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Edward Horton, M.D., '55: Insulin insider

By Jennifer Durgin

They met over a dead body in the early 1960s. Dr. Edward Horton, then a pathology resident at Mary Hitchcock Memorial Hospital, got a call one night to perform an emergency autopsy on the victim of an automobile accident. He phoned the on-call second- year medical student to request his assistance.

"So this young medical student shows up," Horton remembers. "His name was Kenneth Quickel." Thirty years later, Dr. Quickel phoned Horton with a request of his own. Quickel was by then president of the Joslin Diabetes Center in Boston, and Horton was a prominent endocrinologist at the University of Vermont (UVM). Quickel wanted to hire Horton as medical director and director of clinical research at Joslin, but Horton resisted. He was happy chairing the Department of Medicine at UVM, where he had led some of the most influential studies in the history of diabetes research.

Horton's work centers on type II diabetes —once known as adultonset diabetes and most commonly associated with obesity. In type II, the body stops responding correctly to insulin, a pancreatic hormone that is necessary to metabolize sugar. In type I diabetes, the pancreas produces too little insulin or sometimes none at all. Both types of diabetes result in high levels of sugar in the blood and a long list of complications—including heart disease, stroke, kidney disease, eye problems, and nerve damage.

Horton was curious, he says, about "how insulin worked on the cells in the body, how exercise worked to increase glucose uptake in skeletal muscle, and what the effect of physical training was on insulin sensitivity." His interest in understanding the relationship between exercise and glucose metabolism is not surprising, given that he's been an athlete and avid skier his whole life. As an undergraduate at Dartmouth College, he belonged to both the Nordic and Alpine ski teams. Even today, in his mid-seventies, he still zips down the slopes. Some of his colleagues who have skied with him question whether he knows how to turn. "He just goes straight down!" jokes Michael Hirshman, who managed Horton's lab at UVM for many years and now works with him at Joslin.

Among Horton's most notable research projects at UVM were the Vermont Studies on Experimental Obesity in Man. "We did studies from the late 1960s up

Horton, pictured here at Boston's Joslin Diabetes Center, was on the team that confirmed 30 years ago that obesity is not only strongly correlated with diabetes, but that it can actually trigger insulin resistance and lead to the onset of type II diabetes.

and through the mid-1970s, taking normal lean volunteers, who had no history of obesity, no history of diabetes, overfeeding them, and having them gain 25% of their body weight," he explains. Other researchers had recruited obese subjects, reduced their weight, and looked for changes, but no one had done the opposite. "We were the first people," says Horton, "to show that if you overfed people, you made them insulin resistant. We fortunately didn't make anyone diabetic. We didn't cause anybody to have heart attacks or anything like that." Horton acknowledges that such a study, although acceptable at that time, probably would not be allowed today. Nevertheless, it provided important insight into diabetes.

Until Horton's work, it was not known whether insulin resistance was exclusively a genetic problem or whether it had an environmental component, too. Physicians and researchers now know that type II diabetes depends on three factors: genetic predisposition, the development of insulin resistance, and impaired insulin secretion.

In addition to running a lab and chairing the Department of Medicine at UVM, Horton also served on the editorial boards

of several journals and in leadership posts for a couple of national societies. He was president of the American Society for Clinical Nutrition in 1986 and headed the American Diabetes Association in 1990. But of all his activities, Horton most enjoyed mentoring young researchers. And they enjoyed working with him.

"I went to [the University of] Vermont because he was there," says Laurie Goodyear, who worked in Horton's lab as a Ph.D. student. "Any time there'd be visitors or people coming to work in the lab, he'd always have them to his house and really make [them] feel part of what was going on." And, she adds, Horton "really took the time to teach and help you learn."

For example, he taught Goodyear that "you can do good science and be a good researcher, but still be a good person," she says. "You don't have to be cutthroat." Goodyear admires the way Horton combines an upbeat attitude with the passion of a hard-core scientist.

All of Horton's accomplishments made him a top candidate for the Joslin positions. So Quickel "worked on me for about two years," recalls Horton. But "the clincher of the

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Jennifer Durgin is Dartmouth Medicine magazine's senior writer.

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