John Gurdon interviewed by Alan Macfarlane 20th August 2008 0:09:07 Born 1933; our family goes back reliably to 1199 and was well established in a large house in Assington, Suffolk; my grandfather ran out of money as he rented out farming land; the repeal of the corn laws meant that farmers couldn't sell their produce so could not pay the rent; my grandfather had to sell up in 1894; father worked in India and Burma for a while but was then paid a pension by his father to come back and marry and continue the family line; I was brought up on the Surrey-Hampshire border; there is no evidence of any scientific inclination in the family, they were mostly politicians and such like; father was a retiring, meticulous man, and in his later years read an enormous amount and became very good at financial matters which really re-established the family in a relatively comfortable state; my mother encouraged him to do something when he left India and he took up brail transcription of heavy legal textbooks; he had had a rather distinguished war period and was awarded a DCM for gallantry; he was just over age by the Second World War so he was air raid chief warden for the village; he took part in village activities and did quite a bit of voluntary work with my mother; she was born of a Yorkshire farming family and was unusually go-ahead for the time and decided to take a teaching job in America for a time; came back and married; she was very energetic and ran anything that could be run locally; she was extremely supportive of anything so when I took an interest in insects at an early age she would encourage that; by that time my parents had enough money to send me to a private school, Eton; I did one term of science at fifteen and am still amused by the report that the master wrote saying that Gurdon was the worst pupil that it had been his lot to teach, and some talk of Gurdon wanting to be a scientist which would be a total waste of time both from his point of view and those whose job it would be to teach him; I was put onto Greek and Latin which was quite interesting; my real interest has always been in insects and things like that 6:18:14 My interest in insects was probably from the age of eight; I had an aunt who used to catch me butterflies and I liked to set them and find out what they were; for leisure reading in my mid teens I bought a textbook of entomology; my kind mother decided that I really was a scientist at heart so through family connections she arranged an interview with a professor of zoology in Oxford, Alistair Hardy, and somehow persuaded him that I should be allowed to switch from classics to zoology if I did an intervening year in a crammer to get through the 'O' level science; it was a risk as I might not have taken to the subject; having paid my school fees they then had to pay for another year of private tuition in elementary science to be allowed to start at Oxford; that was again a piece of luck because the Admissions Tutor for Christ Church was Trevor-Roper who had more important things on his mind; I got a letter saying that they would accept me under two conditions, one that I came into residence almost immediately and that I should not read the subject in which I had taken the entrance; later I got to know him quite well and he admitted that it had been embarrassing and they had got the numbers wrong and suddenly found they were short of places so anyone who had applied and they had not done much about and could get hold of got in; a back door arrangement that would not be possible now; very fortunate, and thanks to parents for seeing what one's interests really were and to recover for a really bad teacher at school 8:38:12 First school I went to was Frensham Heights, a curious school; remember doing an intelligence test aged eight; remember being asked to draw an orange but I drew it with a stalk which was deemed wrong as what was wanted was a circle; parents received a message that there were difficulties and I would need special education; they then sent me to another school in the village of Edgeborough where we lived; teachers at this school became personal friends; the Headmaster was Charles Mitchell, his deputy Bob Hardy, and the Latin master was Norman Stone, and I remember all of them; a lovely school; during my time at Eton I became interested in squash, partly because you could play it whenever you wanted; I ended up being captain of the school team; I was a keen skier and got into the second University team for that; again, didn't feel I had any particular ability but it was just hard work and practice; I also became secretary of the Natural History Society at Eton; I was never keen on music; I am not very arty, I don't go to theatres or spend much time watching or listening to other people performing 12:03:17 I have a younger sister who became a nurse and then married a farmer who has a big estate in Lincolnshire; I keep up with her very well, being a lifetime friend; at Christ Church, the idea was to do zoology; I was told that I would have to pass the Prelim exams in one year, which was tough; I started by getting rid of chemistry which was really just learning formulae after one term, the physics was very elementary, and that left biology for the summer term; I got through these tests which then meant I could start as an undergraduate after one year, so I was given four years not three; in the second year started to read zoology; Alistair Hardy was the Head of Department, a wonderful man, who became a personal friend; it was a remarkable department; among the eminent people there was Nico Tinbergen; it was rather a boring course, three days of the week we did the animal kingdom, including palaeontology; I was doing badly as a student but something persuaded me to look at all the old exam papers for the last ten years; I classified all the questions and then asked each staff member how I would