A Question About Theories of What Causes Autism
At the lecture on genetics and autism that I heard some of last week, I asked one of the speakers this question: Even though there is more and more evidence in support of a genetic theory of autism, why does so much public opinion seems so hesitant to accept this, and so interested in environmental theories of autism?
The scientist responded with a very clear explanation of the theory of spontaneous vs. heritable autism. He added, “I don’t know what you mean by ‘public opinion.’”
Someone else asked another question and I wasn’t able to say, “Well, there’s this idea that mercury or vaccines causes autism………” to the speaker (who really ought to read this).
Tags: asd, asperger, autism, dna, Genetics, Health, measles, mercury, mmr, Parenting, pdd-nos, shots, Vaccines
22 opinions for A Question About Theories of What Causes Autism
daedalus2u
Mar 10, 2008 at 7:17 pm
I went to a talk on the genetics of autism last week too,
http://web.mit.edu/autism/buxbaum.htm
I thought it was surreal. The speaker had no room in his conceptualization of autism for any non-genetic effects. If a child was diagnosed with autism, and they found a gene deletion, then that was the presumptive cause. He was working toward prenatal diagnostic testing, and had been quoted as saying it was 10 years off (he actually thought it might only be 3 years), and expressed surprise that the neurodiversity community had objections to this type of work.
His talk was filled with “this gene causes 0.5%, that gene causes 1%” sorts of talk. Something like 80%+ of cases there was no genetic explanation for, but by how he was talking, he was completely convinced that it was only a matter of time before there would be 100% found, and that the test would be virtually 100% specific regarding false positives and false negatives.
I asked a question about monozygous twins being discordant for autism, and doesn’t that put a limit on what the false positive rate can be? If you have two genetically identical individuals that are discordant, any genetic test can’t have 100% specificity. His reply was that they were still both on the spectrum. That there were obvious differences in the “severity” (which is a simple term denoting an extremely complex multi-dimensional difference space) which pretty obviously could not be “genetic” was completely lost on him.
There is no understanding at all of what the “mechanism” by which even very well known genetic disorders that “cause” ASD symptoms actually cause them. The MeCP2 defect is very well known, mice have been generated that recapitulate the defect, the symptoms, and that are then cured when the gene function is restored. Yet the “mechanism(s)” remain completely unknown.
I think this is due to the hubris of ignorance. People who are experts in genes are not experts in physiology. There is vastly more about physiology that is not known than that is known. There is no technique to understand and predict the interactions of thousands of non-linear coupled parameters. It is breath-takingly naïve to think that by knowing the genes it will be understood. What causes something as simple as memory is still not understood. How does he expect to predict neuroanatomy based on genes? It is completely preposterous.
My own feeling is that there will never be a genetic test for autism, other than the rare sporadic cases caused by single genes. The global autism spectrum is an inherent part of being human and reflects the trade-off between a “theory of mind” and a “theory of reality”. Humans have that trade-off because the pelvis is too small to allow large enough brains at birth to accommodate both. When times are good, a better ToM is better. When times are hard, a better ToR is better. Any test will have a very high false positive rate because it is the epigenetic programming that determines the final brain phenotype and location along the ASD spectrum.
I think his problem is that his theory of reality is not developed enough and complex enough to actually encompass reality, so he truncates. That is the main problem of NTs. Their well developed ToMs let them communicate well among each other, but their conceptualization of reality isn’t as good as those with a better ToR, but who can’t communicate it as well.
Philomena Roche
Mar 10, 2008 at 7:22 pm
A healthy happy baby, an alert engaged toddler
in the space of a few weeks (3 to be exact), decends gradually to oblivion. Fixates on the patterns on a rug or patterns in a picture. No longer responds immediately to his name with a sweet smile (memories from a home video).
Something happened. If this was an isolated case, any number of “unusual factors” could have caused it. However the story is only too familiar to parents with a child with autism.
The only “unexplained” factor which was not present the month before, was the wellness visit to the pediatrician. If it was any other “environmental factor” his 1 1/2 year old brother should show similar or some symptoms. They have been together at all times (with Mom) for the past 15mths since little brother was born.
The really sad part is that, 6 years later, that happy healthy baby and sweet toddler is still staring at patterns on a rug. Watches the same video over & over (yes for 6 years now). Shows no interest in anything around him………autism.
