Edwin Krebs

Edwin G. Krebs
Born	Edwin Gerhard Krebs 6 6, 1918
Birthplace	Lansing, Iowa, United States
Died	Template:Death date and age Seattle, Washington, United States
Nationality	American
Occupation	Biochemist
Known for	Discovery of reversible protein phosphorylation
Education	M.D., Washington University School of Medicine
Awards	Nobel Prize in Physiology or Medicine (1992)

Edwin Gerhard Krebs (June 6, 1918 – December 21, 2009) was an American biochemist who, together with his longtime colleague Edmond H. Fischer, discovered the process of reversible protein phosphorylation — a fundamental biological regulatory mechanism that governs a vast array of cellular activities, from muscle contraction to cell division and growth. For this discovery, Krebs and Fischer shared the 1992 Nobel Prize in Physiology or Medicine. A soft-spoken Midwesterner who spent much of his career at the University of Washington, Krebs helped illuminate one of the most pervasive and important regulatory processes in biology — a process now understood to play a role in cancer, diabetes, and numerous other diseases. His work, which began with the study of how glycogen is broken down in muscle cells, opened an entire field of research that continues to shape modern medicine and pharmacology. Krebs died on December 21, 2009, in Seattle, Washington, at the age of 91, from progressive heart failure.

Early Life

Edwin Gerhard Krebs was born on June 6, 1918, in Lansing, Iowa, a small town situated along the Mississippi River in the northeastern corner of the state. He grew up in a modest Midwestern environment. Krebs has been described as a "soft-spoken, understated Midwesterner" throughout his life, reflecting the values and temperament of his upbringing.

Details of his childhood, family composition, and formative influences in Lansing are recorded in limited detail in the available sources. What is known is that Krebs developed an early interest in science, which would eventually lead him to pursue a career in medicine and biochemistry. His rural Iowa roots remained a defining characteristic of his personality, and colleagues and acquaintances frequently noted his modesty and unassuming nature, traits that persisted even after he achieved the highest honors in science.

The small-town setting of Lansing, with its close-knit community along the bluffs of the Mississippi, provided the backdrop for Krebs's early years before he departed for higher education. His journey from this quiet river town to the highest echelons of biomedical research would come to represent a remarkable trajectory in American science.

Education

Edwin Krebs pursued his medical education at Washington University School of Medicine in St. Louis, Missouri, where he earned his M.D. degree. Washington University's medical school was one of the leading institutions for biomedical training in the United States, and the education Krebs received there provided the foundation for his subsequent career in biochemistry and enzymology. It was during and after his medical training that Krebs became increasingly drawn to laboratory research rather than clinical practice, a pivot that would define the rest of his professional life.

His medical training gave him a deep understanding of human physiology that informed his later biochemical research. The transition from clinical medicine to basic science research was not uncommon among physician-scientists of his generation, and Krebs would go on to apply his medical knowledge to fundamental questions about how cells regulate their most basic functions.

Career

Early Research and Collaboration with Edmond Fischer

Krebs's career in biochemistry took shape through his long and productive collaboration with Edmond H. Fischer, a Swiss-born American biochemist. The two scientists began working together at the University of Washington in Seattle, where both held faculty positions in the Department of Biochemistry. Their partnership, which would span decades, proved to be one of the most fruitful collaborations in the history of modern biology.

The initial focus of their research was the enzyme glycogen phosphorylase, which is responsible for breaking down glycogen — the stored form of sugar — in muscle cells to release glucose for energy. This process was already known to be important for muscle contraction and energy metabolism, but the precise mechanism by which the enzyme was activated and deactivated within cells remained unclear. Krebs and Fischer set out to understand how the cell controlled this critical metabolic switch.

