…and this is a 
I've gotten some email asking for a simplified executive summary of this paper, so here it is.
A large study of almost a thousand autistic individuals for genetic variations that make them different from control individuals has found that Autism Spectrum Disorder has many different genetic causes: there isn't one single gene responsible for ASD, but a constellation of hundreds, each with the potential to affect the development of the brain and cause the symptoms of autism. They don't know exactly how each of these genes contributes to the disorder, but they have found that many of them are involved in growth and cell communication and the formation of synapses in the brain.
The bottom line is that there are many different ways to cause the symptoms of autism, and it's a mistake to try to pin it all on single, simple causes. Any hope for amelioration lies in understanding the general functional processes that are disrupted by mutations in various pathways.
Coming up with simple, one-size-fits-all answers to serious problems is so tempting and so satisfying. Look at autism, for instance: a mysterious disease with a wide range of expression, so wide that it is more properly called Autism Spectrum Disorder (ASD), and the popular press and various celebrities all want it to be pegged to a simple cause: it's vaccines, or it's mercury, or it's the dose of the vaccines, and all we have to do to fix it is not vaccinate, or reduce the number of vaccinations, or use chelation therapy to extract poisons, and presto, a cure! This is magical thinking, pure and simple, and it doesn't work.
ASD isn't simple, it's not one disease, it doesn't have one cause, and vaccines are definitely not the cause: if there's one thing the research has done, it's to thoroughly rule out the idea that giving kids shots at an early age causes autism. What we're actually discovering more and more is that ASD can be traced to genetic variation.
Again, though, the causes aren't simple. There is no single mutation to which ASD can be pinned.
For example, one hot spot for an association of genes with autism is the long arm of chromosome 22; cases of developmental delays and autistic behavior have been associated with partial deletions in chromosome 22, and the problems have even been narrowed down to one specific gene, SHANK3, which is expressed in neurons and localized to synapses. We know that if you've got a broken copy of this particular gene, you're likely to have ASD.
How many ASD individuals have this specific genetic change? 0.75%. It is a cause in less than 1% of all affected individuals, but it cannot be the sole cause of ASD in all cases. We have to get out of this mindset that tries to find single causes for complex phenomena; ASD is a case where we have a complex range of disorders with multiple, complex causes.
So how do we get a handle on ASD? This is where the work gets interesting: just because something is multi-causal does not mean that science can't get a grip on it and that we can't learn anything interesting about it. We've got lots of new tools for analyzing broad properties of genomes now, and one promising line of attack are methods for measuring and identifying copy number variants in individuals and populations.
Copy number variants (CNVs) are surprisingly common. If you've had any biology instruction at all, you're probably familiar with the Mendelian concept that we have two copies of each chromosome, and two copies of each gene. As it turns out, that is an oversimplification: sometimes, a piece of a chromosome is accidentally duplicated, and then you'll carry two copies of the associated gene on one chromosome, and one copy on another chromosome, for a total of 3 copies. And in some cases, these duplications have occurred often enough that you'll have many more than 3; the median number of copies of the amylase gene (an enzyme that breaks down starch) in European American populations is 7, with a range of 2 to 15 in different individuals. Get used to it, this kind of variation in copy number seems to happen fairly often.
Now in the case of amylase, the effect of this variation is mild — individuals with more copies of the gene produce more of the enzyme and break down starchy foods faster. It does have evolutionary effects, since cultures with diets rich in starch contain individuals who have, on average, more copies of the gene than individuals where starches are less common in the diet. But what if these chance variations in copy number affect genes involved in the function of the brain? We might see more profound effects on behavior or cognitive ability. The defect in SHANK3 mutations is an example of a reduction in copy number of that gene; what if we could screen populations of ASD individuals not for a specific gene variant, but for the more general occurrence of frequent variations in copy number of any genes…and then we could ask which genes are often affected?
It's being done. A new paper in Nature describes a screen of control and ASD individuals to identify rare copy number variants associated with autism. It worked! In fact, it worked maybe a little too well, since we now have an embarrassment of riches, a great many genes that may be related to ASD.
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable (~90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 × 10-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
They analyzed both affected individuals and their parents, and found both familial transmission — that is, the child with ASD had received a copy number variant from a parent who was a carrier — and de novo events — that is, the child had a spontaneous, new mutation that was not present in either parent. There is no one single gene that can be tagged as the cause of autism: they identified 226 de novo and 219 inherited copy number variants in affected individuals. No one individual carries all of these variants, of course — the results tell us that there are many different paths to ASD.
Oh, no, you may be tempted to wail, autism is hundreds of diseases, with even more possible combinations of variants, and every individual is unique — this is no way to get a handle on what's actually happening to autistic kids! Don't despair, though, this is just the start. Although there are many genes involved, we can try to ask what all of them have in common functionally. There may be common consequences from all of these different genes, so maybe we can identify the common errors in the process of building a brain that lead to ASD.
Here's a first stab at puzzling out what these genes do. The genes that have been identified as being deficient in ASD individuals are mapped out by known functions, and what jumps out at you is that the hundreds of specific genes fall into a smaller number of functional categories. Many of them cluster in a few functional roles: cell proliferation (genes that affect the number of cells in a tissues) and cell projection (particularly important in neurons, where cells will extend long processes that project into target regions), and a specific class of cell signaling molecules, RAS-GTPases, which are involved in how cells communicate with one another and are particularly important in synapses, or the linkages between neurons.
(Click for larger image)
Enrichment results were mapped as a network of gene sets (nodes) related by mutual overlap (edges), where the colour (red, blue or yellow) indicates the class of gene set. Node size is proportional to the total number of genes in each set and edge thickness represents the number of overlapping genes between sets. a, Gene sets enriched for deletions are shown (red) with enrichment significance (FDR q-value) represented as a node colour gradient. Groups of functionally related gene sets are circled and labelled (groups, filled green circles; subgroups, dashed line). b, An expanded enrichment map shows the relationship between gene sets enriched in deletions (a) and sets of known ASD/intellectual disability genes. Node colour hue represents the class of gene set (that is, enriched in deletions, red; known disease genes (ASD and/or intellectual disability (ID) genes), blue; enriched only in disease genes, yellow). Edge colour represents the overlap between gene sets enriched in deletions (green), from disease genes to enriched sets (blue), and between sets enriched in deletions and in disease genes or between disease gene-sets only (orange). The major functional groups are highlighted by filled circles (enriched in deletions, green; enriched in ASD/intellectual disability, blue).
The second map above ties the various copy number variants to previously known disease genes involved in ASD, and what catches my eye is the dense cloud of variants associated with central nervous system development. That tells me right there that it is inappropriate to treat ASD as something that is switched on or off by simple causal factors: ASD is the product of long-developing, subtle changes in the growth of the nervous system in embryos and infants.
So the conclusion, as expected, is that ASD is a multi-factorial disorder with a strong genetic component — but definitely not single-locus inheritance, as many different genes are involved.
