Beyond the Wooden Door
	On the Road to Lucky Breaks

Many are likely to go on to careers as professors at major research universities.

On the Road to Lucky Breaks

Thirty-four uncommon Ph.D. students look for what makes people sick.

t the tender age of 26, graduate student Steve Laken has already achieved more public acclaim than most scientists receive in a lifetime. He has been featured on the nightly news of all four networks, in the New York Times, Baltimore Sun and USA Today, and on National Public Radio and the Associated Press radio network.

Laken, in his fourth year of a new Hopkins medical school graduate program in cellular and molecular medicine, is part of a research team headed by Bert Vogelstein and Ken Kinzler, and credited with identifying the first familial genetic mutation that causes colorectal cancer and developing a simple blood test to identify it. The discovery is important in cancer research because it proves that a common type of mutation, previously thought harmless, can cause a predisposition to the disease. The mutation, present in over half a million Ashkenazi Jews, is the most common cancer-related mutation known.

The recognition is heady stuff, but Laken downplays it. “All of us [in the program] are at good labs with great opportunities. It’s highly unusual for a graduate student to come across a finding like ours. We were lucky.”

More lucky breaks like Laken’s are precisely what the University hopes its unique curriculum will engender. Unlike students in traditional Ph.D programs these trainees focus on cellular and molecular biology with an emphasis on what makes people sick. Many are likely to go on to careers as professors focusing on specific diseases—various cancers, for instance—at major research universities. About eight students a year enroll, with 34 now in the pipeline. Generally, students will take four or five years to complete the program. They start their hands-on research, under the guidance of world-renowned researchers like Vogelstein, as soon as they arrive on campus. During the first year, they rotate through several labs, as well as taking core courses.

“Any lab director would feel lucky to have one of these students,” says Paul Bray, associate professor of medicine and pathology. “Typically, they differ from med students because they have already made a commitment to basic biomedical research, which makes them more focused. This is their career.”
By the end of year one, students choose a research lab in which to start their thesis work. They study biology through six core courses: biophysics, biochemistry and cell biology, genetics, molecular biology, and an overview of organ systems. In the second year, students take a course on the molecular basis of disease.

Only a few other top schools—including Harvard, Cornell and Washington University in St. Louis—offer similar programs. That is likely to change. “In the next century, getting Ph.D. training with a clinical relevance will be the major form of medical training. The public and the National Institutes of Health will demand it,” predicts program director Peter Agre. “The public is particularly interested in scientific research that will improve the treatment of human disease. Unfortunately, we all know someone who has suffered from a devastating illness.”

The research projects the students select are highly individualized. One is seeking a molecular understanding of fatal irregular heartbeats. Another is examining the molecular basis for sleeping sickness and how it evades detection. First-year student Michele Nealen, 25, is looking at why women are more susceptible than men to certain heart diseases, and the role estrogen receptors play in heart disease. Another first-year student, Dennis Chesire, 23, is working on the role of T-cell receptors in diseases like multiple sclerosis, lupus and rheumatoid arthritis.

“Most students come here to study cancer or AIDS,” says Shafinaz Akhter, 24, a third- year student from Bangladesh, who’s chosen a disease with a much lower public profile. “The gut doesn’t get as much attention, but diarrhea kills millions of people a year. My mother’s sister died of it,” she explains.

In other graduate programs, students often spend years doing research, without ever encountering a sick patient. Not here. Students regularly consult on cases with doctors on the front line of treatment. Even more than his classmates, David Kirsch, 26, is combining clinical training with academic research. Kirsch will receive an M.D.-Ph.D. when he completes his training. His research project is on cell cycle control and what makes tumor cells different from normal cells. “At times, it’s grueling,” he says of the program, “but you can have a balanced life. You can’t spend 18 hours a day in the lab.’’ He managed to leave the lab long enough to get married recently.

The program’s small size encourages a certain camaraderie. “The first year is very hard, very high stress,” says Akhter. “But we study together, which is a nice change,’’ she says, from her undergraduate days in the Hopkins “pre-med factory,” where she majored in biology.

Besides study groups, another thing these grad students share is the challenge of helping patients on a wide scale through research, rather than one by one. “What motivates me,” Laken says, “is the opportunity to provide cures for the 100,000 people a year who get colorectal cancer. It’s a great feeling to go into the lab every day and think I’m going to make a difference.”