Dr. Francis Collins on Biomedical Research at the National Institutes of Health

Author: Tudor Cisu

Tudor Cisu (JYI): On behalf of the Journal of Young Investigators, we are honored and privileged to be talking to Dr. Francis Collins, Director of the National Institutes of Health. Dr. Collins is a leader in the field of human genetics and was the director of the National Human Genome Research Institute, which has been instrumental in mapping out the human genome. We, today, will be asking him a series of questions about his life, the NIH in general, and the importance of undergraduate research. So, thank you, Dr. Collins, for taking the time to talk to us.

Dr. Collins: Pleasure to chat with you, Tudor.

JYI: So, how did you initially become interested in, you know, medicine and research, in general?

Dr. Collins: I had what you could call a non-linear pathway towards my current role. I got interested in science as a high school student, particularly under the influence of a very charismatic and effective chemistry teacher. That was the first time at which I could imagine science could be my calling because of the way in which science was presented in that 10th grade class. So I went on to college and majored in chemistry, and had a very positive undergraduate research experience. I was working at that time with Carl Trindle, now a full professor at the University of Virginia. I was his first student, and that was a very exciting and enlightening year, when I was a senior working with him on an independent research project.

JYI: Okay, wow.

Dr. Collins: Yeah! I went on to a graduate program in chemistry at Yale, because that’s what I thought my pathway was going to be, to become a physical chemist. But along the way as a graduate student, I realized that biology was more appealing to me than I had previously recognized, and that biology was undergoing a pretty dramatic revolution in terms of understanding the basic principles.

JYI: Sure, yeah.

Dr. Collins: The DNA structure had been determined, the genetic code had been derived, recombinant DNA was being invented – I could see this was going to be a pretty exciting time. I decided at that time to change fields fairly drastically and went to medical school, both to learn about the science of human biology and also to see whether all of these things that were happening in biological science might have benefits for human health, and that I might be able to be part of that.

JYI: Right.

Dr. Collins: Genetics quickly caught my eye as a way to put together my own attraction towards mathematics and digital kinds of science with medicine, and I became pretty sure in my first semester as a medical student that what I really wanted to do was to combine the science of medicine with the science of genetics. And, at least, that part has been consistent ever since; although, the path that I’ve traveled has certainly not been one I would’ve guessed as a medical student in 1973.

JYI: How is it that you got from your love and interest in genetics, eventually, to what is now, your placement as the Director of the NIH?

Dr. Collins: Well, I went ahead and got myself thoroughly trained in clinical medicine – spent 4 years in medical school, 4 years as a medical resident, and then got training in human genetics as a fellow at Yale. And then started my faculty career at the University of Michigan, taking care of patients, conducting research, and teaching. That went relatively well, particularly in the efforts to identify the cystic fibrosis gene, which ultimately were successful by 1989. But it was clear that if we wanted to make progress in human genetics, we needed to have the database called the human genome. As the Human Genome Project began to take shape, I was very enthusiastic about seeing it go forward. I didn’t expect that I would be asked to lead it, and that came as quite a surprise -- but ultimately, that’s what I agreed to do. So I came to NIH in 1993 to lead the Human Genome Project, and over the next 10 years in an amazing series of scientific and technological advances, we actually succeeded at that effort, ahead of schedule and under budget. It surprised everyone, including me, because in 1993, it was a wildly optimistic projection that we could get this done. Since 2003, the applications of genomics to medicine have been moving forward at a dizzying and gratifying pace, including determining the nature of genetic variation in the human species and how that connects to disease risk]. With some reluctance in 2008, I decided I had done this kind of thing for 15 years and I was ready to step down and try something else, without quite knowing what that would mean. I served on the Obama Science Committee and the Obama Transition TeamIn the spring of 2009 I was asked to direct the National Institutes of Health, was nominated by President Obama in July, and confirmed by the Senate in August. That was a big deal - stepping up from being the director of the genome research effort to overseeing the entire biomedical research enterprise that NIH supports, a vast and extremely important institution for furthering our hopes for the future: $31 billion a year, twenty-seven institutes and centers, tens of thousands of grants, hundreds of thousands of researchers, all supported by the NIH.

JYI: Wow! So, here you are!

Dr. Collins: Haha, yeah.

JYI: Quickly going back, for those readers who don’t really know too much about research – what exactly is the NIH, and how does it operate? I know you said it has a lot of scientists, and it manages our budget in regards to biomedical research. Could you give us a few more details?

Dr. Collins: Sure. The vast majority of the NIH budget is made available to investigators who come forward with their most ambitious ideas in the form of grant proposals. They send those in to NIH, and those are peer-reviewed by panels of experts, and are given a priority score, based upon the promise of that research. Those that have scored the best are then given grant funds through the NIH budget process, which is basically tax payers’ money, given to us by the Administration and the Congress. When you hear of an exciting biomedical research breakthrough at Stanford, or Harvard, or the University of Virginia, it will almost always be on the basis of a grant from NIH, because that’s where most academic biomedical research gets its support. NIH supports about 50,000 grants each year -- and each one results in creation of jobs, which happens to be a rather important topic right now. But if you look at the last several decades of Nobel Prizes in Medicine or Physiology, the majority of those are from investigators who were supported by NIH to make the breakthroughs that led to their winning the prize.

