PAUSING to look at the life of Sydney Brenner (1927-2019)

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I was saddened by the passing of Sydney Brenner on April 5, 2019, Below is the finest tribute I read on his life followed by the best interview I ever seen done of him by Alan Macfarlane.

OBITUARY

Sydney Brenner (1927-2019)

Mischievous steward of molecular biology’s golden age.
South African biologist Sydney Brenner in 2002.

Credit: Andrew Cutraro/Redux/eyevine

Sydney Brenner was one of the first to view James Watson and Francis Crick’s double helix model of DNA in April 1953. The 26-year-old biologist from South Africa was then a graduate student at the University of Oxford, UK. So enthralled was he by the insights from the structure that he determined on the spot to devote his life to understanding genes.

Iconoclastic and provocative, he became one of the leading biologists of the twentieth century. Brenner shared in the 2002 Nobel Prize in Physiology or Medicine for deciphering the genetics of programmed cell death and animal development, including how the nervous system forms. He was at the forefront of the 1975 Asilomar meeting to discuss the appropriate use of emerging abilities to alter DNA, was a key proponent of the Human Genome Project, and much more. He died on 5 April.

Brenner was born in 1927 in Germiston, South Africa, to poor immigrant parents. Bored by school, he preferred to read books borrowed (sometimes permanently) from the public library, or to dabble with a self-assembled chemistry set. His extraordinary intellect — he was reading newspapers by the age of four — did not go unnoticed. His teachers secured an award from the town council to send him to medical school.

Brenner entered the University of the Witwatersrand in Johannesburg at the age of 15 (alongside Aaron Klug, another science-giant-in-training). Here, certain faculty members, notably the anatomist Raymond Dart, and fellow research-oriented medical students enriched his interest in science. On finishing his six-year course, his youth legally precluded him from practising medicine, so he devoted two years to learning cell biology at the bench. His passion for research was such that he rarely set foot on the wards — and he initially failed his final examination in internal medicine.

Nobel Prize winners, Sir John Sulston, and Dr. Sydney Brenner, in 2002.

Sydney Brenner (right) with John Sulston, who both shared the Nobel Prize in Physiology or Medicine with Robert Horvitz in 2002.Credit: Steve Russell/Toronto Star/Getty

In 1952 Brenner won a scholarship to the Department of Physical Chemistry at Oxford. His adviser, Cyril Hinshelwood, wanted to pursue the idea that the environment altered observable characteristics of bacteria. Brenner tried to convince him of the role of genetic mutation. Two years later, with doctorate in hand, Brenner spent the summer of 1954 in the United States visiting labs, including Cold Spring Harbor in New York state. Here he caught up with Watson and Crick again.

Impressed, Crick recruited the young South African to the University of Cambridge, UK, in 1956. In the early 1960s, using just bacteria and bacteriophages, Crick and Brenner deciphered many of the essentials of gene function in a breathtaking series of studies.

Brenner had proved theoretically in the mid-1950s that the genetic code is ‘non-overlapping’ — each nucleotide is part of only one triplet (three nucleotides specify each amino acid in a protein) and successive ‘triplet codons’ are read in order. In 1961, Brenner and Crick confirmed this in the lab. The same year, Brenner, with François Jacob and Matthew Meselson, published their demonstration of the existence of messenger RNA. Over the next two years, often with Crick, Brenner showed how the synthesis of proteins encoded by DNA sequences is terminated.

This intellectual partnership dissolved when Brenner began to focus on whole organisms in the mid-1960s. He finally alighted on Caenorhabditis elegans. Studies of this tiny worm in Brenner’s arm of the legendary Laboratory of Molecular Biology (LMB) in Cambridge led to the Nobel for Brenner, Robert Horvitz and John Sulston.

Maxine Singer, Norton Zinder, Sydney Brenner and Paul Berg in 1975.

