Interview with Sir John Kendrew by Peter Farago Farago:
How would you describe your early education and the other factors that led you to a career in science? Kendrew: I was brought up in the old-fashioned classics, to think that the only decent subjects one could study were Latin and Greek. But at 15 1 quite clearly made up my mind that I wanted to do science. My lather was an Oxford don, a climatologist of the old-lashioned kind. I wouldn't have described him as a scientist myself, and I'm sure he wouldn't have described himsell as one. I was at Clifton, and the school happened lo be particularly strong in science, with Holmyard the Head of the Science Department. I was brought up scientifically by him. The school had extremely good physical lacilities, so much so that I remember being dismayed when I took a scholarship examination lor Cambridge, and had to do a practical physics exam in the old Cavendish, which compared most unlavourably with the facilities we had at school. My first shot at a scholarship to Cambridge failed when I was 17. 1 finally went up when I was 19 to read chemistry. I began to lee1 that I was interested in biology as a consequence of the Cambridge system, in which during the first two years you are pretty well compelled to read a subject which you have not read at school. Biochemistry, which I read, was in Cambridge in those days at more or less its peak of excellence. I wanted somehow to get into biology, and, having taken my degree in the summer of '39,and started on research, moved into the physical chemistry department to work on enzyme kinetics with Moelwyn Hughes. But the project only lasted about three months, because I got swept off into the war and put the whole thing to one side. During the war I was on radar research, and then moved into operational research. I was the first scientist to go to RAF Coastal Command, even before Blackeft-and then on to the Middle East. Most of my time was spent in the Middle East and Far East. I had been, while I was an undergraduate, a member of the Cambridge OTC, and, finding parades a bore, I discovered that there was a man called W. B. Lewis then a young lecturer, now the head of Chalk
River, doing research lor the War Office on what in those days was considered to be ultra short wave radio communication on 3 meters. The way of getting out of parades was lo he$ him. When the war came along the Recruiting Board in Cambridge said, "You're a chemist. Stay in Cambridge, and some important war work will be found for you." After three monlhs nothing had happened, and I came to the conclusion that it was really much more a physicist's war than a chemist's. So I wrote to W. B. Lewis, having some inkling of what he was doing, and he brought me into it. I later got into operational research because I wasn't a physicist: I was a chemist, and I felt that I was not going to make the maximum contribution sitting at a lab bench pretending to be a physicist or electronics man. Most people are pretty flexible, at any rate when they are fairly young: the war was full of cases like this. Farago: Were there others who had a great inlloence on you during the War years? Kendrew: The war years, the people one met, had a long-lasting scientific influence on me, because by sheer chance I got to know two biologists: one was Desmond Bernal and the other Waddington. Bernal was a great friend of Mountballen's. When Mountbatten was Chief of Combined Operations in England, Bernal was his Scientific Adviser; when Mountbatten went out to South East Asia, I was at Mountbatfen's headquarters; Bernal, being an old friend as it were, used to come out very often, though he was never
Sir John Kendrew is Fellow of Peterhouse College and Deputy Chairman of the Medical Research Council Laboratory for Molecular Biology at Cambridge University He and Dr. Max Perutz shared the Nobel Prize in Chemistry in 1962 for their work an the structures of proteins using crystallogaphie methods. Professor Kendrew is a member of the Council for Scientific Policy, the Defence Scientific Advisory Council and other science policy-making groups in the United Kingdom. One of his mast popular books is "The Thread of Life," published in 1966. Volume 51. Number 1 1 November 1974
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on the stall there. Though I had met him before, I realty got to know him then. 1 have always been slightly on the left politically, but certainty not anything like as far left as Bernat. I don't think I ever talked politics very much to Bernal; and he would not have thought it worthwhile talking politics to me. He would have regarded me as a good Labour voter, hopelessly bourgeois right wing, and probably immovable. But of course with Bernat you realty talked about almost anything: he knew about everything. Bernal had been in Cambridge up to 1936, and he had his research group, which included Dorothy Hodgkin and Max Perutz. Then Bernat went off to London and Dorothy went to Oxford, and Max, whom I did not know at that time, remained in Cambridge. After the war Bernat offered to take me into his lab at Birkbeck, but he had financial problems. It emerged that I had the unused bit of a Cambridge scholarship lrom before the war. He said, "Since I don't have money, you had better go back to Cambridge." He sent me to see Bragg. Bragg introduced me to Max, and that is how I joined Max, who was already working on the X-ray analysis