When Donald E. Ingber graduated from Yale College in 1977, he had definite ideas about what he wanted to do in life. He was either going to write comedy and raise the standard of the television sitcom or else make his contribution to humanity through science. He admits it wasn’t a conventional career dilemma.

Unfortunately perhaps for prime-time viewers, science won out. Ingber enrolled in the M.D./Ph.D. Program at Yale, spent seven more years in New Haven, then went on to discover the angiogenesis inhibitor TNP470, one of the first in a promising class of compounds that physicians hope will provide effective anti-cancer therapies. Ingber did his postdoc with angiogenesis pioneer Judah Folkman, M.D., at Harvard Medical School, where today he is a professor of pathology and an explorer in the largely uncharted field of “mechanobiology,” studying the role of mechanical forces in cell regulation.

Ingber says that it was a mindset cultivated at Yale that allowed him to connect the basic science of angiogenesis to the clinical relevance of an agent that might starve quickly multiplying tumor cells of their essential blood supply. With one foot planted firmly in the basic sciences and the other in clinical medicine, he was able to see each realm from a more practical perspective.

“By combining them, you really are able to understand what the problems in medicine are and to frame the relevant questions,” he says. “And because you’re trained by the best scientists around, you learn the procedure of attacking the problem and reducing it down to its minimum variables.”

Yale’s M.D./Ph.D. Program, also known as the Medical Scientist Training Program (MSTP), turned 30 last year and celebrated the anniversary with a reunion in November. Graduates of the program, Ingber among them, returned to New Haven to attend a symposium and mix with classmates, professors and many of the 80 currently enrolled students.

The program’s five-year renewal was approved this past summer with a study section recommendation of $12.4 million in funding over that period. An additional slot each year has also been recommended, which could raise the number of participants in the program to as many as 85 by 2005 when additional funding from the medical school and other sources is taken into account.

Nationally, the MSTP traces its roots to 1964 when three schools—NYU, Einstein and Northwestern—received money from the federal government to encourage the training of physician-scientists who would be able to leap nimbly from bench to bedside and back again. Yale joined the ranks in 1969 and is one of 39 MSTPs currently funded by the National Institute of General Medical Sciences (NIGMS), according to Bert Shapiro, Ph.D., the director of the MSTP at NIGMS and chief of the institute’s branch of cell biology. The MSTP got off to a slow start and almost vanished entirely in the early 1970s, when then-President Nixon impounded training funding amid concerns that much of the NIH training program was ineffective. “It funded a lot of residents and they weren’t going into research,” says Shapiro, who says that more than 90 percent of current alumni are in research. In 1974, Congress passed a new act authorizing training grants on a much smaller scale; all the previous programs disappeared and were reformulated. MSTP was one of only a few to survive and grow.

The Yale program has 188 graduates, “98 percent of whom are doing funded research,” according to Director James D. Jamieson, M.D., Ph.D., professor of cell biology. “So the program is doing what it set out to accomplish, which was to train physician-scientists to carry out basic research that would be applicable to medicine.”

The roster of M.D./Ph.D. alumni includes Yale professors Susan J. Baserga and Michael J. Caplan, who administer the program along with Jamieson and Gerald I. Shulman. Others on the Yale faculty include Michael P. DiGiovanna, Peter M. Glazer, Robert J. Homer, Barry M. Kacinski, William L. Krinsky, Richard R. Pelker, Jordan S. Pober, Marc Potenza and Sandra L. Wolin, as well as a half-dozen recent graduates who are fellows and residents at Yale.

These younger graduates are much more likely to pursue careers in research because of the funding provided by MSTP, said Baserga, one of the three associate directors of the Yale program and an associate professor of therapeutic radiology and genetics. Tuition and other academic expenses are covered, and students receive a stipend for six or more years, allowing them to keep their level of debt relatively low and thus resist financial pressures to enter private practice or industry. (According to Shapiro at the NIH, MSTP graduates leave with an average debt of about $10,000, compared to $120,000 for other medical graduates.) “The program was set up to encourage students to go into academic medicine,” says Baserga. “It’s been extremely successful in fulfilling that mandate.”

Although the national program has grown dramatically, from $372,000 in annual funding in 1964 to $31.2 million today, some feel it isn’t large enough to counter a documented decline in the percentage of physician-scientists in the United States. “The size of the program should be doubled or tripled,” says Leon E. Rosenberg, M.D., who served as dean of the School of Medicine from 1984 to 1991 and is a highly vocal advocate of bolstering the ranks of the physician-scientist.

“The NIH budget has risen hundreds of percents over the last 20 years. The size of the MSTP has gone up much more slowly and I think that’s short-sighted,” says Rosenberg, now adjunct professor of genetics at Yale and a professor at Princeton. “If we are to decipher the information from the human genome, if we’re to find out what that book means, we’re going to have to have medically trained scientists involved at the core. If we don’t have them, there’s going to be great difficulty in translating this fundamental information for the benefit of sick people.”