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A historical perspective on leptin

Nature Medicine volume 16, pages 1097–1099 (2010)Cite this article

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As the only child of a self-employed and largely self-taught Canadian radio-and-refrigeration repairman, I spent much of my childhood investigating how things worked by taking them apart. As I grew older, I developed a keen interest in science, and, while I was an undergraduate at McMaster University, my scientific interests converged on biology, geology and chemistry. During this time, a very dynamic biochemistry professor encouraged me to attend graduate school at the University of Wisconsin and study biochemistry. Upon receiving my PhD from the University of Wisconsin in 1958, I knew that the prospects of returning to employment in Canada were poor, and I was offered a position at the Jackson Laboratory in Bar Harbor, Maine. When I accepted this position, my plan was to remain at the Jackson Laboratory for one or two years to further my education in biology, especially genetics and immunology. As things turned out, however, the Laboratory provided a very fertile environment—with excellent colleagues and world-class mouse models of disease—and I spent my entire career in Bar Harbor. I never dreamed that I would work on obesity and diabetes or that my research would one day be deemed important enough to be considered for a major scientific award.

When I began to characterize this new mutation, I wondered whether some circulating factor might control the obese phenotype. For example, could a factor produced in a normal mouse prevent or remediate the metabolic abnormalities? Conversely, might a factor produced by the db/db mutant mouse cause obesity in a normal mouse? If this hypothetical factor were carried through the blood, I reasoned, I could test for its presence by linking the blood supplies of the various mouse strains. Fortunately, two of my colleagues at the Jackson Laboratory were using parabiosis to characterize anemia mutant mice and were pleased to instruct me in this technique. Parabiosis requires the surgical joining of two mice by skin-to-skin anastomosis from the shoulder to the pelvic girdle. Wound healing and cross circulation is established in two to three days. To avoid a vigorous immune-mediated rejection, this technique requires that the mice be on the same genetic background, an issue that would delay some desired pairings (see below). Most parabiosis experiments fail, either because there is no factor or because the factor exchanged is insufficient, owing to the lack of major blood vessels in the skin to mediate the cross-circulation.

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Figure 1
Figure 2: Summary of the parabiosis experiments.

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Acknowledgements

I thank my many mentors, especially A. Renold for continued support and guidance from the beginning of my career in the diabetes-obesity studies up to his death. I also thank the Jackson Laboratory staff in the 1960s, 1970s and 1980s, especially E. Leiter, for continued help and encouragement. Special thanks go to my family, especially my son, Tom, for editing this manuscript. My wife, Beverly, was my strongest supporter for nearly 55 years. She would have been pleased.

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  1. Douglas L. Coleman is at the Jackson Laboratory, Bar Harbor, Maine, USA.,

    Douglas L Coleman

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Correspondence to Douglas L Coleman.

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Coleman, D. A historical perspective on leptin. Nat Med 16, 1097–1099 (2010). https://doi.org/10.1038/nm1010-1097

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