Sydney Brenner

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Sydney Brenner

Sydney Brenner OIST 2008 (33208371153) (cropped).jpg
Brenner in 2008
Born(1927-01-13)13 January 1927
Died5 April 2019(2019-04-05) (aged 92)
Nationality South African
Other namesUncle Syd [1]
Alma mater
Known for Genetics of Caenorhabditis elegans [2] [3]
Spouse(s)
May Covitz
(m. 1952;her death 2010)
[4]
Children3
Awards
Scientific career
Fields Biology
Institutions
Thesis The physical chemistry of cell processes: a study of bacteriophage resistance in Escherichia coli, strain B  (1954)
Doctoral advisor Cyril Hinshelwood [10] [11]
Doctoral students
Influences Fred Sanger [14]
Website salk.edu/faculty/brenner.html

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]

Fellow of the Royal Society Elected Fellow of the Royal Society, including Honorary, Foreign and Royal Fellows

Fellowship of the Royal Society is an award granted to individuals that the Royal Society of London judges to have made a 'substantial contribution to the improvement of natural knowledge, including mathematics, engineering science, and medical science'.

Fellow of the Academy of Medical Sciences award for fellows who are recognised for the excellence of their science, their contribution to medicine and society and the range of their achievements

Fellowship of the Academy of Medical Sciences (FMedSci) is an award for medical scientists who are judged by the Academy of Medical Sciences for the "excellence of their science, their contribution to medicine and society and the range of their achievements".

Membership of the Academia Europaea (MAE) is an award conferred by the Academia Europaea to individuals that have demonstrated "sustained academic excellence".

Contents

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]

Germiston Place in Gauteng, South Africa

Germiston is a small city in the East Rand region of Gauteng, South Africa, administratively forming part of the City of Ekurhuleni Metropolitan Municipality since the latter's establishment in 2000. It functions as the municipal seat of Ekurhuleni, hosting the municipal council and administration.

Gauteng Province of South Africa

Gauteng is one of the nine provinces of South Africa. The name is in Sotho-Tswana and it means "place of gold." Nguni speakers call it eGoli.

Lithuania Republic in Northeastern Europe

Lithuania, officially the Republic of Lithuania, is a country in the Baltic region of Europe. Lithuania is considered to be one of the Baltic states. It is situated along the southeastern shore of the Baltic Sea, to the east of Sweden and Denmark. It is bordered by Latvia to the north, Belarus to the east and south, Poland to the south, and Kaliningrad Oblast to the southwest. Lithuania has an estimated population of 2.8 million people as of 2019, and its capital and largest city is Vilnius. Other major cities are Kaunas and Klaipėda. Lithuanians are Baltic people. The official language, Lithuanian, is one of only two living languages in the Baltic branch of the Indo-European language family, the other being Latvian.

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]

Germiston High School school


Germiston High School is a South African English-medium government school based in Germiston. It is the second oldest high school in Germiston.

University of the Witwatersrand public research university in Johannesburg, South Africa

The University of the Witwatersrand, Johannesburg, is a multi-campus South African public research university situated in the northern areas of central Johannesburg. It is more commonly known as Wits University or Wits. The university has its roots in the mining industry, as do Johannesburg and the Witwatersrand in general. Founded in 1896 as the South African School of Mines in Kimberley, it is the third oldest South African university in continuous operation.

A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years, or a person holding such a degree.

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]

Royal Commission for the Exhibition of 1851

The Royal Commission for the Exhibition of 1851 is an institution founded in 1850 to administer the international exhibition of 1851, officially called the Great Exhibition of the Works of Industry of all Nations. The Great Exhibition was held in The Crystal Palace in Hyde Park London, England. The enormous building was designed by Joseph Paxton for the Exhibition and construction was supervised by William Cubitt using a cast iron space frame for the glass panes, with wooden beams for flooring.