Our findings provide strong support for the involvement of multiple rare genic CNVs, both genome-wide and at specific loci, in ASD. These findings, similar to those recently described in schizophrenia, suggest that at least some of these ASD CNVs (and the genes that they affect) are under purifying selection. Genes previously implicated in ASD by rare variant findings have pointed to functional themes in ASD pathophysiology. Molecules such as NRXN1, NLGN3/4X and SHANK3, localized presynaptically or at the post-synaptic density (PSD), highlight maturation and function of glutamatergic synapses. Our data reveal that SHANK2, SYNGAP1 and DLGAP2 are new ASD loci that also encode proteins in the PSD. We also found intellectual disability genes to be important in ASD. Furthermore, our functional enrichment map identifies new groups such as GTPase/Ras, effectively expanding both the number and connectivity of modules that may be involved in ASD. The next step will be to relate defects or patterns of alterations in these groups to ASD endophenotypes. The combined identification of higher-penetrance rare variants and new biological pathways, including those identified in this study, may broaden the targets amenable to genetic testing and therapeutic intervention.
There aren't any simple answers. There are some hints of hope for future treatment, though, in the recognition that there are a few functional modules that are being commonly impaired by these many different genes — it at least focuses the direction of future research in to some narrower domains.
One fact is so obvious that it's unfortunate I have to mention it: no external agent, such as a vaccine, can generate a consistent pattern of duplication and deletions in an affected individual's cells. These data say it's an error to chase down transient environmental agents given relatively late in life to people.
Pinto D et al. (2010) Functional impact of global rare copy number variation in autism spectrum disorders Nature doi:10.1038/nature09146.
Life Science
Medicine & Health
Comments
Posted by: frustum.myopenid.com
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June 10, 2010 11:32 AM
Hey, the anti-vax movers just showed up. They asked, "Where do you want these goal posts?"
Posted by: Kieranfoy, Faerie Godfather of Death, GMKSC, OED
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June 10, 2010 11:33 AM
You can stuff those goalposts right back up their bums!
Posted by: dpattersonmonroe
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June 10, 2010 11:34 AM
Thanks so much for this article, PZ - as soon as I saw a very short AP article on this issue this morning, I started hoping someone would post a longer and more explanatory article as to what exactly was happening - much appreciated!
Posted by: Yubal
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June 10, 2010 11:36 AM
Question:
Why do cases of ASD increase?
Improved diagnostics or real increase in numbers?
Posted by: raven
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June 10, 2010 11:43 AM
It's been known for some time that autism has a high genetic component. 90% is extraordinarily high for something as complicated as a mental disorder. IIRC, SZ which is the classical inherited illness has an identical twin concordance of ca. 50%.
Clearly there are other factors because the concordance isn't 100%. Could be epigenetic, developmental, or environmental. It could also be a stochastic phenomenon, a matter of chance, the term for that is penetrance of a trait. These can't be the major determinants though.
The antivaxxers could learn this with 5 minutes on google. In fact they have probably had it shoved in their face many times. They do what all crackpots do, put their fingers in their ears and sing La La La, I can't hear anything.
Posted by: Ken
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June 10, 2010 11:44 AM
Yubal #4:
Here's one of the better discussions of this topic I've run across:
http://www.sciencebasedmedicine.org/?p=4726
Posted by: Sastra
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June 10, 2010 11:51 AM
Ah, but, as one of my neo-pagan, alt-med-advocating friends recently told me, "that may be true in your reality, in science. But spiritual truths have their own reality, and all events are rooted in the Spirit. Dis-ease is usually the result of holding on to a resentment."
We materialists are too involved in petty details. No wonder we're so resentful.
Posted by: Evomonkey
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June 10, 2010 11:58 AM
PZ, does this explain your superhuman power to breakdown chewing gum?
Posted by: Brownian, Most Vicious & Petty of Pharyngulites
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June 10, 2010 11:59 AM
tl;dr.
I think autism is caused by—[covers eyes, spins in office chair three times before opening eyes to see]—voicemail buttons...er...voicemail!
Think of it: voicemail only became widespread in the last two to three decades. We're not evolved to hear the disembodied voices of friends and family members talking to us as if we were listening, an hour or day or week ahead of the present, and so our emotional machinery is unequipped to deal with the constant lag time and lack of context for communication!
Really, I think I'm on to something here.
Oh, Ms. McCarthy...
Posted by: daveau
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June 10, 2010 12:00 PM
I saw news reports on this yesterday, which led me to the published study in Nature. Thanks for helping summarize and clarify it for us who are not used to reading Biology papers. (Sorry, I've always leaned toward Physics myself.)
Posted by: raven
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June 10, 2010 12:04 PM
Autism usually manifests early in life, ages 2-4.
How much resentment can a baby-toddler accumulate in such a short time and where does it come from?
I didn't know that existential angst was common in the preschool set.
Posted by: Ewan R
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June 10, 2010 12:06 PM
Bad vibes man. Bad vibes.
Posted by: Nerd of Redhead, OM
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June 10, 2010 12:08 PM
A clear explanation of some excellent research. Appears to confirm what I suspected. Genetic predisoposition, plus possible error in fetal developmental timing, yielding a baby with ASD.
Posted by: randydudek
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June 10, 2010 12:09 PM
@Brownian, OM
And while I know that you were kidding, the problem is that, for the most part, the people who are going to read this and actually accept the science are going to the be the people who didn't need to read this in the first place. The McCarthyites1 are going to, at best, let their eyes wander over the black splotches so they can say that they read it and go back on believing their woo.
1: Does McCarthyism still carry negative connotations across the average US citizen's mind?
Posted by: Sigmund
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June 10, 2010 12:15 PM
So the only common feature with these autistic children is that they all participated in this study?
Wait a second.....
Doesn't that mean they donated blood for the genetic analysis to be performed......?
!!!!!
Which means they all had needles (manufactured by big pharma!) stuck into them!
Finally, firm proof that Jenny McCarthy, Generation Rescue and Age of Autism are correct!
/sarcasm off. Let's face it, there is nothing that would convince the vaccine conspiracy theorists that they might have got it wrong.
Posted by: randydudek
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June 10, 2010 12:15 PM
I really, really, REALLY wanted that cookie.
Posted by: AnneH
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June 10, 2010 12:21 PM
Thanks for posting this, PZ. Myself, my husband, and our son are all on the autism spectrum. I appreciate any thoughtful and informed discussion of autism, as a counterbalance to all the baloney the antivaxxers publicize.
I recently stumbled across discussion of oxytocin as a factor in autism.
http://virginiahughes.com/2010/02/07/autism-trust-hormone/
In my experience, this makes a lot of sense. Oxytocin is released in the brain whenever neurotypical humans interact with each other in a friendly manner. I've always been baffled by the need of my students (I'm a substitute teacher) to spend several minutes socializing before they can settle down and get to work. To me, it looks like they NEED that little oxytocin buzz to function. My family does not feel that need as deeply as neurotypicals seem to do. From my point of view, it is the neurotypicals who are dysfunctional, with their need to constantly interact with each other instead of focusing on their tasks.
I also object strongly to the neurotypical prejudice that all autistic people are diseased, and therefore defective and less valuable. We have talents and abilities that neurotypical people lack.
