Rooms behind a shoe shop
Sydney Brenner was born on January 13, 1927, in Germiston, a small mining town near Johannesburg, South Africa. His parents were Jewish immigrants from Eastern Europe: his father, Morris, came from Lithuania in 1910 and his mother, Leah (Blecher), from Riga in Latvia in 1922. Morris Brenner was a shoe repairer who never learned to read or write, yet spoke English, Yiddish and Russian and picked up Afrikaans and Zulu. The family’s first home was a few rooms at the back of his shop.
Sydney learned to read very early. A customer of his father, Miss Walkinshaw, persuaded the family to let the five-year-old attend her kindergarten free of charge. He raced through primary school and found his true teacher in the Germiston Public Library, one of the many libraries funded by Andrew Carnegie around the world, where he discovered that knowledge could be acquired by reading, a habit he kept all his life. At home he gathered test tubes and chemicals from a pharmacy supplier and discovered that the pigments he extracted from flowers changed colour when he changed the acidity.
A teenage medical student
Brenner matriculated from Germiston High School just before turning fifteen. A bursary of 60 pounds a year from the town council let him enter the University of the Witwatersrand in Johannesburg in 1942 to study medicine; he cycled to the station each morning and took the train, carrying sandwiches for lunch. An uncle gave him a microscope. Because he would be too young to practise medicine when he finished, he was allowed to spend extra years on research degrees in anatomy and physiology, studying with the anthropologists Raymond Dart and Robert Broom and the histologist Joseph Gillman, and teaching himself cytogenetics. He published his first scientific paper at eighteen.
He was, by his own account, an erratic medical student, brilliant in some subjects and dismal in others; he failed medicine at his first attempt and qualified as a doctor in 1951. By then he had decided to do research abroad, in a subject he would later say did not yet exist: molecular biology.
Seeing the double helix
In 1952 a scholarship took Brenner to Oxford to work for a doctorate with the chemist Cyril Hinshelwood on bacterial viruses. In December 1952 he married May Covitz Balkind, a fellow South African studying psychology in London; she brought a son, Jonathan, from her first marriage, and they later had children Belinda, Carla and Stefan. In April 1953, days after Francis Crick and James Watson had built their model of DNA in Cambridge, Brenner drove over with two friends to see it. The moment he saw the paired bases, he wrote, he realised it was the key to all the problems in biology that had seemed intractable. It was the birth of molecular biology, and he resolved to be part of it.
After a summer at Cold Spring Harbor in New York and a drive across America with Watson, he returned to South Africa, where he proved mathematically that the genetic code could not be of the overlapping kind some had proposed. Crick worked hard to bring him to Cambridge, and in December 1956 the Brenners left South Africa for a new life in England.
Cracking the code
For the next twenty years Brenner shared an office with Francis Crick at the Medical Research Council unit in Cambridge that became the Laboratory of Molecular Biology, and the two generated a stream of ideas, right and wrong. With Crick and colleagues he used chemically induced mutations that shift the reading of a gene by one letter to show, in 1961, that the genetic code is read in non-overlapping groups of three letters, or triplets. He later identified the triplets that tell the cell where a protein ends, the stop codons.
In 1961, with François Jacob and Matthew Meselson, he provided the experimental proof of messenger RNA: short-lived copies of genes that carry instructions from DNA to the ribosomes, the cell’s protein factories. This was a central piece of the flow of information from genes to proteins. With Jacob he also proposed the replicon model of how chromosomes are copied, and with R. W. Horne he introduced negative staining, a technique that made high-resolution electron microscopy of viruses and other biological structures possible.
The worm
By the early 1960s Brenner felt that the basic problems of molecular genetics were solved and turned to bigger questions: how genes build a complex animal and its nervous system. He needed a creature simple enough to understand completely. He chose Caenorhabditis elegans, a transparent soil worm about a millimetre long that grows from egg to adult in a few days. In a landmark 1974 paper he showed how to induce mutations in the worm, linked them to about a hundred genes and their effects on the body, and laid out the genetic methods for studying it.