be expected to answer each as I had noticed that the questions were somewhat similar each year; by an amazing piece of luck that got me a good degree which meant I was able to be a Ph.D. student; because of my interest in insects I had gone to the entomology department where fortunately the Professor rejected me as a Ph.D. student; a wonderful man, Michael Fischberg was the embryology teacher and I warmed to him; he offered me a place in his group; that was probably one of the most important steps in my career; he put me onto a rather dull project which I didn't thrive on; then he suggested I try a new thing called nuclear transfer and by an amazing piece of luck it looked like it was working; he then gave me that as a major project; he was immensely supportive and would let me do anything I wanted; so several times I survived the fate that might have overtaken me, like becoming a museum entomologist, or not getting to university at all 17:06:17 A friend from my undergraduate years is Bryan Clarke, who became Professor of Genetics in Nottingham; the best person in the class became Professor of Biology in York, John Curry, whom I keep up with marginally; Bryan Clarke was a Ph.D. student with me and we used to go out most evenings to eat; did play squash but decided to give up trying to get a blue and concentrate on my work; I took no interest in music, drama or politics; on politics I am middle of the road; one thing I do object to are people who do no work and assume that the state must support them; I have respect for people who put a lot into life and contribute; on religion, my father took us to church every Sunday morning; I support the church; in terms of religious views I would say I am agnostic on the grounds of I don't know; there is no scientific proof either way; I support the ethics of the Church of England; I am anti-Roman Catholic as I think they should let people decide for themselves on contraception; I find myself giving lectures to theology students from time to time; this happened because when Master of Magdalene College I thought the sermons were boring; I suggested to the Chaplain at Magdalene that he occasionally asked Fellows to give an address on anything they would like to talk about; the letter was not responded to but the Bishop of Coventry, Simon Barrington-Ward, came back to Magdalene and I mentioned the idea to him; he thought it a good idea and I was asked to give an address; I chose to take as a theme that you should not be prevented from trying to relieve human suffering by your religious views; rather controversial, and the Chaplain didn't like it at all, (by this time I was Master of the College), he got preferment at Windsor and decided that it was interesting and invited me to give it to the theology students in Windsor Castle; I did so and he was very supportive; we disagree on a number of things but I continue do it; these are priests in service who come for revision classes, sent by their Bishop; after the talk I get them to vote; the first time they voted against the line I was taking; the Chaplain suggested that the next time we have a secret vote and then it came out in favour; I like talking on to what extent religion should interfere in the relief of suffering; a classic case is cystic fibrosis and should you get rid of embryos that are going to have it by in vitro-fertilization, and avoid enormous suffering; as Master of Magdalene never found any difficulty in presiding in Chapel; I don't think an agnostic position is inappropriate; I support what the church does very strongly, but the fact that I can't prove what we believe is a good reason to be called agnostic; Richard Dawkins’ views are rather too aggressive but make him good as a television presenter; he was a graduate student shortly after me and worked under Tinbergen; he does interest people in science and that is good though I wouldn't agree with his views on religion 28:11:07 In the 1950's we did not know whether all cells in the body have the same genome or not; the idea was that as an egg turns into an animal with different kinds of cells, maybe the cells lose the genes they don't need any more; your brain cells wouldn't have muscle or skin genes; a perfectly plausible idea and that would be a fundamental principle of how an egg develops into an organism; the point was to test this by experimental means; the idea was to take a specialized cell, take the nucleus out of that and put it into an egg that has no genes of its own; if you can produce an individual that way from, shall we say, the nucleus of an intestine cell, then that intestine cell must quite clearly have retained its genes for muscle, bone, brain etc.; that was the key question which people had been aware of since the 1890's but there was no good test for doing it; then two Americans, Briggs and King, discovered that you could transplant the nucleus of a cell into an egg which they did very successfully; when they tested it a bit later they found that as soon as the embryo developed these nuclei lost the ability to substitute for the egg and sperm; they reached the conclusion that genes were being lost or permanently inactivated; under my supervisor we started work on another frog called Xenopus and the results were roughly the same, but the key point was they were coming out the other way round; even when you took the nucleus of a specialized cell you still managed to get normal development; we eventually had a paper which showed you could get normal fertile adult animals from the nucleus of an intestine cell; that really convinced me and a fair number of other people at the time the opposite conclusion to Briggs and King, that genes were not lost, hence all cells of the body have the same genome; that has come back into popularity recently with the whole stem cell field; the argument is that if all cells have the same genes, in principle you must be able