Of course it was the vaccines. Experienced pediatrician, who have looked at the home video, have no answers, they have not seen anything like it before. Two have requested copies to show colleagues and are convinced of the real danger of vaccines. The others just shrug their shoulders.
The statistics of 1 in 85 boys is horrific to a parent knows that vaccines are the cause, yet 6 years after our sweet child was maimed on his wellness visit, other innocent babies and unsuspecting famalies are still being thrown into the daily abyss of Autism. Once you are there, nobdy wants to listen. “Your problem, don’t bother me……..”
Please someone listen!!!!! Autism is no more caused soley by genes, than by “cold mothering”.
This is probably the biggest tragedy’s of our generation, if not our whole human existance, because this one could have been so easily avoided the scope of its horrir if “someone just listened sooner”.
Philomena
Mom to John age 7, beautiful severly autistic boy.
Kristina Chew, PhD
Mar 10, 2008 at 7:47 pm
@Philomena,
Thank you for writing about John here. What kinds of teaching and school has he had, if I may ask?
@daedalus2u,
Surreal is a good word. I was not surprised at the speaker’s response to my question (he has an autistic child himself). His response rather confirmed what I suspected about the divide between what “the general public” thinks and what some scientists and researchers think.
bev
Mar 10, 2008 at 8:09 pm
What is it that “causes” people to continue using words like “horror,” “tragedy,” “abyss” and “maimed” about their own children? Is it fear or is it willful cruelty? Certainty that correlationd does after all equal causation? Some combination of these things?
Do people really think their children are not aware of these opinions? Is there any other group of people about whom one may make such hateful statements without being seen by all as an obvious bigot?
Didn’t get exactly what you ordered in life? Someone must be at fault. Someone must pay. Well someone surely will. And adding “beautiful” to the string of hateful adjectives won’t do a thing to change that.
Kathy
Mar 10, 2008 at 8:40 pm
I think in Mark’s case that both genetic and environmental factors were involved.
He appeared to be developing normally.
I have a home video of him playing in his cot at eighteen months.He has a small babies brush in his hand.My voice is heard on the video asking Mark to brush his hair. He duly complies.
Some six months later however that skill is completely lost.
Counting to ten, making the appropriate animal noises when asked…all gone.
I don’t believe that vaccines had any part to play in Mark’s autism.
He was vaccinated at 2 and 4 months only.He did not have any reaction to the vaccinations.
These are the only vaccinations(apart from tetanus last year)that he has had.
When he was a baby Mark developed quite a few viral infections, and between twelve months and 2 years spasmodic bouts of tonsilitis, for which he was prescribed antibiotics.
I do wonder whether perhaps the viral infections or the tonsilitis or even the many doses of antibiotics, were somehow a trigger. Who knows.
What I do know, is that early educational and behavioural interventions, have been extremely beneficial to Mark.As has his new medication, strattera, which has eliminated his anxiety and helped him to focus at school.
Mark’s Uncle, as I have mentioned before (we suspected) was autistic.
Another older Uncle also had similar autistic traits.
daedalus2u
Mar 10, 2008 at 8:42 pm
Another example of the breath-taking naïveté of some geneticists. When the honey bee genome was sequenced and published in Nature, they asked the head of the project what was the biggest surprise. His answer was “That we did not come up with breakthroughs in understanding social behaviour of the bee. Many small changes account for this and it is possible that this reflects our limited knowledge of behavioural genetics.”
http://www.nature.com/nature/journal/v443/n7114/full/7114xiiib.html
That is a completely preposterous idea, that the social behaviors of insects would become apparent by looking at their genome. I don’t mean to be harsh on him, and I don’t want to take anything away from the real advance of the bee genome, but the idea that behavioral aspects of bees would be obvious by looking at their genome shows a naïveté that is breath-taking. That level of naïveté is not unexpected when people are working far outside their expertise. The expertise to initiate, receive funding for, direct and manage a consortium of researchers (174 collaborators) to sequence diverse genomes is quite different than the expertise required to understand the behavior of neural networks from the genome of nerve cells. There are very few of us who can be expert in everything ;).
