Sydney Brenner

Sydney Brenner CH FRS FMedSci MAE (13 January 1927 – 5 April 2019)[15] 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.[1] 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,[2][16] and founded the Molecular Sciences Institute in Berkeley, California, United States.[17][18][19][20][21][22][23][24]

Sydney Brenner

CH FRS FMedSci MAE
Brenner in 2008
Born(1927-01-13)13 January 1927
Germiston, Transvaal, Union of South Africa
Died5 April 2019(2019-04-05) (aged 92)
Singapore
NationalitySouth African
Other namesUncle Syd[1]
Alma mater
Known forGenetics of Caenorhabditis elegans[2][3]
Spouse(s)
May Covitz
(m. 1952; her death 2010)
[4]
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[10][11]
Doctoral students
InfluencesFred Sanger[14]
Websitesalk.edu/faculty/brenner.html

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.[4] His parents, Leah[25] (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 sibling, a sister, Phyllis.[26][27]

He was educated at Germiston High School[4] and the University of the Witwatersrand. Having joined 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. He stayed on for two more years doing an Honours degree and then an MSc degree, supporting himself by working part-time as a laboratory technician. During this time he was taught by Joel Mandelstam, Raymond Dart and Robert Broom. His master thesis was in the field of cytogenetics. In 1951 he received the Bachelor of Medicine, Bachelor of Surgery (MBBCh) degree.[26]

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)[11] degree at the University of Oxford as a postgraduate student of Exeter College, Oxford, supervised by Cyril Hinshelwood.[28]

Career and research

Following his DPhil, Brenner did postdoctoral research at the University of California, Berkeley.[29] He spent the next 20 years at the Laboratory of Molecular Biology[30] in Cambridge. There, during the 1960s, he contributed to molecular biology, then an emerging field. In 1976 he joined the Salk Institute in California.[4]

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 the late 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.[31]

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 the adaptor or as it is now known "transfer RNA (tRNA)". 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. that information flows from nucleic acid to protein and never from protein to nucleic acid. Following this adaptor insight, Brenner proposed the concept of a messenger RNA, based on correctly interpreting the work of Elliot "Ken" Volkin and Larry Astrachan.[32] Then, with Francis 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. This insight provided early elucidation of the nature of the genetic code. Leslie Barnett helped set up Sydney Brenner's laboratory in Singapore, many years later.[34][35]

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

Brenner, with George Pieczenik,[36] 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.[37] The published scientific paper is extremely rare in that its collaborators include three authors who independently became Nobel laureates.[38]

Brenner then focused on establishing Caenorhabditis elegans as a model organism for the investigation of animal development including neural development. Brenner 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 set of 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 on 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.[39] In fact, the C. elegans community has grown rapidly in recent decades with researchers working on a wide spectrum of problems.[40]

Brenner founded the Molecular Sciences Institute in Berkeley, California in 1996.[8] 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.[8] In August 2005, Brenner was appointed president of the Okinawa Institute of Science and Technology.[41] He was also on the Board of Scientific Governors at The Scripps Research Institute,[42] as well as being Professor of Genetics there.[7] A scientific biography of Brenner was written by Errol Friedberg in the US, for publication by Cold Spring Harbor Laboratory Press in 2010.[20]

Known for his penetrating scientific insight and acerbic wit, Brenner, for many years, authored a regular column ("Loose Ends") in the journal Current Biology.[43][44] This column was so popular that "Loose ends from Current Biology", a compilation, was published by Current Biology Ltd.[45] and became a collectors' item. Brenner wrote "A Life In Science",[46] a paperback published by BioMed Central. Brenner is also noted for his generosity with ideas and the great number of students and colleagues his ideas have stimulated.[47][48][49][50]

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.[51] 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.[52]

Brenner also gave four lectures on the history of Molecular Biology, its impact on Neuroscience and the great scientific questions that lie ahead.[53] The lectures were adapted into the book, In the Spirit of Science: Lectures by Sydney Brenner on DNA, Worms and Brains.[54]

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.[17][55][56] According to the European plan (sometimes referred to as the British plan), the function of cells is determined by its 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.[57][58]

Awards and honours

Brenner received numerous awards and honours, including:[59][60]

Personal life

Brenner was married to May Brenner (née Covitz, subsequently Balkind)[4] from December 1952 until her death in January 2010;[4] 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.[68][69] He was an atheist.[70]

Brenner died on 5 April 2019, in Singapore, at the age of 92.[1][71][72]

