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'Priests and Prophets'
By Joan Chamberlain
The teachers listened attentively in the dim light of Lipsett Amphitheater, savoring each student's funny stories, appreciative comments and earnest accounts of cracking the secrets of receptor biology and insulin resistance, told as always with the colorful slides that explain the stories of science. The students in this case were alumni of the Diabetes Branch, celebrating its 30th anniversary as part of NIDDK's Division of Intramural Research.
Some were M.D.s who had come to NIH as clinical associates in the 1960s and 1970s to pursue careers in academic medicine. Others, Ph.D.s and M.D./Ph.D.s, came as research associates eager to work with some of the world's leading diabetes investigators. These former students — now top scientists heading labs in prestigious academic centers and drug companies around the country — have gone on to pry open, at least partially, the black boxes of insulin, adrenaline and other hormone receptors as well as syndromes of hormone resistance and the genetics of type 2 diabetes. At a recent 11/2-day event, they paid homage to their mentors in "Celebrating the Diabetes Branch: A Tribute to Jesse Roth and Phil Gorden."
Roth came to NIH in 1963. Intrigued by the mysteries of hormone action, he and coworkers (Pastan, Lefkowitz, and Pricer) were the first to develop an assay for the receptor for ACTH, the pituitary hormone that stimulates the adrenal gland to secrete the hormone cortisol. Their pioneering work inspired an explosion of studies that sought to clarify how hormones bind to cell surface receptors, the first step in hormonal activation of target cells. In 1971, Roth and his co-investigators developed an assay for the insulin receptor. Since then, much of their work focused on understanding disorders of cell receptors and the complexities of insulin resistance, the hallmark of type 2 diabetes.
Roth was chief of the Diabetes Branch from 1974 to 1983 and NIDDK scientific director from 1983 until 1991, when he left NIH to join Johns Hopkins University. He is now geriatrician-in-chief at the North Shore University Hospital/Long Island Jewish Health System in New York and professor of medicine at Albert Einstein School of Medicine.
Gorden was NIDDK clinical director from 1980 to 1986 and chief of the Diabetes Branch from 1983 to 1986. After serving as NIDDK director from 1986 to 1999, he returned to clinical research as chief of the section on clinical and cellular biology in the Diabetes Branch. There he continues to study extreme forms of insulin resistance, disorders involving mutations in the insulin receptor and autoantibodies to the insulin receptor. He and co-workers have shown the effectiveness of leptin therapy in reducing insulin resistance in patients with complete lipodystrophy and extreme forms of insulin resistance.
Stellar as their own research accomplishments are, Roth and Gorden will perhaps be remembered best for the guidance and inspiration they gave the young researchers under their tutelage. They collaborated with and trained an exceptional group of scientists in the United States and overseas, who are making seminal contributions to endocrinology research.
Diabetes Branch alumni attending the event are now directors of diabetes research centers and heads of endocrine divisions in major academic centers around the world. "We've tried to impart to our own students the approaches to scientific inquiry that we learned from these great mentors and that worked so well for us," said Dr. Derek LeRoith, current chief of the Diabetes Branch and an organizer of the event.
Dr. Jean-Louis Carpentier, dean of the University of Geneva's Medical School, remembered the sign that hung behind Roth's desk: "In God We Trust," it said, "All others must show their data."
In his toast to the spirit of intramural NIH, Roth recalled seeking the advice of his predecessor, Dr. Ed Rall, when he assumed the position of NIDDK scientific director 21 years ago. "Pick excellent people, encourage them, don't tell them what to do," Rall advised. "To live up to its creative potential, an institution needs to resist the tyranny genes," Roth warned.He spoke of two approaches to scientific discovery: the priestly tradition, in which each step is an orderly, logical derivative of an earlier step, and the prophetic tradition, where science jumps ahead, coming from inspired, creative thought almost out of nowhere. "The giants come from the prophetic tradition," said Roth, who liked to remind his fellows that NIDDK's four Nobel Prize winners had worked within 150 feet of where he was standing on the 9th floor of Bldg. 10.
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