Professor George Brownlee introduces Dr. Sanger. Sanger was born in the village of Rendcomb in Gloucestershire where his father was the local GP. Dr. Sanger talks about his father whose MD thesis was entitled 'Biological Test for Blood Considered from its Medico-legal Aspect' which was the beginning of immunology at that time. He worked under George Nutall (1862-1937) who was the first Quick Professor at the Molteno Institute.
Sanger senior soon went to China as a missionary and founded a school for the lower classes there. He was a great influence on his two sons. Ill-health forced him to return to live in Rendcomb. Sanger Junior's grandfather on his mother's side was Theodore Crewdson who came from a family of Quakers. Crewdson was a wealthy cotton manufacturer who died when Sanger was about five. He was the only grandparent that Sanger knew. Sanger's favourite uncle was Dilworth Crewdson who farmed at Syde about 8 miles from Rendcomb. Sanger's parents bought a small summer house in Caudle Green, across the valley from Syde, where the family would go on summer holidays and on other occasions.
Sanger talks about his mother Cicely Crewdson, who lived the life of a Victorian lady, and about how his parents met for the first time. He talks about his older brother Theo and his sister May, the youngest for the family. His father converted from Anglicanism to Quakerism and the children were brought up as Quakers.
Sanger describes his Quaker upbringing and its moral influence on him. The truth is of paramount importance to Quakers and to Sanger. When Sanger was about five the family moved to Tamworth-in-Arden in Warwickshire, about twelve miles from Rendcomb. He discusses his father's reasons for the move and his family life there. He lived in Tamworth from age five to age seventeen. His brother got him interested in science at a young age through a shared enthusiasm for wildlife. During his early years he and his siblings had a governess.
SECTION 2, 1927-1932: THE DOWNS SCHOOL. Aged nine Sanger was sent away to a preparatory boarding school, the Downs School, run by the Quakers in Malvern. At school he was usually near the top of his class. He talks about his and his brother Theo's education at the school and the subjects he took.
SECTION 3, 1932-1936: BRYANSTON SCHOOL. Sanger was at the Downs School to age 14, after which he went to Bryanston School which was then a new public school. he enjoyed his time there. The school had a new system of teaching, the Dalton System involving less time in the classroom and more independent work, which suited him. He had good teachers there and speaks particularly of his biology teacher Fraser Hoyle. His chemistry teacher and housemaster was Mr Awdish. His exceptional final year results meant he could get into Cambridge University. He chose St John's College where his father had been. His uncle Hubert 'Tom' Sanger had also been to Cambridge.
He was advised not to apply for a scholarship so he had a free year (1936) and spent a lot of time with Mr Awdish, who allowed him to work a lot in the school lab which he enjoyed more than reading books. By this time he had become more independent of his brother whose interests still lay in animals. Fred became interested in doing things with his hands, especially carpentry. he also had a blacksmith's forge and liked doing ironwork. Ruth Sanger FRS, well known for her work on blood groups, is his first cousin - the daughter of his Uncle Tom who emigrated to Australia where she was born. She is married to Rob Race who also worked on blood groups.
SECTION 4, 1936: SCHOOL EXCHANGE VISIT TO SALEM, GERMANY. Sanger describes his experiences on an exchange visit to Salem School in South Germany in 1936. This was a school founded by Kurt Hahn who also founded Gordonstoun School in Scotland. This was at the height of Hitlerism but Sanger was not very politically aware at that time.
Sanger tells an amusing anecdote of an experience when he and two German boys were caught camping in the grounds of a girls' school which was a rival to Salem.
SECTION 5, 1936-1939: CAMBRIDGE UNIVERSITY UNDERGRADUATE. Sanger's experiences as an undergraduate at St John's College where he decided to study science. Dr Ernest Baldwin (1909-1969) was the supervisor in charge of biochemistry there and he advised Sanger on the subject. That was Sanger's first contact with biochemistry. His choice of subjects for his degree, and his decision to continue and to concentrate on biochemistry.
