Sir Walter Bodmer: Genetics, Cancer & the Future of Humanity | Tomorrow Today

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Sir Walter Bodmer, a pioneering geneticist and oncologist, discusses his groundbreaking work in genetics, cancer research, and the Human Genome Project. From fleeing Nazi Germany as a child to becoming a leading figure i

Key takeaways

• Bodmer was born in 1936 in Nazi Germany and fled to the UK at age 2.5 due to anti-Semitic persecution

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Speaker 1 (0:00) Without the genome project, we could do nothing in the way that we're now studying, any medical problem, any health problems. He's probably the world's most renowned, you know, oncologist and genetic scientist. So it's fundamentally a genetic disease at the cellular level. I don't have any knowledge whatsoever about cancer. I'm deeply curious about it. The most credible claim is that we won't have any knowledge whatsoever about cancer. So it's an incredible honor for me to have my next guest on the show, Sir Walter Bodmer. He's a phenomenal, phenomenal scientist. He's probably the world's most renowned, you know, oncologist, genetic scientist, and basically is also the guy who's gifted to the scientist's community the way to talk to humans. which is the Bodmer Report. So I'm incredibly honored to have him. It's like it's my lifetime dream to like talk to you. Like I've been chasing you down through many different channels. Finally I get to sit down with you here in London. And sir, I don't have any knowledge whatsoever about cancer. I'm deeply curious about it. I'm curious about technology. I'm curious about like where genetic engineering and science is going in general. and I would love for you to unpack it for our audience through this conversation. But before we get rolling on that, I know that, like, you know, you were conferred, Sir Walter Bodmer. So tell us a little bit about that. I'm not sure what I can say, except that I was honored and pleased and surprised. I was relatively young at the time It's now almost exactly 40 years ago since I was made a sir. And I assume it was for my contributions to science in general. That's about all I can say, really I mean, it's a great honor. And was it for like a specific topic that you were like contributing towards? Not as far as I'm aware. You have to find out who promoted me and who's what they said. I think they're going for it. It's hard to decide. I mean, you know, I've been involved in promoting people and helping. I mean, it's a question of what you feel their contribution has been. in a useful way. It can be in sport. It can be in the arts and the humanities or it can be in science in my case. Good. Good. Awesome. Like, you know, so, like, you're such a humble man. So tell me about your origin story. Like, you know, you came from Germany at the age to. My father was Jewish. And I was born in 1936. And already, of course, by that time, Hitler's anti-semitter. and was very, very widespread. So although my father at that time was already a successful physician in Frankfurt, two of a largely Jewish practice, he realized in the end he would have to leave. He didn't think he would need to. And so we left Germany because of Hitler in the middle of 1938 when I was two and a half. So I don't really remember anything about Germany, but it was a difficult time. It was a difficult time for him. He had to retake medical exams so he could practice and so on. When you think back of those times, you're made to realize something that unfortunately some people still suffer from that many people who live in the Western society haven't experienced really what a situation like that that then came with the Second World War, how it can influence, lives. So you were age two at that time? Two and a half. Two and a half. The half makes a difference when you're only two. Why do you say that? Well, the thing that I find strange is that I remember nothing from when I was in Germany and yet I remember things that must have happened fairly soon after we came to England. I had two older brothers and they were, and they were, of course much more conscious of what had been happening in Germany. And my first reaction was refusing to learn how to speak English. I'd only just learned how to speak at all. That was in German. And then having learned some German, I refused some English hour. I refused to learn German again. But then I learned German at school, and it's still reasonably okay. My parents spoke to me in German. So, what is the memories you had of, like, you coming here to UK? Like, well, I, it wasn't a memory of what I had in Germany. It was an experience of what I was having as a very young child. And then during the Second World War in England. And I have to say a strong antipathy against junk mail for many years when I was younger. It was a very difficult time. My father was in a way lucky because being a doctor, they needed doctors. And a lot of the British doctors obviously were going into the services. So that he was able to practice his medicine and in the end did quite well. But he was a general practitioner, a family doctor. He would have liked to have been an academic clinical scientist, to be we would say. But he had a life that he appreciated and enjoyed. And of course, my mother and my two brothers were all together as a family. And he had to go to Manchester because they said they had enough of immigrants in London. So we chose Manchester because through my wife, through my mother, they had friends in Manchester. Very good. So at your heart, like are you a German? Are you a UK citizen or are you like, who are you? I mean, my... Are you a Jew or... I'm not a practicing Jew. You're not a practice. I've never been a practicing religious person. I respect those who are, but I'm not. My whole upbringing was in the UK. I spent nine years at one time in the United States at Stanford University, which is well known and was a wonderful time. marry, wife, first