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Healthy exchange

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Future doctors study the life and learning connection

After class, from left, Hesketh '74 and Dr. Michael Worthington, chief of infectious diseases at Caritas St. Elizabeth's Medical Center, speak with Catherine Sullivan '06 and Kellie Faircloth '05. Photo by Lee Pellegrini

After class, from left, Hesketh '74 and Dr. Michael Worthington, chief of infectious diseases at Caritas St. Elizabeth's Medical Center, speak with Catherine Sullivan '06 and Kellie Faircloth '05. Photo by Lee Pellegrini

CLASSNOTES

Class: BI 403: "Introduction to Clinical Medical Science"

Instructors: Professor of biology Thomas Chiles and Paul Hesketh, MD, '74

Readings: New England Journal of Medicine, Hematology, and other journals


Though not a lab course, Biology 403 owes its existence to Professor Thomas Chiles's lab on the fourth floor of Higgins Hall, a clean, well-lighted 1,500 square-foot space housing items like a liquid nitrogen freezer, which maintains tissue samples at -180 degrees Celsius; several chrome-plated tabletop devices called carbon dioxide water-jacketed temperature-controlled tissue culture incubators; and Chiles's favorite new toy, a $160,000 gray metal box known as a flow cytometer, which can project the image of a single cell from a tissue sample onto a nearby computer screen. This is the lab where Chiles and his team of graduate students, post-doctoral fellows, and undergraduates study the B-lymphocyte, a kind of white blood cell, with a focus on the pathway, or series of proteins, whereby the cells receive signals that tell them when to proliferate.

Chiles is guessing this pathway may be "aberrantly active" in the B-lymphoma cell, the cancerous version of the B-lymphocyte, which proliferates uncontrollably, and the hunch may pay off in the form of saved lives. Increasingly, understanding how disease works at the cellular and genetic levels has paved the way for targeted therapies, new-generation drugs that block pathways that allow disease to flourish. Not only are the best of these therapies more effective and less toxic than standard chemotherapy, they're also easier to discover. "It's not like the old days," Chiles explains, "when you blindly tested everything on your shelf" to see if it worked against a given disease. Knowing exactly what you're trying to accomplish on the level of cell biology takes much of the trial and error out of drug development.


IN THE late 1990s, the state-of-the-art biology labs in newly renovated Higgins, spaces like the one where Thomas Chiles studies the B-lymphocyte, caught the eye of Paul Hesketh '74, chief of the division of hematology/oncology at Caritas St. Elizabeth's Medical Center, a Boston teaching hospital. Seeing the labs as a sign that BC was making a commitment to the life sciences, Hesketh—an occasional visitor to campus in his capacity as director of EagleDocs, a program that sets up mentorships between BC's pre-med students and practicing physicians—approached the University about areas in which the two institutions might profitably collaborate. Discussions ensued—they continue, in fact. So far, they've resulted in a few joint research seminars and also in BI 403, the undergraduate course taught—organized, really—by Chiles and Hesketh, an interactive lecture series, in effect, with speakers drawn from the worlds of research and clinical practice.

Chiles calls the one-credit, pass-fail class, now in its second year, "unique in the sense that we're taking students through the process of how one does biomedical research on a particular disease, and what happens after that—how research goes from the lab bench to become a therapy." Adds Hesketh: "Some exciting things are happening in the life sciences and medicine right now, and one goal of the class is to give our students a sense of that excitement." Hesketh and Chiles teach one of the weekly class sessions each. Guest lecturers from St. Elizabeth's and BC teach the rest of the classes, focusing on biomedical breakthroughs in their areas of expertise, which range from killers like AIDS and cancer to annoyances such as sports injuries.