JYI: Speaking about biomedical research, and I mean, it seems you know some of the trends of the various fields of the research – so, what, in your opinion, is the future of biomedical research? What can the current generation of college students, like myself, expect to see as normal research endeavors in ten to fifteen years from now?

Dr. Collins: I published a paper in Science on January 1st (http://www.sciencemag.org/cgi/content/full/327/5961/36) that your readers might want to look at. It’s just a two-page paper, outlining five major areas of exceptional opportunity right now in biomedical research. One of those is to apply a variety of newly developed powerful, high-throughput technologies to really understand how the cell does what it does, what is the underlying comprehensive basis of life. This involves using techniques like genomics, small molecules, imaging research, and computational biology to make sense of these very complicated systems, and how to figure out what has gone wrong with that complex network of signals when disease occurs. A second area of exceptional opportunity is to take those basic science discoveries about disease that have been pouring out of laboratories in the last few years, and really push the agenda in an aggressive fashion to turn those into therapeutic breakthroughs – treatments for diseases like cancer, diabetes, and heart disease, that we could not have imagined in the past. A third area is more to look at our health care system, and figure out what research needs to be done to optimize that, at a time where health care reform is on everyone’s mind, to make sure we have the data from clinical studies to see what works and what doesn’t -- so that if we’re
trying to devise a health care system, it’s going to produce good outcomes, and hopefully, lower costs. Along with that, the idea of personalized medicine, where you try to get beyond a ‘one size fits all’ approach to prevention and treatment, and consider the special nature of each of us as individuals to improve the outcome, is a big priority. This is becoming increasingly practical, but there’s a lot of research that needs to be done to make that happen. A fourth area, and one, I think, of great importance right now, is to consider not just the health of our own nation, but that of the whole world. Many scientists have turned their attention to problems of global health, feeling that the time is right for the United States to emphasize this as an area of outreach. If we could spend more of our resources as a country doing “soft power”, reaching out as researchers, scientists, and physicians, instead of as armies and soldiers, that would both improve the status of health for people in the developing world, and to improve the image of the United States as the country that is trying to do good things for our neighbors. Scientifically, there are many opportunities right now to make that a reality. Finally, we are going to have to pay attention to the health of the biomedical research enterprise, and to ensure that we are recruiting the best and brightest into the ranks of biomedical researchers for the future. The opportunities, scientifically, are unprecedented, but our most critical resource are the people that are going to do the work, that are going to have the bright and creative ideas, and that are going to be fearless in pursuing innovation. That’s why I’m glad to talk to you, and to the Journal of Young Investigators, because I think your audience is made up of the people that we hope to draw into our ranks to help make these dreams come true.

JYI: Excellent -- Thank you. On that note, what opportunities are available for students, like us, who have recently finished college, and have dabbed about in a lab or two? As an example, I know that the NIH has specific funding for students interested in pursuing careers as physician-scientists, such as yourself, and that’s actually something that I, myself, am interested in – so what can you tell us about these so-called Medical Scientist Training Programs?

Dr. Collins: Well, there are many opportunities. Let me begin with an opportunity that people may want to consider who have finished their undergraduate education, or who are close to finishing it, and are quite not sure yet if research is their calling or not, and might want to spend full-time working in a laboratory to test that out. Here, on the NIH campus, there is a program that pays students to come and spend a year, or sometimes two years, working in a cutting-edge NIH laboratory. There are 17,000 people working here in Bethesda, Maryland, that are experts in almost everything you can think of, including several Nobel Prize winners right here on campus. I run my own research lab, here on campus, and I generally have two or three of these post-bac students in my lab at any given time. They are wonderfully inspiring because of their curiosity and their energy, and they have done extremely well in future efforts once they decide what they want to do, whether it’s graduate school to get a PhD, whether it’s medical school, whether it’s an MD/PhD program, or whether its thing a little different – going to law school to learn patent law, for instance. This is a great springboard for that. This program is very competitive, because we have many, many applicants, but there are dozens of slots available each year, so this might be something people would want to look into. Once people have decided they really are interested in graduate training in biomedical research, NIH supports a lot of those training programs, both for PhDs and for MD/PhDs. In particular, the Medical Scientist Training Program, which supports MD/PhDs, is available in a number of universities that have top-notch training programs of that sort. Individuals who are successful in competing for a slot in one of those programs have considerable financial benefits available to them, in terms of covering tuition and even paying a modest stipend, which can be a way of getting around what otherwise could be a pretty heavy burden of the cost of medical education.

JYI: Going along those lines, why is so important to have, you know, both clinical training and training in the basic sciences? What are the advantages of that? I know you mentioned, in regards to therapeutic research in the future, that could become advantageous to have, but what else?

