Cracking the brain’s genetic code

A conversation with Drs. Joseph T. Coyle and Edward M. Scolnick

Bill Snyder
Published: November, 2003

Two of the nation’s leading experts in neuropsychopharmacology discuss the opportunities and challenges facing scientists as they search for better ways to treat disorders of brain function.

Edward M. Scolnick, M.D., a senior associate member of the Broad Institute of MIT and Harvard, is president emeritus of Merck Research Laboratories. Joseph T. Coyle, M.D., is Eben S. Draper Professor of Psychiatry and Neuroscience, and former chair of Psychiatry at the Harvard Medical School. They were interviewed by Lens magazine in 2003.

What are some of the challenges in developing new drugs for psychiatric disorders?

Photo courtesy of Joseph T. Coyle, M.D.
Coyle: The major challenge that we face for psychiatric disorders is that there is no obvious brain pathology that leaps out at you, unlike neurological disorders where there’s some very clear pathology and clear targets. And so the approach has historically relied on serendipity -- that is, developing novel compounds and looking for behavioral effects. That’s really a very inefficient way to attack these problems. Even the development of SSRIs (serotonin-specific reuptake inhibitors, a new class of anti-depressants that includes Prozac and Paxil) was not linked to a detailed understanding of the pathophysiology of depression.

I think what has taken place over the last 15 years is the development of more powerful strategies to help us out. One strategy is brain imaging, both structural and functional brain imaging, which has allowed us to identify areas of the brain and circuits that do not appear to be working properly. These approaches give us a bit of a functional pathologic signature. The second strategy is genetics and the contributions of the Human Genome Project.

How useful are animal models for developing drugs for cognitive disorders?

Scolnick: They have been useful in many fields of medicine. Finding the genetic predispositions or the causative genes for any number of human diseases has allowed scientists over the last 10 or 20 years to model those diseases in genetically altered mice and rats. It’s been done in the atherosclerosis field, the cancer field; it’s been done somewhat in the field of inflammation, the obesity field. It’s quite remarkable how well and how much information has come from it, even though in some cases, like the lipid field many years ago people didn’t think this was a worthwhile thing to do at all.

Finding risk genes for cognitive disorders will allow scientists over the next decade to put these genes in animals or alter these genes, and then ask, “What can you learn from the behavior of a mouse or rat with a mutated or altered human risk gene that’s been associated with one of these illnesses? Will that become a useful way to test for more drugs?”

Page 1 2 3 4 5 > All

View Related Article: Hunting for the genes that “conspire” to cause disease