Edwin G. Krebs - Chemists, Timeline and Facts

Edwin Gerhard Krebs was born in June 6, 1918, in Lansing, Iowa. His father, William Carl Krebs, was a Presbyterian minister, while his mother, Louise Helen (Stegeman) Krebs, was a teacher before her marriage. Edwin was third of his parents’ four children.

Because of his father’s profession, they were required to move around a lot. Finally, in and around 1924, they settled in Greenville, Illinois. The town had good schools and Edwin enjoyed his life immensely.

He was a good student and also liked hiking, fishing, stamp collecting. Some time now, he made a ham radio just to keep in touch with a friend who had moved to Chicago.

In 1933, William Carl Krebs, died unexpectedly. At that time, Edwin was studying in the first year of the high school and his elder brothers were at the University of Illinois. To cut cost, his mother moved the family to Urbana and Edwin was enrolled at Urbana High School.

Financially, it was a hard time. To make the ends meet, Edwin, like his brothers, took up part time job. At the same time, he began contemplating about his future. Both chemistry and medicine appealed to him because he believed it would be easier to earn his living with them.

In 1936, he entered University of Illinois at Urbana-Champaign with chemistry, physics and biology. By the fourth year, he narrowed his choice to organic chemistry or medicine. This was also the year when he had his first brush with scientific research, an experience he enjoyed very much.

In 1940, after receiving his BS degree from University of Illinois, Edwin Krebs entered Washington University School of Medicine in St. Louis on a scholarship. Here, he was not only trained to become a doctor, but was also introduced to medical research.

Edwin G. Krebs earned his medical degree in 1943 and joined Barnes Hospital, also in St. Louis, for 18-month residency. On its completion, he joined the US Navy as a medical officer on active duty as part of the war service.

In 1946, Krebs was discharged from Navy. Although he wanted to join hospital duty he did not get the scope immediately. Subsequently, he joined Washington University at St. Louis and began to work on the interaction of protamine with rabbit muscle phosphorylase under Carl and Gerty Cori, as postdoctoral fellow.

Krebs’ postdoctoral period came to an end in 1948. By that time he had made up his mind to continue research work. Therefore, when the offer came, he happily joined the University of Washington, Seattle as an Assistant Professor at the Department of Biochemistry.

He first started working on DPNH-X, a derivative of NADH. But when in 1953, Edmond H. Fischer arrived at the university ‘the two Eds’ started working on the enzymology of phosphorylase. As the emphasis in the department was on protein chemistry and enzymology, it provided an excellent environment for their work.

It is to be remembered that before he came here, Krebs had worked with the Coris on phosphorylase on rabbit muscle phosphorylase. There they had found that, for the phosphorylase to function, AMP had to serve as some kind of co-factor.

Before he came here, Fischer had also been working on purification of potato phosphorylase at the University of Geneva with Prof. Kurt H. Meyer, Head of the Department of Organic Chemistry. However, there they did not require AMP.

Now, both Krebs and Fischer knew that every enzyme used the same co-enzyme to catalyze the same kind of reactions. Therefore, it was not possible that muscle phosphorylase would require AMP as a co-factor but not potato phosphorylase. They now decided to solve this dilemma.

However, they failed in their mission; but in the process they found that muscle phosphorylase was regulated by phosphorylation-dephosphorylation and that the process, known as reversible protein phosphorylation, regulates various cellular processes. Malfunctioning of this process leads to many fatal diseases.

In 1957, Krebs was made a full professor at the University of Washington. Some time now, he and Fischer began to work separately on different areas of phosphorylation. Krebs’ team began to concentrate on the molecular mechanism of action of cyclic AMP in promoting the phosphorylase b to a reaction.

In 1968, Krebs left University of Washington, Seattle to join University of California. At the University of California, Krebs became the founding chairman of the Department of Biochemistry. Here he recruited the best faculty and proved that he was equally good in administration.

Sometime now, he also became a member of the editorial board of the ‘Journal of Biological Chemistry and in 1972, he became one of its associate editors. He remained in this position till 1992.

Meanwhile in 1977, Krebs returned to the University of Washington, Seattle, as Chairman of the Department of Pharmacology. Concurrently, he was also appointed an investigator for the Howard Hughes Medical Institute.

In 1983, after he had rebuilt the department, Krebs refocused on research and training of junior scientists. He now started solving new problems in signal transduction. His team contributed significantly to the analysis of phosphotyrosine signaling events. His findings later helped to discover a new phosphorylation cascade - the MAP kinase pathway.

Krebs also had number of books to his credit. ‘The Enzymes’ (1970, with Paul D. Boyer and D S Sigman), ‘Protein Phosphorylation’ (1981, with Ora M Rosen) and ‘Control by Phosphorylation’ (1986, with Paul D. Boyer) are the most significant of them.

Krebs is best known for his work on reversible protein phosphorylation, a biochemical mechanism that regulates the activities of the cells. He began his studies with Edmond H. Fischer to find out how muscles get their energy from glycogen and what role AMP had in phosphorylation.

By the middle of the 1950s they discovered that phosphorylation and dephosphorylation of proteins are regulated by enzymes. A kinase enzyme called protein kinase moves a phosphate group from adenosine triphosphate (ATP) to a protein. This activates the protein and it starts taking part in the biological reactions.

When the job is done, a protein phosphatase deactivates the protein by removing the phosphate. The process regulates a number of biological functions such as mobilization of glucose from glycogen, prevention of transplant rejection, development of a cancer like chronic myeloid leukemia etc.

In 1989, Krebs was awarded Louisa Gross Horwitz Prize for Biology or Biochemistry by Columbia University and Albert Lasker Award for Basic Medical Research by Laskar Foundation.

While working at the Barnes Hospital, Edwin Krebs met Virginia Deedy French, a student nurse at Washington University. They got married on March 10, 1945. Although she earned her degree, she forsook her career to support her husband and was a constant source of inspiration.

Edwin and Deedy remained together till his death in 2007. They had three children, Sally Herman, Robert Krebs and Martha Abrego.

Krebs led a very active life till he was almost eighty years old. In 1997, he finally closed his laboratory at the University of Washington. Even after that he attended research seminars on regular basis and was keenly interested in latest development in the field.

Krebs died on December 21, 2009 from progressive heart failure at a chronic care facility in Seattle Washington. He was survived by his wife, three children, and five grandchildren.