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A Conversation with Francis Collins

A Conversation with Francis Collins

Conversations with giants in medicine A conversation with

We are joined by Francis Collins, a emerged. That idea became a big part of was an interesting juncture, particularly scientist who needs little introduction to my early efforts as a senior postdoc and because it brought the Human the JCI audience. After getting his PhD in then as an assistant professor at the Uni- Project, which had mostly been under the Physical at and versity of Michigan. public’s radar, out into a much more pub- his medical degree at the University of JCI: In Michigan, you really started to lic space. Not all of that was good, as there North Carolina, Collins (Figure 1) zeroed find more of the disease genes. was too much focus on this being a “race in on genetics as his area of concentration Collins: I got to Michigan during a won- for the ” and too much and is noted for his landmark discoveries derful moment when Bill Kelley, the Chair- focus on personalities, in terms of who had of disease genes, and later his leadership of man of Medicine, had recruited people like a yacht — that was him; who had a motor- the Human , which culmi- Jeff Leiden, Craig Thompson, Gary Nabel, cycle — that was me. I mean, who cares? nated in April 2003 with the completion of Jim Wilson, John Lowe, and Dave Ginsburg. Let’s just get the done. a finished sequence of the human genome. What an amazing environment that was! It I was also deeply engaged in the ethical, Since August 2009, Collins has served as really encouraged me to think creatively. I legal, and social issues related to . the director of the NIH, the largest sup- wanted to tackle some significant problems This was a new experiment where a govern- porter of biomedical research in the world. and, based on my own clinical experiences, ment-sponsored, scientific project took The full interview can be seen on the JCI had always been an appeal- responsibility for investigating ethical, website, http://www.jci.org/kiosk/cgm. ing target and one that desperately needed legal, and social issues before they became JCI: Could you tell us a little bit about answers. So, chromosome jumping seemed crises. As individuals increasingly got more your path to medical school? like an appropriate way to go, and then, after information about their , there Collins: My own path was nonlinear. I that, we used it to address Huntington’s dis- was the potential for this information to be never really imagined, as a kid growing ease and neurofibromatosis. It was probably used against them in terms of health insur- up on a small farm in the Shenandoah a little overambitious to take on three major ance and in the workplace. In 1996, the Valley of Virginia, that medical school disease gene hunts at the same time in a very first bill was introduced to try to address was something I would want to do. My small lab, but when you’re young and enthu- these concerns; and after 12 years, it was a parents were in the arts — theater and siastic, you think you can do these things. great day indeed to be in the Oval Office — but when I got to tenth grade JCI: In 1993, you succeeded James Wat- as President George W. Bush signed the chemistry, I had this revelation that sci- son as the head of The National Human Genetic Information Nondiscrimination ence was actually really exciting. I hadn’t Genome Research Institute and embarked Act. I have a copy of the act that he signed necessarily expected that calling. I went on what some might call the most ambi- personally to me on my wall. That was a off and received my college degree in tious biomedical project in history: decod- wonderful partnership between scientists, chemistry and then completed a PhD in ing of the human genome. the government, advocates, public policy quantum mechanics at Yale. But some- Collins: That’s quite a saga. I had started a experts, and people who worried about civil where along the line, I felt this urge to Genome Center at the University of Michi- rights — because in many ways, this is a civil expand my horizons and discovered that gan. I was a Hughes investigator and happy right. You don’t get to choose your DNA; and genetics were truly with my life as a researcher, taking care of therefore, it shouldn’t be used against you. exciting fields. I decided to go to medi- patients, and teaching medical students. All The project certainly helped me learn cal school to focus on the science of biol- of a sudden the phone rings and somebody a lot about team science, about how you ogy, particularly as it applied to humans. says, “We want you to apply to be the next can try to get the best out of every brain After medical school, I did a fellowship director.” And I said, “That’s crazy! A feder- that’s involved in order to make this proj- in human genetics at Yale; those first few al employee? You’ve got to be kidding. The ect something that’s better than any of us months in Sherman Weissman’s lab were one thing my mother told me never to do is could have done alone. And the success of very stressful. I didn’t know how to use work for the government.” So I actually ran that model, attempted for the first time a Pipetman, and an autoclave — what’s away from it for a while. But ultimately, the in biology, has now spun off many oth- that? Remember, my research was in opportunity to stand at the helm of what ers. Whether it’s the 1000 Genomes, the quantum mechanics and most of it was history may regard as the most significant Human Project, the Cancer highly theoretical. scientific effort undertaken in the last many Genome Atlas, or the ENCODE Project, So, I had a rapid learning curve with centuries, how could I turn that down? all have produced this amazing deluge of a lot of bumps along the way, but ulti- We got started and by 1998 we were all information about how the genome func- mately I started to get my legs under me. beginning to believe that this might actual- tions. All build upon the success of the One day Sherm and I were talking about ly succeed; although, getting the sequence , which gives us how you determine where a disease gene of the human genome done in a 15-year confidence that this is a model that works. is located on a chromosome, because the timetable still seemed like it was going to JCI: With regard to team science, what whole idea of using linkage analysis was be a heck of a stretch. Then arriving on the do you say to those who have inferred that emerging. It was clear we needed to cross scene was a challenge from a private entity the NIH is funding more team science large distances in human DNA, and that’s [J. and Celera Genomics] run- rather than more investigator-initiated, where the idea of chromosome jumping ning a parallel sequencing project. That R01-type projects?