Some links illustrating that point:
http://www.ted.com/talks/temple_grandin_the_world_needs_all_kinds_of_minds.html?awesm=on.ted.com_8A29
http://isnt.autistics.org/
A must-read for those who care about autistic people:
http://www.autreat.com/dont_mourn.html
Posted by: chigau (◦_◦)
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June 10, 2010 12:21 PM
raven #11
It must be (must have been) hugely frustrating to be 2 years old. You can't reach anything, you can't open the fridge, you can't make the lights and colours start on the TV and you can't make any of the giants lumbering around your life understand anything. I'd be resentful. In fact, I still am resentful.Posted by: Lee Christensen
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June 10, 2010 12:28 PM
Just because there are underlying genetic causes for autism doesn't mean that environmental toxins such as mercury aren't involved. With the increase in environmental toxins such as mercy, any genetic variability in the ability to metabolize those toxins could contribute to the apparent rise in incidence of the disorder. I just visited Pubmed and typed in "autism" and "mercury", and there are apparently plenty of peer-reviewed studies supporting that link.
Posted by: AnneH
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June 10, 2010 12:29 PM
@Randydudek,
If McCarthyism is defined as 'fearing, rejecting and attacking people who have different thought processes, values, and beliefs', then I think it applies equally to the senator and the brain dead bimbo. ;)
Posted by: Erulóra (formerly KOPD)
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June 10, 2010 12:31 PM
Yes, it does. Even (oddly) to the ones who see commies in every shadow.Posted by: wallacerobert109
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June 10, 2010 12:32 PM
My son has MECP2 duplication syndrome and duplications, triplication,and deletions,not to mention aberrations can cause ASD symptoms as well.the MECP2 is on X.28 or the long arm of the X chromosome
Posted by: Brownian, Most Vicious & Petty of Pharyngulites
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June 10, 2010 12:38 PM
That the case with all science, randydudek. Much ink has been spilled by those more knowledgeable than I on how to create an educated populace capable of understanding (or at least, grasping) the complexities of our universe as revealed through science.
Not anymore. The Texas Board of Education has elevated him to True Patriot™ status, meaning children no longer need to learn who he was or what he did; just that he was Good™ and led the fight against America's Evil Enemies™.
Posted by: Tulse
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June 10, 2010 12:41 PM
Theeeey'rrre HEEEEE-eerrre!
Posted by: Hairhead
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June 10, 2010 12:42 PM
Aargh! Silentnolonger @19, it's been known for over a century that mercury in toxic doses is connected with damage to the brain and dysfunctional behaviour (look up "Mad Hatter", would you?), Time and time again, studies of the mercury levels in vaccines and their effects have shown NO connection between current common mercury levels and autism. NONE!
I am President of society which works with children with learning difficulties, many of whom have been diagnosed as autistic/Asberger's; many of these children respond wonderfully to behavioural therapy, as their brains (despite their dysfunctions), are still in the plastic stage, and can learn new and/or compensatory social, intellectual, and physical skills.
As I have had to read the history of autism, the best answer for the so-called "increase" in autism/Asberger's is simply better diagnosis and detection, and a greater willingness on the part of society to integrate these people, rather than isolating them in bad jobs or mental institutions.
Posted by: Sastra
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June 10, 2010 12:43 PM
raven #11 wrote:
Past lives, or sympathetic magic from the mother. Or make up something -- "bad vibes" is as good as anything else. If reality is a giant Stream of Consciousness, every physical manifestation has something to do with wrong thinking, somewhere, somehow.
Silent No Longer #19 wrote:
True; there are other reasons scientists have ruled out "environmental toxins such as mercury." There is no autism link.
I thought the anti-vaxxers were slowly abandoning the claim that it's mercury -- since it's so clearly misguided -- and have now moved the goalposts on to vague and unspecified "toxins." If you're specific, you can be shown to be mistaken. That's how science works.
Maybe the toxins are really "bad thoughts."
Posted by: ckitching
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June 10, 2010 12:44 PM
I know that the last time I saw a vaccine/autism diagnosis rates chart, I noticed that while there seemed to be a correlation between vaccines and autism diagnosis, there was a much larger correlation between DSM manual releases and autism diagnosis. At each and every new revision, the rate of change in autism diagnosis increased, within that year, or by the next at the very latest.
It seems to me that it's clear that the DSM manual releases are causing the autism epidemic, so we must get the government to outlaw revising this manual! Won't someone think of the children???
Posted by: raven
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June 10, 2010 12:50 PM
I just did that. There aren't "plenty of peer-reviewed studies supporting that link." In fact, the few I read out of 135 hits, said the exact opposite. One 2010 abstract is below. Just read the conclusion at the bottom, in bold.
CONCLUSIONS: After accounting for dietary and other differences in Hg exposures, total Hg in blood was neither elevated nor reduced in CHARGE Study preschoolers with AU/ASD compared with unaffected controls, and resembled those of nationally representative samples.
Silentnolonger is using a common crackpot tactic. Lying.
BTW, the mercury was taken out of vaccines years ago. It made no difference to the rates of autism. None. That is why the antivaxxer kooks took their goalposts and moved them. Silent didn't get that memo, I guess. Nowadays it is vaccines, gluten, MDs, evil spirits, or something else.
Posted by: Shannon
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June 10, 2010 12:51 PM
Thank you for this post. My 2 month old is getting his first round of vaccinations today because I logically know that it's the right thing to do both for my child and for the public. However, there is an irrational, emotional, new parent part of me that is making me second guess myself. This post helped shut up that irrational side. My pediatrician and medical organizations know far more than Jenny McCarthy, and I appreciate the reminder.
Posted by: amphiox
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June 10, 2010 12:58 PM
As they can't actually tell us, and by the time they can, they can't remember, we may never know.
Did you read them? Because if you did, you'd realize that they all mostly demonstrate no link.
For pubmed that's not really that many hits, either. "Lots" of hits is about 500-1000 for a search using two broad terms.
Also redefinition/elimination of older, less specific diagnoses, such that patients diagnosed with the older diagnosis in the past will henceforth become diagnosed with autism instead.
Posted by: Yubal
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June 10, 2010 1:21 PM
Thanks Ken,
This study confirms my idea about the increased ASD diagnosis.
However this finding
would also support the idea of HAS and POP to play a role in-utero. It is not given that people living in a certain radius surely do communicate, but they are definitely exposed to the a similar environment (water, playgrounds etc.). On the other hand, neighbors with little children are more likely to interact than those without.
Posted by: stuv.myopenid.com
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June 10, 2010 1:31 PM
I'd just like to say that comments like Shannon's do seem to make it all worthwhile.
By the way, Shannon, if you do return here, you might want to visit Respectful Insolence for additional information if you haven't done so already.
Posted by: kittywhumpus
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June 10, 2010 1:32 PM
@Shannon #29
I hear you, and I went through much the same thing with my son. I regained my rational side, and he's fully vaccinated and a normal, demanding, curious, crazy-making two-year-old.
I can only hope that other parents who have been tangentially infected by the fear and irrationality that anti-vaxxers create have the same opportunities and resources as we did.
Posted by: Shannon
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June 10, 2010 1:36 PM
stuv.myopenid.com, thanks for the link. I do follow PZ's blog and will add Respectful Insolence to my reader as well.
