Bruce Beutler: Innate Immunity and Toll-Like Receptors

Abstract

From the Dana-Farber Cancer Institute, Boston, MA (D.P.S.), and Mayo Clinic, Rochester, MN (M.A.S., R.A.K.). B ruce Alan Beutler was born in Chicago, Illinois, in 1957 but spent most of his childhood in southern California, where his father, noted hematologist Ernest Beutler (1928-2008), became the Chairman of Medicine at the City of Hope National Medical Center in Duarte, California, in 1959. Young Bruce Beutler’s first intensive exposure to biology was in his father’s laboratory on weekends and school holidays, where he learned how to purify proteins and to assay red cell enzymes such as glucose 6-phosphate dehydrogenase. In high school, he also worked with Susumu Ohno, an immunologist and geneticist at City of Hope who collaborated with his father. Beutler distinguished himself early academically, graduating from the University of California at San Diego at age 18 and from the University of Chicago’s medical school at age 23. (Ernest Beutler had graduated from the same medical school at age 21, and he suggested to his son that medical training would be a good skill “to fall back on” in case his planned scientific career foundered.) Bruce Beutler’s later scientific focus on innate immunity was in part a result of medical school clinical experience with patients with inflammatory diseases and serious infections. Beutler’s medical internship was at the University of Texas Southwestern (UT Southwestern) Medical Center at Dallas, followed by a year as a neurology resident at the same institution. In 1983, he moved to Rockefeller University in New York and to the laboratory of Anthony Cerami, where Beutler was the first to isolate murine tumor necrosis factor (TNF). He discovered that the TNF pathwaymediated some of the potent inflammatory effects of lipopolysaccharide (LPS), a bacterial macromolecule important in the clinical signs of sepsis. In 1986, he joined the faculty of UT Southwestern and also became an assistant