I ntroduction

Choosing between a career in medicine and a career in science is straightforward. If you are interested in patient care, you pursue the M.D. degree and become a physician. If you are interested in research and discovery, you pursue the Ph.D. and become a scientist.

But life isn't quite that simple, because medicine and science intersect in fascinating ways. Science and medicine are interdependent, and they impact each other with often surprising and beneficial consequences. For those captivated by this dance of medicine and science, there is a third career path, that of the physician-scientist.

The purpose of this feature is to provide prospective and current physician-scientist trainees with useful information about the nature of the physician-scientist's life and career and advice on how to prepare. This series will feature contributions from current M.D./Ph.D. students, who will tell how they got where they are and what getting there was like, and from physician-scientist graduates in the midst of highly successful careers, who will share their thoughts on their professional lives, describe the paths that led to their careers, and offer advice derived from years of accumulated experience about preparing for and managing an M.D./Ph.D. career. We will also have essays from program administrators providing practical advice on negotiating the M.D./Ph.D. career path.

But before embarking on any of that, it's important to reflect on a central question: Does the physician-scientist career path fit with your career goals?

The Concept of an M.D./Ph.D. Program

M.D./Ph.D. programs are designed to prepare individuals for careers as physician-scientists: professionals combining the clinical skills and knowledge of a medical doctor with the scientist's deep, nuanced knowledge of and expertise in scientific methodology. In many respects, physician-scientists are neither physicians nor scientists. Their dual training gives them a unique perspective: Well-trained physician-scientists have the experience and instincts to observe clinical syndromes, reflect on symptoms in the light of fundamental biological science, and pursue the study of those diseases through hypothesis-driven research.

The biological sciences and medicine are at quite an extraordinary stage in their mutual, synergistic development. Knowledge generated by basic science is dramatically changing the way medicine is practiced. Fundamental discoveries in biology have yielded powerful tools for the study of human biological systems. Advances in the understanding of the human genome and discoveries in the fields of proteomics, developmental biology, neuroscience, cell biology, immunology, microbiology, and molecular genetics, to name but a few active areas, have begun to influence how diseases are diagnosed and treated.

Medicine's impact on basic science is equally dramatic. Careful attention to phenotyping diseases, facilitated by our knowledge of the human genome and computational analysis, has allowed observant physicians and physician-scientists to identify and categorize diseases in a manner that has informed basic science, given it new contexts, and in many instances provided important new directions for investigation. Medicine has, in some cases, set the agenda for basic science.

Examples of the fruits of this interaction abound. The once-disparate fields of psychiatry and molecular genetics have been merged by physician-scientists who study the correlation between gene expression, transcription, and human behaviors. Many neurodegenerative diseases, such as Alzheimer's and Parkinson's, are being studied beneficially in the light of new knowledge of structural biology and protein folding. Sleep-wake cycles and our understanding of narcolepsy have been advanced by the discovery of orphan receptors, as well as their associated ligand peptide hormones and the genes that code for them. Our fundamental knowledge of gene expression is being applied systematically to more precise diagnosis of disease and its subsequent treatment. These developments have created countless opportunities for advancing our understanding and treating human disease. The opportunities for the next generation of physician-scientists are huge, as medicine and science come together and generate fresh interdisciplinary approaches to scientific and clinical problems old and new.

Why an M.D./Ph.D. and Not an M.D. or Ph.D.?

It is possible to accomplish outstanding biomedical research with just the traditional M.D. degree. Many Nobel laureates are M.D.s, including many whose prizes were awarded for contributions made to the basic biological sciences. But three changes in the medical establishment over the past 2 decades have made it very difficult for traditional M.D.s to pursue research careers. First, the rigor of the science curriculum in medical schools has not kept pace with advances in the biological sciences; M.D. graduates lacking a rigorous science background find it difficult to develop research programs that can equal those of well-trained basic scientists. Second, the economics of the health care delivery system has changed dramatically for academic medical centers, especially in the past decade; increased patient-care responsibilities make it much more difficult for M.D.s to launch research careers. Third, M.D.s often graduate from medical school with significant financial debt; remediation of basic-science deficiencies extends training, prolonging and increasing financial burdens. In contrast, nearly all M.D./Ph.D. trainees are supported by fellowships that pay tuition, a salary, and other expenses as they earn their dual degrees, so they end their training with much less education-related debt.

So why not just earn the Ph.D. and do biomedical research without going to medical school? It can be argued, after all, that Ph.D. scientists accomplish much of what the M.D./Ph.D.s accomplish without investing time, and sometimes expense, in physician training. Physician-scientists, after all, publish their work in the same highly regarded basic science journals as Ph.D. scientists and sometimes investigate similar or even identical systems.

