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[Obituary] Sydney Brenner

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Key player in the development of molecular biology and genetics. He was born in Germiston, South Africa, on Jan 13, 1927, and died in Singapore on April 5, 2019, aged 92 years.

Nobel Prize winner, collaborator in beginning to decipher the genetic code, co-discoverer of messenger RNA, and much else. Sydney Brenner was one of the clutch of gifted scientists whose work underpinned the golden age of molecular biology. Less well known is that Brenner was equally exceptional as a child. Having completed his first 3 years of primary school in a year, he matriculated from his high school at the age of 15 years. He joined the University of Witwatersrand in Johannesburg, South Africa, to study science in preparation for a medical degree. After a year, he moved into the medical school itself. But as he recalled in his Nobel Prize autobiography, “I had begun to see that I was interested in cells and their functions.”

Because he would still be too young to practise medicine, Brenner did a BSc. This confirmed his enthusiasm for science and he went on to complete an MSc, graduating in 1947. Although he continued to do research, he went back to his medical course. But his heart was not in it, and he had to resit some of the exams before receiving his medical degree in 1951. Escape came in an offer to join the Department of Physical Chemistry at Oxford University in the UK. “The subject I was interested in was molecular biology which, of course, did not exist at the time”, he wrote. But it soon would. It was while working for his Oxford PhD, completed in 1954, that he and a group of colleagues drove to Cambridge having heard that two researchers, Francis Crick and James Watson, had solved the structure of DNA. Having seen their model of DNA, Brenner knew where his own future lay.

After a brief stint in the USA at Cold Spring Harbor and other laboratories, he returned to South Africa and set up his own bacteriophage laboratory at the University of Witwatersrand. In 1957, he was appointed to the staff of the UK's Medical Research Council to work for what was to become its celebrated Laboratory of Molecular Biology (LMB) in Cambridge. In 1979, he was appointed the LMB's Director.

It was here that Brenner's passion for molecular biology, and his partnership with Crick, began to bear fruit in studies of gene function and the discovery of messenger RNA. In the early 1960s, Brenner turned his attention to pattern formation in the developmental processes of whole organisms. “Sydney had worked since about 1962, on his own, to find a suitable organism for this”, says Richard Henderson, Emeritus Scientist at the LMB and its Director from 1996 to 2006. Brenner chose the tiny nematode Caenorhabditis elegans, made a series of mutants, and began searching for the genetic basis of the phenotypic changes he witnessed. His colleagues John Sulston and H Robert Horwitz built on Brenner's initial work and all three were awarded the 2002 Nobel Prize for Physiology or Medicine for their discoveries concerning genetic regulation of organ development and programmed cell death. Brenner himself maintained it should have been his second Nobel Prize, his earlier work on genetic coding having, he insisted, been equally worthy. The comment, often repeated, illustrates two features of his personality: a breezy arrogance coupled with an unquenchable sense of humour.

Geneticist Jonathan Hodgkin worked with Brenner for many years at the LMB. Now an Emeritus Fellow at Oxford's Keble College, Hodgkin found him “both distracting and inspiring”. He recalls a common experience of Brenner's colleagues in the 1970s. “If you found something out and told him about it, it would turn out that he'd already found that out and not bothered to write it down.” As Director of the LMB, a job Brenner did not really enjoy, he exhibited a forceful style. “He was impatient”, says Hodgkin. “He was too funny and too rude to people.” But as a scientist he was remarkable. “He remembered everything over a wide range of topics”, Henderson adds. “Exceptionally inventive”, says Hodgkin, “and the breadth of his interest in science was extraordinary.”

In later years, Brenner divided his time between Cambridge and California in the USA, where he worked at the Salk Institute and the Scripps Research Institute. In 1996, he founded the Molecular Sciences Institute in Berkeley. Finally, he moved to Singapore, advising the government on setting up its Molecular Engineering Laboratory. A huge talent, little dimmed by time, Brenner leaves children Belinda, Carla, and Stefan.

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