wife. She was British through and through. And so we thought in the end, we might want to come back to England for the sake of our children and the environment there, which is not to say that we weren't happy in the United States, but there's a certain amount of feeling you belong somewhere that maybe takes you away from where you are, even as you're enjoying it. So growing up, like, you know, what are the things you distinctly remember about your father and mother, the values and the culture and other things? I was greatly influenced by my father that I perhaps only realized later. He was undoubtedly highly intelligent. He's already published a number of papers. He would have liked to have been clinician scientists. he never really could. He was 44 by the time he came back and settled. It was not really possible to change your directions then. And he'd been told, and I have letters about this, by his mentor, who was a leading surgeon in Friedrich, and supported him strongly. He said, you'll never get a proper job in the university because you're Jewish. This was in the 1920s. So he had certainly in the end. and a strong influence because initially, as I'm sure you're going to ask me, I said in months I'd have no idea what else I would do. And my mother was an important influence. She was a student of one of, essentially the founder of modern dance in Germany, Rudolf van one of his early students. And that was an important influence too. I even once took a holiday course in which she taught. And I was involved with the organization of the Labum, the Institute, and that. And I think that was also an influence giving a direction of interest in the artistic time. Very good. Sir, Bodmer, like, you know, you went to Cambridge for mathematics. Yes, I went to a school in Manchester that's very well known, Manchester Gama School. That was interesting When you think about it, my father, who, you know, only just come, and I've only just been able to get to work properly, most of asked, well, what's the best school for my three sons to go to? And in Manchester, he was told him was the Manchester Young School. So that's where my two older brothers and I went at a time when it was, you know, not necessarily all that easy to get into a school like that. And I went into what was called the Modern Science, not scientific. And I was told I was quite good at doing some. And we had a friend who was a teacher, a woman who was a teacher during the war in a boys' school. It was an all-boys school who said, well, you know, if he's any good at maths, he should go into the math six because that's where they all get scholarships to Cambridge and Oxford and so on. And so that's what I did. I mean, I enjoyed the maths. And that's what I did. And eventually got to scholarship. to study maths in Cambridge, in a way that is one of the examples of where being unsuccessful was hugely to my advantage. There are several examples of that in my life. And this was one because it was assumed that the top mathematicians will all get into Trinity College, Cambridge, which is a wonderful college, and I've known it well. And I was put down in a list of colleges by major scholarship and then minor scholarship, which wouldn't do. And then it turned out that Trinity rejected me, but I was picked up by Claire College. I didn't know anything about different colleges. And that was a huge benefit to me because Claire was a wonderful college. I was young. I was too young to essentially go in immediately into Novitus service. and it just was one of the first things that changed my life in a major way. Going there. So not a lot of people, like, you know, I was recently in Oxford University shooting for a talk. Like, you know, they were like interviewing me and I was doing a talk. So not a lot of people know that actually the Oxford University is a collection of a lot of colleges. So it's Cambridge. So it came from. It's not Oxford. Yes, but like, so I'm, so can you actually tell like how the education system here in UK works with these college systems? I think the college system is quite remarkable and it's quite uniquely to Oxford and Cambridge. They have their origins as religious institutions going back to the 13th century. And often small groups would have them were only religious people, would turn into. of this idea of the colleges. And to be a student, whether an undergraduate to a graduate, you have to be a member of a college. And a college is sort of like a microcosm of the university. It has a mixture. Students and the fellows of the college are generally speaking, appointments in the university at various levels. And so you have this mixture of things that I think is very valuable. So even if you're entirely narrowly minded in some scientific area, you're going to meet people who are studying geography or French or classics. And I think that's useful because it's a community that you can belong to. And that's the first thing. The second thing is you have tutorials. You have individual tuition in groups of maybe two or three at the most, which I think hugely beneficial because in our days especially you can watch a good lecture on YouTube but you can't get the sort of advice that can stick with you really for the rest of your lives often because the students have enormous regard for the people who were their tutors who taught them in that way so I think that's a very important area and then there's another aspect if you're like doing a sport and I used to swim, but very often you can't get involved unless you're good enough to be on the university team. But each of these colleges, they're 30 or more. They have their own, they might have their own swimming, but more likely blowing boats, which you do in both places and other sports. And the sport is built up in the university by competition between the colleges. So anybody can take part. You don't have to be totally good. And then the college is learned from each other. I was head of a college for nine