Translational medicine facilitates the rapid, effective application of results in the research laboratory to patients in the clinic. To work in the field, individuals need both a broad understanding of basic life science and a passionate interest in human health.

Children’s Memorial Research Center (http://www.childrensmrc.org)
National Institute of Child Health and Human Development (http://www.nichd.nih.gov)
Northwestern University (http://www.northwestern.edu)
Novartis Institutes for BioMedical Research (http://www.nibr.novartis.com)
SRI International (http://www.sri.com)
University of North Carolina (http://www.unc.edu)
University of South Dakota (http://www.usd.edu )

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The most obvious candidates to participate in translational medicine are M.D.-Ph.D.s. “But those programs have a relatively fixed number of people coming through the pipeline,” Arias says. “However, every medical school has basic science graduate programs that train Ph.D.s, most of whom have interest in pathobiology. Here at the National Institutes of Health, we offer Ph.D. students, postdocs, and staff who are interested in learning about disease and medical problems a course called “Demystifying Medicine.” The course is similar to one we started at Tufts School of Medicine 18 years ago that trains Ph.D.s in pathobiology. The NIH program is generic and attracts people from all institutes.”

Arias bases the course on a simple fact: “It’s a lot easier to demystify medicine for bright Ph.D.s than to take chief residents and put them in a laboratory,” he explains. The course exposes students to clinical and basic science presentations in a format based on old fashioned grand medical rounds, frequently including interviews with patients.

Ph.D.s have responded enthusiastically to the program. Slightly more than 100 scientists joined the course in 2001, the first year that Arias offered it. In the current year, he recalls, over 900 have registered and, on average, 350 regularly attend on site or electronically. Requirements for registration are simple. “The course is self-selecting,” Arias says. “The one ingredient is that participants share a deep and sometimes passionate interest in human health.” The program is accessible worldwide through the NIH’s video archive and the Demystifying Medicine website (http://www1.od.nih.gov/oir/DemystifyingMed).

Scientists with that passion now have a few other options for training in translational medicine. “The National Cancer Institute has started a similar course solely focused on cancer biology, which is more detailed and more like a traditional course,” Arias says. “MIT has an ambitious program that involves bioengineers.” Whoever offers them, the courses have so far produced similarly positive results. “About a third of students selecting this kind of program after finishing their postdoctoral work are in tenure track positions in some of the best clinical departments,” Arias reports.

Mentors and Role Models

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A few universities have started programs that require researchers to understand the basics of translational medicine. “We’re starting an M.D.-Ph.D. program in the fall and looking for mentors and role models; we’re specifically looking for people with M.D. and Ph.D. degrees,” the University of South Dakota’s Miskimins says. Finding those individuals presents one unique problem. “They see the winter here and don’t come back,” Miskimins says. “But it’s getting easier to attract them.”

Students have shown more enthusiasm. “They are quite academically diverse, including chemistry majors, biology majors, a psychology major, and some who have bummed around a while before deciding what they want to do next,” Miskimins says. “All had a strong interest in medicine and then got hooked on research. They decided that making a contribution to the patients they would see as physicians would be an exciting way to go.”

Harris’s program, started at Northwestern two years ago and funded largely by philanthropic donations, aims to develop practical links between the lab and the clinic. “The program already has three principal investigators (PIs) who are working on genetic aspects of neurological disease – projects that tie in clearly with clinical issues that the neurologists and psychologists at Children’s Memorial Hospital are dealing with,” Harris says. “All three are basic scientists, but they are very much crossing the boundary between the molecular advances at the bench and their use in developing new treatments.”

Harris’s requirements for qualified individuals resemble those of Miskimins. “The big recruitment of the moment is for PIs, but we have openings for postdocs also,” she says. “The most important thing is that candidates have to be outstanding basic scientists who are creative and innovative. They also have to be able to see the bigger picture – the application of their research to clinical problems.”

