Azim Surani interviewed by Alan Macfarlane 19th June 2009

0:09:07 Born in a small town called Kisumu on Lake Victoria in western Kenya in 1945; my grandparents came from India; my paternal grandfather went to Madagascar where my father was born; my maternal grandfather settled in what is now Tanzania where my mother was born; my father went to school in Kenya and stayed there rather than going back to Madagascar; I do not know what part of India they came from but it was probably somewhere in Gujarat; I met my paternal grandparents when they visited us briefly in Kenya but I did not know them well; my maternal grandfather died when he was quite young but I remember my grandmother; my father worked for the Colonial Civil Service; he left school at the age of about sixteen; he loved reading, particularly English literature and history, he was also quite interested in politics; this was a small town but one important fact for me was that there was a British Council library; remember my father taking me there and making me a member so that I could borrow books; despite its small size, Kisumu was one of the key towns in western Kenya which could explain why it had this library; there was a Provincial Commissioner located in the area and the railway from Kisumu went to Nairobi and Mombasa; it was also a trading port on Lake Victoria and an administrative centre; I think my father could have become a successful academic if he had had the opportunity to go to university; his pleasure was reading; my mother looked after us; I have two brothers, an older and younger and a younger sister who was adopted; my mother was the eldest child in her family and when her father died her mother took various jobs to keep them, leaving my mother with the care of the family; I was quite close to her; she had married when about seventeen or eighteen, and my older brother was born about a year later, so she spent most of her life looking after people

9:32:20 I belong to a community that are the followers of the Aga Khan, Ismaili Muslims, though I am not a practicing believer any more; both my parents came from this community; the Aga Khan had established some schools in Kenya at that time; I started at the Aga Khan Primary School in Kisumu which was quite good; at eight or nine I went to Kisumu Primary School which was attended by Asians mainly; at about thirteen I went to Kisumu High School and I did my Cambridge ‘O’ levels there; I don’t remember any teachers being particularly influential at primary school; at secondary school I do remember some of them and they had a big part to play in what happened to me subsequently; there were no scientists in my immediate or extended family so there was nothing in my background that led me to think about science; most of the time when thinking about a profession, it was medicine or law; I do remember being generally interested in plants and animals; I remember a small laboratory where I think they were doing research on malaria; I did not go inside but would watch them working through a window; I was curious about living things; mathematics was not a very strong subject; I remember when about seven or eight I would go off collecting butterflies; I also went fishing fro small and colorful Tilapia that were plentiful in the lake.  I found living things very attractive and wanted to be close to them

15:30:02 We did not have a choice in the ‘O’ levels we did; it was not a very big school so the range was small; there were very few opportunities to learn a musical instrument; we had history, geography, English literature which I enjoyed very much, and sciences; I love listening to music of all sorts and I love going to King’s Chapel; I like Schubert but my taste is wide; I like listening to radio so I get a variety of music; I do find that it inspires me but I find it distracting when working in the lab; when I was at school I used to like playing tennis and cricket, and I also played hockey; I don’t think I was very good at it but I did enjoy tennis particularly; it is not something I have kept up; started wearing glasses at fourteen-fifteen for short-sightedness

20:00:13 I remember my biology teacher in particular, Edwin de Mello, he must have been Goan in origin, and he was a wonderful teacher; he was always asking us to go out and collect things from ponds etc., then he would spend time showing us what we had collected, trying to describe them under the microscope; I always used to volunteer whenever he wanted some specimens; when I was brought up there was very little mixing between different racial groups, so the Asians, Africans and Europeans (mainly British) kept apart; there was one swimming pool at a club, but that was exclusively for Europeans and we were not allowed to go in there; as a result I never learned to swim as the lake was full of crocodiles; at the time I was growing up it did feel strange that there were some areas where we were not allowed to go; the residential areas were all segregated; I don’t know whether it was written down but it was fairly clear that some areas were reserved for Europeans; at school the teachers were mostly non-white though we did have a white English teacher; the students were exclusively Asian, and the Africans were kept separate; the only Africans I came into contact with when I was growing up were people that came and worked in our house as servants; everybody had servants then; the school was very good and we had things like drama and a debating society, both of which I took part in; I became a Boy Scout and we would go out camping and it was tremendous fun; we had to generate our own excitement - there was no television although there were two small cinemas

