So, essentially, mutations to transcription factors?

Yeah, things that change the balance of connectivity in the brain, for example. They're important to find because they hold promise of being able to modify the outcome of the disorder, if you can detect it early enough.

Things that are modifiers are likely to be, in my opinion, common polymorphisms. The things that are strongly contributory, I don't think are going to be common in the genome. They're going to be things that arose from mutation and survive in the human gene pool for one, two or three generations before getting eliminated because they're really nasty.

Is that why spontaneous mutations would most likely result in autism for males?

The model is that most sporadic cases are in fact these lightning strikes, which nobody likes to think about. I'm used to thinking about it because I'm a cancer researcher and when you get cancer, it's a lightning strike. You hear people say, "Oh I eat all the right things, I exercise, I don't smoke," and they still get cancer. I think it's natural for people to want to finger some cause that's controllable, but random processes are not controllable. People are very reluctant to accept randomness as a factor in their lives.

How confident can you be attributing a large part of your theory to randomness with all the reports of increased incidence of autism in recent years?

There are a couple of things that draw a lot of attention. One of them is the apparent increased incidence. Another is the sense of many parents that there child is doing well and developing normally and then fairly suddenly seems to develop symptomatology. Those are the two things that I think are driving people to think in terms of models that are not genetic. So, we should probably talk about them separately.

On the increased frequency, I am not an epidemiologist, but I have heard a very convincing talk by a Canadian epidemiologist, who did a very careful analysis and came to the conclusion that there was no real measurable increase in frequency—that it is largely a factor of more people being diagnosed. And I have heard this theme in other people's talks who are not professional epidemiologists, but there seems to be a general consensus that when the diagnostic criterion was solidified in the mid-'90s, that more or less correlates with the sudden change in slope of diagnoses—that the rate of diagnoses started to rise.

And with regard to the increased incidence being caused by thimerosal in vaccines, the rate has continued to climb, even with the chemical being removed from immunizations more than six years ago.

I am not familiar with data on vaccines and what people have done with that. I can tell you that my own bias—and it's really a bias—is that there's nothing in that. But you can't print that without also printing that I haven't seen the data, that's just my intuition. So, in that sense, I am just like an ordinary citizen.

So, the increased incidence is largely increase in diagnosis. There could be reasons why there could be small increases. That could have to do with the age at which couples are having children. There could be something about the pattern of marriages that somehow increase the rate, but then we start getting into dangerous terrain.

Then, regarding the unified theory, where do environmental factors come in?

Just because something is genetic doesn't mean it's not environmental—that's number one. If you have 100 people and they're all exposed to the same environment and one reacts badly to it, that's genetics and environment. So, just by saying something is genetic says nothing about that it might not be also environmental. That's the main point. The secondary point, we said our model assumes that—the population genetic analysis that we did makes an assumption that—it's genetic. You can't turn around then and say it proves that it's genetic.

1 Comments

1. 1. Teresa Brito-Robinson 07:17 AM 1/19/08

   As a biochemist/molecular biology scientist and mother of an autistic 7 year old girl I am very interested in this new vision. It has been very frustrating the wait during the autism gene hunting leading to more and more unanswered questions rather than answers. I am glad Dr. Wigler and colleagues are seriously looking at the problem coming with the cancer genetics experience. I am a mother daugther pair looking for answers. I see a cluster of traits in my family: ADD, depression, anxiety,panic disorder more ADD among us parents and older daugther. One girl only with autism and ADHD with no mental retardation and no epilepsy in her. Count me in, in donating tissue samples.

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