Much media attention has been given to some recent studies on the genetics of autismshowing some abnormalities on chromosome 5. Whether this is a major breakthrough in autism or just some other studies that have provoked some hype and hustle is open to question.
What is not surprising to this blogger is that Kev Leitch of left brain/right brain and founder of the neurodiversity autism hub has used these media reports to further a neurodiversity political agenda. However a number of Kev's contentions (and possibly by extension other neurodiversitites) are premature and unwarranted. Right off the bat, Kev makes an error and states that the article quotes the scientist as saying that if we could remove this variant as much as 25% of autism would disappear. Actually the number was 15%.
Using the 25% number (rather than the 15%) Kev then goes on to ask the question 25% of what, the individual? Autism's more disabling aspects? 25% of the population of autistics? Kev then goes on further stating that it is time for some sort of bioethics debate. That members of "the autistic community" should have a "respectful debate" with the scientific community on how this new technology should be used. By autistic community Kev obviously means neurodiversitites, since this does not include me nor probably the vast majority of persons on the autism spectrum who are too impaired to comment on write a blog post on this subject. Once again we have the phenomenon of the "royal we" that Harold Doherty so frequently writes about. Also when used by a neurodiversitite the term respectful debate has to be one of the biggest oxymorons in history. Though there are exceptions to the rule, neurodiversitites rarely treat anyone with respect. It is always, insult, attack, be abusive and "you are using this technology to try to destroy me" nonsense. As I have written before, neurodiversity is an ideology that is only driven by hatred as well as the two Freudian defense mechanisms of denial and reaction formation. They rarely want a respectful debate.
This is the age old propaganda of neurodiversity, genetic research on autism is only done with the intent of finding a way to abort autistic fetuses. What Kev and other ND's fail to understand is that genetic research is done with the intent of finding a way from preventing someone from becoming crippled and sick. Autism is a disease and a disorder regardless of ND denial. (I won't use the term disability anymore because I know that Janet Bain and other NDs will counteract that argument). If something could be done to manipulate the gene in utero in theory autism could be prevented and the individual would lead a healthy existence and not be incapacitated. This is the reason for genetic research. Or to perhaps find a way to cure autism if that is possible, but not for abortion.
In fact all Kev has to do is read what Dr. Hakonarson, the principal investigator has to say in the article I linked to which will answer his question:
With the new discovery, the hope is to identify children having these variants at birth or even in utero so intervention can begin early, Hakonarson says. Eventually, he says, the goal would be to create specific treatments to correct the gene variant.
all Kev had to do was read this one paragraph in this article and it would have answered all of his questions.
Of course Kev acts like this is something new. That these few studies have somehow elucidated some breakthrough which could cause such a great understanding of the genetics of all ASD's that the chance of aborting an autistic fetus or changing 15-25% of an individual's personality and makeup are really on the horizon. But is it new? For years, the mutation that causes fragile X has been known. Also known are forms of autism that can sometimes be transmitted via autosomal dominance in the case of tuberous sclerosis. Many other genetic etiologies are known. The genetic etiologies have probably been known for at least 10% of all ASD's for quite a while. So far the technology does not exist to either treat these individuals, abort them as fetuses or change their personalities.
Kev is not the first to be confused on this issue. Temple Grandin and Simon Baron-Cohen have also proposed that autism genes confer some sort of advantage to a person or even genius. This is in spite of the fact that in all of the genetic studies that have been done on autism, there have been findings on X chromosomes, also autosomes on many different chromosomes. An abnormality on chromosome 22 which causes DiGeorge syndrome often is associated with autism. Abnormalities on chromosome 15 and many others have been found as well. There is no evidence that any specific autism gene is responsible for a person being a great inventor or saving civilization as Grandin and SBC often claim. I have written an essay debunking this notion
Recently I went to a lecture that Dan Geschwind gave at UCLA. He is one of the people who apparently was involved in these new genetic studies. He seemed to state that one of the problems with research on genetics in autism was the fact that the sample sizes were far too small and because autism had many different genetic etiologies that they could not get a great deal of homogeneity. But with larger samples and more money spent on research it might be possible to get more homogeneity where we might be able to find a single genetic deficiency in a fair proportion of persons with autism. This could lead to better treatments or even prevention (again not abortion).
Therefore for all of these reasons I think Kev's claims are quite premature and it will most likely be quite some time before a real debate is needed for ethical issues. However, I have no qualms about funding genetic research if at some point it will help us understand this horrific disability and lead to treatments, even possibly cures and preventions and I brook no quarters there.
