Stanley J. Korsmeyer

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Obituary misregulation of cell death has a major role in human disease. Stanley J. Korsmeyer (1950–2005) That a deficit in apoptosis can cause tumours implied that cancers might be When Stan Korsmeyer was in the eighth treated by reactivating apoptosis and grade and looking forward to playing high- causing tumour cells to self-destruct. school sports, he was told by the school Korsmeyer’s research elegantly coach that he would have to grow six demonstrated that cancer cells can be inches before he would be allowed on induced to die either by blocking anti-cell- any of the teams. Being determined but death genes such as Bcl-2, or by activating nonetheless pragmatic, Korsmeyer decided pro-cell-death genes such as Bax.As a DANA-FARBER CANCER INST. DANA-FARBER to focus his energies in an alternative consequence, the Bcl-2 family has become direction — raising hogs. Raise hogs a promising target for anticancer drugs. he did, and at age 14 Korsmeyer became Korsmeyer himself worked directly to the youngest person in the history of develop new treatments for cancer based on the Illinois State Fair to show the Grand his knowledge of apoptosis. Although we Champion pair of Hampshire hogs. Two met frequently at scientific meetings, it was old-time Illinois farmers were heard in the context of our serving as consultants discussing the competition. One asked, to a start-up biotechnology company “Who showed the Grand Champions this focused on apoptosis that I got to know year?” The other replied,“Just some kid.” Korsmeyer best. His science and advice It was not “just some kid”.It was Stan helped to make Bcl-2 a major target, and Korsmeyer, who even then dedicated as a consequence a drug that blocks Bcl-2 himself to and excelled at whatever he did. action is currently under development Korsmeyer was born on 8 June 1950, at a major pharmaceutical company. on a farm among the cornfields of Korsmeyer’s drive to develop an southern Illinois, and he planned anticancer drug and to cure cancer patients to be a veterinarian. However, as an was tempered by his concern about the undergraduate at the University of Illinois risks of clinical trials.“I would never want in Urbana, he became interested in curing to be involved in the trial of a drug that people instead of livestock. In 1976 he I wouldn’t be willing to test on my own earned an MD at the University of Illinois sons,”he once told me. Those sons, Evan in Chicago. A move to the University of Trailblazer in the and Jason, as well as his wife Susan, were California, San Francisco, allowed him to understanding and at the centre of his life, and his statement continue his medical training and to meet treatment of cancer about drug trials reflected Korsmeyer’s his wife-to-be Susan, an oncology nurse. deep empathy for others. This move also introduced Korsmeyer Korsmeyer had a farm boy’s work ethic, to sailing and fishing, two passions that survive instead, elevated expression of dedication, energy and modesty. He also continued throughout his life. Bcl-2 can allow those cells to accumulate had an unshakeable determination, as well Korsmeyer’s next move was to the additional mutations and become as a great sense of humour, a joyous and opposite coast (in part to continue his cancerous. immediately recognizable laugh, enormous proximity to an ocean), to the National Korsmeyer also discovered other personal warmth, an optimism about Cancer Institute in Bethesda, Maryland, members of the Bcl-2 gene family and people, and an infectious and constantly where, as a fellow in molecular oncology, found that they too regulate cell death. upbeat approach to life. I never knew he trained with leading cancer researchers Whereas members such as Bcl-2 protect anyone who did not like him. He cared Thomas Waldmann and Philip Leder. cells from dying, others, including Bax, enormously about the young scientists Korsmeyer continued his career as an Bad and Bid, cause cells to die. Korsmeyer who trained with him; he was a superb independent researcher at the NCI, and proposed a rheostat model for the mentor and seeded the biomedical world then as an investigator of the Howard regulation of cell death, in which the with his scientific offspring. He received Hughes Medical Institute, first at crucial ‘life versus death’ decision made many well-deserved prizes and honours Washington University in St Louis and by each cell is determined by the balance for his discoveries. later at the Dana-Farber Cancer Institute between the activities of antagonistic Stan Korsmeyer, a non-smoker, died and Harvard Medical School in Boston. survival and killer genes. He also on 31 March of lung cancer. His death Korsmeyer opened new doors to the discovered that Bcl-2 family members is a tragic loss to science, medicine and understanding and treatment of cancer. are associated with mitochondria, the humanity. He may never have grown the He co-discovered the oncogene Bcl-2, power plants of cells, and thus implicated six inches demanded by his high-school which when overexpressed can lead to mitochondria in the process of apoptosis. coach, but he was nonetheless a giant follicular lymphoma. His studies provided Korsmeyer’s studies helped to establish — as a scientist, a mentor, a friend and evidence that Bcl-2 was the first member that many human disorders — including a human being. H. Robert Horvitz of a new category of cancer-causing genes lymphomas and other cancers — can be H. Robert Horvitz is an investigator of the — genes that work not by driving cells caused by a misregulation of apoptosis. Howard Hughes Medical Institute at the to proliferate, but rather by preventing In short, he made crucial contributions Department of Biology, Massachusetts Institute of them from dying via a process known to the elucidation of the molecular-genetic Technology, 77 Massachusetts Avenue, Cambridge, as programmed cell death, or apoptosis. pathway that controls cell survival and Massachusetts 02139, USA. By causing cells that normally die to cell death and to the discovery that the e-mail: [email protected]