Posters of children line the hallway leading to Eileen Shore's laboratory  at the University of Pennsylvania School of Medicine . Every day, the faces remind her lab workers why they're slinging test tubes: to cure a pair of disorders in which bone grows where it shouldn't. The rare, debilitating genetic diseases, fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia, strike in childhood and lead to years of pain and early death.
Shore is a Ph.D. scientist, and yet she and her lab members know most of the patients and families who come to Penn to see orthopedist Frederick Kaplan, one of the few clinicians who specializes in the diseases. Working closely with Kaplan, Shore and her postdoctoral fellows and graduate students attend patient examinations, host lab tours for families, and generally stay connected to the small, close-knit FOP community.
"They all get to interact with patients at some point," Shore says of her team. "Having the patient contact makes the research much more personal. You start thinking you're doing this to help this person with a name."
Before inviting lab members to the clinic, Kaplan asks a family's permission--and has always gotten a "yes." Kaplan introduces the scientists and their work before examining a patient, usually a child, as the scientists observe, ask questions, and chat with patients and families. "I bring them in as important partners," Kaplan says of the bench scientists.
Kaplan and Shore say the close connection they've forged between lab and patient is unusual, perhaps even unique. Yet opportunities for lab scientists to interact with patients appear to be growing at academic medical centers. Expanding graduate programs in translational medicine send lab-bound students to the clinic and invite patients into the classroom. Informal interactions on an ad hoc, lab-by-lab basis--such as those in Shore's lab--are also possible. The arrangement is embraced by patients and their families. "I've never had anyone question me ... about why these scientists are there," Kaplan says. "And in fact, [the families] are often disappointed when they come to see me and [the scientists] are not there."
Says Kaplan: "It's important for residents, fellows, and postdocs to understand that [this disease] is not just a biochemical problem, not just a genetic problem, a molecular, or cellular problem. It's a human problem."
Lab scientists who've met patients say the experience enriches their research and points them toward more clinically relevant questions.
Michael Dyer, a Ph.D. biologist who studies the childhood eye cancer retinoblastoma at St. Jude Children's Research Hospital  in Memphis, Tennessee, says a day with patients back in 2004 was the "single most important event" in his career. Before that day, Dyer had spent years working in medical schools but had "never once met a physician, or a patient, or their family." Then, at the invitation of clinicians at St. Jude, Dyer met with patients and their families. Dyer asked the clinicians if the 1986 discovery of the gene responsible for retinoblastoma--a milestone discovery in basic research, as it was the first human-disease gene to be cloned--had made a difference in the lives of the patients. "They said it's had no impact at all," Dyer says. "That was a big eye-opener, and it really made me think, 'Why was that?' "
Meeting children who had lost eyes to retinoblastoma motivated Dyer to build a clinically relevant research program. So far, he's been successful. He quickly helped develop the first mouse model of retinoblastoma, identified potential new treatments for the disease, and moved new therapies into clinical trials. The patient connection "shifted the focus of my lab to try to bridge that gap" between the lab and the clinic, he says.
A burgeoning crop of new programs in translational medicine aims to instill the importance of the patient connection in budding scientists. In 2006, the Howard Hughes Medical Institute  (HHMI) funded 13 such programs, which operate at the certificate, master's degree, and Ph.D. levels. (See "Programs Aim to Train Translational Scientists .") HHMI plans to announce additional sites for the program, called Med Into Grad , later this year.
At the Cleveland Clinic Lerner College of Medicine  in Ohio, students in the molecular medicine Ph.D. program  choose a clinical mentor in addition to a thesis mentor. Together, the student and the clinical mentor design a relevant patient-oriented agenda. For instance, if the student chooses a prostate cancer project for her thesis, "she would link up with a prostate cancer doctor, and he would teach her all about urology," says Martha Cathcart, director of graduate education at the Cleveland Clinic . "She would see prostate cancer patients, she would go to radiation therapy, ... she would go to pathology, she would see how to diagnose the disease."
