Frederick Sanger

For more information on Frederick Sanger, visit Britannica.com.

British biochemist (1918–)

Sanger, a physician's son from Rendcombe in England, received both his BA and his PhD from Cambridge University (in 1939 and 1943 respectively). He continued his research at the university and from 1951 until 1983 was a member of the scientific staff of the Medical Research Council. In 1955, after some ten years' work, Sanger established the complete amino-acid sequence of the protein bovine insulin. This was one of the first protein structures identified, and Sanger received the Nobel Prize for chemistry in 1958 in recognition of his achievement. Sanger's work enabled chemists to synthesize insulin artificially and generally stimulated research in protein structure.

In 1977 Sanger's team at the MRC laboratories, Cambridge, published the complete nucleotide (base) sequence of the genetic material (DNA) of the virus Phi X 174. This involves determining the order of 5400 nucleotides along the single circular DNA strand. Moreover they found two cases of genes located within genes. Previously it had been thought that genes could not overlap. Sanger's research required the development of new techniques for splitting the DNA into different-sized fragments. These are radioactively labeled and then separated by electrophoresis. The base sequence can then be worked out because it is known which base is located at the end of each fragment due to the specificity of the enzymes (the so-called restriction enzymes) used to split the DNA. Sanger was awarded the Nobel Prize for chemistry a second time (1980) for his work on determining the base sequences of nucleic acids.

Molecular Biologist
1918-

Born August 13, 1918, in Rendcombe, Gloucestershire, United Kingdom, Fred Sanger has been breaking new ground in chemistry for decades. In fact, he is the only person to have won a Nobel Prize in chemistry twice, and is only one of four people ever to have won a Nobel Prize more than once.

While at Cambridge University in England he developed a new method for sequencing amino acids in proteins, which he used to identify the complete sequence of insulin. For this he was awarded his first Nobel Prize in chemistry in 1958. After this success, in 1961 Sanger moved to the MRC Laboratory of Molecular Biology, where he became head of the division of protein chemistry. His colleagues' interest in nucleic acids inspired him to turn his interest in sequencing to the research of nucleic acids.

In 1977 Sanger developed a sequencing method, called the "dideoxy" method, with which he determined the entire sequence of a bacterial virus called phi-X174. This was the first time a complete sequence of a DNA molecule had been established. For this achievement he was awarded the 1980 Nobel Prize in chemistry, shared jointly with Walter Gilbert of Harvard University who had concurrently developed an alternative DNA sequencing method. Sanger's original sequence contained only 5,375 nucleotides, but his technology is now being used to determine sequences that are millions of nucleotides longer, including, importantly, the human genome. In his honor one of the major DNA sequencing centers in the world is named the Wellcome Trust Sanger Institute, at the Wellcome Trust Genome Campus, Cambridge, England.

Bibliography

Internet Resource

"About Frederick Sanger." Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/Info/Intro/sanger.shtml.

—Jeffery M. Vance

The English biochemist Frederick Sanger (born 1918) was awarded the Nobel Prize in Chemistry for his discovery of the chemical structure of insulin.

Frederick Sanger, son of Frederick Sanger, a medical practitioner, was born at Rendcombe, Gloucester-shire, on Aug. 13, 1918. Entering St. John's College, Cambridge, in 1936, he graduated with the degree of bachelor of arts (in natural sciences) in 1939. In 1943 he received his doctorate of philosophy (in chemistry) with a thesis on lysine. He held a Beit Memorial Fellowship from 1944 to 1951 and then joined the staff of the Medical Research Council. He later became director of the Division of Protein Chemistry in the Council's Laboratory for Molecular Biology at Cambridge.

Sanger worked entirely on the chemical structure of the proteins, especially insulin. About 1900 Emil Fisher had succeeded in breaking down proteins into polypeptides, consisting of their ultimate constituents, amino acids. About 25 different amino acids occur in nature, and of these 20 are found in most mammalian proteins.

By 1943 it was known that proteins consisted of long chains of amino acid residues bound together by peptide linkages. A. C. Chibnall and others knew the 51 amino acid residues that composed insulin; they also knew that phenylalanine was at the end of one of the chains. The insulin molecule appeared to consist of a large number of polypeptide chains, and it was held that what was important biologically was the sequence in which the amino acids followed each other in the chains. This sequence was unknown for any protein.

Sanger introduced the reagent fluorodinitrobenzene (FDNB), which reacted with the free amino acid at the end of a chain to form a dinitrophenyl derivative (DNP) combined with that amino acid. The DNP acids were bright yellow. If the chains were then split by hydrolysis, the colored terminal acid of each link could be identified by chromatographic and electrophoretic methods. Sanger at first thought that the insulin molecule contained four long chains; but he later concluded that it consisted of only two chains containing 21 and 30 amino acids respectively. He then split the bridges joining the chains by oxidation with performic acid and dealt with each chain individually. The chain was separated into successively shorter links, and in each link the terminal amino acid was identified. He was able to determine the exact sequence of amino acids in each chain.

Sanger then determined that the two chains were linked by two disulfide bridges of cystine residues, with a third bridge linking two parts of the short chain. The determination of the exact positions of these bridges enabled Sanger, after over 12 years of research, to give a diagram for the structure of insulin. For this work he was awarded the Nobel Prize in Chemistry in 1958.

