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I talk to a lot of undergraduates about applying to M.D.-Ph.D. programs. Three questions come up repeatedly: Is attending an M.D.-Ph.D. program the right choice for me? If I decide that is what I want to do, where should I apply? If I have a choice, where should I go?

The experience of applying to M.D.-Ph.D. programs is very different from applying to college. The issues are different, the stakes are higher, and the long-term career implications are much greater. This article will answer the questions above, drawing on my experiences as an M.D.-Ph.D. student, an M.D.-Ph.D. program director, a physician-scientist, and a mentor, as well as conversations with other program directors and administrators who in their outreach efforts get asked the same questions.

Medical schools and graduate schools have fundamentally different goals. Medical schools focus on teaching the art and science of the practice of medicine. Graduate school, on the other hand, is intended to train you in the art and science of investigation.

Question #1: Is an M.D.-Ph.D. program the right choice for me?

The answer to this question depends on your interests and career plans. Do you want to be a physician-investigator? Is doing research and making discoveries really important to you? If so, is the field you hope to work in one that is traditionally associated with Ph.D.-level training? For example, if you know that you want to do basic research and run a lab in the biological sciences, the appropriate graduate degree is a Ph.D. However, if you intend to do clinical research, a master's degree (in combination with your medical degree) may be what you need. You can pursue a master's degree either during medical school or after completing residency training.

Although you don't need to know precisely what research project you want to tackle 20 years from now, you do need to decide before you apply to M.D.-Ph.D. programs whether a Ph.D. is the appropriate preparation for you.

Before applying to M.D.-Ph.D. programs, you also need to decide under which broad discipline your interests fall: Biomedical sciences? Engineering? Social sciences? Economics? Anthropology? Most current and past M.D.-Ph.D. students (nearly 90% in a recent survey) pursue Ph.D.s in the biomedical sciences. The next largest percentage is in engineering fields. The remaining 5% or so are in diverse fields including the social sciences, humanities, economics, anthropology, and epidemiology. Moving within a general field (for example, molecular biology to immunology) is common and done easily. Moving between entirely different disciplines (for example, engineering to economics) happens much less frequently and may be more difficult.

Medical schools and graduate schools have fundamentally different goals. Medical schools focus on teaching the art and science of the practice of medicine. Although they may include wonderful opportunities to do research, most of the curriculum is about training you to be a clinician, not about preparing you for a research career. Graduate school, on the other hand, is intended to train you in the art and science of investigation, including the skills needed to be an independent investigator. Medical schools emphasize the acquisition and application of existing knowledge; graduate schools emphasize the discovery of new knowledge.

M.D.-Ph.D. programs integrate medical school and graduate school training to make you an effective physician-investigator, working to discover and apply new knowledge about the mechanisms, diagnosis, and treatment of human disease. Their goal is to help you become a true chimera: a physician whose skills and interests are informed by his or her training as an investigator, and an investigator whose research interests are informed by a deep understanding of people, their biology, and their disorders. Combined degree programs are intended to be preparation for a research-driven career; most M.D.-Ph.D. graduates spend much more time on research than on clinical practice and are employed in academia or at research institutions and in industry. Is that where you are headed?

Of course, M.D.-Ph.D. programs are not the only way to become a physician-scientist. Many physician-investigators who did not go to graduate school have enjoyed successful careers; some have even won Nobel Prizes. So why bother with an M.D.-Ph.D. program? Why not just go to medical school? This is a question I hear a lot, especially from undergraduates receiving well-meant advice from scientists who completed their training some time ago.

Things have changed since then. Recall the point made earlier: 4-year medical schools do not normally include research training. If you choose to attend medical school but not an M.D.-Ph.D. program, you will end up spending considerable time as a postdoc after your clinical training learning how to do research. Consider the data: M.D.s and M.D.-Ph.D.s who successfully compete for their first National Institutes of Health (NIH) grant typically reach that point at approximately the same age. Avoiding an M.D.-Ph.D. program won't save you time if you intend to be a scientist.

If you are sure you want to be a physician but less sure about your goal of becoming a physician-investigator, start medical school. If you change your mind about the role of research in your future career, you may be able to transfer into an M.D.-Ph.D. program at the same school. If not, you can complete your research training after medical school. Conversely, if you are sure you want to be a scientist but less convinced that you want to be a doctor, go to graduate school. You may be able to transfer into an M.D.-Ph.D. program before you start your thesis project, or you can go to medical school after you complete graduate school. It takes longer that way and is more expensive, but it is definitely doable.