In translational medicine programs, patients often visit classes to describe what living with their disease is like. Anna Poukchanski, a student in Stanford University's Masters of Medicine program , recalled a woman with polycystic kidney disease visiting one of her disease-oriented classes. The woman's kidneys weighed 20 pounds apiece, and people often asked her if she was pregnant. "It was very humbling," says Poukchanski, who plans to study infectious parasites for her Ph.D. in microbiology and immunology.
Each program is unique. At Stanford, for example, students must first be admitted as Ph.D. candidates. Then they apply separately to the Masters of Medicine program, which takes just six students a year. For their first five quarters, students enroll in many 1st-year medical school courses--such as gross anatomy--in addition to their Ph.D. coursework. It's a heavy load, but Poukchanski says it made her appreciate the challenges physicians face.
Graduate students attend grand rounds in some programs, such as the one hosted by the Institute for Molecular Medicine (IMED) at the University of California, Los Angeles (UCLA). These sessions, in which physicians present case details, don't afford direct patient contact, but they offer Ph.D. students a chance to find holes in diagnosis and treatment that their research might help fill. Michael Teitell, a professor at IMED, says grand rounds expose Ph.D. students to "the phraseology of medicine," clinical problem solving, differential diagnosis, and state-of-the-art patient care.
Teitell added that the visceral response of seeing disease processes up close can help motivate students. "They are shocked when they see someone cutting across a coronary artery and they hear a crunching sound, and the cross section is a pinhole where the blood should be flowing. It's eye-opening."
Whenever members of Shore's lab visit the clinic, an M.D.--usually Kaplan--is present. Likewise, patients who visit classes consent and waive their right to anonymity. Shore says that anyone who works with patient materials--even if they never meet a patient--has to complete an online course provided by the university explaining federal patient privacy rules as spelled out in the Health Insurance Portability and Accountability Act  of 1996. At UCLA, all patient identifiers are masked when scientists or Ph.D. students attend grand rounds and hear case presentations, Teitell says.
Professors in translational medicine programs say they hope the patient focus will help speed new discoveries into the clinic. HHMI is tracking the 200-plus students in the programs they fund, measuring how many papers they co-author with physicians, for instance. Ben Barres, a neuroscientist and the director of Stanford's program, says, "My hope is that they become better scientists, better biomedical researchers, and that they do way more disease-oriented research" than they otherwise would.
Once scientists start interacting with patients, they may face a dilemma familiar to physicians. It's easy to "get too emotionally involved," Shore says. "It's a fine line, and you want a certain amount of objectivity. Still, you start thinking about these people as your friends. ... It does make you feel differently about why you're doing what you're doing. You know that if you can find a drug that would slow progression of bone, it will really have an impact on people's lives."
- University of Alabama, Birmingham  (Ph.D. in Translational Research and Drug Discovery)
- Baylor College of Medicine  (Translational Biology & Molecular Medicine Ph.D.)
- Cleveland Clinic Lerner College of Medicine/Case Western Reserve University  (Molecular Medicine Ph.D.)
- Harvard Medical School  (Leder Medical Sciences Program)
- Massachusetts Institute of Technology  (Graduate Education in Medical Sciences)
- Rice University  (Ph.D. training in Translational Bioengineering for Cancer Diagnostics and Therapeutics)
- Stanford University School of Medicine  (Master of Science in Medicine)
- University of California, Davis , School of Medicine (Integrating Medicine into Basic Science)
- University of California, San Diego, School of Medicine  (Integrating Medical Knowledge into Graduate Training)
- University of North Carolina, Chapel Hill  (Program in Translational Medicine)
- University of Pennsylvania School of Medicine  (Graduate Training in Medical Sciences Certificate Program)
- University of Washington  (Molecular Medicine Training Program)
- Yale University  (Medical Research Scholars Program)
- Johns Hopkins University School of Medicine  (Graduate Program in Cellular and Molecular Medicine)
- Wake Forest University School of Medicine  (Molecular Medicine and Translational Science Graduate Degree)
- Mayo Clinic College of Medicine  (Clinical and Translational Science)
- University of Rochester  (Translational Biomedical Science Ph.D.)
Note: This program list was originally published in the article "Programs Aim to Train Translational Scientists ."
Brian Vastag is a freelance science journalist in Washington, D.C.