Ari Neeman and his merry band of crusaders at ASAN have called for a moratorium on genetic research until the issues that Kev brings up are resolved.
Neurodiversity claims to be about human rights for all people regardless of their neurologic makeup. Well, how about the right to treatment or the right to have something prevent you from becoming crippled and sick in the first place?
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13 comments:
To be honest, I am not afraid that the ND stuff will ever convince the scientists that autism is "just difference" and not an illness.
Yet, my fear is that the politicians will have an open ear to such nonsense. Imagine that the US government will declare, solely on political basis, that autism is not an illness but a neural variance. Quite soon all the other countries will follow suit.
Such situation will change radically the funding given to autism research (where such research is conducted) as well as the funding given to assistance for autistic people (in all the countries).
In other words, "if you're just different, do it on your own". While such attitude will change very little the lives of people like Ari Neeman, it would have disastrous effects on the autistics who need help and have to rely on public services for it.
I have tried to get hold of the Hakonarson’s recent papers but PubMed abstracts are ahead of publication; if anyone is able to access the online versions let me know.
Without reading these papers, I cannot really comment of the quality of the studies. i.e.I do not know how confident we can be that the genetic abnormalities reported are indeed related to autism in the studied cases. A duplication, or single nucleotide polymorphism does not necessarily cause a phenotype. The genes mentioned makes sense within a paradigm of neurological brain development disorder but we should not forget that many of these genes, e.g. cadherins, CNTN4, ubiquitin actually also have function in regulating the immune system. If these mutations are genuinely related to autism, is that because they cause abnormalities of brain development or make the individual more susceptible to insult of an immune origin? I am afraid the studies very unlikely address this question, even as hypothetical possibility in the discussion section (let’s see though). The question can only be addressed in animal model, a “Knock In”, as we call it, which replaces a gene with a potentially “mutant” version of, it in the mouse genome.
Generally speaking though, even if a developmental gene, is involved in as little as 1% of the ASD population (1% is today’s rate of Fragile X Jonathan, not 8-9% as it was 15 years ago, the population is changing), even with as little at 1% of the overall contribution, that would be an important finding. But the point is, should a study that identify plausible cause of a condition in only 1% of individuals and that requires huge sums of money be conducted? Isn’t it a little bit like going to the moon? And what is that for? This is where one should look behind the scene, what are the true motivations behind these studies. Sorry to say, but it has, as often, little to do with science and health.
True ethical prioritization in the research in causalities of autism comes with a full account its current features: Gene- environment- involving the immune system, the gut, the behavioral features of autism, and the regressive aspects of it.
I await to read the story in full to form a definite opinion, but personally, I think finding genes involved in immune regulation is potentially very interesting. Also, finding de novo mutations, definitely suggests some environmental factors at play.
Kev: I notice one of your commentors said the same thing. I only saw the 15%. I guess the error was made by whomever did the piece not you, if that is the case I stand corrected.
SM69: I have no idea if it is in the brain or immune system. I think they were saying that this gene was involved in neuronal connectivity, though and might not necessarily make someone more susceptible to an immune deficiency. I heard the time as being knock out rather than knock in. Of course maybe a different term is used in the UK than in the USA, I don't know. I am not sure how beneficial a knock out mouse study would be in that mice are probably a very limited animal model for autism as they don't speak so we won't know if they have a speech delay and since they don't handwrite we don't know if they have a fine motor coordination problem of the type i have.
Also, once again I think you missed some of the points in my post. It is not a question of just studying fragile X or one type of genetic deficiency, but rather to find as many genetic deficiencies as possible in ASD's. If you re-read my blog post you will find that I quoted Dan Geschwind as saying that one of the problems with lack of homogeneity in these genetic studies was the small sample size. It is possible that if enough capital could be invested we could do gene sequencing on thousands of persons with ASD and get more heterogeneity and make a definite pinpointing of some of the genetic causes of idiopathic autism.
With money going both to biomed concerns (which I know you are a part of) and neurodiversity concerns, this takes capital away from really practical things that could help prevent and cure this horrible affliction.
"Knock-in" is a term used anywhere in the world and it is not a knock-out but one more level of sophistication: you knock a gene out and you replace it with a mutant version. Knock it out is to remove it fully, knock it IN is to put IN a new one instead. That is the only way to find out if an allele (as identified in a human population) can indeed cause a condition.
I agree, knock out or knock in are essentially a waste of time, it takes ages (several years), cost a lot of money, and very often, there is no phenotype identified, even when you knock out genes that are highly evolutionary conserved (been there, painful). The reason is that sometimes, one can only find things if the technology is in place, or when the anaimal is challenged under specific environmental settings (or genetic backgrounds) to find a phenotype. Other time, the gene that was thought to be involved in brain development for example is found to have a primary function in the immune system. Science is compartmentalized, though not as much as medicine is.