Posted by: kittywhumpus
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June 10, 2010 1:37 PM
@#32
Absolutely. While I had come to my senses before I found "Respectful Insolence," that blog has given me a better understanding of the anti-vax movement's tactics and access to necessary scientific information--on loads of health-woo.
Posted by: Shannon
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June 10, 2010 1:46 PM
Sorry, I've got to comment once more. I went to Respectful Insolence and immediately found what I needed. Even after this blog, I was still thinking, "Well, maybe we should do a delayed schedule. Fewer vaccinations surely would pose a lesser risk, right?"
http://scienceblogs.com/insolence/2010/05/no_difference_between_too_many_too_soon.php
Wrong.
Oh, science. You're there for me again.
Posted by: randydudek
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June 10, 2010 2:01 PM
That's what I was afraid of. And for a split second, I'd liked resurrecting the term. Nevermind. Move on.
Posted by: Samantha
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June 10, 2010 2:03 PM
For a non-scientist, could someone explain what this means:
It's mostly the numbers for "fold" and "P" that are confusing me. I vaguely remember there being "r" and "p" in my Psych classes when they listed correlation and causation studies, but I don't even remember what those letters stood for.
Posted by: Eamon Knight
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June 10, 2010 2:05 PM
It seems to me that this supports the concept of autism as the extreme end of a continuum of human behaviour, rather than a distinct category. Get a few of these genetic features, and you're on the introverted side of average. Some more, and you're into Asperger territory. A whole bunch, and you're full-blown autistic. "Disorder" just means you have significant and persistent problems coping with normal society.
Me, I'm somewhere down on the border of Asperger-land. Given that my wife is the same, we're probably lucky that neither of our kids is autistic (though neither could be described as social butterflies, either).
Posted by: Ted Zissou
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June 10, 2010 2:14 PM
Thanks, I'm bookmarking this post.
Posted by: Ewan R
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June 10, 2010 2:20 PM
#38 - fold change is what you'd multiply by to see the difference in the populations, so 1.29 fold change is a 29% increase (control population incidence * 1.29)
P-value is a measure of statistical significance, a p of 0.012 means that there is a 1.2% chance of the difference in results being purely down to chance alone. The smaller your p-value the more confidence you have that differences seen are "real" rather than just by chance.
Ish - if I've majorly screwed either of those up hopefully someone a little better versed in statistics can intervene.
Posted by: Robert Thille
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June 10, 2010 2:32 PM
Um, this biology stuff seems too complicated. Can't we just say 'goddidit'? :-)
Posted by: rippingrich
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June 10, 2010 2:33 PM
So your telling us that a DNA profile may lead to the information of the most suitable diet for our body type. That one body may process red meat better than another and one body is more suited to a starch diet and another may be more suitable for a vegetable or fruit diet.
Boy this sounds like a whack of cash just waiting to be made.
just thinking....
Posted by: mswzebo
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June 10, 2010 2:43 PM
Two perhaps non-obvious points for people wavering about the vaccine/autism connection:
First, it is expected and normal for children to develop sudden-onset disorders, including some in the autism spectrum, on the very day that they are vaccinated. Even more children are expected to develop sudden onset disorders 'Within days of being vaccinated". This is expected even though the vaccines don't cause the disorders. There are a little more than 4 million children between the ages of 3 and 4 in the US, and ~2.5% of them (100,000 children) will develop a sudden-onset disorder in the autism spectrum during this year. If these 100,000 children get one round of vaccines between the ages of 3 and 4, then the probability that they get vaccinated the same week they come down with the sudden-onset disorder is 1/52 x 1/52. This means that every year in the US, we expect about 37 children between the ages of 3 and 4 to come down with a sudden-onset disorder in the autism spectrum in the same week that they are vaccinated, even though the vaccines don't cause the sudden-onset disorders. Worldwide, even more children are expected to be affected each year by a disorder near the time they are vaccinated. Over years, we expect there to be thousands of such cases.
It is perfectly natural for the parents of these affected children to conclude that correlation implies causation. However, it doesn't. We know that the vaccines don't cause the sudden-onset disorders because the disorders occur at the same rate (2.5%) in both vaccinated children and in unvaccinated children. It also unfortunately appears natural for unscrupulous individuals to try to make money by claiming a connection between vaccines and autism, and showcasing these children as 'evidence'.
The second perhaps non-obvious point is that, if we do enough studies, we expect a small number of those studies to show that the autism disorders occur at a higher rate in vaccinated children, even though the disorders don't occur at a higher rate in vaccinated children. For example, if you wanted to determine if a coin was balanced, you might flip it 100 times, to see if you got about 50 heads and 50 tails. If you got 55 heads and 45 tails, you might decide to repeat the experiment of flipping the coin 100 times. If you did the experiment enough times, you might get a result of 30 heads and 70 tails, just by chance, even though the coin is balanced. Most of your experiments would have been about 50/50. Thus, even if a small number of studies were to show that the autism disorders occur at a higher rate in vaccinated children, it doesn't support the idea that the disorders occur at a higher rate in vaccinated children. You need to look at a preponderance of evidence -- and almost all studies show the disorders occur at the same rate in both vaccinated children and in unvaccinated children.
Posted by: YetAnotherAtheist
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June 10, 2010 2:58 PM
Boy, God sure is a sloppy creator. Junk DNA, duplicate DNA, genetically-caused diseases... was he drunk or something? ;)
Posted by: palefury
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June 10, 2010 3:10 PM
To agree with Ken.
My understanding is that the rates of diagnosis of autism and mental retardation inversely correlate indicating that previously autism was miss-diagnosed as mental retardation (or that autism has become a more popular diagnosis). The increase in rates of autism is almost entirely accounted for by the decrease in mental retardation diagnosis.
Though this again is just a correlation, it seems more plausible to me.
Posted by: Brownian, Most Vicious & Petty of Pharyngulites
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June 10, 2010 3:11 PM
I appreciate reading that, Shannon. Those of us who don't have kids often don't understand the pressure parents—especially new ones—face in trying to make the right choices for their children. I write this not to excuse irrationality, but to understand it better.
Posted by: Brownian, Most Vicious & Petty of Pharyngulites
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June 10, 2010 3:17 PM
I appreciate reading that, Shannon. Those of us who don't have kids often don't understand the pressure parents—especially new ones—face in trying to make the right choices for their children. I write this not to excuse irrationality, but to understand it better.
Posted by: Jolo5309
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June 10, 2010 3:23 PM
Boy, God sure is a sloppy creator. Junk DNA, duplicate DNA, genetically-caused diseases... was he drunk or something?
Mankind was built on a Saturday, God had already worked a full week. Of course there were some mistakes as there was probably a party that night and he was still hungover from the previous night.
Posted by: mswzebo
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June 10, 2010 3:38 PM
Actually, I think I was off by a factor of 52 - wouldn't the probability that two independent events occur in the same week be 1/52, rather than 1/52 x 1/52? So we would expect closer to 2000 children between the ages of 3 and 4 to come down with a sudden-onset disorder in the autism spectrum in the same week that they are vaccinated, even though the vaccines don't cause the sudden-onset disorders.
