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...