of proteins. I got involved with some trepidation, because I had never read crystallography as a subject at all. I started from the angle thst I was interested in proteins, and since the best way of studying them seemed to be X-rays, you had to learn X-rays in order to do proteins. Farago: Did you think of yourself as a chemist white working with Max Peruh? Kendrew: One of the problems was the tack of a professional label. By profession I was a chemist working on a biological problem in a physics tab, because Max Perutz was in the Cavendish. Most biologists would not have thought what I was doing was biology. One of the people whom I also got to know during the war. A. V. Hilt, said. " 0 1 course, that is not reattv biology at all-it is crystals, and (paraphrasing what he said) unless it wriggles A crystal . . it isn't biology." .. is about as far removed lrom the living system as you could get. Biochemists had to be convinced thst the molecules which we studied in the crystal were stilt the same molecules as those in a physiological situation. 1 think even today there are some biologists who would regard molecular biology as far removed lrom what !hey would call real biology. The chemists provided all kinds of answers lor biochemists, but I do not see that the chemists could ever have provided the answer to DNA, One of the triumphs of classical stereochemistry was that peoD k like Pasteur were able to talk about the threedimensional structure of molecules. Later the topic became tremendously sophisticated, and one could envisage a tot about the three-dimensional structure of organic molecules, even fairly complex ones. Nevertheless, chemists accepted that there was no hope 01 discovering the three-dimensional structure 01 a protein molecule by classical chemical techniques; but one could not understand the function of a protein molecule or DNA without a knowledge of its three-dimensional structure, because what is important is the actual spatial relationship between the dilferent groups. Classical stereochemistry deals with molecules such as tartaric acid or somewhat more complicated ones, having perhaps 20-30 atoms. It has to be remembered that one of Bernal's major contributions was to put people on the right track lor the struclure of the steroids by X-rey analysis, when chemists had got it wrong. On the other hand to the chemists' credit, let us remember that it was Chargaff who established me base ratios of DNA by pure702
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ty chemical techniques, an essential part of the Watson and Crick work on the double helix. We really owe it to Bragg and Keilin that the protein work got off the ground at all. When I started we had no biochemical facilities in the Cavendish, and Keitin, who was then Professor of Parasitology, gave US Some space to make crystah in his tab. Both Max and I had temporary research grants which were running out. Neither of us were physicists, so Bragg could hardly appoint us to stat1 positions in the physics lab, but Bragg and Keitin came up with the idea of persuading the MRC to lake us over. There was a terrific enthusiasm from Bragg. The story about Bragg's tack of enthusiasm on DNA has been overdone. The actual situation was that Francis Crick, who had joined us, was writing a PhD thesis on protein structure, and was of an age when people said, "he had better get his PhD quickly." He was always liable to shoot oft at a tangent in other directions, and Bragg, who probably didn't realize the biological importance of DNA, linding that Crick was spending time playing with DNA, told him he had better get down to his thesis or he wouldn't get a PhD. But when he and Jim Watson did produce the structure, Bragg was immediately convinced of its importance and realized that this was not just one more structure, but something of very great, very wide implications. Just before DNA came out-1951-52-we were absolutely in the doldrums, Nobody knew how to solve a protein structure, and indeed most of the professional crystallographers thought we were wasting our time. Both Max and I had written a series of papers, which in the event turned out to be simply wrong. Bragg had taken a tot of interest because he was a very good theoretical crystallographer, and he failed to produce any solutions. Farago: How did the determination of the DNA sEbcture allect your thinking and that of the other crystaltographers? Kendrew: The protein crystals were enormously more complicated than those normally solved by the current techniques of X-ray analysis as their molecules contain several thousand atoms. Conventional crystattographers were solving at that time structures with 20 atoms. The prolessionals said the increase in orders of magnitude was too big. The way proteins were solved involved the heavy atom technique, which had been proposed before the war, when it had been used for solving the structure of alums, isomorphous structures with different metal atoms. Before the war Bernat gave a lecture in which he discussed the possibility of applying the heavy atom method to proteins, but nobody ever did it, because the job of putting in the heavy atom seemed very dillicutt, and because people had never done the catculations properly. It was thought that one heavy atom, even the uranium atom, is so tiny compared with the rest of the molecule that it will not produce any measurable difference. This was a feeling people had, but they were wrong: it doer produce a measurable difference. We had a chemist called Vernon lngram, now at MtT, interested in sulfhydryt groups; hemoglobin had sulfhydryt groups, and he attached a mercury atom to each. Max crystallized the hemoglobin with mercury attached and found that the X-ray pattern was quite substantially dillerent. He started a long way ahead of me, because he got his heavy atom in and I didn't-my protein had no sulfhydryl groups-then h e ran into technical dilficutties. In the end it happened to be my own protein which came out tirst. Another important factor was the use of electronic computers, because