Posted by: Michael Cooper
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June 10, 2010 4:10 PM
I definitely appreciate that this study included the broad autism phenotype as a one of the categories regarding autism. Functional MRI studies have shown a tendency for "unaffected" siblings & parents to share some differential activation from neurotypical controls that were closer in character to the affected individual. (I can reply back with those citations if anyone is dying to see those and can't otherwise find them.)
Prior to this study the most comprehensive article I'd read was this one by Abrahams & Geschwind in 2008.
Posted by: Peter Ashby
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June 10, 2010 4:17 PM
@Yubal
One hypothesis and at the moment it is just that for a possible increase in autism rates (though it would be slow) is the coincident between the expansion of higher education across the Western world in the early '70s and the rise in the number of women attending university. The idea is that autistic spectrum effects are an excess of the same process that makes people, men especially good systematisers so Engineers, Mathematicians and Scientists.
The point about the coincidence is that for perhaps the first time in history it allowed male and female systematisers to meet and fall in love, or at least lust. If as this paper suggests 90% of autistic effects are genetic then having two systematisers as parents would increase your chance of having a spectrum effect.
AIUI studies have suggested that those whose parents and grandparents are employed or qualified in systematiser careers have a higher chance of having children with such conditions.
As someone with two grandparents and a father who were engineers and who is a scientist and married to a woman with degrees in Maths and CompSci I should perhaps be grateful we only had daughters and the eldest's long early relationship with a guy doing Engineering, she perhaps escaped more than the heightened risk of red haired kids that would have resulted.
We have friends who have a kid just skating across the bottom of the spectrum (with some spikes). He is a lovely boy, but not exactly normal, very mentally precocious and fiercely interested in all things technical and scientific. We hit it off very well when he discovered I would talk for hours about science in response to his endless, literally, series of 'but what if . . .?' questions. I can't resist an attentive audience. Makes a change from my own family.
Posted by: Vicki, Chief Assistant to the Assistant Chief
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June 10, 2010 4:24 PM
mswzebo--
While I agree with your basic point, that people are reading meaning into coincidence, your numbers look too high. If 2.5% of children between the ages of 3 and 4 develop sudden-onset disorders in the autistic spectrum each year, then the incidence of autism should be significantly higher than that (since it's not all sudden-onset). But the usual estimates for incidence are around 1% (numbers like 1 in 116). I realize that not all children with autism will grow up to be autistic adults--developmental delay doesn't mean lack of development--but is it as low as 1 in 3?
Posted by: stuv.myopenid.com
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June 10, 2010 4:54 PM
Shannon, might I suggest...
http://store.xkcd.com/xkcd/#Science
Posted by: codedlife
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June 10, 2010 5:50 PM
I wrote another take on this more-or-less at the same time as PZ: Autism genetics: how do you copy?
Written in the wee hours, so I wasn't up to mimicking PZ's breezy style, but hopefully it's not that bad!
Posted by: mswzebo
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June 10, 2010 5:58 PM
Vicki, yes, sigh, another mistake. Let's try .25% instead of 2.5%. Still that's 200 cases per year in the US where the sudden onset would happen in the same week as the vaccination.
Posted by: Lee Christensen
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June 10, 2010 6:06 PM
Whoa, there, Hairhead and Raven. Take a deep breath. I am *not* talking about vaccinations and autism. I merely went to Pubmed, typed in "mercury" and "autism" and looked at the first few abstracts. Here are summary lines from the first three that popped up:
A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism spectrum disorder. "...The results show an association between the apparent level of mercury toxicity as measured by recognized urinary porphyrin biomarkers of mercury toxicity and the magnitude of the specific hallmark features of autism as assessed by ATEC."
Porphyrinuria in Korean children with autism: correlation with oxidative stress: "...In agreement with published data, the present results demonstrated that measurement of porphyrins serves as a reliable tool for diagnosis of heavy metal involvement in ASD."
Mercury induces inflammatory mediator release from human mast cells: "...As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis."
Now, I'm not a scientist, and I'm not intimately familiar with the literature. I accept that there is absolutely no evidence linking vaccinations to autism. I just checked out a few abstracts, and it seems that the link between autism and mercury is still being researched as of 2010; the question is not closed.
I know that this blog sometimes gets brutal, but could you tell me how you came to the conclusion that I am a "lying crackpot"? Or is it your first impulse to be extremely rude first and ask questions later? The participants of this blog seem very devoted to evidence (as I try to be). Your evidence that I am a crackpot would be … what? (I'm wearing a target here. Shoot away.)
Posted by: Nerd of Redhead, OM
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June 10, 2010 6:12 PM
Then you listen to scientists, not tell them things.And heavy metals may include mercury, but most likely lead from old gasoline and paints. The case is essential closed, but small possibilities are not conclusive evidence, without a clear and evident mechanism for causing ASD, which still eludes those trying to show vaccine/environmental factors for ASD. That is the point of most of us here.Posted by: MosesZD
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June 10, 2010 6:25 PM
But Jenny McCarthy has a VAGINA. And how can you argue mere facts and science against the power of Vaginal-Based mommy-woo...
Posted by: Lee Christensen
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June 10, 2010 6:49 PM
Nerd of Redhead: I do listen to scientists, every day. I am a professional researcher in the field of bioinformatics; I just don't think of myself as a "scientist".
For what it's worth, here are some snippets from the first page of abstracts from a Pubmed query, with a summary of whether they lean positive or negative on the environmental mercury / autism question. If scientists are still asking that question in 2010, the case is not closed. However, it's closed for me as I have to get back to work.
Article 1: Leans positive: "The results of the study indicated that the participants' overall ATEC scores and their scores on each of the ATEC subscales … were linearly related to urinary porphyrins associated with mercury toxicity."
Article 2: Leans positive: "Various studies correlated elevated heavy metal body burden with ASD diagnoses as evidenced by increased urinary porphyrin levels in patients… Significant increases were found in patients diagnosed with ASD for proporphyrins…"
Article 3: Leans positive: "…the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis"
Article 5: Leans positive: "Mutations in human neuroligin genes are associated with autism spectrum disorders in some families… neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders"
Article 6: Leans negative: "The analysis suggests Hg emissions are not consistently associated with autism prevalence in Texas school districts"
Article 8- Negative link: "After accounting for dietary and other differences in Hg exposures, total Hg in blood was neither elevated nor reduced in CHARGE Study preschoolers with AU/ASD compared with unaffected controls, and resembled those of nationally representative samples."
Article 9: Leans positive: "These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children."
Posted by: Carlie of the lacy, gently wafting adjectives
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June 10, 2010 6:57 PM
I was a BAD MOTHER. Effin' women, screwing everything up. [/snark]
Since this is halfway on topic, just to make sure everyone knows, Autism Speaks is a pile of shit organization.
Also, this is awesome.
Sorry, back to the research. I find it perfectly logical that multiple repeats and different genes have something to do with it, because the spectrum is so incredibly broad - it boggles the imagination to think that it could be one simple cause.
