John B. Hibbs Jr. is an American physician-scientist and educator. He is Distinguished Professor Emeritus in the Department of Medicine at the University of Utah. He is known for the discovery of the direct synthesis of L-citrulline and nitrogen oxides from L-arginine by murine activated macrophages, published in January 1987. This reaction was inhibited strongly by the non-toxic NG-monomethyl-L-arginine molecule. These observations provided the biochemical tools needed to establish the new and unexpected field of nitric oxide biochemistry and made possible its rapid initial progress in cardiovascular and neural physiology. In 1988, he directly measured the gas nitric oxide, simultaneously with Michael Marletta, showing that it is the proximal nitrogen oxide produced during the biological oxidation of a terminal guanidino nitrogen atom of L-arginine.
Hibbs joined the University of Utah School of Medicine faculty as an Assistant Professor in 1971. He rose through the academic ranks to become a Distinguished Professor in 1999. He served as Chief of the Infectious Diseases Division of the University affiliated Veterans Affairs Medical Center from 1971 to 1989 and Chief of Infectious Diseases Division of the University of UtahHealth Sciences Center from 1989 to 2011.
Research
In 1964, as a medical officer in the U.S. Army, Hibbs participated in the Bolivian hemorrhagic fever outbreak investigation directed by Karl Johnson. This experience stimulated his interest in infectious diseases and in research. As a result, after completing training in Internal Medicine at the University of Oregon, he began Infectious Diseases Fellowship training at Stanford University in 1969. The research portion of the training was in the laboratory of Jack Remington. There he showed that mice with chronic infection with intracellular protozoan parasites, which act as a persistent stimulus for cytokine production and macrophage activation, had increased resistance to malignant cell growth. In vitro activated macrophages from these mice expressed nonspecific cytotoxicity for malignant cells. Prior to these experiments, macrophage mediated cytotoxicity for malignant cells was thought to be due only to immunologically specific mechanisms. After completing Infectious Diseases training in 1971, Hibbs joined the Infectious Diseases Division faculty at the University of Utah. There he began a search for a biochemical explanation for nonspecific cytotoxicity mediated by activated macrophages. These experiments led to the discovery of the synthesis of L-citrulline and nitrogen oxides, including nitric oxide per se, from L-arginine, by mouse activated macrophages. He then, with colleagues, described a pattern of metabolic inhibition caused by nitric oxide in mammalian target cells and the involvement of nitric oxide in mouse activated macrophage antimicrobial activity. This work established nitric oxide as an important component of the inflammatory response. He also showed that humans receiving the cytokine interleukin-2 for treatment of refractory malignant disease produced high levels of nitric oxide.Hibbs JB Jr., Westenfelder C., Taintor RR. et al., 1992. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J. Clin. Invest. 89: 867-877. https://doi.org/10.1172/JCI115666 More recently he discovered extracellular energy producing metabolism carried out in highly diluted lysates of human peripheral blood leukocytes.
The Biology of Nitric Oxide 1. Physiological and Clinical Aspects. Edited by S. Moncada, M.A. Marletta, J.B. Hibbs Jr, and E.A. Higgs. Portland Press. London and Chapel Hill, 1992,
The Biology of Nitric Oxide 2. Enzymology, Biochemistry, and Immunology. Edited by S. Moncada, M.A. Marletta, J.B. Hibbs Jr, and E.A. Higgs. Portland Press. London and Chapel Hill, 1992.
