our children!", let me point out one thing:
The mutations are in the germ cells (i.e. sperm and eggs) of the parents of the autistic children. For these mutations to happen in a child and cause autism, it would have to happen at the single-cell stage (immediately after fertilization).
I encourage people to read the article for themselves - it's available free online. Don't just take my word for it. It's not an easy read, but even if you can't understand it all, you should come away with the idea that [a] this looks less and less like a simple case of "environmental toxicity" and [b] it is a much more complex issue than many of the autism "advocates" would have you believe.
Happy reading!
Prometheus
In their study - "A unified genetic theory for sporadic and inherited autism." - the authors describe exactly how spontaneous mutations could cause both sporadic autism (autism in families without a family history of autism) and familial or inherited autism.
You see, this has been the real mystery in autism (not the faux myteries of "poor excretion" and "mercury poisoning") - how families with inherited autism can show the same mutation in all affected members yet not have the same mutation as other families with inherited autism (for example, see here, here, here, here and here).
The answer, it appears, is that females with mutations associated with autism may be resistant to developing autism. Why this is so is not yet clear, but it has been shown pretty conclusively. These women may have one of the many mutations that cause autism but they do not develop the disorder themselves.
However, even those who don't develop autism are still carriers of that genetic mutation and (on average) 50% of their sons will receive that the mutation. Of the sons receiving the mutation, a high percentage of will develop autism. Additionally, about 50% of their daughters will also get the mutation, although only a few will develop autism (all who receive the mutation will be carriers).
This, of course, is not the entire story, but it is a reasonable lay summary of the article.
For those people who will immediately say, "Aha! It's those nasty chemicals/viruses/cell phones that are causing mutations in our children!", let me point out one thing:
The mutations are in the germ cells (i.e. sperm and eggs) of the parents of the autistic children. For these mutations to happen in a child and cause autism, it would have to happen at the single-cell stage (immediately after fertilization).
I encourage people to read the article for themselves - it's available free online. Don't just take my word for it. It's not an easy read, but even if you can't understand it all, you should come away with the idea that [a] this looks less and less like a simple case of "environmental toxicity" and [b] it is a much more complex issue than many of the autism "advocates" would have you believe.
Happy reading!
Prometheus
posted by Prometheus at 1:33 PM
16 Comments:
Prometheus, I confess I'm a little confused. Can males be carriers of the mutation too, without presenting autism symptoms?
You see, I can trace autism in my family starting on my grandmother (my father's side) and cousin (same side of the family), both women with Asperger's. Then I have my son with autism (high functioning).
Is my NT brother at risk of having autistic offspring?
Thank you,
So, it must be some genetic mutation that began at 8 years of age that started reversing the symptoms of autism and not the chelation. That makes sense, if genes can mutate to cause autism, they must also mutate to cure it. Thanks for letting me know this.
Thanks for the simple terms Prometheus.
I'm waiting for the headline: Chinese-Made Toys Linked to Autism story to break any minute.
Great post as usual. But do you think that this kind of science is going to mean anything to the mercury militia?
Another Autistic Mom,
According to this study, males can be asymptomatic carriers as well as females. The difference is that males are more likely to develop autism (symptomatic) from the mutations, so there will be fewer male carriers and more males with autism.
Fore Sam,
You seem to be stuck on the idea that autism is a syndrome of developmental stasis. It's not! It is a syndrome of developmental delay.
If you follow any autistic child through time, you will see them make progress - some more than others.
I have seen autistic kids go from completely non-verbal and no eye contact or social interaction to being indistinguishable (on casual observation) from their "typical" peers without any of the "biomedical" interventions you are so fond of.
Likewise, I have seen autistic children get the "whole enchilada" - from DAN! to nuts - and remain non-verbal and socially isolated. Their progress seems to be completely unrelated to the "therapies" they get.
The finding that mutations in many different areas of the genome can cause autism explains much of the diversity we see in autistic children - and in autistic adults. It may be more useful to think of autism as a symptom than as a disorder.
Bart,
As Fore Sam so kindly demonstrated, the "true believers" aren't going to be persuaded by anything. Not science, not reason, not even if God himself wrote it in big letters in the sky.
My purpose is to provide an alternative viewpoint for people who haven't made up their minds yet - people who can still be reached by reason.
Mekei,
I'm sure that headline is coming. It's just that Dan Olmsted is in the process of moving to a new office. Just wait, he'll get to it as soon as he can.
Prometheus
Right. I suppose my father and I are carriers; my sisters, who had NT kids only, may not be. My brother, who hasn't had kids yet, may or may not be a carrier.