At the University of North Carolina, meanwhile, Narayan wants scientists with practical experience. “I’m looking for people who can translate a lot of our research in novel materials into practical devices,” he says. “We want multidisciplinary and interdisciplinary skills in processing, characterizing, and modeling devices, as well as preclinical testing, animal modeling, and the clinical end of testing on human subjects. We want people who can take a device and interact with a clinical subject for testing and evaluation.”

Accelerating the Transition

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However well academic programs work, they often fail to bridge the gap between research and usable products, in the form of drugs and devices intended to improve human health. That has emerged as a particular problem in recent years, as pharmaceutical and biotechnology companies have focused more on the later stages of their drug pipelines. “Early in this decade I saw a shift of money and emphasis on the drugs already in the clinic and a real need to chaperone new drugs,” SRI’s Spack recalls.

In response, his company linked up with Stanford University and the University of California faculties at Berkeley, San Diego, and San Francisco to create PharmaSTART, a consortium intended to accelerate the transition of new drugs from discovery into clinical use. “We’re providing development plans that lay out roadmaps for how to make the transition, including advice on funding sources,” says Spack, who is PharmaSTART’s senior director. “We’re also providing a forum for discussions on translational medicine with angel investors, the U.S. Food and Drug Administration, and other interested parties. And we’re bringing groups together for translational development grant opportunities.”

The consortium’s variety of programs creates a demand for versatile recruits. “We’re getting all sorts of projects, from gene therapy for an orphan disease to a small molecule for cancer,” Spack says. “We need to triage projects quickly, to understand what the clinical application is, and to fill the pathways. So we need people with broad experience who can communicate with basic scientists: people who can translate translation. It also requires a certain level of marketing savvy to understand opportunities, some business acumen, and some feel for government.” Fortunately, he adds, “we don’t necessarily need all those skills in one person.”

For individuals seeking a career in life science, the ability to think in multidisciplinary terms has become little short of essential. Nowhere is that ability more necessary than at the conjunction of basic science and clinical medicine. Translational medicine, as the field is known, aims to convert research results into clinical developments of use to actual patients. It demands an understanding of both basic research and clinical medicine, and it is growing in popularity. “This is the hot area,” says Roger Narayan, associate professor in the joint department of biomedical engineering at the University of North Carolina.

Defining translational medicine isn’t easy. Indeed, it has almost as many definitions as practitioners. “It reminds me of the story about the blind men and elephant; people tend to define translation as their part of drug development,” jokes Edward Spack, senior director of biosciences business development at SRI International. “Speak to anybody from any company or academic institution and they’ll have a new focus on it and a host of names,” adds Trevor Mundel, global head of early clinical development at the Novartis Institutes for BioMedical Research.

However, researchers agree on the broad outlines of the field. “I define it as a global approach to extracting clinically useful information from advances in basic science and bringing those advances directly into clinical care,” says Ann Harris, director of the human molecular genetics program at Children’s Memorial Hospital’s Children’s Memorial Research Center and Northwestern University. Robin Miskimins, professor of basic biomedical sciences at the University of South Dakota, takes a similar view. “I think of it as medicine that seeks to implement the newest in treatment options by taking them from the research options to usable medical technology in as few steps as possible,” she points out.

Bridge Building
Irwin Arias, adjunct investigator and head of the unit of cellular polarity at the National Institute of Child Health and Human Development and professor of physiology and medicine at Tufts University, summarizes those thoughts. “To me, translational medicine is a term that means almost the same thing as bridge building between science and medicine; others call it bench to bedside,” he explains. “The principle is: How do you link up the incredible advances in science with better medicine? As with the metaphorical structure, this type of bridge building requires many different structural components. There is no single cure-all.”

In almost all cases, the field involves movement of intellectual property from the laboratory to the clinic. “It’s hard to overestimate the amount of good medical treatment that comes out of good basic research,” Miskimins says. However, the activity can also move in the opposite direction. “A lot of people talk about the reverse of the bench to the bedside approach: taking things you can learn from the patient population to gain new insights into fundamental biology,” Narayan explains.

