Sydney Brenner

Sydney Brenner
CH FRS FMedSci MAE
Brenner in 2008
Born(1927-01-13)13 January 1927
Germiston, Transvaal, South Africa
Died5 April 2019(2019-04-05) (aged 92)
Singapore
Other namesUncle Syd[10]
Alma mater
Known forGenetics of Caenorhabditis elegans[11][12]
Spouse
May Covitz
​
​
(m. 1952; died 2010)​
[2]
Children3
Awards
Scientific career
FieldsBiology
Institutions
ThesisThe physical chemistry of cell processes: a study of bacteriophage resistance in Escherichia coli, strain B (1954)
Doctoral advisorCyril Hinshelwood[6][7]
Doctoral students

Sydney Brenner CH FRS FMedSci MAE (13 January 1927 – 5 April 2019)[13][14] 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.[10] 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,[11][15] and founded the Molecular Sciences Institute in Berkeley, California, United States.[16][17][18][19][20][21][22][23]

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.[2] His parents, Leah[24] (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.[25][26]

He was educated at Germiston High School[2] 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.[25]

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).[25]

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)[7] degree at the University of Oxford as a postgraduate student of Exeter College, Oxford, supervised by Cyril Hinshelwood.[27]

Career and research

Following his DPhil, Brenner did postdoctoral research at the University of California, Berkeley.[28] He spent the next 20 years at the Laboratory of Molecular Biology[29] in Cambridge. There, during the 1960s, he contributed to molecular biology, then an emerging field. In 1976 he joined the Salk Institute in California.[2]

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.[30]

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 transfer the genetic information from RNA to proteins. Brenner gave the name "adaptor hypothesis" in 1955.[31] 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.[32] 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,[33] 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.[34]

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.[35] Barnett helped set up Sydney Brenner's laboratory in Singapore, many years later.[36][37]

Esther Lederberg, Gunther Stent, Sydney Brenner and Joshua Lederberg pictured in 1965

Brenner, with George Pieczenik,[38] 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.[39] The published scientific paper is extremely rare in that its collaborators include three authors who independently became Nobel laureates.[40]

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.[41] In fact, the C. elegans community has grown rapidly in recent decades with researchers working on a wide spectrum of problems.[42]

Brenner founded the Molecular Sciences Institute in Berkeley, California in 1996.[4] As of 2015 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.[4] In August 2005, Brenner was appointed president of the Okinawa Institute of Science and Technology.[43] He was also on the Board of Scientific Governors at The Scripps Research Institute,[44] as well as being Professor of Genetics there.[3] A scientific biography of Brenner was written by Errol Friedberg in the US, for publication by Cold Spring Harbor Laboratory Press in 2010.[19]

Known for his penetrating scientific insight and acerbic wit, Brenner, for many years, authored a regular column ("Loose Ends") in the journal Current Biology.[45][46] This column was so popular that "Loose ends from Current Biology", a compilation, was published by Current Biology Ltd.[47] and became a collectors' item. Brenner wrote "A Life in Science",[48] 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.[49][50][51][52]

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.[53] 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.[54]

Brenner also gave four lectures on the history of molecular biology, its impact on neuroscience and the great scientific questions that lie ahead.[55] The lectures were adapted into the book, In the Spirit of Science: Lectures by Sydney Brenner on DNA, Worms and Brains.[56]

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.[16][57][58] 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.[59][60]

Awards and honours

Brenner received numerous awards and honours, including:[61][62]

Personal life

Brenner was married to May Brenner (née Covitz, subsequently Balkind)[2] from December 1952 until her death in January 2010;[2] 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.[70][71] He was an atheist.[72]

Brenner died on 5 April 2019, in Singapore, at the age of 92.[10][73][74]

