Monday, 3 April 2017

From Cumbria to California

Dennis Burton currently holds the following academic positions. He is Chairman and Professor of the Department of Immunology and Microbiology at the Scripps Research Institute, La Jolla, California; the James and Jessie Minor Chair in Immunology, in the same Department; the Director of the NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and the Scientific Director of the IAVI Neutralizing Antibody Consortium. He was born in the town of Whitehaven, on the outskirts of the Lake District, Cumberland (now Cumbria), educated at the Universities of Oxford and Lund in Sweden and, before he left the UK, he was a Senior Lecturer at the University of Sheffield, during most of the 1980s. I first met Dennis in 1981, while I was measuring some enzyme reaction rates on "his" spectrophotometer as a young PhD student: he didn't seem to mind, but I hadn't asked! In this Blog post, Dennis has been kind enough to respond to a series of questions ion which I am hoping to give you some insight into the journey that Dennis, like many successful scientists, have travelled. He has also given his own personal views on the traits that he believes are important for a rewarding career in Science. Of course, Dennis has spent 40 years in Science, and the world has changed significantly in many ways. Nevertheless, I believe we can all take something from listening or reading the views of those who have been successful and who continue to strive, in Dennis's case, towards the goal of limiting the tragedy of diseases such as AIDS, working alongside young scientists throughout his career.

The format of the post is one I have used before. I sent Dennis a set of questions after an informal chat and he recorded an interview and sent me the transcript. I will intersperse the commentary with supporting information, to help clarify any of the Science, where appropriate and I will point to references from the literature and the Internet, where I think it may be helpful. There's a lot to get through, so let's begin! [Just for your guidance, my words are in red and my questions are in blue: Dennis's words are in black; so you can skip mine to get to the important stuff!]

How did you end up studying Chemistry at Oxford and where there any "role model" teachers who inspired/encouraged you? There are 3 factors here with regard to Chemistry. First of all, I always had an interest in Chemistry from quite an early age. I remember being at junior school and doing chemistry experiments in the outhouse. It certainly would not be possible these days, but I remember distilling water, making bromine and making hydrogen sulphide, using acids and glass equipment.  I would be very surprised if you’re still allowed do those these days, but you could in those days just go to the chemist and buy the chemicals needed. The experiments were very interesting to do, not to say quite exciting at times. The second factor was we had a chemistry teacher, who had a Ph.D. He actually came from the nuclear power Industry at Sellafield, nearby to where I lived in Whitehaven, Cumbria. He decided to give that up and become a teacher. He was a very good and inspirational teacher and that also got me on the track of being interested in chemistry. [In 1952, the Windscale Nuclear Power Plant (above, RHS) in Cumberland opened for business. Whitehaven had been an historic port, rivalling Liverpool in the early 19th century and remains architecturally, very significant since its Georgian "foundations". Windscale changed its name to Sellafield in the 1980s.]

Then finally since I did grow up on the outskirts of the Lake District, I developed an interest in walking and geography; and really loved geography, and even considered pursuing that after school, until at some point, I had a careers interview with the deputy headmaster, and he suggested – he was actually a geography teacher - that geography was not really a particularly good vocation, and he encouraged me to pursue chemistry rather than geography. So that’s broadly how I ended up doing chemistry.

And what about Oxford as a choice of University? I guess I was told that that was the best place to do chemistry. And it had a long famous history of chemistry and so I took the exams and got in. So that’s where I went! It seems difficult to imagine now, but the culture of education was quite different in the  1950s-1960s. Far fewer students went to University (an interesting statistic from the Government Office of Statistics, shows that in 1950, 17,300 first degrees and 2,400 Masters/PhDs were awarded. By 2010, these numbers had risen to 330, 000 and 182, 600 respectively: and the population has remained pretty constant. In addition, the 1950s and '60s was a period when many students were the first in their families to make it to University, let alone the prestigious Universities of Oxford and Cambridge. It is also worth pointing out that until 1992, Universities co-existed with Polytechnics (a system largely developed by Sir Fred Dainton, a Sheffield "lad" who rose through the ranks of academia and politics, from a very humble start in the heartland of the Sheffield steel industry in the 1920s, and who was the Chancellor at Sheffield, when Dennis was appointed). In 1992, the Higher Education sector began the transformation into the shape it occupies today, with all Polytechnics becoming Universities. This process has recently been augmented by the 2016 education bill, which paves the way for an expansion of Private Universities.

