Disease Models & Mechanisms 3, 672-675 (2010) doi:10.1242/dmm.006882 A MODEL FOR LIFE © 2010. Published by The Company of Biologists Ltd Targeting cancer: an interview with Tyler Jacks Tyler Jacks is one of the world’s foremost experts on mouse models of cancer and has pioneered the use of gene targeting in the mouse to construct more accurate pre-clinical models. Here, he discusses his early influences and motivation, and his hopes for the future of cancer research. he development and exploitation fond feelings towards MIT based on those of mouse models of human cancer early connections; it was somewhere very has led to fundamental break- familiar. My brother was an undergraduate throughs in cancer research. here as well. Throughout his career, first as a Tpostdoctoral fellow in Robert Weinberg’s And your mother was an actress? laboratory and then as an independent She went to Yale drama school and the researcher, Tyler Jacks has made key contri- American Academy in New York with the butions to this field. He made and studied intention of being a full-time professional mice lacking the retinoblastoma (Rb1), neu- actress, and then got side tracked into rofibromatosis (Nf1) and p53 tumour sup- starting a family. But she lived out her pressor genes, and latterly engineered novel interests in the theatre by teaching drama DMM mouse strains that accurately mimic human at the private school in our town and cancers both in their genetics and their directing and acting in community theatre. symptoms. Mice developed in his laboratory are used around the world to study different Were you never tempted to follow in her types of cancer, including lung, pancreatic, footsteps? colon and ovarian cancers, and his work has I did my share. Nothing that you would ever helped to define new approaches to studying have seen, I assure you! what we’re talking about is rooted in the cancer in an intact animal. In 2001, Jacks was work that has been done by us or by others appointed director of the Massachusetts What I’m leading up to is that there has in our lab, so it’s not made up, but never- Institute of Technology (MIT) Cancer always been a certain air of self assurance theless I think you do put on a performance. Research Center, and has overseen its recent about you, so my question is: is this real So, in that sense, the version of me that you rebirth as the Koch Institute. Under his or feigned? And if it’s real, where do you see is perhaps different from the day-to-day leadership, the Institute is moving into a new think it comes from? version – an amplified version. I don’t think building, scheduled to open in December Well, I would say that I do go into situations it’s a completely different person. At least I 2010, which will be home to a unique inter- with confidence that things are going to work hope it isn’t. disciplinary group of cancer biologists and out, but I’m not sure where that comes Disease Models & Mechanisms engineers. from. I guess I’ve had successes in school and Science is supposed to be a meritocracy, professionally, which built my confidence. I but the people who seem to be the most Tyler, you’re currently director of the don’t think it necessarily derives from the successful are often the good communi- Koch Institute at MIT, but you also have fact that my father was a university professor, cators. Do you think we should pay a lot a family connection to MIT, don’t you? although that probably did make me more more attention to that in training scien- My father was a professor here in the Sloan comfortable with academic life – I could tists? School of Management. He started in the envision what it would be like to move in There’s no doubt that being able to com- late 50s before I was born and was on the this direction. So, that may have influenced municate makes one’s visibility greater. faculty through the mid-80s. He retired my perception of things and people’s per- People who can communicate are asked to about the time I finished college. I didn’t ception of me. Your question about my present in different settings, and that gets grow up near the campus – our house was mother is probably relevant in that, in our their name and their work out there. I about 30 minutes away – but I did experi- business, communication – being able to learned how to organise material and ence the campus at some level and I had describe what you are doing, or performing, present it most effectively from both Harold if you will – is important, and I certainly Varmus, when I was a PhD student, and Tyler Jacks is Director of the David H. Koch Institute inherited a lot of that stuff from my mother. from Bob Weinberg, during my postdoc. for Integrative Cancer Research at Massachusetts Bob goes out of his way at the beginning of Institute of Technology (MIT), the David H. Koch So you’re a performance? Is there a each year to talk to the trainees about the Professor of Biology, a Daniel K. Ludwig Scholar and a different Tyler somewhere? importance of giving a good talk, echoing Howard Hughes Medical Institute (HHMI) Investigator. I think that all of us are performing when what we’ve just been discussing. It’s really e-mail: [email protected] we give public presentations. Obviously, not meritocracy, it’s that plus those indi- 672 dmm.biologists.org Tyler Jacks A MODEL FOR LIFE viduals who can most effectively commu- because I’d worked as a rotation student on work until winter ’91. There were incre- nicate what they are doing. a project about ribosomal frameshifting, I mental advances – we were able to make Parenthetically, I also think that scientists went off in that direction. To be honest, I ES cells with targeted mutations after some have an obligation to explain the impor- knew I wouldn’t be doing that long term. It time, and we were able to derive teratomas tance of their work, so not only should we worked like a charm and it was a great expe- from them, so we could do some work on be giving good talks to our peers, but we rience and I enjoyed it and learned a lot in those. Then we could make chimeric mice also need to be able to communicate in the process, but it was something of a from which we could derive fibroblasts, but order to convince the public in general stepping stone. It really wasn’t medically it took until the winter of ’91 to get germline about the importance of their investment oriented enough for me. transmission. I hadn’t published a paper in in research and the value of research to Bob’s lab when I went off on the job market. them. It’s certainly been said that we as a “I’d like to cure somebody! If community are not nearly as effective as we Was there a point when your resolve need to be in explaining to the lay public I could feel that I had cured faltered? and government officials why what we do just one person I would feel I didn’t lose hope. I was confident that we is important. I’ve tried to do that to a satisfied. I’m being slightly would get there. I knew that it should work, limited degree but, frankly, I need to be as there was no reason why it shouldn’t. doing a better job of it myself. facetious there but actually Others had succeeded with other genes by I’m serious” then. It was early days; it was one of those I’d like to turn to your career now. You situations where technical improvements started off as an MD/PhD student? After graduate work with Harold were likely to happen, and did. I simply Not exactly, but you’re almost right. When Varmus, you then went off to postdoc in employed the new methods – like using I left college I went into the UCSF PhD Bob Weinberg’s lab. What made you isogenic DNA, for example. Anton Berns’ DMM program, but, shortly after arriving there, I choose Bob? lab made the discovery that isogenic DNA started interacting with two people, Dave It relates in part to what we were just talking made a huge difference in targeting effi- Cox and Don Ganem, both of whom were about. You recall I had gotten very interested ciency, so we adopted that method and, involved in the MD/PhD program. The in tumour suppressor genes. The very first sure enough, we went from having 0 out of program was of interest to me because I had work from Web Cavenee came out in the 6000 clones screened by Southern blotting always been interested, if not in practising mid-80s, and then there was a flood of other to 10% targeting efficiency. medicine, in just learning about it. They both papers demonstrating the importance of encouraged me to apply to the program, and this new class. Weinberg’s lab had cloned the Have you any advice for someone in that I got in. However, by the time I was accepted Rb gene, and Mario Capecchi and Martin position now? I’d already begun my work in Harold’s lab Evans and others figured out how to target It’s a good question and I struggle with that and so, rather than jumping into the medical mutations in ES cells.