Stanford Report - April 20th, 2009 - by Bruce Goldman
Last fall, Anna Poukchanski shared a rite of passage with several dozen first-year medical students at the School of Medicine during their course in gross anatomy: getting assigned a cadaver to dissect. By and large, her classmates viewed this vital step toward their MDs with unbridled enthusiasm.
Poukchanski defers. "Gross anatomy is called 'gross' for a reason," she said. "The class is well-taught, and I see why it's necessary to see the body and all its parts. But I have no interest in practicing medicine."
How can young research scientists be informed about the real world of human disease in order to raise the odds that they will tackle medically relevant problems and, ultimately, translate their results into diagnostic tools and treatments?
Poukchanski is no slacker. As eager to learn about human biology and disease as any hell-bound-for-stethoscope fast-tracker in her anatomy class, she's a "flask-tracker": not a medical student at all, but one of a half-dozen graduate students with no intention of becoming physicians. Eventually, they'll return to their first love, laboratory research. But first, they're taking an early, partial detour from their PhD training to master the mysteries of the human body, courtesy of the medical school's Master's of Science in Medicine program. The program, now in its third year of operation, allows students on the PhD track to earn a master's degree in medical science.
"I've always been mildly obsessed about microbiology," said Poukchanski, a first-year microbiology and immunology PhD candidate who decided she wanted to do medical research at age 6, when she read Paul de Kruif's classic, The Microbe Hunters. "But if a patient came to me with a disease, I would be far more interested in the disease than in the patient. And I feel that's the wrong attitude for your doctor to have."
The master's program, affectionately known by the acronym MOM, was spearheaded by neurobiology professor Ben Barres, MD, PhD, with solid encouragement from medical school dean, Philip Pizzo, MD, to solve a growing problem. Young research scientists—even those initially motivated by a desire to cure disease—are getting increasingly intensive training in increasingly narrow areas. How can they be informed about the real world of human disease in order to raise the odds that they will tackle medically relevant problems and, ultimately, translate their results into diagnostic tools and treatments?
Funding for such programs is always a problem, owing to their interdisciplinary, neither-fish-nor-fowl nature. Fortunately, a few private foundations—notably the Howard Hughes Medical Institute, which kicked in $1 million—got MOM up and running. As knowledge in molecular genetics and cell biology has exploded, its translation into medical practice has lagged, said Peter Bruns, HHMI's vice president for grants and special programs. Stanford is one of 13 top-tier medical schools that received funds from HHMI in 2006 as part of a coordinated effort to ground research-oriented doctoral candidates in human biology and disease, and ultimately to increase the pool of scientists who are doing medically oriented research.
The Master's of Science in Medicine program appears to be the most demanding such effort around. "Stanford is way over at one end of the spectrum," said Bruns. "There, graduate students are completely immersed in the medical curriculum."
Still, MOM is nowhere near as long a haul as traditional MD/PhD programs, a course of study encouraged by many institutions seeking to produce research scientists who can translate basic-science discoveries into bedside treatments. Stanford's MD/PhD program annually enrolls eight to 10 students who spend their first two years in medical school, the next four doing PhD research, and a final two years taking the clinically oriented upper-division medical school courses. They typically then go on to internships and residencies. By contrast, MOM adds only about a year, plus or minus six months, to the entire PhD package.
There are fewer people now doing MD/PhDs than there were in 1980. "That's because in the last 30 years, everything—in clinical medicine, as well as in research—has gotten more specialized," said Barres. "So if you want to train in both, it just keeps taking longer and longer." The MOM program, whose Web site is http://msm.stanford.edu, is not meant to replace the MD/PhD programs, but to provide another path for students who have a clear focus on their research orientation.
So far, it's been wildly popular. As many as 20 percent of newly admitted bioscience graduate students apply, as do a number of new PhD candidates in other science and engineering programs. Six are accepted each year. (There's space for as many as 15 new students per year, if more funding can be found.)
The idea, said Barres, is to train scientists who can do research as well as understand how their research applies to disease—and then do research that delves deeper into disease processes. "Basic research can lead to new insights about disease, but you have to know what the diseases are and something about the disease processes," he said. "This is something most PhD programs don't teach students about."
