A Personal Interest in Autism

Dr. Michael Wigler has made wide-ranging contributions to biomedical research in genetics, cancer, and cognitive disorders. Dr. Wigler attended Princeton University as an undergraduate, majoring in Mathematics, and Columbia University for graduate studies in Microbiology. After receiving his Ph.D., he began his scientific studies at Cold Spring Harbor Laboratory, where he continues his work to this day as an American Cancer Society Research Professor.

Early in his career, Dr. Wigler developed methods for engineering animal cells with his collaborators at Columbia University, Richard Axel and Saul Silverstein. These methods are the basis for many discoveries in genetics, and the means for producing medicines used to treat heart disease, cancer, and strokes. Dr. Wigler continued his genetic explorations, and in the early 1980s isolated the first human cancer genes. In the mid 80s, Dr. Wigler and his collaborators demonstrated conservation of cellular pathways in humans and yeast, thereby providing deep insights into the function of the cancer genes.

In the early 1990s, Drs. Wigler and Clark Still developed a method for building vast chemically indexed libraries of compounds, an approach that is still in use for drug discovery. During the same period, Wigler’s group developed the concept and applications of representational analysis, RDA, which led to identifying new cancer genes and viruses. He later enhanced this concept through use of microarrays, a method now widely used commercially for genetic typing.

Dr. Wigler’s research is presently focused on the genomics of cancer and genetic disorders. He expects this work will eventually improve the targeting of cancer treatment and lead to early detection tests for cancer. His studies in human genetics led to the discovery of a vast source of genetic variability known as copy number variation (CNV), and to the breakthrough that spontaneous germline mutation is likely to be a contributing factor in autism. His genetic theories and methods suggest to new approaches to understand many other cognitive and physical abnormalities.

For his fundamental contributions to biomedical research, Dr. Wigler is a recipient of numerous awards and honors and is a member of the National Academy of Science and the American Academy of Arts and Sciences.
  • Transcript

TRANSCRIPT

Question: How did you become interested in autism?

Michael Wigler: My personal interest in autism dates from when I was a child, and I had a friend whose brother was quite strange.  And when I was in medical school, I realized that he had autism.  It was actually Asperger’s. He was a very bright kid, never looked you in the face, constantly was throwing his arms up like that as though he had made some great discovery; and knew everything about baseball statistics. And so it made an imprint on me at an early age. And it’s sort of a wonderful, it was sort of a wonderful thing to see this fellow who actually grew up to, I think he had a successful career as a disc jockey.  So, I was always interested in autism and because I come from a family that’s somewhat left-wing, always looking for ways I can do something that is a benefit to society.  And it struck me that autism was not a disorder that was studied by the scientific community very deeply.  But in the worst cases, it was tragic for the families that had an autistic child. 

So, I was motivated by both of those things to have an interest in autism.  And when we began to study cancer, which was in the early 1980’s, I knew at the time they were studying cancer that the tools that we were developing could later be applied to genetic disorders.  Not the kind of genetic disorders where you inherit something from your parents, but the kind of genetic disorders that arise spontaneously because of mutation in the parent’s germ line. 

An example of those kinds of mutations that everybody’s familiar with is Down syndrome; or Trisomy 21 I guess is the clinically correct way to refer to it.  These are new mutations.  You don’t inherit it in the classical sense, but it was obvious to people who thought about it that human genome is not static; it changes over time.  That’s how we evolve.  And most of those changes are not good.  They result in some disorder or another, but they’re hard to study.  Most people who study genetic disorders study inherited kinds of genetic disorders.  I was interested in the other kind of genetic disorders that result from new mutation.  And new mutations are what we study when we look at cancers.  When we’re comparing a cancer to the normal person’s genome, the cancers differ by new mutation.  That’s called somatic mutation. 

The same tools that find somatic mutation can find germ line mutations if you compare the child to the parents.  The incidence of autism being relatively high—and by and large, these children are so different from their parents—it seemed to me that it was likely, just a priori, that autism was the result of new mutation in the germ line possibly affecting many, many, many genes that result in the same end behavior, or similar end behaviors, and that was being ignored by the community. 

So, when we had the tools to go look at this, we did so.  And so it was a combination of opportunism because we had developed the tools, and intrinsic interest from both a social point of view, the social good, and also from a personal point of view.  That is, I had a personal interest in how does the brain go from being what we would recognize as belonging to a normal person to somebody who is, in wondrous ways, very different from us.


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