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Cancer Obituary Research Let's Raise a Glass to Sydney: In Memoriam (1927-2019) Ronald M. Evans Shortly after receiving the 2002 Nobel Prize in Medicine or protein chain termination mutations allowed him to use the Physiology, I congratulated Sydney Brenner with a magnum of same technology to establish collinearity of the gene with the 1995 Chateau Latour. He said, "Oh Ron, it's lovely but a bit young. growing polypeptide chain as well as establishing messenger Let's wait and we'll toast when it's ready." Well, a bit like the wine, RNA as the mediator. Not done yet, mutations outside of the when Sydney finished his medical training he was too young to coding sequence led to the discovery of "stop codons." The practice medicine. He was told "you're not ready." Though born, resulting interlocking concepts represent an enormous advance raised, and educated in South Africa, the capricious absence of a and, for me, are my favorite discoveries from the entire Brenner job took him to Oxford in 1952, where he received a PhD in opus. Physical Chemistry in 1954. But the milestone event of his By establishing the flow of genetic information from the DNA training was perhaps the April 1953 drive he made to the Cavend- template to an RNA intermediate and via the triplet code from ish Laboratory in Cambridge, England to see first-hand the new mRNA to protein, Brenner confirmed Francis Crick's "Central Watson and Crick model for the structure of DNA. In his own Dogma," DNA!RNA!Protein. words, "This was it ...the curtain had been lifted and everything In 1962, Brenner expanded his interests beyond genetic coding was now clear as to what to do." With research in his blood, he to consider the larger problem of organismal development with a moved back to the Department of Physiology in the Medical focus on the nervous system. This fit well into his earlier medical School in South Africa in 1954, where he began work on a training in anatomy, physiology, and cell–cell communication. bacteriophage system, which might be useful in cracking the He chose as his model the translucent nematode, C. elegans, whose genetic code. Solid progress led Brenner back to the MRC Labo- simple brain is comprised of only 302 neurons. Using genetic ratory of Molecular Biology (previously the Cavendish Labora- dissection as a molecular scalpel, Brenner and his colleagues, in tory) in 1956, where he joined the unit for Molecular Structure particular John Sulston and Robert Horvitz, not only produced a and was director from 1979 to 1986. This transitional move complete blueprint of the nervous system but went on to discover landed him in the emerging epicenter of molecular biology. As novel developmental mechanisms such as programmed cell luck would have it, he wound up sharing an office with Francis death. This opened new frontiers in understanding animal devel- Crick (for 20 years), where an earthly form of the Vulcan mind opment and was recognized by the 2002 Nobel Prize in Physi- meld would allow them to conceptualize how information stored ology and Medicine. In addition to the Nobel Prize, Sydney in DNA is transformed and ultimately translated into proteins. received numerous other awards including the Albert Lasker This work propelled Sydney into a role as one of the most Awards for Special Achievement in Science and Basic Medical influential scientists of our era. Research, and the King Faisal International Prize for Science, Krebs While Crick was a theoretician, Sydney was an experimentalist Medal, Royal and Copley Medals of the Royal Society, Harvey whose skills were further honed by work with Francois¸ Jacob and Prize, Kyoto Prize, and Gairdner Foundation International Award. Matt Meselson. By focusing on bacteriophage as a model and by He was also a member of the Royal Society of London, foreign working with acridine dye–induced mutations, Brenner devel- associate of the US National Academy of Sciences, fellow of the oped the concept of frame-shift mutations. This, in turn, provided American Association for Cancer Research, and foreign member the genetic proof of a triplet code. Subsequent work on induced of the Academy of Science, Paris, and fellow of the American Association for Cancer Research Academy. Salk Institute, La Jolla, California. In the mid-nineties, Francis Crick convinced Sydney to join the Salk faculty, reuniting the dynamic duo as perhaps the most Corresponding Author: Ronald M. Evans, Salk Institute, 10010 N. Torrey Pines fi RD, La Jolla, CA 92037. Phone: 858-453-4100; Fax: 858-455-1349; E-mail: interesting colleague one could wish for. Scienti croyaltywas [email protected] in our midst, and they loved to hold court. While I stored Sydney's celebratory bottle for all these years, we never got to Cancer Res 2019;79:2797 share it—so we will open it in his honor at our next annual doi: 10.1158/0008-5472.CAN-19-1267 Sydney Brenner lecture. In the meantime, let's all raise a glass to Ó2019 American Association for Cancer Research. Sydney. www.aacrjournals.org 2797 Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 2019 American Association for Cancer Research. Let's Raise a Glass to Sydney: In Memoriam (1927-2019) Ronald M. Evans Cancer Res 2019;79:2797. 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