Sydney Brenner

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Template:Short description Template:Use dmy dates Template:Use South African English Template:Infobox scientist

Sydney Brenner Template:Postnominals (13 January 1927 – 5 April 2019)<ref>Template:Cite news</ref><ref>Template:Cite journal</ref> was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston.<ref name=fried>Template:Cite journal</ref> Brenner made significant contributions to work on the genetic code, and other areas of molecular biology while working in the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England. He established the roundworm Caenorhabditis elegans as a model organism for the investigation of developmental biology,<ref name=celegans/><ref name=hodgkin>Template:Cite journal</ref> and founded the Molecular Sciences Institute in Berkeley, California, United States.<ref name=wade>The Science Times Book of the Brain 1998. Edited by Nicholas Wade. The Lyons Press</ref><ref name=eighthday>Horace Freeland Judson The Eighth Day of Creation (1979), pp. 10–11 Makers of the Revolution in Biology; Penguin Books 1995, first published by Jonathan Cape, 1977; Template:ISBN.</ref><ref name="BrennerElgar1993">Template:Cite journal</ref><ref name=errol>"Sydney Brenner: A Biography" by Errol Friedberg, pub. CSHL Press October 2010, Template:ISBN.</ref><ref name="de Chadarevian2009">Template:Cite journal</ref><ref name="Friedberg2008">Template:Cite journal</ref><ref name=scopus>Template:Scopus</ref><ref name=googlescholar>Template:Cite web</ref>

Education and early life

Brenner was born in the town of Germiston in the then Transvaal (today in Gauteng), South Africa, on 13 January 1927.<ref name=whoswho/> His parents, Leah<ref>Template:Cite web</ref> (née Blecher) and Morris Brenner, were Jewish immigrants. His father, a cobbler, came to South Africa from Lithuania in 1910, and his mother from Riga, Latvia, in 1922. He had one sister, Phyllis.<ref name="autobiography">Template:Cite web</ref><ref>Template:Cite web</ref>

He was educated at Germiston High School<ref name=whoswho>Template:Who's Who</ref> and the University of the Witwatersrand. Having joined the university at the age of 15, it was noted during his second year that he would be too young to qualify for the practice of medicine at the conclusion of his six-year medical course, and he was therefore allowed to complete a Bachelor of Science degree in Anatomy and Physiology. During this time he was taught physical chemistry by Joel Mandelstam, microscopy by Alfred Oettle and neurology by Harold Daitz. He also received an introduction to anthropology and paleontology from Raymond Dart and Robert Broom. The histologist Joseph Gillman and director of research in the Anatomy Department persuaded Brenner to continue towards an honours degree and beyond towards an MSc. Brenner accepted though this would mean he would not graduate from medical school and his bursary would be discontinued. He supported himself during this time by working as a laboratory technician. It was during this time, in 1945, that Brenner would publish his first scientific works. His masters thesis was in the field of cytogenetics and publications during this time in the field Brenner would later call Cell Physiology.<ref name="autobiography"/>

In 1946 Wilfred Le Gros Clark invited Brenner to his Department of Anatomy in Oxford, during a visit to South Africa. Brenner was persuaded to finish his medical education instead. Brenner returned to medical school where he failed Medicine, nearly failed Surgery and achieved a First Class in Obstetrics and Gynecology. Six months later Brenner had finished repeating Medicine and Surgery and in 1951 received the degrees of Bachelor of Medicine, Bachelor of Surgery (MBBCh).<ref name="autobiography"/>

Brenner received an 1851 Exhibition Scholarship from the Royal Commission for the Exhibition of 1851 which enabled him to complete a Doctor of Philosophy (DPhil)<ref name=phd>Template:Cite thesis</ref> degree at the University of Oxford as a postgraduate student of Exeter College, Oxford, supervised by Cyril Hinshelwood.<ref>Template:Cite web</ref>

Career and research

Following his DPhil, Brenner did postdoctoral research at the University of California, Berkeley.<ref name=berkeley>Template:Cite web</ref> He spent the next 20 years at the Laboratory of Molecular Biology<ref>John Finch; 'A Nobel Fellow on Every Floor', Medical Research Council 2008; Template:ISBN
This book is all about the MRC Laboratory of Molecular Biology, Cambridge.</ref> in Cambridge. There, during the 1960s, he contributed to molecular biology, then an emerging field. In 1976 he joined the Salk Institute in California.<ref name=whoswho/>