26:20:06 I don’t think I was very deeply religious but it did provide a place to meet in this small town - a kind of club; there were services in the Mosque and my parents were quite keen that we should go, but I don’t remember taking it very seriously although my parents were fairly serious followers; I could not relate to it as it did not make a lot of sense to me; it ceased to have any real meaning for me; I have no religion now though I would probably describe myself as agnostic; I find it difficult to accept the concept that something has designed everything but it is not something that I spend much time thinking about; it is not a subject that I feel strongly about

30:10:12 I was doing pretty well at school; the country was then undergoing a big change with the approach of independence in the early 1960s; we could feel that things were changing and one of the consequences of this were that the standards started to deteriorate as people started to leave; it destabilized the existing structure; I went to a school in Nairobi, the Kenya Polytechnic, to do my ‘A’ levels, but it was clear that the standard of teaching was very poor; I spent a couple of years there but didn’t get very good ‘A’ level results; I stayed with relatives in Nairobi; I did biology, chemistry and physics; I was unhappy because I had previously done well at school; I was sad that my parents were very upset; they were concerned about all of us as I remember my father saying that we were entering uncertain times  and that a good education was the only way that we could survive; the family went through pretty dramatic times when I was at high school because  my father decided to leave his job, which was a good one, to start a business; I don’t think he was really cut out to be a businessman and it failed badly; things were then bad financially; my parents had worked hard to see me through school and I was so anxious not to disappoint them that it was particularly hard for me not to have done well; because we were approaching Independence my parents were wondering what to do; my brother had been to the UK doing civil engineering; they decided that I should go there, although they would stay, as there were no real opportunities for me in universities in Kenya

36:14:06 I came to the UK around 1963; I did not have any funding and spent the first year in London doing some casual jobs, basically trying to survive and think about what I was going to do next; there were two options, one was to do my ‘A’ levels again and get into university, or to go somewhere to get a degree of some kind; discussed this with my father and he thought it not worthwhile trying to do ‘A’ levels again; I went to what is now Plymouth University where they had London external degrees; I did a degree in natural sciences, in biology, chemistry and zoology; that is what I had at the end of three years, and it was not sufficient to take me forward; coming to England from a small, segregated town, arriving in London and finding myself in the middle of England, was quite a shock; I did experience minor racial incidents but nothing major; I met some very nice people when I came and made some good friends of all types, Asian and others, which was quite a revelation; when a lot of Asians started to come from East Africa a few years later, then there was much stronger racism, but when I arrived I didn’t detect that

40:28:13 The teaching at Plymouth was pretty bad; the problem was that I didn’t have a lot of money though my parents were trying to support me; I was working whenever I had free time to make some money; I used to do a twelve-hour shift in a bakery which was very well paid; survival was also important so I did not have much spare time or cash; I did not enjoy this time very much; I realized that doing nothing after this was not an option; I had the ambition to have some kind of career in science and I had an inner belief that I could make it; because my first degree was not very good I realized I had to do something else; I decided to do an MSc in biochemistry and went to the University of Strathclyde; there I met some very wonderful people; the science was by research rather than coursework; I started to enjoy this as I was doing things with my hands; started to feel that it was really something that I would like to do; I stayed there for a couple of years; the lecturers in the Department of Biochemistry were very good and were encouraging; they suggested I stayed an extra year and then I would get a PhD rather than an MSc; I liked the idea and went to see the Head of Department, Professor Heald, and he refused to let me stay on; he said that as far as he was concerned all the people that came from the Commonwealth should really go back, and he refused me on those grounds rather than on my ability; I was completely devastated and went to talk to one or two lecturers and they were not surprised; that same day I wrote to Professor Alec Psychoyos in Paris whom I had got to know; he had just come back from the States and had set up his unit in Paris; he immediately sent me an air ticket to Paris; I knew what he was working on and I had told him what I had done; I went to Paris and he offered me a job, so I ended up in Paris in 1970