The behaviors of individual nerve cells are not obvious from their genetics (let alone the anatomy and collective behavior of neural networks) a hypothesis that they are is hopelessly naïve and could not possibly be correct. That is true in bees, it is certainly true in humans who have much more complicated nervous systems and behaviors (many orders of magnitude more complicated).
Marla
Mar 10, 2008 at 8:59 pm
I can’t believe he did not understand what was meant by ‘public opinion’. Seems hard to believe.
daedalus2u
Mar 10, 2008 at 9:59 pm
I think the reason there is such antipathy toward people on the spectrum relates to what is called the “uncanny valley”.
http://en.wikipedia.org/wiki/Uncanny_valley
My hypothesis of this is that it relates to the theory of mind that NTs have, and that when they encounter someone with a different ToM, that it induces xenophobia. That in effect what people do when they encounter another individual is do a Turing test, to determine if they are “human enough” to be a potential ally, friend, mate or what ever. Some of that relates to cultural differences, some to early imprinting, some to things that we have no idea about. I think a major part of it is mediated through mirror neurons, through ToM, and through the body language that is disrupted in ASDs.
http://en.wikipedia.org/wiki/Turing_test
I think when the error rate in the non-verbal communication goes up, then xenophobia gets invoked. NTs don’t have a choice, they are neurologically programmed to react this way. It takes conscious effort to not respond this way. I think this is the source of the extreme nuttery surrounding what causes autism. When a parent feels xenophobia toward their child, it causes cognitive and emotional dissonance. They have to externalize the bad feelings, they have to project them onto something else. That something else is the evil pharmaceutical industry.
I think this is also the source of the extreme bullying that ASD individuals are subjected to.
Emily
Mar 10, 2008 at 10:17 pm
Interesting interesting ideas, Daedalus.
Kristina Chew, PhD
Mar 10, 2008 at 11:44 pm
@Marla,
I wasn’t surprised, but saddened—whatever one thinks is the cause of autism (genetic, in the speaker’s case), it’s necessary to acknowledge what others think and to understand why they think that. If there had been more time for discussion (and I hadn’t been still sick—this was last Wednesday), I would have launched into saying a bit more…..
@daedalus2u,
As you know, I’m very interested in genetic theories of autism (and, Kathy, I’ve relatives on the spectrum and Jim too—-Charlie’s development was always extremely slow and uneven, in subtle ways, never enough that a doctor said “get him evaluated!”, though I think that would be the case now).
Nonetheless, I’ve been struck by all the things you point out, about the percentages of persons that the theories refer to. Maybe this is a bit of an over-generalizing statement, but perhaps there’s too much mystique about genes and DNA as holding “the secret of life”—-there is plenty to learn from them, but part of a very big picture.
There are so many similarities between Charlie and myself, and between Charlie and my husband, that we could never think him not our child, and not like us. He has tremendous limitations and impairments, if I may use their terms, but when I say he’s “disabled,” I certainly don’t mean “maimed.”
And the tragedy to me, is not being able to see the comedy in it all, and to enjoy a lot of good times and laughs with Charlie.
bj
Mar 11, 2008 at 12:01 am
Which scientist are you talking about, Kristina? I know a few scientists who study autism, some of whom seem quite probably on the spectrum themselves, and who model quirks quite beautifully when they are asked questions by the “public.”
Cliff
Mar 11, 2008 at 2:59 am
Since Uncanny Valley originally applied to robotics, I wouldn’t have necessarily put it next to autism, but once put there it makes sense in terms of the general sense of familiarity.
But here’s some helpful criticism, or just thoughts.
To start, I’m not a scientist, and while I have an extremely limited knowledge of such things, I’m going to focus far more on the context exterior of that too much.
I’ll note that in order to construct such a duality, ToM and ToR, there’s a lot that needs to be explained, and some odd testability factors.
Let me just start with a question; assuming that both the ToM or the ToR effects are totally distinct, and affected directly not having for proper room, wouldn’t that mean that they would have more room develop given a larger pelvis size? Basically, wouldn’t that make it so that general intellectual and communicational capacity was based on brain size, since that would be the only distinct benefit of a larger pelvis?
