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Advances in molecular biology foster greater interdependency among physicians, researchers The province of the scientist traditionally has been one of theory and experiment, exploration and discovery--contrasting sharply with the practical concerns of the physician. But times have changed. Today, physicians find themselves in need of knowledge in such esoteric matters as the polymerase chain reaction and restriction fragment-length polymorphism maps. Meanwhile, scientists are having to acquaint themselves with the world beyond the lab--talking, for instance, to the families who supply the DNA samples stored in their refrigerators, a task generally left up to clinicians. Increasingly, lines that traditionally separate the researcher and physician are blurring. Crossover between the professions is still unusual, however; of 600,000 physicians in the United States, only 16,560 are involved in clinical research, according to the American Medical Association. The M.D.-Ph.D. dual degree is one approach to bridging the gap (The Scientist, April 13, 1992, page 12)--and many professionals on both sides are pushing for a graceful, effective union between the heretofore disjunct pursuits. However, while 111 United States schools offer M.D.-Ph.D. programs, many physicians eschew that route as they strive to hone their molecular skills. Rather, they are opting to gain knowledge of research breakthroughs by stepping up interaction with lab scientists. "The whole field of biology is molecular now," says P. Michael Conneally, a Ph.D. medical geneticist at the Indiana University School of Medicine in Indianapolis, referring to the various types of professionals a physician can consult. "Physicians learn it every which way. I don't think you can boil it down to just one way," genetecist Conneally observes. Consider cystic fibrosis, just one of an ever-growing list of diseases being dissected at the molecular level. A generation ago, cystic fibrosis was treated symptomatically--pounding on the chest to loosen secretions, antibiotics to fight infection, enzyme supplements to assist the clogged pancreas. It worked, to a point. Today, the armamentarium engaged in combating the disorder has grown and shifted focus to its cause, and includes several promising agents to compensate for the underlying malfunctioning ion channels in affected cells. None of this would have been possible without the identification of the cystic fibrosis gene and its protein product in 1989, by a huge team of investigators led by Lap-Chee Tsui and John Riordan at Toronto's Hospital for Sick Children, and Francis Collins of the Howard Hughes Medical Institute at the University of Michigan, Ann Arbor. Their findings were published in back-to-back papers in Science (245:1059, 1066, 1073, 1989). Discoveries such as this are coming from laboratories with an eclectic mix of physicians and scientists, some wearing both hats, backed up by students, postdocs, and technicians. Staying Up-To-Date For young and future physicians, being at ease with molecular biology shouldn't be a problem--it's part of their training. "All pre-med courses have labs in molecular biology, and they do lots of experiments," says Conneally. And many undergraduates participate in research. But for established physicians, keeping up may take quite an effort--and the public is demanding it as the evening news and talk shows serve up new technologies daily. Can a family physician or pediatrician accustomed to swabbing a child's red throat and relying on a bacterial culture to diagnose strep throat segue into the monoclonal antibody- or DNA probe-based quickie diagnostic tests that patients now request? The American Academy of Pediatrics offers no continuing medical education program in molecular biology; interested members must go here. Even a physician who does not directly implement the new tools and technologies must stay up-to-date. "I'm 63, and I thought that I could go safely to my grave never having to learn molecular biology. But it is impossible. I can write a prescription this week for stuff that a bacterium made last week," says Nicholas M. Nelson, a professor of pediatrics at the Milton S. Hershey Medical Center in Hershey, Pa. He jokingly longs for the old days when "exon" meant an oil company, and not part of a gene. So, how do the docs do it? Fellowships A fellowship for physicians usually entails financial support to work at a place like the National Institutes of Health's Bethesda, Md., campus, or in an academic laboratory. Such an intense learning experience-- typically lasting two to four years--is a necessary supplement to medical training, says Margaret Wallace, an assistant professor in the department of pediatrics in the division of genetics at the University of Florida Health Science Center in Gainesville. "It's so hard in medical school. You can dabble in research--a summer here, a rotation there--but it is not a very prolonged training. So most [physician/scientists] do fellowships," she says. Wallace began her career in an M.D.-Ph.D. program at Indiana University in Indianapolis and, fascinated by pursuing genes, switched to the Ph.D.