Sydney Brenner (1927-2019) Mischievous Steward of Molecular Biology’S Golden Age

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OBITUARY COMMENT Sydney Brenner (1927-2019) Mischievous steward of molecular biology’s golden age.

ydney Brenner was one of the first He served as director of the LMB for about to view James Watson and Francis a decade. Despite describing the experience Crick’s double helix model of DNA in as the biggest mistake in his life, he took the SApril 1953. The 26-year-old biologist from lab (with its stable of Nobel laureates and South Africa was then a graduate student at distinguished staff) to unprecedented prom- the University of Oxford, UK. So enthralled inence. In 1986, he moved to a new Medical was he by the insights from the structure that Research Council (MRC) unit of molecular he determined on the spot to devote his life genetics at the city’s Addenbrooke’s Hospital, to understanding genes. and began work in the emerging discipline of Iconoclastic and provocative, he became evolutionary genomics. Brenner also orches- one of the leading biologists of the twen- trated Britain’s involvement in the Human tieth century. Brenner shared in the 2002 Genome Project in the early 1990s. Nobel Prize in Physiology or Medicine for From the late 1980s, Brenner steered deciphering the genetics of programmed the development of biomedical research in cell death and animal development, includ- Singapore. Here he masterminded Biopolis, ing how the nervous system forms. He was at a spectacular conglomerate of chrome and

ANDREW CU TRARO/REDUX/EYEVINE the forefront of the 1975 Asilomar meeting glass buildings dedicated to biomedical to discuss the appropriate use of emerging research. He also helped to guide the Janelia abilities to alter DNA, was a key proponent South African to the University of Farm campus of the Howard Hughes Medi- of the Human Genome Project, and much Cambridge, UK, in 1956. In the early 1960s, cal Institute in Ashburn, Virginia, and to more. He died on 5 April. using just bacteria and bacteriophages, Crick restructure molecular biology in Japan. Brenner was born in 1927 in Germiston, and Brenner deciphered many of the essen- Brenner dazzled, amused and some- South Africa to poor immigrant parents. tials of gene function in a breathtaking series times offended audiences with his humour, Bored by school, he preferred to read books of studies. irony and disdain of authority and dogma borrowed (sometimes permanently) from Brenner had proved theoretically in — prompting someone to describe him as the public library, or to dabble with a self- the mid-1950s that the genetic code is “one of biology’s mischievous children; the assembled chemistry set. His extraordinary ‘non-overlapping’ — each nucleotide is part witty trickster who delights in stirring things intellect — he was reading newspapers by of only one triplet (three nucleotides specify up.” His popular columns in Current Biology the age of four — did not go unnoticed. His each amino acid in a protein) and successive (titled ‘Loose Ends’ and, later, ‘False Starts’) teachers secured an award from the town ‘triplet codons’ are read in order. In 1961, in the mid-1990s led some seminar hosts to council to send him to medical school. Brenner and Crick confirmed this in the lab. introduce him as Uncle Syd, a pen name he Brenner entered the University of the The same year, Brenner, with François Jacob ultimately adopted. Witwatersrand in Johannesburg at the age of and Matthew Meselson, published their Sydney was aware of the debt he owed 15 (alongside Aaron Klug, another science- demonstration of the existence of messenger to being in the right place at the right time. giant-in-training). Here, certain faculty RNA. Over the next two years, often with He attributed his successes to having to members, notably the anatomist Raymond Crick, Brenner showed how the synthesis learn scientific independence in a remote Dart, and fellow research-oriented medical of proteins encoded by DNA sequences is part of the world, with few role models students enriched his interest in science. terminated. and even fewer mentors. He recounted the On finishing his six-year course, his youth This intellectual partnership dissolved importance of arriving in Oxford with few legally precluded him from practising med- when Brenner began to focus on whole scientific biases, and leaving with the convic- icine, so he devoted two years to learning organisms in the mid-1960s. He finally tion that seeing the double helix model one cell biology at the bench. His passion for alighted on Caenorhabditis elegans. Stud- chilly April morning would be a defining research was such that he rarely set foot on ies of this tiny worm in Brenner’s arm of the moment in his life. the wards — and he initially failed his final legendary Laboratory of Molecular Biology The Brenner laboratories (he often oper- examination in internal medicine. (LMB) in Cambridge led to the Nobel for ated more than one) spawned a generation of In 1952 Brenner won a scholarship to Brenner, Robert Horvitz and John Sulston. outstanding protégés, including five Nobel the Department of Physical Chemistry at And his contributions went well beyond laureates. Those who dedicated their careers Oxford. His adviser, Cyril Hinshelwood, the lab. In 1975, with Paul Berg and others, to understanding the workings of C. elegans wanted to pursue the idea that the environ- he organized a meeting at Asilomar, Califor- now number in the thousands. Science will ment altered observable characteristics of nia, to draft a position paper on the United be considerably poorer without Sydney. But bacteria. Brenner tried to convince him of States’ use of recombinant DNA technology his name will live forever in the annals of the role of genetic mutation. Two years later, — introducing genes from one species into biology. ■ with doctorate in hand, Brenner spent the another, usually bacteria. Brenner was influ- summer of 1954 in the United States visiting ential in persuading attendees to treat ethical Errol Friedberg is an emeritus professor at labs, including Cold Spring Harbor in New and societal concerns seriously. He stressed the University of Texas Southwestern Medical York state. Here he caught up with Watson the importance of thoughtful guidelines for Center at Dallas, USA, and author of Sydney and Crick again. deploying the technology to avoid overly Brenner: A Biography. Impressed, Crick recruited the young restrictive regulation. e-mail: [email protected]