UW News

December 23, 2009

University of Washington’s Dr. Edwin G. Krebs, recipient of 1992 Nobel Prize for discovering biological switch in cells, dies at 91

UW Health Sciences/UW Medicine

Dr. Edwin G. Krebs, who shared the 1992 Nobel Prize in physiology or medicine for discovering a biological regulatory mechanism in cells, died Monday, Dec. 21, in Seattle. The cause was complications from progressive heart failure. He was 91.

Dr. Krebs joined the faculty at the University of Washington School of Medicine in 1948, two years after the school opened. He spent most of his career at the UW. For decades after his retirement as professor emeritus of pharmacology and biochemistry, he walked regularly from his home to his UW lab to conduct research and meet with graduate students and postdoctoral fellows. He was an impeccable gentleman with a ready smile who liked a good story.

In the early 1950s, Dr. Krebs and his UW colleague, Dr. Edmond Fisher, were working on another scientific problem when they made an unexpected finding. They noticed that an enzyme that helps liberate energy in muscle cells (called glycogen phosphorylase) was activated by chemical reaction with phosphate, and de-activated by its removal. Adding and removing the phosphate was like turning on and off the switch that controlled the enzyme’s activity.

Their findings were published without acclaim in the mid-1950s. Many years elapsed before scientists realized from the subsequent work of Drs. Krebs and Fischer and many others that this reversible process of adding phosphate (called phosphorylation) affects countless numbers of cellular proteins, and is a key regulator of many cellular activities.

Phosphorylation/de-phosphorylation is now known to govern the function of proteins for the relaxation and contraction of muscles, for various aspects of cell metabolism, for the release and reception of hormone and nerve signals, for learning and memory, for cell shape, motility, and division, and for the transcription of genetic information and the manufacture of proteins. Problems with this key regulatory process are behind many disorders like cancer, diabetes, nerve diseases and heart conditions. Many 21st century efforts at drug discovery are directed at the phosphorylation process.

Dr. Krebs frequently pointed out that scientific curiosity, not a targeted clinical goal directed at a specific illness, led to this fundamental discovery and its role in many aspects of health and disease.

Dr. Krebs was trained as a physician. In 1943 he graduated from medical school at Washington University in St. Louis, where he learned to appreciate the rigors of his science courses and the opportunity to participate in laboratory projects. During his clinical internship, he met his future wife Deedy, a student nurse at the hospital. He did residency training in internal medicine at Barnes Hospital until 1945, when, shortly after he and Deedy were married, he was sent on active duty in the U.S. Navy as a medical officer. This was the last time he used his medical training. He said he believed he would have been happy practicing medicine, but added “This was not to be.”

After World War II ended, he went back to St. Louis with the intent of continuing his residency training and becoming an academic internist. However, physicians returning earlier from military duty had already filled local hospital positions. While waiting for an opening, he was asked by Dr. Carl Cori, who received the Nobel Prize in 1947 for elucidating carbohydrate metabolism, to do postdoctoral research in biological chemistry at Washington University in St. Louis. When his fellowship was over, Dr. Krebs was offered a position as an assistant professor at the then-new medical school in Seattle.

He said: “I jumped at the chance. I remembered when my Navy ship had docked in Puget Sound, and the many beautiful gardens I had seen.” Uncertain of his ability to succeed in research, he became licensed and registered as a physician in Washington state.

At the fledgling medical school, Dr. Krebs was motivated not only by his research interest, but also by his enjoyment of teaching medical students and of various aspects of administration. The administrative experience led to his acceptance of a post as department chair in 1969 at the University of California Davis medical school. He served as chair of biological chemistry there for eight years. In 1977, the UW offered him the chairmanship of the Department of Pharmacology. What he liked most about both positions, he said, was the responsibility of selecting good faculty members for the departments. At the UW he was also appointed an investigator in the Howard Hughes Medical Institute.

After completing his goals as department chair, Dr. Krebs re-focused his efforts on research and teaching, as well as on the training of graduate students in the biomedical sciences. He furthered his work on protein phosphorylation, carbohydrate metabolism, and cell signaling. At a late stage in his career, he also contributed to discovery of an entirely new phosphorylation pathway, called the MAP kinase pathway, which is important in many aspects of cell regulation.

In the late 1980’s, Dr. Krebs began receiving many major scientific awards for his insights into the principles governing cellular regulation and for his contributions to understanding human biology in health and disease. Among those honors were the Passano Foundation Award (1988), the Horwitz Prize (1989), the Lasker Research Award (1989), the 3M Life Sciences Award (1989) and the Welch Award in Chemistry (1991).

At age 74 he heard that he and his friend and research colleague Dr. Edmond Fischer would be honored with the 1992 Nobel Prize in physiology or medicine for the discovery they made almost 40 years before, and its ongoing influence in many scientific and biomedical fields.

This was a surprise and a delight to a man born in Lansing, Iowa, the son of a minister and a school teacher who remembered himself as “not a highly intellectual child.” The closest he came to a scientific interest as a boy was making gunpowder from materials borrowed from his older brother’s chemistry set. When his father died suddenly during the Great Depression, his mother moved 15-year old Ed and the rest of the family to Urbana, Ill., where his two older brothers were attending the University of Illinois. Despite their limited means, his mother was determined that her four children would have college educations. Dr. Krebs’ decisions about a future career hinged on whether he could earn a livelihood. He gravitated toward science, not because of an abiding interest in learning about the unknown, but because it seemed secure.

Dr. Krebs wanted a career that was concerned with people, but didn’t feel called into the ministry like his father. He studied chemistry at the University of Illinois in a self-directed program that also allowed him to take courses in math, physics, and biology. He was torn between becoming a chemist or a physician. A scholarship to medical school settled the question.

He recalled that his “first truly fun course” was organic chemistry. He was permitted to spend unlimited time in the laboratory. His mentors were biomedical scientists who introduced him to research, for which, he said in his Nobel Prize autobiography, he was always grateful.

In the same autobiographical sketch, he told how important his children and grandchildren and other family members were to him. He singled out his wife as a constant source of help to him in his career and in his life. He mentioned that they shared in all of the major decisions in their lives.

Krebs is survived by his wife of 64 years, Virginia “Deedy” Krebs; three children, Sally Herman, Robert Krebs and Martha Abrego and their spouses, Dan Herman and Phil Abrego; grandchildren Emily Herman Kelly, Poppy Abrego Patterson, Kipp Abrego and Taylor Abrego; and six great-grandchildren.

Plans for a memorial service are pending.

Remembrances may be made through gifts to the Edwin G. Krebs-Hilma Speights Professorship in Cell Signaling and Cancer Biology at the University of Washington. Checks can be made payable to the “UW Foundation,” and sent to:

UW Medicine Advancement
815 Mercer Street C-5, Box 358045
Seattle, WA 98109

Please indicate that your gift is in memory of Dr. Edwin Krebs.