Prior to Jeffrey M. Friedman’s groundbreaking research, little was known about the components of the biologic system that controls weight, and many scientists questioned the very existence of such a system. Dr. Friedman’s 1994 identification of the weight- and appetite-regulating hormone leptin, however, provided a genetic explanation of obesity and has challenged the popular belief that lack of willpower causes people to be obese. For his discovery of leptin, which ultimately opened obesity research to molecular exploration, Dr. Friedman was awarded the 2010 Albert Lasker Basic Medical Research Award.
In December 1994, Dr. Friedman and his colleagues published a landmark paper in the journal Nature, in which they identified a gene in mice and humans called obese (ob) that codes for a hormone he later named leptin, after the Greek word leptos, for thin. Dr. Friedman and colleagues showed that leptin is a hormonal signal made by the body’s fat cells that regulates food intake and energy expenditure. Leptin has powerful effects on reproduction, metabolism, other endocrine systems and even immune function.
Mice that lack ob, and thus do not produce leptin, are massively obese, weighing as much as three times more than their normal littermates. Dr. Friedman showed that after normal and ob-deficient mice are injected with synthetic leptin, they are more active and lose weight.
In humans, the lack of leptin has been linked to overeating, with people who do not produce enough leptin often eating copious amounts and becoming massively obese. Dr. Friedman has treated some leptin-deficient obese individuals with leptin, and has shown it can lead to massive weight loss. The dramatic effect of leptin in these patients has established a key role for this hormone in human physiology.
However, the majority of obese people have very high levels of leptin circulating in their blood. Dr. Friedman’s lab went on to show that high leptin levels are often associated with resistance to leptin, and they uncovered evidence which suggests that animals destined to be obese increase their production of leptin to satisfy a higher set point for weight. These observations have reframed views on the pathogenesis of obesity and suggested that the development of approaches to improve leptin response in resistant individuals could provide new treatments for obesity.
With the discovery of leptin and Friedman’s subsequent studies, the logic of an entirely new physiological system has been established with direct implications for the pathophysiology of human obesity. In addition to providing scientists with a new target for treating obesity, the discovery has helped scientists develop treatments for other metabolic conditions, such as diabetes, and for women with hypothalamic amenorrhea.
Dr. Friedman graduated from Rensselaer Polytechnic Institute and, in 1977 at the age of 22, received his M.D. from Albany Medical College of Union University. After completing two residencies at Albany Medical Center Hospital, Dr. Friedman came to Rockefeller as a postgraduate fellow and associate physician in 1980. In 1986 he received his Ph.D., working in the lab of James E. Darnell Jr., and was appointed assistant professor. In 1991 he was named head of laboratory, and in 1995 he was promoted to professor. He was appointed the Marilyn M. Simpson Professor in 1999. He has been an investigator at the Howard Hughes Medical Institute since 1986, and he directs the university’s Starr Center for Human Genetics.
A member of the National Academy of Sciences and its Institute of Medicine, Dr. Friedman’s previous honors include the 2009 Shaw Prize in Life Science and Medicine, 14th annual Keio Medical Science Prize, the 2007 Jessie Stevenson Kovalenko Medal, the sixth Danone International Prize for Nutrition, the 2004 Gairdner Foundation International Award and the 2004 Passano Foundation Award.