Tuesday, March 28, 2006

Autism - It’s Not Always A Natural Variation

Okay, I finally decided to start blogging. I like to think of myself as a moderate in the autism debates, able to see both sides (albeit sometimes with a bit of prodding), and I have learned from people of all opinions. But I also see a discussion that is increasingly polarizing, in which accepting that others have different views is giving way to an advocacy that rejects other viewpoints as unenlightened, wrong, or not yet at their level of "awakening". This used to be a hallmark of the more activist element within the anti-vaccine crowd, but is also becoming increasingly apparent in the “autism is natural variation” crowd too. It is one thing to oppose some of the more contentious attempts to cure autism, e.g. chelation, or lupron (which IMHO is just nuts), or to reject the concept of treatment for oneself. But as this challenge to the more contentious bio-med practices is morphing into a more direct challenge against even mainstream accepted methods of investigating and potentially treating autism, I think it is time for more moderates to join the debate.

So, let’s start out with the basic premise that autism is genetic. An occurrence rate in the general population of 1 in 166 (approx. 0.6%) is widely accepted. Within families in which one sibling is autistic, the odds of another being autistic is approximately 10% (Constantino JN et al, 2006). Among monozygotic (identical) twin pairs the concordance rate for autism ranges from 36% to 91%, with 60% being a widely accepted number (as far as I can tell, e.g. Bailey et al 1995). In addition, one study found that 77% of discordant monozygotic twins had social and communication deficits. Within dyzygotic twin pairs there were some studies showing an increased risk for autism, but other studies have shown only a slight to moderate increase in risk vs. singletons, with ascertainment bias as a potential explanation. So where does this leave us? Basically, since the rate of sibling autism is significantly higher than background rate, this clearly points to a genetic link. In addition, the high concordance among MZ twins vs. DZ twins, and the only slight to moderate and potentially explainable increase in DZ twins over singletons further suggests that genetics, as distinct from prenatal complications of merely being a twin, are a major explanation for the occurrence of autism.

But here’s the issue. If autism is strictly genetic, then why do so many MZ twins of autistics NOT have autism? MZ twins share the same genetic blueprint. Epigenetics, i.e. the regulation of the expression of genes, could be a significant factor, but a recent study published in the Proceedings of the National Academy of Sciences indicates that twins are epigenetically indistinguishable during the early years of life, with differences in their patterns of epigenetic modification developing as they age. So inherited epigenetic differences are likely not great enough to explain why one twin becomes autistic and the other does not.

So, if genetics and inherited epigenetics do not explain why one MZ twin is autistic and the other is not, then presumably the cause is exogenous. To throw some math at this, at a 60% concordance rate of autism, a minimum of 25% of MZ autistic twins needed an additional factor to “cause” their autism. Again, an MZ twin study found that a significant proportion of discordant MZ twins in their sample (77%) had social and communication deficits. But it has been suggested “that in such families a genetic substrate for autism may produce the social and cognitive deficits that are included in the broader phenotype but that an interaction between the genetic substrate and unknown deleterious environmental factors culminates in a 'second hit' that ultimately produces the narrow phenotype for autism.” While one could suggest that the 'second hit' is the result of twinning, the rate of autism in DZ twins vs. singletons suggests that this is not the explanation (if it were then the DZ rate should presumably be significantly higher than singleton rates). And unless one wants to argue that MZ twin autism is different from non-MZ twin autism then the minimum 25% factor would presumably apply to non-MZ twin autistics too.

So, if the logic above is correct then it means that a significant percentage of cases of autism are acquired rather than genetically or epigenetically predetermined or inherited. The 25% is a floor, not a ceiling. The actual number may be 30%, or 50% or 100%. The number itself is not as important as the fact that the logic (assuming it is not fatally flawed, which is a possibility) indicates that an external factor or cause is required in at least some cases, the absence of which would render the person non-autistic.

This logic does not support the conclusion that no autism is purely genetic (75% could still theoretically be purely genetic - or more if the 60% concordance rate is too low). In fact, it supports the conclusion that autism in a significant number of cases involves at a minimum a degree of genetic susceptibility. It does not prove or disprove that the 'second hit' is thimerosal or mercury. It does not argue for or against chelation. It does not suggest that autism originates either in the womb or after birth. It does not suggest or refute the possibility that autism is curable, or that a cure is or is not desirable.

What it does support is the conclusion that at least some autism has a cause other than “natural variation”. If this is the case then investigating and potentially treating autism in those cases in which it is 'caused' rather than inherited is not a priori an ethical violation of one’s natural genetic expression or right to "be" autistic.

More on this to follow.

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Update - Related posts:

Autism, Genetics, and Evolution (Apr 19, 2006)

Autism and Minicolumns (Sept 5, 2006)

Autism and the Evolution of the Brain (Oct 13, 2006)

28 comments:

María Luján said...