Together with Jack Dunitz, Dorothy Hodgkin, Leslie Orgel, and Beryl M. Oughton, he was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson; at the time he and the other scientists were working at the University of Oxford's Chemistry Department. All were impressed by the new DNA model, especially Brenner, who subsequently worked with Crick in the Cavendish Laboratory at the University of Cambridge and the newly opened Medical Research Council (MRC) Laboratory of Molecular Biology (LMB). According to Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA.<ref>Olby, Robert, Francis Crick: Hunter of Life's Secrets, Cold Spring Harbor Laboratory Press, 2009, Chapter 10, pg. 181; Template:ISBN</ref>

Brenner made several seminal contributions to the emerging field of molecular biology in the 1960s (see Phage group). The first was to prove that all overlapping genetic coding sequences were impossible. This insight separated the coding function from structural constraints as proposed in a clever code by George Gamow. This led Francis Crick to propose the concept of a hypothetical molecule (later identified as transfer RNA or tRNA) that transfers the genetic information from RNA to proteins. Brenner gave the name "adaptor hypothesis" in 1955.<ref name=":0">Template:Cite web</ref> The physical separation between the anticodon and the amino acid on a tRNA is the basis for the unidirectional flow of information in coded biological systems. This is commonly known as the central dogma of molecular biology, i.e. information flows from nucleic acid to protein and never from protein to nucleic acid. Following this adaptor insight, Brenner conceived of the concept of messenger RNA during an April 1960 conversation with Crick and François Jacob, and together with Jacob and Matthew Meselson went on to prove its existence later that summer.<ref name="Cobb">Template:Cite journal</ref> Then, with Crick, Leslie Barnett, and Richard J. Watts-Tobin, Brenner genetically demonstrated the triplet nature of the code of protein translation through the Crick, Brenner, Barnett, Watts-Tobin et al. experiment of 1961,<ref>Template:Cite journal</ref> which discovered frameshift mutations. Brenner collaborating with Sarabhai, Stretton and Bolle in 1964, using amber mutants defective in the bacteriophage T4D major head protein, showed that the nucleotide sequence of the gene is co-linear with the amino acid sequence of the encoded polypeptide chain.<ref>Sarabhai AS, Stretton AO, Brenner S, Bolle A. Co-linearity of the gene with the polypeptide chain. Nature. 1964 Jan 4;201:13-7. doi: 10.1038/201013a0. PMID 14085558</ref>

Together with the decoding work of Marshall Warren Nirenberg and others, the discovery of the triplet nature of the genetic code was critical to deciphering the code.<ref name=NautilusGoldstein>Template:Cite web</ref> Barnett helped set up Sydney Brenner's laboratory in Singapore, many years later.<ref>Template:Cite web</ref><ref>Template:Cite report</ref>

File:EMLederberg GStent SBrenner JLederberg 1965 wiki.jpg
Esther Lederberg, Gunther Stent, Sydney Brenner and Joshua Lederberg pictured in 1965

Brenner, with George Pieczenik,<ref>Template:Cite web</ref> created the first computer matrix analysis of nucleic acids using TRAC, which Brenner continued to use. Crick, Brenner, Klug and Pieczenik returned to their early work on deciphering the genetic code with a pioneering paper on the origin of protein synthesis, where constraints on mRNA and tRNA co-evolved allowing for a five-base interaction with a flip of the anticodon loop, and thereby creating a triplet code translating system without requiring a ribosome. This model requires a partially overlapping code.<ref name="Klug">Template:Cite journal</ref> The published scientific paper is extremely rare in that its collaborators include three authors who independently became Nobel laureates.<ref name="Another">Crick won a Nobel prize in 1962, Brenner in 2002, and Klug in 1982. However, this is not the only case. See Template:Cite journal Barton (1969), Prelog (1975) and Woodward (1965) all became Nobel winners.</ref>

Brenner then focused on establishing a free-living roundworm Caenorhabditis elegans as a model organism for the investigation of animal development including neural development. He chose this 1-millimeter-long soil roundworm mainly because it is simple, is easy to grow in bulk populations, and turned out to be quite convenient for genetic analysis. One of the key methods for identifying important function genes was the screen for roundworms that had some functional defect, such as being uncoordinated, leading to the identification of new sets of proteins, such as the UNC proteins. For this work, he shared the 2002 Nobel Prize in Physiology or Medicine with H. Robert Horvitz and John Sulston. The title of his Nobel lecture in December 2002, "Nature's Gift to Science", is a homage to this nematode; in it, he considered that having chosen the right organism turned out to be as important as having addressed the right problems to work on.<ref>Template:Nobelprize including the Nobel Lecture 8 December 2002 Nature's Gift to Science</ref> In fact, the C. elegans community has grown rapidly in recent decades with researchers working on a wide spectrum of problems.<ref>Template:Cite journal</ref>

