FOCUS | June 22, 2007 | CLASS SYMPOSIUM I: Class of ’82 Recounts Paradigms Passed

Three hundred million years ago, when reptiles ruled the Earth, sex was determined by an egg’s temperature as it incubated. X and Y chromosomes did not yet exist. Then a mutation arose that kept an ordinary chromosome from properly recombining with its partner. The chromosome began to lose genes. Some have predicted that the now puny swatch of genetic material will someday self-destruct.

“These are not the only sort of insults hurled at the Y chromosome,” said David Page, director of the Whitehead Institute. He was speaking at the symposium of the HMS 25th reunion class of 1982, which was held on June 7. Page has spent the last 25 years “defending the honor of this little guy in the face of innumerable threats to its character.” He was not the only speaker on a mission. Members of the HMS Class of 1982 have embarked on all manner of quests, professional and personal. They recounted their exploits, engagingly and often humorously, in the daylong symposium.

“We want to hear what touches, moves, and inspires you,” said symposium moderator, Abraham Morgentaler, HMS associate clinical professor of surgery at Beth Israel Deaconess Medical Center, at the opening of the morning session. (For an account of the afternoon session, see companion story). Several speakers pointed to former dean for medical education Daniel Federman as an important influence on their lives. Federman pointed right back. “Your class was my inspiration,” he said. Federman gave up a chairmanship at Stanford University to become dean the year the HMS Class of ’82 arrived. “I was unsure about it until the first day I met your class,” he said.

Taking to heart a long-ago remark by Federman—that “you have the ability to take what we teach you and morph it somehow”—Roger Macklis described his quest to develop an antidote to radiation poisoning. His interest was piqued in 1985 when he came across a story from the early 1930s about William Bailey, a Harvard dropout who was amassing a fortune bottling radium water—thought to have therapeutic effects—until a wealthy Yalie, Eben Byers, “drank many cases of the water and died a terrible death.” When an article Macklis wrote on the story was picked up by the media, a reporter asked whether a radiation antidote had been developed. “I had never considered the possibility,” said Macklis, chairman of radiology at the Cleveland Clinic.

Steve Gilbert
The Y chromosome gets no respect and yet it is full of surprises, said David Page. He and colleagues discovered “mirror image repeats of
previously unimaginable scale and precision” in the apparently diminutive chromosome. “It took my breath away,” Page said.

Michael Mendelsohn undertook his own odyssey in 2002 when the Women’s Health Initiative reported that hormone replacement therapy leads to higher rates of cardiovascular disease in older postmenopausal women. Yet his research, and that of others, had shown that estrogen receptors are required for healthy blood vessel function, which led to a conundrum: how can estrogen lead to both health and disease? He hit upon a solution in 2004 when he discovered evidence that older, already sclerotic blood vessels respond differently to estrogen than young healthy ones. “The answer, like lots of things in life, is timing,” said Mendelsohn, professor of medicine and physiology at Tufts University School of Medicine.

Neurologists have been in thrall to a timing hypothesis of their own, said Ramon Gilberto Gonzalez, namely that the clot-busting drug TPA can only be given during the first three hours of a stroke. In fact, some strokes may be arrested as many as nine hours after they start. On the other hand, even within the three-hour period, TPA may do more harm than good. “In stroke, we’re at a point of crisis. We’re treating all strokes as if they’re the same,” said Gonzalez, HMS professor of radiology at Massachusetts General Hospital. As a student, he had a passion for imaging and has since used MRI and other methods to reveal the physiological basis of different strokes which, in turn, has led to life-saving treatments. “We need to shift from using time as a parameter to using physiology,” he said.

Dogma had an equally contrary and positive effect in the case of Kent Ucel. He had no idea what he wanted to do when he left HMS. In 1987, during an imaging fellowship, he was told that MRI would never be good for imaging blood vessels. “That finally gave me a little guidance,” he said. Several years later, he injected contrast medium during an actual scan and got surprisingly good results. His approach was developed by others and is now routinely used to image aneurysms and other conditions.

“None of this work was grant supported—it was done as an adjunct to clinical practice,” he said. In the ’80s the pace of medicine was different. “You could really play around without worrying about reimbursement rates,” said Ucel. “I worry about the future of translational research. How can we know what we haven’t got because we gave away that time?”

—Misia Landau

top