to create one cell from the nucleus of another cell; if you take a skin or bone marrow cell you can take its nucleus out, send it through an egg and recreate brain or nerve, or anything else, hence you will get the idea of patient-specific cell replacement; by use of own cells there is no immunorejection; that has become very fashionable now thanks to a Japanese man, Yamanaka, who discovered a much simpler way of making this transition; I am lucky in that the work that we did had a certain fundamental basis to it of a scientific kind; that has become useful to people for purposes of cell replacement 32:32:09 The American results were different because when they used a different kind of American frog, Rana pipiens, in which, for reasons we don't understand, it doesn't work very well; luckily for me it worked rather well on a South African frog; the first successful experiment came in 1958 and we kept the animals and published what was the most important paper at that time in the field on the generation of sexually mature normal adult animals from the nucleus of a specialized cell; published in the early 1960's; the first response was not to believe it; the two Americans were highly respected and I would have drawn the same conclusion from their experiments; there was a natural reluctance to believe some foreign graduate student who challenged these masters and pioneers of the technique; gradually, over time, people concluded that our experiments were right; we had no real difficulty with them working; the key feature of them, thanks to Fischberg, who found a genetic marker; when you do this experiment you transplant a nucleus into an egg and you have to be able to show that the embryo or animal you get back carries the genetic marker of the nucleus you put in rather than the marker of the egg whose own nucleus you hoped you had removed; the marker Fischberg discovered was of crucial importance to our work and came at just the right time; the frog cells are very big so you can do this by very primitive methods; we made most of our own equipment to make the pipettes or needles you use and some of them I still use now; it became more refined and when the work was transferred to mammals they use more sophisticated means of doing everything; the major problem was that the frog egg was almost completely impenetrable which meant that you put a needle in it and it would just push the membrane through the other side; thanks to Fischberg having bought a new microscope with an ultra-violet source it turned out that the ultra-violet light permeabilized the membrane which solved the problem 37:06:19 I was still in my twenties when this work was done; I stayed in Oxford until I was thirty-nine; I had become a Research Fellow at Christ Church, first in a junior research post then senior; I did not have much teaching to do so it was a favoured position; I then became part of the teaching staff of the Department of Zoology; John Pringle took over as Professor from Sir Alistair Hardy and he appointed me; he said he would like me to start off with twenty-four lectures, which was tough; the following year this was reduced to sixteen, and later on, to eight; by the time I left I was down to about four; I had attracted a lot of graduate students but was grateful of being relieved of teaching; I don't really liked undergraduate teaching; I objected in principle that the students could fill in a report form and say whatever they wanted, could be as rude as they liked; I was spared the worst but there were some offensive reports, and they aren't signed 39:50:24 After my Ph.D. I went for a post-doc period to California, again thanks to the good advice of my supervisor; I went to Caltech which was a good place, and got to know a lot of the senior professors; I worked on bacteriophage genetics but couldn't make them work so after that year I went back to embryology, but having learnt a great deal; I did not have a job at the end of my post-doc period so I did look at jobs in America; I was interviewed at Columbia University for an assistant professorship; the Head of Department said they couldn't offer me the job but added that if I could persuade my supervisor at Caltech to go there they would give him a full professorship at any time; I was tempted later by an offer from Stanford, but I have been lucky with jobs in this country 42:35:07 While at Oxford I got a letter from Max Perutz to say they had an appointment and would I be interested in moving to the MRC Laboratory in Cambridge; that was the ultra-famous lab with spectacular people, so it was an enormously attractive career move for someone who hadn't really learnt any molecular biology; I came to talk to Max and other; Max was a wonderful person and very supportive and I was offered the job; there was a whole set of rooms; the Oxford people had been good to me and had got me the offer of an MRC unit with quite a significant amount of research support with four or five positions, but the Head of Department was unable to give me space where I could have a coherent group, so it was tempting to come here; I accepted the job and then heads of other departments in Oxford, most notably Rodney Porter, the Head of Biochemistry, mounted a counter move to keep me in Oxford; however my Head of Department stuck to his guns; as I had a house and family in Oxford I was very tempted to stay and Max wrote a very nice letter wishing me well but keeping the offer open; when I failed to get the terms I wanted I wrote to Max again, accepted the job and moved into his institute; Max was an amazing person, very mild in character; as head of what I think was the most successful lab in history with fifteen Nobel prizes, he insisted on being chairman rather than director; if one wanted to talk to him one waited until he was in the coffee queue to do so; no appointment made with his secretary, all extremely low key