Aaron Klug interviewed by Alan Macfarlane 11th December 2007

0:09:07 Born in Lithuania in 1926; father's father was a cattle dealer and had a farm which was unusual for a Jew; father was trained as a saddler but went back to the farm to help his father as a cattle dealer; realized there was not much future in Lithuania and moved to South Africa in 1929; mother's family had emigrated there in 1900 (her family name was Gevisser) and had established a business in Durban so that is where we went; learnt English early; have an elder brother; father employed in the Gevisser firm as a hide merchant; he had gone ahead to Durban and found a place to live and the family followed; father's brother later emigrated to Johannesburg; father much concerned with making a good living and had been regarded as clever; he would go to the synagogue and was interested in the Talmud and when he retired he went for weekly study; when I married in England he sent extracts by post; mother died when I was about six of pneumonia; mother's younger sister had come with us and later married my father; told that one of the older Gevisser cousins had said it was her duty to marry my father and help bring us up; we still continued to call her aunt though later realized she was our mother and changed to mum

8:36:12 Went to a primary school; lived near the bush; Durban had a white population of 100,000, mainly of English origin who thought of England as home; Britain had taken Natal from the Dutch and in 1870 there was a large emigration to Durban; on our first holiday in England we went to Swanage and noticed that the beach huts there had been copied in Durban, so had the post boxes; as a child knew a lot about England so when I came here knew exactly where I was; later moved to Durban High School where the philosophy was that if you were bright you went into the Latin class (Greek had been abandoned as we had to do Afrikaans as a second language); if you were middling you went into the science class, and the rest made do with geography; I was very good at school and always came first and my brother, second; he was in the same class although two years older; I had been pushed up but he was my protector; we did do one science subject; was very good at Latin; also brother and I went to Hebrew classes and I was pretty fluent in Afrikaans; later when I began collecting ancient coins could read the inscriptions; later when one of my sons started doing Latin at school got an interlingua text but found the Latin word order had been changed to fit the English so threw it away in disgust

15:56:08 Thing that mattered most at Durban High School was sport which occupied four afternoons a week; had cadets on the fifth day; brother was a good cricketer; I was not good at sport and later when undergoing an army medical found that I had an optic atrophy in my right eye; brother keen on music and I began to listen to serious music in last few years at school; in primary school I couldn't sing in tune; my wife is musical so I do listen; she ran the Cambridge University modern dance group at some time and experimented with Stockhausen and electronic music

19:46:13 No particular inspirational teacher at school; was good at all subjects; at one time became seriously interested in Egyptology and tried to teach myself hieroglyphics and learnt a good deal on the origins of the alphabet; at school read a book by Paul de Kruif called 'Microbe Hunters' which turns out to have influenced many people; he was a Dutch science writer and in this book he told the stories of Pasteur and Koch; made me think I should become a microbiologist; at fifteen went to university to do medicine (as did Sidney Brenner) as two years ahead of my age group; no medical school in Durban so went to University of Witwatersrand in Johannesburg; sailed through my first year; stayed in my father's brother's house; had won a scholarship so did not have any fees; in my second year started doing anatomy, physiology and physiological chemistry; enjoyed dissection to begin with and found physiology and biochemistry much more interesting so decided I should learn some chemistry and give up medicine; went to see the Dean of Science who agreed that I should do a range of subjects - chemistry, physiology, histology, physics and maths; did a four year course instead of three; got firsts in every subject

25:56:05 No particularly inspiring teachers but a man who gave a popular talk on the Schrödinger wave equation had inspired me to do physics; I had intellectual curiosity and found everything interesting; always read history and have continued to do so; where I got inspired was in Cape Town where they were offering a master's degree in physics; kept myself by teaching practical classes which gave me enough to live on; lived simply in a room in the old slave quarters; parents sent me money but I returned it as wanted to be independent; the Professor was R.W. James and he was an inspiration, not only because of himself but where he had been; he had gone with Shackleton on his polar expedition and been marooned on Elephant Island; he was recruited by Shackleton when just out of Cambridge; was a contemporary of Lawrence Bragg; Shackleton asked him if he could sing as they had to supply their own entertainment; I did apply to the South African Antarctic Survey but they wouldn't take me as I wore glasses; met my future wife, Liebe, in Cape Town; she was a music student at the University and later went to modern dance school; fell in love and was absorbed in the wider culture of a beautiful old city; Durban was provincial in comparison although it had a good library 