My point was that genes that are involved both in neurological and immunological processes as a whole might carry alleles that will predominantly affect their immune role. We don’t know. It’s wrong to say these genes are neuronal genes only, they are not.
I got your point, I understood it, at least I think so. I forge my opinion not just on what you wrote, or what others wrote, e.g. Blaxill on AoA (which was quite good), but on how I think about this all, and how I view the data presented wiping away from my mind what everyone has said about them because news reports are very misleading, blogs even more!.
Biomed is not what I think research in autism should be in. Don't fool yourself, no significant research money has been put into this, nor as it in the ND issues. I am a total advocate for academic research in the causality of genetic-environmental origins, perhaps you never quite understood when I tried to explain this to you? I got the point on the genetic diversity, it’s very obviously the case, isn’t it? We don't need a Nature paper to know that. But I can say one thing, if a given gene was involved in as many as 15% of today’s cases, it would have been found already. We are talking about a much more complex genetic here (I mean for the whole population); epigenetic as I have said is the most plausible and appealing model.
Let me clarify what I posted last night regarding biomedical autism research.
Biomedical does not mean DAN! And I assumed you meant DAN!, the use of vitamins, chelation, that sort of bag of approaches. In fact biomedical relates to the activities and applications of science to clinical medicine. The University of Edinburgh has set up a huge biomedical institute in the hospital ground and let me clarify, they don’t do DAN! on rats. Biomedical is an established field of science.
What I meant was that we do not need more research to show that orange juice is beneficial to health. We don’t need to show that nutrition improves cognition, that sort of questions that should be established by now, even if this is not yet translated to radical changes of life style, see for example the schools diner provided in the UK.
In the Biomedical field of autism, we need to understand regressive autism, the connection between behavior and the immune system, behavior and gut health. We need to redefine the diagnosis in sub-phenotypes, with common developmental clinical, biomedical, and behavioural characteristics. How could the environment interfere so much in the development and behaviour of genetically susceptible individuals?
We also need to report individual cases with detailed biomedical profiles, being someone with regressive autism as a consequence of herpes encephalitis as Gillberg has reported in adults and teenagers, or issues of mitochondrial dysfunction as reported in Poling case, or cases of intermittent acute porphyria, or cases of fetal alcohol exposure related to autism, or of course any single mutation found in families etc.
We need to understand the overlap between autism, ADHD, OCD, BP, schizophrenia, epilepsy, and MS, firbromyalgia, ME, arthritis, asthma, allergy (these commonly run in the families of ASD kids). We need to understand the role of oxidative stress in the condition.
We need to find markers of a biomedical or clinical nature to enable the individual’s health to be monitored longitudinally. And we need to identify susceptibility markers, genetic as well as environmental.
In term of intervention, there is no point to set up studies that will look at one single aspect of what parents are doing now, say, MB12 for example, because that is not what families are doing. Families are putting many interventions together and that is the combination of them that seem to be effective. For this reason, we, at our trust, have proposed a RCT design for a combined intervention of a dietary, nutritional and pharmacological nature. We would assess the benefit of the whole package.
But beside this, there is all the support needed to learning that needs researched, Biofeedback, FastForWords, motor activities to stimulate the cerebellum, etc etc.
These types of research have direct outcomes to improving the life of people with autism. Which is not the case of genetic research. Because so far, we are born with our genes and cannot change them, stem cell therapy is a long way from becoming a reality in autism. I understand Jonathan that you hold the belief that you have received unfairly the wrong set of genes and that might indeed be the case. Of course it would be nice to know why that is, but the chances are very high that the explanation that might be true for you will not be that true across the ASD population. We have a lot more consistent findings to look at, in priority, which hold wider promises in term of interventions and understand of the condition.
You are neither crippled nor sick -you're just a crybaby wuss.Hi Clay, is that you? Normally I would not publish a comment like this, but it is so ironic coming from an ND who are among the biggest crybabies and wusses in the world that I had to publish it. These are people who hide behind computer monitors and attack and bully people and usually refuse to sign their real names. These are people who complain about trivial things like the ransom notes campaign or the nonmalicious use of the word retard in a movie. They try to prevent anyone who writes stuff that disagree with their warped agenda from publishing it or posting links to it.
If any group of people are the biggest crybabies and wusses that ever lived it is the neurodiversitites.
SM69: Yes I guess basically i meant things like DAN or things like it. The terms biomed and DAN can be sorta interchangeable.