administration; think that this was why he was able to keep this amazing group of people - Fred Sanger, Francis Crick, Cesar Milstein, Aaron Klug - in his institute, some for their whole working life, whereas any one of them could have taken an enormously prestigious job anywhere else in the world; Max somehow kept the whole lot going and I've never really understood how he did it; when we in due course came to start our own institute we set ourselves up with a chairman, not a director to try and emulate Max's style 48:31:12 Cesar Milstein, Max Perutz and I used to go skating in the Fens; Cesar was extremely interesting; have been working a little recently with Aaron Klug on zinc fingers; Aaron's phenomenal memory; Fred Sanger was extremely low key and if you didn't know who he was you could take him for the janitor; when we went to the MRC we were invited to join his research group; Sydney Brenner was undoubtedly too clever for me and I found it difficult to follow what he was saying; Francis Crick was a member of Churchill College where I was too, and I had immense admiration for his mind; I didn't know him socially as well as I did Max Perutz; curiously, those I knew better socially were not particularly close to my field; Sydney would have been nearer in interests but I never had any real scientific conversations with him; knew Hugh Huxley well, and John Walker; can't really understand why the lab was so successful; for instance, Crick and Brenner had to share an office for the whole of their time as there was minimal space; I suspect it was that the concept of a chairman can be more effective than a director; hard to do when you have to have people who govern a place, but Max did it in a way that displeased no one, except in a trivial way; when I joined it was in its present building in Addenbrookes; it was quite far from the centre so people there were rather divorced from College life; Max, Aaron and Sydney had college fellowships, Francis was at Churchill; Richard Keynes arranged for me to be a Fellow at Churchill which I missed, having had a strong college connection in Oxford; I was a Research Fellow at Churchill for about twenty years which was a benefit I have always appreciated; I hardly ever went in to lunch but I did find dinners very pleasant; I feel I have not done enough to support the college system but I do appreciate it a great deal; my Christ Church days were very different; if you went to high table, anything scientific or technological was inappropriate conversation, whereas now in most of the colleges I have been involved with, more often than not it is because it is interesting; a big change over the years 57:47:07 I got an unexpected letter from an unknown person who said it was his job to appoint the Master of Magdalene College and that he would value an opportunity to discuss this; I took it to mean discussing candidates whom he thought I would know about; I was invited to Lord Braybrooke’s place, Audley End, where we had a nice lunch, talking about everything from trains to skiing to holidays; he then asked me if I would be interested in the Mastership; after further conversations and thought, went to Magdalene to be interviewed in a mild and uninvasive manner; later got a call from Lord Braybrooke asking if I would do the job; as I wouldn't have to give up my lab we agreed to do it; they had interviewed my wife too which was very wise; she made a huge contribution to College, more than I was able to do, which was very much appreciated; she gave her whole time to it; we have two children; Jean kept the domestic side of life running when I was extremely busy Second Part 0:09:07 Fred Sanger's retirement tea party; about 1982 I got a letter from the Vice Chancellor inviting me to be the John Humphrey Plummer Professorship, previously held by Alan Hodgkin; natural inclination was to wonder why one should give up an excellent job in a famous lab to take on teaching and administration; told Max about the offer and he suggested I should not accept; then I discovered that a close colleague, Ron Laskey, who was an early graduate student and with whom I had worked on and off all my life, had also been offered a professorship in Zoology; Ron suggested we thought further and when we looked we found that our positions at the MRC had been whittled away so that we didn't have staff positions any more; thought that if we moved into Zoology and get a reasonable research grant this would help a great deal; we decided we would move and asked for time to get some funding from the Cancer Campaign; in the course of time we did and that turned out all to be due to Gabriel Horn; a clever manoeuvre to get both of us to move; gave us a floor in his Department, we got the money and moved in; it was a key event because it meant that we started with a medium sized research group; we did our teaching which was nice, it was a lovely Department under Gabriel; the work went rather well and the Cancer Campaign who sponsored us at that time asked if we would be interested in expanding a bit; we thought that would be nice but what Ron and I wanted was a small institute; they said they couldn't produce that much money but could make a contribution; by good fortune, the Wellcome Trust came into money at that time and we had an approach from them; we asked if we could put the two together and they agreed; I most particularly emphasised the pivotal role that Gabriel Horn played in this; we had enough money to build a small institute and many of the barons would have been hostile, but Gabriel thought it a good idea and actually helped it along; he spoke to the Secretary General who would ask the General Board if this was a good idea, who agreed; finally asked the heads of departments; this was how it survived; we got the money for the first addition to this institute; Gabriel was the chairman of our advisory board which was immensely