Tuesday, September 7, 2010

Shopping for Autism Research

I have been privileged to see many fascinating and insightful proposals for autism research in the context of my service on the NIH and Autism Speaks review boards. In the proposals scientists share their ideas and to some extent, their hopes and dreams for future autism study.

When these proposals come in, I consider it an honor to advocate on behalf of the ones I believe have the best chance of benefiting today’s autistic population. I’ve discussed and spoken up for al kinds of research on behalf of many scientists and institutions. Yet there are some proposals I think about . . . but I have not seen.

You might say I am dreaming of research. Things I wish people would propose. Projects I’d like to see. Here are two:

1 Studying Geek Success

There is an awful lot of talk about “Almost Asperger Geniuses.” People banter names like Bill Gates, and they say things like, “One third of the science faculty at my university has Asperger’s.” It’s clear that there is a popular perception that many successful geeks are either on the spectrum or close to it. Yet those people are not disabled; far from it. Instead, they are exceptionally successful.


There are a number of screening tools that pick up Asperger/Autism personality traits that fall short of an ASD diagnosis. One good example would be Simon Baron Cohen’s AQ, EQ, and SQ tests. You can explore those tests yourself at www.cambridgepsychology.com

Why doesn’t some intrepid grad student gather a bunch of successful geeks who score high on something like the AQ, yet are successful in life, and look at the reasons for their success. Ideally, those people might be compared to a diagnosed Asperger group who has similar AQ scores yet have an official diagnosis and a disability.

If the scores are similar, what sets one group apart from the other? Why is one person with a high AQ score earning seven figures while someone else with the same score is on social security disability? Are there insights that could transfer from the more successful group to the less successful one?

Is the less successful group missing a particular set of traits? Do they have “extra” traits that make them less successful?

We talk at great length about the great things these exceptional people have brought society. Yet I am not aware of any comprehensive study that examined how this might have come to pass.

This spring, Autism Speaks funded a 25-year follow up study of people with more sever autism. The goal of that study is similar to what I describe here, but for a different population. The folks in that study are much more disabled as many had DSM III autism diagnoses. If the people at the very top of the spectrum are so successful, why don’t we try to learn how they do it and transfer that knowledge to others?

Can it be done?

I think that would be a fascinating piece of work.

2 Attacking the Environmental part of the puzzle

At the profoundly disabled end of the autism spectrum, we look at genetic defects or mutations that result in very severe autistim. In the latest studies, scientists are finding a significant number of de novo, or new, mutations.

That means the parents do not have a particular genetic problem, yet the child does.

Intuition tells us that some of these de novo mutations are caused by a complex inheritance mechanism we just don’t understand. Yet the same intuition tells us a good number of the mutations are the result of some kind of environmental trigger. Probably many environmental triggers.

I would like to see some well thought through studies to explore those possible environmental triggers for some of these newfound mutations.

This is a really hard question to attack. But it must be done.

You can look at genetic data from a disabled person’s blood, and compare his genome to that of a someone else who’s not autistic. The differences put us on the trail of genes that are implicated in the autism puzzle.

I say that as if it’s easy . . . it’s not! It’s very hard work. But we have a plan to attack the problem, and it’s being attacked on many fronts right now. That’s why we are moving faster on the genetic side than the environmental side . . .we know how to attack the problem and get results.

Yet that’s only part of the puzzle. We’re finding mutations, but it’s much, much harder to figure out how they came to be. Where do you start?

You can subject developing cells to bombardment from chemicals, light, noise, magnetism, radiation . . . there’s no limit to the environmental contaminants we can assault cells with. The problem is knowing which bombardments are happening to real people, and which cause damage?

How do we know what’s really happening out there in the world?

We’ve implicated some chemicals in recent years, and ruled out others. We are nowhere close to answering this fundamental question.

I think the environmental question needs to be attacked on the public health/statistical analysis front first. Where are the “pockets of autism?” I hear about school districts, counties, parts of Silicon Valley, and other places in the news. What’s real? What does the statistic data suggest in terms of exposures or agents?

I don’t know how these environmental studies should be structured. But Hesh on the Sopranos had it right when he said, “I don’t know how to write the songs, but I know a hit when I hear it.”

I feel the same way. Bring me a hit for environmental research.

Monday, September 6, 2010

When Pigs Fly

This is what it looks like. Two pigs, one track. Eight legs in the air. Near forty miles an hour, some say. This is just below liftoff speed.

And the best part . . . when these two went airborne, Number Four - Tammy Fay Bacon - moved into the lead for a surprise victory that paid off eleven to one.

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.

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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.