Retrospective. Edwin G. Krebs (1918-2009).

537 PERSPECTIVES E dwin G. Krebs, a giant of biomedical science in the 20th century, died on 21 December from congestive heart failure in Seattle at the age of 91. His discovery (with Edmond H. Fischer) of protein phosphorylation as a regulatory mechanism touched all aspects of biomedical science and profoundly infl uenced therapeutic approaches now used in clinical care. Ed's life epitomizes commitment to family, excellence in research, and academic service. son of a Presbyterian minister and a schoolteacher. His father died suddenly when Ed was 15 and, at the height of the Depression, the family moved to Urbana, Illinois, where Ed earned a degree in chemistry from the University of Illinois in 1940. As an undergraduate, he became enamored with organic chemistry but eventually chose to study medicine at the Washington University School of Medicine in St. Louis, Missouri. Although the principal responsibility of a medical school during World War II was to train physicians for the armed forces, Ed also participated in medical research. After medical school and residency training at Barnes Hospital in St. Louis, he went on active duty as a medical offi cer in the Navy. Following his discharge in 1946, he returned to St. Louis and was accepted as a postdoctoral fellow in the laboratory of Nobel Laureates Carl and Gerty Cori in the Department of Biochemistry. After 2 years of postdoctoral research on the interaction of protamine (a small sperm protein) with rabbit muscle phosphorylase, Ed became so captivated with biochemistry that he never returned to clinical medicine. During his naval service, Ed enjoyed a brief visit to Puget Sound, so he happily accepted a position as assistant professor of biochemistry in the fl edgling University of Washing-ton School of Medicine in 1948. Under the visionary leadership of Hans Neurath, the Department of Biochemistry expanded in protein chemistry and enzymology, including recruitment in 1953 of Edmond Fischer, a talented and charismatic Swiss biochemist studying potato phosphorylase. Thus, a lifelong friendship and a formidable research partnership were forged. Together Ed (Krebs) and Eddy (Fischer) determined the mechanism by which adeno-sine 5′-monophosphate (AMP) served as an activator of phosphorylase b in skeletal muscle. They found that ade-nosine 5′-triphosphate (ATP) was required for phospho-rylase activation, and in an unusual experiment discovered that calcium, leaching from fi lter paper used to clarify the muscle extract, was an important cofactor. They demonstrated that phosphate was incorporated into …