valuable; without him I don't think it would ever have come into existence; it was very good of him as it wasn't obviously helping his department but he could see its value from the University's point of view; the initial operation, which cost Ł4,000,000, went well and in time we had the opportunity to expand; for this building we got Ł23,000,000; we have now over two hundred people here and bring in quite a lot of money for the University; although it had been against the advise of Max Perutz he nevertheless remained a very good friend 7:34:10 Feel I know Gabriel very well and have immense admiration for him; he is not only nice but an amazingly interesting person; he really transformed the Zoology Department; when he took it over it was pretty low but by the time he had finished he had fourteen FRS in his Department; he was a highly successful Master of Sidney Sussex; he's a kind of genius at managing things and people; he had also set up a way of getting scientists to advise the Government; I participated in one of these; it was a clever manoeuvre to get the Government to be interested in science; Prill, Gabriel's wife 9:43:20 I was very privileged and enormously lucky to end up at Magdalene; I had been sounded out by other colleges but in retrospect I am glad that I wasn't chosen; Magdalene was wonderful to belong to, very small with a highly experienced Bursar who knew everybody; did not attempt to shake up the College; was advised that if you wanted to do something you would suggest it to someone else, then it would pass to others, and gradually a consensus would emerge which then you would ask the governing body to consider it; I was probably seen as a pretty ineffective Master, nevertheless the College did well and it was a happy place; I was very grateful to them for allowing me to keep on my own lab work so when the time came to stop I still had a lab to go to and be active again in my own field; Magdalene also has a President who is a senior Fellow, and is in many respects more powerful than the Master; he is the head of the Fellowship; the role of College teaching must be done but took the view that every Fellow had a significant research contribution; it worried me seeing younger Fellows having to do terrible jobs like Tutor for Admissions; in my time we survived without damaging the careers of younger Fellows; it is a problem how you get these tiresome jobs done; encouraged the use of secretaries who could take on part of the burden; teaching is very important but for a university like Cambridge which is trying to compete with the rest of the world, we have to have people who are pre-eminent in their field; a good example is that some of my colleagues spent their time marking first year exam papers, not a good use of time in my view 15:13:17 The Institute has always been one third cancer and two thirds developmental biology; this was historically how we got our money and it still works that way; no one is going to solve cancer overnight because it is multiple different disorders and can only be analysed individually; we are fortunate in having some very good groups in this institute who are working in aspects of cancer; delighted to say that in the last two years we have had two of our home-bred staff members elected to the Royal Society, one on the cancer side the other on the Wellcome side; Stephen Jackson this year's Royal Society appointee, has made real inroads into DNA repair; all the time our genes are being damaged and this is a major cause of cancer; he has been meticulously analysing step by step what goes wrong with a view to trying to see if eventually one can alleviate the process of DNA damage by various chemicals which have favourable effects; he started a company called Kudos which saw the commercial side of this; it was then sold for a large sum recently; when I was chairman here I strongly encouraged the commercial side; these people are not well paid and without this commercial side we would have lost them all; another very successful younger person, Daniel St Johnson, who works on the development biology side analysing how it is that the components of an egg arise because they form the basis of how the whole development occurs; an egg is a template for the rest of life and a key question is how does this amazing cell come to be possessed with these components to enable it to start the next life; those are two good examples of younger people who have thrived in this environment, making successful careers for themselves; Stephen Jackson and Tony Kouzarides both started companies; we are charity funded and you can't do commercial work in a charitable organization; they had their companies in the Science Park or elsewhere and guided the activity; both have now sold them; Tony sponsored a company called Abcam which was very successful in making antibodies, a good Cambridge company; that emerged out of someone in his group and he could see the commercial side of it; it has to be kept separate from us as a charity, but that works fine; for sure it is not easy to balance these two things but it must surely be the way forward for university academics to have a significant commercial interest if possible; Government must want this and it gives employment; the University has not interfered in either of these two cases 23:48:15 Hope that I have mentioned all those who have been instrumental in what has been an amazingly fortuitous career; I have talked about Gabriel Horn, but would like to mention Ron Laskey who has been crucial in getting this institute going; he is a Professor in the University but works at another institute at the hospital; these two have been particularly supportive; also my great gratitude to Magdalene and Churchill College who are so good to me; I feel a bit parasitic, but feel privileged to have had a career in a place like Cambridge; and of course, to Max Perutz for bringing me here