Discovery of Reversible Protein Phosphorylation

The central discovery for which Krebs and Fischer received the Nobel Prize was the identification of reversible protein phosphorylation as a fundamental mechanism of cellular regulation. Through their research on glycogen phosphorylase, Krebs and Fischer demonstrated that the enzyme could be converted from an inactive form to an active form through the addition of a phosphate group — a process catalyzed by another enzyme they identified as phosphorylase kinase. The reverse process, in which a phosphate group is removed to deactivate the enzyme, is carried out by enzymes known as phosphatases.

This process — the addition (phosphorylation) and removal (dephosphorylation) of phosphate groups on proteins — turned out to be far more than a mechanism specific to glycogen metabolism. As the Nobel Prize press release stated, the 1992 Nobel Prize in Physiology or Medicine was awarded to the two American biochemists for this discovery of a fundamental regulatory mechanism. Krebs and Fischer had uncovered what amounts to a universal biological switch: a way for cells to turn proteins on and off in response to signals from hormones, growth factors, and other stimuli.

The implications of this discovery were enormous. Reversible protein phosphorylation is now known to regulate an extraordinary range of cellular processes, including muscle contraction, the shape and division of cells, gene expression, immune responses, and neuronal signaling. As The New York Times noted in its obituary, Krebs shared a Nobel Prize "for discovering a crucial bodily process that helps govern the movement of muscles, the shape and division" of cells, and many other fundamental functions.

Protein Kinases and the Expanding Field

Following their initial discovery, Krebs and Fischer continued to explore the broader significance of protein phosphorylation. One of the key contributions of their work was the identification and characterization of protein kinases — the enzymes that attach phosphate groups to proteins. The human genome is now known to encode hundreds of different protein kinases, each targeting specific proteins in specific signaling pathways. This vast family of enzymes, whose importance was first illuminated by the work of Krebs and Fischer, has become one of the most intensively studied groups of molecules in modern biology and pharmacology.

Krebs's research helped establish that protein kinases do not operate in isolation but rather function as components of complex signaling cascades. A single extracellular signal — such as a hormone binding to a receptor on the cell surface — can trigger a chain of phosphorylation events inside the cell, with one kinase activating another in a carefully orchestrated sequence. This cascade architecture allows cells to amplify signals and coordinate multiple responses simultaneously.

The discovery of this "biological switch," as the University of Washington described it, had profound implications for understanding disease. Abnormal protein phosphorylation has been implicated in a wide range of diseases, including various forms of cancer, diabetes, inflammatory conditions, and neurodegenerative disorders. Many modern drugs, including numerous cancer therapeutics, work by targeting specific protein kinases — a therapeutic strategy that traces directly back to the foundational work of Krebs and Fischer.

Career at the University of Washington

The University of Washington in Seattle served as the primary institutional home for much of Krebs's career. He was a member of the faculty in the Department of Biochemistry at the UW School of Medicine, and the university became closely associated with his scientific achievements.

The University of Washington recognized Krebs as one of its most distinguished faculty members. In its announcement of his death, the university described him as having discovered "a biological regulatory mechanism in cells" and highlighted the significance of his Nobel Prize-winning work. The UW's Department of Biochemistry, bolstered by the presence of both Krebs and Fischer, became one of the leading centers for research in enzyme regulation and cell signaling in the world.

Krebs also held positions at other institutions during his career, including a period at the University of California, Davis, but it was at the University of Washington that he carried out the bulk of his Nobel Prize-winning research and spent the most productive years of his scientific life.

Distinction from Hans Krebs

One recurring source of confusion throughout Edwin Krebs's career was the similarity of his surname to that of Hans Krebs, the German-born British biochemist who won the Nobel Prize in Physiology or Medicine in 1953 for his discovery of the citric acid cycle (also known as the Krebs cycle). Despite sharing a surname and working in related areas of biochemistry, the two scientists were not related. Edwin Krebs was known to express occasional frustration at being confused with his more famous namesake, particularly since both were Nobel laureates in the same field. As one University of Washington profile noted, this mix-up was one of the few things that "gets his goat."