Of the class's 30 students, virtually all are upperclassmen, and almost all are in BC's pre-health program, which comprises 1,200 pre-med, pre-dental, and pre-veterinary undergraduates—13 percent of the student body, in all—according to Robert Wolff, a biology professor and the program's director. Most of the students in BI 403 are majoring in biology or biochemistry, though a few come from the humanities: theology, philosophy, English, math. In preparation for class, students read journal articles peppered with terms like "trisomy 12," "complex karyotypes," and "monoclonal gammopathies of undetermined significance." They're also asked to prepare three questions for the day's lecturer.

Early in the term, Hesketh, a tall, dark-haired man who comes to class in a nylon windbreaker, a white shirt, and a pastel necktie, lectured on chronic myelogenous leukemia (CML), in his words "until recently a very cruel disease." Typically diagnosed via routine blood work, it was usually managed quite easily with relatively non-toxic chemotherapy drugs for the first four to five years, during which time the patient would remain asymptomatic. However, the disease would inevitably enter an accelerated phase terminating in "blast crisis," which was essentially untreatable, and the patient would die within weeks. For the last two decades, the only certain cure was bone marrow transplantation, a technique that required a suitable donor and was itself often fatal. As for anti-CML drugs, many had substantial side effects and were unable to cure CML patients.

Then came the targeted therapy era. The personable Hesketh, aided by a set of PowerPoint slides, took the class through the last 40 years of lab research into CML, including the discovery, over several decades, that a chromosome in CML cells had an irregular gene, that the aberrant gene resulted from a fusion between two other genes, and finally that the product of the fused gene was a novel tyrosine kinase, an enzyme that deregulates the growth of cells. Based on this last discovery, researchers at Novartis, the Swiss drug firm, screened a number of compounds known to block the effects of a variety of tyrosine kinase. In time they came up with imatinib (brand name: Gleevec), a drug that has proven so nontoxic and so spectacularly effective against CML that a few years after initial trials it's become the standard treatment for the disease. (According to Hesketh, the typical time from initial trials to FDA approval of a drug is 10 years; it takes another 10 years before most newly approved drugs are widely prescribed.)

Students repeatedly interrupted Hesketh's lecture with questions, something Hesketh and Chiles have strongly encouraged. After class, a half dozen of them remained behind for another half hour, milling around Hesketh with additional queries, some closely related to the lecture topic and others germane but farther afield. Does exposure to air cause a cancer to spread? Why can't my friend who has cancer give blood? Can a single mutation cause a cancer? Does imatinib block the CML cells from reproducing?

Though he missed class that week (he was off in California, being trained to use that flow cytometer), Chiles, who tries to lead the class by example, is often the first one to pose a question to the guest speaker. A soft-spoken native Floridian—with his marathoner's build and military haircut, he brings to mind an astronaut from the early days of NASA—he interrogates the lecturers from various angles: on whether an ultra-new lab technique called fluorescence in situ hybridization (FISH) is already being used in hospitals, say, or whether clinicians who experience a needlestick-related HIV scare are more likely to suffer post-traumatic stress disorder than those who experience a needlestick-related hepatitis scare.


AS A one-credit course, BI 403 is a labor of love, for the professors and students alike. Though their particular reasons for signing up vary, students take the course because they want to. Junior Patrick Forcelli, who plans to enter an MD/Ph.D. program when he finishes up at BC, says it offers the exact mix of basic research, clinical research, and clinical practice he would like to have in his career. Senior pre-med student Peter Kim says he's taking the course for the chance to get familiar with the kinds of medical journals he will have to read as a practicing physician. (The readings are extremely challenging, he says, even for a biology major like himself, "but you're going to be stretched and challenged throughout life, whether you go into medicine or not.")

Juniors Feng Chang (pre-med) and Erin O'Brien (pre-veterinary) see the course as a chance to learn about real-world applications of the science they study in other classes. "It's much different learning about a disease from a doctor who's treated people who have it," O'Brien says.

O'Brien also finds a purity in the course's one-credit, pass-fail status. "Kids are really just there to learn," she says, with mild astonishment.

David Reich

 

David Reich is a freelance writer based in Boston.

 

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