Hi Ian
Congratulations for your blog!
I also do think that environmental insult plays an important role in autism. I will return on weekend for more comments about your post.
María Luján

Wade Rankin said...

I am most heartened by the last sentence of your post, and am looking forward to much more from you.

Brett said...

Ian, welcome to the discussion. Like you, I find myself in the "middle" of the question, many times with both sides tugging equally against the middle.

Is all autism mercury poisoning? Absolutly not.

Is some autism caused by mercury poisoning? Absolutely possibly.

At the same time, no matter the cause of the autism, autistics need to be - DESERVE to be - treated with the respect and acceptance offered to everyone.

I agree with Wade, I'm looking forward to more of your thoughts on this in the future.

Brett

Bonnie Ventura said...

Hello Ian. You'd probably be interested in the recent discussion of epigenetics on Mike Stanton's blog.

Ian Parker said...

Hi All,

Thanks for the kind words, and Bonnie, thanks for the link to Mike Stanton's discussion.

Also, Brett, I like the idea behind the "Autism for Parents" blog.

Kev said...

Ian said:

"But as this challenge to the more contentious bio-med practices is morphing into a more direct challenge against even mainstream accepted methods of investigating and potentially treating autism, I think it is time for more moderates to join the debate."

I have to admit to a degree of ignorance here Ian in that I'm not entirely sure what you're referring to.

"What it does support is the conclusion that at least some autism has a cause other than “natural variation”. If this is the case then investigating and potentially treating autism in those cases in which it is 'caused' rather than inherited is not a priori an ethical violation of one’s natural genetic expression or right to "be" autistic."

I'm not so sure about this. I follow your logic but I'm not sure that anyone should not have their right to be autistic, if thats who they are, challenged.

I guess we're back to the thorny issue of what 'treating autism' entails. I can't imagine anyone anywhere thinks that neglecting to 'treat' their childs inabaility to communicate is acceptable. But autsim is more than that. 'Treating' socialisation can be a good idea too - within bounds the person concerned can handle - but autism is more than that too.

So - what does 'treating autism' actually mean? Treating the things that we as parents percieve to be 'wrong' with our children? We already know that that is a process that is wide open to individual perception. I could (and have) percieved that my child is mercury poisoned in which case chelating is entirely justified. Or I could (and do) percieve that my child is a person with differing abilities and that they needed to be challenged and worked with in a way that she feels most comfortable with. At her pace, on her agenda. People present anecdotal evidence that chelation 'treated' their kids. I can present anecdotal evidence that love, acceptance and patience is 'treating' mine.

In this instance, I don't feel that parental perception of what is OK as treatment is enough. My next step therefore is to ask someone who thinks in a way that is most similar to my daughter. That is not me. I am not autistic. So I turn to autistic people themselves and read about what they think is best in terms of 'treating'. There is no consensus - Michelle Dawson is not a fan of ABA whereas Phil Schwarz is for example - but where there is unity is the idea that there is intrinsic respect in the condition of being autistic. I know that that idea would endure whether or not there is an environmetal trigger or not. Whether autism is inhereted or caused I would argue that the state of being is still valid.

That is not to infer that you are not respectful of autism Ian. What I am suggesting is that you and I as NT parents of autistic children cannot empathise inately with our autistic children in the way that we can with our NT children. I cannot therefore say that it is OK to define 'treat' as not an ethical violation of one's natural genetic expression. The point being that the state of being is already defined - the cause in this respect is irrelevant.

I play a theoretical game with myself sometimes regarding 'cure'. I imagine how I would feel if we raise our daughter to be able to consider the state of herself as an autistic person. I would feel great. I themn consider how I would feel if with this ability she reasoned that she wanted to be cured. Have her autism eradicated (please note that I am creating the hypothetical situation that there is a magic pill in existence that removes all traces of autism from a person) totally.

Would I help her?

Of course I would. And for the same reason that I have misgivings about 'treating' now - I believe that it should be her decision. Not mine. I might not like it but I would have to respect it.

María Luján said...

Hi Kevin
I share with Ian a lot of thoughts about autism. I respect profoundly the autistic kid my son is-and also autistic teens and adults- in terms of genetics, but I think is my right and my duty to detect and to treat the best I can the -allow me please call so- comorbilities when I have the responsability now, when he is a child. How these comorbilities are related/not related to his autism-behaviorally diagnosed- I do not know if I do not treat them. I consider that all of us make the best we consider for our children, so I am not presenting this as THE approach, only mine. I hope you understand this way, Kevin, because it is not my intention that my words imply any kind of generalization.
You say
I believe that it should be her decision. Not mine. I might not like it but I would have to respect it.