What advice would you give to young students who want to follow in your footsteps? Things are so very different now from when I grew up in the 60s. I’m not sure that I’m qualified to offer advice or whether it’s possible to follow in the same footsteps. I think young people have to look at the the situation as it is now, and make their own choices. In my time I don’t think we thought a lot, in any detail, about profession(s). In a sense, we trusted more that things would somehow, just work out. It seems to me that things are more competitive these days, and that people are forced more into choosing a subject not necessarily based upon an academic interest, but based on being able to secure a job. I would say that perhaps the only advice I could offer would be to work hard, but also to play hard; to try to do something day to day that you actually enjoy doing. But I know that can be very hard to find. I think that it is worth striving as hard as possible to be able to do something that you really enjoy doing. And for sure you won’t enjoy it all the time, but at least most of the time.

What do you think schools do well and what changes would you like to see?
You know, I’ve been living in the United States for the last 27 years. I am not sure how well I really understand or know what is happening in British schools. But I can say that for American schools, there is probably too much emphasis on rote learning or learning of facts, rather than understanding concepts. There are too many multiple choice type of evaluations and not enough evaluation of creativity in terms of, for example, essay writing and understanding of concepts. Those are things that schools don't do so well from what I have seen. I think that what schools do well, perhaps in comparison to when I was at school is that they are probably better at instilling a sense of confidence in students; confidence in their own ability. I would say probably also that in some respects, particularly in terms of science, there is more emphasis on hands-on experience, which is always useful. The biggest change I would like to see is undoubtedly a greater emphasis on contemplative thought on trying to solve problems by thinking about them; just sitting down and thinking, not necessarily by writing or the production of facts. Of course one enormous difference from earlier times is the availability of the Internet, which means that one really doesn’t need to store vast amounts of data in one’s head, it can be readily accessed via the Internet, so one can spend longer even, at least in theory, in terms of trying to grasp important concepts and understand them. Any other comments on Science at school and its priorities. No, I think I covered most of my thoughts there. As said I’ve no experience of UK schools for a very long time so my remarks are not informed by deep knowledge.

You grew up near the Lake District, how did you find life at Oxford University in comparison? Yes, very different. I really missed the vicinity of the fells, the open countryside and generally the North. I always found the North of England to be friendlier in some aspects than the South and I missed that. In addition, Oxford University is a very special place in the sense that, at least when I was there, more than 50% of the students came from public schools and a fairly wealthy background. I came from a grammar school and a very modest working class background so that was contrast with a very different sector of society, and, as now, I think that Britain still has a great deal of class structure even if it seeks to deny it.

At Oxford you took Natural Sciences, can you tell me what the course was like and who influenced you to stay in Science and move towards more Biological problems. (Actually this is not true, it was Chemistry. Natural Sciences is at Cambridge). Yes the course in Chemistry at Oxford was phenomenally good. Some of the teachers, relatively young at the time, became world-renowned chemists, and some eventually wrote famous text books, or became leaders of world renowned institutions such as Harvard University, the Medical Research Council, and so on and so on.  My move towards biological problems was dictated entirely by a lecture series that was given to chemists in our third year at Oxford. This was the early days of Chemistry and Biology, and two individuals gave this course on enzymes, entitled: "The molecular basis of the activity of enzymes". One was George Radda (with his right leg inside an NMR instrument!) who later became the head of the MRC and the other was Jeremy Knowles (looking much more distinguished), who later became a leader at Harvard after he moved to the United States. They gave, as I recall it, tremendous lectures. They were completely inspiring. I just thought well this is absolutely terrific, and this is really the future of chemistry.  It was so interesting, it was exciting, it was different. You could see it had impact upon human health. So I decided through that lecture series to move into biology, and the course in chemistry at Oxford was a 4-year course so I did my part 2, as it’s called, in research in the Biochemistry Department working on the structure of chromatin with Ian Walker, who was a well-known researcher in that area. Dennis graduated in 1974.

You left Oxford for Sweden: this seems an unusual decision for a young, aspiring PhD student? What's the story there and how did Science in Lund compare with Oxford? Yes, I got a fellowship. I wanted to live in a different country. I had already spent  7 months living in the United States between finishing school and being at Oxford. I wanted to live in a European country, experience a European country. I got a fellowship from Ciba-Geigy to study anywhere in Europe. I had a particular interest in nuclear magnetic resonance, which was a growing technique in biology at that time. Of course these days it’s well known for imaging. That gave me a couple of possibilities -- I was most interested in Sweden, in part because of its political structure and the opportunities that it provided there. There was a very well known NMR Professor in Lund in the south of Sweden, Sture Forsen, and so I applied, went and did my PhD with him. The science in Lund is tremendously good. The Swedes have a long, long, history of experience in research in biology and they’re very very good and creative at it. They’re also the keepers of the Nobel Prize, so scientists from across the world tend to pay homage to Swedish scientists so that’s always an advantage. It was a tremendous place to do a Ph.D. and I had a very good time there.