Sanger describes the biochemistry course at the Department of Biochemistry in Cambridge headed by F. Gowland Hopkins. He had lectures from Malcolm Dixon (1899- 1985), Joseph Needham and Ernest Baldwin whose great interest was comparative biochemistry on which he had written a textbook in 1937. At this period just before the Second World War he was strongly Quaker and pacifist and a conscientious objector. He got unconditional exemption from military service and was a member of the Peace Pledge Union. During his first year at college both his parents died of cancer.
Sanger describes how he met his future wife just before the war through the Scientists' Anti-War Group. They married in December 1940. At this time Sanger had not quite decided to go into research. He explains why. To his surprise he got a First in his exams and this gave him the possibility of doing research. Before he started his research he took a course for conscientious objectors run by the Quakers at the Spiceland Training Centre in Devon. The object of the course was to help people save rather than take lives. After that he worked as an orderly in a hospital - this was about the time of Dunkirk.
He wrote to Gowland Hopkins asking him if he could come back to Cambridge to do research but got no reply. He then went to Cambridge where Ernest Gale and N.W. 'Bill' Pirie, both at the Cambridge Biological Laboratory, were keen to have him. Pirie persuaded him that he should come to work with him. In October 1940 Sanger went to work with Bill Pirie. It was possible to do research in Cambridge at that time. Sanger recalls only one bomb falling on the city. Pirie was particularly interested in making edible protein from grass so Sanger, as a Ph.D. student, was asked to work on this. A month later, however, Pirie left to take up another job. Albert Neuberger then took over as Sanger's Ph.D. adviser and worked with him for three years. Sanger's thesis in 1943 was entitled 'The Metabolism of the Amino Acid Lysine in the Animal Body', but the main project he was working on was trying to synthesise the keto acid corresponding to lysine. He was Neuberger's only Ph.D. student at the time and worked very closely with him. He regards Neuberger as having been his main teacher. He talks about Neuberger. For his thesis Sanger was examined by Charles Harington (1897-1972) and Professor Albert Charles Chibnall (1894-1099).
Sanger discusses his thesis and related work which involved a lot of chemistry. He talks about how he and his colleagues, including Joseph Needham, used to firewatch during World War Two. Needham greatly impressed him. Sanger's general impressions of the Cambridge Department of Biochemistry and the then aged Gowland Hopkins.
Hopkins spoke to Sanger about the essay that Sanger had written for his Part 2 biochemistry examination on comparative biochemistry, at the end of which he proposed that survival of the fittest molecule was perhaps as important a concept as survival of the fittest species. Hopkins had been particularly impressed by it. Sanger briefly responds to a question about running his own laboratory years later. End of Part One.
PART TWO. SECTION 7, 1944-1949: EARLY STUDIES ON INSULIN COMPOSITION AND AMINO ACID SEQUENCES. Sanger discusses how he became interested in insulin in 1943. It was a question of a new job. Neuberger had left the lab and Sanger had finished his Ph.D. Professor Charles Chibnall was appointed to succeed Gowland Hopkins. Chibnall, who was an expert on amino acids and proteins, offered Sanger an MRC job and put Sanger to work on insulin. This was Sanger's first paid job. He had lived on his independent means until then. Chibnall was an organiser and not a lab worker. The laboratory had already done a lot of work on insulin by then. (At that time it was a pure protein available from Boots the Chemists in a bottle). They had done an estimation of the free amino groups
Chibnall suggested the first problem that Sanger should work on, the derivatisation of the N-terminal of amino acid and identify the free amino groups of insulin. The first reagents he tried were the methane-sulphonyl derivatives. He was looking for something that he could fractionate by partition chromatography (discovered by Archer J.P. Martin and Richard L. Millington Synge - joint Nobel Prize winners for Chemistry 1952). G.R. Tristram, one of Chibnall's colleagues, was already analysing proteins using partition chromatography. The paper 'Partition Chromatography in the Study of Protein Constituents' (1942) by A.H. Gordon, Martin and Synge. Sanger discusses his and others' research methodology in labelling and fractionating N-groups or free amino groups. He made DNP derivatives with chlorodinitrobenzene. Sanger's first paper on insulin, 'The Free Amino Groups of Insulin' (1945). He used chlorodinitrobenzene but found that this reagent was not reactive enough so they had to make some other derivative. They opted for fluorodinitrobenzene rather than trinitrobenzene. Chibnall found through a chemist colleague D.C. Saunders [surname spelling?] a ready supply of fluorodinitrobenzene which had been produced for the war effort. (Fluoro compounds were being produced either as poison gas or antidotes.) Sanger's team got some of this and it did the trick. They were able to label up the insulin, make the DNP-insulin under mild conditions and obtain the DNP-amino acids. They identified the two N-groups of insulin, DNP-glycine and DNP-phenylalanine and that accounted for all the amino groups.
