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Rudolph Leibel

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Leibel's co-discovery at Rockefeller University of the hormone leptin, and cloning of the leptin and leptin receptor genes, has had a major role in the area of understanding human obesity. Leibel has published hundreds of scientific papers on obesity, and has authored and co-authored 70 scientific papers on the topic of leptin specifically.

Research on the "obesity gene": Leptin

Having encountered obesity in children as a medical doctor in the 1970s, Leibel believed that biology played a stronger role than "willpower" in human obesity and joined Jules Hirsch in theorizing about the psychobiology of obesity - a belief that body weight was the result of complex interactions between genes and the environment rather than a simple matter of free will. In 1978, based on his theory that genetics played a major role in determining body weight regulation in humans, Leibel left Harvard University to join Jules Hirsch at Rockefeller University with the goal of finding the factor that drove eating. In collaboration with Douglas Coleman, Leibel determined that a mutation of the ob gene resulted in mice that were unable to manufacture a working satiety-signaling protein and that a db mutation resulted in mice that had the protein, but lacked the ability to detect the signal.

Leibel and Hirsch began a series of scientific investigations aimed at determining any connections between genetics and obesity. Over the course of eight years, Leibel's work ranged from studies of glycerol to the development of a radioisotopic technique for analysis of free fatty acid re-esterification in human adipose tissue to the metabolic characterization of obesity. After concluding that the tools of molecular genetics were key to moving his research forward and finding the obesity gene, Leibel initiated a collaboration with Rockefeller University faculty member and molecular biologist Jeffrey Friedman in 1986, and began to assemble a team of researchers including Streamson C. Chua, Nathan Bahary, Don Siegel, Yiying Zhang, Ricardo Proenca and others. Leibel obtained ongoing funding from the National Institutes of Health and other sources, allowing the team to develop and utilize new techniques in their research such as chromosome microdissection.

As their research progressed, Leibel at al published a series of papers in scientific journals that reported the mapping of the ob gene, the first of these being a 1990 paper in World Review of Nutrition and Dietetics entitled "Genetic Variation and Nutrition in Obesity: Approaches to the Molecular Genetics of Obesity", and another 1990 paper in the Proceedings of the National Academy of Sciences entitled "Molecular Mapping of the Mouse db Mutation".

Among numerous additional papers published on the topic between 1991 and 1994, Leibel was the lead author of a paper entitled "Strategies for the Molecular Genetic Analysis of Obesity in Humans" in 1993. In 1994, Friedman published a scientific paper that discovered and isolated the ob gene. Leibel was not a co-author of this paper, however, although Leibel was acknowledged in fine print at the end of the paper as an "important contributor to the early phases of this work". Leibel was bitter about not being included as a full co-author and being relegated to a section of special thanks that included Friedman's fiancée, who was not a scientist; various theories surrounding the omission of Leibel as co-author of this important paper are presented in Ellen Ruppel Shell's 2002 book The Hungry Gene.

Leibel continued to author and co-author numerous papers on the connection between genetics and obesity. In 1997, he published a paper in the scientific journal Nature Genetics titled "And Finally, Genes for Human Obesity". Leibel and others involved with the discovery of the obesity gene eventually left Rockefeller University to establish a research base at Columbia University where Leibel became the head of the Division of Molecular Genetics.

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