31:56:03 James had worked with Bragg and in 1937 emigrated to Cape Town to take the Chair; Bragg moved to Cambridge in 1938 when Rutherford died; it is possible that when I came to Cambridge they wanted me to do crystallography as I'd started in X-ray crystallography in Cape Town as James had done; James represented to me the modern Cambridge position; I did the two year M.Sc. course in one year and actually solved the crystal structure of an organic molecule by a new method using Fourier transforms; on the strength of this James thought I should go to Cambridge; I had toyed with the idea of going to London as the crystal structure I had solved was rather unusual and I had taught myself quantum chemistry so when I came to Cambridge I wanted to do something unusual in X-ray crystallography; had heard of the MRC unit doing work on haemoglobin and myoglobin; went to see Bragg on arrival who told me the unit was full; don't believe that was true but one of my predecessors from Cape Town had been a lady, Virginia Martin, who proved to be very clever but hopeless at research; asked Bragg what I should do who said there was an interesting problem in order disorder in silicates; I now find them fascinating but didn't think so at the time; boat took two weeks from Cape Town and for the first two months in Cambridge still had no supervisor; was at Trinity where my tutor was William Hamilton who was not much help; originally thought I might do a Part II but he thought I knew enough for a PhD; finally taken on by D.R. Hartree, Professor of Mathematical Physics, to work on a problem left over from the war on the cooling of steel; in the end I had learnt a lot of metallurgy and worked out a model of phase transition to account for the dissipation of heat; I modelled this on a computer; never published my PhD thesis; Hartree was not a good supervisor; he was a train addict, but not inspiring; enjoyed my time going to mathematical lectures and learnt group theory, which later stood me in good stead

40:53:01 Married very young and wife went off to live in London to study at the Joos-Leeder School of Modern Dance; the school had been housed by Alice Roughton in Adams Road, Cambridge, during the war but had moved by the time we arrived in Cambridge; my wife kept herself by teaching in a Secondary Modern school; never worked with Bragg; now realize that he may have thought me odd as I only wanted to do things that interested me; however, when I worked on the assembly of tobacco mosaic virus people were trying to understand how the virus assembled and they mixed protein and the RNA and waited twenty-four hours; I managed to do it in two to three hours using the model of nucleational growth that I had developed for my Ph.D. thesis to understand my experiments on tobacco mosaic virus (description)

46:05:14 Spent a year with F.J.W. Roughton, the husband of Alice; worked with him solving the mathematics required for the problem of the combination of oxygen with haemoglobin where both simultaneous diffusion and chemical reaction occur at the same time; used the mathematics developed for PhD; went back to crystallography in London but continued doing things for Roughton; memory of Roughton household in Adams Road; saw advertisement for a Nuffield Fellowship at Birkbeck College where J.D. Bernal was; he was an amazing man who never carried anything through to completion as always interested in the next problem; went to work on protein crystallography with Harry Carlisle who Bernal had recruited from Dorothy Hodgkin; he was trying to solve a protein by some method that didn't work and he refused to see it; I was banished but still had my Nuffield Fellowship and I found myself in a room next to Rosalind Franklin; I had been there for four months already but had not met her before; she showed me her pictures of tobacco mosaic virus; she changed my life as she introduced me to an important and difficult problem that would take years; I worked with her from 1955 to 1958 when she died; she had come from King's College to work on the tobacco mosaic virus, work which Bernal had started in the 1930's but which was interrupted by the war; as a person she was brisk, to the point, and not at all the person painted in Watson's book 'The Double Helix'; she was a rationalist; I got on with her quite well and she treated me as an equal; when she died I took over her three post-graduate assistants including Kenneth  Holmes and John Finch who later moved with me to Cambridge; we managed to get a grant from the United States National Institute for Health as we were the only group working on virus structure; in 1958 after her death I took up the problem of polio virus structure which she had started; through the introduction of a new kind of glass managed to solve polio in 1959; showed Bernal the first X-ray picture of polio virus crystals and he said that the picture was worth £10,000; I had not realized that Bernal had to keep raising money to fund his lab; Rosalind Franklin had been hired to work on coals and carbons not on plant viruses; Bernal's idea was to raise money from applied research to fund pure research; [shows the model of RNA on the staircase of the MRC unit in Cambridge]

Second part

0:09:07 Bernal was a Communist in those days and I didn't get on with him; in 1956 when the Soviet Union invaded Hungary there was a meeting of University College, Birkbeck and the Fabian Society; Bernal spoke about knowledge of the purges only since Khrushchev’s speech in June that year; later got to understand him and to realize that he looked with  the long eye of history where revolutions move things on; Rosalind Franklin never complained about not having recognition for the important part she played in Crick and Watson's discovery; blamed herself for not noticing the two fold axis of symmetry in her photograph; she did not know enough crystallography; when at King's she had worked out the A and B forms of crystal symmetry of DNA; she knew the B form was helical and said so but the A form eluded her; Watson recognised the relationship between the two forms and they got hold of her report which had been sent to all MRC units and he and Crick used her data; had she lived, she should have shared their Nobel prize but there was also Wilkins; he was shy and he and Franklin would never have got on; he was clever and had chosen DNA as a problem but had no punch to go ahead; Franklin had been brought in by Randall, the Professor at King's, to put more muscle into the DNA effort; irony was that Wilkins, Stokes and Franklin had all attended Bernal's courses in Cambridge in the 1930's in crystallography and had all learnt about space groups; none of them twigged to it except Crick; only came out later when he and Watson wrote their paper in 1954, on their route to the discovery of the double helix