Doctor of Philosophy Postgraduate academic degree awarded by universities in many countries

A Doctor of Philosophy is the highest university degree that is conferred after a course of study by universities in most countries. PhDs are awarded for programs across the whole breadth of academic fields. As an earned research degree, those studying for a PhD are usually required to produce original research that expands the boundaries of knowledge, normally in the form of a thesis or dissertation, and defend their work against experts in the field. The completion of a PhD is often a requirement for employment as a university professor, researcher, or scientist in many fields. Individuals who have earned a Doctor of Philosophy degree may, in many jurisdictions, use the title Doctor or, in non-English-speaking countries, variants such as "Dr. phil." with their name, although the proper etiquette associated with this usage may also be subject to the professional ethics of their own scholarly field, culture, or society. Those who teach at universities or work in academic, educational, or research fields are usually addressed by this title "professionally and socially in a salutation or conversation." Alternatively, holders may use post-nominal letters such as "Ph.D.", "PhD", or "DPhil". It is, however, considered incorrect to use both the title and post-nominals at the same time.

University of Oxford university in Oxford, United Kingdom

The University of Oxford is a collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the world's second-oldest university in continuous operation after the University of Bologna. It grew rapidly from 1167 when Henry II banned English students from attending the University of Paris. After disputes between students and Oxford townsfolk in 1209, some academics fled north-east to Cambridge where they established what became the University of Cambridge. The two 'ancient universities' are frequently jointly called 'Oxbridge'. The history and influence of the University of Oxford has made it one of the most prestigious universities in the world.

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]

University of California, Berkeley Public university in California, USA

The University of California, Berkeley is a public research university in Berkeley, California. It was founded in 1868 and serves as the flagship campus of the ten campuses of the University of California. Berkeley has since grown to instruct over 40,000 students in approximately 350 undergraduate and graduate degree programs covering numerous disciplines.

Laboratory of Molecular Biology

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory with a much broader focus.

California U.S. state in the United States

California is a state in the Pacific Region of the United States. With 39.6 million residents across a total area of about 163,696 square miles (423,970 km2), California is the most populous U.S. state and the third-largest by area. The state capital is Sacramento. The Greater Los Angeles Area and the San Francisco Bay Area are the nation's second- and fifth-most populous urban regions, with 18.7 million and 9.7 million residents respectively. Los Angeles is California's most populous city, and the country's second-most populous, after New York City. California also has the nation's most populous county, Los Angeles County, and its largest county by area, San Bernardino County. The City and County of San Francisco is both the country's second-most densely populated major city after New York City and the fifth-most densely populated county, behind only four of the five New York City boroughs.

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]

Jack David Dunitz FRS is a British chemist and widely known chemical crystallographer. He was Professor of Chemical Crystallography at the ETH Zurich from 1957 until his official retirement in 1990. He has held Visiting Professorships in the United States, Israel, Japan, Canada, Spain and the United Kingdom.

Dorothy Hodgkin British chemist

Dorothy Mary Crowfoot Hodgkin was a British chemist who developed protein crystallography, for which she won the Nobel Prize in Chemistry in 1964.

Leslie Orgel British chemist

Leslie Eleazer Orgel FRS was a British chemist. He is known for his theories on the origin of life.

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 EMLederberg GStent SBrenner JLederberg 1965 wiki.jpg
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. [67] [68] He was an atheist. [69]

Brenner died on 5 April 2019, in Singapore, at the age of 92. [1] [70] [71]

Related Research Articles

Francis Crick British molecular biologist, biophysicist, neuroscientist; co-discoverer of the structure of DNA

Francis Harry Compton Crick was a British molecular biologist, biophysicist, and neuroscientist. In 1953, he co-authored with James Watson the academic paper proposing the double helix structure of the DNA molecule. Together with Watson and Maurice Wilkins, he was jointly awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material". The results were based partly on fundamental studies done by Rosalind Franklin, Raymond Gosling and Wilkins.

James Watson American molecular biologist, geneticist, and zoologist

James Dewey Watson is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick, and Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

<i>Caenorhabditis elegans</i> free-living species of nematode

Caenorhabditis elegans is a free-living, transparent nematode, about 1 mm in length, that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek caeno- (recent), rhabditis (rod-like) and Latin elegans (elegant). In 1900, Maupas initially named it Rhabditides elegans, Osche placed it in the subgenus Caenorhabditis in 1952, and in 1955, Dougherty raised Caenorhabditis to the status of genus.

Howard Robert Horvitz is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston.