At that time the molecular weight of insulin was believed to be higher than it was. Sanger explains why this was so. The next thing he and his colleagues succeeded in doing was to separate the chains in the insulin molecule. The assumption was that these chains would be joined together by disulphide bridges of the cysteine residues. Sanger describes the non-chromatographic methodology used in separating the chains. His paper 'Fractionation of Oxidized Insulin' (1949).
The next stage in Sanger's career was to try and sequence. This was an extension of the DNP method. If you do complete hydrolysis you get DNP amino acids, if you do partial hydrolysis you get peptides. His paper 'The Terminal Peptides of Insulin' (1949). He describes his methodology using silica-gel column separation of DNP, derivatives and paper chromatography - a great advance, the work of A.J.P. Martin and R.L. Millington Synge, then at the Wool Industries Research Association in Leeds. Sanger greatly admires A.J.P. Martin who had followed Synge to the NIMR in London in 1951. Martin later discovered gas chromatography.
SECTION 8, THE AMINO ACID SEQUENCE OF THE PHENYLALANINE CHAIN OF INSULIN. Sanger's work was the first time that any sequence had been done in a protein. He regards his 1949 paper on the partial digestion of the DNPs as more important than the original DNP paper on the N-groups. It also showed that proteins were real chemicals with a defined sequence. Next came the task of embarking on the whole sequence of insulin. He was joined by Hans Tuppy, the Austrian biochemist, who went to work on the phenylalanine chain and finished it in the one year he was at Cambridge. Their paper, 'The Amino-acid Sequence in the Phenylalanyl Chain of Insulin. 1: The Identification of Lower Peptides from Partial Hydrolysates' (1951). They also used enzymic hydrolysis in their methodology. The problems with enzymes at that time - he outlines advice he received from colleagues at the Cambridge Biological Laboratory. It was believed at this time that enzymes acted in a reversible manner, which could lead, for example, to reassembly of polypeptides following their enzymic breakdown. But Sanger and Tuppy found no evidence of resynthesis after using proteolytic enzymes to break down insulin, and were able to complete the sequence, resulting in their second paper 'The Amino-acid Sequence in the Phenylalanyl Chain of Insulin. 2: The Investigation of Peptides from Enzymic Hydrolysates' (1951).
SECTION 9, THE SEQUENCE OF THE GLYCYL CHAIN OF INSULIN. After Tuppy left Sanger was joined by E.O.P. 'Ted' Thompson from Australia. Their joint paper 'The Amino-acid Sequence in the Glycyl Chain of Insulin. 1: The Identification of Lower Peptides from Partial Hydrolysates' (1952). The glycyl chain ('fraction A') was somewhat more difficult than the phenylalanine chain. Their second paper 'The Amino-acid Sequence in the Glycyl Chain of Insulin. 2: The Investigation of Peptides from Enzymic Hydrolysates' (1952). Sanger discusses their research techniques and especially the problem of dealing with amides. The work was successfully completed, with a further paper, 'The Amide Groups of Insulin' (1954), written in collaboration with Ruth Kitai. Most of their work was qualitative. They assumed all along that there was just one structure there. There was no evidence of heterogeneity.
