Veterinarian Scientists Bring Unique Perspectives to Translational Research

Like many academic clinician-scientists, Susan Volk juggles patient cases with research. Some days, she spends mornings in surgery or the clinic and afternoons in the lab trying to use progenitor cells to improve wound healing. Other days require her full attention on patient care or a research problem.

Less typical than many other clinician-scientists are Volk's patients, who tend to be furry and respond with barks and meows. Now an assistant professor of surgery at the University of Pennsylvania's School of Veterinary Medicine, Volk holds a veterinary degree (called a V.M.D. at Penn and D.V.M. elsewhere) and a Ph.D. from Penn's V.M.D.-Ph.D. program.

Volk went to Penn as an undergraduate intending to become a veterinarian; she caught the research bug working in a lab at the veterinary school. She decided to pursue a dual degree and never looked back. "I always knew I wanted to have some degree of clinical practice," Volk says. "But I really wanted to make a difference at the research level as well."

Although the D.V.M.-Ph.D. approach isn't very common, it's increasingly recognized as excellent preparation for a career in translational research. Graduates with this degree are uniquely qualified to develop and do research in animal models, compare basic biology across animals, and translate research findings to different species -- including humans. As such, opportunities for veterinary medical scientists run the gamut from biomedical and pharmaceutical research to public health and academia.

"Our goal for the program is to train diverse scientists, and I think we are doing that," says Michael Atchison, director of Penn's V.M.D.-Ph.D. Program. "Our graduates know how to ask the right medical questions and the right scientific questions. They really have the whole package."

Charting a course in biomedical science

A 2005 National Academy of Sciences report documented a shortage of veterinarian scientists in the biomedical enterprise, noting that few National Institutes of Health (NIH)-funded competitive grants involving animals were awarded to principal investigators with veterinary training. The report called on vet schools to put more emphasis on training veterinarians to become researchers.

Despite this new research-training emphasis, the dual D.V.M.-Ph.D. approach is not new. Penn's program began with NIH funding in the 1960s, and several schools around the country have established combined D.V.M.-Ph.D. programs. [See box below for a list.]

Veterinary school is structured much the same as medical school: 2 years of preclinical coursework followed by 2 years of clinical rotations. Like their medical school counterparts, veterinarians often choose to pursue a residency in a specialty after receiving their degrees. Likewise, D.V.M.-Ph.D. programs are similar to M.D.-Ph.D. programs, lasting 7 to 8 years in total, with the 3 to 4 years of Ph.D. training occurring between class work and clinical rotations.

Core courses for veterinary students and medical students tend to look very similar, too: gross anatomy, physiology, biochemistry, pharmacology, and neuroscience, to name a few. The principal difference, from the perspective of most vets, is that whereas medical students focus on one animal, vet students study these subjects in the context of a whole array of animals, large and small.

It's this comparative approach to medicine that's so valuable for translational research. "It is a very simple fact that most research that is going to be medically relevant is going to be done in animals first," Atchison says. "For example, cancer research is heavily reliant on mouse models, and as a result we've become very good at curing mice, but that hasn't translated very well to humans. It's extremely important to choose the appropriate animal models, and veterinarians have the training to do that."

"I think I have a big advantage being a veterinarian in understanding the whole process of wound healing and understanding the unique aspects of healing in different species," Volk says of her research specialty. "For example, a cat heals differently than a dog. I know those differences, and as a result I know what models to use and the limitations of those models."

Career options

D.V.M.-Ph.D.s have a wide variety of career opportunities, although most choose academic research. Overall numbers are hard to come by, but Penn's V.M.D.-Ph.D. graduates provide a glimpse: 55% go into academic research; 15% enter the pharmaceutical or biotech industry, most in leadership positions; and 7% enter private veterinary practice. The rest are in postdoctoral or residency training, working in government health agencies, or serving in other research-support capacities.

Jaime Modiano is one of the graduates who elected to focus on academic research. After completing the V.M.D.-Ph.D. program at Penn, Modiano went to Colorado State University for a residency in pathology. At the end of his residency, he realized that "you can't go into science with just a Ph.D. and clinical training. I really needed to do a postdoc." He joined the lab of Erwin Gelfand at the National Jewish Center for Immunology and Respiratory Medicine (now National Jewish Health) to do research on T-cell activation, the subject of his Ph.D. research. He soon realized, however, that his residency training in pathology and his research interest in immunology didn't mesh well professionally.