See also

References

  1. ^ "Louis-Jeantet Prize". Archived from the original on 4 September 2018. Retrieved 4 September 2018.
  2. ^ a b c d e f g h Anon (2015). "Brenner, Sydney". Who's Who (online Oxford University Press ed.). A & C Black. doi:10.1093/ww/9780199540884.013.U8635. (Subscription or UK public library membership required.)
  3. ^ a b "Sydney Brenner PhD". scripps.edu. Archived from the original on 2 February 2012.
  4. ^ a b c "Janelia Farm: Sydney Brenner". hhmi.org. Archived from the original on 27 December 2007.
  5. ^ "Research Units | Okinawa Institute of Science and Technology Graduate University OIST". Oist.jp. 1 February 2016. Archived from the original on 17 May 2020. Retrieved 1 December 2016.
  6. ^ Thompson, H. (1973). "Cyril Norman Hinshelwood 1897-1967". Biographical Memoirs of Fellows of the Royal Society. 19: 374–431. doi:10.1098/rsbm.1973.0015. PMID 11615727. S2CID 12385145.
  7. ^ a b Brenner, Syndney (1954). The physical chemistry of cell processes: a study of bacteriophage resistance in Escherichia coli, strain B (DPhil thesis). University of Oxford. OCLC 775695643. EThOS uk.bl.ethos.672365. Archived from the original on 23 October 2020. Retrieved 25 August 2015.
  8. ^ Rubin, Gerald Mayer (1974). Studies on 5.8 S Ribosomal RNA (PhD thesis). University of Cambridge. OCLC 500553465. EThOS uk.bl.ethos.471132. Archived from the original on 6 April 2019. Retrieved 13 November 2017.
  9. ^ White, John Graham (1974). Computer Aided Reconstruction of the Nervous System of Caenorhabditis Elegans (PhD thesis). University of Cambridge. OCLC 180702071. EThOS uk.bl.ethos.477040. Archived from the original on 6 April 2019. Retrieved 13 November 2017.
  10. ^ a b c Friedberg, Errol (2019). "Sydney Brenner (1927–2019) Mischievous steward of molecular biology's golden age". Nature. 568 (7753): 459. doi:10.1038/d41586-019-01192-9. ISSN 0028-0836. PMID 30988427.
  11. ^ a b Brenner, Sydney (1974). "The genetics of Caenorhabditis elegans". Genetics. 77 (1): 71–94. doi:10.1093/genetics/77.1.71. PMC 1213120. PMID 4366476.
  12. ^ Sulston, J.; Brenner, S. (1974). "The DNA of Caenorhabditis elegans". Genetics. 77 (1): 95–104. doi:10.1093/genetics/77.1.95. PMC 1213121. PMID 4858229.
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  16. ^ a b The Science Times Book of the Brain 1998. Edited by Nicholas Wade. The Lyons Press
  17. ^ 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; ISBN 0-14-017800-7.
  18. ^ Brenner, S.; Elgar, G.; Sanford, R.; Macrae, A.; Venkatesh, B.; Aparicio, S. (1993). "Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome". Nature. 366 (6452): 265–68. Bibcode:1993Natur.366..265B. doi:10.1038/366265a0. ISSN 0028-0836. PMID 8232585. S2CID 2715056.
  19. ^ a b "Sydney Brenner: A Biography" by Errol Friedberg, pub. CSHL Press October 2010, ISBN 0-87969-947-7.
  20. ^ de Chadarevian, Soraya (2009). "Interview with Sydney Brenner". Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences. 40 (1): 65–71. doi:10.1016/j.shpsc.2008.12.008. ISSN 1369-8486. PMID 19268875.
  21. ^ Friedberg, Errol C. (2008). "Sydney Brenner". Nature Reviews Molecular Cell Biology. 9 (1): 8–9. doi:10.1038/nrm2320. ISSN 1471-0072. PMID 18159633. S2CID 1037231.
  22. ^ Sydney Brenner's publications indexed by the Scopus bibliographic database. (subscription required)
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  28. ^ "Sydney Brenner: Senior Distinguished Fellow of the Crick-Jacobs Center". Salk Institute. Archived from the original on 1 October 2015. Retrieved 25 August 2015.
  29. ^ John Finch; 'A Nobel Fellow on Every Floor', Medical Research Council 2008; ISBN 978-1-84046-940-0
    This book is all about the MRC Laboratory of Molecular Biology, Cambridge.
  30. ^ Olby, Robert, Francis Crick: Hunter of Life's Secrets, Cold Spring Harbor Laboratory Press, 2009, Chapter 10, pg. 181; ISBN 978-0-87969-798-3
  31. ^ Crick, Francis (1955). "On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club". National Library of Medicine. Archived from the original on 16 August 2022. Retrieved 21 July 2022.
  32. ^ Cobb, Matthew (29 June 2015). "Who discovered messenger RNA?". Current Biology. 25 (13): R526 – R532. Bibcode:2015CBio...25.R526C. doi:10.1016/j.cub.2015.05.032. PMID 26126273.
