The Mayo Clinic Board of Trustees approved the establishment of an M.D.–Ph.D. program in 1983. Just the year before, Mayo had become a degree-granting institution.
To understand how the program has evolved since then, Mayo Clinic Alumni magazine talked to leaders and students from its early years. Their recollections show a program in its infancy at an institution renowned for clinical expertise.
The growing pains the program's leaders and students describe helped to forge the path to a mature program that now has more than 135 M.D.–Ph.D. graduates and more than 60 current students.
David Clapham, M.D., Ph.D., had completed his internal medicine residency at Brigham and Women's Hospital and was an assistant professor at Harvard University when he was recruited to Mayo Clinic's Department of Pharmacology in 1987.
He started a lab at Mayo and ultimately was asked to lead the M.D.–Ph.D. program, which he led from 1990 to 1994.
David McKean, Ph.D., emeritus Mayo Clinic staff member, was dean of Mayo Clinic Graduate School of Biomedical Sciences from 1987 to 1991. "When I became dean, we wanted to expand the number of students," he says. "Dr. Clapham was one of few M.D.–Ph.D.s in research at Mayo at the time, so he was an obvious person to be program director. He was a productive researcher and motivated to organize the program so it could succeed."
Dr. Clapham says the program's goal was to produce academics.
"The M.D.–Ph.D. program was very demanding, in part, because of the time pressure for students to complete the Ph.D. portion and get back to medical school. In the early years, we lost some students because it was too difficult," he says.
"We became better at selecting students whose expectations aligned with those of our faculty," he says. "We attracted really academically gifted top-notch students, and our labs competed to get them. The students were very productive in publishing their research."
In the early days, the graduate school didn't have activities where M.D.–Ph.D. students encountered each other.
"They met each other at the beginning of the Ph.D. portion of the program and then usually only related to the people in their chosen labs," says Dr. Clapham. "Then they saw each other again at graduation."
As the program matured, its leaders worked to better engage and re-integrate the students into the medical school portion of the program, he says.
In 1997, Dr. Clapham returned to Harvard Medical School and Boston Children's Hospital, where he was the Aldo Castañeda Professor of Cardiovascular Research and became a Howard Hughes Medical Institute investigator, and later, vice president and chief scientific officer. Dr. Clapham received the Mayo Clinic Distinguished Alumni Award in 2010.
Moses Rodriguez, M.D., now an emeritus member of the Mayo Clinic staff, was director of the M.D.–Ph.D. program from 1994 until 2006.
Dr. Rodriguez worked side by side with Richard "Rick" McGee, Ph.D., who was recruited to Mayo Clinic in 1991 to be associate director of the program and help it secure National Institutes of Health funding. Dr. McGee had been an associate dean at the Medical College of Ohio and started M.D.–Ph.D. programs there and at Georgetown University.
Mayo's program had already applied for NIH funding without success.
"Every time the NIH team made a site visit, they said we were a clinical enterprise, not a research enterprise," says Dr. McGee, who is now associate dean for professional development at Northwestern University Feinberg School of Medicine.
"Every time the NIH team made a site visit, they said we were a clinical enterprise, not a research enterprise. Mayo Clinic wasn't used to being rejected."Every time the NIH team made a site visit, they said we were a clinical enterprise, not a research enterprise. Mayo Clinic wasn't used to being rejected."Richard McGee, Ph.D
"Mayo Clinic wasn't used to being rejected," he says. "We put incredible effort into every NIH application for funding and site visit. We felt frustrated when we didn't succeed because we knew we had top students and a very strong program."
The program's leaders were determined to set the record straight.
"In 2002, Moses Rodriguez asked me to go to the NIH in person with him to discuss our research strengths with the Medical Scientist Training Program director," Dr. McGee says. "That visit turned the tide. The next time we applied, our program was funded."
It was a big deal — a celebratory occasion across the institution, he says. "Now, we were seen as a legitimate program and could participate in the National Association of MD–PhD Programs."
Dr. Rodriguez says it was a bold move to visit the National Institutes of Health to attempt to convince the Medical Scientist Training Programs director to reconsider their view of research and recognize Mayo's program as a Medical Scientist Training Program.
"We'd been operating as if we already were an MSTP, but we didn't have the official status. It was an extremely competitive process because the amount of money the NIH provided to MSTPs was fixed," he says.
"When we got the pink sheet (summary statement) back from the NIH with our next review and then the final word a few months later, we had a huge celebration," he says. "Mayo Clinic had finally made it in offering an NIH-supported combined degree. It was considered a badge of honor."
The designation covered students' costs for the medical and graduate school portions of the program plus a stipend for the duration. Until then, Mayo Clinic had covered those costs.