-only track. She was the person on the Huntington disease team who realized, sitting at a computer screen late one muggy night in 1983, that that elusive disease's first marker had been identified by the computer. Later, as a postdoc in the laboratory of Francis Collins of cystic fibrosis fame (who has an M.D. and a Ph.D. in physical chemistry) at the University of Michigan, Wallace identified the gene for neuro-fibromatosis. A wide variety of fellowships beckon the physician who is a scientist at heart. A research fellowship in endocrinology, genetics, gastroenterology, and hepatology at the National Institute of Diabetes and Digestive and Kidney Diseases, for example, stresses laboratory skills, allowing the fellow to "bridge the gap between basic sciences and clinical care," according to literature describing the program. A good example of this crossroads of medicine and science is a fellowship at the National Heart, Lung and Blood Institute's laboratory of molecular cardiology. Here, a cardiology-bound, newly minted physician, or a more experienced clinician, can focus on the genetic control of contractile proteins. Private foundations sponsor fellowships for physicians, too. The Howard Hughes Medical Institute, for example, funds such a program "for physicians interested in doing research directed to understanding basic biological processes and disease mechanisms in the broad areas of cell biology, genetics, immunology, neuroscience, and structural biology," says Barbara Filner, grants program officer. On-The-Job Training Some physicians learn on the job, obtaining faculty positions and lab space, and then picking up and honing scientific skills by linking up with labs whose members are willing to share and teach. "These physicians get their faculty positions and go through a transitional stage for the first few years, actually working in someone s lab at the research level, while performing other faculty duties," says Wallace. And, as is true of many other fields, knowing how to hire knowledgeable support staff helps. "One neurosurgeon was given a lab, and he didn't really have the training to do research. But he had good ideas, hired someone good, and collaborated with another lab," says Wallace. Many a technician and postdoc has had his or her brain picked by eager physicians-turned-scientists. Wallace recalls being very impressed by the young physicians passing through Collins's lab. "They tried to understand everything, and were always very up on the literature. Doctors who run research labs do a really good job. You'd think they would need a Ph.D. to do the kind of job they do, but they don't," she says. Physician-Scientist Interactions Information flow goes both ways. Just as physicians rely on scientists for molecular biology savvy, scientists-in-training are increasingly learning from physicians. At the University of Oklahoma's Center for Molecular Medicine in Oklahoma City, for example, Ph.D. students can choose from 62 faculty in a variety of fields, including many physicians. And established scientists are increasingly seeking a clinical view to complement their laboratory expertise. Says Doris Zallen, an associate professor of science studies and humanities at Virginia Polytechnic Institute and State University in Blacksburg, who has a Ph.D. in genetics, "I'm very comfortable with statistics and the scientific aspects of disease. I'm not as aware of what goes on in the clinic. I wanted to see more of a clinical perspective so I could understand what the medical community faces." At the same time, scientists who find themselves in the position of educating physicians must be sensitive to the diverse backgrounds of their audiences. Nicholas Nelson describes his frustration with molecular jargon: "Last week, a guy giving a talk to 30 practicing pediatricians used the term `open reading frame' twice. So, wanting him to use something remotely resembling English, I asked what it was. Half of the doctors, younger, knew." Nelson went back to his texts and quickly refreshed his memory. Zallen agrees that scientists must recognize the vastness of the challenge for physicians who are trying to remain current. "A practitioner who is not a specialist in genetics really can't keep up. Ph.D.'s involved in advancing the science are obligated, I feel, to serve as resources for physicians, letting them know the pros and cons of emerging technologies," she says. Patients, Lawyers, And More Both physicians and scientists, and M.D.-Ph.D. hybrids, can learn from patients, as well as from other types of professionals who deal with the repercussions of advances in molecular biology. The demand for such interaction is great, as Zallen recently discovered when she organized an interactive videoconference on the Human Genome Project, part of a series called "Choices and Challenges." "The goal was to bring physicians and scientists together with people who are directly dealing with the implications of the Human Genome Project, to help sensitize them. "We advertised it very aggressively [in medical journals], but did not anticipate that hundreds of people would be interested," she says. Some 500 people flocked to a very rural location in Blacksburg, Va., making it a resounding success, Zallen says. "I think the physicians like `Choices and Challenges' because it puts them into contact with a wider audience. "We had lawyers, insurance companies, people who had genetic disorders in the family. The physicians had the opportunity to tap into a large number of constituencies to which they wouldn't ordinarily have access," she says. The images of the physician as a black-bag-toting healer and of the scientist as an unfeeling investigator surrounded by test tubes and rats may soon go the way of the dodo, as the professions continue to overlap. These professionals have much to learn from each other--and all will benefit from the symbiosis. Ricki Lewis teaches biology at the State University of New York, Albany, and is the author of Life, a college biology text (Dubuque, Iowa, Wm. C. Brown, 1992).

A New Symbiosis For MD's And Scientists

Jun 21, 1992

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