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The paradigm established by Goldstein and Brown classifies research into three categories: basic science research, disease-oriented research, or patient-oriented research.1 Goldstein and Brown define patient-oriented research as research conducted by investigators who "shake the hand of the patient during the course of the research." Because of the direct patient contact, the preponderance of patient-oriented research is conducted by individuals with medical training. Graduates of MD/PhD programs should be ideally trained to pursue patient-oriented research, i.e., to take observations made in the clinic to the laboratory to understand the molecular basis of diseases and to take discoveries in the laboratory to the clinic to improve patient care. Indeed, the original goal of NIH's MD/PhD dual-degree program, the Medical Scientist Training Program (MSTP), was to train scientists to do patient-oriented research.

Yet, assessment of the most commonly used pathway to train MD/PhDs suggests that this pathway may not be the optimal way to train physician scientists to do patient-oriented research. Data on graduates of MSTPs indicate that these programs are successful in producing productive researchers, who obtain NIH grants and are promoted through the ranks of academic medicine. Yet the overall conclusion of these studies is that this success is typically in basic science, and not in patient-oriented or clinical research. This article suggests a different pathway to train physician scientists for careers in patient-oriented research.

In the late 1950s, the first combined MD/PhD programs were initiated, and the NIH began to fund MSTPs a few years later. What began in 1964 with three programs has now grown to 41 MSTP programs across the U.S., funded through the National Research Service Act.2 Traditional MSTP programs are organized in a standard format: 2 years of medical school followed by several years of study and research toward the PhD degree, then the completion of the last 2 years of medical school. Students often choose to do their dissertation research in a laboratory, conducting basic science research with distant ties to human diseases or clinical problems. Indeed, some programs actively encourage combined-degree students to pursue research in basic science areas. Following an extended period of dissertation research, students face the difficult problem of reintegrating themselves into clinical training, after three or more years away from clinical medicine and patient contact. The initial organization of MSTP training in this format was not intended to optimize the training of patient-oriented researchers. It was designed, rather, to prevent students from completing the third year of medical school before the PhD; it was feared that students would choose to complete the medical degree and not spend the additional years required to complete the dissertation.

The success of the MSTP programs has been analyzed in various studies that examine the results of both the NIH-funded MSTP programs and non-MSTP combined degree programs.3-8 Martin, in 1991, summarized the career outcomes of graduates from eight MSTP programs, documenting the achievement of MSTP graduates in establishing research careers. He reported that more than 90% of the MSTP graduates obtained positions in academia or research institutes.3 This number is consistent with data from programs publishing their own studies, with the proportion of MSTP graduates establishing research careers ranging from 74% to 95%.4-6

Other studies have attempted to determine how the research activities of MSTP graduates differ from those of other groups of MD and MD/PhD recipients.7-10 Although the data from these studies suggest that a large majority of MSTP graduates hold appointments in clinical departments, and that most have clinical responsibilities, MSTP graduates are less likely than other groups of physician-investigators to publish in journals containing high proportions of clinical observations and clinical studies. With respect to research funding, Sutton and Killian found that applications for NIH research grants submitted by MSTP graduates were often classified as "laboratory research" much like proposals from applicants who had received only the PhD degree.9 These data indicate that MSTP graduates are not filling the role initially intended for them. Instead of functioning as physician scientists, these graduates are often excellent basic scientists who happen to have a medical degree. These findings suggest that MSTP training could be modified so as to train physician scientists more competently for patient-oriented research.

A different pathway is used to train students in the combined degree program at the University of Texas Health Science Center at Houston (UT Houston) and the University of Texas M. D. Anderson Cancer Center, where the goal is to produce physician-scientists who will pursue careers in clinical research. Students in this program are encouraged to complete the first 3 years of medical school before initiating their dissertation research. When they begin their PhD research, these trainees have completed the first 2 years of didactic education in basic biology and pathology; they have also completed the third year, where they are involved in the care and management of patients with diseases.

To use an analogy, the students learn about the parts of the bicycle during the first year and study how the components of the bike work together to turn the wheels during the second year. But they do not get on the bike and ride it until the third year of medical school. Hence, combined degree students at UT Houston and the Anderson Cancer Center commence their graduate school years with clinical skills and a deep awareness of patient-care issues. It is not unusual for the students to change their mind as to the research project after the third year of medical school and move from a basic science project to a disease-oriented or patient-oriented project, having experienced clinical care and become more comfortable dealing with patients.