The initial five-year funding award led more applicants to the program — doubling in only one year. Today, the program gets 450 applications for nine slots in Rochester and two slots in Arizona.
Dr. McGee says that during his time as associate director, the program fine-tuned its recruitment strategy to focus on students who were driven by curiosity and comfortable with ambiguity, not by wanting to provide direct patient care.
"We'd lost students who, when exposed to patient care, decided they wanted to do that instead of focusing their careers on research," he says.
The path to an M.D.–Ph.D. career is long. It takes seven or eight years to earn the degrees, three years in clinical residency, and often three or more years in postdoctoral training.
"It's an extraordinarily long time to wait to start a career, and it's important to select students who understand the deferred gratification and realities of being a scientist and having to continuously seek funding for research, Dr. McGee says.
Among the many enhancements they made to the program, Drs. Rodriguez and McGee introduced ways for students to ease transitions. They added courses and activities to provide a foundation and cohesion to the program and established a pipeline program for college students between the junior and senior years to familiarize them with Mayo's Ph.D. programs.
Today, ongoing activities bring the M.D.– Ph.D. students in all years of training together on a regular basis, including weekly conferences, bench-to-bedside lectures, meetings with the director, progress evaluations, an annual retreat, and local and national meetings and conferences.
Preceding Dr. Clapham's arrival at Mayo Clinic by at least four years were 17 students in various stages of the M.D.–Ph.D. program.
Bradley Erickson, M.D., Ph.D., Division of Neuroradiology and Department of Quantitative Health Sciences at Mayo Clinic in Rochester, was in what is considered to be the first official group of M.D.–Ph.D. students at Mayo Clinic — starting medical school in 1983.
"Dr. Franklyn Prendergast (Mayo Clinic Emeriti Staff) was instrumental in my making the decision to pursue an M.D.–Ph.D.," says Dr. Erickson. "I had done some work in his lab. It's an honor to be among the first in the program."
Today Dr. Erickson splits his time evenly between clinical and research activities. In Dr. Erickson's class of M.D.–Ph.D. students were Denise Dupras, M.D., Ph.D.; Steffan Ho, M.D., Ph.D.; and Karen Fink, M.D., Ph.D.
Dr. Dupras, Division of Community Internal Medicine, Geriatrics, and Palliative Care at Mayo Clinic in Rochester and an assistant dean of Mayo Clinic Alix School of Medicine, says she's proud to have both degrees.
"Having an M.D.–Ph.D. puts you in an elite group and implies a level of achievement and commitment to learning," she says.
Ultimately, she decided that being a clinician–scientist wasn't for her.
"I was a primary care doctor in my heart," she says. "I didn't want to write and apply for grants. Ph.D. training taught me to think differently, but taking care of patients is what makes getting up in the morning worthwhile. Figuring that out changed my career trajectory."
Dr. Ho had been a chemistry and biology major in college and applied only to Ph.D. and M.D.–Ph.D. programs.
"The driving force for me was science as it applies to medicine," he says. "I was accepted to Harvard's pharmacology Ph.D. program and Mayo Clinic's M.D.–Ph.D. program. I chose Mayo Clinic."
After completing the program, he embarked on a residency in pathology at Stanford University Medical Center and a postdoctoral fellowship in molecular immunology at the Howard Hughes Medical Institute at Stanford. He had positions including pathology faculty at the University of California San Diego and drug development at Biogen. For the last 12 years, he's been at Pfizer, where he's a vice president and head of translational oncology.
Dr. Ho says the M.D.–Ph.D. training program allowed him to pursue a career path that supports his interests — understanding the science and its link to medicine.
"If I had to do it over again, I would take the exact same path," he says. "A combined M.D.–Ph.D. program selects for people who can tolerate the frustrations and delayed gratification that are inherent to the research process. I have a mindset that's amenable to research. It's a hybrid personality that's quite different from a typical physician."
As the first group of students was starting its last two years of medical school, William Morice II, M.D., Ph.D., Division of Hematopathology at Mayo Clinic in Rochester and president and CEO of Mayo Clinic Collaborative Services/ Mayo Clinic Laboratories, entered the M.D.–Ph.D. program.
"The newness of the M.D.–Ph.D. program created challenges for the early students," he says. "But it also makes it gratifying to have fumbled through and helped the institution build something great."
Dr. Morice says he'd do it all over again.
"Getting a Ph.D. is a significant time commitment and requires a high level of maturity. With medical school, the hard part is getting in. With graduate school, the hard part is getting out," he says.