Posted by: Nerd of Redhead, OM
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June 10, 2010 7:17 PM
1&2 That is a proxy, not mercury levels themselves, which can be measured to parts per trillion levels. There may be biochemical differences in ASD causing the increase in such porphyrin proxies. Want me to draw a porphyrin for you? 3, what did they use to determine levels and mechanism? What happened to 4? 5 follows PZ's review. 6&8 old news. 7? 9 no mechanism shown, just suggested. And gene related like PZ's study. A few researchers are still looking at heavy metal for various reasons, including them being True Believers™, but no "smoking gun" evidence. The epidemiological studies like 6 are where the real action is. If environmental factors are the cause, clusters would be seen with increased concentrations of known toxins. It seems the parents are more important than the environment. That must mean parents are toxic. I thought most kids waited until they were teenagers for that thought.Posted by: raven
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June 10, 2010 7:40 PM
Just because something is listed on pubmed, doesn't mean it is peer reviewed or done by legitimate scientists any more. The quacks have their own journals and pubmed abstracts them.
A lot of the mercury "research" has been done by a quack named Geier and his son. It is bogus. He also "treats" autism patients with a variety of unproven procedurs including chemical castration with a potent drug called lupron and chelation therapy. I'm surprised he hasn't had his MD license yanked yet. Hell, I'm surprised he hasn't been sued for malpractice or sent to jail.
Autism is a favorite hunting ground for quacks. I'm aware of several children who have been killed by chelation therapy, an unproven treatment based on nonscience.
Posted by: Lee Christensen
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June 10, 2010 7:46 PM
Nerd: Thanks! That reply helps. There are lots of us "non-scientists" out here who really are devoted to good evidence, and don't want to or consider ourselves qualified to argue with people who really understand a field, but aren't sure what to think because they hear opposing voices from the scientific community. Comments like "he's a lying crackpot" earlier in this blog aren't only bad manners, they really don't help the cause. This does. Thanks again.
Posted by: Yubal
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June 10, 2010 9:33 PM
Peter Ashby,
That is also an explanation, but it would only explain the ASD phenotypes of genes that are inherited recessively. I was pointing to a putative link between endocrine disruptors (artificial substances that can act like hormones) and ASD.
I stumbled across this idea the first time when I read this review in Science. and they have good points for this idea. More recently, there was a little experimental data published. Too little, but there is still work to be done.
Posted by: kb
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June 10, 2010 10:16 PM
"How much resentment can a baby-toddler accumulate in such a short time and where does it come from?"
If you ask former baby-toddlers why they are so resentful they gave themselves a dis-ease, their resentment boils over into anger at you. It's hard to know why, but asking questions reveals the deep seated anger that was already there, so we know they're definitely very resentful.
Posted by: broboxley OT
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June 10, 2010 11:01 PM
2 things to note. Better diagnosis and with more literature more misdiagnoses.
My son was diagnosed with "intermittent anger disorder" many many years ago, now anyone who acts out in public is diagnosed the same almost as if psychs watch Oprah before they go to the office for the day.
So there is a genetic marker for propensity for this disorder. Whether long term environmental factors are meddling with this genetic sequence and whether the actual affect of this genetic marker is effected by nurturing remains very much in doubt.
A disorder is just that, its how your self organizes shit, learn how that is done in the overmind and recognise hints that things are not going well in the undermind and adjust as needed. Voila we now have a feasable human being
Posted by: clausentum
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June 11, 2010 3:07 AM
Peter Ashby #52 :
even if it has to be qualified (Yubal #65), that strikes me as quite an insight.
I've sometimes ruminated on the negative effects (in myself) of assortative mating in my own family.
Posted by: DLC
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June 11, 2010 4:01 AM
A nice summary of the recent science, PZ.
Thanks.
Posted by: a_ray_in_dilbert_space, OM, A little FUCKING ray of sunshine
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June 11, 2010 4:08 AM
Thanks for the summary. I've been reading a biography of physicist Paul Dirac, who was very probably somewhere on the autism spectrum.
As Dirac is the one who defined reality as a ray in hilbert space, he was part of the inspiration behing my moniker--the dilbert-esque landscape of working as a scientist in a world of woo being the other.
Posted by: Paul123z
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June 11, 2010 5:25 AM
While certain genetic alleles might affect the propensity to develop autism, if we accept the CDC' Morbidity and Mortality Weekly statistics, the incidence of autism has increased some 10 fold in a generation. This can not be due to a generational change in genetics. Therefore we have environmental/infectious etiologies to consider. Seeing as a significant minority of parents of autistic children have stated that their child's autism developed subsequent to a vaccine inoculation and considering these vaccines often contain preservatives designed to "kill cellular life", this provides a very reasonable avenue for intense investigation. Or will we just call them the "refrigerator mothers" of the 21st century?
Paul Maher, MD MPH
http://healthjournalclub.blogspot.com/
Posted by: raven
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June 11, 2010 6:20 AM
Another quack. Paul Maher.
Thimerosal the mercury containing agent was removed from virtually all vaccines years ago. The perceived incidence of autism just kept going up. There is no evidence that mercury had or has anything to do with autism.
FWIW, I supported the intitial FDA decision a decade ago to remove thimerosal. Just in case and there are other ways to keep vaccines sterile.
Correlation doesn't prove causation. It is well known that the increase in autism diagnosis is due to awareness and cultural and social mores.
I really, really despise these quacks. At best they are exploiting desperate parents for financial gain. At worst they are killing patients, some of whom are young children. Some of the autism "treatments" based on pseudoscience such as chelation therapy to remove the imaginary toxic mercury have killed people.
Posted by: Peter Ashby
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June 11, 2010 8:03 AM
@Silentnolonger
One rule of science you should learn is that correlation is not causation. Most of the studies you quote are correlations only and there is now way to tell if the relationship is causal in which direction? For eg it could be that people with ASD handle heavy metals differently, not that the heavy metals cause ASD. That would be perfectly consistent with most of the studies you cite.
Also the ones claiming causation make the assumption that the causation is late. They mistake what they see as a change in their children with a change when it is more likely the failure of a normal change and the beginning of a different arc. The base genetic causes of autism may well be of the type that build slowly not being manifest until the developing brain is required to do something critical at which point failures that have been building all through in utero development but have just been teetering all combine and fall.
That picture suggested by the genetics would make the other 'causative' mechanisms way too little and way too late and as PZ points out nowhere near complex enough to do all the necessary things we know are changed in people with ASD. Environmental toxins don't work that way, not even thalidomide. As a developmental biologist I am familiar with the actions of a number of teratogenic substances and what is remarkable is not what they can do but what they cannot, how limited they are.
ASD does not look like that sort of phenomenon, not to those of us who know development, who understand the complexity. It is naive simplistic thinking to imagine that they can. The hope is understandable, but that does not make it true.
As to people still doing studies, there is still money to be had from campaigning groups to do them, so someone will. There are still occasional international conferences on all sorts of quackery, quantum consciousness for eg, still people working on cold fusion. What keeps them going is the old story of wanting to be the maverick, the outsider and simply taking a punt, with long odds. If they are right the potential pay off in terms of money and prestige, not to mention revenge are huge. So they continue to dream. Scientists are human too. Still doesn't make them right.