In 1951 Sanger was awarded the Corday-Morgan Medal of the Chemical Society. In 1954 he was elected a Fellow of the Royal Society and a Fellow of King's College, Cambridge; and in 1958 he was elected a Foreign Honorary Member of the American Academy of Arts and Sciences.

In 1980 Sanger shared the Nobel Prize for Chemistry with two other scientists for work determining the sequences of nucleic acids in DNA molecules. Their combined work has been lauded for its application to the research of congenital defects and hereditary diseases. It also proved vitally important in producing the artificial genes that go into the manufacture of insulin and interferon, two substances which are used to treat a variety of diseases. Sanger retired from research in 1983.

Further Reading

There was a biography of Sanger in Nobel Lectures, Chemistry, 1942-1962 (1964). This work also included his Nobel Lecture, which gave an admirable summary of his work. For the chemical background see P. Karrer, Organic Chemistry (4th ed. 1950). See also the article "Sequences, Sequences, and Sequences" in Annual Review of Biochemistry (1988, pages 1-28), and Nobel Prize Winners (H. W. Wilson, ed. 1987, pages 921-924).

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 1 Early years 2 Research 3 Later life 4 Awards and honours 5 References 6 Books containing references to Fred Sanger 7 External links

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.

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

This section may require cleanup to meet Wikipedia's quality standards. Please improve this section if you can. (October 2007)

• Fellow of the Royal Society - 1954
• Commander of the Order of the British Empire - 1963
• Order of the Companions of Honour - 1981
• Order of Merit (Commonwealth) - 1986
• Nobel Prize in Chemistry - 1958, 1980

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

• The Sanger Institute
• About Fred Sanger, biography from the Sanger Institute
• About the 1958 Nobel Prize
• About the 1980 Nobel Prize
• Association of Biomolecular Resource Facilities 1994 Award
• Fred Sanger Freeview Video Documentary by The Vega Science Trust
• National Portrait Gallery
• Autobiography
• The Official Site of Louisa Gross Horwitz Prize
• Frederick Sanger interviewed by Alan Macfarlane, 24th August 2007 (film)

v • d • e Nobel Laureates in Chemistry 1901–1925 van 't Hoff (1901) · E. Fischer (1902) · Arrhenius (1903) · Ramsay (1904) · von Baeyer (1905) · Moissan (1906) · Buchner (1907) · Rutherford (1908) · Ostwald (1909) · Wallach (1910) · Curie (1911) · Grignard / Sabatier (1912) · Werner (1913) · Richards (1914) · Willstätter (1915) · Haber (1918) · Nernst (1920) · Soddy (1921) · Aston (1922) · Pregl (1923) · Zsigmondy (1925) 1926–1950 Svedberg (1926) · Wieland (1927) · Windaus (1928) · Harden / von Euler-Chelpin (1929) · H. Fischer (1930) · Bosch / Bergius (1931) · Langmuir (1932) · Urey (1934) · F. Joliot-Curie / I. Joliot-Curie (1935) · Debye (1936) · Haworth / Karrer (1937) · Kuhn (1938) · Butenandt / Ružička (1939) · de Hevesy (1943) · Hahn (1944) · Virtanen (1945) · Sumner / Northrop / Stanley (1946) · Robinson (1947) · Tiselius (1948) · Giauque (1949) · Diels / Alder (1950) 1951–1975 McMillan / Seaborg (1951) · Martin / Synge (1952) · Staudinger (1953) · Pauling (1954) · du Vigneaud (1955) · Hinshelwood / Semyonov (1956) · Todd (1957) · Sanger (1958) · Heyrovský (1959) · Libby (1960) · Calvin (1961) · Perutz / Kendrew (1962) · Ziegler / Natta (1963) · Hodgkin (1964) · Woodward (1965) · Mulliken (1966) · Eigen / Norrish / Porter (1967) · Onsager (1968) · Barton / Hassel (1969) · Leloir (1970) · Herzberg (1971) · Anfinsen / Moore / Stein (1972) · E. O. Fischer / Wilkinson (1973) · Flory (1974) · Cornforth / Prelog (1975) 1976–2000 Lipscomb (1976) · Prigogine (1977) · Mitchell (1978) · Brown / Wittig (1979) · Berg / Gilbert / Sanger (1980) · Fukui / Hoffmann (1981) · Klug (1982) · Taube (1983) · Merrifield (1984) · Hauptman / Karle (1985) · Herschbach / Lee / Polanyi (1986) · Cram / Lehn / Pedersen (1987) · Deisenhofer / Huber / Michel (1988) · Altman / Cech (1989) · Corey (1990) · Ernst (1991) · Marcus (1992) · Mullis / Smith (1993) · Olah (1994) · Crutzen / Molina / Rowland (1995) · Curl / Kroto / Smalley (1996) · Boyer / Walker / Skou (1997) · Kohn / Pople (1998) · Zewail (1999) · Heeger / MacDiarmid / Shirakawa (2000) 2001–present Knowles / Noyori / Sharpless (2001) · Fenn / Tanaka / Wüthrich (2002) · Agre / MacKinnon (2003) · Ciechanover / Hershko / Rose (2004) · Grubbs / Schrock / Chauvin (2005) · Kornberg (2006) · Ertl (2007) · Shimomura / Chalfie / Tsien (2008) Venkatraman Ramakrishnan / Thomas A. Steitz / Ada E. Yonath (2009) Complete roster · 1901–1925 · 1926–1950 · 1951–1975 · 1976–2000 · 2001–present

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)