Edmond H. Fischer (1920 – 2021)

Cosmopolitan, cultured, creative and caring. These characteristics were embodied in the life of Edmond (Eddy) Fischer – Nobel laureate, musician and global scientific celebrity – who died on August 27 at the age of 101 in Seattle, Washington.

Edmond (Eddy) Fischer

Eddy was born on April 6, 1920, in the French concession of Shanghai, the son of a French mother and an Austrian father. Until the age of 7, he attended the French Children’s School in Shanghai. During the summers, because Shanghai was extremely hot and humid, her family would travel to Lake Hakone in Japan by boat from Shanghai to Yokohama. So from an early age he experienced a multicultural lifestyle that shaped his outlook, relationships and science in the years to come.

In 1927, the family left for Europe by taking the Trans-Siberian railway. In Switzerland, Eddy was educated at the international school of La Châtaigneraie, where he became fascinated by science and the emerging field of biological chemistry. His curiosity was aroused by a childhood admiration for the bacteriologist Louis Pasteur and the fortuitous gift of a research-quality microscope. This scientific instrument allowed him to conduct experiments and first experience the adrenaline of discovery.

Eddy’s cosmopolitan upbringing fostered a love of history, music, and art. At the age of 14, just after moving to Geneva to attend Calvin College, he attended a performance of Beethoven’s Emperor Concerto by Swiss maestro Johnny Aubert, piano teacher at the prestigious Geneva Conservatory of Music. The next day, Eddy addresses the director of the conservatory and asks him to become Aubert’s pupil. During the audition which follows, Eddy impresses Aubert by interpreting the Polonaise in A major by Chopin and the Rondo Capriccioso by Mendelssohn. Eddy studied with Aubert for 7 years, and they became good friends. From then on, Eddy regularly entertained friends and colleagues by playing the piano.

The Fischer family in Shanghai, China, in 1926. From left to right: Oscar (father),
Edmond, Georges, Renée (mother) and Raoul.

A high school graduate a few weeks before the outbreak of World War II, Eddy remained in neutral Switzerland. After obtaining a bachelor’s degree in organic chemistry from the University of Geneva, he obtained a doctorate. under the supervision of Kurt Meyer on the structure of polysaccharides and alpha-amylases, enzymes that catalyze the hydrolysis of starch to sugars. In 1953, Eddy joined the Department of Biochemistry at the University of Washington, where he remained an active faculty member until his death. Shortly after arriving in Seattle, Eddy teamed up with UW biochemist Edwin G. Krebs; the two embarked on a long-standing friendship and remarkable collaboration.

Fischer and Krebs studied the metabolism of glycogen in skeletal muscle. They focused on how glycogen phosphorylase, the enzyme that catalyzes the limiting step of glycogenolysis, is regulated. They knew that the phosphorylase a form was active without the addition of adenosine monophosphate, or AMP, and that the phosphorylase b form was inactive without AMP. Through a series of ingenious and sometimes fortuitous experiments, they concluded that the interconversion of phosphorylase a to form b occurs as “direct phosphorylation of the enzyme”. This marked the advent of the study of protein phosphorylation as a major mode of cellular regulation. Since then, protein kinases have become the most important class of target drugs in the pharmaceutical industry for fighting cancer and inflammation. Many kinase inhibitor drugs are approved for clinical use, and hundreds more are in clinical trials. Fischer and Krebs received the 1992 Nobel Prize in Physiology or Medicine “for their findings concerning the reversible phosphorylation of proteins as a biological regulatory mechanism,” wrote the Nobel Assembly.

Eddy Fischer played the piano at the wedding of his eldest son, François, in 1984.

Eddy’s scientific contributions went well beyond the discovery of protein phosphorylation. He was a formidable mentor whose scientific lineage includes world leaders in cell signaling. In the 1970s, 1980s and 1990s he was at the forefront of research into phosphatase, arguably the most important reverse step in protein phosphorylation. Among the luminaries passing through his lab were Philip Cohen (University of Dundee, Scotland), who went on to classify the protein phosphatase family and define subcellular targeting as a vital signal termination mechanism; David Brautigan (University of Virginia), who discerned the mechanisms of action of protein phosphatase 1; and Nicholas Tonks (Cold Spring Harbor Laboratory), who discovered protein tyrosine phosphatases, enzymes that frequently neutralize oncogenes. Each intern benefited from creative and thoughtful conversations with Eddy. These precious touchpoints have sparked unprecedented loyalty and pride in being part of Fischer’s (and Krebs’) scientific family tree.