You returned to the UK and Oxford before you took up a lectureship in Biochemistry at the start of the 1980s. How different was it then as a young lecturer than today? I think it was very different indeed. I would say that as a postdoc I was still basically pursuing science as an academic career and didn't give much thought to what the future held or what I would do or where I would go next. I was mostly interested in doing what I was doing and trying to do it as well as possible. At some point, someone mentioned to me that basically one could not be postdoc forever; that one should really try to establish your own lab. I probably was aware of this, but had not given it a great deal of thought.  I saw an advert for a job in Sheffield and I applied for it and I got it, and that determined where I went next. In Sheffield I continued with the kind of research that I was doing which was on the functional activity of antibodies (an early picture of Sir Rodney Porter, who shared the Nobel Prize with Gerald Edelman for their work on Antibody structure and function: Sir Rodney was a Lancashire lad himself, from Newton-Le-Willows. Actually Dennis is officially a Lancastrian by birth, having spent his first 9 months in Preston) – I moved that to a new area which was a logical first progression and set about solving one particular problem, which we did.
You proceeded to build your research group with funding and more importantly young PhD students and post docs. Perhaps you could describe that period of your academic life in Sheffield. What were the highs and lows and was collaboration an important part of your early career? Yes, my first PhD student turned out also to be a Cumbrian, Jenny Woof, who was studying at Sheffield (and now in Dundee). Jenny and I worked on the antibody problem that I mentioned and we started to make considerable headway, and I was able to get some more funding from the Research Councils to get a couple of more fellows, and we began to get more and more answers and this all helped. The highs were that we made progress at solving a scientific problem which was basically how cells bind antibodies to get rid of pathogens and tumors at the molecular level and I think that’s what you have to do in research – you have to solve problems – you can’t shirk from that – it sometimes takes a long time, the problems can be difficult, but in the end there is a very clear record as to whether you’ve succeeded or not. I think since then I’ve always followed that kind of path – let’s try and solve the problem however difficult it is. The highs were probably the independence of research, the working with folks, the successes. The lows were probably the difficulties of doing research, the frustrations, the many wrong paths that you follow, the many failures to get to where you’re trying to get. The inevitable clashes in laboratories—if you have more than 2 people you’re going to have some personnel clashes, and you’re going to have to get used to that and not be too upset with it and deal with it. Collaboration was always a very important part of my scientific career – I’ve always enjoyed that greatly. I don’t think in modern science you can really advance very far unless you’re pretty adept at collaboration. To solve problems these days you need so many different skills that you really have to collaborate, and if you enjoy it, then all the better.
You decided to visit Richard Lerner's laboratory at the end of the 1980s, what motivated you and how did this affect you and the people in your group at the time? I was working on human antibodies and Richard Lerner was developing a new method for making human antibodies, and I knew I had to try and be a part of the development of that technology and so I got a sabbatical in his lab. Of course it changed things greatly for me because I now got a first hand look at American science and its awesome power and scope and funding. For the people who were in my lab (back in Sheffield), most of them were moving towards finishing and they did. Two or three people actually came out to the United States to work, and subsequently, one of them has stayed in the United States, another one stayed for a very long time and is now running a Biotech concern in the UK. So I think it ultimately benefited all involved because my position became stronger and I could do more for the folk who had been involved with me, although at the time it was undoubtedly disruptive for some folks.
What would you say were your most significant achievements at Sheffield?
Two-fold, first of all, showing to myself that I could take on a problem and make significant contributions to solving the problem, which is the essence of research. Second, establishing a viable lab and showing that I could manage people in the lab and get people through PhDs, get them through postdocs, so that they could then establish careers of their own. So these are important things to do for self-confidence and understanding that you may have a future in science.

For the record Dennis has published over 200 papers since his PhD in Professor Sture Forsén's group in Lund (and  Sture Forsén still plays a role in Swedish Science as an Emeritus Professor at.....). He joined Sheffield in 1981 following the publication of an incredibly influential piece of work published in Nature on the structure and function of members of the complement cascade in human immunity. He went on with Jenny Woof to determine the molecular basis of antibody:receptor recognition in the human immune system and to establish the technology for making monoclonal antibodies with Lynda Partridge at Sheffield. Dennis was a major influence in the development of the Krebs Institute at Sheffield and since he left for Scripps in the early 1990s, where he joined the world renowned laboratory of Richard Lerner, he has risen to the positions above. During this time, he has built a powerful team of multidisciplinary scientists and collaborated extensively to help understand and ultimately eradicate AIDS. you can read his most recent work, published in the journal Science here. I hope you have found Dennis's story as fascinating as I have and I am delighted to be able to share it with you. Many thanks Dennis!