Summing up: M.D.-Ph.D. programs are a wonderful option if 1) your goal is to become a physician-investigator, 2) you have the necessary academic credentials and research experience prior to applying, and 3) you make the decision early enough to apply as a combined degree candidate.

See also:

- Why get a Ph.D. with an M.D.?

- What research areas can I pursue?

- What if I decide to pursue an M.D.-Ph.D. after starting medical school?

"An unexpected fork in the road"

For all the work you'll do during your bachelor's degree and the careful consideration you'll put into choosing the right doctoral program, it's important to remember that you've only just set out on the journey--and you can change routes.

"I was very anti-premed when I was in college," says Karla Leavens, now a 5th-year student in the M.D.-Ph.D. program at the University of Pennsylvania. "I really loved biology and science." But during her junior year, she took an endocrinology course and discovered that she really enjoyed the clinical application of biology. At that point, she hadn't taken the MCAT or otherwise prepared to apply to medical school, so she went ahead with graduate school applications and continued with her initial plan for a career in research. "I never figured I could switch [degree programs], but I figured I could get some sort of training--go to med school afterwards or ... take some clinically oriented classes," she says.

After she started her Ph.D. in the cell biology and physiology program at Penn, she noticed that many people were doing both clinical work and research--and that was the path she decided to take. She took the MCAT the summer after starting at Penn and applied to the M.D.-Ph.D. program that fall. The following year, 2 years after starting her Ph.D., she entered the M.D.-Ph.D. program. "It really helps to keep options open," Leavens advises. "Ultimately, it's your life and your career, and you have to decide what that is."

Jonathan Brestoff is taking a somewhat nontraditional route as well but in a different direction: He wrapped up his first year in Penn's M.D.-Ph.D. program this summer and is now taking a year out to do a master's of public health degree at University College Cork in Ireland on a George J. Mitchell Scholarship.

"My goal is to understand public health policy better," Brestoff says. "I'm planning to use that knowledge to take scientific concepts in the future in my career and translate that into public health policies, in addition to therapeutics and treatment strategies."

A key requirement of Brestoff's scholarship was the support of his academic program, which is led by Lawrence "Skip" Brass (author of the accompanying Perspective). "In general, programs try to be as flexible as they can. I think we have to do that," Brass says. He advises students who are considering a different degree program, Ph.D. discipline, or any kind of nontraditional path to talk to their advisers as soon as possible to find out what the options are.

"I try to do what most other program directors do, having made a commitment to a student when they matriculated," Brass says. "I try to help them get as far as possible on the path that they choose, even if there is an unexpected fork in the road." --Kate Travis

Question #2: Where should I apply?

This question is often reduced to "how many" and "which ones," but there is much more to it than that. M.D.-Ph.D. program applicants can choose from among 70 to 80 programs, 42 of which currently receive financial support from NIH in the form of an NIGMS Medical Scientist Training Program (MSTP) grant.

In 2007, the average candidate applied to 10 different programs, but some applied to only one program, and one applied to 90! Applying to M.D.-Ph.D. programs can be time-consuming and--when the costs of interview visits are factored in--quite costly. (If the cost of applying is an issue for you, please note that many schools offer to waive application fees for candidates in financial need, and some will subsidize or even completely cover interview costs.) I advise applying to approximately the mean number of schools--10--rather than either extreme.

The decision of where to apply should be informed by the strength of your qualifications. M.D.-Ph.D. admissions committees are looking for strong academic and research credentials, along with exceptional letters of recommendation from faculty members with whom you did research, and a well-articulated reason for becoming a physician-investigator. They will also look at whether you have had experiences in the clinical setting to confirm your decision to go to medical school. Assess your chances realistically, and seek knowledgeable, objective advice.

What should you look for in a program? There is no single answer to this question; the answer will depend largely on what factors are important to you. Here are some things to consider:

1) Research infrastructure: All medical schools train physicians, but some have made a large investment in the faculty and infrastructure needed to do research. Those are the places where you are most likely to end up working, and arguably they are the places that you should experience as a trainee.

2) Role models: Role models are important for any professional career. Look for medical centers that employ physician-scientists

3) Training support: The presence of an NIH MSTP grant doesn't guarantee that the program is the right one for you, nor does the absence of an MSTP grant mean that the program is less worthy of your consideration. However, MSTP status does guarantee that the program will be subjected to regular external review and critical feedback.

