The Synergy of Research

By Ruth SoRelle, M.P.H.

Dr. Mary-Claire King, professor of genome sciences and medicine at the University of Washington School of Medicine, is best known for finding the first inherited breast cancer-related gene – BRCA1 – but during a recent keynote discussion, she talked about human variation, evolution and the consequences for gene discovery in common complex human diseases. Her speech was a challenge as well to a room full of potential translational scientists at the first annual retreat of Baylor College of Medicine's Translational Biology and Molecular Medicine Graduate Program.

Anything but simple

For example, she said, she has studied inherited hearing loss along with many in her field. There are mutations in more than 100 genes associated with inherited hearing loss.

"Inherited hearing loss is not the exception," she said. "It is the rule. Most affected families have private (specific) mutations."

"I think of it as the Anna Karenina model – every family is unhappy in its own way," she said, referring to the Russian novel by Leo Tolstoy. "Diseases seem complex until the responsible genes are found. Then they seem simple. The trick is to enjoy that 20 minutes."

She sees similar situations in other common inherited diseases, and she expects more to be revealed.

"Thousands of mutations will occur in hundreds of genes that affect dozens of (cellular) pathways," she said.

Think creatively

She challenged the young scientists to think creatively about the science and to find clinical partners – physicians interested in research in the disease associated with the genes they study.

The questions

As they pursue their research, she advised them to ask:

• What are the critical questions?
• What are the critical genes?
• What are the functional consequences of mutations?
• In what pathways do the mutant genes converge?
• What does this mean for treatment?

Graduate program well suited

BCM's program graduates are well situated to pose these questions and seek answer. King said she came to BCM's retreat because she wanted to see if this program was as good as her colleagues said it is.

She feared that it was no more than "a watered-down M.D./Ph.D. program" and was glad to see it's not. While she sees an important role for physicians with a Ph.D. and a research bent, "this program trains youngsters who want to do basic science research to think about that research in a translational way. They have created something for Ph.D.s who pursue basic science but whose mindset is how that basic science will be used in a human disease context."

"I have developed that sense," said King, who received her Ph.D. from the University of California - Berkeley. "But it's taken me 30 years to do that. If this program had existed when I was in school, I probably would have done it."

"This is what teaching is all about and graduate teaching in particular. It enables bright youngsters to think about the links (between basic and clinical science) with guidance," she said.

Importance of mentors

She said she watched as the students presented their projects during the retreat and they seemed to go seamlessly back both between basic and clinical science. "They were doing it without even thinking about it. I think this is unique."

"They are exposed from the beginning to what physicians do. It's the continuous exposure and the co-mentor system," she said. Students in the program have both a physician and a Ph.D. mentor who guide them through their education. "They are always interacting with a clinical mentor so they understand what the challenges are in making the transition. They see how a clinician uses rules and how long the process is."

Leadership

Dr. Mary Estes, professor of molecular virology and microbiology, and Dr. Ignatia B. Van den Veyver, associate professor of obstetrics and gynecology and molecular and human genetics, are program co-directors. Estes is a Ph.D. and Van den Veyver is an M.D. Both are translational scientists.