"My research in immunology was so disconnected from [my clinical work] that I had to make a choice because I wasn't being excellent at either aspect of my career," Modiano says. He decided to stick with research and joined the staff of the University of Colorado-affiliated AMC Cancer Research Center while serving as an associate professor of immunology at the School of Medicine of the University of Colorado, Denver. "It was kind of fun being at a medical school and known as the weird guy who worked with dogs," says Modiano, who is now a professor of comparative oncology at the University of Minnesota College of Veterinary Medicine and the Masonic Cancer Center, where his research focuses on immunology, cancer cell biology, cancer genetics, and applications of gene therapy.

Modiano also dipped his toe into the biotechnology milieu while he was in Denver as one of the founders of ApopLogic Pharmaceuticals Inc in Aurora, Colorado. There, he guided the animal studies for Fasaret, a cancer therapeutic that triggers cell death, launching the product into phase I clinical trials. "There are many opportunities for veterinary scientists to work in drug development in industry, academia, contract research, and even patent law. We need to make sure that we educate students about the opportunities in the real world," Modiano says.

Not everyone with a dual degree gives up clinical practice or research. Anne Zajac, an associate professor in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland Regional College of Veterinary Medicine in Blacksburg, Virginia, does research on gastrointestinal parasites found in small ruminants such as sheep and goats. She also serves as the parasitologist on staff for the large- and small-animal hospitals associated with the school.

Originally interested in parasitic disease such as malaria, Zajac chose to pursue a veterinary degree at Michigan State University in East Lansing and a Ph.D. at Ohio State University, Columbus. "My focus was on human parasites, but through my training I became more interested in parasites that infect animals because those parasites can have a tremendous impact on humans in terms of their livelihoods being dependent on the health of their animals," Zajac says.

Volk, too, maintains her clinical perspective by serving as a general surgeon at Penn's small-animal hospital. "One big advantage of doing a combined degree is learning to integrate the two aspects of your career," Volk says. "It is very easy to focus on one job at a time; this program is training for how to run your career."

Curing humans and their companions

Irrespective of the path that their careers have taken, D.V.M.-Ph.D.s have opportunities to make significant contributions to biomedical research, for the benefit of both humans and animals. This becomes apparent in diseases such as cancer: Dogs and cats suffer from naturally occurring cancers similar to human cancers. Unlike rodent models, which are developed from inbred strains of mice kept in controlled environments, companion animals, like humans, are genetically diverse and are exposed to many of the same environmental influences as their owners are.

Studying drugs in companion animals before introducing them in humans could improve the success rate of cancer-therapeutics development. That premise has fueled much of the work of Mark Dewhirst, a professor of radiation biology at Duke University School of Medicine in Durham, North Carolina, who pursued both a veterinary professional degree and a Ph.D. at Colorado State University in the early 1970s. "These pet-animal studies have been extremely helpful in making decisions on whether to go into human clinical trials."

A critical barrier to using companion animals in preclinical research is organizing those studies. It's a problem that Chand Khanna recognized when he arrived at the National Cancer Institute (NCI) in 1997 to do a postdoc. "I came with the intent to study molecular biology techniques," says Khanna, a D.V.M-Ph.D. who is now a senior scientist in NCI's pediatric oncology branch. "But I also came with the veterinarian perspective, and as I talked to people, I realized there was an opportunity to answer questions in dogs with cancer that can't be answered in either humans or mice. And that is critical for the development of new drugs."

To that end, Khanna created the Comparative Oncology Program within NCI's Center for Cancer Research. By linking together veterinary scientists at research centers across the country and in Canada, the studies completed through the program's Comparative Oncology Trials Consortium provide valuable information needed to design human clinical trials.

Khanna believes companion animals will play an ever-increasing role in biomedical research on cancer and other diseases. As such, he believes there is an obvious role for dual-degree veterinarians. Penn's Volk agrees: "For me and most of my colleagues, ... we are thrilled to make a difference for our animal patients," Volk says. "But really, there is an opportunity with appropriate animal models to make a huge difference for the human community as well."

Lisa Seachrist Chiu is a science writer in Washington, D.C.

10.1126/science.caredit.a1000070