Maxine Singer, Norton Zinder, Sydney Brenner and Paul Berg (left to right) at the 1975 meeting on recombinant DNA technology in Asilomar, California.Credit: NAS

And his contributions went well beyond the lab. In 1975, with Paul Berg and others, he organized a meeting at Asilomar, California, to draft a position paper on the United States’ use of recombinant DNA technology — introducing genes from one species into another, usually bacteria. Brenner was influential in persuading attendees to treat ethical and societal concerns seriously. He stressed the importance of thoughtful guidelines for deploying the technology to avoid overly restrictive regulation.

He served as director of the LMB for about a decade. Despite describing the experience as the biggest mistake in his life, he took the lab (with its stable of Nobel laureates and distinguished staff) to unprecedented prominence. In 1986, he moved to a new Medical Research Council (MRC) unit of molecular genetics at the city’s Addenbrooke’s Hospital, and began work in the emerging discipline of evolutionary genomics. Brenner also orchestrated Britain’s involvement in the Human Genome Project in the early 1990s.

From the late 1980s, Brenner steered the development of biomedical research in Singapore. Here he masterminded Biopolis, a spectacular conglomerate of chrome and glass buildings dedicated to biomedical research. He also helped to guide the Janelia Farm campus of the Howard Hughes Medical Institute in Ashburn, Virginia, and to restructure molecular biology in Japan.

Brenner dazzled, amused and sometimes offended audiences with his humour, irony and disdain of authority and dogma — prompting someone to describe him as “one of biology’s mischievous children; the witty trickster who delights in stirring things up.” His popular columns in Current Biology (titled ‘Loose Ends’ and, later, ‘False Starts’) in the mid-1990s led some seminar hosts to introduce him as Uncle Syd, a pen name he ultimately adopted.

Sydney was aware of the debt he owed to being in the right place at the right time. He attributed his successes to having to learn scientific independence in a remote part of the world, with few role models and even fewer mentors. He recounted the importance of arriving in Oxford with few scientific biases, and leaving with the conviction that seeing the double helix model one chilly April morning would be a defining moment in his life.

The Brenner laboratories (he often operated more than one) spawned a generation of outstanding protégés, including five Nobel laureates. Those who dedicated their careers to understanding the workings of C. elegans now number in the thousands. Science will be considerably poorer without Sydney. But his name will live forever in the annals of biology.

Nature 568, 459 (2019)

doi: 10.1038/d41586-019-01192-9

Interview with Sydney Brenner – August 2007 – part 1

Full interview with Sydney Brenner, 2007 – part 2

Transcript:

0:09:07 Born in Germiston near Johannesburg 13th January 1927; father emigrated from Lithuania to South Africa where he had a brother in about 1911; mother came from Latvia and she emigrated in 1922 and had lived through the revolution; father repaired shoes and we lived initially in rooms at the back of his shop; mother has ambitions for her children; father was illiterate but had a gift for languages; mother encouraged me to read which I learnt to do from newspapers; went to a kindergarten run by a customer of my father’s who had found me there reading a newspaper on the floor; did first three years of primary school in one year; went directly into standard 2 at the government primary school aged six; meant I was always about two years younger than the rest of the class which was not helpful

5:12:10 After High School matriculated when under fifteen; had won a scholarship to

university to study medicine; had a lab of my own in a garage; can’t remember being influenced by any teacher at the school and got most of my education in the public library; as a child interested in nature and took flies apart and wondered how you could put them back together again; went to University of Witwatersrand aged fifteen; commuted every day, by bicycle, train, then walking; tough regime with lectures or laboratory sessions every day including Saturday morning from 8am; enjoyed it as there did meet interesting people; a man in the botany department working on chromatography let me work in his lab; we did four subject – botany, zoology, chemistry and physics; after the first year moved to the medical school where I did anatomy and physiology; discovered that I couldn’t qualify as a doctor as I would be under twenty-one so I was able to take a year out to do a Bachelor of Science degree in anatomy and physiology; took out three years and did a B.Sc., B.Sc. Hons. then Master of Science by which time I was already doing scientific research; realized I was not a good medical student but did complete another four years to qualify for the sake of a safe job; finished at the end of 1950 and I did go abroad in 1952; had been at Witwatersrand for almost nine years; had become a lecturer while still a medical student teaching physiology; became an expert on calorie intake