48:23:05 It was an interesting period politically in Paris, and quite exciting; I met many people who were not scientists, but were doing French literature or philosophy; the bad thing was that Psychoyos had just come back from the States so his lab was not in a very good state for doing research; he was very kind and encouraging, and excited about his work; in the end I don’t think I did much work as I was enjoying Paris too much; although I didn’t go much to the lab I did learn a lot about many different things; I was there for two years but it was not taking me any further; my ambition was still to get into some scientific profession and to do some serious research; the French system was very strange as you could be given tenure while you were doing the equivalent of your PhD; Psychoyos said I could join the French system and actually work there; I was preparing some documents towards this application but somehow I was not convinced that this was the place for me; maybe the people around me in the lab did not create the right atmosphere for me, and was lacking something; I couldn’t see myself establishing a career in scientific reheard in that setup; it was an INSERM Institute based at a hospital in the southern part of Paris; I then had a lucky break; in 1972 I went to a meeting in Nottingham without much of a plan in my head; I had gone to the bar before supper and Bob Edwards walked in; he was the pioneer of test-tube babies with Patrick Steptoe; I had never met him before and we started chatting as nobody else was there; he asked me what I was interested in, what I had done, and what I was doing; after chatting for about half an hour he suggested that I come to Cambridge and do a PhD; I liked the idea but said I had no money; he said that he would get me an MRC studentship; I went back to Paris and thought no more about it; three weeks later I got a letter from Bob saying that he had talked to the Professor and had got me a studentship; I was amazed; I came to Cambridge in October 1972 as an MRC PhD student; that was the luckiest break as it happened completely by chance; somehow, based on this brief conversation he was convinced; this was the Department of Physiology on the Downing Site

57:46:04 Coming to Cambridge was enormously exciting; as soon as I walked in I thought the environment and atmosphere of the labs fantastic; even the sorts of casual conversations that I was starting to have with people were much more interesting; the things they were interested in were much more exciting and you could sense that it was possible to do things; you could ask questions and find ways of answering; there were colleagues around, facilities, everything was possible; when I arrived I had discussions with Bob and I thought that he was very happy with whatever I wanted to do; this was the time that he was trying to develop IVF and was very involved in working with Patrick Steptoe in Oldham, so was frequently going away; although he was away quite a lot he was very inspiring and wonderful to talk to; even a short conversation was very uplifting; when I came he thought I could work on early embryos and particularly to work on events that lead up to the implantation of the embryo; he was interested in this as they were trying to develop these embryos in vitro and wanted to put them back, and one of the problems was with implantation as they were trying to synchronize the embryo and the uterine sensitivity; that he thought would be a good topic for me; I did work on this area of implantation but increasingly I think my area was very strongly in the early development of the embryo; that was the thing that really excited me; I was fascinated particularly by early mammalian development because there were very little known about it at the time when I started

Second Part

0:09:07 As a result of Bob’s absences I had quite a lot of freedom to do the things that excited me; there were a lot of interesting people in the lab so it was a rich environment; Richard Gardner was there and was just developing his micro techniques for looking at early mouse lineages which became very important subsequently towards understanding mammalian development; the particular contact I had was with Matt Kaufman; he was working on parthenogenetic development in mice; this was the area that excited me; parthenogenesis in plain English is virgin birth; what you can do is take mouse oocyte and put them in culture without fertilization and trigger the onset of early development; one of the things you can do to initiate development is to dunk (culture) them in 7% alcohol for seven minutes and they start developing as if they were fertilized; if you transfer some of these embryos back into foster mothers they would develop up to nearly mid-gestation before dying; the question that became intriguing was why did they stop at this particular point; there are other vertebrates like fish and frogs which had been shown to be capable of development right through to term and it was intriguing why mammalian embryos couldn’t do that; the main difference is that mammalian embryos grow in utero so have to have the placenta to support their nutrition and development; this became my main passion at this point; there were many theories at the time and one of the ideas was that somehow the sperm not only contributed the genetic material but also non-genetic material, and that somehow this was important for development; we did some experiments which disproved this; there were other experiments taking place at the time and papers published which made the claim that parthenogenetic embryos could develop to term, but this was still a big puzzle; around 1979 I had finished my PhD and was still in the Department of Physiology with a grant from the MRC to continue; when the grant ended I was thinking of going off to the States or Canada; by then my family had moved to Canada; in the meantime there was a job advertised at the Babraham Institute, or more strictly an institute on Huntingdon Road, a research unit of the Agricultural Research Council; they immediately offered me the job so I decided to stay on in Cambridge

