At least since 1992, I think. We only had the methodology in a robust form in about 2001. It started with RDA [representational difference analysis, a microarray method for quickly scanning for differences between two genomes] and it was still too painful to do. And when it became ROMA [representational oligonucleotide microarray analysis, the next generation of the technology], it was feasible to do, but we didn't have the funding. And I didn't have any real hope of getting funding.

But by a marvelous coincidence, there was a philanthropist that was interested in supporting us, Jim Simons, who I knew through some completely different interaction. Jim called me to get my advice on a grant he was going to give to deCODE [the Icelandic genetic research company]. So, I gave Jim a phone call and I said "Autism, autism! We'd love to study autism!" So, I explained to him what our approach was and he liked it. And he gave us a small initial grant, which was actually, for us, a lot of money at the time. I think his funding started prior to the 2003 paper; we were already driving to that.

And then through another lucky coincidence, I had a colleague at Columbia, Conrad Gilliam [now at the University of Chicago]. He was part of the AGRE [Autism Genetic Resource Exchange] consortium, and so we had access to the AGRE samples and his enthusiastic backing. There is sort of an irony there because the AGREs were multiplex, and I actually wanted to study simplex because we're less likely to see spontaneous mutation in multiplex families, more likely to see them as the cause in simplex families. Conrad felt that we would see what we would see with the multiplex. Finally, I came to him and said we really want to study simplex. Conrad told us about Jim Sutcliffe [a molecular physiologist at Vanderbilt University, who had a collection of simplex families]. So, Conrad was really instrumental in connecting us to the community.

Had you had any experience with any autism sufferers that stoked your interest in the disorder?

I was aware of it because my [high school] girlfriend's brother had autism. I didn't know it was autism at the time. And then, through our kids, I met friends in the neighborhood who had autistic children. So, I was very aware of its devastating consequences to a family. Since much of my last 20 years has been spent raising a family, I am very sensitive to family issues

If you're a biologist, if you're a geneticist, you are in a culture where you hear repetitively the problems that people are being frustrated by. And if you're at all sensitive to the culture that you live in, these things are like neon signs; they're not obscure things. And it was clear that there are a host of genetic problems that were not getting solved by the classical methods, and some of them were socially devastating. Schizophrenia was the most obvious but autism was just as abundant as schizophrenia and it's probably socially more devastating. Probably the most devastating of all is alcoholism.

Unless you're tone deaf, you're aware that autism is a large, unsolved problem. Also, if you're at all sensitive to the public support for biomedical research, you realize the public's been disappointed. It's a little bit like solving multiple equations in one fell swoop. Number one, there's a crying unsolved problem. Number two, the public has been losing faith in the return for investing in molecular biology, in particular, in the Human Genome Project.

And then, I'm an opportunist. To be alive is to be an opportunist. And we had a methodology that could be used for cancer and we were doing that. But we also had a methodology that could be used for genetic disease. And so, there's kind of an inevitability to work on this glaring problem that no one's making progress on. And people were not making progress on it because I think you need to have a genetic understanding of a disorder before you can go anywhere. Unless it's some sort of thing you can correct surgically.

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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