Frederick Sanger

Born 13th August, 1918 (Gloucestershire, England, United Kingdom) - Died 19th November, 2013 (Cambridge)

The first to determine the DNA sequence of insulin, Sanger proved proteins have a defined chemical composition. He was also pivotal to the development of the dideoxy chain-termination method for sequencing DNA molecules, known as the Sanger method. This provided a breakthrough in the sequencing of long stretches of DNA in terms of speed and accuracy and laid the foundation for the Human Genome Project.

Fred Sanger in his laboratory at the Laboratory of Molecular Biology, c. 1969. (Photo credit: MRC, Laboratory of Molecilar Biology)

Family

Fred Sanger was the middle son of three children. His father, Frederick, started his work life as an Anglican medical missionary in China, but poor health forced him back to England where he took up a position as a general medical practitioner. Sanger's father converted to Quakerism soon after Fred's birth and raised the children as Quakers. Although Sanger's mother, Cicely (neƩ Crewdson), was the daughter of a wealthy Quaker cotton manufacturer she did not follow Quakerism. Sanger grew up in Rencomb, Gloucestershire, until he was fives years old, and thereafter lived with his family to Tanworth-in-Arden, a small village in Warwickshire. Both of Sanger parents died from cancer when he was in his second year at university. In December 1940, Sanger married Margaret Joan Howe, an economics student who was based at Newnham College, Cambridge. The two of them met through the Cambridge Scientists' Anti-War Group. Fred and Margaret had two sons and one daughter. Sanger highly valued Margaret claiming that she had aided his scientific work more than anyone else. Her contribution, he argued, was maintaining a peaceful and happy home.

Education

Sanger was initially taught by a governess and then from the age of nine boarded at Downs School, a residential Quaker preparatory school near Malvern, Worcestershire. In 1932, when he was 14, Sanger was sent to Bryanston School, Dorset, which tailored its education in line with the Dalton Plan. The Plan encouraged students to be schooled according to their needs and to foster in them a sense of independence and responsibility for others. Sanger enjoyed Bryanston's liberal ethos and particularly liked studying science while there. After receiving good results in his School Certificate examinations, in 1936, Sanger went to St John's College, Cambridge, to study the natural sciences and took biochemistry in the final part of the course. In October 1940 Sanger began a doctorate investigating whether an edible protein could be obtained from grass under N.W. 'Bill' Pirie. When Pirie left Cambridge, a month later, Sanger switched to the supervision of Albert Neuberger, under whom he studied the metabolism of lysine, an essential amino acid for humans, and worked for a government sponsored research project examining the nitrogen content of potatoes. Sanger completed his doctorate in 1943.

Career

Sanger originally wanted to pursue a career in medicine like his father, but soon realised he was better suited to science. During the Second World War Sanger registered as a conscientious objector and did some training in social relief work before briefly serving as a hospital orderly. After completing his doctorate, Sanger became a post-doctoral researcher in the Biochemistry Department, Cambridge University, working with the protein chemist Charles Chibnall and his team on the chemical structure of proteins. This was done using chromatography, a newly developed technique. Sanger's first project involved investigating the amino acid composition of insulin. One of the advantages of studying insulin was the fact that its chemical structure was small. It also could provide some understanding for diseases such as diabetes. Sanger's work was aided by the fact that insulin was one of the few pure proteins then available in large quantities, being collected from cattle. The objective of the research was to determine the exact chemical structure of insulin. Sanger initially struggled to get funding for his project because most scientists believed amino acids in proteins were randomly arranged and their pattern could not be determined. In 1944, however, he was awarded a Beit Memorial Fellowship for Medical Research. Six years later he was appointed a member of the external staff of the Medical Research Council (MRC) in recognition of the importance of his work. Sanger moved his laboratory from the Biochemistry Department to the MRC's newly opened Laboratory of Molecular Biology in 1962 where he was to head up the Laboratory's Protein Chemistry division until 1983 when he retired.

Achievements

Sanger was one of the few scientists to have been twice awarded a Nobel prize for Chemistry. He won the prize the first time in 1958 for developing methods for sequencing amino acids. This he developed in his quest to understand the structure of insulin. His method involved marking the terminal amino acid and then splitting it away from the insulin protein for identification. After 8 years of repeating this painstaking process, Sanger eventually determined insulin was made up of 51 amino acids. His research, published in 1955, provided the first conclusive evidence that proteins have a defined sequence. Following his work on insulin, Sanger turned his attention to sequencing the building blocks in DNA, called bases. By this time it was known that DNA had a linear code, but no methods existed for reading it. Sanger saw the challenge as a natural extension of his protein sequencing work. Helped by Bart Barrell, Alan Coulson and George Brownlee, Sanger explored a number of methods over 15 years. In 1975 he and his team published a paper outlining what they called the 'Plus and Minus' technique. This enabled the sequencing of 80 nucleotides in one go. Sanger and his team used it to sequence the genome of the virus phi X 174, the first DNA-based genome ever sequenced. The work showed for the first time that some genes overlapped with the other. Following this, in 1977, Sanger and his colleagues announced another method, known as the 'dideoxy' chain-termination technique or the 'Sanger method'. This allowed for the rapid and accurate sequencing of long stretches of DNA. As many as 3,000,000,000 base-pairs, 500 bases, could be read at one time. The technique earned Sanger his second Nobel prize, in 1980, which he shared with Walter Gilbert and Paul Berg and provided the blueprint for sequencing the whole human genome. In 1981 Sanger was awarded a knighthood, but he turned it down because he did not want to be called 'Sir'. Five years later he was awarded the Order of Merit which he accepted.

