Bruce A. Beutler (born December 29, 1957,Chicago,Illinois, U.S.) is an American immunologist and corecipient, with French immunologistJules A. Hoffmann and Canadian immunologist and cell biologistRalph M. Steinman, of the 2011Nobel Prize for Physiology or Medicine for his “discoveries concerning the activation of theinnateimmune system.” Theinnate immune system is the body’s first line of defense against infection by potential pathogens (disease-causing entities), which includeviruses andbacteria.

Beutler was raised inArcadia, California, a small city in Los Angeles county. His father was a scientist and physician and his mother a technical writer. From a young age, Beutler was interested in nature andbiology, and, after reading American geneticist and biophysicistJames D. Watson’sMolecular Biology of the Gene (1965), he became interested in the then-burgeoning field ofmolecular biology. By age 14 Beutler could purifyproteins and characterizeenzymes, skills he learned in his father’s laboratory at the City of Hope Medical Center in Duarte (near Arcadia). The young Beutler also worked in the laboratory of Japanese-born American geneticist and evolutionary biologist Susumu Ohno, who was known for his research onsex determination and gene duplication.

Beutler was aprecocious student, skipping several grades inhigh school and graduating from theUniversity of California,San Diego, with a degree in biology at age 18. Taking his father’s advice, Beutler next decided to acquire a deeper knowledge ofpathology andpharmacology and enrolled as a medical student at theUniversity of Chicago, graduating in 1981. In 1983, following an internship ininternal medicine and a residency in neurology at theUniversity of Texas, Southwestern Medical Center atDallas, Beutler became a researcher atRockefeller University inNew York City, later joining the university’s faculty and working as a physician at the university’s hospital. In 1986 he returned to the Southwestern Medical Center, this time working as an investigator for theHoward Hughes Medical Institute and as a professor in the department of internal medicine. He transferred to the Scripps Research Institute in La Jolla, California, in 2000, where he served as a professor in the department ofimmunology and, beginning in 2007, as chairman of the department of genetics. In 2011 he announced his return to the Southwestern Medical Center.

Beutler’s Nobel Prize-winning research took place primarily between 1984 and 1998. During that time he made a series of discoveries that revealed howcells detect infection and how the innate immune system is activated in response to infection. This work began with the isolation of mousetumour necrosis factor (TNF), a protein that regulates inflammatory and immune responses. Beutler subsequently discovered and characterized properties of TNF that suggested it contributed to immune system-generatedinflammation. Usingrecombinant DNA technology, he proceeded to create molecules capable ofinhibiting TNF, which proved effective inmitigating inflammation. One of these inhibitors, etanercept (Enbrel), became widely used in the treatment of chronic inflammatory diseases, includingrheumatoid arthritis, ankylosingspondylitis, andpsoriasis.

The last of Beutler’s major breakthroughs was his discovery of thereceptor molecule forlipopolysaccharide (LPS; sometimes also called endotoxin), which he first encountered during research as an undergraduate. The discovery provided further insight into the initial steps leading to inflammation and led to his involvement in the discovery in the late 1990s ofmutations in a mousegene known asTlr4 (toll-like receptor 4) that contribute toseptic shock. Whereas the normal Tlr4 protein recognizes LPS and thereby mediates theimmune response to bacteria carrying the toxin, the mutated version results in unchecked bacterial growth, such that when the body reacts, large quantities of bacteria-destroying immune molecules are released into the bloodstream. This violent attack results in a massive release of LPS, causing tissue damage, lowblood pressure, and reducedorgan function—symptoms typical of septic shock. Much of Beutler’s later research maintained a focus on elucidating the role ofgenetics inimmunity.

Beutler was the recipient of multiple awards, including the 2004 Robert Koch Prize (shared with Hoffmann and Japanese scientist Shizuo Akira), the 2009 Albany Medical Center Prize in Medicine and Biomedical Research (shared with Steinman and American immunologist Charles A. Dinarello), and the 2011 Shaw Prize (shared with Hoffmann and Russian scientist Ruslan M. Medzhitov). Beutler was also elected to theNational Academy of Sciences (2008).