References
  1. 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.
  2. Brenner, Sydney (1974). "The genetics of Caenorhabditis elegans". Genetics. 77 (1): 71–94. PMC 1213120. PMID 4366476.
  3. Sulston, J.; Brenner, S. (1974). "The DNA of Caenorhabditis elegans". Genetics. 77 (1): 95–104. PMC 1213121. PMID 4858229.
  4. Anon (2015). "Brenner, Sydney". Who's Who (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. doi:10.1093/ww/9780199540884.013.U8635. (subscription or UK public library membership required) (subscription required)
  5. "Sydney Brenner EMBO profile". people.embo.org. Heidelberg: European Molecular Biology Organization.
  6. Louis-Jeantet Prize
  7. "Sydney Brenner PhD". scripps.edu. Archived from the original on 2 February 2012.
  8. "Janelia Farm: Sydney Brenner". hhmi.org. Archived from the original on 27 December 2007.
  9. "Research Units | Okinawa Institute of Science and Technology Graduate University OIST". Oist.jp. 1 February 2016. Retrieved 1 December 2016.
  10. 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.
  11. 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.
  12. Rubin, Gerald Mayer (1974). Studies on 5.8 S Ribosomal RNA (PhD thesis). University of Cambridge. OCLC 500553465. EThOS uk.bl.ethos.471132.
  13. 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.
  14. Elizabeth Dzeng (2014). "How Academia and Publishing are Destroying Scientific Innovation: A Conversation with Sydney Brenner". kingsreview.co.uk. Archived from the original on 5 February 2015.
  15. Wade, Nicholas (5 April 2019). "Sydney Brenner, a Decipherer of the Genetic Code, Is Dead at 92". The New York Times.
  16. Hodgkin, JA; Brenner, S (1977). "Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans". Genetics. 86 (2 Pt. 1): 275–87. ISSN 0016-6731. PMC 1213677. PMID 560330.
  17. The Science Times Book of the Brain 1998. Edited by Nicholas Wade. The Lyons Press
  18. 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.
  19. 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.
  20. "Sydney Brenner: A Biography" by Errol Friedberg, pub. CSHL Press October 2010, ISBN 0-87969-947-7.
  21. 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.
  22. Friedberg, Errol C. (2008). "Sydney Brenner". Nature Reviews Molecular Cell Biology. 9 (1): 8–9. doi:10.1038/nrm2320. ISSN 1471-0072. PMID 18159633.
  23. Sydney Brenner's publications indexed by the Scopus bibliographic database. (subscription required)
  24. "Sydney Brenner publications". Google Scholar. Retrieved 28 September 2008.
  25. "Errol C. Friedberg. Sydney Brenner: A Biography" (PDF). cshlpress.com.
  26. "Sydney Brenner, Biographical". nobelprize.org. Retrieved 6 April 2019.
  27. "Brenner, Sydney (1927– ) World of Microbiology and Immunology". encyclopedia.com. Retrieved 27 July 2016.
  28. "Dr Sydney Brenner". Exeter College. Retrieved 6 April 2019.
  29. "Sydney Brenner: Senior Distinguished Fellow of the Crick-Jacobs Center". Salk Institute.
  30. 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.
  31. 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
  32. Volkin, Elliot; Astrachan, L. (1956). "Phosphorus incorporation in Escherichia coli ribonucleic acid after infection with bacteriophage T2". Virology. 2 (2): 149–161. doi:10.1016/0042-6822(56)90016-2. ISSN 0042-6822. PMID 13312220.
  33. Crick FH, Barnett L, Brenner S, Watts-Tobin RJ (1961). "General nature of the genetic code for proteins". Nature. 192 (4809): 1227–32. Bibcode:1961Natur.192.1227C. doi:10.1038/1921227a0. PMID 13882203.CS1 maint: multiple names: authors list (link)
  34. Kaplish, L. (19 February 2014). "Uncovering a scientific life in the archives". Wellcome Library blog. Retrieved 5 April 2019.
  35. Lloyd-Evans, L. P. M. (January 2005). A Study into the Prospects for Marine Biotechnology Development in the United Kingdom (PDF) (Report). Volume 2 – Background & Appendices. Foresight Marine Panel Marine Biotechnology Group. p. 237. Retrieved 5 April 2019.
  36. "Letter by Brenner (primary source)" (PDF). rutgers.edu.
  37. 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. Retrieved 8 March 2018.
  38. 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. Barton (1969), Prelog (1975) and Woodward (1965) all became Nobel winners.
  39. Sydney Brenner on Nobelprize.org including the Nobel Lecture December 8, 2002 Nature's Gift to Science
  40. 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.
  41. "Dr. Sydney Brenner | Okinawa Institute of Science and Technology Graduate University OIST". Oist.jp. 12 January 2010. Archived from the original on 18 December 2015. Retrieved 1 December 2016.
  42. Profile, Scripps.edu; accessed 28 July 2016.
  43. "Library: Sydney Brenner's Loose Ends". cell.com.
  44. Brenner, Sydney (1994). "Loose Ends". Current Biology. 4 (1): 88. doi:10.1016/S0960-9822(00)00023-3. ISSN 0960-9822.
  45. Loose ends from Current Biology (1997) ISBN 1 85922 325 7
  46. A Life in Science (2001) ISBN 0-9540278-0-9
  47. Brenner, Sydney. "Coming from Eastern European stock" – via www.webofstories.com.
  48. "Sydney Brenner interviewed by Alan Macfarlane, 2007-08-23 (film)". alanmacfarlane.com.
  49. "Genomes Tell Us About the Past: Sydney Brenner". iBiology.org.
  50. "The Sydney Brenner papers". Wellcome Library. 25 October 2016. Retrieved 1 December 2016.
  51. "10-on-10: The Chronicles of Evolution".
  52. Sydney Brenner's 10-on-10: The Chronicles of Evolution. Wildtype Books. 9 November 2018. ISBN 978-9811187186.
  53. "Sydney Brenner's lectures".
  54. 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.
  55. Gilbert, S.F. (2000). "The Developmental Mechanics of Cell Specification". Developmental Biology. Sunderland (MA): Sinauer Associates. ISBN 978-0-87893-243-6.
  56. 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.
  57. 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.
  58. Rensberger, Boyce (1998). Life Itself: Exploring the Realm of the Living Cell. Oxford University Press. p. 162. ISBN 9780195125009.
  59. "Sydney Brenner CV" (PDF). ETH Zurich. Retrieved 6 April 2019.
  60. "Sydney Brenner Curriculum Vitae". NobelPrize.org. Retrieved 6 April 2019.
  61. "All Gairdner Winners". The Canada Gairdner Awards. Retrieved 5 April 2019.
  62. "2002 Nobel Prize". nobelprize.org. Retrieved 28 September 2008.
  63. "Dan David Prize laureate 2002: Sydney Brenner". dandavidprize.org. Archived from the original on 23 July 2011. Retrieved 28 September 2008.
  64. March of Dimes and Richard B. Johnston, Jr., MD Prize in Developmental Biology Awardees (PDF), retrieved 5 April 2019
  65. Sudhausi, Walter; Kiontke, Karin (25 April 2007). "Comparison of the cryptic nematode species Caenorhabditis brenneri sp. n" (PDF). Zootaxa. 1456: 45–62. doi:10.11646/zootaxa.1456.1.2. Retrieved 28 September 2008.
  66. "Sydney Brenner Institute for Molecular Bioscience". University of the Witwatersrand. Retrieved 28 September 2008.
  67. "There's a New Squid in Town". Okinawa Institute of Science and Technology Graduate University OIST. 11 December 2019. Retrieved 15 February 2020.
  68. "Loose Ends" : Collection of Loose Ends/False Starts columns by 'Uncle Syd.' from January 1994 to December 2000 (Current Biology, 1997) ISBN 1859223257
  69. 'My Life in Science', with Lewis Wolpert, edited by Errol C. Friedberg and Eleanor Lawrence, BioMed Central, 2001; ISBN 0-9540278-0-9
  70. István Hargittai; Magdolna Hargittai (2006). Candid Science VI: More Conversations with Famous Scientists. p. 32. ISBN 9781908977533.
  71. Shuzhen, Sim (5 April 2019). "Sydney Brenner, 'father of the worm' and decoder of DNA, dies at 92". asianscientist.com. Retrieved 5 April 2019.
  72. "Sydney Brenner (1927–2019)". MRC Laboratory of Molecular Biology. 5 April 2019. Retrieved 6 April 2019.