The Crick, Brenner et al. experiment (1961) was a scientific experiment performed by Francis Crick, Sydney Brenner, Leslie Barnett and R.J. Watts-Tobin. This study demonstrated that the genetic code is made up of a series of three base pair codons which code for individual amino acids. The experiment also elucidated the nature of gene expression and frame-shift mutations.

The Nirenberg and Matthaei experiment was a scientific experiment performed on May 15, 1961, by Marshall W. Nirenberg and his post doctoral fellow, J. Heinrich Matthaei. The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.

Nirenberg and Leder experiment

The Nirenberg and Leder experiment was a scientific experiment performed in 1964 by Marshall W. Nirenberg and Philip Leder. The experiment elucidated the triplet nature of the genetic code and allowed the remaining ambiguous codons in the genetic code to be deciphered.

John Sulston British biologist and Nobel laureate

Sir John Edward Sulston was a British biologist and academic who won the Nobel Prize in Physiology or Medicine for his work on the cell lineage and genome of the worm Caenorhabditis elegans in 2002 with his colleagues Sydney Brenner and Robert Horvitz. He was a leader in human genome research and Chair of the Institute for Science, Ethics and Innovation at the University of Manchester. Sulston was in favour of science in the public interest, such as free public access of scientific information and against the patenting of genes and the privatisation of genetic technologies.

Crick Lecture

The Francis Crick Medal and Lecture is a prize lecture of the Royal Society established in 2003 with an endowment from Sydney Brenner, the late Francis Crick's close friend and former colleague. It is delivered annually in biology, particularly the areas which Francis Crick worked, and also to theoretical work. The medal is also intended for young scientists, i.e. under 40, or at career stage corresponding to being under 40 should their career have been interrupted.

Andrew Fire American biologist

Andrew Zachary Fire is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Craig C. Mello, for the discovery of RNA interference (RNAi). This research was conducted at the Carnegie Institution of Washington and published in 1998.

Cynthia Kenyon US molecular biologist

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John Graham White is a Professor Emeritus of Anatomy and Molecular Biology at the University of Wisconsin–Madison.

The nematode worm Caenorhabditis elegans was first studied in the laboratory by Victor Nigon and Ellsworth Dougherty in the 1940s, but came to prominence after being adopted by Sydney Brenner in 1963 as a model organism for the study of developmental biology using genetics. In 1974, Brenner published the results of his first genetic screen, which isolated hundreds of mutants with morphological and functional phenotypes, such as being uncoordinated. In the 1980s, John Sulston and co-workers identified the lineage of all 959 cells in the adult hermaphrodite, the first genes were cloned, and the physical map began to be constructed. In 1998, the worm became the first multi-cellular organism to have its genome sequenced. Notable research using C. elegans includes the discoveries of caspases, RNA interference, and microRNAs. Six scientists have won the Nobel prize for their work on C. elegans.

Leslie Barnett was a British biologist who worked with Francis Crick, Sydney Brenner, and Richard J. Watts-Tobin to genetically demonstrate the triplet nature of the code of protein translation through the Crick, Brenner, Barnett, Watts-Tobin et al. experiment of 1961, which discovered frameshift mutations; this insight provided early elucidation of the nature of the genetic code.

Jonathan Alan Hodgkin is a British biochemist, Professor of Genetics at the University of Oxford, and an emeritus fellow of Keble College, Oxford.

Alison Woollard is a British biologist. She is a lecturer in the Department of Biochemistry at the University of Oxford where she is also a Fellow of Hertford College, Oxford.

Julie Ann Ahringer FMedSci is an American Professor of Genetics and Genomics, and a Wellcome Trust Senior Research Fellow at the Gurdon Institute and the Department of Genetics at the University of Cambridge. She leads a research lab investigating the control of gene expression.

Cell lineage list of cell divisions that have led to the emergence of a cell considered

Cell lineage denotes the developmental history of a tissue or organ from the fertilized embryo. Cell lineage can be studied by marking a cell and following its progeny after cell division. Some organisms, such as C. elegans, have a predetermined pattern of cell progeny and the adult male will always consist of 1031 cells, this is because cell division in C. elegans is genetically determined and known as eutely. This causes the cell lineage and cell fate to be highly correlated. Other organisms, such as humans, have variable lineages and somatic cell numbers.

References

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Further reading