Posted by: mikerattlesnake
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June 11, 2010 9:00 AM
@71
Funny you don't even mention diagnostic substitution, widening of the spectrum, and increased awareness. Those sort of poke a few holes in your theory, so better just to ignore them, eh?
Posted by: Flex
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June 11, 2010 4:22 PM
Late to this party, but while reading the summary one statement did leap out at me.
From PZ's article, "There are some hints of hope for future treatment,..."
Meaning that we may have the tools to identify severity of ASD and use genetic therapy to induce additional cell proliferation, cell projection or increased generation of cell signaling molecules in children?
I believe that the brain is sufficiently plastic to remain adaptable should an 'optimal' range of fetal and childhood levels of cell proliferation, cell projection or cell signaling molecules be determined.
ASD may, in fact, move into the same category as children who are deficient in human growth hormone. The causes of having a deficiency in human growth hormone are myriad, but there appears to be a fairly simple therapy to correct the deficiency to the point of a child getting to the range of typical growth levels.
Clearly treatments for ASD may require a quite more complex therapy, but it also suggests that there will be an even more specific diagnostic criteria (as well as allowances for individual variation and the judgement of doctors) to determine when treatment for ASD would be appropriate and when untreated development patterns would be preferred.
The moral concerns surrounding human growth hormone deficiencies appear to be limited. Would there be a greater moral concern about ASD therapies?
Of course, I'm simply a layman in these subjects, so I may be completely speaking through my hat here.
Posted by: Nova
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June 12, 2010 12:26 AM
The idea of Autism being something curable at all seems ridiculous to me, and PZ calling it a "disease" doesn't help, as that implies something discrete with the possibility of removal.
Something I have always thought and that this research only reinforces is that Autism and associated Aspergers Syndrome are merely differences in certain parameters or wiring in the brain. This is why the idea of a cure makes no sense: greatly oversimplified, those parameters would have to be set to something non-autistic, but there are many non-autistic things they could be wired up as, one of which may be classified as schizophrenic, and a huge number of which could be considered neurotypical.
Short form: if you get rid of an Autistic or Aspergic personality in a person, it must be replaced by one of millions of possible neurotypical personalities. Most people seem to have this vision of Autism or Aspergers as a disease: something which infects the pure and beautiful ordinary personality, but ffs the Autism/Aspergers is that persons personality (and Aspergers isn't all negative either as is often depicted). There is no clean cut divide between the neurotypical, the Aspergic and the Autistic, we put those divides there for convenience, it's a sliding scale of millions of parameters.
Posted by: Nova
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June 12, 2010 12:41 AM
Actually I just thought of a good analogy: trying to cure Autism or Aspergers is much like trying to cure homosexuality or left-handedness.
Posted by: Flex
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June 12, 2010 11:56 AM
Nova, maybe your comment wasn't aimed at me, but as I suspect it might have been, I also suspect that my comment wasn't as clear as it may have been.
Autism is not a disease, it is a condition apparently resulting from a different rate of development outside of what we consider to be normal development. There are undoubtedly many reasons why this delay in development may occur, probably including environmental as well as genetic factors (although vaccines have been completely ruled out as a potential environmental cause).
This doesn't make people with ASD diseased. In the worst manifestation of the condition, it can make them unable to completely integrate into modern society. Which does not, I repeat, does not diminish their worth as human beings.
In mild manifestations of ASD, your comparisons of ASD to left-handedness may be apt. It can cause mild annoyances. However, ASD is not exclusively a mild condition. Your analogy of handedness would have to show a spectrum like ASD to be an equivalent metaphor. Maybe the spectrum from a right-handed person, through left-handed people with two hands, to left-handed people missing their right hand, to people with no hands at all. At every point along that spectrum there are increasing difficulties in functioning in a modern society.
Finally, it is a disorder in development. There is unlikely to ever be a cure for adults who have ASD. Just like it is unlikely that there will ever be a cure for adults who as children suffered a deficiency in human growth hormone. Having passed through that developmental stage, those adults have to learn to cope with the results of that deficiency in their development. What I've read suggests to me that to speak of curing autism is absurd, but detecting and developing therapies to avoid the highly dysfunctional cases of autism may, in fact, be possible.
Now, possible is only half the battle. Because it also seems that some of the developmental events which, if interrupted, can lead to ASD occur in the womb. So we are talking about finding ways to discover neural signaling molecules in a fetus. Technically that would be a huge challenge. Even if that can be done, there would have to be a therapy which brings those signalling molecules levels into an acceptable range to allow reasonable development.
The above technical challenges may be overstated, since we are talking about a period of very rapid neural development a therapy immediately after birth may be sufficient.
This will no more eliminate the spectrum of human behavior than the discovery and therapeutic use of human growth hormone has made everyone exactly 6'2" tall. Human growth hormone therapy is not used for every child who is growing slowly, it is only used on children who have an identifiable lack of growth, I have to imagine that any treatment for ASD will be similarly confined to those children who are clearly having severe developmental problems. Just because your child falls on the mild end of the ASD spectrum doesn't mean that your child will get treatment.
Lastly, I don't know what you are talking about when you say that getting rid of an autistic or aspergic personality in a person will require it to be replaced with another personality. I don't think you can call ASD a personality any more than you can all schizophrenia a personality. ASD is a collection of traits, but a personality has far more traits than simply those defined in the ASD diagnostic criteria.
Maybe your suggestion of schizophrenia is a good example of what I mean here. A person with schizophrenia, full-blown life-altering schizophrenia, can also display humor, knowledge, compassion, laughter, etc. The personality of the person is affected by, but not limited to, their schizophrenia. In a Venn Diagram, if you create a circle for the entire personality of the person, there would be a smaller circle completely inside the first showing the part of their personality which is affected by their schizophrenia.
Similarly with ASD. A person who has ASD does not have their personality defined by their ASD. Their personality is affected by their ASD, but is not defined by it. There are very cheerful people will advanced autism, and very gloomy ones.
To go back to my human growth hormone therapy analogy again, there are basketball players who are shorter than non-basketball players. Your skill at basketball is influenced, but not defined, by your height. Saying that one collection of traits is the only important part of someone's personality is absurd.
I completely disagree with your statement that " Autism/Aspergers is that persons personality". It is an influence, and possibly a huge influence, but it is not that person's personality. If it were, than all people with Autism/Aspergers would react identically and that is manifestly not true.
Posted by: Nova
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June 12, 2010 9:08 PM
As it happens it wasn't directed at you Flex, but what you have said in response is interesting. Of course I didn't mean that an ASD persons personality was defined entirely by the condition, but that the condition is a part of their personality, not some perverse infection of it as is often depicted. So to "cure" ASD you would have to change all the traits that define ASD in a given person so that they no longer defined ASD, but there is no natural "normal" set of traits in the same way that there is a normal human body temperature, normal traits are defined by us. You appear to be treating ASD as a deficiency, but how can this be possible when it describes such a great range of possible differences in behaviour? Now many of these differences may indeed be negative, especially when integrating into a society which does not easily accept strange behaviour. But in particular in mild cases of Aspergers there are also notable advantages, such as an increased capacity to remember facts and figures or even less of an inclination to impute agency into random events. Even in extreme cases of Austism we sometimes find savants who can perform incredible mathematical feats. So while I think discussion of how to deal with the negative consequences of ASD is perfectly legitimate, it is wrong to talk about curing or mitigating the whole thing, since it describes such a wide range of possible symptoms.