Also, isn’t drawing a statistical fact into the equation already blurring the line between the two, because we are dealing with another mental conception within a specific framework? Or is the difference mainly one of a discreet factoid versus a conception, and can we distinguish one over the other discernibly as “reality”. The discreet information is individual manipulable and not inherently true, no? If we were to stick to a strict basis of logical reality, we’d never get anywhere, either stuck in skepticism or the mental (being generous). We certainly couldn’t use science; it relies on inductive reasoning, which is inherently flawed (it is not a logical truth that the past repeats itself or that time-space has patterns. Tell me if I need to go into this further).
Also, that such a dichotomy would be split between ASD individuals and NT individuals is interesting, because I’m not sure it’s so clean. After all, systemization is an inherently conceptual act much more along the lines of mind cognition than direct recognition.
Interesting as well, just thinking about things, is how we’re conversing about a very different thing than might be simply described by the DSM, and yet this is understood. Might even be framed as ToM about something which is poorly defined, and yet it’d be hard to say that we were working on simple attribution. Oh, I’ll tangent into more of my project, so I’m leaving that there.
Onto the second post.
It’s noteworthy that, though I never would have phrased it in terms of the Uncanny Valley, this applies to almost all of xenophobia. Considering some of the discrimination that involves, say, Italians, it’s interesting to note that much of the features described aren’t different. While this isn’t to say that Italians get more (hardly), they get much for comparatively little differences.
So we’re really back within the context of the normative, and not even necessarily within the context of the “human” (though note that even here the normative is making statements about the human).
Error rate, by the way, might be described in larger terms; the way one holds his/her body, where he/she moves the eyes, and other nonverbal cues would contribute to the xenophobia. Message content would matter here, too.
Anyway, I’m very interested to hear more.
Cliff
Cliff
Mar 11, 2008 at 3:01 am
Err… wow, what just happened there?
That top paragraph was supposed to be way down at the front of the second discussion, and I did want to note that I was directing this toward daedalus2u’s theories.
Someone’s been studying a bit too long…
Cliff
daedalus2u
Mar 11, 2008 at 8:35 am
I disagree that the uncanny valley is about robots. It is about humans and how humans feel about robots depending on how similar (or not) that robot is to their normative idea of what is human. Any such behavioral system didn’t evolve to deal with robots, it evolved to deal with other humans, non-humans or near humans (non-human hominids that are now extinct? maybe the uncanny valley is what caused humans to make them extinct?).
In no way am I trying to over simplify the complexity of human behaviors or the neuroanatomy which leads to those behaviors.
Emily
Mar 11, 2008 at 9:49 am
I also wanted to comment on genome sequencing: Sequencing the genome is like taking a novel and identifying all of the letters in the novel in order, but without spaces. When you look at the result, you’re not going to “read” anything there, you’re not going to find the sense in it. Sequencing the genome is just the beginning. That sequence must then be “mined” for data, compared to sequences of other species, to sequences within the species. So, it would be useless to take a genome sequence and hope that it provides information about behavior.
The concept of emergent properties tells us that very simply. Daedalus mentioned neurons. A neuron is simply a cell. No one could predict what a bundle of these cells can do together, but in us, in combination with the rest of us, properties emerge that for now are completely unpredictable to us. Table salt is probably the most simple example of emergent properties. Sodium. Chlorine. Nasty things separately, but beautiful delicious table salt emerges when you put them together. It’s not predictable based on their individual characteristics. The same applies to series of nucleotides or the letters in a novel without markers for spaces, periods, commas, and paragraphs. The sense only emerges when specific combinations are demarcated.
RAJ
Mar 11, 2008 at 9:54 am
for Daedalus2U
Interpretation of twin studies is a marvelous example of how autism genetic theorists (who Rutter has described as genetic evangelists) interpret (or perhaps misinterpret) the meaning of twin studies. If there is a higher concordance rate for any condition in identical twins vs fraternal twins the condition ergo is ‘genetic’. Mathematical computations compute a theoretical heritability estimate which some autism researchers have placed as high as being 90% heritable.
These century old type of archaeic twin studies say nothing about whether a condition represents genetic heritability or genetic susceptability. Genetic susceptability simply does not equate to genetic inevitability.
THere is a condition that might be considered to be the Gold Standard for a gene-environment interaction model where genetic studies published over many decades are strikingly imilar to the genetic studies published in autism research.