7:58:09 At this point there were conflicting papers on parthenogenesis and I decided to pursue the subject further; I started to get some indications around 1982-3 that there was something very unusual and interesting going on; basically the experiment that we did was using micro manipulation we were able to create eggs which either had two maternal genomes or two paternal genomes with the control of one of each; we started to compare them, and found that you did require a maternal and paternal genome for normal development through to term; if you made embryos with two female genomes or two male genomes they died sometime after implantation; what was really important about these experiments was that genetically we could create an embryo with two maternal genomes which had come from different eggs so they were as diverse genetically as making an embryo of one male and female genome; we realized that there were functional differences in the two parental genomes; bringing all the data together we found that the maternal genome seemed to be much more important for the development of the embryo whereas the paternal genome seemed more important for the development of the placenta; this was quite amazing as it was not something that people were aware of, that the parental origin of the genome made a difference to development; we called this phenomenon ‘imprinting’ because what it seemed to suggest was that the parental genomes carried some kind of imprint of the parental origin and that this provided the information that made them functionally distinct from each other; the difference was not a genetic one but it was epigenetic, not in the DNA sequence but something else; this was the start of the work of investigating this additional layer that was necessary for development to take place; around 1983 people in Cambridge were starting to hear about these strange experiments and I was invited to give a seminar in the Department of Genetics; I could see they were very sceptical, but I was convinced; I didn’t know what the mechanism was but I was convinced that the observations were correct

13:47:05 I think that pursuing it was a risk; it could be a complete dead end and there might be some trivial explanation, and it wasn’t considered that important anyway; I was doing some other projects on the side which were safer while continuing with this risky pursuit; when I was doing my PhD I was given a lot of freedom to think and do things that I wanted to do so I believed that it was fine to ask questions if they interested you; somehow I felt that this was very important, and particularly when I got this job I thought I could now take a risk; I think that students starting now in science have less opportunity to do this; when I was doing my PhD I was not required to write reports each year; I went in the first day, had a chat with my supervisor, and then was more or less free until I finished my thesis three years later; nowadays I think the students are over-supervised so they are constantly worrying whether they have enough results for their yearly reports; there is also the phenomenon of getting publications in specific journals; this was not the case when I was doing my PhD; we did the experiments and when we had enough results we published them, and did not worry about where it was published

17:30:22 I have been offered various jobs in other places but have always found that Cambridge is a very special environment and I have really felt at home here; it is certainly a very beautiful place; the history gives a sense that you are somewhere very special; it is a small town with a very high density of scientists so you can have casual conversations with people about ideas and can have an impact on how you think about things; these are things that you can’t really quantify; in terms of the facilities and resources, there are many labs in the States which are much better; that might be an advantage for us; because we have limited resources we have to do much more lateral thinking; I talk to my colleagues in the States about this; their style of working is different because they have a lot of resources and money; what they tend to do is to cover a large area of the field they are interested in and make the assessment of what is important retrospectively once they have all the results; we can’t do that here as we don’t have that kind of money or manpower, so we have to think very hard first about what we want to do; it is a different way of working but it is a style that I prefer; I sadly don’t do experiments myself now because the nature of biological research has changed quite dramatically; the tools are much more sophisticated so it is much more of a group exercise; if you are head of a lab you have to get a team of people with different expertise and work as a group; this is what I am doing now, so sadly I am much more an administrator; there are so many regulations now including Home Office regulations to do with animals, health and safety regulations, plus the fact that I have to report on all my students which Bob never had to do; I don’t think he had to write a single report, but now I have write a report and read their reports every year; I have about five or six PhD students; I also lecture; I always grumble when the time comes but have always found the experience very enjoyable; I now only teach final year students and have found them extremely bright and interesting; I also do supervisions; I do about ten lectures a year so my teaching load is not very heavy; what I find increasingly is that my students will contact me by email so there is quite a lot of informal exchange