SECTION 10, 1945: FIRST Ph.D. STUDENT In 1945 Rodney Robert Porter joined Sanger as a Ph.D. student. He had earlier been at Liverpool University and went off to war with his colleague S.V. 'Sam' Perry. Sanger talks about Porter who was to be awarded the 1972 Nobel Prize for Physiology or Medicine (jointly with Gerald M. Edelman) for his work on the chemical structure of antibodies. Their joint paper 'The Free Amino Groups of Haemoglobins' (1947). While with Sanger, Porter read the book 'The Specificity of Serological Reactions' (1936) by Karl Landsteiner of the Rockefeller Institute for Medical Research in New York. This prompted him to do the N-groups of gamma globulin and he got a sensible result with a limited number of these groups. After he did his Ph.D. he went to NIMR at Mill Hill and doggedly continued his research, for a time without success, until suddenly he managed to separate the chains of the antibodies and show the basic structure of the antibody molecules. This opened up a new field completely. SECTION 11: EARLY RECOGNITION OF THE IMPORTANCE OF THE INSULIN SEQUENCE WORK. At this time Sanger's work was becoming recognised and he was invited to give popular lectures on how he deduced the sequence of amino acids. He talks about this and shows the simple visual aids he used in his lectures. The aids were used to demonstrate the overlap principle of how the polypeptide chains are built up from the peptide sequences they had derived.
SECTION 12: ARRANGEMENT OF THE DISULPHIDE BRIDGES OF INSULIN. The problem now was that Sanger and his colleagues had the chains but they did not know the arrangement of the disulphide bridges. This proved the most difficult part. He explains the methodology used to finish the structure of insulin. The problem of splitting between the two cysteines. A.P. Ryle's and Sanger's paper 'Disulphide Interchange Reactions' (1954). The split between the two cysteines was solved, largely due to the work of Leslie Smith. The paper 'The Disulphide Bonds of Insulin' (1954) by A.P. Ryle, F. Sanger, L.F. Smith and Ruth Kitai. Sanger outlines his reasons for preferring the oxidation method. The final paper about their work was published in 1955. The work was finished in 1954.
SECTION 13, 1958: THE FIRST NOBEL PRIZE. He was awarded the Nobel Prize in 1958 (photographs of the ceremony and celebrations) but did not do as some others who give up working in the lab. SECTION 14: PROBING AMINO ACID SEQUENCES IN ENZYME ACTIVE CENTRES. After receiving his prize Sanger returned to working in his laboratory as usual. The prize was a stimulus to carrying on. He discusses the research which led to the change he made from the study of proteins to nucleic acids. The change wasn't immediate. They studies insulin in different species at first. The papers 'The Structure of Pig and Sheep Insulins' (1954) by H. Brown, F. Sanger and Ruth Kitai, and 'The Structure of Insulin' (1955) by F. Sanger and Leslie F. Smith.