6:55:14 John Griffiths' part in the DNA saga not relevant but Franklin's work was the key but she had nobody to talk to; if I had been there a bit earlier I would have seen it; [article: 'The Discovery of the DNA Double Helix' amended and signed]; Maurice Wilkins was slow and careful whereas Rosalind was quick and decisive, sometimes brusque, so they would never have got on, it was not because she was a woman; worked at Birkbeck 1954-58 and during that time worked out the overall structure of the tobacco mosaic virus and I also developed analytical methods for turning the X-ray data into a map; wrote papers, one with Crick, on how you do this; after Franklin died her students, Finch and Holmes, came with me to Cambridge in 1962 and continued the work; Holmes went off to be Professor of Crystallography at Heidelberg and John Finch stayed with me; Holmes gradually worked out the three-dimensional structure of tobacco mosaic virue but we had an outline of the structure as early as 1958 which is the model on the stairs [see end of film]

13:03:12 In October 1962 I came to Peterhouse as a teaching fellow; John Kendrew was the Director of Studies and I later succeeded him; at Peterhouse I taught a number of subjects as there were not many teaching fellows including crystallography, microspectroscopy and chemistry, and always taught physics; I was later a Nobel prize winner in chemistry, worked in a biological lab. and taught physics; I enjoyed physics and was quite a good teacher; Ken Holmes had been taught by Fred Hoyle and Abdus Salam but never learnt anything as they would just dash off a problem; I was a good teacher as I had to work my way through it; physics stood me in good stead as before I developed three-dimensional image reconstruction I did various optical experiments which I wouldn't have done if I had not been teaching optics; I occasionally lectured for the University in place of Perutz; later when I introduced three-dimension electron microscopy I was asked to give some lectures; awarded a Nobel prize in 1982 but went on teaching until about 1984 when Hugh Dacre, the Master, said I should become a supernumerary fellow with no teaching duties; accepted but still continued teaching for a few years until I became more involved with the zinc finger work; in 1986 became head of the lab after becoming President of the Royal Society in 1985

16:34:10 Was President for five years; had turned it down five years before and found that I was the only person to have refused it since Faraday, but I had just started a new division at the Lab and I thought that being head of the MRC Lab was just as prestigious; I introduced a department of neuroscience here which we had not had before; as President of the Royal Society had to deal with a lot of issues such as genetically modified organisms which, by the way, with zinc fingers we can do much better now; this is producing what has been called a game change in plant agriculture; zinc fingers are used to modify genes and you can put genes into a specified place; had to deal with privatization from Mrs Thatcher as she wanted to sell off all our laboratories; also started on global warming; every year in my anniversary address I, like the elder Cato, would bring up the subject; started work here with John Sulston on the human genome; Sydney Brenner and others were going round the world creating the Human Genome Organization; John Sulston started out using any sequencing facilities that there were and made huge progress; Brenner had wanted him to work on the products of the genes, the proteins produced by the genes, and to sequence those, or rather to sequence the RNA which is the intermediate between the DNA; I, in contrast, encouraged Sulston to do the whole genome because there you get not just the products of the genes but, probably equally important, the DNA sequences for binding the regulatory machinery; now, ironically, I am working on zinc fingers which are the most powerful weapon for intervening in gene regulation; after turning down the Presidency I did not think they would ask me again at the age of sixty-nine but Alex Todd had been the same age so there was a precedent; my wife enjoyed the challenge and we opened up the place by having lunches and improving the menu; we had a flat in London and I had thought we'd go to theatres and galleries, but was too busy as it also overlapped with being head of the lab