The Journal of Clinical Investigation http://www.jci.org Volume 122 Number 11 November 2012 3797 conversations with giants in medicine

to make that one in six chance of receiv- ing an NIH grant go back to one in three without having the overall base of support heading in the right direction. That’s not just a job for me, although I do everything I can to make that case, it’s a job for all of us. The whole biomedical research community needs to recognize and articulate that NIH funding is actually a wonderful investment that the public makes. All of us need to take some part of our time, in a way that doesn’t misrepresent the facts, to explain to the public and to our elected representatives why NIH fund- ing is such an important investment for the US, and what the damage would be if we allow this continued deterioration. We could lose important fractions of the new- Figure 1 est generation of young scientists, who may Ushma Neill interviews Francis Collins on September 21, 2012, in New York City. Image credit: simply decide it isn’t worth it to keep bang- Semyon Maltsev. ing their head against this wall. This is a very serious circumstance, and no one out there who cares about this can assume that Collins: I don’t think that’s an NIH deci- evidence that we provide to undergird what somebody else is going to send that mes- sion. I don’t think people should be anxious NIH has done to advance the cause of human sage. We have to do this together. that there’s somehow a top-down plot here, health in the last few decades is overwhelm- JCI: What would you have done if you or a conspiracy to force scientists into team ing. The evidence that the NIH has also been were not an MD and scientist? efforts that they don’t want to be part of. a major source of economic growth for our Collins: I was on a path to become an aca- There’s a quote from Harry Truman, “It’s country is also overwhelming. But funding demic professor of chemistry, and I might amazing what you can get done if you don’t support for biomedical research in the US very well have followed that track. But I’m care too much about who gets the credit.” has been under considerable stress. We had really honored and delighted by the doors That has certainly been true of many of these that wonderful doubling of the NIH budget that have opened since then. I could never large team efforts. I talk a lot to investigators between 1998 and 2003, but since then, fund- have imagined this path as a kid growing who’ve been part of these teams at the junior ing support for biomedical research has gone up on a dirt farm with no plumbing in the Assistant Professor level and have asked flat and inflation has eroded it further — we Shenandoah Valley. them, “Did this hurt you? Did you somehow now actually have about 20% less in terms of I have a message for anybody who’s lis- get lost in the shuffle because of a large proj- resources to put into than tening to this, particularly who’s in an early ect with many participants? Have you been we did 10 years ago. That is extremely frus- phase of their own career: if you feel like you injured?” I’ve never heard anybody say, “Yes.” trating when you see the potential for break- haven’t quite got it straight yet in terms of I’ve heard a lot a people say, “This has helped throughs that we are trying to pursue and what your path should be, don’t worry. If me hugely. I’ve made all of these connec- that could be achieved so much faster. you do have it all figured out, you’re prob- tions. I gained access to the kind of science I If Congress takes no action between now ably wrong! Be available to opportunities could never have done myself. I built collabo- and January 2, 2013, then sequestration will you didn’t expect, doors that open that you rations on future projects. This was great.” kick in — that would mean an 8.2% cut in didn’t know were there. Be flexible — if a JCI: You speak frequently with politi- NIH support, which would be about $2.5 bil- door that you thought you were about to cians, congress people, and even Presidents. lion disappearing. This could be an extreme- walk through seems to be closing, that’s a Collins: A big part of the NIH director’s ly dark year for researchers coming in for chance to be creative about other options. job is to be immediately responsive to any the first time trying to get funding support Science offers you so many opportunities request from Congress for information. because, while it might be an 8% cut in terms to do fascinating things. Nobody should Over the course of the last 18 months, I have of the overall NIH budget, it would be more imagine that you can just plan a linear path- visited one-on-one with close to 200 mem- like a 30% cut in the new and competing way for your career and have it turn out that bers of Congress in the House and the Sen- grant pool. That would drop success rates to way — because it won’t. We have a chance ate, answering their questions and trying historic lows. It’s a matter of great concern. to have a scientific life that is truly broad, to make the case for why medical research JCI: When I told my PhD mentor that I was truly remarkable, truly rewarding, and the has arrived at such an important and excit- going to get a chance to talk to you, he wrote chance to work with lots of other interest- ing juncture in terms of its implication for me in an e-mail, “Tell Francis I said hello and ing people and do things for humanity that advances in health. And also, why it’s such to do something about the paylines.” are happening at a dramatic pace. What a a great investment in our own economy. Collins: I would say he’s exactly right; we great time to be working in this field. Every single one of those conversations has need to do something about the paylines. gone well because our case is so strong. The But there is no magic dial that we can turn Ushma S. Neill

3798 The Journal of Clinical Investigation http://www.jci.org Volume 122 Number 11 November 2012

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