24:59:15 I became a Fellow of King’s in 1994; it has been both enriching and enjoyable; I am slightly sad that I haven’t spent as much time actively at King’s as I would have liked; my research takes up quite a lot of time and I like to be close to the lab; I leave my door open so my students can come and talk to me, thus I am in my lab many hours a day; I also travel quite a bit to meetings; since 2000 I have been quite heavily involved trying to get a stem cell institute established in Cambridge; that has now been set up successfully; I am on the advisory board but there are other people in charge of it; a lot of the meetings I go to are in the States but I also go to Japan quite a bit; I have also been to India and Singapore; China is also beginning to emerge as a big player; they have large resources but haven’t quite found their direction yet; I have not been to Africa since 1973 when my father died; I would like to go back but have mixed feelings about it as it must have changed a lot; I have very happy memories of growing up there; if I don’t go back to Kenya I might go to another part of Africa; I am married and have two teenaged daughters; my wife trained as a speech therapist and worked for many years with children; when we had children she decided to stop working for a while, and then she decided she didn’t want to work with children any more

30:09:08 This is the twenty-fifth anniversary of the paper we published in ‘Nature’ in 1984 on imprinting; that has become much more important than even I had thought; there is now a whole field of epigenetics which has grown up and that phenomenon is central to it; the human genome has been sequenced and we know what the genetic code looks like, but it is important to figure out how this genetic code is then translated into various cells and tissues; although each cell contains the same genetic material the cells themselves are very different; this is where the research on epigenetics is important because this area of research is to do with understanding how different genes are selected for expression and repression to create the diversity of cell types; this is one of the major areas of research and it also has implications for stem cell research; if you are starting with an embryonic stem cell there is a potential to give rise to all the different types; we really have to know how these cell fate decisions are made which requires an understanding at the epigenetic level, how the cell deals with selecting the right set of genes to be turned on and off; it is also the area which can inform us about when you have a terminally differentiated cell, what are the mechanisms that can take it back to be more like an embryonic cell; these mechanisms operating in cells, especially in early stages where the decisions are being made in response to signals that come from outside and are then converted into this epigenetic form, are quite central to many areas of research now; there is also increasing awareness that some of the things that go wrong, for example when some cells become cancerous, also could be examined from the perspective of the epigenetic mechanisms that have gone wrong; instead of these cells behaving normally they have got locked into a particular state and are just continually proliferating rather than stopping and differentiating; I think that this may also have some value in trying to design various therapeutic agents to combat diseases; there are a large number of pharmaceutical companies that are exploring epigenetic mechanisms to understand what these key enzymes are that are involved in this kind of modification and trying to find agents which can stop these enzymes from malfunctioning; I am funded by the Wellcome Trust and about eight years ago some people from the Trust came to see me; they thought that some of the work that I was doing was important and could be useful in the context of some translational research; through their encouragement we set up a spinout company called CellCentric; the lab is now trying to understand the detailed mechanisms involved in epigenetics, and trying to find the key molecules and genes; the understanding we get from this basic research is then used by the company to see if some of the genes might also feature, particularly in cancers; the idea is that once we identify these genes then we can maybe look for therapeutic agents that interfere with their activity; if the work that we do is interesting we will publish it anyway so it will come into the public domain; I was reluctant to get into any kind of commercial things myself for quite a long time, but I certainly now think that it is very important to use discoveries if they are exploitable especially in trying to deal with nasty diseases; as a University spinout company I don’t own it although I have shares in it, and I don’t have day to day dealings with it and I am not a director; I sit on the board as an observer but don’t try to influence what they do, neither do they try to influence me; as far as the intellectual property is concerned it is very clear that it is owned by the University unless they didn’t want it; one of the criticisms that used to be made of the Wellcome Trust was that they were funding basic research for millions of pounds and what was the UK getting out of it; the Trust responded by going round to the people they funded to see if there was anything that could be spun off into a company

41:09:05 Of the big Cambridge figures, Sydney Brenner comes to mind as hugely inspiring with such originality; John Gurdon is another; also when I was working at Babraham I had interactions with both Aaron Klug and CÈsar Milstein; I remember very interesting discussions with CÈsar although our fields were diverse; Anne McLaren was another very close colleague and when she retired she came to Cambridge and her lab was next door to mine; she came to all our group meetings and we had really good discussions; leaving aside big names, what is very interesting is bumping into post docs and people just starting up new groups; some of my students are inspiring and come up with amazing observations and reflections; it is on many levels and the whole thing is very special; for young hopeful scientists, the key thing that they must sort out in their heads is what is it that excites them; the next question is why is it important; if they can sort that out then they are on their way