The money that goes to bogus fringe treatments like chelation, GCFC diets, secretin etc, that DAN practitioners such as yourself advocate is wasted money. Money that could be spent on research to find real cures and preventions.
Hi Jonathan
There are certainly not millions spent towards evaluating commonly used biomedical interventions in autism such as the ones you listed but just the opposite! And this is a big problem. Take the example of GF/CF diet, there are perhaps 2-3 studies at most that have a proper RCT design that can be used to determine if the intervention is beneficial or not, in total, perhaps 10 studies, not well designed have addressed this question. These studies were not done in the USA so they did not drain the money available in your country for research. The outcome of the suitably designed ones shows benefit. I am only aware of one properly designed NIH founded study on orla DMSA chelation that was discontinued following a child’s death because of incorrect administration of iv Magnesium EDTA. The death of that child was of course very upsetting but the evaluation of safety and efficacy of oral DMSA (a different intervention that is FDA approved for lead removal in children) in suitably designed study, with full ethical approval should continue, because parents do this anyway, so proper evaluations are needed. Regarding secretine, well, I have not used it, but my guess is that the isolated reports of benefit were real, the problem is that we don’t know why. This is why it is important to break down Autism in sub-phenotypes as I have explained earlier, because you need a group that is as homogenized as possible to evaluate an intervention. You are entitled to have your opinion on the money spent towards this sort of studies, but I am afraid, nothing substantial by comparison to what has been spent on genetic studies (that have had zero beneficial outcomes in term of improving the life of ASD people). And you are entitled to say they do not work, but I tell you, they do, though not for everyone and not to the same extent for anyone. They work, and this is why people continue to do them, on their kids, even though no proper evaluation has been done. This is a major problem in my opinion. Why would you not see proper evaluation of therapies that have been found anecdotally to work being an absolute necessity in order to suitbaly advise parents on what they should do and in order to provide these interventions freely? Is that because you don’t want people to be helped? Is that because you think nothing can help you? Is that because you are so convinced this is a waste of time and money, even though you clearly do not actually know about the real potential benefits of these interventions can have?
I won't keep arguing, I promise, so I'm off the blog fo the rest of the weekend!
Why would you not see proper evaluation of therapies that have been found anecdotally to work being an absolute necessity in order to suitbaly advise parents on what they should do and in order to provide these interventions freely? Is that because you don’t want people to be helped? Is that because you think nothing can help you? Is that because you are so convinced this is a waste of time and money, even though you clearly do not actually know about the real potential benefits of these interventions can have?I believe that even anectodotal reports of certain treatments do warrant studies, quite the contrary to what you are saying.
However, for most DAN treatments when these studies have been done they have invariably been shown these treatments are worthless.
In spite of 15 studies absolutely refuting any benefit of secretin your leader of DAN Steve Edelson insists that this is one of the most potentially promising treatments for autism. He misrepresents the work of Janet Kern on secretin by saying that it showed an improvement of all persons with autism and not just the one's with GI problems which were a small percent of her sample of persons in the JADD study to which he refers to. Most parents of children have never read that study and never will.
There is no point in doing a trial of chelation unless there is evidence for mercury being involved in the etiology of autism. About 17 studies have refuted any involvement of vaccines in autism. There is no evidence that mercury is involved in autism Karin Nelson and Margaret Bauman's paper certainly provides compelling evidence if you have read this paper. I did not use the word "crap" that we ascribed to me in describing Ray Palmer's studies but actually that is a very apt description. Ray Palmer's studies were crap, he is a crap scientist and the editorial boards of the journals that published his low quality studies are incompetent. So there is no reason for chelation trials to be done and it makes it all the much worse that a child had to die for nothing.
I don't know as much about the GFCF diet studies, but I know there was at least one study published in JADD that showed this treatment to be ineffective though i have not read the study so i cnanot comment further.
But in sum, DAN practitioners have no interest in science or providing empirical evidence for any of their treatments and they continue to sell these treatments in spite of overwhelming empirical evidence against them.
Yes, I want autistics to be helped, I want autism to be prevented and cured. Though genetic studies have not lead to any practical treatments or prevention of someone becoming crippled and sick does not mean that they won't be at some point in time, so I see no reason why genetic research should not continue.