I also don't see how you can put ASD down to a simple "delay in development". ASD is a hugely wide ranging thing, most of it is a disability but some parts of it can be advantageous. So you'd have to define what symptoms of ASD are a delay in development, and define development as well.
Posted by: Flex
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June 13, 2010 12:01 AM
Nova,
I suspected that I read too much into your comment. So, should I have given offence by suggesting that you were unaware of how personality is broader than a set of traits, I apologize.
As for your other thoughts, as I suggested with my analogies previously, I suspect that our current broad definition of ASD may, in fact, be broader than any reasonably treatment possible.
Where you suggest that calling ASD a delay in development is too simple a definition, I consider calling it a delay in development fairly accurate to describe both the positive and negative aspects of ASD you assign.
Your examples of idiot-savants who have a highly developed mental ability in one area may well be the result of this area being reinforced during development when other areas of the brain are less responsive. Mind you, this is speculation, I don't know that we really have enough detail of how the brain operates to be certain of this point.
However, it strikes me that suggesting that there is usefulness in allowing the occasional mathematical genius who is not functional in other areas of life is similar to suggesting that the short stature of dwarfs can provide advantages that people within the typical range of height of humanity don't have. Under this reasoning, human growth hormone therapy shouldn't be applied because we, as a society, would lose the benefits of having dwarfs around.
Which is not to say that dwarfs are not human, and don't deserve all the rights and responsibilities of humans. It's simply that recognizing that while there are some benefits to being a dwarf, it doesn't mean we should stop human growth hormone therapy.
Now, of course, my analogy of ASD to human growth hormone deficiency is flawed. The biggest one is that the mind is far more complex. There appear to be anywhere from 25-200 separate modules in the mind which are developing all at the same time (and I've read some authorities who suggest far more than that). A delay in the growth of one module may well allow resources to be used to enhance another. And delays can be temporary or permanent.
So, in my opinion, calling ASD a delay in development, is really saying that there are billions of possibilities of delays in hundreds of combinations of modules which might be related to the traits observed in ASD. In extreme cases the delays may be permanent, but with the broadening of the diagnostic criteria it also includes partial and temporary delays in development.
As I see it, as therapies are developed, I wouldn't be surprised to see narrowing and an increased number of sub-classifications of ASD over time. Why would this occur? Simply because there are varying degrees of ASD ranging from very mild, not requiring treatment, to very severe cases which require specialized treatment.
Am I treating ASD as a deficiency? I would have to say both yes and no to that accusation. There is a wide range of papers dealing with ASD and neural development. As the paper which PZ has reported on suggests, deficiencies in cell proliferation, cell projection and cell signaling molecules during development are all strongly linked to ASD symptoms.
However, I would argue strenuously that simply because the brain of a person may have had reduced cell proliferation, cell projection and cell signaling molecule in certain modules during childhood development that this does not mean that the person as a whole is deficient.
I am certain that all of us had differences in cell proliferation, cell projection cell signaling molecules during development, and that even between mental modules within our brains we have had differences in neural development. (Which is why I am very skeptical of the whole 'Baby Einstein' idea. Environment can have a large impact on neurological development, but as far as I've read, we don't seem to have any consensus on what aspects of an environment are important. I keep going back to William James' and Jean Piaget's work and I'm often surprised at how little we've learned about the neurology of children, regardless of the forests of paper expended on the subject over the past 50 years.)
As you correctly point out, a person is not defined by any chemical deficiencies during their development. A person is defined by their activities during their life. There are some abilities that people on the ASD spectrum have, due to their being on the ASD spectrum, which are advantageous to modern life.
Again, and in an attempt to be as clear as possible, as I see the current state of our knowledge about the causes of ASD, it is likely to be a deficiency in one of three areas; cell proliferation, cell projection or cell signaling molecules. I'd place my money on the majority of ASD causes are related to a deficiency in cell signalling molecules, but I'm not an expert on the subject.
But this does not mean that people with ASD symptoms are themselves deficient in any way. Only that they are, as you say, wired differently than other people.
Are the differences in the wiring beneficial or detrimental in their ability to survive in their environment? In extreme cases, ASD is clearly detrimental. In extreme cases of human growth hormone deficiency the results are also typically detrimental (albeit less so). In severe cases of sickle-cell anemia the deficiency in hemoglobin formation is detrimental to survival. So therapies to help reduce this deficiency caused by ASD, or a lack of human growth hormone, or the sickling of hemoglobin are all benefits for the individual.
Posted by: SEF
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June 13, 2010 9:56 AM
@ Flex #78:
It does! Between the right-handers and the left-handers, and before any extremes of limblessness, there are those of us who are ambidextrous (to varying degrees). We are the subset whose superiority the normals (right-handers in this case) sometimes try to dismiss in the same way as neurotypicals try to downplay the evident superiorities of the high-functioning "Aspergers" people, for not sharing their religious etc flaws.
Posted by: Nova
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June 14, 2010 4:01 PM
Yes, that's a reasonable hypothesis, that slower development in some areas leads to increased areas in others, that would explain increased aptitude in certain areas. I wouldn't necessarily be against treatment of a savant, actually the main cases in which I think treatment would be a detrimental waste of time would be the high functioning mild cases of Aspergers, which results in people who are socially inept (though still often unnoticeably so) but may have a greatly increased ability to understand certain subjects which interest them (as well as apparently a lesser inclination to attribute intention to randomness).
Here I think Aspergers positive aspects might even outweigh its negative ones. Though of course individual cases vary dramatically, and some may get disproportionally the negative, and a few disproportionally the positive.
Posted by: Nova
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June 14, 2010 4:26 PM
Oh and one more thing, there is a difference between arguing that a dwarf's height could be advantages and considering the possible advantages of Aspergers. The difference is that in the dwarf's case the advantage and the disadvantage are one and the same - reduced height, whereas in the case of Aspergers they are different - social ineptness being a disadvantage, increased memory of facts being an advantage. Aspergers can have some qualities which, looked at in isolation, are only a good thing.
Posted by: BisserR
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June 28, 2010 6:37 PM
"One fact is so obvious that it's unfortunate I have to mention it: no external agent, such as a vaccine, can generate a consistent pattern of duplication and deletions in an affected individual's cells. These data say it's an error to chase down transient environmental agents given relatively late in life to people."
I looks like you are looking for simplistic answers here :)
The fact that there is a genetic predisposition associated with something does not imply that there is no external agent causing it. Look at Celiac disease. Is it gluten that causes the disease or the DQ2 and DQ8 variants of the HLA-DQ gene?
Posted by: skv
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August 1, 2010 6:18 PM
Fantastic Blog. What would be be valid reason for the regressive autism. I have seen from my son who had words at 18 months and stopped completely at 24 months.