Edmond Fischer

Edmond H. Fischer
Born	Edmond Henri Fischer 6 4, 1920
Birthplace	Shanghai, China
Died	Template:Death date and age
Nationality	Swiss, American
Occupation	Biochemist, academic
Title	Professor Emeritus, Department of Biochemistry
Employer	University of Washington
Known for	Discovery of reversible protein phosphorylation
Education	PhD, University of Geneva
Awards	Nobel Prize in Physiology or Medicine (1992)

Edmond Henri Fischer, known to friends and colleagues as "Eddy," was a Swiss-American biochemist whose groundbreaking research on cellular regulation transformed the understanding of how cells communicate and function. Together with his longtime collaborator Edwin Krebs at the University of Washington, Fischer discovered the mechanism of reversible protein phosphorylation — the process by which enzymes are switched on and off through the addition and removal of phosphate groups. This discovery, which the Nobel Assembly recognized with the 1992 Nobel Prize in Physiology or Medicine, revealed a fundamental regulatory mechanism that governs most aspects of cell life, from growth and division to memory formation and immune response. Born in Shanghai, raised in Switzerland, and trained at the University of Geneva, Fischer spent the vast majority of his scientific career at the University of Washington in Seattle, where he served as a professor of biochemistry for decades. He died on August 27, 2021, at the age of 101, in Seattle, the city he had adopted as his home more than six decades earlier.

Early Life

Edmond Henri Fischer was born on April 6, 1920, in Shanghai, China. His early years were shaped by an international upbringing that would later be reflected in his cosmopolitan outlook and multilingual abilities. Fischer grew up in Switzerland, where he received his primary and secondary education.

Fischer's formative years in Switzerland exposed him to a rigorous European scientific tradition. The cultural and intellectual environment of Switzerland, with its strong tradition in the natural sciences, provided fertile ground for his developing interest in chemistry and biology. From an early age, Fischer displayed an aptitude for music as well as science, and he maintained a lifelong love of the piano — a pursuit that colleagues later described as reflecting the same precision and artistry he brought to his laboratory work. His scientific obituary in Science described him as a "biochemical virtuoso," a term that captured both his musical sensibility and his extraordinary skill at the laboratory bench.

The circumstances of Fischer's birth in Shanghai reflected the international character of his family's background, though he identified primarily with Swiss culture and carried Swiss nationality throughout his early life. His eventual immigration to the United States and adoption of American citizenship added another dimension to his multicultural identity.

Education

Fischer pursued his higher education at the University of Geneva in Switzerland, one of the country's leading research institutions. He completed his doctoral studies there, earning a PhD in chemistry and biochemistry. His training at Geneva provided him with a strong foundation in enzymology and biochemical techniques that would prove essential to his later research on protein phosphorylation.

The University of Geneva had a strong tradition in biochemistry and biological chemistry, and Fischer's doctoral work there equipped him with the skills and knowledge base necessary for the enzyme research that would define his career. His education in the Swiss system, which emphasized both theoretical understanding and practical laboratory skills, prepared him for the rigorous experimental work he would later undertake in the United States.

Career

Move to the University of Washington

After completing his education in Switzerland, Fischer moved to the United States and joined the faculty of the University of Washington in Seattle. The university's Department of Biochemistry became his academic home for the remainder of his career. He eventually attained the rank of professor and later became professor emeritus in the Department of Biochemistry at the University of Washington School of Medicine.

Fischer's decision to relocate to Seattle proved consequential not only for his own career but for the broader field of biochemistry. At the University of Washington, he encountered Edwin G. Krebs, a fellow biochemist with complementary interests and expertise. The partnership between Fischer and Krebs would become one of the most productive and celebrated collaborations in the history of biomedical research.

In an interview conducted at the meeting of Nobel Laureates in Lindau, Germany, in June 2000, Fischer reflected on how he came into science and the path that led him to his most important discoveries. The conversation, conducted by Hans Jörnvall, provided insight into Fischer's motivations and the intellectual curiosity that drove his research over many decades.

