Edmond H. Fischer, a Nobel Prize-winning biochemist whose help in discovering a basic regulatory mechanism in cells paved the way for the development of drugs for cancer, diabetes, and other diseases, died in Seattle on August 27. He was 101.
The Lindau Nobel Laureate Meeting in Germany, at which Dr. Fischer was a frequent speaker at the organization’s annual forums, announcing the death.
When Dr. Fischer came as a researcher at the University of Washington in Seattle in the 1950s, he learned that a fellow university scientist, the biochemist Edwin G. Krebs, was researching a question that he too wanted to solve: How do muscles work? do you find the energy you need to contract?
They teamed up to study an enzyme discovered by biochemists Carl and Gerty Cori, a married couple who shared the Nobel Prize in 1947 for their work. Dr. Krebs had previously studied the enzyme in muscle tissue, and Dr. Fischer had examined the enzyme in a potato. But the muscle enzyme seemed to need an additional chemical to function while the potato enzyme didn’t.
When the two scientists examined this apparent discrepancy, they discovered that the muscle enzyme is regulated by adding and removing phosphate groups, a process known as reversible phosphorylation.
Many processes in cells are controlled by phosphorylation, in which a phosphate molecule is attached to a protein. Phosphorylation determines how a cell grows, divides, differentiates, and dies; it also regulates how hormones work in the body and how cancer reproduces. Adding or removing the phosphate acts as a biological switch that turns a variety of important cellular events on or off. Dr. Fischer and Dr. Krebs identified the enzyme that performs reversible phosphorylation.
The discovery turned out to be one of the fundamental mechanisms of cell signaling: how cells communicate with each other.
John Scott, chairman of the department of pharmacology at the University of Washington School of Medicine, compared the Fischer cancer breakthrough to two groundbreaking discoveries that shaped modern science: the shape of DNA as a double helix and the gene manipulation tool CRISPR-Cas9 . “It’s so fundamentally important,” he said in a telephone interview.
When phosphorylation regulation fails, diseases such as cancer, heart disease, and diabetes can develop. Many modern drugs build on the work of Dr. Fischer and Dr. Cancer by trying to manipulate this process.
The significance of their discovery was not fully understood when they published their results in 1955. But its amazing effects unfolded over time. Now “it is the key to understanding cancer,” said Trisha Davis, chair of the Department of Biochemistry at the University of Washington. “It’s hard to imagine how anyone could have a greater impact on the life sciences.”
Dr. Fischer and Dr. Cancer received the 1992 Nobel Prize in Physiology or Medicine. (Dr. Krebs died in 2009.)
“The beauty of science is that you know where to start but you never know where you will end up,” said Dr. Fischer in an interview with the Lindau Nobel Laureate Meetings 2020.
Edmond Henri Fischer was born on April 6, 1920 in Shanghai to Renée Tapernoux and Oscar Fischer. Eddy – as everyone called him – grew up speaking French and attended a Swiss boarding school with a view of Lake Geneva. There he took up mountaineering and skiing. He also studied piano at the Geneva Conservatory of Music and briefly considered a career as a pianist.
But at 14, he was inspired by Louis Pasteur’s work to become a microbiologist. The decision was driven in part by his father’s death of tuberculosis. He later switched to chemistry.
Dr. Fischer moved to the United States in the early 1950s to do research at the California Institute of Technology in Pasadena. But as soon as he arrived, he was offered a similar job at the University of Washington. While considering the offer, he and his wife visited Seattle and found that the towering trees and mountains surrounding the city reminded him of Switzerland. He was beaten, he remembered, and took the job.
Dr. Fischer became a full-time professor at the university in 1961 and remained connected to it throughout his life. After he retired in 1990, he continued to attend biochemistry presentations, usually sitting in the front row with his friend, biochemist Earl Davie, always engaging the speaker.
“Even after his 100th birthday, Eddy kept asking questions,” says Nicholas Tonks, a cancer researcher who worked with Dr. Fischer and now works at the Cold Spring Harbor Laboratory in New York. “And they’re still some of the best questions in the room.”
Dr. Fischer’s granddaughter, Élyse Fischer, a graduate student in molecular biology at the University of Cambridge in England, said she was in awe of him as a child and unsure of her own ability to achieve great things in science. “But he has never lacked confidence in me,” she said in a telephone interview, adding that she will graduate at the same age as her grandfather: 27.
Dr. Fischer played the piano all his life and often played sonatas by Mozart or Beethoven for colleagues and friends. At 101, he played at a grandson’s wedding on Lopez Island, Washington.
In addition to Ms. Fischer, Dr. Fischer’s two sons, François and Henri; a stepdaughter, Paula Dandliker, from a second marriage; and three other grandchildren. His first wife, Nelly Gagnaux, died in 1961. In 1963 he married Beverly Bullock, who died in 2006.
In 2017, Dr. Fischer, then 97, attended a march protesting the Trump administration’s proposed budget cuts at the National Institutes of Health and the Environmental Protection Agency. He walked with a stick and carried a sign that said, “Ask me about reversible phosphorylation (I know a thing or two about it).”