Frederick Sanger: Wikis

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Frederick Sanger

Born August 13, 1918 (1918-08-13) (age 91)
Gloucestershire, England
Nationality United Kingdom
Fields Biochemist
Institutions Laboratory of Molecular Biology
Alma mater St John's College, Cambridge
Notable awards Nobel Prize in Chemistry (1958)
Nobel Prize in Chemistry (1980)

Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and twice a Nobel laureate in chemistry. He is the fourth (and only living) person to have been awarded two Nobel Prizes.

Contents

Early years

Sanger was born in Rendcomb, a small village in Gloucestershire, the second son of Frederick Sanger, a medical practitioner, and his wife, Cicely. He was born on August 13, 1918, and educated at The Downs School (Herefordshire) and Bryanston School and then completed his Bachelor of Arts in natural sciences from St John's College, Cambridge in 1939. Raised as a Quaker, he learned to abhor violence, and during the Second World War he was a conscientious objector, being allowed to continue his research for a Ph.D.

He originally intended to study medicine, but became interested in biochemistry; some of the leading biochemists in the world were at Cambridge at the time. He completed his Ph.D. in 1943 under A. Neuberger, on lysine metabolism and a more practical problem concerning the nitrogen of potatoes.

Research

Sanger's first triumph was to determine the complete amino acid sequence of the two polypeptide chains of insulin in 1955. Prior to this it was widely assumed that proteins were somewhat amorphous. In determining these sequences, Sanger proved that proteins have a defined chemical composition. For this purpose he used the "Sanger Reagent", fluorodinitrobenzene (FDNB), to react with the exposed amino groups in the protein and in particular with the N-terminal amino group at one end of the polypeptide chain. He then partially hydrolysed the insulin into short peptides (either with hydrochloric acid or using an enzyme such as trypsin). The mixture of peptides was fractionated in two dimensions on a sheet of filter paper: first by electrophoresis in one dimension and then, perpendicular to that, by chromatography in the other. The different peptide fragments of insulin, detected with ninhydrin, moved to different positions on the paper, creating a distinct pattern which Sanger called “fingerprints”. The peptide from the N-terminus could be recognised by the yellow colour imparted by the FDNB label and the identity of the labelled amino acid at the end of the peptide determined by complete acid hydrolysis and discovering which dinitrophenyl-amino acid was there. By repeating this type of procedure Sanger was able to determine the sequences of the many peptides generated using different methods for the initial partial hydrolysis. These could then be assembled into the longer sequences to deduce the complete structure of insulin. Sanger's principal conclusion was that the two polypeptide chains of the protein insulin had precise amino acid sequences and, by extension, that every protein had a unique sequence. It was this achievement that earned him his first Nobel prize in Chemistry in 1958. This discovery was crucial for the later sequence hypothesis of Crick and Watson for developing ideas of how DNA codes for proteins.

In the 1960s he turned his attention to RNA molecules and again developed methods for separating fragments of these generated with specific nucleases. In the course of this he discovered in 1964, with Kjeld Marcker, the formylmethionine tRNA which initiates protein synthesis (in bacteria; this is closely related to the initiator methionine tRNA which was later discovered in eukaryotes). By 1967 he had determined the nucleotide sequence of the 5S ribosomal RNA from Escherichia coli, a small RNA about 115 nucleotides long. He then turned to DNA and, by 1975, had developed the “dideoxy” method for sequencing DNA molecules, also known as the Sanger method.[1] Two years later Sanger used his technique to successfully sequence the genome of the Phage Φ-X174; the first fully sequenced DNA-based genome. He did this entirely by hand. This has been of key importance in such projects as the Human Genome Project and earned him his second Nobel prize in Chemistry in 1980, which he shared with Walter Gilbert and Paul Berg. He is thus far (2009) the only person to have been awarded two Nobel Prizes in Chemistry, and one of only four two-time Nobel laureates: the other three were Marie Curie (Physics, 1903 and Chemistry, 1911), Linus Pauling (Chemistry, 1954 and Peace, 1962) and John Bardeen (twice Physics, 1956 and 1972). In 1979, he was awarded the Louisa Gross Horwitz Prize from Columbia University together with Walter Gilbert and Paul Berg.

Sanger's techniques used random distributions to get ordered sequence. The homochromatography was made from randomized RNA polymers. The plus-minus sequencing system used the random termination of polymerase to get a population of DNA polymers of each size. The dideoxy system took advantage of the random insertion of dideoxy nucleotides at every sequence position. The ordering of the phi X 174 genome used random shot-gun sequencing (later employed by Venter) and then closing the sequence circle by computer alignment. Professor Pieczenik used Sanger logic i.e. random distribution of nucleotides to create the first combinatorial libraries of peptides. http://www2.mrc-lmb.cam.ac.uk/archive/g_pieczenik.html

Later life

Sanger retired in 1983 to his home, “Far Leys”, in Swaffham Bulbeck outside Cambridge where he became an avid gardener. Adjacent to his extensive garden is “Sanger Wood”. In 1992, the Wellcome Trust and the Medical Research Council founded the Sanger Centre (now the Sanger Institute), named after him. The Sanger Institute, located near Cambridge, England, is one of the world's most important centres for genome research and played a prominent role in sequencing the human genome.

Almost his only public utterance in two decades was to put his name to a letter by other UK Nobel laureates protesting about the Iraq war. Referring to his youthful conscientious objection, he said, "I still hate war. That is why I signed that letter".

In 2007 the British Biochemical Society was given a grant by the Wellcome Trust to catalogue and preserve the 35 laboratory notebooks in which Sanger recorded his remarkable research from 1958 to 1983. In reporting this matter, Science magazine noted that Sanger, "the most self-effacing person you could hope to meet", now was spending his time gardening at his Cambridgeshire home.[2]

Even in retirement Sanger has used his extensive knowledge of DNA to aid modern scientists and academics in their work.

Awards and honours

References

  1. ^ Sanger F, Nicklen S, Coulson AR., DNA sequencing with chain-terminating inhibitors, Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
  2. ^ "A Life in Science" from the "Newsmakers" page edited by Yudhijit Bhattachjee, Science 317: 879, 2007

Books containing references to Fred Sanger

  • John Finch; 'A Nobel Fellow On Every Floor', Medical Research Council 2008, 381 pp, ISBN 978-1840469-40-0; this book is all about the MRC Laboratory of Molecular Biology, Cambridge.

External links

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Simple English

Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist. He was awarded the Nobel Prize in chemistry twice. He is the fourth (and only living) person to have been awarded two Nobel Prizes.


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