Discovery of Reversible Protein Phosphorylation

The central achievement of Fischer's scientific career was the discovery, together with Edwin Krebs, of the mechanism of reversible protein phosphorylation. This work, carried out at the University of Washington beginning in the 1950s, revealed how cells regulate the activity of their enzymes — and by extension, virtually all cellular processes — through the addition and removal of phosphate groups to and from proteins.

Fischer and Krebs focused their initial investigations on glycogen phosphorylase, an enzyme involved in the breakdown of glycogen (the storage form of glucose) in muscle cells. They sought to understand how this enzyme was activated and deactivated within living cells. Through careful biochemical experimentation, they discovered that the enzyme could be switched between an active and an inactive form through the action of other enzymes — specifically, a kinase that added a phosphate group to the protein (phosphorylation) and a phosphatase that removed the phosphate group (dephosphorylation).

This was the first demonstration of reversible protein phosphorylation as a regulatory mechanism. Fischer and Krebs showed that phosphorylation was not merely a chemical modification but a fundamental switch that could turn enzyme activity on or off. Their discovery of the first protein kinase — the enzyme responsible for adding the phosphate group — opened an entirely new field of biological research.

The significance of their finding extended far beyond glycogen metabolism. Reversible protein phosphorylation turned out to be one of the most ubiquitous regulatory mechanisms in biology. Subsequent research by scientists around the world revealed that phosphorylation controls a vast array of cellular processes, including cell growth, cell division, signal transduction, gene expression, immune responses, and neuronal function. As described in Fischer's obituary in Nature, the process of reversible protein phosphorylation "regulates most aspects of cell life."

The discovery also had profound implications for medicine. Abnormalities in protein phosphorylation have been linked to numerous diseases, including cancer, diabetes, inflammatory disorders, and neurodegenerative conditions. The understanding of kinase signaling pathways that grew out of Fischer and Krebs's initial discovery led directly to the development of a new class of targeted therapies — kinase inhibitors — that have transformed the treatment of certain cancers and other diseases.

Broader Research Contributions

While the discovery of reversible protein phosphorylation remained the cornerstone of Fischer's scientific legacy, his research interests encompassed a broader range of topics in enzymology and biochemistry. Throughout his career at the University of Washington, Fischer continued to investigate the mechanisms by which enzymes are regulated, contributing to the growing understanding of signal transduction pathways in cells.

Fischer's laboratory at the University of Washington trained numerous graduate students and postdoctoral researchers who went on to make their own contributions to biochemistry and molecular biology. His mentorship and the intellectual environment he helped create in the Department of Biochemistry contributed to the university's reputation as a leading center for biomedical research.

His colleagues at the University of Washington, including John D. Scott, Trisha N. Davis, Rachel E. Klevit, and William A. Catterall, authored a tribute to Fischer in the journal Science following his death, describing the breadth and depth of his contributions to the field.

Later Career and Emeritus Status

Fischer continued to be active in the scientific community well into his later years. Even after achieving emeritus status at the University of Washington, he remained engaged with research and participated in scientific meetings. His attendance at the meeting of Nobel Laureates in Lindau, Germany, where he gave an interview in 2000, reflected his ongoing commitment to the scientific enterprise and to mentoring younger generations of scientists.

His longevity — Fischer lived to the age of 101 — allowed him to witness the extraordinary expansion of the field he had helped create. By the time of his death in 2021, the human genome had been found to encode more than 500 protein kinases, and kinase inhibitors had become one of the most important classes of drugs in modern medicine. The impact of his initial discovery with Krebs had multiplied far beyond what either scientist could have anticipated when they first observed the phosphorylation of glycogen phosphorylase in the 1950s.

Personal Life

Edmond Fischer was known to his friends and colleagues by the nickname "Eddy," a name that reflected his approachable and warm personality despite his towering scientific accomplishments. He made Seattle his permanent home after joining the University of Washington, and the city remained his adopted hometown for the rest of his life.

