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Dr. Edwin G. Krebs, a Nobel laureate whose codiscovery of reversible phosphorylation would ultimately affect research in the fields of heart disease, diabetes, cancer, and nerve disease, died Dec. 21 in Seattle. He was 91.

Dr. Krebs, who spent most of his career at Seattle's University of Washington School of Medicine (he joined the faculty in 1948, 2 years after the school opened), died of complications from progressive heart failure.

Although the Lansing, Iowa, native had designs on becoming a physician when he started his undergraduate studies at the University of Illinois, it was his fascination with research work that motivated him to change course after his graduation from Washington University School of Medicine in St. Louis in 1943.

After serving in the United States Navy during World War II as a medical officer, Dr. Krebs was recruited by the husband-and-wife team of Carl and Gerty Cori (1947 Nobel laureates for their research in carbohydrate metabolism and enzymes) to conduct postdoctoral research in biological chemistry at Washington University.

Dr. Krebs then went to Seattle to take a faculty position in the medical school at the University of Washington.

It was there that he met Dr. Edmond H. Fischer, starting a professional partnership and personal friendship that would last for 60 years.

The two made what Dr. Krebs would later describe as an accidental discovery in the early 1950s: that the enzyme glycogen phosphorylase, which affects the energy in muscle cells, was activated by a chemical reaction with phosphate, and deactivated by its removal. The process became known as reversible phosphorylation.

Subsequent research by Dr. Krebs and Dr. Fischer, as well as that of other scientists, led to the discovery that reversible phosphorylation affects cellular proteins, and is key in the regulation of cellular processes.

It was a breakthrough that, among other things, eventually led to the development of techniques to help prevent the rejection of transplanted organs.

In 1992, 40 years after their initial discovery, Dr. Krebs and Dr. Fischer were awarded the Nobel Prize in Physiology or Medicine.

In his autobiographical notes for the Nobel Foundation, Dr. Krebs said that as a youngster, he did not aspire to a career in science, but he liked to make gunpowder using his brother's chemistry set, and “the closest that I came to expressing an interest in biology was the maintaining of a balanced aquarium.”

In 1933, when Dr. Krebs was 15, he and his siblings moved with their newly widowed mother to Urbana, Ill.

Dr. Krebs recalled being fascinated by his undergraduate research in organic chemistry at the University of Illinois, where he spent a lot of time in the laboratory. He first heard about phosphorylase while attending medical school in St. Louis, and his research there with the Coris, which involved the study of protamine with rabbit muscle phosphorylase, sealed his destiny as a biochemist, he wrote.

His long career at the University of Washington in Seattle, where he started as an assistant professor of biochemistry, was interrupted only by a stint as founding chair of the biological chemistry department at the University of California, Davis, from 1968 to 1977, after which he returned to UW to chair the department of pharmacology.

He was a recipient of an Albert Lasker Basic Medicine Research Award, a Gairdner Foundation Award from Canada, and Columbia University's Louisa Gross Horwitz Prize, among many other honors.

Dr. Krebs is survived by his wife of 65 years, Virginia Krebs, three children, four grandchildren, and six great-grandchildren.

He also is survived by Dr. Fischer, 89, who remembered him as “the epitome of a gentleman” in a statement a few days after Krebs' death. “It marks the end of an extraordinary and wonderful friendship.”

Source DR. EDWIN G. KREBS

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