years. And one of your people you get to know best of the other heads of colleges. And it's not a competitive thing. Of course, you're tired to be as good as everybody else, but you can learn from them too. So I think it's a remarkably effective way of managing an organization. I think many organizations could do better by having that split up and then taking the advantage that each tries to do as well as they possibly can as an entity, but learns from the other and work as a group. So I think it's a uniquely valuable... Why is this sort of system only here in UK? Why not in the rest of the world? Well, it started historically in the UK and Americans universities like Harvard and Yale and even for the English universities. Joe, it somehow took a long time to build up into what it is now. It's hard to start it from Scroach. Got it. And I think it's the historical background that makes it work here. It's very difficult to start it from Scutche. And I don't think it's worked in the way that people are like in the Ivy League universities in the States might have wanted. So they abandoned it. Because I find it extraordinarily interesting, this concept of like colleges and there. Well, it's a collegiate university. Yes. And it's important. And the current Vice Chancellor has had the experience of being ahead of a college, ahead of a department, and a very good scientist, which is, it's important to have those qualities in judging how things should work together. Well, it's no accident that you became a mathematician. Like, you know, like you say that was... I didn't become a mathematician in the sense of becoming a professional. mathematical. I studied maths. I had the clue of what I was going to do with him. But how did you land in Ronald Fisher? I can tell you. It's an interesting story. I was able to do the main part of the degree at that time because I had a major scholarship. I did a reasonably good things. That after my two years, the third year was a bit more like a master's course would be now. and in my second year there was a lecture series from a very famous statistician David Cox or David Cox and he's and I got very interested in statistics and so I talked to him about that and he said well you know you can do statistics in the next year but then this guy there's this guy R.A. Fisher who's one of the world's best very important statisticians And he also talks about genetics and how maths can do that. So I thought that sounded interesting, and I would take those lectures. And so in the summer before the beginning of the third year, I started reading textbooks, some difficult books by Fisher, a good general textbook on genetics. And it just enteeed me it had a sort of analytical quality, which it does, that appealed to me as a mathematician. there was something that hadn't been only discovered hundreds of years ago, so to speak. And so I took those. That was the first time I learned any biology. I never learned any biology at school. No formal teaching in biology. And I went to start with Fisher's lectures. And I was fascinated by them. So before the end of the first term in my third year, I went to him and I said, would you consider taking me on as a PhD student? and he said yes and because he'd have very few mathematicians who'd ever gone to work with him. But you said you're not a mathematician, but you said you're not a math guy. I was a math student but that turned me into something else. And you know, that was another of these just remarkable steps. Again, that's a thing that changed by whole life to be moving away from I never thought I could be a good mathematician. Not good enough to be a professional. I was taught in the tutorial system, they called it supervisors there. I had two amazing supervisors. One was Michael Ateer, who was both president of the Royal Society and the Royal Society of Edinburgh, one of the world's outstanding mathematicians, and Abdu Salam, who was the first Nobel Prize winner from Pakistan. And I just feel like I can never be what they were. So why start a profession when you realize you can never be the best? You might never be the best of something else. So I never thought that I did think I might take up statistics. But then that's what drove me more towards what I did with Fisher. It was a huge, huge change for me. And I think there again, my father's influence was important because he was dealing with living things as a doctor. And I suppose somehow that had an influence on my moving in that direction in my own work. Yeah. But like what about genetics that drew you? Well, genetics, Fisher, let's say, the modern genetics, as we know it in a way, started with Mendel. And he was studying primros, and he was studying the way the things were inherited and came up with really fairly simple. rules of how this works, which are two today. It's in a way that's known. I mean, in some ways, if you think of males and females, a male has an X and a Y, a female has two X's, and of the children, on a half will get a Y from the father and be male, and the other half will get an X. That's a very simple form of inheritance where you expect two proportions to be equal. And he pointed out, similar sort of in houses, not with that, with, with peas. And said if you get peas that have a different structure that are crooked a bit, if you make those, cross them with the one that isn't, then on average, you can get a half that are like the normal p and a half that are crossed. And he formulated these rules, which were quite remarkable. from the observations that he made. So that's the start of genetics. And then its gradual progression is to say, well, where did it all come from? And then you start talking about chromosomes that carry the genes. And then you start talking about how they divide and how can you get two cells that have the same genetic components as the parent cell have. And then, of course, you get into the chemistry. All this, everything is made up of chemicals in one way or another. what are the