Edwin Krebs, 91; Nobelist was giant in study of the cell

Dr. Edwin G. Krebs, 91, the University of Washington Nobel laureate who co-discovered the mechanism by which a wide variety of processes are turned on and off within the cell and thereby led to an explosion of knowledge about how cells grow, change, divide, and die, died Dec. 21 in Seattle from progressive heart failure.

Dr. Krebs and co-laureate Edmond H. Fischer discovered that most processes within cells - ranging from fundamental metabolic reactions to the initiation of cancer - are triggered when key proteins are activated by a process called phosphorylation, in which a phosphate molecule is added to the protein.

Adding and removing the phosphate functions like a switch that turns an enzyme's activity on and off. Dr. Krebs and Fischer were the first to identify and characterize an enzyme that carries out this reaction, which is the basis of all biological function.

The process is so important that fully 1 percent of the human genome is devoted to blueprints for the production of the enzymes that carry out phosphorylation, according to the Nobel Prize citation for their work.

Their work has helped researchers understand such disparate biological problems as how the drug cyclosporine prevents rejection of transplanted organs, why certain cancers develop, how hormones affect the body, how genetic information is transcribed into proteins, and how the body mobilizes sugar to produce energy.

Defects in regulation of phosphorylation are at the heart of many disorders such as cancer, diabetes, nerve diseases, and heart conditions, and a wide variety of modern drug research is targeted at the manipulation of this process.

The pair's collaboration began in 1955 shortly after Fischer arrived at the University of Washington from his native Switzerland and learned that he and Dr. Krebs were investigating the same problem - how muscles obtain the energy to contract.

"Krebs slapped me on the back and said, 'Let's take a crack at that problem,' " Fischer recalled in 1992 when they received the Nobel Prize for physiology or medicine. Initially, they worked so closely together that if one had to leave to deliver a lecture, the other could run the experiment of the day.

While searching for that energy source, Fischer added, they "happened to stumble on a reaction that regulates the activity of a muscle enzyme. We had no idea how widespread this reaction would be... whether it would be something very unique or very unimportant."

Other scientists also had no idea, and it took a decade before they began to see the reaction's significance. Then, Nobel committee member Hans Wigzell said at the time, "it took off like a rocket. Now 10 percent of all biology articles in journals like Nature or Science deal with their field."

Dr. Krebs is survived by his wife of 64 years, Virginia; two daughters, Sally Herman and Martha Abrego; a son, Robert; four grandchildren; and six great-grandchildren.