Now, in regards to the discussion of causation - if you go to the IAN website, they are emphasizing that this theory supports the argument that an environmental event caused the spontaneous mutation. Parental age is a huge influence, but it can't be the reason for all cases.
In my opinion, whatever this environmental agent may be, it will be very hard to avoid, since autism is pretty much present all over the world no matter how healthy a community is. I think the vaccine theory is crap, and autism parents need to rationally look at data available to see that it will take many years, maybe never, until science figures out what causes that mutation.
Another Autism Mom,
I'd be a bit cautious about assigning carrier status to any of your family members. Autism is, after all, one of the most rapidly growing diagnoses in pediatric mental health and, as such, has quite a bit of "faddishness".
From what I've seen - and I'm not a psychiatrist or psychologist - children are often labeled as "autistic" based on "educational criteria", which are generally (90+% of the time) much looser and less defined than the medical diagnosis of autism.
Even diagnoses made by a physician are often suspect, as there are a number of less-than-skilled physicians who are happy to slap that label on a child and then start pumping them full of vitamins, supplements, chelators and hyperbaric oxygen.
The thing to remember is that true familial (inherited) autism is the exception. Most of the cases appear to be de novo, meaning that the mutation is present in the child but not in the parents or siblings.
Another critically important point is that these mutations are germ cell mutations. This means that the mutation occurred in the sperm or egg that went on to form the embryo that is now the autistic child. The mutation happened in the parent. It was not due to any exposure that occurred after birth - or even before birth, unless it happened right after fertilization and before the first or second cell division.
If you want to look at possible causes of the mutation, you need look no farther than the air around you. The most common cause of mutations is oxidative damage to the DNA caused by oxygen.
While advanced maternal and paternal age play a role (primarily through accumulating mutations in the germ cell line), almost any other mutagen could be responsible (including the All Time Winner - oxygen!).
If you want to look at environmental exposures, you should be looking, not in the 21st century, but in the late 20th century. And you should look at exposures that the parents received, not the children.
Prometheus
Recently I saw a comment in a blog (I think it was GR's blog) where a parent said something like: "How can it be spontaneous mutations, considering I have 3 autistic children?" Somewhere else another parent said something like this: "How can it be genetic, considering I have one autistic child and one typical child?"
I thought it was funny.
Clearly, autism is often inherited from parents, and often the result of a de novo mutation, and sometimes it could be both. We're probably not talking about a single gene either, but maybe a practically unmappable array of genes. Plus there's no doubt environmental factors that make an autism diagnosis more or less likely.
It's not likely to be something as simple as a predisposing gene with a clear-cut environmental "trigger", such that everyone who has the gene and the trigger is autistic, and everyone how is autistic has the gene and experienced the trigger. Reality is rarely that simple.
Because it is possible that environmental factors pay a role in determining the way in which genes are being expressed, I don't think that a loose description of genetic factors excludes environmental factors.
As a matter or personal opinion, I don't think environmental factors are very important. I think it is mostly a social phenomenon having a lot to do with how kids socialize and what we expect of them now as compared with a generation or two ago.
Nonetheless, the findings you mention would do little to convince me that biological environmental factors are not involved.
Joseph,
The Sebat et al paper in Science (20 April 2007) found a large number of different mutations - all de novo mutations - in subjects with autism. This reinforces my hypothesis that autism is not a discrete disorder, but is a sign or symptom of several conditions.
There is still room under the autism "umbrella" for environmental causes and genetic sensitivities to environmental exposures. However, nobody has yet come up with data to support any particular environmental exposure or "toxin". The data on mercury, for instance, seems to indicate that it is not a significant cause of autism.
VAB,
To be sure, "genetic" does not rule out environmental sensitivities that are genetically determined. In fact, one could argue that a large fraction of disease - and even injury - has some degree of genetic determination, even if it is simply a genetic predisposition to risk-taking.
However, I must reiterate that the mutations found in the Sebat et al study originated in the parents (in their sperm or egg cells) and are not the result of environmental exposures to the children.
That said, it is entirely possible that these mutations cause the children to be sensitive to some factor in their environment - as yet undetermined - that resulted in autism. It is also at least as likely that these children would have developed autism no matter what their environment had been.
Another question that is often raised is, "How can genetics explain why my child was perfect until right after they were exposed to [fill in the blank]?"
One of the most rapidly expanding fields of genetics is developmental genetics - how genes control the development of complex, multicellular organisms, such as ourselves). In the process of development, and especially in early childhood, a dizzying number of genes are turned on, turned off, and modulated in some fashion or another.