I think that I am giving him the tools to make his own decissions when he grow up. Now, I have to do it by him so I research as much as I can to make the best decissions. When he grows upand become a teen he will have the position to select the choices he consider after discussion and his voice would be extremely important for me because it is his life.
This is a post of mine in Mike Stanton blog I think presents other view
In my personal opinion, for my son, autism can be both, intrinsic and extrinsic. I think that there is a different genetics in him therefore this is intrinsic to him. In this sense he is autistic. But also there are a lot of comorbilities We have detected on him. Therefore these comorbilities are extrinsic.Because I think that these comorbilities are related to different biochemistry in him and the different impact of environmental insult on his overall systems, in this sense he has autism.
Detecting properly and treating his comorbilities I can allow him to be the best autistic he can be and in the sense of diversity of human beings how do I know what the combined effect of development, emotional support love acceptance and treatment can give him?. Because there is no clear research to clarify the role of comorbilities in the symptomatology, this is open to further research, besides genetics to other fields of epigenetics and environmental insult in children born biochemically different such as is the case of ASD chldren.
Only if comorbilities are not detected or discarded after proper testing this can be considered for me. I do not think in the placebo effect by proxy or the developmental change per se as the only point, especially if you detect properly comorbilities and you see behavioral changes correlated with adequately treated and tested biochemical changes. I think they collaborate-development and placebo effects-, but it is no the overall picture, at least in several children with ASD.
You say
So - what does 'treating autism' actually mean? Treating the things that we as parents percieve to be 'wrong' with our children?
We already know that that is a process that is wide open to individual perception. I could (and have) percieved that my child is mercury poisoned in which case chelating is entirely justified. Or I could (and do) percieve that my child is a person with differing abilities and that they needed to be challenged and worked with in a way that she feels most comfortable with. At her pace, on her agenda.
Kev, I consider both ideas in my son´s case. I think they are not incompatible.
Kev you say
The point being that the state of being is already defined - the cause in this respect is irrelevant.
This is controversial for me. The state of being can not be defined by DSMIV. Again, if a child has a lot of medical conditions -perhaps unnoticed, perhaps untreated because they are unnoticed- how can a state of being be defined?
I respect your idea Kevin, only presenting you other point of view that is different.
I have problems with the word "cure". In the sense of "treat" for example hypothiroidism or gluten allergy, I can do it, but I will not cure his autism. BUT treating and reversing the effect of comorbilities can have a strong impact in symptomatology and /or make life much much easier for children with autism in my personal opinion .
Kevin, I respect profoundly you and your approach. But I think different. I hope you appreciate that my words are not presented to you as a rebuttal, but as another point of view on a very emotional and important aspect of our lives as parents of autistic children.
Thank you for understanding in this sense.
MAría Luján

Linda Betzold said...

Ian,

Welcome to the cyberspace conversation that is autism. We are parents and young bloggers, too. It has been a very worthwhile experience so far. I thank you for a thoughtful and balanced first post. I certainly look forward to reading your thoughts on a regular basis.
Thanks.

Ian Parker said...

Hi Kev,

Thank you for your comment. Just up front, you and I have exchanged enough thoughts that you do not need to worry that I will take anything you say to suggest I am not respectful of autism, unless of course you explicitly state it.

You said:

"I follow your logic but I'm not sure that anyone should not have their right to be autistic, if thats who they are, challenged."

and

"...where there is unity is the idea that there is intrinsic respect in the condition of being autistic. I know that that idea would endure whether or not there is an environmetal trigger or not. Whether autism is inhereted or caused I would argue that the state of being is still valid."


I agree. In no way would I suggest that someone does not have the right to be autistic, if that is their choice. Nor would I suggest that an autistic state of being is not valid, even if it is exogenously caused.

What I would say though is that someone who is autistic does have at least a theoretical right to treatment for autism, if that is their choice. My interpretation from your comment is that you do not disagree with me on this (although you would not be an advocate for treatment), if this becomes a choice that you consider is available to be made.

What I'm detecting more of these days (and it might just be because I'm getting out more) is that there is a definite leaning amongst what I'll term the neurodiversity community (and I'm not suggesting that all within that community share this POV) that medical research into the causes of autism, especially if involves a search for a cure, is not welcome or even justified. While this is an old link, I’d wager that the sentiment today is stronger than ever, e.g. here . In that post, I find the attempt to link research with eugenics to be disturbing.