Personal Life

Edwin Krebs was known for his modest and unassuming personality, traits frequently attributed to his Midwestern upbringing in Lansing, Iowa. He spent much of his adult life in Seattle, Washington, where he was affiliated with the University of Washington for decades.

Krebs died on Monday, December 21, 2009, at the age of 91. The cause of death was progressive heart failure, according to The Lancet. His death was announced by the University of Washington on December 23, 2009, and was widely reported in the scientific community and major news outlets, including The New York Times and The Lancet.

The University of Washington Magazine published a tribute to Krebs in its March 2010 issue, summarizing his life and contributions to science. His colleague and co-laureate Edmond Fischer survived him by more than a decade, dying in 2021 at the age of 101.

Recognition

Nobel Prize in Physiology or Medicine (1992)

The most significant recognition of Edwin Krebs's scientific contributions was the 1992 Nobel Prize in Physiology or Medicine, which he shared equally with Edmond H. Fischer. The prize was awarded by the Nobel Assembly at the Karolinska Institute for their discovery of reversible protein phosphorylation as a biological regulatory mechanism.

The Nobel Prize press release described the work of Krebs and Fischer as having revealed a fundamental mechanism by which cells regulate their activities. The discovery was recognized not only for its intrinsic scientific importance but also for the enormous downstream impact it had on understanding disease processes and developing new therapeutic strategies. By the time the prize was awarded in 1992, the field of protein phosphorylation that Krebs and Fischer had founded had grown into one of the largest and most active areas of biomedical research in the world.

The award placed Krebs among a select group of scientists at the University of Washington to have received the Nobel Prize, reinforcing the university's reputation as a center of excellence in the biomedical sciences.

Other Honors

Krebs received recognition from the University of Washington throughout his career and after his death. The university publicly honored him as one of its most distinguished scientists, and his contributions were memorialized in university publications. His obituary in The Lancet, one of the world's leading medical journals, described him as a "Nobel Prize-winning biochemist who discovered reversible protein phosphorylation," summarizing the significance of his life's work in a single phrase.

Legacy

Edwin Krebs's discovery of reversible protein phosphorylation, made in collaboration with Edmond Fischer, is considered one of the most important findings in the history of biochemistry and cell biology. The process they uncovered is now recognized as a ubiquitous regulatory mechanism operating in virtually every cell of every organism. It is estimated that approximately one-third of all proteins in the human body are regulated by phosphorylation at some point during their functional life, underscoring the pervasiveness of the mechanism that Krebs and Fischer first described.

The practical consequences of this discovery have been far-reaching. The pharmaceutical industry has developed numerous drugs that target protein kinases, particularly in the treatment of cancer. Kinase inhibitors — drugs that block the activity of specific protein kinases — represent one of the most successful classes of targeted cancer therapies developed in the late 20th and early 21st centuries. These therapeutic advances trace a direct lineage back to the basic research conducted by Krebs and Fischer at the University of Washington.

In its announcement of Krebs's death, the University of Washington emphasized that his discovery of a "biological switch in cells" had fundamentally changed the understanding of how cells communicate and regulate their functions. The New York Times described the process he discovered as "a crucial bodily process," noting its role in governing muscle movement, cell shape and division, and many other biological functions.

The collaboration between Krebs and Fischer also served as a model for productive scientific partnership. The two men worked together for decades, complementing each other's strengths and sharing credit for their discoveries. Their partnership demonstrated the value of sustained, cooperative research in making fundamental scientific breakthroughs. When Fischer died in 2021, the University of Washington noted that he had shared the Nobel Prize with his "UW School of Medicine colleague Edwin Krebs," a testament to the enduring institutional memory of their collaboration.

Krebs's legacy extends beyond his specific discoveries to encompass the broader field of signal transduction research that his work helped create. The study of how cells receive, process, and respond to signals from their environment is now a central discipline within biology, and protein phosphorylation remains at its core. In this sense, Edwin Krebs's contributions continue to shape the direction of biomedical research decades after his initial discoveries.