Leprosy is caused by exposure to the bacteria Myobacterium Laprae. Twin studies have shown the same high concordance rates in MZ twins ( 60 - 85% ) and the same rapid falloff in concordance rates in DZ twin pairs ( 5 - 20%). Identical to autism. Leprosy is also known to cluster within kinships with a sib recurrance risk rate identical to autism. Heritability estimates for leprosy using mathematical calcualtions based on the incidence of multiple incidence families has been reported as leprosy being over 80% heritable.
http://www.nature.com/ng/journal/v27/n4/full/ng0401_439.html
There is also a very strong genetic compnent in determing who is and who is not susceptabile to developing leprosy after exposure the the bacteria. The disease is now considered to involve a polygenic susceptability model interacting with a known strong environmental component.. exposure to Myobacterium Laprae
Patrick
Mar 11, 2008 at 2:21 pm
I suggest that the reason that many people still cling to their pet cause or theory, instead of acknowledging that the new evidences indicate a more full understanding, is that they believe they have already found the truth, or that they are ‘right’.
I cannot say that my condition was caused by either genetics or vaccines, or a combination of both, because I am willing to acknowledge that Science/Medicine has not done enough work.
I can do nothing but pity those who are living in their delusions of truth. (Though sometimes they make me want to get right in their face and ask them if they or the autist they are whining about is the dumber of the two.)
Cliff
Mar 11, 2008 at 5:49 pm
Err… you are right, and I misphrased the point that the field in which the term is usually applied is robotics, not that it’s not about people. My bad.
I know, indeed. I was just pointing out that MY notes were oversimplified as to their implications, not yours.
Sorry for the tiny errors.
Indeed, Patrick, that is a basic grasp at it, regarding the nature of pet theories. At this level it seems the discussion is pushing for a “why”, which isn’t particularly clear. Thus, the theories that get thrown out.
I don’t particularly make ultimate claims as to the “cause” of my condition (and, honestly, I’m not sure I all care. It’s meaningless, and the only thing that might come out of it is personal modification, which I’m not, well, thrilled about).
Noted, though.
Cliff
Kristina Chew, PhD
Mar 11, 2008 at 7:04 pm
@bj: You wrote,
Which scientist are you talking about, Kristina? I know a few scientists who study autism, some of whom seem quite probably on the spectrum themselves, and who model quirks quite beautifully when they are asked questions by the “public.”
The scientist referred to is the chemistry professor from Princeton who spoke; he talked about Michael Wigler’s theory about de novo and hereditary autism. I had thought of the “spectrum factor”—thanks for pointing that out.
RAJ
Mar 12, 2008 at 9:43 am
“The scientist referred to is the chemistry professor from Princeton who spoke; he talked about Michael Wigler’s theory about de novo and hereditary autism. I had thought of the “spectrum factor”—thanks for pointing that out”.
Professor Wigler reported that in his sample 90% of cases were sporadic, the parents did not have the abnormal copy number variation and that 10% were inherited copy number variations.
SInce 90% of the parents were unaffected, the whole concept of the broad autism phenotype has been rendered by this study as nothing more than psychoabble.
Kristina you either have to accept Wigler’s study or accept his conclusions as invalid, you can’t have it both ways.
dr ramesh k k
Mar 13, 2008 at 1:01 pm
respected sirs,
If you all do not do anything quickly,I will assure
you that in another ten years time all these
autistics and ASPIES will end up in the neurosurgery
theatre to have their brains scooped out or
current passed into their thalamus and caudate
nucleus through microelectrodes.A genre of
neurosurgeons are now getting specialised
in deep brain stimulation and ablation of
certain areas of brain like cingulate cortex.
Their contention ie the neurosurgeons
believe that lack of sensory integration
is the pathology of ASPIES and so they will
stimulate it through microelectrodes
and if an ASPIE gets aggressive or is
mispercieved to be so then an ablative procedure
would be the treatment of choice.I am presently
working as an observer in neurosurgery and
I am an Asperger.My father worked as a
painter in CT scan unit of Siemens India limited.