  33. ^ Crick, Francis; Barnett, Leslie; Brenner, Sydney; Watts-Tobin, Richard J (1961). "General nature of the genetic code for proteins". Nature. 192 (4809): 1227–32. Bibcode:1961Natur.192.1227C. doi:10.1038/1921227a0. PMID 13882203. S2CID 4276146.
  34. ^ 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
  35. ^ Goldstein, Bob (30 May 2019). "The Thrill of Defeat: What Francis Crick and Sydney Brenner taught me about being scooped". Nautilus. Archived from the original on 10 December 2021. Retrieved 21 January 2021.
  36. ^ Kaplish, L. (19 February 2014). "Uncovering a scientific life in the archives". Wellcome Library blog. Archived from the original on 23 October 2020. Retrieved 5 April 2019.
  37. ^ Lloyd-Evans, L. P. M. (January 2005). A Study into the Prospects for Marine Biotechnology Development in the United Kingdom (PDF) (Report). Vol. 2 – Background & Appendices. Foresight Marine Panel Marine Biotechnology Group. p. 237. Archived (PDF) from the original on 23 October 2020. Retrieved 5 April 2019.
  38. ^ "Letter by Brenner (primary source)" (PDF). rutgers.edu. Archived from the original (PDF) on 7 November 2004. Retrieved 8 April 2019.
  39. ^ Crick, FH; Brenner, S; Klug, A; Pieczenik, G (December 1976). "A speculation on the origin of protein synthesis". Origins of Life. 7 (4): 389–97. Bibcode:1976OrLi....7..389C. doi:10.1007/BF00927934. PMID 1023138. S2CID 42319222.
  40. ^ Crick won a Nobel prize in 1962, Brenner in 2002, and Klug in 1982. However, this is not the only case. See Barton, D. H. R.; Jeger, O.; Prelog, V.; Woodward, R. B. (March 1954). "The constitutions of cevine and some related alkaloids". Experientia. 10 (3): 81–90. doi:10.1007/BF02158513. PMID 13161888. S2CID 27430632. Barton (1969), Prelog (1975) and Woodward (1965) all became Nobel winners.
  41. ^ Sydney Brenner on Nobelprize.org Edit this at Wikidata including the Nobel Lecture 8 December 2002 Nature's Gift to Science
  42. ^ Brenner, Sydney (1 June 2009). "In the Beginning Was the Worm …". Genetics. 182 (2): 413–415. doi:10.1534/genetics.109.104976. ISSN 0016-6731. PMC 2691750. PMID 19506024.
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  44. ^ Profile Archived 9 July 2018 at the Wayback Machine, Scripps.edu; accessed 28 July 2016.
  45. ^ "Library: Sydney Brenner's Loose Ends". cell.com. Archived from the original on 6 May 2016. Retrieved 25 August 2015.
  46. ^ Brenner, Sydney (1994). "Loose Ends". Current Biology. 4 (1): 88. Bibcode:1994CBio....4...88B. doi:10.1016/S0960-9822(00)00023-3. ISSN 0960-9822.
  47. ^ Loose ends from Current Biology (1997) ISBN 1 85922 325 7
  48. ^ A Life in Science (2001) ISBN 0-9540278-0-9
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  54. ^ Sydney Brenner's 10-on-10: The Chronicles of Evolution. Wildtype Books. 9 November 2018. ISBN 978-9811187186.
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  56. ^ Brenner, Sydney; Sejnowski, Terrence (2018). In the Spirit of Science: Lectures by Sydney Brenner on DNA, Worms and Brains. World Scientific Publishing Co. doi:10.1142/11029. ISBN 978-981-3271-73-9.
  57. ^ Gilbert, S.F. (2000). "The Developmental Mechanics of Cell Specification". Developmental Biology. Sunderland (MA): Sinauer Associates. ISBN 978-0-87893-243-6.
  58. ^ McKay, R. (1997). "The Origins of the Central Nervous System". In Gage, F.H.; Christen, Y. (eds.). Isolation, Characterization and Utilization of CNS Stem Cells. Berlin Heidelberg: Springer-Verlag. pp. 169–170. ISBN 978-3-642-80308-6. Archived from the original on 24 September 2023. Retrieved 13 August 2019.
  59. ^ Marcus, Gary Fred (2004). The Birth of the Mind: How a Tiny Number of Genes Creates the Complexities of Human Thought. Basic Books. p. 64. ISBN 9780465044054. Archived from the original on 24 September 2023. Retrieved 6 April 2019.
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  69. ^ "There's a New Squid in Town". Okinawa Institute of Science and Technology Graduate University OIST. 11 December 2019. Archived from the original on 15 February 2020. Retrieved 15 February 2020.
  70. ^ "Loose Ends" : Collection of Loose Ends/False Starts columns by 'Uncle Syd.' from January 1994 to December 2000 (Current Biology, 1997) ISBN 1859223257
  71. ^ 'My Life in Science', with Lewis Wolpert, edited by Errol C. Friedberg and Eleanor Lawrence, BioMed Central, 2001; ISBN 0-9540278-0-9
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