12 I n t e r v i e w By Dr Toh Han Chong, Editor Interview with Professor Peter Doherty, 1996 Winner of Nobel Prize for Physiology or Medicine Professor Peter C Doherty is the recipient of the Nobel Prize in Physiology or Medicine in 1996. With a research focus on the immune system, he and Professor Rolf M Zinkernagel, the co-recipient of the Nobel Prize in Physiology or Medicine in 1996, discovered how T cells recognise their target antigens in combination with major histocompatibility complex (MHC) proteins. Professor Doherty currently spends three months of the year conducting research at St Jude Children’s Research Hospital in Memphis, Tennessee, where he is a faculty member at the University of Tennessee Health Science Centre. For the other nine months of the year, he resides at the University of Melbourne, Victoria. THC: What has life been like since you won the so forth – but I expected that. On top of that, I Nobel Prize for Physiology or Medicine in 1996? was at the St Jude Children’s Research Hospital in Memphis, Tennessee, which has an enormous PROF DOHERTY: The Nobel Prize puts you in fundraising corporation, and I did a lot of the public arena, and that is very unfamiliar for a publicity stuff with the actress Marlo Thomas. basic scientist like me. A medical doctor like you She was Jennifer Aniston’s mother in Friends, and would be used to dealing with the public, but we her father, the actor-comedian Danny Thomas scientists do not deal with them very much. The founded the hospital. Australia also called me up year after the Nobel Prize was a very heavy year and made me Australian of the Year in 1997 even with a lot of people wanting you to give talks and though I have been living in Memphis for years! Page 13 S M A N e w s August 2006 Vol 38 (8) 13 Page 12 – Interview with Professor Peter Doherty THC: So everybody wants you after the Nobel PROF DOHERTY: We knew we hit something really Prize! big when we saw the results at the first experiment. That was totally unexpected. It was very clear and PROF DOHERTY: Yes, everybody loves you. we had a very good experimental system, and we Also, I was the first person with a veterinary were able to work it out really fast. What we really training who won the Nobel Prize. I spent a lot built on was the whole transplantation genetics that of time, particularly in Australia, talking to broad has been done by George Snell, and we were able to public audiences, giving talks in city halls. I made map it straightaway using their recombinant mice. a few mistakes, but I learnt, very quickly, about the media and public communication. I tried THC: In a nutshell, how would you explain the to convey to the public a sense of why science is significance of the Nobel-winning research? important and why we need to do it. Back then, there was a retreat from science and a poorer PROF DOHERTY: At the time we were doing public image of science in the United States, our research, people had just come to the Europe and Australia. So I was trying to talk very conclusion that there were actually separate T positively about science. cells. That was still controversial in some minds, I have been doing that for about 10 years now, but most scientists accepted it. So we had the which is why I eventually wrote The Beginner’s circulating white blood cells and we knew they Guide to Winning the Nobel Prize. Despite the had some specificity against foreign entities. title, it is a book about science and how it works, Other scientists had taken T cells and injected where it comes from, how we do it, and what the them into mice, and shown there was some opportunities are, and also about the history of the protection against infection. But we had no idea development of the science of immunity. There is how that worked. So what we discovered was some biography in it but it was never intended as that the T cells circulating in the blood were one. The book was written for a lay audience and very potent killer cells. They were not directly the people who have said they enjoyed it a lot are specific for the virus. But they are specific for people like high school kids, undergraduates and something to do with the virus. We did not people who have done science because it is familiar fully understand the virus-T cell interaction in to them. It was not written for a highly intellectual a molecular sense, but we did propose the idea audience but some of it may be a bit difficult, like of “altered self”, where parts of the virus (or the story of immunity. The book is meant for foreign protein) was combined with a self protein everyone, and it is easy to read. from the host presenting cell called the major histocompatibility complex (MHC). THC: Was there the proverbial phone call in the We showed that T cells used a T cell receptor middle of the night formally informing you that that targeted the virus-infected cells and did you had won the Nobel Prize? not directly attack the virus itself. That was enormously important because while the PROF DOHERTY: You get a phone call, which is antibody recognises the virus, T cells do not about 10 o’clock, Stockholm time in the morning. directly interact with the virus; they ignore What happens is that they have (the Nobel the virus and go to the virus-infected cells that Committee) a very long process that goes through present parts of the virus in relation to a self- months. They look at about 300 candidates and protein MHC on the presenting host cell. get information on all of them, but they gradually For the first time, we also understood whittle it down, and finally choose who they think why we had a transplantation system – why are their leading candidates. Then they put that we need an immune system that understood to the full group of professors at the Karolinska how to recognise foreign proteins but not self- Institute. If they approve of the final candidates, proteins, and how T cells are able to achieve this. they go ahead and call the people, and tell them they have about 15 minutes to call friends and relatives THC: Was this landmark work done in Australia? because they are going to officially announce the Prize winners to the public. Once that happens, PROF DOHERTY: It was all done in Canberra your telephone goes crazy! It becomes a whole at the Australian National University’s John media event for October every year. Curtin School of Medical Research during 1973 and 1975. We then both went off in different THC: Was there a Eureka moment in your Nobel directions. In 1975, Rolf Zinkernagel went to discovery? the Scripps Institute in California, and I went Page 14 S M A N e w s August 2006 Vol 38 (8) 14 Page 13 – Interview with Professor Peter Doherty PROF DOHERTY: Well, it was just a to Wistar Institute in Philadelphia. We never beginning of the stage when they were starting worked together after that; we were in other to expand. Brisbane, like a lot of Australian communities. So it was about two and a half cities, had a system of private schools. So we years of work together. would all put our kids there. But my parents did not have much money and they just about THC: Going back to your PhD years in saved enough to send me to public school Edinburgh, were you not working on the – that is, a government school. The school I sheep virus? went to was in its first year, so we were the first graduating class. At that stage, I do not PROF DOHERTY: I was studying virus think they taught Biology to boys in any of the infections of the central nervous system of state high schools – of course, they do now. sheep. I was then really working as a paid But at that stage, it was physics and chemistry, diagnostic neuropathologist. I had a job and which actually, I think is not a bad thing. I I did my PhD part-time and just wrote up think we often start to learn biology too soon, a thesis. I used to see my supervisor once and we get stuck with a lot of details and stuff a year and tell him what I had been doing, that can best be understood with the basics of and he would only say, physics and chemistry, and “That’s very interesting.” maths. [Laughs] I graduated from And I think it is veterinary school when important, if you are going I was just 22, and I have to do things like science really been running my and medicine, to learn own research since then, language. And the other although I have never been thing, which is absolutely trained properly – I am essential, is they should very badly trained and I learn how to write clearly. would not recommend If you do not write well, that! I had scientific you do not make any sense training as a vet because even in science – unless the veterinary course was you employ someone to designed towards animal write for you. reproduction. So we learnt a lot of population THC: Were you a good genetics, pathology, student? infectious diseases and control, breeding, and all that.