Sanger tried to do sequences with radioactive labels. Chris Anfinsen had come to the lab as a visitor and introduced them to radioisotopes. Sanger's team tried to make radioactive insulin with 35S. They did some radioactive labelling experiments on a 'little pig' to isolate the insulin - this had to be done at Mill Hill as they were not allowed to experiment on the pig at Cambridge. Sanger tells an amusing anecdote about their efforts to radioactively label a chicken with 32P. This series of experiments led to more specific labelling, e.g. the labelling of proteolytic enzymes with radioactive phosphates in their active centres. Use of DFP in these experiments. Radioautographs were made. Sanger explains these initial radioactive methods of determining sequences. He talks about active centres of amino acids and mobility of peptides. You could get information about charge from behaviour shown on a chromatogram or through paper electrophoresis. In this way you could gradually build up a library of sequences. Sanger's collaboration with Cesar Milstein [Nobel Prize winner for Medicine 1984]. Their paper 'An Amino Acid Sequence in the Active Centre of Phosphoglucomutase' (1961)
SECTION 15: THE MOVE TO THE NEW CAMBRIDGE MRC LABORATORY OF MOLECULAR BIOLOGY. Sanger talks about those involved in the move to the new laboratory in 1961. There were three groups: Structural Studies headed by Max Perutz, Cell Biology headed by Francis Crick (with Sidney Brenner) and Protein Chemistry headed by Sanger. The colleagues who joined Sanger were Leslie Smith, Ieuan Harris and Brian Hartley. They were soon to be joined by Cesar Milstein.
SECTION 16: SEQUENCE STUDIES OF RNA IN THE EARLY 1960s. Shortly after the move to the new Laboratory of Molecular Biology Sanger started working on RNA [ribonucleic acid]. He discusses the change of emphasis in his research. About that time the tRNAs were discovered. George Brownlee's joining his team as a Ph.D. student in 1962 was the main impetus that turned them on to RNA. Sanger's first success was using radioactive methods that he thought of with proteins and applying the principle to nucleic acids. Sequencing was usually done by column procedures. The main technical problem in sequencing was fractionation. Paper techniques as against ion exchange columns. Sangster's team developed a system which was a two-dimensional fractionation procedure which gave very nice separations.
Sanger shows and discusses a sample radioautograph of ribosomal RNA.Sanger outlines how these nucleotide sequences were derived and how they can be plotted on a graph to give a net-like illustration called a graticule. This was a way of getting composition directly from position. His, G. G. Brownlee's and B.G. Barrell's paper 'A Two-dimensional Fractionation Procedure for Radioactive Nucleotides' (1965) was the team's first contribution to RNA sequencing. In America, Robert W. Holley and his team just beat then to the first pure alanine tRNA structure by applying the classical methods of protein chemistry.
G.G. Brownlee's and Sanger's papers 'Nucleotide Sequences from the Low Molecular Weight Ribosomal RNA of Escherichia coli' (1967) and 'The Sequence of 5s Ribosomal Ribonucleic Acid (1968). The problems with minor bases. Sanger developed a method called homochromatography which was applied extensively in the work on a larger RNA, R17. He explains the methodology of how they sequenced little fragments out of the two-dimensional system using simpler methods, e.g. the 'wandering spot' method developed by Victor Ling. Sanger shows an illustration of a partial exonuclease digest of a fragment of DNA ending in 'G' and discusses this.
Displacement chromatography, which Sanger developed, and the work on R17. Sanger discusses the change from working on a smaller molecule to R17, which is 3,000 residues long. Jerry Adams decided to experiment on the large molecule and did a partial digest on the R17 - a radioautograph using 32P of the result is shown. Then with Peter Jeppesen they sequenced one of the fragments which was quite pure. This fragment had a nucleotide sequence which was related to the genetic code to a known amino acid sequence in the coat-protein of R17. The paper 'Nucleotide Sequences of Two Fragments from the Coat-protein Cistron of Bacteriophage R17 Ribonucleic Acid' (1972) by P.J.N. Jeppesen, B.G. Barrell, F. Sanger and A.R. Coulsen. This work was a good confirmation of the genetic code which had already been broken. Sanger's collaboration with Bart Barrell on tRNA sequences. Their joint paper 'The Sequence of Phenylalanine tRNA from E. coli' (1969). The methionine tRNAs were done in the laboratory. Sanger's and K. Marcker's paper 'N-Formyl-methionyl-S-RNA' (1964). End of Part Two.