Ricardo Dolmetsch, PhD, an assistant professor of neurobiology who serves on the program's steering and admissions committees, agreed. "The people who are the best at doing research sometimes don't get a very good introduction to clinical problems," he said. "With most PhD programs you get lots of information about how neurons work or how different subsystems of the brain do things, but not very much information about how that is important for pain, or mood, or how nutrition matters. Medical school is all about giving people the big picture."
Barres, who chairs the neurobiology department, already had his MD degree and a neurology residency in hand when he began pursuing a neurobiology PhD at Harvard University. "I still remember my shock in realizing that Harvard was granting PhDs in neurobiology to people who had never seen a human brain. That's like trying to train engineers without teaching them basic electronics.
"You can't teach neurobiology to graduate students as if there's this brain floating in space, not connected to a kidney or a heart or a liver or an immune system," he explained. "Every neurological disease involves all of those things. Disease is, by its nature, interdisciplinary. You don't have a 'brain disease' that just affects the neurons and not the blood vessels or the immune cells. You have to know about other tissues in order to put all the pieces together to understand disease processes."
MOM gives PhDs a chance to get the same intensive foundation of human-disease training the medical students get, but without having to do all the clinical training—how to use a stethoscope, perform an abdominal exam, take a medical history, read X-rays, draw blood—that's absolutely necessary for people who are actually going to be practicing physicians.
MOM students essentially blend in with the medical students for the first year and a half. In addition to standard first-year "building-block" medical courses in anatomy, physiology, genetics, biochemistry, immunology and pathology, they take four quarters of a composite class, "Human Health and Disease," which methodically explores the body's organ systems—nervous, cardiovascular, etc.—and the different diseases associated with each. They concurrently take some PhD courses and do their lab rotations. The med-school courses are clustered on four weekday mornings, and are taped every day and posted online. So if students are in the lab and miss a class, they can watch it later that night. MOM students also do a one- to two-month clinical rotation—basically, tagging along with physician/mentors to get the feel of how they work, the environment they work in and the impact disease has on the lives of their very real patients—sometime before the end of their PhD program.
There's a huge need, not only in the academic world but in the pharmaceutical world, for more scientists who know about disease, said Barres, who noted that the amount of money being spent by pharmaceutical companies on new drug development keeps going up. But the number of new drugs approved by the FDA each year has been going down. "The question is, why? I think our training systems are the problem."
It's not that anybody does it on purpose, he added, but simply the way most educational programs are structured. "There are plenty of people who don't want to see patients, but who are really interested in treating or curing disease. They get into our PhD programs and we teach them about flies and worms and fish, and they never hear again about human biology or human disease. In fact, we actually guide them away from it."
Susanna Wen, a chemical and systems biology PhD student now in her second year of the MOM program, hasn't picked her thesis topic yet, but she has picked her advisor: Dolmetsch, whom she first encountered when he taught the neuroanatomy section of one of her MOM courses in the winter term of her first year. Wen has developed a simple animal model for autism (a focus of Dolmetsch's lab) by engineering into fruit flies a mutated gene that, in humans, causes a form of that disease. Wen learned her genetics in the medical-school introductory course she took as a MOM student. "Without that course, I might not have conceived of this project," she said.
Barres drew his inspiration for starting MOM from an experimental curriculum called the Markey program set up by Franklin Bunn, MD, a professor at Harvard Medical School, while Barres was a graduate student there. The program enrolled 57 students over a seven-year period between the late 1980s and mid-1990s. "Then we lost our funding," said Bunn, even though the program seemed highly successful.
MOM is among the most intensive training programs ever generated at Stanford—"like being connected to a hose," said Dolmetsch. That intensity requires an exacting balance between the stethoscope and the microscope.
"The program gives me a clinical perspective on disease—how to look at the patient in a holistic way, rather than through a microscope—without making me go through the last two years of medical school," said Poukchanski. "Whenever you learn about a muscle, you learn about what it does, what controls it and how muscles act together to manipulate your movement and allow you to chew. And did you know that your jaw doesn't actually drop, it slides forward?"
But in the end, her heart is in the lab. "Research keeps me sane," she said. "I walk into a lab, and I'm back on my turf where I know what I'm doing, rather than in a med-school class, going, 'the temporal lobe does what?'"