Further reading
  • Soraya De Chadarevian; Designs For Life: Molecular Biology After World War II, CUP 2002, 444 pp; ISBN 0-521-57078-6
  • Francis Crick; What Mad Pursuit: A Personal View of Scientific Discovery (Basic Books reprint edition, 1990) ISBN 0-465-09138-5
  • Georgina Ferry; 'Max Perutz and the Secret of Life', (Chatto & Windus 2007) 352pp, ISBN 978-0-7011-7695-2. For uncaptioned picture.
  • Robert Olby; Francis Crick: Hunter of Life's Secrets, Cold Spring Harbor Laboratory Press, ISBN 978-0-87969-798-3, published on 25 August 2009.
  • Max Perutz; What a Time I am Having: Selected Letters., CSHL Press 2008, 506pp ISBN 978-0-87969-864-5. For captioned picture.
  • Matt Ridley; Francis Crick: Discoverer of the Genetic Code (Eminent Lives) first published in June 2006 in the US and then in the UK September 2006, by HarperCollins Publishers; 192 pp, ISBN 0-06-082333-X; in paperback, by Atlas Books (with index), ISBN 978-0-00-721331-3.
  • Sydney Brenner Collection Cold Spring Harbor Laboratory Archives
  • Lewis Wolpert; How We Live and Why We Die, Faber and Faber 2009, 240 pp; ISBN 978-0-571-23912-2
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