My sister had long bone dysplasia and
features of pseudohypoparathyridism and
my brother has a hemiparesis.So isnt there a
link between lead of paintspray used to paint
CT scanners.We lived for nearly four decades
in Bombay,which was quite polluted.We could
have consumed fishes which had consumed
mercury from sea or other heavy metals as
well.I have taken many vaccines including
small pox vaccine.One more thing.Genes and
the physical body constitute the phenotype and
the genotype.But what about mind and conciousness?Where will you put them?It is
true knowing genes is not the same thing as
knowing the person.What does the geneticist
know about the INTRONS which are the non
coding regions in a chromosome and which
forms the bulk of genetic material.They say it is
probably linked to evolution.The coding region
called the EXONS are smaller.Trace all the
medical doctors and other professionals
who are ASPIES and let them all fight this out.
Americans are interested in war.So let this
Autism movement too be debated and discussed
on a war footing by all those who are affected
by it.That is the only way to sell Autism.
You will have to fight the toxins,the vaccines
and the ablative neurosurgery.Take this issue
to the WHO where under the secretary general
Dr Margaret Chang they are reconfiguring the
neurological illness.First of all bring this
autism related disorders under the Neurology
speciality.That is the first safe move to be
attempted.Remember all specialities are
moving towards intervention oriented treatment
protocol because it fetches money and
ASPIES will soon become easy targets.Under
psychiatry discipline ASPIES are not safe.
The stigmata will only compound the general
lack of acceptance.Plan a mass crusade to the
White house and the governors.Employ as many
socially prominent ASPIES like Bill Gates and
Temple Gardin and other work of art and poems.
The movement has to jump out of the
internet into the Real world.Otherwise the
movement will be overshadowed by the
Iraq and the oil crisis.Remember the energy
crisis will become very severe within the next seventy five years the time when the renewable
energy or fossil fuel will be depleted.So now is the time or else the oil race will overtake the Autism
race.And the latter is disadvantageous on
the communication front and so the stumbling
blocks are more.In these remaining seventy odd years what chances are there that an absolute and undeniable connection between a toxin
and autism is made?The industry will keep
pushing it aside.And the more they push it aside
the more they will weaken the movement.Let a
cess be imposed on all such industries to
support the autism education and livelihood.
The more articulate must project the ASPIES
as part of a neurodiversity as often as possible
and in as different way as possible.The
conciousness study center in Berkely is a
good center to launch such literature and maybe
even for research.Lastly what has the intelligent
jews got to say about Autism?Are the ASPIES
and the jews neurogenetically similar?Then
let us migrate to Israel and set up an ASPIE
nation.The jews have been bullied all the time
and so are the ASPIES.Do we possess a holocaust gene or a bully suppresed gene.
Man is one third gene,one third body and one
third conciousness.You cannot put the cart ahead of the horse.Who is the cart and who is the horse amongst these three?Thank you.
daedalus2u
Mar 13, 2008 at 2:36 pm
RAJ, excellent point. Thank you for linking to the paper on leprosy. That is an obvious example of a condition that is highly heritable, but is obviously not genetic.
Monozygous twins also share an in utero environment. Fraternal twins do also, and there is excess ASD concordance among fraternal twins than there is among siblings implicating the in utero environment. It is in utero that the major neural structures of the brain are formed, and it is these structures that have been shown to be affected in children and adults with ASDs. The only time those structures can change their morphology is in utero.
A complex genetic hypothesis of ASDs has a hard time explaining the common phenotype. If the ASD phenotype is an emergent property of many genes, how can such an emergent property evolve and be maintained in the gene pool?
My hypothesis is that the broader ASD phenotype is an emergent property of a human nervous system that develops under certain kinds of “stress”, with low NO being the “final common pathway” by which the epigenetic programming that results in the ASD phenotype are mediated.
Wigglers study didn’t really look at what the actual copy number of the different genes actually was. What they did was look at markers all along the genome, and if some were missing, they looked in detail in that vicinity. The most common deletion they observed was in genes associated with the SNARE complex, a complex of genes that is necessary for synapse formation and activity. Someone asked a question pointing out that that complex is duplicated multiple times in the genome. A loss of one copy may have no functional significance. They didn’t discuss what the actual total number of copies of the genes were, only if the copy at the region they looked at was missing.
The loss of genes that they found also seemed to be associated with telomeres in that they tended to be close to the ends of the chromosomes. The samples they looked at were from blood, peripheral mononuclear cells. These are blood cells which have replicated many more times than the cells which comprise the brain.
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