I’m not a big fan of the word cure these days, although sometimes I slip up and inaccurately use the word. The word ‘treat’ better reflects our approach. I have no issues with autism as a different cognitive approach to the world. As I interpret it, cognitive differences per se are not even part of the DSM-IV criteria. My issues are with the difficulties that my daughter faces that are part of the DSM-IV, especially communications issues, plus sensory integration issues that are not part of the criteria. I figure that if we can help her with this then the ‘social’ will more easily fall into place. By giving her a “voice” we can head off some of the frustrations that she may feel in being unable to make herself understood. As for the stuff in section A3, my daughter only qualifies for c), and we don’t consider this as a matter to be ‘fixed’. We define help in terms of both learning interventions (e.g. PECS, ‘communications’ therapy, OT, and IBI) and dealing with co-morbidities through moderate bio-medical interventions to address issues that show up on very mainstream medical tests. In this my views are similar to what Maria Luján has written above.

Ian Parker said...

Hi Linda,

Thanks for stopping by and for the encouraging words.

Wendy said...

Ian - Thanks for stopping by my blog and for the encouraging words. Your thoughts on twins and autism is very interesting. Looking forward to hearing more of your opinions and thoughts in the future. Wendy

Bartholomew Cubbins said...

Hi Ian,

I enjoyed your post but have a problem with the importance of the numbers involved the distribution of autism among twins.

The inheritence of autism becomes incredibly complex when one considers not one gene but several or many.

The simplistic way I look at complex conditions like autism is by supposing that there is likely a common phenotype such as synaptic deficiency (very general and doesn't mean a lot as a description). There are hundreds, if not thousands of ways to develop this phenotype. So the cause might be a combination of genes from mom and dad or it might be an actual mutation in gene X. Why couldn't this gene exacerbate a partially defective pathway caused by mom and dad's genes? The possbilities are endless. MicroRNAs, maternal RNAs (btw, has anyone ever measured the distribution of maternal RNAs - specific transcripts - to twins), etc.

So I'm of the opinion that it's too difficult to say that exogenous factors are a likely contributor due to the breakdown of autistic traits among twins.

I admire the PNAS article but have to say that it examines one gene and two mechanisms of epigenetic inheritence. Even though this field gets a lot of press, it's still in its infancy. How many other forms of epigenetics are functioning today and how to they operate? (haven't looked at Mike's blog about this yet)

While I am not a fan of epidemiology, I am a fan of (someone other than me) comparing disorders and conditions like MS (which has a wierd geographical component), peanut allergies, and asthma against autism. I think that these numbers could shed more light on a possible exogenous factor than by looking at the numbers involved in familial distribution.

I am of the opinion that autism won't be completely understood until the brain is completely understood. For me the thought is sometimes depressing and often the reason I get out of bed in the morning.

Ian Parker said...

Hi Bart,

Thanks for taking a look at this. I really appreciate the feedback, and it definitely helps me learn more about this.

I definitely agree that autism probably results from a combination of several genes, and that there may be more than one combination that can contribute to the diagnosis (which could help explain the variety of presentations). I also understand that mutations and/or errors in RNA transcription could cause autism.

My issue with this though is that, assuming that the concordance rate among MZ twins of 60% is correct, could these mutations or errors explain a divergence in outcomes in 40% of cases? My understanding is that both twins start out genetically identical (exception: XXY MZ-twins), i.e. same DNA, same RNA polymerase, and therefore same RNA transcription process. So while a post-division mutation may explain differential outcomes (but unlikely in anything close to 40% of cases?), wouldn’t any RNA ‘error’ be very likely to affect both twins?

On epigenetic differences between twins, it makes sense that differences will emerge over time, but it strikes me that a significant divergence between MZ twins at an age early enough to allow for autism to develop in one and not in the other up to 40% of the time would require an exogenous ‘push’ in at least some cases.

In all of the above cases that 40% seems to be a pretty high hurdle rate.

Bartholomew Cubbins said...

Hi Ian,

The way I approach this is the way I've approached systems modeling. Much like a complex electrical circuit or a complex chemical reaction, the outcome might be rather seemingly sporadic and unpredictable at first glance, yet could be accurately modeled given the right parameters. This is why I enjoyed that section of Burbacher's last paper.

Here's the rub with modeling: given enough steps/states one could precisely model any set of data. But is it accurate/significant/relevant? So I fall back on Occam's razor ~ the most simple explanation is the most likely. Then comes the opinion. Is it more likely/simple that a single exogenous factor causes the autistic traits or is it more likely that one or more of many different mutations could team up and cause them?

I don't have an answer for this one. But my feeling is that autism is a molecular peculiarity (maybe synaptic deficiency) possibly localized to a very specific section of the brain and possibly occuring at a very specific time during development.

I like the way you're trying to tie together known numbers with a cause, but I'm afraid that the overriding assumption of a single gene causing the traits will dictate the need for an exogenous trigger.

Ian Parker said...

Hi Bart,

Just to clarify my assumptions, I don't see autism as being caused by a single gene, but believe that it is probably the result of 4 to 5 to many genes acting in concert, and not necessarily the same combination of genes for each occurrence. We're on the same page on this.