Translational medicine has a history. “It’s not a new concept,” asserts Arias, whom many observers regard as the godfather of the field. “The link between medicine and science was very strong in the 1950s, 1960s, and into the 1970s. It was not unheard of then for basic scientists to attend grand rounds.” But rapid advances in fundamental biology since then have focused basic researchers more on their lab work while changes in the nature of health care have made it increasingly difficult for clinical researchers to collaborate with their colleagues in fundamental science.

Those factors still hinder the progress of translational medicine. “Today, the opportunities to improve medical diagnosis and treatment based on science are extraordinary,” Arias says. “But we’re frustrated by changes in the health delivery system and medical education and the high degree of specialization in the progress of basic science.”

Several Specialists


Success in translational medicine demands a wide variety of capabilities. “You have all the basic medical science disciplines – biochemistry, chemistry, pharmacology, physiology, and toxicology, as well as some of the physical sciences and engineering,” Narayan says. “All these areas that can interface with clinical medicine are now doing so. Federal and private funding are making it possible.” An understanding of development and application can also help. “Basic research is only part of the training needed,” Spack explains. “Chemists may be good basic chemists but lack experience in formulation. Some companies have very strong engineers but little knowledge of regulatory affairs. Universities often lack regulatory expertise. One of the advantages we have here at SRI is technological divisions that can bring groups to bear on multidisciplinary challenges such as medical devices.”

Recruiters don’t ignore specialized skills. “All our translational medicine studies are based on biochemical or imaging markers,” Novartis’s Mundel says. “So our scientists need great familiarity with imaging techniques and their deficiencies.”

However, a feel for multidisciplinary matters certainly helps scientists involved in translational medicine. “Those working most successfully are working across disciplinary boundaries,” Northwestern’s Harris points out. That doesn’t necessarily demand broad training. “The skills don’t need to be in one person, but must exist within the team,” Narayan explains. “You can be largely trained as a specialist in one field,” Harris agrees. “What’s most important is to think broadly and think about subjects in a variety of ways. You need to be able to communicate with the people caring for patients – listening to them as well as explaining what you are doing.”

Not many individuals fill the necessary criteria. “The number of people who fit into this is vanishingly small,” Mundel says. “Within the cardiovascular metabolism area I must have reviewed 286 CVs of interested people. We got this down to a short list of six to eight scientists. Ultimately the one who joined us had actual clinical experience.”

Pathobiology for Ph.D.s

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What personality traits make for successful specialists in translational medicine? “It is important that they can communicate well with scientific and nonscientific stakeholders, such as ethics committees, internal review boards, regulatory agencies, and – importantly – research subjects,” Narayan says.

Collegiality is equally critical. “Some people seem to have a certain knack of being able to work in a matrix without being trapped by it,” Mundel says. “I see very bright people coming in and generating so many antibodies to their activities that they can’t be successful.” Harris agrees that the solo scientist has no place in translational medicine. “The people who are going to be successful in this field are not solely focused and completely absorbed by their research,” she says. “They need to be energetic and to go out into the clinic. The field takes an outgoing, enthusiastic, highly energetic person.”

Miskimins sees the need for two other characteristics. “One is problem-solving skills,” she says. “You’re going to deal with hospitals, drug companies, patients, and others, and encounter all sorts of hurdles and rules and regulations; you’ll have to find solutions. The other factor is persistence. Not everything works the first time. You need the will to work at it when things aren’t going well.”

A former science editor of Newsweek, Peter Gwynne (pgwynne767@aol.com) covers science and technology from his base on Cape Cod, Massachusetts, U.S.A.

DOI: 10.1126/science.opms.r0600011

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http://www.sciencemag.org/about/podcast.dtl Industrial-style thinking is also crucial to Novartis as it recruits scientists for its work on translational medicine. “In the universities it’s very difficult to have the sort of cross-fertilization that you need for translational medicine,” Mundel explains. “There’s also not the volume. We see projects turning over on a yearly basis; academics tend to think in spans of five years, 10 years, and more.” Mundel seeks mainly senior scientists who can train their own replacements in what he calls “a kind of translational medicine university inside the company.”

Traits for Success

10.1126/science.opms.r0600011