Three researchers – from Canada, the U.S. and Denmark – are among this year’s winners of the Canada Gairdner International Award for work that has led to major advances in the treatment of Type 2 diabetes, obesity and other metabolic disorders.
On Wednesday, Daniel Drucker, a clinician-scientist at the Lunenfeld-Tanenbaum Research Institute at Toronto’s Mount Sinai Hospital, was named a co-winner along with Joel Habener, a Harvard professor and endocrinologist at Massachusetts General Hospital, and Jens Holst, a professor and research director at the University of Copenhagen.
Between them, the trio discovered and studied a pair of intestinal hormones that are crucial for regulating insulin as well as the body’s ability to absorb nourishment.
The award, open to researchers around the globe, is widely regarded as Canada’s most prestigious medical science prize. It was announced on Wednesday by Toronto’s Gairdner Foundation along with two associated honours, the Wightman Award for excellence and leadership in Canadian health research and the John Dirks Award for advancing global health.
Dr. Drucker, who is a professor at the University of Toronto, is the first Canadian to be honoured with an international Gairdner award in four years.
His award this year carries additional historic resonance because of its connection to insulin. The substance was first discovered and employed to treat diabetes just a short walk from where Dr. Drucker works today. The breakthrough led to Canada’s first Nobel Prize, awarded to Sir Frederick Banting and John Macleod 100 years ago.
“It’s a classic example of serendipity,” Dr. Drucker said, speaking of the chain of events that set him on his own path of discovery.
Born in Montreal, Dr. Drucker attended high school in Ottawa and did his medical training at Johns Hopkins University and the University of Toronto. While looking for a research opportunity, he became aware of Dr. Habener’s lab in Boston and accepted a fellowship there in 1984. His goal was to work on a project related to his principal interest, the thyroid gland.
“But when I got there, there was no room on the project, they were winding it down,” Dr. Drucker said. Reluctantly at first, he began working on another initiative related to glucagon, a protein produced in the pancreas that opposes the action of insulin. Together, insulin and glucagon work to keep blood sugar levels balanced.
Dr. Habener, an early pioneer of the use of recombinant DNA technology, had already identified the gene that produces glucagon, after receiving an unlikely assist from anglerfish. The pancreas of the toothy fish is different from that of humans in that its hormone-producing cells are clustered together and easier to extract and work with.
“We got the notion that the fish would be a good model to study,” said Dr. Habener, who added that he was able to obtain plenty of specimens from commercial fishermen in Boston harbour.
The studies that Dr. Drucker conducted showed that the same gene that makes glucagon in the pancreas makes two other hormones in the intestine, dubbed “glucagon-like proteins,” or simply GLP-1 and GLP-2. He was able to show the biological role that GLP-1 plays in stimulating insulin secretion.
In Copenhagen, Dr. Holst had independently arrived at a similar result through an elegant series of biochemistry experiments. The two teams published their findings within two weeks of each other in February, 1987.
The significance of the discovery was apparent once it was clear that the power of GLP-1 depended on blood sugar levels. It would switch off when no longer needed, which in turn prevented the pancreas from going overboard and producing too much insulin. The finely tuned system suggested that a drug that could imitate the effect of the hormone might be useful as a treatment for Type 2 diabetes.
“That’s when the excitement really started,” said Dr. Holst, who also demonstrated that GLP-1 also served as a signalling hormone that could reduce appetite and treat patients struggling with obesity.
Dr. Drucker returned to Toronto and continued working on GLP-2, which turned out to be important for maintaining the cells in the lining of the intestine that absorb food. The finding led to a drug based on GLP-2 used to treat short bowel syndrome, a development that reduced the need for intravenous feeding tubes in those who are born with the disorder or acquire it when part of their intestine is damaged or removed during surgery.
“There’s no greater feeling or reward for physicians than to know they’re helping people,” Dr. Drucker said.
Sir Stephen O’Rahilly, who directs the Wellcome-MRC Institute of Metabolic Science at Cambridge University in the U.K., said the full impact of the award-winning work is still to come in the form of better and more effective therapies.
“It’s a great story, and it shows the way science works,” he said. “It takes time for the basic research to bubble up through the system with slow, patient, detailed work. And eventually things that have a human benefit emerge.”
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