Where I’d go further is that I’d suggest that the difference in outcomes within some MZ twin-sets (40% of all MZ twin-sets in which autism is present) indicates a requirement for a further exogenous factor (or maybe more than one) in at least these – and potentially many more – cases, within MZ-twins and, by extrapolation, the wider autistic population. To be clear, I definitely see that exogenous factor as also requiring at a minimum a genetic predisposition or susceptibility, hence the 165 in 166 who are not autistic.

Further, at this point my mind is open as to what that exogenous factor or factors might be. I am definitely not wedded to (or, to be clear, discounting) the idea that the exogenous factor is the result of an injection.

María Luján said...

Hi Bart
Why can´t we think in both situations taking place at least in some ASD children?
You say
So I fall back on Occam's razor ~ the most simple explanation is the most likely. Then comes the opinion. Is it more likely/simple that a single exogenous factor causes the autistic traits or is it more likely that one or more of many different mutations could team up and cause them?

The problem I have with this logic-that is basically correct for me in the presentation of the problem-is that sometimes biology does not follow the Occam's razor.


But my feeling is that autism is a molecular peculiarity (maybe synaptic deficiency) possibly localized to a very specific section of the brain and possibly occuring at a very specific time during development.

But for me it is not only one, not specific for all but specific for any individual, as a result of at least 4/5 genes and as much as 16 and this does not exclude the possibility of an exogenous factor. If this exogenous factor is making worse the situation, being the trigger to the situation to be manifested more clearly because of negative impact in a susceptible individual is something open to further research today, although we have only some clues about. Again I avoid the word cause because the root is genetic for me, I prefer the word collaborator or insult that participate in the autistic symptoms. Root of autistic symptoms can be several medical conditions together, for me, including individual genetics.

María Luján

notmercury said...

Hi All,
Sorry if I'm late to the party here.

Ian, congrats on your blog and thanks for a thought provoking first entry. I appreciate your (and Maria's) moderate position and I think we may agree on more things than we all imagine.

There is a lot to learn about autism but the one thing that we know for a fact is that "autism" is really many different things with a similar set of behaviors.

On the Magic Pill scenario; this is something that we should all try to ask ourselves within the context of what autism is to each of us.

Suppose we had such a pill, let's suppose it worked for all types of autism, and let's suppose it worked in ways that none of us had imagined.

I'm reminded of the Joan Osbourne song, "What if God was one of us" and the line:
If seeing meant that you would have to believe

So what if this hypothetical pill corrected genetic or epigenetic differences that couldn't possibly have anything to do with thimerosal? Would the mercury parents stand by their beliefs or ask for the pill?

What if the pill corrected a metabolic pathway that was altered by an exogenous factor and didn't have anything to do with genetic inheritance?

What if we had a pill that magically removed every last atom of mercury but didn't "cure" autism?

You get the picture, there are probably hundreds of variations on the scenario but each are loaded with ethical and moral dilemmas.

Maybe this would be a good topic for your next blog entry? If you narrow it down to a list of scenarios and choices I bet you'll be surprised by the honest comments.

Bartholomew Cubbins said...

"Why can´t we think in both situations taking place at least in some ASD children?"

In my opinion the analysis of these numbers cannot distinguish between any of these possibilities other than to say if a single gene is involved then an exogenous factor must be invoked. Further, I am satisfied with the idea the disribution of autism among twins being consistent with several or many networked genes functioning (or failing to function) in one or several of many combinations.

To beat the horse, imagine you have a Nusselt function with a step function as an argument and multiply the quantity by a hyperbolic function. Only 3 different functions - but take the plot of the data and try to make sense of it not knowing what went into making it in the first place. Nightmare.

"The problem I have with this logic-that is basically correct for me in the presentation of the problem-is that sometimes biology does not follow the Occam's razor."

I'd be interested in hearing about that system. Molecular complexity evolves in accordance with the pressures applied. It's true that there might be a more efficient way to construct an individual pathway in the brain, but taking all the pathways and their interconnectedness together, I'd think it's pretty difficult to reduce the current model down and retain function. In short, I bet that Occam's razor holds pretty well at the cellular level.

notmercury re: pill
you need to stop watching Alice in Wonderland and turn down the Petty while you're at it! /insert favorite wink thingee/

María Luján said...

Hi Bart
I found these manuscripts very interesting

J. Clin. Invest. 111:801-803 (2003).
The challenge of molecular medicine: complexity versus Occam’s razor
Eric A. Sobie1,2, Silvia Guatimosim1, Long-Sheng Song1 and W.J. Lederer1
http://www.jci.org/cgi/content/full/111/6/801?ct

and, as an introduction
http://www.ccwu.edu/Thesis_Moynihan/Chapter4.htm

References
http://cfpm.org/pub/combib/complbib.txt

About your comment, yes I think that in autism we have UP to 20 genes in combination with a myriad of potential problems during the pregnancy, plus interactions prenatal and postnatally with environmental insult, at and individual level. Nightmare indeed.

