M.D.-Ph.D. Program Uniquely Equipped to Prepare Next Generation of Physician-Scientists

By April Wilkerson 
Writer, OU College of Medicine

To deeply understand both the clinical world of a physician and the scientific realm of a researcher, a select group of students are drawn to the M.D.-Ph.D. program, a multi-year commitment that prepares them for careers as physician-scientists.

David Sparling, M.D., Ph.D., conducts research in his field of pediatric diabetes. After finishing his education, Sparling returned to the OU College of Medicine as a faculty member.

The M.D.-Ph.D. program, jointly administered by the OU Health Sciences Center and the Oklahoma Medical Research Foundation, has been operating in its current framework for the last 15 years. However, because of the program’s lengthy obligation, the first groups of graduates are just now securing their first positions. And the outcomes are extremely gratifying: All graduates thus far, with the exception of one, have accepted faculty positions in academic settings, where they will leverage their time with patients to ask better questions in the research lab, and use their scientific investigations to bring new answers and continued hope for the patients they serve.

“For a Ph.D. scientist to ask relevant questions in biomedical research, it’s important to have an understanding of medicine so that the research is driven by clinical problems,” said Ann Louise Olson, Ph.D., a professor of biochemistry and molecular biology in the OU College of Medicine and co-director of the M.D.-Ph.D. program. “Conversely, medicine is changing all the time and physicians benefit from a solid scientific foundation. People who hold M.D.-Ph.D. degrees understand both sides profoundly and are often leaders in shaping how the rest of us approach our jobs.”

Olson directs the program in conjunction with Rodger McEver, M.D., chair of the Cardiovascular Biology Research Program at OMRF. Through a grant from the Presbyterian Health Foundation that was awarded 15 years ago, the program took on a formal role within the OU College of Medicine. That grant has since ended, but the program’s leaders are hopeful that new grant funding will arrive so that additional students can be admitted. Currently, one new student is admitted each year, though administrators would like to admit two or three. Grant funding helps students manage the long-term commitment; they receive paid tuition for both medical school and graduate school, as well as a $25,000 yearly stipend.

Ann Louise Olson, Ph.D., a professor in the Department of Biochemistry and Molecular Biology and co-director of the M.D.-Ph.D. program, is pictured with David Sparling, M.D.-Ph.D., one of its graduates.

The framework of the M.D.-Ph.D. program was designed to immerse students in both worlds over a period of years. For the first two years, students begin medical school, taking all the preclinical courses required. Then students leave the medical school track and spend the next four to seven years working toward their doctorate, in areas ranging from pathology and biochemistry/molecular biology to cell biology and microbiology/immunology. After they earn their Ph.D., students rejoin medical school, completing their third and fourth years in the clinical setting. After graduating from medical school, they begin residency as all new physicians do. Finally, after the completion of residency, they embark on a research-intensive specialty fellowship.

“The program, though long, is a joint commitment from the beginning, Olson said. Students who are drawn to the program are often unique individuals who have a long-term vision of how their careers will blend clinical medicine and bench research. Applicants are carefully screened to ensure they bring a dedication to the program and an understanding of its relevance to the practice of medicine.

 “Our students are incredibly smart and analytical, but they’re also not afraid of failure,” Olson said. “In order to be a successful scientist, you have to do a lot of experiments and accept the fact that your hypothesis will not be correct many times. But our students seem to understand quickly that failures in the lab are opportunities to try something else. They know they have a great capacity for learning and thinking, so they are wide open to possibility.”

Amanda Templeton is a current student in the M.D.-Ph.D. program. This spring, she will defend her dissertation, then begin her third year of medical school in the summer.

The typical physician-scientist career will be 80 percent dedicated to research and 20 percent to seeing patients. One graduate of OU’s program who has recently returned home to begin his career is David Sparling, M.D., Ph.D., assistant professor in the Department of Pediatrics. Sparling has long had an interest in diabetes in children, and he discovered the M.D.-Ph.D. track was the ideal path toward his goals. After graduating from the OU College of Medicine in 2009 (having completed his doctorate in biochemistry/molecular biology two years before), Sparling was accepted to residency in pediatrics at Columbia University in New York, where he went on to complete his clinical and research fellowship in pediatric endocrinology.

At the OU College of Medicine, as was the case in his fellowship, Sparling’s 80-20 split in research and patient care is protected time, which gives him the resources to start his own lab and seek top federal funding. Although his career is just getting started, he can already see the value of his M.D.-Ph.D. training. As the axiom goes, children are not simply “little adults” -- the treatments for children with diabetes are not the same as for adults, nor has research yielded sufficient evidence about the pediatric diabetes population. Sparling hopes to be part of finding new answers.

 “The treatments and the disease processes of diabetes in children and adults have similarities, but they are very different too,” Sparling said. “We need avenues for new treatments, and hopefully that’s where I’m headed. I believe the M.D.-Ph.D. program gave me a way to think about questions and apply them to the broader picture. Hypothesis-driven research and developing a differential diagnosis are two sides of the same coin.”

Amanda Templeton looks at images of her zebrafish research model. She studies functional mutations of cancer patients.

People who earn degrees through the M.D.-Ph.D. program also serve as “bridges” between the clinic and the research lab and can speak the languages of each. Amanda Templeton, who will defend her doctoral dissertation this spring and will begin her third year of medical school in July, said she anticipates her doctoral work will guide her approach to the challenges she will face in the clinical setting. 

Unfortunately, medicine isn’t as simple as identifying challenges in the patient setting and going into the lab to select an answer. Templeton said she expects to have endless questions about patient care, but also that her doctoral work will point her toward research investigations that have the potential to translate from the “bench to the bedside.”

 “I think the foundation of translational medicine is in basic science,” Templeton said. “But the approach is actually more about ‘bedside to the bench and back to the bedside.’ You begin with patient-derived questions and then search for answers within the structure of research.”

In her doctoral work at OMRF, under the guidance of David Jones, Ph.D., chair of the Functional and Chemical Genomics Research Program, Templeton has studied functional mutations in cancer patients, using zebrafish as her model. With the advent of next-generation sequencing, researchers have discovered that cancer tumors don’t just have one mutation; they harbor many. However, whether each of those mutations contributes to a patient’s cancer is unknown. Using the development of zebrafish as a marker for the functional capacity of cancer mutations, Templeton can gather data as to whether the same mutation would have functional consequences in humans. The next step is to determine whether a targeted therapeutic exists for a specific mutation and whether the drug would work.

“It is personalized medicine,” Templeton said. “After determining that a previously uncharacterized mutation is functional, we can then go to work identifying the best targeted therapeutics. With this approach, we no longer consider what cancer type the drug was designed for; we consider what it targets at the molecular level. This raises new opportunities to use existing drugs. However, because of the many untoward side effects of chemotherapeutic agents, it is morally wrong to whimsically try these drugs on clinical patients with uncharacterized mutations in hopes that they will work. Using our zebrafish model, we can rapidly work to pair the molecular signature of a patient’s tumor with the best available targeted therapeutic. These results can then give the oncologist confidence in a novel treatment plan for each patient. This tag-team approach puts the focus right where it should be – not on patients, but on each individual patient.”

Olson said interacting with people like Sparling and Templeton is enormously gratifying because they have the potential to help shape research in academic settings. Funding agencies are increasingly awarding grants for translational projects, and M.D.-Ph.D. graduates are uniquely poised to feel confident in that arena.

“These are the people who will be leaders, and they can help their colleagues stay current,” Olson said. “They can always ask questions that have clinical relevance.”

For more information, go online to http://mdphd.ouhsc.edu/.