chemicals, what are the structures that lie behind genes, and then you get into DNA. And they are know the famous Watson Cook structure of DNA, which showed what the actual genes are physically made of and how they can work, which was a remarkable discovery, one of the greatest discoveries in biology, if you will, in 1953 actually made in Cambridge when Jim Watson was was a pupil at Clare College where I was, although I didn't know him at that time, because their work had only just been published when I started being an undergraduate studied maths. So that's the sort of pathway, but it's hugely complicated since then and many different things one has to understand. So if you think about the science, like genetics as a science at that time, to where it is right now, like can you can you explain like at the snapshot when you started what it looked like at that time like what was discovered already what did people know what was yet to be discovered first of all Fisher you have to understand Darwinism Darwin isn't evolution it's evolution by natural selection it's evolution by the fact that if you have a certain inherited makeup and it changes a bit and it gives an advantage in terms of essentially reproductivity and whether you die less likely to die before a certain age, whether you're more likely to have children. And that was the idea about evolution. And the ideas that it might be explained by the simple inheritance that Mendel had described didn't seem to fit together to a lot of famous people like Francis Galton at that time. And it was Fisher largely together with two other outstanding genesis, Holden and Sulagite, who put together the idea that if you looked at it, especially as Fisher did from a mathematical point of view, you could write down equations which could show you how the type of inheritance that Mendel had suggested would work in terms of the natural selection that Darwin had discussed. So that there was a mathematical theory of population genetics, which is one of the things that Woodfisher taught. And that was an important part of my thesis. But at the same time, he was, while himself essentially mathematical and statistical, in an outstanding way, also a great believer that you should, if you're analyzing data, you should know how it was obtained and do with it yourself. So he himself did a... experiment. So he had mouse colonies and I was looking at certain types of inherited differences in mice. And that was part of my thesis too. Also he had looked at primula, the common primrose mostly has what's called pins and thumbs where they have either the recipient for the pollen at the top or at the bottom and they're the two types that make each other. But sometimes you find an abnormal one where they're both at the same height and he'd studied this as a genetic thing and essentially he collected data on the frequency which you find these so-called homoestiles in different parts of Cornwall and proposed the problem of you know how can you explain this in terms of theoretical analysis of the advantages or disadvantages of being able to sell fertiliser as it's not and so that was that was all part of my theory. with a bit of statistics thrown in. So it gradually led into a greater and greater interest in doing the sorts of experimental work that can help you understand what genetics is about. So switching gears a little bit. So then you reached out to the Nobel Prize winner, Joshua, in Stanford, and he declined you first time. And then like, you kept like persisting with him. with him. This is another story of where a disadvantage was a huge advantage. Yes. Actually, Francis Higg of Watson & King was quite friendly with Fisher. And that's almost certainly possibly how I first met him. But I went to a lecture by a famous Nobel Prize when I later to Max Delbrook, geneticists who was of theoretical physicists who then worked with phage, which are the viruses that attack bacteria. And somehow at that point, Francis Crick had talked to Delbrook and he suggested that I should go and work with Delbrook as an introduction, let's say, to molecular biology because it seemed obvious if you were going to learn more about genetics, you had to do it at that sort of level so i applied for scholarship to work with max delvo at caltech and to my good fortune i didn't get it and at that point i decided to take things into my own control and i'd heard about lederberry joshel lederberg who of course was that remarkably young age got a Nobel prize for really showing that you could do genetics with bacteria which was the whole origin of genetic engineering and what you do there And so out of the blue, I wrote to him because I thought Stanford was a nice place. He was obviously a very intelligent and able guy. And the first thing he wrote back as he said, I want to come next year. By that time I know, which already had three children and a wife, and that's probably why they didn't give me the scholarship to go and work with Delbrook. And he said, well, go and work with this guy at Cal Texas. This is another person there. And I said, I said, no, I want to work with you. So I have his letter in his own handwriting, Nobel Prize winner, dear Bodmer, your persistence is flattery. Yes. So that's what got me to work with Tolfia Lederberg and his friend, First White, Esther Leverberg. And he was another remarkable mentor, an outstanding scientist. So how do you explain this persistence? Like, where did it come from? My persistence? I don't know. I don't know whether it came from my genes or what I was taught or what. It just is, it was there. I think, I think it's important. So if I were a layman, like, you know, in, in 1940s and 50s, like, how would you explain genetic engineering at that time? Oh, there was, there was hardly anything that you could call genetic engineering then. It started with Ledrberg showing you could do genetics with bacteria, but it really didn't come into its own until the whole discovery of what the gene was. It