Everything should be made as simple as possible, but not simpler.

—Albert Einstein’s comment on Occam’s Razor

María Luján

Bartholomew Cubbins said...

Thanks Maria, I'll take a look at those review papers.

"Everything should be made as simple as possible, but not simpler."

This quote is hilarious (can't make something more simple than simple as possible) and I'm not sure if he meant it as such, but I agree with Al if he meant to say "Everything should be made as simple as possible, but not [too simple such that obvious fact is being ignored thus making the model useless]." Maybe someone should let these people in on that notion.

María Luján said...

Hi Bart
I found the quote as hilarious as you, but I also think that there can be not obvious things related to what we do not know.
Some models are very good in one time and totally useless/wrong when time brings new knowledge.
I always take in my mind how the atomic theory was up to Bohr theory and how Quantum mechanics and Schrodinger changed the view of what atom/bonding is.
I can imagine many words but simple is not one of them when I try to teach my students the hyper-basics of quantum chemistry.
Considering history-and chemistry history!...I try to analyze everything in ASD field the best I can :)

María Luján

Ian Parker said...

Hi All,

First, NotMercury, thanks for stopping by and for the kind words. I’m currently writing my next post (there’s just a small matter of finding the time to complete it), but I like your thought. I also think that there is a lot that we all agree on, which is one of the places I’m hoping to take this blog. But first I think it is necessary to carve out a moderate position in the ongoing debate, which I think has become incredibly polarized. It amazes me that when I say I’m a moderate bio-med that all sorts of interventions are assumed, and opinions and goals are automatically assigned to me I have not stated and do not hold. For me this is not ideological – it is about my daughter. The conduct of the debate tends to be very black and white, which obscures the middle grey zone that I believe many more of us inhabit than the tone and conduct of the debate would suggest.

Bart, I’m not convinced that the numbers do not support room for an exogenous factor (or more than one) to be behind at least some cases of autism, but I also recognize that your understanding of this subject is much greater than mine.

My understanding of genetics is that most bodily systems and functions are the result of the interplay of many genes, and yet in MZ twins the outcome at birth is pretty much identical, after allowing for variations due to differences in the resources available to each twin. And yet in the case of autism the concordance rate is only 60%, and even within the 60% there can be significant differences in diagnosis.

I understand that even with an identical genetic and epigenetic heritage that variations in transcription or expression can occur within one twin but not the other. But if the rate of discordance is as high as 40% in the case of autism then I would suggest that it is a logical assumption that the rate could be as high in the development of other ‘systems’ too, to the point that ‘identical twins’ would be a meaningless term. Although identical twins are not truly identical, they are similar enough that a discordance rate of 40% seems too high to me to be accounted for by differences in the expression of the same genetic or inherited epigenetic variation. So while I understand the concept of Occam’s razor, I have trouble accepting the idea that the simplest or most logical explanation is significant variation within the expression of identical genes, rather than ‘interference’ in the expression of identical genes via an external factor. One of the papers I linked to also cited support for the concept of a ‘second hit’ on top of underlying genetic factors. So, I’m not ready to rule this out, but I do accept that I could be wrong.

María Luján, thanks for contributing so much to the overall autism debate, as well as to the discussion here. I’m impressed as ever by your input and your energy and grateful that you have taken the time to join in the discussion and argue points of view in which I see much merit.

Camille said...

You can have "identical" genes in two kids, but for example which individual cells in a female have the X chromosome that came from the mother "shrunk" and shut (turned into a Barr body) and which cells have the X from the dad turned into a Barr body is entirely random. So a few disorders that are on the X chromosome are obvious on the surface of a woman's body, you can see which of her skin cells have the dad's X chromosome "online" and which cells have the mom's. This is the whole "calico" cat thing, and why you can't clone a calico cat and ever expect any of the kittens to look much like the cloned cat. The arrangements of spots is entirely random. I'm pretty sure this is what they mean by a disorder being mosaic... though "mosaic" might work with other than "x" chromosomes... I forget.

I gave an analogy of how epigenetics works on "autism natural variation," I think... it was about placing numbered BB's like a hundred of them in each of your hands in the exact same order and dropping them onto two identical trays. The same numbered BB's would not all end up in the same place on each of the 2 trays. There are things that happen in development that are different for each developing embryo, you can not ever grow twins within a woman that will have identical brains. Not possible. The twin concordance personality thing is overstated, too. There are some confounds in the well know "twins separated at birth" studies that account for some of the "identical" outcomes... not all but some.

