The Key to Translation ...

Funding for translational research flows from government agencies and through foundations and associations. At meetings around the world, the pleas go out for more researchers to join the field. Yet if you ask 10 researchers to define "translational re-search," you're likely to get 10 different definitions, ranging from "translating a laboratory discovery into a clinical application up to, but not including Phase III clinical trials" to "all research involving human beings."

By | September 30, 2002

Funding for translational research flows from government agencies and through foundations and associations. At meetings around the world, the pleas go out for more researchers to join the field. Yet if you ask 10 researchers to define "translational re-search," you're likely to get 10 different definitions, ranging from "translating a laboratory discovery into a clinical application up to, but not including Phase III clinical trials" to "all research involving human beings." A middle-of-the-road but widely accepted definition is "research that takes a laboratory discovery into clinical use, then takes clinical research results back to the laboratory," hence the often used phrase "bench to bedside and back to the bench."

Although the term is ill-defined, the necessity of recruiting more researchers to bridge bench work and early clinical work is clear. Katherine High, a pediatric hematologist at University of Pennsylvania, says, "It's probably more important now than ever to train people who are interested in translational research, because there is so much going on in the laboratory; somebody has to be interested in realizing that and translating that into clinical protocol[s]."

Photo: Courtesy of Children’s Hospital of Philadelphia
 Katherine High

High says she was torn between going to graduate school and going to medical school. She chose medical school and then went into research while serving as a faculty member at a blood coagulation research division affiliated with a large hemophilia treatment center.

Budding translational researchers are not the same as clinicians. William Hait, director of the Cancer Institute of New Jersey in New Brunswick and chair of the American Association for Cancer Research's committee on clinical and translational research, refers to the love of research as an "addiction, just like anything you love to do. People who love research often start doing it, even as undergraduates."

A QUESTION OF TRAINING But the question is: How do you interest medical students in melding lab work with clinical work? Current programs usually require an MD student or recent MD to become involved in laboratory research. "I'm not sure we have a good mechanism in this country to train clinical researchers," says Hait, a graduate of an MD/PhD program, which is the major type of formal program producing physician-scientists. He believes that these programs fail to adequately address the dearth of translational researchers. "We've got to come up with creative ways to train individuals interested in this research," he notes. "For these programs to be successful, they have to be part of the fabric of American medical schools, a path students can enter early on in training, and not after they've accumulated hundreds of thousands of dollars' worth of debt [from college and medical school loans]."

One program to help recruit such students is the Howard Hughes Medical Institute (HHMI)-National Institutes of Health Research Scholars Program. The original program, notes James Gavin, who directed that program at HHMI until June before becoming president of Morehouse School of Medicine in Atlanta, was to expose medically trained persons to basic research. That program has become one that is "now trying to prepare people to do translational research," says Gavin. Students enter the program after their second or third year of medical school and stay for one or two years. During that time, they live on the NIH campus in heavily subsidized housing and are paid a small stipend. Also, if payback of their loans is negotiable, HHMI will negotiate with lending institutions to relieve the students of their payment responsibilities while they are in the program. The program accepts about 40 students per year who are mentored by NIH scientists engaged in research, and they attend lectures by translational researchers.

Photo: Courtesy of Howard Hughes Medical Institute
 James Gavin

Kristen Carr, who is returning to medical school at the University of Wisconsin, Madison, after two years in the HHMI-NIH program, explains that she already had a master's degree in neurobiology and physiology. Working at NIH with Jeffrey Trent, scientific director of the National Human Genome Research Institute, she used complementary DNA microarray technology to study the relationship between gene expression profiles of cutaneous melanoma and clinical outcome. Her experience has convinced Carr to apply for a residency in internal medicine with the goal of studying hematology/oncology. Hyung Chun, a graduate of the HHMI-NIH program, did research in immune responses at Harvard School of Public Health while still an undergraduate at Harvard College. He is beginning a residency in radiation oncology at Stanford University and wants to work in research that would provide direct benefit to the patients.

NIH has several additional mechanisms to provide support for medical students interested in translational research, through a new Mentored Clinical Research Scholar (CRS) Program recently awarded to 10 institutions. This program, for which each institution may recruit three candidatesfor each of the first three years, and a total of 12 canidates over five years, also provides tuition suport for an MS, MPH, or PhD in a relevant field. This program will support physicians and dentists to work two to five years with a mentor. The program not only will provide a stipend, it also will allow loan forgiveness for up to $35,000 and will cover federal taxes for the stipend for those years. NIH has also begun a program to allow medical students a year off to work with a mentor to design protocols and work with patients. Judith Vaitukaitis, director of NIH's National Center for Research Resources, explains that the students are carefully monitored "to make sure they really are developing their research skills, learning how to design research projects, and in other areas including bioethics, all needed for clinical research. The CRS program provides money for the trainee and the mentor.

Photo: Courtesy of Brendan Lee
 Brendan Lee

Individual schools may start their own programs. Brendan Lee, a pediatrics researcher in the Department of Molecular and Human Genetics at Baylor College of Medicine, Houston, started a one-year apprenticeship at Baylor that essentially is "stretching out medical school [from] four to five years." But, he adds, "One intentional year of research at a medical school doesn't make you a physician-scientist. It opens you to that aspect of medicine."

Those setting out on the journey can take heart from the example of Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who is board certified in internal medicine, infectious diseases, and allergy and immunology. While in medical school, he had no intention of becoming a clinical researcher. "My primary motivation in medical school was to be a physician to take care of patients." But after his residency, he went to NIH and began doing research. "Not only did I like it; I was good at it," he remarks. He then confronted the question: Should he go into basic research or should he combine it with patient-oriented research? His decision led him to translational research, which satisfies the physician in him while also satisfying his desire to do research.

BUILDING A PROGRAM Finding people to train is one thing. Finding places to train them is another. At New York University (NYU) School of Medicine, the administration realizes that a new building to house clinical/translational research is essential. Construction of the 13-story Smilow Research Building will begin this fall, according to John Deeley, NYU School of Medicine's vice dean for administration. The building will house clinical research facilities for cancer, cardiovascular biology, genomics, neuroscience, dermatology, and other research areas "to link up with the basic science that's already going on [at NYU]," says Deeley. The medical school has NIH funding for medical students to be trained in clinical research. But the new building "will just afford more of an opportunity in these areas that we're going to focus on," Deeley says. Expected completion date is mid-2005.

The road to filling the pipeline with translational researchers is a long and arduous one, involving years of training and sacrifice. But the reward can be great. As Baylor's Lee says, "As I tell my fellows, the next patient can give you a Nobel Prize-winning insight."

Myrna E. Watanabe is a freelance science writer in Patterson, NY.

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