13:58:22 At Witwatersrand a most important influence was Raymond Dart the Professor of Anatomy but more so was a man called Joseph Gillman who was a lecturer in histology and later Professor of Physiology; working in the laboratory was a tremendous experience; nothing there so had to make amino acid for an experiment, for example; also built an ultracentrifuge and used it; parents supportive throughout although mother would have been much happier to see me as a specialist doctor; was interested in molecular biology which had not yet been invented; Waddington came out to South Africa for a time and encouraged me to apply to Cambridge which I did; they never replied to my letter; I won a rare scholarship linked to the 1851 exhibition in 1950; Principal recommended me to go to work with Cyril Hinshelwood, Professor of Physical Chemistry at Oxford; accepted to do a DPhil in physical chemistry and went in 1952

19:06:04 In South Africa made films with a group and had made one on Dylan Thomas; had to imagine what England was like from reading but it was a shock when I came here; arrived during the time of food rationing and for two years just dreamt of food; married after a term in Oxford; May was in London doing a PhD; settled in Oxford and both finished in two years; I won a travelling scholarship from the Carnegie Foundation to go to America for four months; had a very good friend in Oxford called Jack Dunitz; had come to Oxford with the idea that I could determine the structure of DNA; heard about Crick and Watson and went to Cambridge to see them in April 1953 with Jack and Leslie Orgel; they had already discovered the structure of DNA which we saw and the implications were just blindingly clear; immediately saw the problems or coding and copying and the work that needed to be done

25:00:21 On that day Francis wouldn’t stop talking but Jim gave me the impression of an irritated bird; they had made a breakthrough but no notice was taken of it for quite a time except for a tiny band of people who saw that this had reformulated major questions in biology; at Oxford there was a club called the Alembic Club of chemists and Fred Sanger came to talk in 1953 as he had just assembled insulin; Robert Robinson said it was remarkable because Sanger had proved that proteins actually had a chemical structure; Sanger was an unique scientist as he saw that determining how the sequence was arranged is important; he devised simple techniques to achieve this; he liked to work in the lab and when he retired he put down his pipette and said “That’s it” and walked out

33:47:19 John Griffith’s role in the discovery of DNA; after D.Phil went to America for four months but in the meantime started to discuss with Francis about coming back to join him in the MRC unit; had to go back to South Africa to fulfil obligations attached to my scholarship but two years later, at the end of 1956, I came to Cambridge; had a three year job at £1100 a year and three children; beginning of an incredibly exciting time in science; Francis read all the time and when he left Cambridge the entire room was full of books on the brain; value of conversation with Crick resulting in productive thoughts; I would try them out in the lab to see if they were right; value of guessing; correct theories and true theories; science similar to a medieval guild with a very good journeymen and apprentices; blinding flashes of illumination; work with Francois Jacob.

SECOND PART

0:09:07 Became a fellow of King’s in 1959; Noel Annan had wanted to get Crick as a fellow earlier but not successful; wanted someone from molecular biology and John Kendrew suggested me; was offered a fellowship at Churchill but preferred to try for King’s and was elected; quite often had tea with Morgan Foster as a benefit of the college was to have friends outside science; other friends at King’s included Francis Haskell, Michael Jaffe, and Dadie Rylands; Bernard Williams and Robert Bolgar; Edmund Leach, Meyer Fortes – always been fascinated by anthropology; did archaeology and palaeontology as a hobby; interested in creating a new anthropology which would include biology and the place of man in the animal world, the natural world and the world of our own creation; we may have the genome of Neanderthal man pretty soon