Twins do not have the same fingerprints. If you think about brains as being fingerprints... it's easy to see how the genes could push toward the spectrum and one baby could be quite obviously autistic and the other just quite quirky so that you'd have to really look carefully to see the autistic traits.

There is no brain disorder/condition that is more heritable than autism.

That says something.

Nearly all autistics have relatives on the spectrum, if not their identical twin.

The math has been done, statistically it appears that there are about 15 different genes contributing to autism, with about 4 or 5 of them being present in each kid with an ASD diagnosis. Really, you can figure these numbers out with math. Now, where are the 15... well, they've got some really hot leads on 4 or 5 the last time I looked, the rest are harder to find. One hopes that finding them doesn't mean "oh, goody, now we can do prenatal testing and bring humanity up to a glowing state of perfection by aborting all the dross."

It is interesting that so far none of the genes that have a high occurence in autism populations seem to have a particular interaction with mercury or other heavy metals.

You said something like "just because I say I am moderate in biomed that doesn't mean that I think x, y and z"

Autistic adults are accused of horrible things and people put words in our mouths constantly. I don't know of any autistic adult who would be anything vaguely like the "biomed" that Dr. Bauman does for about 1% of her autistic patients. They have mitochondrial disorders. The disorders are rationally tested for and she rationally prescribes what basically are OTC supplements. Bless her heart. Gotta love a woman who finds a solution in the health food store. But look how she got there! Science. There isn't a "margaretbauman.com" website. Good clue that she's not a quack.

I've never heard of an autistic adult that is entirely against trying the GFCF diet. I'm not. I just think it's over hyped, and that it helps *some* kids not to feel like junk. I'm glad that it's being studied carefully.

But we are portrayed as saying "let the children rot", "ignore their physical pains and symptoms", "never teach them anything." The portrayal of us like that is libelous and quite deliberate, and can be traced to Lenny Schafer, most likely. He hates us with a red hot passion. Maybe one of "polarized" sides is not as "polarized" as you think it is.

One more thing. People tend to discuss "taking away autism" as if what you would have left would be perfect. Making a child "not autistic" doesn't leave you with a perfect child. Now you have a kid who can grow up to be a bank robber or drug dealer/prostitute, white collar criminal, used car salesman, child porn producer .. might hate your guts and never speak to you again. Not a pretty thought, but true. Kids don't come with guarantees. Autistic is not the worst thing a child can be.

Ian Parker said...

Hi Camille,

Thanks for stopping by (really).

But I'm afraid you have me at a bit of a loss. For a start, I'm not sure if and where we're agreeing or disagreeing?

Regarding concordance in MZ twins, I believe that everything I've written and cited is very mainstream and peer-reviewed, and I can produce more regarding autism, genetics, and possible environmental influences straight out of PubMed. My interpretation also seems pretty mainstream, based on what I'm reading (not a DAN! publication in sight). I’m actually surprised that I never saw it written up elsewhere first. I think maybe that is because everyone is too focused on another bone of contention?

I agree on the gene count, and with your view on the implications of genetic testing. Maybe I’ll post on this down the road. I have a definite viewpoint on this and have walked the talk on it, unlike most who argue the issue one way or the other.

Regarding mercury, I find it very interesting that I'm the one who hasn't raised the issue, other than to say that the logic of an exogenous factor is not evidence for either 'side'. Many others have brought it up. I've deliberately tried to stay away from it, as it has nothing to do with the point I was trying to make. To be frank, I don't think you can find a post or comment by me anywhere where I've ever suggested a link between mercury and autism, which may tell people something about my thoughts, if they care to drop the stereotypes and listen.

Re: Dr Bauman - I'm a fan like you. Regarding science and testing, I'm thinking about a future post on this. To be honest, probably one of the greatest influencers of my philosophy on testing is Kev.

Re: interventions, we're pretty moderate, and re: GFCF, I was lactose intolerant as a child, which should give a hint.

Regarding your statements:

“Autistic adults are accused of horrible things and people put words in our mouths constantly.”

And

"But we are portrayed as saying "let the children rot", "ignore their physical pains and symptoms", "never teach them anything." The portrayal of us like that is libelous and quite deliberate, and can be traced to Lenny Schafer, most likely. He hates us with a red hot passion. Maybe one of "polarized" sides is not as "polarized" as you think it is."

And now a quote of my own:

“But I also see a discussion that is increasingly polarizing, in which accepting that others have different views is giving way to an advocacy that rejects other viewpoints as unenlightened, wrong, or not yet at their level of "awakening". This used to be a hallmark of the more activist element within the anti-vaccine crowd, but is also becoming increasingly apparent in the “autism is natural variation” crowd too.”

