Albert Lasker
Basic Medical Research Award

Acceptance Remarks by Douglas Coleman

I am overwhelmed and humbled to be selected as a co-winner of the 2010 Lasker Basic Medical Research Award. I have always viewed the Lasker as one of the most esteemed biomedical awards, and it is with great pride that I accept this honor.

As the only son of parents who had little formal education, I was encouraged to excel in school. During undergraduate studies at McMaster University, a very dynamic professor taught me the rudiments of biochemistry and an appreciation of the scientific method. With his enthusiastic support, I entered graduate school at the University of Wisconsin and received my Ph.D. in 1958. Rather than starting postdoctoral studies or a career in academia or industry, I became a Research Scientist at The Jackson Laboratory. This decision was transformative: The Jackson Laboratory had fascinating genetic disease models, interactive colleagues, and Acadia National Park as a backyard.

Initially, I had no intention of studying the diabetes/obesity syndrome, but in 1965 a spontaneous mouse mutation was discovered and I began research that would consume much of my scientific thought for the better part of three decades. This new mutant was similar to a previously characterized obese mutant, except that it displayed severe life-shortening diabetes. Operating on the hypothesis that a blood-borne factor might regulate the severity of diabetes in these mutants, I used a technique called parabiosis to mix and match mutant and wildtype blood supplies. Based on these experiments, I concluded that the diabetes mutant over-produced, but did not respond to, a blood-borne "satiety factor," while the obese mutant recognized this factor, but was unable to produce it. Subsequent studies suggested that adipocytes synthesized this factor and the hypothalamus contained its receptor. The scientific community did not readily accept these conclusions because obesity was considered strictly a behavioral problem, not a physiological problem.

Definitive proof of my conclusions required isolating the satiety factor — a feat that resisted rigorous experimentation. Finally, in 1994 Jeffrey Friedman succeeded in identifying the obese gene and demonstrated that it encoded the powerful hormone leptin. With the subsequent cloning of the leptin receptor, the field exploded. Essentially all of my predictions were verified: the obese mutant lacks active leptin, which is normally produced in adipose tissue; the diabetes mutant lacks an active leptin receptor, which is normally expressed in the hypothalamus. With these findings, two long-standing misconceptions were definitively laid to rest: obesity was not merely a behavioral problem but rather had a significant physiological component; and adipose tissue was not merely a fat-storage site but rather an important endocrine organ.

In closing, special thanks go to my family who were not only supportive of my work but a welcome diversion from it. My wife for nearly 55 years, Beverly, merits my strongest gratitude because she, more than anyone, built the love, support and understanding that was the foundation on which I functioned. She would have been delighted to share in the accolades from this most prestigious award.