Moreover, because the students have completed their third year of medical school and have clinical skills that are useful to clinicians staffing clinics, they are given the option throughout their years of dissertation research of working at a clinic one half-day a week. Every attempt is made to guide the student into a clinic that is related to their dissertation research. For example, one student was working in a laboratory deleting a gene in the Mycobacterium tuberculosis genome to determine what genes affected virulence of M. tuberculosis. This student was able to spend one half-day a week in the city AIDS clinic to accommodate her interest in infectious diseases and to follow patients with tuberculosis infections. Another student who was using phage-display technology to identify new molecular markers in ovarian cancer attended a clinic in gynecologic oncology once a week throughout her dissertation research.

Students comment that their patient interactions can often provide a different perspective to their science. An additional advantage of continuing patient interaction is that our students no longer have the problem of reintegrating into the clinic after being away during their dissertation research. Students in our program often comment that continuing with some sort of patient interaction during their dissertation research makes the transition back into the fourth year of medical school easier.

The ability to move back and forth from the clinic to the laboratory, bridging two very different worlds, is an essential skill for physician-scientists doing patient-oriented research, and it is an important skill to learn early in training. The difficult balancing act that must occur in the career of an MD/PhD takes practice to be done correctly. Providing an opportunity for practice during training is important for future physician scientists who will do patient-oriented research.

An additional feature of the UT Houston program is that the student can participate and contribute to ongoing research projects in the Health Science Center's University Clinical Research Center (UCRC). The activities in the UCRC allow the students to be introduced to issues related to Institutional Review Board approval of protocols and consenting subjects for research. They have the opportunity to be exposed to a wide variety of clinical and patient-oriented research, from Phase I, II, and III trials to collection of samples and clinical data used to identify genetic variation that leads to human disease.

The MD/PhD program at UT Houston and the Anderson Cancer Center was designed to train investigators who could better bridge the gap between basic science and clinical research, and as an alternative to the traditional MSTP program model. It remains to be seen if the UT Houston model is more successful in training patient-oriented scientists; outcome data are needed for the graduates of the handful of programs that pursue alternative pathways for training combined degree students. By varying the model and studying alternative pathways to train combined degree students for patient-oriented research, better pathways may be identified to train these individuals optimally for the unique role they play in biomedical research.

References

1. J. L. Goldstein and M. S. Brown, "The clinical investigator: bewitched, bothered, and bewildered--but still beloved," J Clin Invest 99, 2803 (1997)

2. National Institutes of Health, "NIH predoctoral research training in the biomedical and behavioral sciences: outcomes for 1982-92 Ph.D.s" (Report in preparation)

3. J. B. Martin, "Training physician-scientists for the 1990s," Academic Medicine 66, 123 (1991)

4. National Institute of General Medical Sciences, MSTP evaluation (NIGMS Publication No. 79-401. Bethesda, MD: NIGMS, NIH, 1980)

5. C. Frieden, B. J. Fox, "Career choices of graduates from Washington University's Medical Scientist Training Program," Academic Medicine 66, 162 (1991)

6. D. A. McClellan and P. Talalay, "MD, PhD training at the Johns Hopkins University School of Medicine, 1962-1991," Academic Medicine 67, 36 (1992)

7. C. R. Sherman, H. P. Jolly, T. E. Morgan, E. J. Higgins, D. Hollander, T. Bryll, E. R. Sevilla, On the status of medical school faculty and clinical research manpower, 1968-1990: a report to the clinical sciences panel of the committee on a study of national needs for biomedical and behavioral research personnel (NIH Publication No. 82-2458. Bethesda, MD: NIH, 1981)

8. E. H. Ahrens Jr., The crisis in clinical research: overcoming institutional obstacles (New York: Oxford University Press, 1992)

9. J. Sutton and C. D. Killian, "The MD, PhD researcher: what species of investigator?" Academic Medicine 71, 454 (1996). W. D. Bradford, S. Pizzo, A. C. Christakos, "Careers and professional activities of graduates of a medical scientist training program," Journal of Medical Education 61, 915 (1986)

10. W. D. Bradford, D. Anthony, C. T. Chu, S. V. Pizzo, "Career characteristics of graduates of a medical scientist training program, 1970-1990," Academic Medicine 71, 484 (1996)