A few thoughts:

a) I think my quote is suggestive of who I think started ‘it’. Don’t you?

b) I'm really not sure who Lenny Schafer is (honestly), other than a vague sense that he is connected with your opposite ‘side’. I’ve never read anything written by him. Ever. Should I know him?

c) I'm hoping the implication of the above is not that I've said any of those things. If so, as I've said to you before and elsewhere, show me where I’ve said these things and I'll apologize.

d) I too have had a few words put into my mouth by some and I’ve called them on it.

e) I’d suggest that your approach to me here is proving the existence of one of the poles in spades. Rather than read what I’ve said you’re looking to use my words to associate me with a viewpoint that I have not articulated. I don’t think that you’ll be the last to do that, either. Perhaps that is because the debate has become so black and white that people can’t comprehend that there may be some who are a shade of grey.

Regarding:

“One more thing. People tend to discuss "taking away autism" as if what you would have left would be perfect. Making a child "not autistic" doesn't leave you with a perfect child. Now you have a kid who can grow up to be a bank robber or drug dealer/prostitute, white collar criminal, used car salesman, child porn producer .. might hate your guts and never speak to you again. Not a pretty thought, but true. Kids don't come with guarantees. Autistic is not the worst thing a child can be.”

I’m not really sure what you’re saying here, who you’re saying it to, or why you think you need to say it?

Anyway, if you’re interested, we may one day be able to have a serious dialogue during which you may find out that your views and mine are not very far apart in a lot of areas. My blog is open, but it’s up to you to decide if you can get past the stereotype.

Now all I need is for ForeSam to show up.

Tara Marshall said...

This would certainly explain why changes in diet, especially when introduced to a young child, can seem to have such a dramatic effect on their functional levels. In general, the children I have worked with who went on the Gluten/Casein/Soy free diet have done much better when the diet was introduced prior to puberty than when it was introduced later - more language, more social skills, etc.

I'm not discounting other influences, such as availability of speech and occupational therapy, parental support groups, and other things that have developed to help autistics and their parents over the past several decades. These all have their influence, and as an aspiring SLPA, I certainly hope to have a positive effect on children's development.

As a person on the autism spectrum myself, I see Autism as a natural variation on brain development. In my family, I suspect it is as much genetic as epigenetic, since we've had people on the spectrum for three generations on Dad's side of the family. My Dad was a computer engineer who didn't speak until he was 6. He had an uncle that family lore calls "deaf mute". My mother has a sister who was diagnosed with mental retardation and schizophrenia when she was five back in 1950, who really needs to be rediagnosed as Autistic.

My childhood diagnosis was Elective Mutism with Autistic Features, since High-Functioning Autism wasn't a concept back then. I met the DSM-III criteria that were in place for Autism, but I wasn't self-injurious. I was classically echolalic until age 8, quite hyperlexic, and just didn't fit the stereotypes. I have an adult diagnosis of Asperger's, but feel that HFA would have been more appropriate.

I'm gluten, casein, and soy free myself, as well as removing all the artificial colors, flavors, and preservatives from my diet. I hope that this may help any children I have be HFA or Aspergers rather than lower-functioning. I'm still not sure what I would do with a Neurotypical child, I don't even like larval Neurotypicals, even though I adore kids on the spectrum.

But it certainly makes sense that if diet can affect the expression of genes that affect cancer and other diseases in monozygotic twins, it can affect autism and its severity.

Ian Parker said...

Hi Tara,

Thanks for stopping by.

I also see autism as at least partially a natural variation - actually, as a developmental disorder on top of a pre-existing natural variation. My 'ASD as a Developmental Disorder' post here discusses this a bit further, but I plan to write an 'Acceptance' post on this too to more closely link the two ideas.

Glad to hear that you've seen some success with 'the diet'. My daughter (the Bear) is on it too. We saw some initial improvements, but by now it is so second-nature that we don't really think about it anymore.

mark1958 said...

I dont want to add to the GRAY
Briefly,
EVERY human condition IS genetic
(searching here adds to the GREY)

I came to your file with the search Separated+at birth+identical+twins +autism.

Raw data has not been collected, so that it can be screened and qualified and analyzed .

Modeling of complex systems may permit a more balanced understanding of the possibilities.

For instance a study of normal mz twins should be a start point.
Then normal separated twins. This may lead to sufficient trends to emerge in brain type to map the off normal areas.

Parallel studies of Dz types should also be fully mapped

The reason why these studies have not been funded is also complex.this is the solvable problem whereas an individual with autism may be a gift from God.

Ian Parker said...

Hi Mark1958,

"EVERY human condition IS genetic"

I don't even know where to start to disagree with that statement. Perhaps a good place might be with one word - epigenetics - and leave it at that, long before getting into a nature vs nurture discussion.

Regarding "adding to the gray/grey", the 'Grey' refers to my location on the quite polarized spectrum of opinion regarding autism from black to white. It does not refer to my thoughts on the condition or relative merits of 'being' autistic.