PART THREE. SECTION 17: EARLY 1970's SEQUENCE STUDIES OF DNA. Sanger's important work on DNA which has been described as 'the ultimate challenge'. The first work on DNA in his lab was done by Ken Murray. The problem with DNA for sequencing was the very large size of its molecules, e.g. the single-stranded bacteriophage phiX-174 which had 5,000 nucleotides. The other problem was that there wasn't a suitable enzyme that would degrade DNA nice and cleanly. There wasn't anything like the tRNAs in the DNA field. Sanger found a way around these size and specificity problems. He describes the copying procedure he used, referring to the work of R. Wu and A.D. Kaiser who were the first people to use copying on DNA, using DNA polymerase, who mapped the nucleotides of the DNA of the bacteriophage lambda. Wu's and Kaiser's procedure was only applicable to the sticky ends of lambda from which they obtained twelve residues. Sanger and his team wanted to go further and develop a general method using primers, which had not been used before. Nucleotide synthesis was extremely difficult and was being pioneered in the laboratory of Har Gobind Khorana.
At a conference Sanger met Dr. Hans Koessel who had worked with Khorana and had similar ideas on copying to Sanger's. They decided to collaborate. Koessel and D. Fisher made an oligonucleotide and synthesised eight residues. This was the basis for the next stage of Sanger's work as it provided the team with a nice piece of radioactive DNA with which to develop their techniques. The second problem was how to mimic the T-1 ribonuclease of the RNA field, i.e. how to get a specific cut. The next step in Sanger's research was based on Paul Berg's work with DNA polymerase. Sanger explains his methodology and the ribo-C method which John Donelson, Alan Coulsen and he employed using displacement chromatography techniques. The papers 'Use of DNA Polymerase 1 Primed by a Synthetic Oligonucleotide to Determine a Nucleotide Sequence in Phage f1 DNA' (1973) by Sanger, Donelson, Coulsen, Koessel and Fisher, and 'Determination of a Nucleotide Sequence in Bacteriophage f1 DNA by Primed Synthesis with DNA Polymerase' (1974) by Sanger, Donelson and Coulsen. Using these methods they were able to get a sequence of up to eighty residues in DNA chains and that was their first real DNA sequencing method. This was quite an advance on anything that had gone before.
SECTION 18: THE DIDEOXY METHOD OF DNA SEQUENCING. While using the copying method Sanger was thinking of a degradative method and is now best known for his method of dideoxy sequencing. This represented another jump in his way of thinking. The paper 'DNA Sequencing with Chain-terminating Inhibitors' (1977) by Sanger, S.Nicklen and A.R. Coulsen. Sanger details how they developed this new dideoxy technique which made use of a copying procedure with DNA polymerase. He shows a radioautograph of the fragments ending in 't', all separated on a three-dimensional gel and reads off a sequence from it.
Sanger discusses the preliminary work, e.g. the use of terminators and the gel technology, from the early 1970s which led to the development of the simple and fast read-off method. The ribose-C degradation method and the use of the 'wandering spot' to study fragments. This work was based on the method with T-4 polymerase developed by Paul T. Englund in 1971 and 1972. From this they developed what they called their 'minor system,' using three nucleotides and missing out one nucleotide. Sanger's and A.R. Coulsen's paper, 'A Rapid Method for Determining Sequences in DNA by Primed Synthesis with DNA Polymerase' (1974).
Sanger shows a handwritten note of June 1972 which he had done for himself to explain how to do this sequencing method. But he wasn't satisfied with the quality of the data produced by the plus and minus methods, even though they were a great improvement on what had gone before. He talks about how gel technology developed over the years and his collaboration with John Donelson at Cambridge. This led to an improvement in resolution. His and A. R. Coulsen's paper 'The Use of Thin Acrylamide Gels for DNA Sequencing' (1978). They found that they could separate fragments according to size on an acrylamide gel.