Brenner founded the Molecular Sciences Institute in Berkeley, California in 1996.<ref name=hhmi/> Template:As of he was associated with the Salk Institute, the Institute of Molecular and Cell Biology, the Singapore Biomedical Research Council, the Janelia Farm Research Campus, and the Howard Hughes Medical Institute.<ref name=hhmi/> In August 2005, Brenner was appointed president of the Okinawa Institute of Science and Technology.<ref>Template:Cite web</ref> He was also on the Board of Scientific Governors at The Scripps Research Institute,<ref>Profile Template:Webarchive, Scripps.edu; accessed 28 July 2016.</ref> as well as being Professor of Genetics there.<ref name=scripps>Template:Cite web</ref> A scientific biography of Brenner was written by Errol Friedberg in the US, for publication by Cold Spring Harbor Laboratory Press in 2010.<ref name=errol/>

Known for his penetrating scientific insight and acerbic wit, Brenner, for many years, authored a regular column ("Loose Ends") in the journal Current Biology.<ref>Template:Cite web</ref><ref name="Brenner1994">Template:Cite journal</ref> This column was so popular that "Loose ends from Current Biology", a compilation, was published by Current Biology Ltd.<ref>Loose ends from Current Biology (1997) Template:ISBN</ref> and became a collector's item. Brenner wrote "A Life in Science",<ref>A Life in Science (2001) Template:ISBN</ref> a paperback published by BioMed Central. He is also noted for his generosity with ideas and the great number of students and colleagues his ideas have stimulated.<ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref>

In 2017, Brenner co-organized a seminal lecture series in Singapore describing ten logarithmic scales of time from the Big Bang to the present, spanning the appearance of multicellular life forms, the evolution of humans, and the emergence of language, culture and technology.<ref>Template:Cite web</ref> Prominent scientists and thinkers, including W. Brian Arthur, Svante Pääbo, Helga Nowotny and Jack Szostak, spoke during the lecture series. In 2018, the lectures were adapted into a popular science book titled Sydney Brenner's 10-on-10: The Chronicles of Evolution, published by Wildtype Books.<ref>Template:Cite book</ref>

Brenner also gave four lectures on the history of molecular biology, its impact on neuroscience and the great scientific questions that lie ahead.<ref>Template:Cite web</ref> The lectures were adapted into the book, In the Spirit of Science: Lectures by Sydney Brenner on DNA, Worms and Brains.<ref>Template:Cite book</ref>

American plan and European plan

The "American plan" and "European plan" were proposed by Sydney Brenner as competing models for the way brain cells determine their neural functions.<ref name=wade/><ref>Template:Cite book</ref><ref>Template:Cite book</ref> According to the European plan (sometimes referred to as the British plan), the function of cells is determined by their genetic lineage. According to the American plan, a cell's function is determined by the function of its neighbours after cell migration. Further research has shown that most species follow some combination of these methods, albeit in varying degrees, to transfer information to new cells.<ref>Template:Cite book</ref><ref>Template:Cite book</ref>

Awards and honours

Brenner received numerous awards and honours, including:<ref>Template:Cite web</ref><ref>Template:Cite web</ref> Template:Div col

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Personal life

Brenner was married to May Brenner (Template:Nee, subsequently Balkind)<ref name=whoswho/> from December 1952 until her death in January 2010;<ref name=whoswho/> their children include Belinda, Carla, Stefan, and his stepson Jonathan Balkind from his wife's first marriage to Marcus Balkind. He lived in Ely, Cambridgeshire.<ref>"Loose Ends" : Collection of Loose Ends/False Starts columns by 'Uncle Syd.' from January 1994 to December 2000 (Current Biology, 1997) Template:ISBN</ref><ref>'My Life in Science', with Lewis Wolpert, edited by Errol C. Friedberg and Eleanor Lawrence, BioMed Central, 2001; Template:ISBN</ref> He was an atheist.<ref>Template:Cite book</ref>

Brenner died on 5 April 2019, in Singapore, at the age of 92.<ref name=fried/><ref name=asianscientist>Template:Cite web</ref><ref>Template:Cite web</ref>

See also

References

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Further reading

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