23:10:20 Started in the Lab in 1962 and had my own group, but did spend time working with Crick on chromatin; we published very few things together; had a very good post-doc., Roger Kornberg, who got a Nobel prize last year, and together investigated the sub-structure of chromatin; he discovered working on the chemical analysis of chromatin samples that the histones which are used for packaging the DNA on their own form aggregates; the psychological breakthrough was that the proteins form a globular aggregate like haemoglobin and here could not be sitting in the grooves of the DNA as people like Wilkins had assumed; Kornberg discovered the nucleosome; I did not put my name on the paper though might have done; got him to see not "beads on a string" but string of DNA on beads; I also started work on tRNA; also started an Alzheimer group which is flourishing as I thought we should be doing something that is relevant to medical research; had not realized that Alzheimer’s disease was specific to certain areas of the brain; realized that it must be caused by a malfunction; work had been in the hands of neurophysiologists and they had been cutting sections of Alzheimer brains; I said we must get the material out as had been done with chromatin; introduced chemical separation methods which we'd used on chromatin, chopping up the material with enzymes etc. so we discovered the filaments; work continues but I moved on to zinc fingers

27:43:04 Max Perutz was head of the Lab when I came here as a group leader; John Kendrew was the head of one of the divisions in the lab called Protein Crystallography; Hugh Huxley was working on the structure of muscle; I was working on viruses; Perutz and Kendrew were working on single proteins; we worked on biological assemblies using both X-rays and electron microscopy; Hugh Huxley was the best electron microscopist of his time, a mystery why he did not get a Nobel prize for his work on muscle; Max was single-minded and determined; wasn't very learned but as he went along he learnt; not highly imaginative but solved, over a period of years, the structures of haemoglobin both in the oxygenated form and the deoxygenated form and shown the structural transition between them; John Kendrew was very different; a marvellous staff officer, very well organized with a meticulous filing system using a form of punch card; when I told Max how tobacco mosaic virus assembles [shows figures from Nobel Prize lecture] he didn't believe it; own work on spherical viruses described; collaboration with Donald Caspar [shows model of a spherical virus]; in 1966 Max gave an interview for 'Science' and spoke about all the successes of the lab - Nobel prize for Crick and Watson in 1962, and himself and Kendrew, Sydney Brenner's work on the messenger RNA, and "Klug's work is very satisfying" but was "very far fetched"; his gift as Director was to let me get on with my work without believing in it; Crick understood it immediately and I know that he put me up for the Nobel Prize; spherical viruses and Buckminster Fuller geodesic domes

40:06:05 Electron microscopy takes a two-dimensional image; 3D image construction allows you to combine all the 2D views mathematically using a computer and producing and three-dimensional image which is the basis of the X-ray CAT scanner; some thought I should have got a Nobel Prize for this work but Hounsfield patented the machine not the technique; felt a bit sore in 1979 when he got the Nobel Prize because he knew my papers and referred to them and I'd exhibited with him at the Royal Society [shows images of electron micrographs of virus particles and describes use of tilting experiments using computer methods leading on to the method for the CAT scanner]; my paper came out in January 1968 and in August Hounsfield took out a patent for building a machine at EMI; to begin with it produced nonsense as he did not collect enough views for the detail he was looking for; however, in 1982 I got the Nobel Prize on my own for chemistry; earlier tried to interest radiologists to take up computer automated tomography based on image construction techniques but they thought it would be too harmful to take a series of X-ray photographs

51:22:18 Work on zinc fingers; became interested in active chromatin which has become susceptible to enzymes which will attack the “open” DNA which correlated with genes which were going to be activated; began looking for a source of active chromatin in large quantities; found that the gene of ‘Xenopus Leavis’, the South African frog or toad, which was present in large amounts; colleague Hugh Pelham had actually worked on it; decided to work on the 5S RNA genes which in this case gets incorporated into ribosomes which are protein synthesis factories; had a new post-doc, Jonathan Miller, and uncovered by purely biochemical experiments over a number of years that this had a repeating structure [shows diagram and the amino acid sequence that came out]; went on from strength to strength [shows number of zinc finger genes from simple forms to human] a marvellous modular system where each finger has a different amino acid sequence which can recognise a short sequence of DNA; so suggested to me a tool for making synthetic fingers having access to genes; now a big technology; with my colleague Yen Choo who formed a company call Gendaq; MRC hold the patents; in the lab started to make libraries of zinc fingers and began to work out the rules of recognition; Gendaq was bought out by an astute American who created a biotech business called Sangamo which may be successful and make some money; now the method of choice, 'game-changing' technology; know I've been noted for another Nobel Prize for it; I didn't set out to be a benefactor of mankind but just out of curiosity which is the driving force; its not only thinking but also doing; we used to make fingers in the lab chemically so I had to learn how to synthesise these things; the first paper on zinc fingers appeared 1985; when I wrote it, I thought it was unlikely to be confined to a lowly gene in a lowly animal; needs not just intelligence but also imaginative powers of the "what if" kind; also need some technical expertise unlike Linus Pauling who often proposed things that were unrealizable as he didn't have enough technical understanding; the truth is in the detail...