Jonathan, I will answer your comment in a few days, I am not moving away from this, but for now, he is a short answer:
Don’t mix up, DAN and Biomed, Don’t mix up, science and DAN, don’t mix up the sort of things we do and DAN. I can totally justify our approach and I am totally honest and clear to parents about what is known and what is still unknown. Also, don’t mix up chelation and mercury (there are a lot more heavy metals and toxins in the body than mercury and we have reliable tests to asses this, this was published), don’t mix up vaccine and mercury either. All what you said can be argued and discussed, and I will address each points at some stage. Meanwhile I am absolutely NOT aware of the many studies you mention on DAN! evaluation, why don’t you give me the references so I look them up? . I do not know what Edelson has said on Secretin or not, but I’d be very amazed he mentioned that it works on anyone. In fact I read in the parent evaluation on the ARI web site, regarding the benefits and side effects of intervention the following for secretin:
Secretin: Intravenous
7% 49% 44% 6.3:1 468
Secretin: Transdermal
10% 53% 37% 3.6:1 196
The first figure is got worse, the second is no effect, the third is got better, the 4th is better:worse ratio and the last is the number of parents rating this.
Of course this does not equal to a study of any kind, and we have no idea how reliable parent’s ratings are, nor do we know how much this has helped and what else they did at the same time. This is what is problematic in this kind of report, though I agree with you on Secretin side, studies were conducted with good design, though using a very heterogeneous population as sample and found no efficacy. There has been a lot more studies on Secretin than on any other aspects of the intervention, why? Because it is patented and one can make money on it, which is not the case of many other supplements or even generic drugs, like LDN that is very beneficial in ASD. I am not aware of any DAN practitioner currently advocating the use of Secretin, I think it is way too expensive and the chances of no effect are very high until we have understood why it has worked in isolated cases. DAN does not mean much, I am afraid, I don’t think there is any kind of serious training other than attending to a conference, it’s like a label that say, well we can do that type of things, but it does not give any indication of rigor. Most medical practitioners are not trained to conduct research and seem totally unaware of what it takes to demonstrate rigorously efficacy. This is not the case of everyone, but the vast majority of them. I pretend to be seperate from that.
Fine I look forward to your next post. As far as Edelson's take on Secretin I wrote a post about that on autism's gadfly some time ago. I think this was before you started reading my blog. I gave the link to the ARI webpage where Edelson claims that secretin had the potential to be one of the most promising treatments for autism and he misrepresented Janet Kern's study. I don't have the exact reference from Kern's work, but it was published in JADD and i am sure you can find it. Though I don't have the exact link of the gadfly post handy you can find it either by searching on google or by going through the archives of this blog. Adam Sandler and Michael Chez have both done studies on secretin and there are many others. i might email you the link on gadfly after i find it.
I gave you Karin Nelson's and Margaret Bauman's studies on why the neuroanatomy of autism is totally inconsistent with mercury poisoning, this probably applies to other heavy metals as well. There is no credible evidence that heavy metals play any etiologic role in autism or I will believe it when I see the proof you furnish.
There are many studies refuting vaccines as the cause of autism. You can also read my essay showing no temporal relationship between rates of increase in autism in california regional centers (the data that DAN people use to push chelation) between 1970 and 1990. At the risk of sounding immodest, if the researchers refuting thimerosal had looked at the data the way I did, many of the studies about thimerosal and vaccines would not needed to have been done at all. Unfortunately I did not think of this lack of a temporal relationship until well after the 2003 california report was published, but when I did I wrote the essay I linked to.
Not sure what other references I could give. Most germane to the question of chelation is Nelson and Bauman's paper, unless you can show some evidence that metals other than mercury cause an increase (rather than a decrease) in brain weight and affect purkinje cells rather than granule cells. I am not positive, but i don't think this is the case of other metals besides mercury.
Hi
I am only coming back on the subject because I had said, I would, and I don’t like leaving things with a sense of being unfinished ;-), though we have had some exchanges on the Secretin stuff. It’s not that we have agreed to disagree, but in my opinion Sectretin is not DAN! and vice versa, though Jonathan thinks differently. There might be money involved, I am certain this is indeed the case, as this is patented. But I don’t think most practitioners advocate to use of Secretin, we don’t. I am aware of one person only in the UK proposing it and to be honest I find amazing that he still manages to find parents to agree to it.
As for my question regarding the evaluation of biomed approach in autism or elements of it, no, I am afraid, there is no significant research here. A few on GF/CF diet, some on essential fatty acids, some on MB12, glutathione, some on LDN, of course plenty on all the drugs (as these are patented), but there is nothing that really that addresses the benefits/side effect of what parents actually do as packaged intervention.
In my opinion that needs to be done. And there is not a great deal of money required. I can send you the costing of one of these studies, you can do a pilot around 95K and a RCT around 400K, completed in 18 months. Nothing compare to what the genetic works takes, nothing.
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