Roughly 170 miles up the highway from New Haven, at the southwest tip of Cape Cod, lies Woods Hole, Mass. Nestled in this seaside village, between Eel Pond and the Atlantic coast, is the Marine Biological Laboratory (MBL), founded in 1888.
A dozen or so Yale scientists head to the MBL every summer, joining some 500 other researchers and trainees from institutions around the world who also spend their summers making use of the MBL’s unique resources and collegial environment. Discoveries by investigators at or affiliated with the MBL have produced more than 50 Nobel prizes since 1920.
Hematologist Jack Levin, MD ’57, took full advantage of what Woods Hole offers. During a research fellowship at the Johns Hopkins Hospital in the early 1960s, which had immersed him in research on platelets—the cells in blood that contribute to blood coagulation—Levin spent a summer at the MBL. Hopkins professor Frederik Bang, MD, was there working on Limulus polyphemus, the Atlantic horseshoe crab. Their collaboration led to a major scientific discovery about blood coagulation in Limulus, and also to the use of Limulus as a model organism to provide new insights into the non-hemostatic functions of human platelets. The discovery’s significance was such that a resulting product was later commercialized.
In recognition of MBL’s influence on Levin’s career and the opportunities it can offer to Yale medical students, he and his wife Francine have made a philanthropic commitment to establish the Jack and Francine Levin Yale-at-MBL Initiative for Student Research.
Second-year medical student Shobana Subramanian was selected as the first Levin Fellow in 2018 and spent this past summer at the MBL conducting research on synaptic conditions alongside Leonard Kaczmarek, PhD, professor of pharmacology and of cellular and molecular biology, and Elizabeth A. Jonas, MD, professor of medicine (endocrinology) and of neuroscience.
The MBL, an affiliate of the University of Chicago, provides access to, and training in, super-resolution and high-resolution microscopy. The necessary instrumentation is offered at no cost by such specialty manufacturers as Zeiss and Olympus. Subramanian became adept with these imaging techniques and used them to examine the structural dynamics of synapses in rodent brains, studying how the synapses’ cytoskeletal structure changes under various conditions.
Subramanian “was of course so brilliant and was able to learn this really complex super-resolution microscopy, and she learned how to process the images,” Jonas says. “She got amazing data by the end of the summer.” Jonas and Subramanian are working together to prepare their results for publication.
The Levin Fellowship will support up to five Yale medical students next summer and possibly a greater number in future years. Its aim is to enable YSM students to engage in biomedical research related to human health at the MBL and encourage them to consider careers that include original biomedical research. The Levins hope that over time their initiative will encourage the formation of a self-renewing community of YSM students and faculty at the MBL.
Kaczmarek has been a summer regular at the MBL since 1986. “When medical students hear ‘marine biology’ they initially think it may not be related to their interests,” he says, “but the fact is that the world’s top scientists go to the MBL to meet and collaborate on key questions in medical science and basic biology.”
Levin’s experience at the MBL in the 1960s epitomized this rich scientific atmosphere. During their work on Limulus, anticoagulants that he and Bang had expected to prevent coagulation had no effect on the crab’s blood, which continued to clot. In what he calls “an act of scientific desperation,” Levin prepared glassware that was free of endotoxin, which is a component of Gram-negative bacteria like E. coli. When he collected Limulus blood using the endotoxin-free glassware, the blood did not clot, and so Levin and Bang established that the blood coagulation mechanism in Limulus was sensitive to bacterial endotoxin.
This observation paved the way for the development of what is known as the Limulus amebocyte lysate (LAL) test for bacterial endotoxin, which was commercialized in the U.S. in the ’70s and makes it possible for drug companies to detect minute concentrations of potentially deadly endotoxin during the manufacturing process and thereby prevent contamination.
Levin subsequently spent more than 20 summers doing research at the MBL. He was a faculty member at the Johns Hopkins University School of Medicine for 17 years and then moved to the University of California, San Francisco School of Medicine, where he remains a member of the faculty of the departments of Laboratory Medicine and Medicine. Francine Levin was an important scientific collaborator and a co-author of many of his papers.
Jack Levin sees medical school as a formative period in which scientific exploration can yield tremendous payoffs. His advice: “One should never hesitate to tackle a new unusual project because you’re unfamiliar with it.” He hopes that future Levin Fellows will also have the experience of serendipity that he encountered at Woods Hole more than five decades ago and shaped an important component of his life’s work.