His team, with John White, Nicol Thomson and others, then reconstructed the worm’s entire anatomy from thousands of electron microscope images, producing the first complete wiring diagram of an animal’s nervous system, every one of its neurons and connections. John Sulston traced the lineage of every cell from the fertilised egg, and Robert Horvitz used the worm to discover genes that control programmed cell death. In 2002 Brenner, Sulston and Horvitz shared the Nobel Prize in Physiology or Medicine; the Nobel committee said Brenner’s discoveries laid the foundation for the prize.
From worms to medicine
The humble worm became one of the most important animals in biology. Genes that control development and cell death in C. elegans turned out to have close counterparts in humans. The Nobel committee noted that understanding programmed cell death sheds light on how viruses and bacteria invade cells, why cells are lost in AIDS, stroke, heart attacks and neurodegenerative diseases, and why cancer cells survive when they should die; many cancer treatments work by switching the cells’ suicide programme back on. Laboratories around the world now use the worm to study ageing, the nervous system, and the action of drugs.
Brenner’s earlier discovery of messenger RNA is equally alive in medicine. Techniques that measure which genes are active in a cell work by reading messenger RNA, and in recent years messenger RNA itself has become the basis of a new kind of vaccine. His mapping of the worm’s nervous system is now recognised, in the words of a later director of his laboratory, as the absolute starting point of the effort to understand the brain in its full complexity.
Builder of institutions
Brenner directed the Laboratory of Molecular Biology from 1979 to 1986, steering it through years of high inflation. He was an early and active advocate of sequencing the human genome and supported Britain’s participation in the Human Genome Project. He promoted the Japanese pufferfish, Fugu, as a model whose compact genome would make vertebrate genes easier to read, and at the company Lynx he helped develop a new massively parallel method of sequencing DNA.
Later in life he spent much of his time in California and Asia. He founded the Molecular Sciences Institute in 1995, became a distinguished professor at the Salk Institute in 2001, rejoining Crick, and in 2005 was appointed president of the Okinawa Institute of Science and Technology in Japan. He was a key adviser in building biomedical research in Singapore. He also took part in the 1975 Asilomar conference on the risks of recombinant DNA, where, his former laboratory recalled, a strong sense of ethical responsibility was a key motivator.
A Jewish South African
Brenner’s life began in a Jewish immigrant family in a South African mining town, with a father from Lithuania who spoke Yiddish among his many languages and a mother from Latvia. His parents, he wrote, would have preferred him to be a surgeon or physician, but were understanding of their son’s ambitions. Like many scientists of his generation he was not religious and described himself as an atheist, yet his story of a self-taught boy rising from rooms behind a cobbler’s shop through public libraries and scholarships is one shared by many children of Jewish immigrants.
He was famous for his wit. For years he wrote a column called Loose Ends in the journal Current Biology, so popular that it was collected as a book. Colleagues described him as eager, high-spirited and creative, a dazzling theorist and a master of the minimal experiment. Francis Crick said his great strength was in choosing experiments that were both important and ingenious.
Legacy
Sydney Brenner died in Singapore on April 5, 2019, aged 92. His wife, May, had died in 2010. He was made a Companion of Honour in Britain in 1987 and received many other honours, but he insisted that a scientist should be judged by the people he helped to train.
By that measure, too, his legacy is immense. Generations of biologists were trained in his laboratories or in the worm community he founded. His work helped reveal how genetic information is written and read, and the simple animal he chose gave medicine a window into development, cell death and the brain. Few scientists have done as much to create the modern science of life.
Sources & further reading
Sydney Brenner, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 2002, NobelPrize.org · Sydney Brenner 1927–2019, MRC Laboratory of Molecular Biology · Sydney Brenner, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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