Frederick Sanger: timeline of key events

The first to determine the DNA sequence of insulin, Sanger proved proteins have a defined chemical composition. He was also pivotal to the development of the dideoxy chain-termination method for sequencing DNA molecules, known as the Sanger method. This provided a breakthrough in the sequencing of long stretches of DNA in terms of speed and accuracy and laid the foundation for the Human Genome Project. 1918-08-13T00:00:00+00001932-01-01T00:00:00+0000Studies a combination of chemistry, physics, maths and physiology and specialises in biochemistry in his final year.1936-01-01T00:00:00+0000Initially supervised by Bill Pirie, and then by Albert Neuberger, in the Department of Biochemistry. Thesis: 'On the metabolism of the amino acid lysine in the animal body'. 1940-01-01T00:00:00+0000Sanger undertakes the research as part of team working with Albert Chibnall in Department of Biochemistry. His work is initially supported by a Beit Memorial Fellowship from 1944 and then by Medical Research Council from 1951. 1944-01-01T00:00:00+0000Sanger's insulin results establish for the first time that proteins are chemical entities with a defined sequence. The technique Sanger develops for sequencing insulin later becomes known as the degradation or DNP method. It provides the basis for his later development of sequencing tecdhniques for nucleic acids, including RNA and DNA.1955-01-01T00:00:00+0000Ingram shows that the difference between sickle-cell and normal haemoglobulin lies in just one amino acid. 1957-01-01T00:00:00+0000Prize awarded to Sanger 'for his work on the structure of proteins, especially that of insulin'.1958-01-01T00:00:00+00001960-01-01T00:00:00+0000Sanger now has close contact with protein crystallographers, molecular geneticists and protein chemists1962-01-01T00:00:00+0000Tested on ribosomal RNA1965-01-01T00:00:00+0000The method enables 80 nucleotides to be sequenced in one go. Represents radical new approach which allows direct visual scanning of a sequence. 1975-01-01T00:00:00+0000This is found to contain 5,385 nucleotides. It is the first DNA based organism to have its complete genome sequenced. Sanger and his team use the plus and minus technique to determine the sequence. 1977-01-01T00:00:00+0000Two separate teams, one led by Fred Sanger at the MRC Laboratory of Molecular Biology, Cambridge, UK, and one composed of Allan Maxam, and Walter Gilbert at Harvard University publish two different methods for sequencing DNA. The first, known as the Sanger Method, or dideoxy sequencing, involves the breaking down and then building up of DNA sequences. The second, the Maxam-Gilbert method, involves the partial chemical modification of nucleotides in DNA. 1977-02-01T00:00:00+0000Prize shared with Walter Gilbert. Awarded on the basis of their 'contributions concerning the determination of base sequences in nucleic acids.' 1980-01-01T00:00:00+00001983-01-01T00:00:00+00002013-11-19T00:00:00+0000
Date Event People Places
13 Aug 1918Frederick Sanger, twice Nobel Prize winner, bornSangerRendcomb, Gloucestershire, United Kingdom
1932Sanger attends Bryanston School, Dorset, as boarderSanger 
1936 - 1936Sanger takes degree in Natural Sciences at Cambridge UniversitySangerCambridge University
1940 - 1940Sanger studies for a doctorate at Cambridge UniversitySangerCambridge University
1944Sanger starts working on amino acid composition of insulinSangerCambridge University
1955Sanger completes the full sequence of amino acids in insulinSangerCambridge University
1957Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing techniqueIngram, SangerCambridge University
1958Sanger awarded his first Nobel Prize in ChemistrySangerCambridge University
1960Sanger begins to devise ways to sequence nucleic acids, starting with RNASangerCambridge University
1962Sanger moves to the newly created Laboratory of Molecular Biology in CambridgeSangerLaboratory of Molecular Biololgy
1965Sanger and colleagues publish two-dimension partition sequencing methodSanger, Brownlee, BarrellLaboratory of Molecular Biology
1975Sanger and Coulson publish their plus minus method for DNA sequencingSanger, CoulsonLaboratory of Molecular Biology
1977Complete sequence of bacteriophage phi X174 DNA determinedSangerLaboratory of Molecular Biology
February 1977Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNASanger, Maxam, GilbertHarvard University, Laboratory of Molecular Biology
1980Sanger awarded his second Nobel Prize in ChemistrySanger, GilbertHarvard University, Laboratory of Molecular Biology
1983Sanger retiresSangerLaboratory of Molecular Biology
19 Nov 2013Sanger, the inventor of DNA sequencing, died at the age of 95SangerCambridge

13 Aug 1918

Frederick Sanger, twice Nobel Prize winner, born

1932

Sanger attends Bryanston School, Dorset, as boarder

1936 - 1940

Sanger takes degree in Natural Sciences at Cambridge University

1940 - 1943

Sanger studies for a doctorate at Cambridge University

1944

Sanger starts working on amino acid composition of insulin

1955

Sanger completes the full sequence of amino acids in insulin

1957

Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing technique

1958

Sanger awarded his first Nobel Prize in Chemistry

1960

Sanger begins to devise ways to sequence nucleic acids, starting with RNA

1962

Sanger moves to the newly created Laboratory of Molecular Biology in Cambridge

1965

Sanger and colleagues publish two-dimension partition sequencing method

1975

Sanger and Coulson publish their plus minus method for DNA sequencing

1977

Complete sequence of bacteriophage phi X174 DNA determined

Feb 1977

Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNA

1980

Sanger awarded his second Nobel Prize in Chemistry

1983

Sanger retires

19 Nov 2013

Sanger, the inventor of DNA sequencing, died at the age of 95