4) Curriculum integration: In the early days of M.D.-Ph.D. programs (40 years ago), the curriculum was basically the sum of medical school and graduate school; there were few cross-connections between the two. Now it is generally accepted that the best way to train students for well-integrated careers as physician-investigators is to blend the training elements together as much as possible. Different schools do this in different ways and to different extents.

5) Presence of an appropriate Ph.D. program: If your plan is to obtain a Ph.D. in cell and molecular biology, biochemistry, or the neurosciences, you will find programs everywhere. If you seek a Ph.D. in bioengineering, sociology, health care economics, or anthropology (to name a few less-common disciplines), your choices may be more limited. Not every M.D.-Ph.D. program offers opportunities in these areas, either because they are not located at a university that offers doctoral training in them or because the medical school is not currently partnering with the school or department involved. Be sure to check before you apply.

6) Perceived difficulty in obtaining admission: My usual advice to even the strongest candidates is to apply to schools with a range of selectivity. Every year I see candidates who are accepted by one highly competitive program but rejected by another program that is equally or less competitive. There are the obvious objective metrics, such as mean grade point average and MCAT scores; but considerable weight is given to the interviews, which are highly subjective.

No M.D.-Ph.D. program is easy to get in to, but some are definitely tougher than others. It is emphatically not true that you need a 4.0 GPA and 40 on the MCATs to be a successful M.D.-Ph.D. candidate, though your chances grow more remote if your GPA is below 3.5 and your MCAT scores are below 30. I usually advise undergrads to take the test early enough that there is time to take it again before applying.

7) Program size: The current average size of an M.D.-Ph.D. program is about 90 students; but programs vary enormously, with a range from about 25 to about 180 students. That's as few as three new students a year on up to 30. There are advantages and disadvantages associated with all sizes of programs, and this is one of the things that you will want to ask about when you visit.

Be an informed consumer; consult a variety of resources and people to gather information. Mentors and role models who are physician-scientists can be particularly helpful. If you can identify someone whose career has the elements that you hope to have in yours, ask him or her how they came to be where they are. Program directors and administrators of the programs you're interested in are usually happy to answer questions about physician-investigator training in general, as well as about their own programs. Other candidates (past and present) may share their experiences, but keep in mind that their perspective, however well meant, may be limited. You should definitely consult more than one source.

Your college's prehealth adviser may also be able to answer questions, especially if you are at a college that regularly sends candidates to M.D.-Ph.D. programs. You may find answers to some of your questions on the Association of American Medical Colleges' Web site, Considering a Career in Medical Research, which contains links to the programs as well as some highly useful advice. Web sites for the individual programs will describe the program and its guiding philosophy and provide links to the constituent Ph.D. programs and information about activities sponsored by the program.

Finally, try to learn as much as you can about M.D.-Ph.D. training before your first interview visit. Read about the programs that you are visiting before you arrive and have some idea about faculty members whom you might like to meet. Some schools will even ask for your requests before your visit and arrange for you to meet with those faculty members. They do this in part to help you learn about the school and in part to see whether your interests fit within the range of faculty interests in the Ph.D. program. Take notes on your visits and impressions; months may pass between when you visit a school and when you have to make a decision to enroll.

See also:

- What factors should I consider when applying to and selecting an M.D.-Ph.D. program?

- What are the prerequisites for applying to M.D.-Ph.D. programs?

- What will M.D.-Ph.D. admissions committees be looking for in my application?

- What is the interview process like?

Be prepared--for the unexpected

You will do a lot of research, interviewing, and soul-searching when deciding what degree program to pursue, which school to attend, and which research area to go in to. No matter how much you prepare, though, there are some things you'll have to learn along the way.

Alex Chavez is from a family of physicians and wasn't particularly concerned with the clinical-care aspect of medical school before starting the M.D.-Ph.D. program at Penn, where he's now in his 6th year. Nevertheless, he learned a valuable lesson about patient care in the rotations he and his peers did in their first 2 years of medical school: "That's where I learned I really didn't like it," he says. "I'm glad I know now, though. It makes me try harder [in my research]."

Chavez plans to do a residency in pathology (which tends to involve little direct patient care) and then get back to his research in DNA repair. He has no regrets about his decision to pursue dual degrees. "I do value my medical knowledge," he says. "I think the way we think is different from the way regular physicians or regular scientists think."

