Saturday, September 4, 2010

The promise of genetic research for autism



This summer, the Autism Genome Project announced the discovery of several new genes that are implicated in autism. Their report is the culmination of a study that compared genetic data from 1,000 people with autism to a slightly larger number of non-autistic controls. The results are fascinating.

The first interesting discovery is that a significant number of genetic errors in the autistic subjects were not present at all in their parents. Scientists call these spontaneous occurrences "de novo." Are de novo errors a result of environmental factors that affected the developing fetus, or are they caused by an inheritance mechanism that we just don't understand yet? We don't know, but many scientists are working to answer this question right now.

Researchers have now identified a number of genes that are implicated in autism. Some of them are also implicated in other conditions, like intellectual disability. That leads scientists to the realization that a number of psychiatric conditions may have similar biological foundations.

The genes implicated in autism affect us in very different ways. Some genes change the balance of gray and white matter in our brains. Others affect the way our brain cells signal each other. Others affect the rate at which our brains grow and develop. Even if the observed result - an autistic person - looks similar, the biological causes of disability are not the same at all. We're beginning to realize that autism is really a catchall phrase for a number of brain differences that happen to look similar when seen from the outside.

What does that mean for the concept of neurodiversity; the idea that autistic people should be accepted but not "fixed?"

For one thing, it may explain why some autistic people have a combination of gifts and disabilities, while others are seen or see themselves as disabled; the underlying cause of their particular autism has conferred no discernable benefit. The autistic population may indeed consist of several distinctly different subgroups.

One group may indeed be best left alone. They can make great contributions to society vie their unique way of thinking. At the same time, we have another population who is profoundly disabled and in need of substantial help. If those two groups are separated by fundamental genetic differences it's no surprise they would have totally different treatment or accommodation needs.

One group consists of people who are stable and potentially successful despite being "different." Those folks need accommodation, behavioral counseling, and societal support. The other group is indeed in search of a cure for something that provides them no benefit and a substantial measure of disability.

So is a cure for those people on the horizon? Is that where this genetic research is leading?

The answer is . . . maybe, and we hope so.

We have made a huge step by learning that certain genetic defects cause profound autistic disability. What we need to figure out now is how to help the affected population. So far, we do not know how to repair damaged genetic data; we can only treat the results. For example, if a particular genetic defect causes the body to make too much or too little of a particular chemical the brain needs to function, we may be able to fix that situation with medication.

There is tremendous promise but we have a long way to go.

The biggest complication is that we have so many different genetic problems to deal with. Even though they produce a similar outcome - autism - they work in very different ways at a biological level. None of the "autism genes" we identified so far are present in more than one to two percent of the autistic population. There is no such thing as a single "autism gene." Rather, there are many genes that push us toward autistic outcomes when they go wrong.

That means we may have to develop ten or even a hundred different treatment strategies, to address the multitude of genetic errors that lead to autism. How do we begin?

Genetic testing may allow us to identify babies with gene defects that will lead to autism before their brains have developed on the autistic pathway. If we intervene early enough, we may be able to head off autism in those children. How would we do that? We might use drugs to speed or slow development, or replace chemicals the baby is not making for himself. We might use new therapies like TMS to change plasticity in the developing brain. There is tremendous promise, especially in the case of genetic errors that lead to the most severe autism.

In my earlier writing I have discussed the philosophical issues that surround treatment of autism in children. I used the example of a kid who was a social cripple, friendless; but a computer genius. If we had a treatment to turn on social awareness for that child, should we do it? He would surely be happier, but at what cost? Would we be turning the future Einstein or Newton into a jolly friendly sales manager? What are the ethical and social implications of such a power?

That remains a valid question at the upper end of the autism spectrum. However, those kids won't have the genetic errors that lead to profound disability. If we treat children who have a genetic abnormality that leads to an IQ or 50 and total disability, we do not make any ethical tradeoff at the other end of the range. Instead, we give a child who might have grown up crippled a chance to develop reasonably normally.

There are plenty of "good sides" to autism like mine. That's why I don't want a "cure" for myself. At the same time, I recognize the autism spectrum is very broad, and people at different points on it may feel very differently, as might their parents. If people like me represent one extreme of the spectrum, the other end comprises significant disability. There is no good side to a rare genetic defect that results in an autistic child who can't talk or take care of himself. An IQ of 50 does not confer any hidden benefit; it's crippling, pure and simple.

