NEW YORK — Douglas L. Coleman, a Canadian-born scientist who upset scientific dogma by discovering that genes — not willpower, eating habits, or other behaviors — could cause obesity in some people, died April 16 at his home in Lamoine, Maine. He was 82.
The cause was basal cell cancer, said a spokeswoman for the Jackson Laboratory in Bar Harbor, Maine, where Dr. Coleman spent his entire research career.
Beginning in the 1960s, Dr. Coleman’s research showed that a blood-borne substance could curb hunger. In the 1990s, his findings led Jeffrey M. Friedman’s team at the Rockefeller University in Manhattan to identify the gene that produces the appetite suppressant leptin, which is released by fat cells.
For their work, Dr. Coleman and Friedman shared the prestigious Lasker Award for basic medical research in 2010. Their discoveries upended the conventional wisdom that fat cells are simply energy storage bins, and demonstrated that fat tissue is an endocrine organ required for normal development.
Scientists have learned from their research and others’ that fat produces a variety of hormones, cytokines and other chemicals in the body’s natural weight-control system.
Born in Stratford, Ontario, and influenced by his father, Leonard, who repaired radios and refrigerators for a living, Dr. Coleman spent much of his youth investigating how things worked by taking them apart. He earned a chemistry degree from McMaster University in Hamilton, Ontario, and a doctorate in biochemistry from the University of Wisconsin.
In 1958, facing poor employment prospects in academia or industry in Canada, he became a research scientist at the Jackson Laboratory, which studies mouse genetics to learn about human disease. He intended to spend a year or two there to gain experience in genetics and immunology, but stayed until he retired in 1991. After retiring, he turned a tract of land he owned into a nature preserve.
In the mid-1960s, when Margaret Dickie and Priscilla Lane of the Jackson Laboratory discovered a mutant strain of obese mice — called db, for diabetes — Dr. Coleman helped compare it with the only other known strain of obese mice, called ob. Both strains rapidly develop marked obesity. But db mice also become thirsty and diabetic, and die younger.
Dr. Coleman deduced that normal mice might have a blood-borne factor that prevented obesity. Conversely, he speculated that transferring blood-borne factors from a diabetic mouse might make a normal mouse obese.
To test his theories, he merged the blood circulation of the mutant mouse strains.
In a key experiment, he sewed the skin of a db mouse to that of a normal one and fed them the same diet. When the normal mouse died, Dr. Coleman blamed himself for being a poor surgeon. But repeat experiments produced the same fatal results. Further testing showed that the normal mouse’s blood sugar had fallen to starvation levels.
Dr. Coleman concluded that the db mice produced a blood-borne chemical so powerful that it could fatally starve the normal partners. He also found that the ob mutants did not produce the factor, but responded when db or normal mice donated it.
Additional experiments strengthened his hypothesis that some factor in the blood prevented overeating by causing satiety, but most obesity experts were not convinced. They held to the position that the cause of obesity was entirely behavioral, not physiological.
Proof required identifying the satiety factor. But experiments with that goal conducted by Dr. Coleman and a few other scientists were unsuccessful.
The conclusive proof came in the 1990s, when Friedman’s team in Manhattan used new laboratory techniques to identify the satiety factor as leptin. As fat accumulates, the team found, it exudes leptin, which binds to a molecular receptor in the hypothalamus area of the brain, quelling the desire to eat.
The findings created a surge of interest among scientists. But hopes that leptin would be a panacea for obesity have not been realized. Tests have shown that human leptin mutants are rare, but for those few, Dr. Coleman said in 2010, leptin replacement therapy has been “a godsend” in making them thinner.
Lack of leptin can lead to obesity, but a vast majority of obese people have large amounts of leptin, and for unknown reasons their bodies resist it.
Dr. Coleman was awarded a total of $1.5 million through science prizes and donated the money to charity.