Fischer maintained a lifelong passion for music, particularly the piano. His colleagues and friends frequently remarked upon the parallels between his musical abilities and his scientific work, noting that both required precision, creativity, and deep engagement. The description of Fischer as a "biochemical virtuoso" in his Science obituary captured this dual nature of his talents.

Fischer held both Swiss and American citizenship, reflecting his international background — born in Shanghai, raised and educated in Switzerland, and building his career in the United States. This multinational perspective informed both his personal worldview and his approach to science as a collaborative, international endeavor.

Edmond Fischer died on August 27, 2021, in Seattle, Washington. He was 101 years old. His death was reported by the University of Washington, The Washington Post, Nature, Science, The Scientist, and the American Society for Biochemistry and Molecular Biology, among other institutions and publications, reflecting the magnitude of his contributions to science and medicine.

Recognition

Nobel Prize

Fischer's most prominent recognition came in 1992, when he and Edwin Krebs were jointly awarded the Nobel Prize in Physiology or Medicine. The Nobel Assembly at the Karolinska Institute awarded the prize for their discovery concerning "reversible protein phosphorylation as a biological regulatory mechanism." The award recognized not only the specific biochemical discovery but also its vast implications for understanding cellular regulation and its relevance to medicine.

The Nobel Prize brought international attention to work that had been conducted over several decades at the University of Washington. Fischer and Krebs's collaboration represented a model of sustained, rigorous scientific inquiry that yielded insights of fundamental importance.

Other Honors and Tributes

Following Fischer's death in August 2021, tributes were published in several of the world's leading scientific journals. Nature published an obituary noting that Fischer had "discovered the first example of reversible protein phosphorylation, a process that regulates most aspects of cell life." Science published a tribute authored by his University of Washington colleagues, describing him as a "biochemical virtuoso." The American Society for Biochemistry and Molecular Biology published a memorial noting his status as an emeritus professor at the University of Washington School of Medicine.

The University of Washington issued an official statement commemorating Fischer's life and contributions, noting the significance of his Nobel Prize-winning discovery and its impact on the treatment of disease. The Washington Post published an obituary describing how his work on cellular enzymes "led to major advances in the treatment of disease." The Scientist also published an obituary, noting that Fischer "codiscovered the mechanism of reversible phosphorylation alongside Edwin Krebs" and that he died "in his adopted hometown" of Seattle.

Legacy

Edmond Fischer's discovery of reversible protein phosphorylation, made in collaboration with Edwin Krebs, is considered one of the most important findings in the history of biochemistry and cell biology. The mechanism they identified — the enzymatic addition and removal of phosphate groups as a means of regulating protein function — proved to be a universal principle of cellular regulation, operative in organisms ranging from single-celled bacteria to humans.

The field that Fischer and Krebs opened has grown enormously since their initial observations in the 1950s. Protein kinases — the enzymes that catalyze phosphorylation — constitute one of the largest gene families in the human genome. The study of kinase signaling pathways has become a central discipline within modern molecular biology and has yielded profound insights into the mechanisms of health and disease.

In medicine, the practical consequences of Fischer's discovery have been substantial. The understanding that aberrant kinase activity underlies many diseases, particularly cancers, led to the development of kinase inhibitors as therapeutic agents. Drugs such as imatinib (Gleevec), used to treat chronic myeloid leukemia, represent direct descendants of the fundamental research initiated by Fischer and Krebs. The development of these targeted therapies has improved outcomes for patients with a range of conditions and represents one of the clearest examples of basic scientific research translating into clinical benefit.

Fischer's influence extended beyond his specific scientific discoveries to encompass his role as a mentor and colleague. His decades at the University of Washington helped establish the institution as a major center for biochemical research. The students and postdoctoral fellows he trained went on to populate laboratories and medical schools around the world, carrying forward the experimental traditions and intellectual rigor they learned under his guidance.

At the time of his death at the age of 101, Fischer was among the oldest living Nobel laureates. His long life allowed him to witness the full flowering of the field he had helped to create — from the initial characterization of a single regulated enzyme to a comprehensive understanding of cellular signaling networks that underpins modern molecular medicine.