The ability to tell our different forms of autism apart will open the door to many treatment options in years to come. Plenty of gifted autistics will choose to stay as they are, but we all share a duty to those who want help. The promise of using genetic knowledge to head off the most severe autism in infancy is tremendously exciting to me, and to many researchers in the field.

* * *

I am an autistic person who serves on review boards for the National Institutes of Mental Health and Autism Speaks, the two largest sources of autism research funding. In my work on the scientific review boards, I seek to advance science that offers hope for improving the lives of today's autistic population, and the as-yet-unborn population to come. Genetic research is a poorly understood and controversial area of autism study; one I hope to elucidate a bit more clearly with these writings.

16 comments:

Meg said...

It's such a relief to find a source of information about autism which is both helpful and hopeful. Having been a great admirer of your brother's books for many years, I wanted so much to read yours, but passed it by time and again. I'd had strong suspicions about my son, and wasn't quite prepared to see those things that concerned me corroborated in your writing. Not ready to see how challenging my own son's life might be. Now, I look forward to every post and I'm thrilled to see someone on the spectrum with such a dedication to educating others, and with such dedication to the research. Just- thank you.

Valerie Foley said...

This is incredibly exciting to me.

I'm not autistic but my son is, as are two of his cousins. The genetic link is there, and as a family we'd like to know more about the hows and whys... for our next generation and for the next generation.

I also agree that those of us with the higher functioning autistic traits, should embrace the chance to shine some light on the whole of the spectrum. Who knows what we all might see.

Thanks, John.

www.jumpontherollercoaster.blogspot.com

Janice Morse said...
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jmorse281 said...

This is very interesting to read since people find it hard to believe when I say I don't necessarily want my son "fixed". He has Asperger's and is very high functioning. He was severe when he was first diagnosed but that's only because we didn't know what was going on so he had no treatment. And by treatment I mean the right teachers and therapies. Not that I'm against medication if necessary. But my son is 14 now, well adjusted and brilliant. Yes, he can be awkward at times and he's a bit of a loner. But I've seen him come out of his shell to the point where HE'S comfortable and that's good enough for me. He's thrives reading and writing and he aspires to write science fiction one day. He's the most compassionate and caring 14 year old you could ever meet. I wouldn't change that for anything. He's perfectly comfortable with who he is. He's not superficial in ANY way and if THAT doesn't make him unique in today's society then I don't know what does. If he didn't have Asperger's he might just be some bratty teenager with average grades and low self esteem. Granted, he IS very high functioning, be he wasn't always that way. I think our allowing him to feel like it was ok to be "the way he is" allowed him to come out of his shell more and feel more comfortable seeking out friendships. The spectrum is VERY broad as we all know and I think some Autistics do need help. But we have to stop trying to FIX everyone and medicating all of these poor kids and just help them develop into the best version of themselves.

cath c said...

i found this very interesting, seeing a multitude of 'causes' or 'presentations' in the brain. it seems the more we learn about autism, the more worms come out of the can. this is good, though it may take longer to put appropriate treatments into action in individuals of differing types. our family is fortunate to have a 12 year old who is in the aspie range, and unmedicated. he may not be an easy personality, but he is very funny. i would not want to change that or plenty else about him. but i have seen plenty at a deeper end of the range, and what those families go through, and i'm sure they would really appreciate access to the personality and functionality hiding behind the autism.

Kris said...

This was a fascinating post. I just am sure there are many reasons for what we call "autism". As a former oncology nurse, I am well aware that "cancer" is not one disease with one cause. I also think autism, while not a disease, also has more than one cause and can manifest in many different ways.

My son is a true "puzzle". He has been evaluated numerous times simply because no on can seem to tell us exactly what his dx is. He has symptoms of autism but not enough for an ASD dx. He has sensory processing disorder and a language disorder which has features that are "unusual" according to his doctor. His language problems are not typical of autism but affect him anyway. Two doctors have told me he has autistic features but the root of the problem is different. In the end, he faces many of the same challenges as kids with autism. Even though he would definitely be considered "high functioning" I don't see a lot of benefit for him. It seems many kids with high functioning autism or Asperger's have great strengths in some areas - not true of my son. While not profoundly affected in any area, he does not have the "gifts" many Aspies seem to have. He is lower functioning than typical in most areas. It is hopeful to me that one day the mystery of kids like my son could be solved.

Asperger Ninja said...
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Asperger Ninja said...

I am one of those parents who do not desire a "cure" for my son's Aspergers Syndrome & ADHD.

