- Person
- Edmond H. Fischer
- Lived
- 1920–2021
- Field
- Biochemistry
- From
- Swiss-American
The story
Edmond Fischer was born in Shanghai in 1920 to a Viennese Jewish father and a French mother, grew up in Swiss boarding schools, and almost became a concert pianist. Instead he became a biochemist, and in 1953 he joined the new medical school of the University of Washington in Seattle. There he teamed up with a colleague, Edwin Krebs, to solve a puzzle left by the Nobel laureates Carl and Gerty Cori: why does glycogen phosphorylase, the muscle enzyme that releases sugar for energy, exist in both an inactive and an active form?
Working side by side at a single bench, Fischer and Krebs had the answer within eighteen months. A clue came by accident: muscle extracts filtered through paper became active because calcium leached from the paper, while extracts spun in a centrifuge stayed inactive. They found that activation needed ATP, the cell’s energy molecule, and showed that a second enzyme, which they called phosphorylase kinase, switches the muscle enzyme on by attaching a phosphate group to it. Another enzyme, a phosphatase, switches it off by removing the phosphate. They published the discovery in 1955.
At first it seemed a quirk of sugar metabolism. Over the following decades it turned out that reversible phosphorylation is the main way cells control almost everything they do, including growth, division, response to hormones and death. Many cancer-causing genes proved to be kinases jammed in the on position, and the receptors for insulin and growth factors proved to be kinases as well. Fischer and Krebs shared the 1992 Nobel Prize in Physiology or Medicine.
Because faulty switches drive so many diseases, kinases became a major target for new medicines. In 2001 imatinib, sold as Gleevec, became the first kinase inhibitor approved for clinical use, turning chronic myeloid leukaemia from a rapidly fatal disease into a manageable condition. Fischer’s National Academy of Sciences memoir records that more than 75 kinase-inhibiting drugs have since been approved, transforming the treatment of many cancers. The phosphatase side matters too: the transplant drug cyclosporin works by blocking one.
Why it matters
The phosphorylation switch Fischer co-discovered is the target of more than 75 approved kinase-inhibitor drugs, which have transformed treatment for leukaemia and many other cancers.
About Edmond H. Fischer
Shanghai-born biochemist who co-discovered reversible protein phosphorylation, the cell’s main on-off switch, now the target of more than 75 cancer drugs such as imatinib.
Sources
- Edmond H. Fischer 1920–2021, Biographical Memoir by Philip Cohen National Academy of Sciences
- Edmond H. Fischer, Biographical NobelPrize.org
- In Memoriam: Nobel Laureate Edmond Fischer UW Medicine Newsroom
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.