Autism:There's Hope on the Horizon

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


Question: What will be the impact of your research on autism treatment?

Michael Wigler: Yes, well there are two ways in which our work could inform clinical treatment.  In the area of early diagnosis.  If there’s a child and it’s developing—it’s giving off developmental clues there might be something wrong, if we had a list of the kind of genetic lesions we could screen for, we might be able to determine early on that this child is going to develop a form of autism.  And if it’s correct—most disorders are correctable to the extent that they are correctable, are more correctable early than late, when we know how to correct or treat, we’ll be able to start that sooner.  So, early diagnosis is going to be important for any disorder.  That’s one way. 

Another way is children with a particular genetic abnormality, that is, those children who share genetic abnormality, may have one particular way of treating them that’s different than children who have a different abnormality.  We will only learn about that once we can separate these children according to their genetic abnormalities.  That’s going to take many, many years. 

The third way is that in some cases, we will be identifying genes, who by their very nature, tell us this is a correctable, treatable, syndrome.  For example, we find a gene that’s involved in metabolism.  This child is perhaps got really a storage disorder of some type, but altering the diet in those cases might be able to treat the child.  But unfortunately, we don’t yet know the identities of the autism genes.  We have regions and there’s a huge effort underway.  I would say, in particular by doing very exhaustive sequence comparisons of children to their parents, we will identify the actual culprit genes.  And that will take us two to four years.  And there may be, unfortunately, I’m estimating around 400 such genes that each one of which can cause autism.  But when we have those genes, we see what they do; we can see what pathways they are interacting with, some of those will suggest immediately treatments that can be tested.  We will be able to make animal models and test drugs in animals to correct these things. 

So, in general, the way to understand a disorder is to understand its causes and then address those causes.  In the case of autism, most people would agree, I think most scientists would agree the causes are genetic, and we have a pathway to discover the genes.  So it will be easier to diagnose, classify by diagnosis into behavioral and even drug treatments, and discover new drug treatments.

Recorded April 12, 2010