I also understand folks whose children have more lower functioning autism who do want to make their children not suffer and yearn to give them a better quality of life.

I would like to have future generations not have to suffer with autism, but I am wary of using such genetic tweaking.

bonnie said...

I finished reading your book today. My son was originally diagnosed with sensory integration dysfunction when he was little. As he got to an age where social skills like not being extremely self centered, and able to sit still, and be accepted by peers came into play, at around fourth grade, he started to look more like a kids with Aspergers. As the school year begins and we enter the third school in three years, I say we because school is something we all experience. The affects of a good or bad school day permeate my family as my son crosses the front door threshold. The frustration my son experiences at trying to fit it, at actually connecting with people initially, because his is Typical looking and smart, and then loosing the connection very quickly because he is so intense and only sees what he wants and needs from others and not what they would appreciate in him, that relationship are give and take and those with aspbergers have a hard time navigating that dance.
I always knew that my son got his sensory "stuff" from me to some degree, although, I think in the days where if you carried on, eventually someone would check you with a spanking, I think my fear kept me in check as where my parenting with kindness doesn't always let my son know where he has crossed but I know the larger message that you are safe and understood, I hope will give him what children who don't have a diagnosis and parents who shown them grace get, which I hope is less of the drunk monkey I had, my husband had and you had..
And I was amazed to read how you felt a balance came later in life. I have often felt the same. What part of it comes to people on the spectrum vs people who grow through maturity, I'll often ponder.
John, thank you so much for writing your book. For giving me hope that all kids on this journey do not end up after the bullying-drawn to suicide as we have seen highly publicized in the last year, and dot always turn to drugs -even though self medicating is not uncommon, and for writing your book in such a way that shares the streaming though of the inside of your brain. I have already repeated the story you share about smiling at notification of death. It makes me smile because I totally get it.

John, had your parents known your condition and been in a better state themselves, they would have received the greatest gifts in their own life. The creativity and specifity with which I speak to my son have vastly improved my comminication with everyone. In fact, I think it's why most of my clients are engineers or engineer "types"' which most people in my industry detest for their thoroughness. My son has given me perspective. I take more time to think about what the person I am communicating with is thiinking or needing and how to give them what they need, the way they need it.
My son is 12 and my challenges are many. He has a 3 year old sister who seems more typical but if she stops eating a food or doesn't like the way a sock fits, it catches my attention. But really what will it matter. It is what it is and she and I have a different dance, which I don't anticipate will be any easier or harder, just different.
Thank you for sharing your story. It is a gift to those like me who read it.

a.yonan said...

I just finished listening to you read your book "Look Me in the Eye". Thank you so much for sharing your life with the public. I was deeply touvhed by it.

Lynn said...

Thanks for being so understanding of parents with more severely impacted children. Too often I see high-functioning aspies or parents of them being so insensitive to those parents. My daughter is in the middle and I have often wondered what I would do if suddenly a magic bullet appeared on the scene. Probably I will not have to make this choice...by the time something like that were to come along, she will likely already be grown and can make the decision for herself. I hope that by then she will be a contributing member of society who has accepted herself for who she is.

Me said...

What a great perspective and written with such clarity! You have given me a great point of reference to give to my own son who is struggling with the desire for a cure so he can 'slow my brain down' and fit in.

jess said...

The ability to tell our different forms of autism apart will open the door to many treatment options in years to come. Plenty of gifted autistics will choose to stay as they are, but we all share a duty to those who want help.

YES. we stand together.

r.b. said...

You wiggle your ears for comments, eh?

The only person I've known who could do that was Roger W. in the third grade at St. Patricks Elementary School. I still think it was a trick, an illusion...but even now I can't begin to think how.

Of course, I've always been easily amused....

Lisa Jo Rudy said...

John - is there really any good reason to think that we can define the genetic makeup of "profound" versus "not so profound" autism?

How would we distinguish between "Newton-like genius with social quirks" and "Ordinary intelligence with learning disabilities and anxiety?"

Would we treat someone with ordinary intelligence, but not someone with genius genes?

I have to say that this looks like a very slippery slope, especially if we are thinking of selecting individuals for treatment on the basis of their genetic makeup. After all, our feelings about which traits are "preferred" are based as much on our culture and our historic period as on some kind of objective truth.

Lisa

Mel ~ said...

Thank you thank you thank you for being here. Thank you for writing. Thank you for being you. I'm glad I found yoursite! Do you mind if I quote you and send others your way?!