Frederick Sanger interviewed by Alan Macfarlane 24th August 2007 0:09:07 Born 1918 at Rendcombe in the Cotswolds where father was a doctor who had previously been a missionary in China; think that he came back as he contracted TB; he became a Quaker later on and my brother and I used to go to Friends Meetings; brother was a year older and an extrovert; I was more bookish and interested in using my hands; did a lot of carpentry and also had a little forge; mother came from a fairly wealthy family; grandfather was in the cotton trade in Manchester 7:34:00 First school was in Colwall near Malvern, a Quaker boarding school, where I went at the age of nine where brother had preceded me; went on to Bryanston which I enjoyed much more for its freedom and common sense; remember the chemistry teacher, Mr Ordish, particularly; during my last year I had already qualified for Cambridge and I was allowed to go to the lab and experiment which was my first real taste of chemistry; started at Cambridge doing physics as well as chemistry but gave up physics in second year and did physiology instead as my maths was not good enough 11:04:07 Chose St John's Cambridge because my father had been there; Baldwin was my supervisor, an enthusiastic teacher if not that brilliant as a scientist; no great role models in chemistry at the time; came up just before the war and stayed on in Cambridge as a conscientious objector; when I went to Cambridge still going to Quaker meetings though never actually joined; had no musical skills but played squash a little; got a 2:1; stayed on a fourth year and did biochemistry where I got a first; my initial supervisor was Albert Neuberger who was interested in proteins; department rather neglected, Hopkins was the Professor but was old; towards the end of the War Professor Chibnall came who was also interested in proteins; my first paper was on nitrogen of the potato 20:59:23 I was starting on a research degree at that stage and worked with Neuberger for a year or two and when he left, taken on by Chibnall who suggested work on insulin, protein chemistry which turned out to be very successful; without him I would have continued metabolic work which would not have come to much; Chibnall had been working on amino acid analysis of protein; something a bit odd about insulin which was about the only protein that could be obtained in a pure form; Chibnall had found there were more free amino groups in it than you would have expected from the concentration of lysine which is the one amino acid that has free amino groups and asked me to look into it; that was really where my work started as I did find there were extra amino groups which were at the end of the protein chains; I was able to develop a chemical method for identifying the end terminals of the amino groups and showing that insulin was composed of two chains and identifying the amino acids at the ends; at that time all that was known was that proteins were chains of amino acids and no one had any idea of what order they were in or how they were arranged; I was able to identify two amino acids at the end of the insulin chain which was quite a breakthrough as it was the first time that any amino acid was identified in a particular position in a protein; from then on that was my main interest in determining the amino acids' composition and structure of proteins; in the initial bit when looking for the amino groups you had a reagent and made a DNP compound, a nitrophenyl, and could isolate those bits; later on did more random digestion, breaking them into little bits and fractionating them; that developed in parallel with the new techniques for separating compounds; later on you could just cut it up like a jigsaw puzzle, look at the different bits and then put them together; I did not actually design methods but methods of fractionation came along and I was quick to use them; my work has centred on separating compounds 27:56:16 Work mainly alone with a technical assistant and sometimes with a colleague; the first was Hans Tuppy, an Austrian, an enthusiast with whom I did the whole chain of insulin which was quite a breakthrough and contributed to getting first Nobel prize; originally in St John's but invited to become a Fellow of King's, probably in the late 1950's; never became a real college man 31:27:09 Worked in the biochemistry department firstly in the basement with Tuppy; when Young became the Professor he was interested in me working with him on physiological matters; I did not want to do that but to get on with my studies on insulin; Chibnall had retired but had the protein hut which was outside; I was supposed to work in the main building; had two students, one was Hal Dixon, who was more interested in hormones, and the other was Ted Thompson who was working with me on the sequence of insulin; Ted was put in the protein hut but I spent most of my time there finishing off the sequencing rather than working in the main building where I had been assigned; later moved out to the MRC unit run by Max Perutz; he was a very fair, kind, man and devoted to science; he did not influence me as he was more of a physical chemist but he was very supportive of me 37:17:15 Work on phage followed on from the sequencing of insulin; people had got interested in nucleic acids, RNA and DNA; when I started they didn't know what nucleic acids were doing but it became clearer just how important they were; I switched first to RNA and did some sequence work; the techniques were different; with proteins have twenty different amino acids and the protein size is a few hundred amino acids long whereas in nucleic acids you have four components and they are much longer so it needed quite a change in technology; luckily I was not in the position where I had to produce papers at speed and Max was sympathetic to my going into the nucleic acid field; I had quite a time before I made any progress but eventually we developed methods; first sequenced RNA but as it became more obvious of the function of DNA I switched to it; difficult to get pure DNA; got it from small organisms, essentially viruses; a phage is a virus in a micro-organism, a bacteria, and this is what was sequenced 43:16:13 Thoughts on Crick and Watson; John Griffiths an extremely bright person who came to the labs and could always tell us what was happening but didn't do experiments at all; Archie Martin also very good on the theoretical side; he and Synge had a famous paper at the beginning of sequencing and he came up with marvellous techniques; sadly got Alzheimer's when still young and faded out; most of the fractionation techniques that I used were devised by Martin 48:21:05 Remained in Cambridge but did go for a couple of months to North Western University and they were anxious for me to stay on; found Cambridge a good environment for research and I like England; very lucky not to have to do any administration; did give a few lectures in the biochemistry lab but don't enjoy lecturing; do not enjoy writing either; now I don't read at all, my memory is hopeless; when I retired I really retired; I'd got the sequencing work going pretty well on DNA and had done a bacteriophage phi X 174 and had got to the stage of mass production of sequencing to get the human genome; was by then sixty-five and not interested in continuing as it would not have been much fun; feel that the sequencing of DNA was the thing I was most satisfied by because it is fundamental to know who we really are