Jonathan Brestoff was struck by the contrast between his medical school classes and his Ph.D. classes in his first year of the M.D.-Ph.D. program. "I was surprised at how medical school was so memorization-oriented and wasn't focused much on how biological processes work," he says. "In the couple of graduate classes I've had so far, ... the orientation is much more critical about research."

One thing medical students often aren't prepared for is failure in the lab, says David Raizen, an assistant professor of neurology at Penn. "You're going to fail, no matter how top-notch a scientist you are. You're going to come across a problem where the hypothesis is wrong, or technically you can't get things to work," he says. "If that happens for the first time in the third year of your thesis, you're going to be in trouble because you're not going to know how to deal with it."

The best way to prepare, he says, is to spend time in the lab learning how science works, what works and what doesn't, and how to troubleshoot when things go wrong. "When you're measured by metrics such as grades or MCATS or GREs or SATs, then it's much easier to succeed because you have a defined goal you can work toward," Raizen says. "But the metrics in science are much more nebulous and harder to define. And sometimes the skills that are important in the lab are not the same skills needed to make that perfect grade point average." --K.T.

Kate Travis is the editor of CTSciNet, the Clinical and Translational Science Network. Interviews were conducted at the University of Pennsylvania School of Medicine Combined Degree Program Annual Retreat on 5 August 2009.

Question #3: Where should I go?

Let's look ahead a bit. Most people apply in the summer and fall, interview in the winter, and make a final decision in the spring when they see what offers they have received. Some candidates find that deciding where to go is straightforward; as offer(s) come in, they use their personal "wish list" to decide which offers to hold on to and which ones to either set aside or not wait for. Others find this decision exceedingly difficult and go down to the wire before making their final choice.

Here are some of the factors that might go into making that choice. You may have others. Keep in mind that everyone weights these factors differently.

1) Impressions. Begin with all of the attributes listed in Question #2 that informed your decision about where to apply. Compare your notes on what the school was really like with your reasons for applying to it. You will likely find that some programs moved up on your wish list and others moved down.

2) Community. What did you think of the students you met when you did your interview visit? The students who enter with you are likely to have similar characteristics. Did they seem committed to the goal of becoming a physician-investigator? Were they happy with their choice of an M.D.-Ph.D. program? Did they make you feel welcome?

3) Geography. Is the location one where you would like to live for an average of 8 years? Is housing available and affordable on your stipend? Are your nonscholarly interests well-represented?

4) The two (or more) body problem. Do you have a significant other who is also applying to schools and has to end up with an offer in the same location? Or, if your partner will be looking for a job, is her or she likely to find something suitable in that location?

5) Outcomes. The goal of an M.D.-Ph.D. program is to train physician-investigators. Most programs do pretty well at this; but if a program's outcomes data show that large numbers of their graduates are in full-time private practice, you should be concerned. Ask about this during your interview or afterward if it didn't come up.

6) The perception of prestige. Many candidates use their sense of the university's prestige or US News and World Report rankings to decide where to go, just as they did when applying to college. My advice is to not put too much weight on those rankings. Pick the program that seems the most appealing to you after you weigh all the factors.

Conversely, there are some factors that should have less weight in your decision-making process:

1) The program that accepts you first. The first offer will undoubtedly fill you with a sense of relief that someone wants you, but it may not be the program that best fits your goals and dreams. If it is, then go for it. If not, be patient and see what other options appear.

2) The size of the stipend. One of the really great things about being accepted into an M.D.-Ph.D. program is that most of them offer fellowships that cover tuition for medical school and graduate school and offer a stipend that can be anywhere from $20,000 to $30,000 per year. Don't spend too much time weighing differences in stipend amounts. Ask the students in the program whether the stipend that they receive is adequate for the costs of living in the community where the school is located.

3) Time to degree. Although some programs claim that their students finish faster than students in other programs, data from a recent survey of 61 M.D.-Ph.D. programs show that the average time is 8 years, with little variation.

4) The presence or absence of a particular faculty member. Some candidates seek training with a particular faculty member whose interests (and/or fame) aligns particularly well with their goals. However, most candidates seek programs with broad strengths, recognizing that their interests may change as they learn about new fields and new problems.

5) Location as an index of how good the program is. Geography may be very important to you for personal or family reasons, but do not assume that all of the great programs are located in just one part of the country. It isn't true.

Summing up: Applying to M.D.-Ph.D. programs can be a daunting process; it will consume much of your time and energy during the year you do it. I have tried to demystify the process and help you prepare for it. I hope it helps, because I believe that a physician-investigator is one of the very best careers a person can have.

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