M.D.-Ph.D. Program Harvard Medical School Fall 1994 Newsletter

Articles in this issue:

• New Director Sets Course, Lauds Success of Combined Training
• Flexibility, Feasibility Are Key to Best Career Choices, Panel Says
• Neuronal Death on the Mississippi

New Director Sets Course, Lauds Success of Combined Training

by Dennis A. Ausiello, M.D.

There are abundant facts over the last decade that demonstrate the extraordinary success of the M.D.-Ph.D. in the biomedical environment in the United States. Physician-scientists have led the list of federal-funded grantees and appointments to prestigious academic positions. These statistics, however, can seem remote as students make decisions about their own careers. It is in this regard that we hope to institute important changes that will allow for a more cohesive approach to obtaining dual degrees.

I have asked four interested and committed physician-scientists to serve as hospital co-directors for the M.D.-Ph.D. Program: Merton Bernfield (Children's Hospital), Lee Kaplan (Massachusetts General Hospital), Tom Stossel (Brigham & Women's Hospital), and Vikas Sukhatme (Beth Israel Hospital). This committee, chaired by Dr. Stossel, will provide activities designed to enhance advising and explore career opportunities at their institutions where many Harvard M.D. -Ph.D. students will serve as future faculty.

At a time when the rapidly changing health care delivery system is causing consternation and uncertainty even among the leadership within our own community, it is certainly not surprising that a group of students, as talented and self-confident as they might be, have a significant amount of anxiety as they enter an educational experience that may last 7 or more years, and are entering a field that will certainly be quite different at its endpoint than it is at its onset. To each of these students, however, I can say take heart. You continue to be among the best and brightest admitted to our medical and graduate schools and you will, indeed, be the focus of interest of those centers of excellence that will certainly survive the changes in academic medicine. You will be dedicated to the mission of quality health care delivery and bench-to-bedside therapeutics in which the new generation of physician-scientists will be deeply immersed. I believe strongly that the M.D.-Ph.D. Program is a unique milieu in which to develop a passion for caring and a science for curing. We are on the verge of changing the way we diagnose and treat patients as never before encountered in medicine. Such approaches will not only require technological expertise, but a sophistication of understanding of clinical medicine and basic science. It is in this regard that the joint degree pathway offers a perspective that neither degree alone may bring to the job. That is not to say that there are not many ways to achieve competence in medicine and science, and certainly the M.D.-Ph.D. can not claim uniqueness in that regard. However, in the near future, though there may be fewer centers of excellence, each will demand more stringent approaches to teaching, research and diagnosis and therapy that will require the kinds of insights and sophistication that the M.D.-Ph.D. can bring. These are the reasons to choose the M.D.-Ph.D. pathway.

Having made this decision, however, the question is asked, where do I begin? Many students feel that they must continue the same type of research that they have begun in college. Although these early experiences have served them well, and have contributed to their being accepted into the program in the first place, I strongly urge incoming students to think about dedifferentiation during the first year or two of medical school to allow themselves the broadest opportunity to find an area for which they can be passionate. There are many, many ways by which we choose our careers, but there has never been a successful choice without passion. It is quite easy to be programmed early on in one's career, to have achieved success and feel reluctant to venture far from it, assuming that this success has gained one both entrance into a prestigious school and will guarantee success in the future. While there will be many who continue to pursue their interests in areas developed at an early stage of their careers, there should be an equal number who have explored new venues, obtained new ideas and who willnow build upon their previous deeds to find even more exciting areas for themselves. We will try to provide a diversity of activities during the first two years that will be unique to M.D.-Ph.D. training and which we hope will provide insight for decision-making.

For those finishing a dual degree, frequently the difficult decision is how much clinical training to undertake. I would argue that the value of the joint degree comes somewhat more from the physician component of the physician-scientist. I believe, therefore, it is important to continue postgraduate clinical training since this will become the basis for one's insights in bench and clinical research. Although it is true that not all postgraduate clinical activities lend themselves practically to the joint degree student, particularly with regard to the large variation in the length of time in training, there are many areas of medicine that with 2 or 3 years of additional training, a sufficient understanding of the fundamental pathology in human disease will provide an important foundation for one's scientific career.

A second concern to new physician-scientists is what happens to their scientific career during that interlude of clinical training. Students are often very successful during their Ph.D. years and have been immersed in cutting-edge science at the forefront of a rapidly expanding and competitive field. It is here, again, that interaction with experienced physician-scientists can answer some of these questions and provide models for decision making. In an era where orthopedic surgeons and pediatricians work side-by-side at the bench on fundamental areas of, for example, cellular and molecular biology, it is important to realize that the focused area for which one has prepared oneself is not a unique enterprise. Rather this experience provides for fundamental insights in extensive areas of science. While, of course, all areas of science will continue to move at a very rapid rate, the extraordinary preparation and foundation achieved by those who earned a dual degree should allow trainees to insert themselves into environments of their choosing with relative ease. As I look back at the careers of many of my colleagues who have been physician-scientists for twenty or more years, it never ceases to surprise me that many individuals are doing today what they could not have even contemplated five years ago. It is this kind of phenomenon that occurs, not only within the science itself, but by the individuals producing the science. I think M.D.-Ph.D. students can be given cheer that their years in clinical training will not have been wasted ones and will allow them to build on their extensive scientific training that will be brought back to the bench if they choose so.