"Getting a Ph.D. is a significant time commitment and requires a high level of maturity. With medical school, the hard part is getting in. With graduate school, the hard part is getting out."William Morice II, M.D., Ph.D
"I developed a great deal of expertise that I've used throughout my career as a translational scientist that has enabled me to design really good clinical studies and prove the value of the diagnostic tools I've created," he says. "I'm not sure I'd have pursued academic medicine without the Ph.D. Having both degrees helps you establish credibility even if you're not pursuing extramural funding."
Daniel Brat, M.D., Ph.D., the Magerstadt Professor and chair of Pathology at Northwestern University Feinberg School of Medicine in Chicago, was in the program with Dr. Morice. He explains his perspective about the difference in science and clinical medicine cultures, which he says is vital for students considering an M.D.–Ph.D. program to understand.
"Clinical medicine is structured and protocol-driven and hierarchical and has short-term gratification. Physicians go home at the end of the day knowing they did their best to advance someone's health by providing patient care," he says. "The scientific world has a relatively flat organizational structure, with everyone on a first-name basis, and a looser environment with differing work habits but still requiring teamwork.
"Physicians in training who want research experience are often surprised by the different culture in the lab environment," he says. "Scientists need to be able to cope with delayed gratification. If you have a good idea for discovery, you may not publish for two, three or four years. You also have to learn to engage and motivate a team of four to 15 people in the lab and, of course, you need to secure funding and go through many rounds of failed grant submissions. Not everyone is meant for the commitment to research and balancing clinical and investigative careers, but we absolutely need more physician-scientists to span the gulf between the two cultures."
Michael Ackerman, M.D., Ph.D., Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology & Experimental Therapeutics at Mayo Clinic in Rochester and the Windland Smith Rice Cardiovascular Genomics Research Professor, followed on the heels of Drs. Morice and Brat in the program.
"In grad school, when my work with my mentor Dr. Clapham was finally published in Cell, and I was returning to medical school, I vowed that I would never ever do research again and told Dr. Clapham so," Dr. Ackerman says. "He smiled and said, 'You'll be back.' What he meant was that, if you're an explorer, you'll miss being creative and exploring if you're a physician. As it would turn out, he was right — again."
"In grad school ... I vowed that I would never ever do research again and told Dr. Clapham so. He smiled and said, 'You'll be back.'"Michael Ackerman, M.D., Ph.D
During his subsequent pediatric residency at Mayo Clinic, Dr. Ackerman cared for a young boy who had almost drowned while racing his brother in a pool. The patient had been defibrillated by first responders.
"Most pediatric drownings don't need treatment for cardiac arrest," says Dr. Ackerman. "I wondered if it was long-QT syndrome."
Dr. Ackerman told his residency program director that he wanted to do postdoctoral research on finding his new patient's LQTS causative mutation. After finishing that pediatric intensive care unit rotation, Dr. Ackerman joined the lab of Stephen Thibodeau, Ph.D., Mayo Clinic Division of Laboratory Genetics and Genomics and the William H. Donner Professor, to find the cause.
"That close encounter with this child that night was my epiphany that showed me who I'd be when I 'grew up,'" says Dr. Ackerman. "I would embark on a physician-scientist journey where, as a physician, I would be dedicated to families at risk of sudden cardiac death from genetic heart conditions like LQTS and, as a scientist, I would be devoted to getting smarter about their conditions in terms of discovering new genetic causes and new therapies.
"Within the year, Dr. Clapham and I wrote a review article for the New England Journal of Medicine about cardiac channelopathies and human disease related to ion channel problems. Dr. Clapham said, 'I knew you'd be back.' My training in the worlds of medicine and science and learning how to constantly integrate and finesse the back-and-forth has served me well," he says.
Dr. Ackerman was on Mayo's M.D.–Ph.D. program recruitment committee for 19 years and says it's important to recruit the right students.
"If you enter this program at 22, you'll likely be in it until you're at least 29. People change a lot during those years," he says. "We look for people who are highly independent, enthusiastic and passionate about science and discovery, and who want to pursue an investigative career.
"The mandate from the NIH is to create scientists who are trained in science and the art of medicine, not necessarily to train physicians who know a little bit about science," he says. "M.D.–Ph.D. programs create a different kind of professional. Hopefully, being a scientist has made me a better physician, and being a physician has helped me become a better scientist than I otherwise would have been."
Dr. Ackerman was named a Mayo Clinic Distinguished Clinician in 2015 and a Distinguished Investigator in 2021.
This story was originally published in Mayo Clinic Alumni magazine. Mayo Clinic's medical school marked its 50th anniversary in 2022. Each issue of the magazine this year explores a facet of the school, known as Mayo Clinic Alix School of Medicine since 2018.
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