11:57:10 Originally we were housed in the Cavendish Laboratory; Crick very good at getting extra space and at the end of our time there we were in seven buildings on the site; prior to this the MRC had decided they might have a building somewhere but we did not want to be in a large place with everyone; got agreement for an MRC laboratory of molecular biology and joined up with Fred Sanger who was in urgent need of space; Hugh Huxley and Aaron Klug joined us; I officially became the director in 1979 before which Max Perutz was chairman; retired from the directorship at sixty and got my own small unit to return to science; on final retirement from the MRC managed to raise enough money to continue the lab for some time

19:54:22 Work on nematode worms; genes build the nervous system which then performs the behaviour; needed to determine the structure of the nervous system, it should be a small nervous system so could be finite and that we could make mutations and see how it altered behaviour; then we would hope to see what changes in the nervous system the mutations would produce and then would be able to map those onto the altered behaviour; that program has been partly carried out but effectively it involved doing the anatomy, the full embryology; big advantage of nematodes is according to the literature they had stereotype nervous system, constant number of cells and, it was thought, the same for every nematode of the same genetic composition; could ask under what conditions do you build a nervous system with the same genetic program; nematode ideal as easy to keep in the lab and easy for anyone to work on

29:48:12 Nobel prize awarded to me with John Sulston and Robert Horvitz; “don’t worry” hypothesis described; the virtue of ignorance

38:20:05 Went to Singapore in 1984 and encouraged them to set up a graduate department of molecular biology; from 1999 a huge surge forward and I have been involved in setting up a gigantic operation there but have just retired; advice to a young scientist would be to go to a lab where there is a good mentor; big challenge that interests me is how to reconstruct the past from what we now know; science is a way of solving problems and for a young person, find a good problem and try to solve it though getting into the whole apparatus of science, which is difficult

On November 21, 2014 I received a letter from Nobel Laureate Harry Kroto and it said:

…Please click on this URL http://vimeo.com/26991975

and you will hear what far smarter people than I have to say on this matter. I agree with them.

Harry Kroto

Nick Gathergood, David-Birkett, Harry-Kroto

I have attempted to respond to all of Dr. Kroto’s friends arguments and I have posted my responses one per week for over a year now. Here are some of my earlier posts:

Arif Ahmed, Sir David AttenboroughMark Balaguer, Horace Barlow, Michael BatePatricia ChurchlandAaron CiechanoverNoam Chomsky,Alan DershowitzHubert Dreyfus, Bart Ehrman, Stephan FeuchtwangDavid Friend,  Riccardo GiacconiIvar Giaever , Roy GlauberRebecca GoldsteinDavid J. Gross,  Brian Greene, Susan GreenfieldStephen F Gudeman,  Alan Guth, Jonathan HaidtTheodor W. Hänsch, Brian Harrison,  Hermann HauserRoald Hoffmann,  Bruce HoodHerbert Huppert,  Gareth Stedman Jones, Steve JonesShelly KaganMichio Kaku,  Stuart Kauffman,  Lawrence KraussHarry Kroto, George LakoffElizabeth Loftus,  Alan MacfarlanePeter MillicanMarvin MinskyLeonard Mlodinow,  Yujin NagasawaAlva NoeDouglas Osheroff,  Jonathan Parry,  Saul PerlmutterHerman Philipse,  Carolyn PorcoRobert M. PriceLisa RandallLord Martin Rees,  Oliver Sacks, John SearleMarcus du SautoySimon SchafferJ. L. Schellenberg,   Lee Silver Peter Singer,  Walter Sinnott-ArmstrongRonald de Sousa, Victor StengerBarry Supple,   Leonard Susskind, Raymond TallisNeil deGrasse Tyson,  .Alexander Vilenkin, Sir John WalkerFrank WilczekSteven Weinberg, and  Lewis Wolpert,

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