In closing, I can say that it is with a great deal of pride and enthusiasm that I take over the directorship of the M.D.-Ph.D. Program. Its future is bright and will almost certainly provide the leaders for those centers of excellence that will be at the forefront of the most extraordinary changes in health care delivery.

Dennis A. Ausiello, M.D., is Director of the M.D.-Ph.D. Program, Professor of Medicine, and Chief of the Renal Unit and Vice-Chair of the Department of Medicine at MGH.

Flexibility, Feasibility Are Key to Best Career Choices, Panel Says

by Rob Hurford

Each panelist provided an introduction about their experiences and thoughts on the M.D.-Ph.D. pathway. Phil Starr, a 1989 graduate of the Harvard M.D.-Ph.D. Program, completed a four year residency in neurosurgery and is currently working in a lab. Although he enjoyed many different subspecialties, he decided to specialize in epilepsy surgery in order to match his clinical focus with research interests. When he started the program, he thought that he would primarily spend his time doing research. In the future, however, the majority of his commitment will be to clinical work.

Rick van Etten received his dual degree from Stanford and stressed the importance of finishing an M.D.-Ph.D. as soon as possible since residency and additional research training require considerable time commitments. For first and second year students, he encouraged them to choose a lab carefully and consider how long other students in that lab have taken to complete their Ph.D.s. After graduating, Dr. van Etten fast tracked during his internal medicine residency (2 years instead of the normal 3 years) and spent one year as a clinical fellow in a medical subspecialty. He encouraged everyone interested in internal medicine to fast track.

Nancy Andrews, who graduated from the Harvard M.D.-Ph.D. Program in 1986, also fast tracked her residency in pediatrics at Children's Hospital. She is currently focused on research involving iron metabolism. She still finds time for some clinical work, and her research is related to clinical problems in the field. Importantly, Dr. Andrews felt that clinical training cultivated her self confidence and thus improved her research skills.

Keith Blackwell, who earned an M.D.-Ph.D. at Columbia, decided to pursue his research career full time, forgoing a residency. He is now setting up a lab at the Center for Blood Research and spends about 25% of his time at the bench. During his training, he reached the point where it was clear that the bench-to-bedside approach was not what he wanted. He followed his interest in science and is happy with his career choice. Dr. Blackwell made the observation that people often do not have the foresight to decide what they will want to be doing in 10 years, so it is important to remain flexible.

Lee Kaplan, an M.D.-Ph.D. on the Harvard faculty who joined the discussion, pointed out that one doesn't develop research ideas by seeing patients. It is best, he feels, to choose a solid research project and try to make an impact during one's career with one or two great ideas. Still, Dr. Kapan believes that clinical training helps improve decision making skills and provides a broader perspective about the goals of research.

Albert Shaw, a recent graduate of the Harvard dual degree program, told of his own decision not to fast track during his internal medicine residency at MGH. He believes one of the problems M.D.-Ph.D.'s face with fast tracking is having to know what specialty they are interested in from the beginning of their residence. If one is indecisive, it is certainly reasonable to make the decision later after gaining more exposure to medicine.

It is interesting to note how often all participants discussed the increased number of opportunities that result from an M.D.-Ph.D. degree. Given the complexities of modern research and medicine, however, graduates must focus their careers. Still, it would seem to be a mistake to try to make all of these decisions early in the process. The panelists were satisfied pursuing career paths different from what they had originally envisioned for themselves. Thus, candidates in the M.D.-Ph.D. Program should keep an open mind during the program and then follow their evolving research and/or medical interests in the future.

Rob Hurford is an M.D.-Ph.D. candidate in Genetics.

Neuronal Death on the Mississippi

by Frank McKeon, M.D.

This fact will change, he promised, within five years. Dr. Choi sees a major problem in stroke as the collateral damage induced by the major neural neuro-transmitter glutamate diffusing from ischemic tissues. This transmitter goes on to hyperactivate a set of ion channels known as N-methyl-D-aspartate (NMDA) receptors in the otherwise healthy, surrounding tissues, which in turn appears to induce a chain of responses leading to neuronal cell death.

Dr. Choi expressed a strong belief that early intervention with drugs to block these calcium-mediated events would greatly reduce the overall damage due to stroke. Dr. Choi presented evidence from his work with cortical neurons in culture that glutamate induces cell death that is dependent on a rise in the intracellular calcium, and that drugs that block the NMDA receptor also block rapid cell death. He went on to mention that other glutamate targets, including AMPA and kainate receptors, may play a role in late onset cell death and therefore may also represent important targets of future clinical intervention.

Dr. Choi concluded with exciting predictions of early stroke intervention that include the aggressive use of agents to block cell death. He left the lasting impression that insights from the laboratory can be rapidly converted to therapies which have profound effects on human health.

Dr. McKeon is an Associate Professor of Cell Biology.

top