There is, however, one very important difference between physician-scientists and basic scientists. The differences in their training generally lead them down different paths of inquiry. Ph.D. scientists seek to understanding a basic biological principle or mechanism. The physician-scientist may study the same properties of the same molecule but for a different reason: because he or she believes that those studies will provide information on the fundamental pathology of a disease or insight into human biology that will provide a better understanding of healthy versus diseased states.

Science itself provides the context within which basic scientists work. For the physician-scientist, however, that context is provided by human biology and the quest to understand the pathology of disease. Because of their highly developed clinical skills, physician-scientists are attuned to observing a panoply of phenotypic phenomena in patients, thus providing a unique context and direction for their science that is not available to Ph.D. scientists. Neither of these approaches to science is superior to the other, but they are undeniably quite different. Both approaches have led to remarkable discoveries. However, for those with a clinical orientation, whose primary scientific interest is in human biology and human disease, exposure to, and training in, the human context of the medical clinic is essential.

Where Are These Programs?

There are more than 90 M.D./Ph.D. programs in the United States, ranging in total enrollment from as few as five to more than 120 students. Some have been in existence for more than 30 years, whereas others are relatively new. Each program has its own emphasis and strengths, and the programs vary in quality. Prospective applicants should contact the programs directly to learn more about them. Most important, the applicant should discuss these programs with as many people who are qualified to assess them as possible. An excellent starting place for your research into M.D./Ph.D. programs is the Web site of the American Association of Medical Colleges.

Another good source of information on M.D./Ph.D. programs is the Web site of the National Institute of General Medical Sciences (NIGMS), which provides support on a competitive basis for combined-degree training to about 40 of the 90 U.S.-based M.D./Ph.D. programs. M.D./Ph.D. programs supported by NIGMS are called Medical Scientist Training Programs (MSTPs). NIGMS regularly reviews these programs through on-site visits, assessing MSTPs by examining the quality of their faculties and their scientific output; the organization of each program, especially the way it integrates science and medicine; the mentoring provided to students; the quality of the students and their thesis work; and the success of the programs' graduates.

Currently funded programs are listed on the NIGMS Web site. Each year, non-MSTP programs compete for funding, and some are successful in earning it. It is generally agreed that if the National Institutes of Health's budget would allow, more programs would be funded; excellent programs exist that are not funded by NIH.

How Does an Undergraduate Student Prepare for a Career as a Physician-Scientist?

The more rigorous the science background of the undergraduate, the better prepared they are for an M.D./Ph.D. program. That being said, the most important preparation is the hands-on experience of laboratory research mentored by first-rate scientists and educators. The only way to be sure that a career in research is something you relish and are good at is for you to do it for a significant length of time. Most science courses, even with laboratories, do not convey the open-endedness, the intellectual exchanges, the frustrations (well, maybe the frustrations!), and the excitement of scientific inquiry.

M.D./Ph.D. programs are looking for excellent students, but more importantly, they are looking for students who have experienced scientific inquiry, are good at it, and have a passion for it. Good grades and MCAT scores are necessary, but demonstrated potential in research is essential. Letters of recommendation from undergraduate research mentors are by far the best indicators of an applicant's level of passion for science. Research mentors see you in the laboratory at your best and at your worst and tend to write the most comprehensive assessments of your potential as a scientist. You must also demonstrate a passion for medicine, as this equally important half of your M.D./Ph.D. training defines you as a physician-scientist. This does not mean summers full of volunteer work at the local community hospital; those summers should be set aside for laboratory research experiences.

What this does call for, however, is a demonstration that you genuinely share the basic commitments of the physician-scientist: an appreciation of the potential of thorough clinical knowledge teamed with your scientific passion, and a demonstrated understanding that this clinical knowledge requires contact with patients and skill and interest in observing and listening. Undergraduate experiences that point to your receptiveness to people and eagerness for such interactions are excellent indicators of your potential as a clinician.

A Final Word

By necessity, this is only the briefest overview of an academic path to a career as a physician-scientist. Much more could be said. This series on M.D./Ph.D. careers is intended as a starting point for people who wish to explore a career that brings together medicine and basic science.

The image of the physician-scientist tending to patients in the clinic in the morning and then rushing off to the laboratory in the afternoon in search of a cure for the diseases observed a few hours earlier is mythical; this rarely occurs. Nevertheless, physician-scientists? medical and scientific educations place them at an ideal intellectual vantage point to facilitate the transfer of clinical observation and insight to laboratory research and discovery, and to help return to the clinic a better understanding of human disease: the bedside to bench to bedside cycle that moves both medicine and science forward.

If you are interested in such a career, talk to people who are already in it, as many as you can. Although we encourage you to explore the essays included in this feature, this is just a starting point.

Rod Ulane is Associate Dean for Graduate Biomedical Education at the New York University School of Medicine.