the kind of calculations needed to solve the sbucture 01 a protein were too big to be done by hand methods. The first Cambridge electronic computer-EDSAC Mark I -just came into use at about the right lime, and I happened to be interested and learned programming. I believe I was ihe lirst crystallographer ever to do cakulations on an electronic computer as a matter 01 routine. We all were discouraged during this period, and indeed all of us were playing around with alternative projects. I was interested at one stage in developing micro-techniques lor X-ray crystallography, thinking of looking at systems like muscles or chromosomes. 1 had a research student, Hugh Huxley, who started on that side. His work took off in a very big way, and he became later one 01 the foremost authorities on muscle structure. I might have gone in that or another direction if the protein work had not come out. Is it lair to say that the groups at Cambridge during Farago: this period were the lounders 01 modern molecular biology? Kendrew: Internationally, molecular biology grew up in twoessentially independent-schools. On the one side was the struchlral school, including Pauling but consisling mainly 01 British scientists: Astbury, Bernal and Perulz. On the other hand was Delbruck's school at CalTech working on phage genetics. Eventually the two schools got together, but before Jim Wabon's joining Cambridge from CalTech there was very little cognizance of what the other group was doing. The lirst time we got the myoglobin structure was a really exciting moment. We just got out the low resolution structure and aN you could see were kind of sausages. We cakulated it one Saturday night on the EDSAC computer, and finished late at night. We plotted the lines till about 4 in the morning; and we only had the plots on pieces 01 paper. But you could see that there were these sausages running through it: clearly there was something there. To go from that to the original model took about three weeks. The problem in crystallography is that one does not know where one molecule ends and the other begins; and if there are some errors in ihe analysis one may get bridges between one molecule and the next which can lead one astray. I must say the Nobel Prize was exceedingly unexpected when it came, because Max and I got it the same year as Crick and Watson and Wilkins. The Swedish Academy announces the prizes on different dates. The medical prize, which they got, is always announced a month ahead of chemisiry and physics. When they go1 it, the last thing that Max and I thought was that by any conceivable slretch they would give another one in the same field in the same year. It really was a total surprise to get it that same year. In retrospect, what has lostered and sustained your Farago: interest in science? Kendrew: Science has always interested me in a number of ways. First 01 all, I rather liked working with my hands; and secondly I liked it intellectually and phiIosophically-I was interested in the kind 01 world view one might have, and science seemed to be a way of getting to grips with that. I am sure thal real scientilic discoveries are essentially inspiration, rather than causally worked out logical sequences. Good scientists gel inspirations or ideas which should be, if they are to be uselul, educated ideas, in the sense that they take account of all the known lacts. The process consists in trying to prove you are wrongand if you can't then at least your theory is a good starter. I completely agree with Karl Popper's gener-
al thesis about the way scientists work, and it does seem to me to represent the way it actually happens. In one sense molecular biology is already disappearing. There is a whole lot of what is called molecular biology, which is really straight biochemistry. The whole area 01 the mechanism of protein synthesis 01 ribosomes is just straight biochemistry; the techniques are biochemical, though running through it all the time is the knowledge of the lhree-dimensional structure. One of the great unsolved problems is how the protein is assembled on a ribosome, a very complicated three-dimensional objecl. We shall not really understand it until we know what the structure of the ribosome is. This is again a ihreedimensional problem. But a lot 01 the work, the techniques used, are totally indistinguishable lrom those in any biochemistry laboratory, so in a sense the boundaries 01 the lield are getting blurred. There are molecular biologists interested in the structure of the central nervous system; a blurred boundary with neuro-physiology. There is a very blurred boundary wilh cell biology, because now people who call themselves molecular biologists are leaving the study of bacteria and becoming interested in animal cells, and doing the experiments