Jeff Friedman receives Lasker Award for discovery of leptin

Jeffrey M. Friedman, who first came to Rockefeller as a postdoc in 1980 and has been head of laboratory since 1991, is one of two recipients of this year’s Albert Lasker Award for Basic Medical Research, considered the most prestigious American prize in science. The Lasker award recognized him for his “discovery of leptin, a hormone that regulates appetite and body weight, a breakthrough that opened obesity research to molecular exploration.” He is the 21st Lasker recipient associated with the university.

Prior to Dr. Friedman’s groundbreaking research, little was known about the components of the biologic system that controls weight, with many scientists questioning the very existence of such a homeostatic system. The discovery of leptin provided a genetic explanation of obesity and has challenged the popular belief that lack of willpower causes people to be obese.

“The identification of leptin by Jeff and his colleagues established a new paradigm for understanding how the body regulates weight,” says Paul Nurse, the university’s president. “It is an outstanding contribution to science and has enormous implications for improved therapies for obesity as well as other metabolic conditions for which leptin plays a crucial role.” Dr. Nurse was a recipient of the Lasker Award in 1998.

In December 1994, Dr. Friedman, who is Marilyn M. Simpson Professor and head of the Laboratory of Molecular Genetics, 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 the size of 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 addition, humans lacking leptin eat copious amounts and are massively obese. Leptin treatment of these individuals leads to substantial weight loss. The dramatic effect of leptin in these patients establishes 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 associated with resistance to leptin and provided evidence to suggest 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.
Dr. Friedman’s studies have elucidated the logic of an entirely new physiological system with direct implications for the pathophysiology of human obesity. In addition to providing scientists with a new target for treating obesity, the discovery of leptin has helped scientists develop treatments for other metabolic conditions, including certain forms of diabetes and for women with hypothalamic amenorrhea, infertility that is sometimes seen in extremely lean women.

“It is enormously gratifying and a tremendous honor to receive the Lasker Award,” says Dr. Friedman. “Discovering a previously unknown hormone and establishing its physiological function was the greatest professional pleasure that I have known. It was the result of good fortune, the talent of many previous laboratory members and the support provided by the university and the Howard Hughes Medical Institute.”

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 a medical and chief residency 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.

Dr. Friedman shares the Lasker Award with Douglas L. Coleman, emeritus scientist at The Jackson Laboratory. It was Dr. Coleman who, in the mid-1960s, first became interested in ob mice, then known as diabetes (db)mutant mice, for his studies of metabolic pathways. Dr. Coleman conducted a series of experiments that led him, in 1973, to propose the existence of a “satiety factor” (later identified as leptin) that the obese mice fail to produce and that the diabetes mice produce but do not respond to. He later wrote that his work with the obese and diabetes mice “established that the severity of the diabetes was dependent on unknown modifying genes.”

Now in its 65th year, the Lasker Award is the nation’s most distinguished honor for outstanding contributions to basic and clinical medical research. Seventy-nine Lasker laureates have received the Nobel Prize, including 30 in the last two decades. Dr. Friedman’s award was presented at a luncheon ceremony on Friday, October 1, in New York City.