Eddy’s first and preferred language was French. His Franco-Swiss flamboyance often contrasted with Ed Krebs’ Midwestern sensibilities. Their language interface was something to see. In Eddy’s own words, “I remember the amused expressions of my colleagues sitting at the back of the classroom listening to my fractured English at the medical student conference. I also remember Ed Krebs’ wide smile every time I fell in French. What Ed didn’t realize, however, is that in two years, while my English hasn’t improved much, his has deteriorated completely!

Publishing is at the heart of scientific discovery. Working with Fischer and Krebs on manuscripts has been an absolute joy, but not without challenges. The scientific world knew this pair as Eddy and Ed. Yet while Fischer always referred to Krebs as Ed, Krebs invariably referred to Eddy as Ed. Most correspondence started with the greeting “Ed” and ended with the greeting “Ed” – often leaving the reader confused in the uncertainty of whether the message was from Fischer to Krebs or from Krebs to Fischer. This puzzling joke made “publishing” manuscripts an intimidating prospect.

Both Eds were superb writers and confident in their own grammatical prowess. Fischer was section editor for the journal Biochemistry, and Krebs was associate editor for the Journal of Biological Chemistry. As a result, a first author sitting in between during editing sessions often donned the mantle of a tennis referee as scientific and grammatical points were served diplomatically across the table and returned with courtesy. On rare occasions, the first author would venture into the fray, offering his own syntactic suggestion, only to be repelled with the politeness and precision of a JBC rejection. Thus, each intern received not only superb scientific training but also invaluable linguistic instruction at the feet of Fischer and Krebs. As it was often said, “Two hEd are better than one.

Both Ed in 1992 at the annual Fischer and Krebs Lab retreat in Pack Forest, Washington. This photo was taken shortly after they won the Nobel Prize.

Eddy’s dedication to science does not detract from his dedication to his family. Whether it was a family Christmas dinner or a gathering of friends, he always insisted on hosting, even though he never had enough table or chairs. He enjoyed cooking traditional Swiss dishes, including endives with ham, fondue and aspic, which were always drenched in fat and often devoid of vegetables. Even at the age of 101, he loved to cook for everyone.

Eddy was particularly close to his granddaughter and family protégé, Élyse Fischer (author of this Retrospective). He was proud that she attended the University of St. Andrews in Scotland. He had always appreciated her diverse upbringing and upbringing and believed the experience would be good for her. As a native of Scotland, I (John Scott, author of this retrospective) remember being asked by Eddy about the benefits of an education in St. Andrew’s and the value of Elyse’s proximity to the city of Dundee. , the home of his protégé Philip Cohen. and Cohen’s wife, Tricia, both of whom became important mentors to Élyse. I enthusiastically accepted.

Eddy was even happier when Élyse chose to study the structural determination of proteins for his doctorate. with David Barford at the Molecular Biology Laboratory of the Medical Research Council, University of Cambridge. Perhaps dedicated to genetics, Élyse has succeeded in unveiling a molecular mechanism for regulating the cell cycle by phosphorylation.

Eddy’s enthusiasm for science, music, friends and family never waned. In June 2021, he participated in the 70th Lindau Nobel Laureates Meeting on Zoom, inspiring young scientists and playing the piano for the Lindau Virtual Symphony Orchestra. Less than a month before his death, he played the piano at his grandson’s wedding as the groom and bride walked down the aisle.

Fischer-au-piano-890x663.jpg

Eddy plays the piano with his family at his grandson Leo’s wedding on July 31, 2021. Élyse Fischer is on the far left.

We end with Eddy’s own words: “As for what has always attracted me to scientific research … must be applied to solve a given problem. Science is based on science, where each result obtained suggests a number of questions, and each question asked suggests the next experiment. You have to follow these leads just like a detective follows different leads to solve a murder mystery, never knowing whether it will lead you to a dead end or the next big breakthrough. Because in science, you cannot order a great discovery at will, or buy it at any price because there is no way to predict when and where it will come from.

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