that people who call themselves cell biologists do. The lield is becoming more and more blurred--and why not? In the old days when Hopkins left physiology, the ofd-lashioned physiologist said there was no such thing as biochemistry: it was all part 01 physiology. This time a lot of biochemists say there is no such thing as molecular biology, /hat it is all part of biochemistry. What do you see as the role 01 the scientist in sociFarago: ety? Kendrew: f have never thought scientists make good politicians; they have no special role in thinking about the way society should be run. But they do have special knowledge, and their most important responsibility is communication; because it is bad enough to try and loresee the effects of some scientific or technological advance given all the facts, but wilhoul them it is impossible. Since we happen to be in a society in which very lew of the people who run the country are scientists or had much scientilic content in their education, it is a11 the more importanl for scientists to communicate and make what they are doing understood at government level and publicly through the media. I have been very heavily involved with advice to the government, and still am both in this country and abroad. People's temperaments are dillerent. I remember Rabi recounting a conversation with Linus Pauling alter the war when they were both very concerned about social problems. In those days it was the ellect 01 the bomb; knowing them both well, I think they were equally concerned, but they more or less agreed that Rabi had the kind of temperament which worked best behind the scenes-he was a good commillee man-and Paulincl absolutely was not. The consequence was that Rabi sat as a member 01 the Presideni's Science Advisory Commiltee, and Pauling walked up and down outside the White House with placards. Both made a major conbibution, and neilher could have made the other's; it was just a temperamental difference. I suppose I am more of the Rabi type. The exponential growth 01 science ihat has gone on so long obviously had to Natten sometime. You could demonstrate, as Derek Price did, lhal, if the exponential continued, aN citizens of the Uniled States would be scientists by the year 2000. It was also clear that the llaltening process was going to be pretty uncomfortable for all concerned, because it Volume 51. Number 11. November 1974
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changed the whole career structure. In the old days any bright young man could assume that, by the time he was grown up, so to speak, there would be a new prolessorship created lor him. Now this isn't any longer so, and it has obviously caused a lot 01 trouble and dilliculty in the States, and here, and now in Germany. Farago: Where are we heading? Kendrew: Parlicularly with the flattening of research budgets, lhere will be more and more Impetus towards sharing lacilities internationally. Everything does not have to be international like the molecular biology lab at Heidelberg; there could be joint lacilities, or one may set up a mechanism to avoid duplication. I have been very heavily involved in the international biological laboratory at Heidelberg. It all began with the loundation 01 EM60 ten years ago, a private body with no money and two major programs: one was the lab, and the other to get money for feltowships and summercourser. It turned out that the latter was easier than the lormer, so we got the lellowships and courses going some years ago. The lab was quite a hard struggle. Ten governments signed on the dotted line last May. The Agreement doesn't actually take legal effect until the home governments have ratified, which takes some governments more than a year. In eflecl it will be ratilied next spring, we think. The population would be about 300 people. The scienlilic stan will be relatively small-about 60-because the whole object is to hsve a lot of vis-
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itors, post-docs, and so on. There are dangers in general courses in science. A lot 01 universities have started such courses; they are good up to a point. However, there are some subjects which are in my opinion absolutely basic to the way a scientist works, especially mathematics. One must not be broad at the expense 01 these basic subjects. I had to learn all the biology I know, 90% of it after my degree, just by doing It, and all the crystallography I used not lrom university courses, but as I went along. I do not think I could have done it if 1 had not had the basic training in physics and mathematics at school. To turn out good scientists you have to keep their noses to the grindstone quite a tot, but you must at the same time try and stimulate lheir interests on a broad front, so that, when they do reach the stage 01 being independent creative people, they will go 011 into new lields; and this is very dillicult. We are probably producing too many scientists at the moment, because our system is still geared to the exponential growth phase, which has now stopped. There is a lag, and we are not lully accommodated to the new situation. While we are producing too many scientists, the dillusion of scientific thought and knowledge and science among educated people at large has not gone lar enough. Maybe we need fewer professional scientists, but rather more good people h other walks of life who hsve learned some science at school and university.