They used different pHs and denaturing with a good concentration of urea. This kept the DNA absolutely denatured. Sanger discusses how he and Coulsen got hold of a supply of dideoxy nucleotide triphosphate. The other three dideoxys had never been made and were unavailable anywhere so they and their colleagues had to make them themselves over a period of a year. Nucleotide synthesis is quite specialised so it wasn't easy.
Sequencing developments after Sanger had published this work on single-stranded DNA. They made use of Walter Gilbert's and Allan Maxam's new partial hydrolysis technique for obtaining fragments. Gilbert and Sanger shared the 1980 Nobel Prize for Chemistry [with Paul Berg]. SECTION 19: THE SECOND NOBEL PRIZE. Sanger discusses his second prize and the nature of experimentation. The first prize enabled him to try 'way-out' experiments, many of which failed but which led to the DNA sequencing procedures. He talks about the ceremonies in Stockholm.
SECTION 20: EARLY CLONING WORK WITH SINGLE STRAND BACTERIOPHAGES. Sanger's participation in early cloning work. He discusses the advances made possible by the work of B. Gronenborn and J. Messing who developed a method for cloning fragments of double-stranded DNA into a single-stranded bacteriophage M13. This discovery made the dideoxy method universal.
Sanger discusses the use of computers in research. The assistance his team received from Roger Staden and Michael Smith. They used the program brought in by Smith to complete the nucleotide sequence of the bacteriophage phiX174. Sanger discusses and illustrates the stages in the development of sequences up to the Epstein-Barr virus in 1984.
SECTION 21: SEQUENCING GENOMES. Advances in the human genome since Sanger retired. Sanger's views on the desirability of doing the human genome. He is in favour of the initiative, a logical conclusion to the work he had accomplished. From the medical point of view it is likely to prove useful. Alan R. Coulsen and John Sulston are now working on the nematode genome which is a very big project. They have developed the mapping procedures and are now on to sequencing. The whole sequencing method has been automated now, e.g. the use of the Applied Biosystems Automatic Nucleic Acid Sequencer and the Laser Scanning Device to detect fluorescent bands. Reference to the work on insulin of Stanford Moore and William H. Stein [Nobel Prize winners for Chemistry 1972].
SECTION 22: OVERLAPPING GENE DNA SEQUENCES. Sanger discusses his team's phiX work in relation to overlapping genes. The paper 'Nucleotide Sequence of Bacteriophage [Lambda] DNA' (1982) by Sanger, Coulsen, G.F. Hong, D.F. Hill and G.B. Petersen. SECTION 23: MITOCHONDRIAL DNA AND tRNA SEQUENCES. Sanger discusses his collaboration on mitochondrial DNA with Bart Barrell. Implications of the UGA terminator. First sign that the genetic code which was thought to be universal was not universal. The team produced a paper 'Sequence and Organisation of the Human Mitochondrial Genome'. This research led on to work on transfer RNAs and a paper on the different patterns of codon recognition by mammalian mitochondrial tRNAs.
SECTION 24: THE NEW SANGER INSTITUTE IN CAMBRIDGE. [This became known as the Sanger Centre and is based at the Wellcome Trust Genome Campus in Cambridge]. Though still (at the time of filming) on the drawing board, and was to be headed by John Sulston. The idea initially is to finish the nematode genome on which Sulston and Alan Coulsen have been working and then extend the work to the human genome. Work on the genome is an international effort and already people are beginning to find out things about hereditary diseases.
SECTION 25, 1983: RETIREMENT. Sanger retired in 1983, aged 65. Since retiring he has spent a lot of time gardening. He talks about his wife and his happy family life. The implications of this for his scientific research. His children, now adults. He is now a grandfather. His interest in boating and sailing. He owns a river boat, the inside of which he himself constructed (as a boy he liked doing carpentry which he had learned at Bryanston School), based at Ely.
His children did not follow him into science. He talks about their careers. SECTION 26: LOOKING BACK. Sanger reflects on his life in biochemistry from the 1940s to the 1980s. The collaborators he had and their interchange of ideas. Credits.