Dr. Collins: Well, I think it depends a bit on what the individuals’ basic interests are, as far as what area of research appeals to them. We certainly have MD investigators who do full-time clinical research, and we need that in order to develop and test new therapeutic ideas. But also it’s a good idea for anybody contemplating spending their career in research to be fully grounded in the basic research that lies at the foundation for those future developments in medicine. Many of those MD/PhD students end up doing their research in a more basic arena, and then aim to try to apply that in therapeutics down the road. We need that mix. But if there’s an area that we’re particularly interested now in building, it’s clinical researchers, because the opportunities to be able to develop and treat patients with very brand new and exciting therapies have never been better. We may be facing a bit of a shortfall of researchers who are clinically qualified to do that.

JYI: Sure. I know time is running short, but I have three more questions. As it relates to the greater feeling of scientific curiosity and a love for science, what role does undergraduate research play in our society? I know you experienced some undergraduate research, I do, I know other staff members do, and many of our readers do. So, how can it help us?

Dr. Collins: I don’t know how one could really discern one’s own attraction to research without participating in undergraduate research. It’s one thing to sit in the classroom and have information shared with you about how scientific advances have been made, and that’s important because you need that grounding in the fundamentals. But if you’re interested in spending your life in active, primary research, you need the chance, as soon as possible, to have that experience yourself and see how it feels. Undergraduates in leading universities and colleges have that opportunity, if they will seek it out. Most faculty are delighted to have that interest expressed, so anyone who is seriously considering that career path ought to look into this and see what’s available. I’ve mentioned some opportunities here at NIH which people can take advantage of, but let me be quick to say almost all universities have such opportunities both during the academic year and the summer. Usually, they have an office that supports the distribution of information about what kinds of training opportunities students could have access to, and every advantage should be taken of that by people who are contemplating going down this road.

JYI: Yeah, that’s very true. I know that here, at the University of Virginia, has a summer program, and most universities do. Quickly going back to your background, and to your life, when did you experience that feeling of success in research for the first time? Did it act like a spark – did it make you want to do more research?

Dr. Collins: Yeah. I guess I’d go back to my senior year at the University of Virginia, working with Carl Trindle. He had just arrived from Yale – it was his first year on the faculty, and I was his first student. He gave me a very challenging project to work on, which was a computational analysis of a particular kind of organic reaction, to try to see if that could be modeled using quantum mechanics. The first month or two that I was working on this, I was pretty puzzled about what was going on because this was pretty sophisticated stuff, and a little bit over my head. But as I got deeper into it, I began to grasp the principles and how we could apply them. Ultimately I was able to be an author on a publication in the International Journal of Quantum Chemistry. That was quite a rush, having accomplished something that somebody else might want to read about (you can read the abstract: http://www3.interscience.wiley.com/journal/122460012/abstract). That was the point, I think, that ignited the spark that led me to this confidence that research was something I could do, and I really wanted to do!

JYI: Sure – and so what about the opposite, failure? How do you cope with failure in the lab?

Dr. Collins: That’s a great question, Tudor, because I think especially early in one’s career, where you’re so anxious to make progress, and your own ego is tied up in the success or failure of your experiments, having something not pan out can be quite a blow. When I came to the point of moving into molecular biology as my research area of focus, many years later after I had gone through all of my clinical training, I had a very tough time during the first six months that I was working in a research lab, trying to learn the techniques of recombinant DNA. Most of the people around me knew a lot more about this than I did. My first project, frankly, was a complete bust. After six months, it was pretty clear that it was just not going to work, and it was time to abandon that strategy altogether, and start over on something else. That was very hard, and I seriously considered whether I should move on and become some other kind of a physician, maybe just focus completely on clinical practice. People do! The failure in the project felt like a personal failure. Looking back on it, it was a project that was risky, and it was doomed from the start, but I didn’t know that until I did some experiments to prove it. But a later project came together nicely, and I was reinvigorated. Based on this experience, I would really want to encourage your readers who are going through that experience of failure, that it is an unavoidable part of the process. If your experiments are always working, then you’re probably not involved in an area of research that is very interesting. You have to consider occasional failures as part of the package if you’re doing science that’s worthwhile.

JYI: On a closing point, do you have last words of advice for undergraduates who are reading this?

Dr. Collins: I would say that there has never been a more exciting time to get involved in biomedical research. This century, the 21st century, is going to be the time when we derive answers to questions that have vexed us for all of history. This will be the time where those revelations will result in a revolution in medicine that will provide answers to diseases that have previously not been understood. To be part of that process of discovery and application could be, I think, the most exciting way for somebody to spend their life. If people reading this interview have an interest in science, I would encourage them to pursue that with all due vigor, and expect great things, because those will be possible in the coming years.

JYI: Awesome – great advice. Thank you very much for your time, Dr. Collins. We, at the Journal of Young Investigators, really do appreciate it, and I’m sure that undergraduates will find some encouragement in this. So, thank you!

For more information about opportunities for research at the National Institutes of Health, please check out the following websites:

NIH General Information
http://www.nih.gov/

NIH Summer Internship Program, and other Student Programs
http://www.training.nih.gov/student/sip/

NIGMS Medical Scientist Training Program
http://www.nigms.nih.gov/Training/InstPredoc/PredocOverview-MSTP.htm