If there is a mutation in a gene that causes it to not turn on, not turn off, or fail to do the proper action to the next gene in the process, then there will be a failure in development. It is not hard to see how a mutation in such a gene could remain invisible until it was supposed to be turned on (or turned off). Only at that point would development go awry and the defect in the gene become apparent.
Considering how many genes are being regulated in the developmental stages where most parents report the onset of autistic signs, it comes as no surprise that a mutation in one of those genes would manifest itself at that time.
For people who want examples of genetic disorders that only manifest later in life, I provide a short list:
Huntington's Chorea
Parkinson's Disease
Schizophrenia
Danon Disease (LAMP-2 mutation)
Duchenne Muscular Dystrophy
Prometheus
Fore Sam,
I deleted your offensive comment - you will now be placed in the "penalty box" for a month.
To answer your question, early studies suggested that LSD might cause chromosomal breaks, but subsequent studies failed to replicate those findings. Currently, LSD is thought to be generally free of genetic toxicity at typical doses.
That doesn't make LSD a safe drug to use, so don't try to put those words in my mouth.
Your question revealed not only your appalling lack of basic human decency, it also showed that you have poor reading comprehension skills.
Mutations in adults (or near adults) will not cause autism. Even mutations later in embryonic development will not cause autism. The mutations have to happen either before fertilization (i.e. in the parents - as I have said only about a half-dozen times) or before the zygote has undergone more than a few cell divisions.
Prometheus
Another genetic disorder that shows up later in life is hypertrophic cardiomyopathy:
http://www.4hcm.org/WCMS/index.php?id=80,0,0,1,0,0 ... which says "Keep in mind that the genetic predisposition to HCM (i.e., the mutant gene) does not always trace back many generations in the same family but may occur spontaneously and for the first time in a member of the most recent generation. This is known as a de novo mutation. At present, the environmental factors that may trigger HCM mutations are unknown."
Also BRCA1 and BRCA2 can cause breast and ovarian cancer in women after they turn 20 years old (those two genes only seem to be implicated in 2% of breast cancer, but it is a type that hits young women).
Here is an interesting notification from the HCM website about the Genetic Information Nondiscrimination Act:
http://www.4hcm.org/WCMS/index.php?aid=162
If you want to look at possible causes of the mutation, you need look no farther than the air around you. The most common cause of mutations is oxidative damage to the DNA caused by oxygen.
Just think, all the parents and children are being intentionally and repeatedly exposed to a known cytotoxin.
"In fact, the government apparently encourages exposure to this known cytotoxin. Here's just one of many examples. The IOM has published guidelines for AI (adequate intake) of water for several age groups (beginning immediately at birth). Informed people know that water is almost 50% oxygen (a known cytotoxin) by weight."
Perhaps the X-Men analogy is not as farfetched as it seemed at first glance...
DoC,
In fact, water is 89% oxygen by weight. And water is a source of some of the most damaging free radicals. We could pretty much stop aging if we could eliminate both water and oxygen (gas) from our lives.
Prometheus
This may not be the approved line of thinking, but I can't help, as I read that autism is most likely genetic with the potential for some unidentified/unidentifiable environmental trigger, comparing this to the spectrum of sexuality.
My family presents a pretty strong (if anectdotal) argument for sexuality being an inherited genetic mutation: I'm about a 4 on the Kinsey scale (bi/lesbian), my father is gay, his younger sister is gay (there are 5 children in their family), and various more distant relatives are gay. In other families, the mutation may be spontaneous. In both the case of autism and gayness, afflicted family members, in less tolerant times, might have been sent away or forced to behave as 'normally' as possible, likely to their detriment as people.
I pretty strongly believe sexuality is genetically determined and then culturally influenced. Someone who is predisposed to a given sexuality may act on this earlier or later depending on the people around him and other cultural issues. Obviously, being raised by divorced parents, still friends and one of them gay, I felt comfortable coming out at a relatively young age (19) whereas my dad didn't come out until 36. I'd love to see the stigma of autism lessen until people are comfortable having autistic children and accepting them for who they are with all the bonuses and detriments that autism can be rather than trying to 'fix' them. Luckily, a lot of the glbt community has made this progress, so I have strong hopes for the autistic community.
Incidentally, I doubt the ONE gene for gayness or autism will ever be found. It seems impossible something so complex as sexuality or autism could be caused by a single gene, especially given the broad spectrum in each of them.
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