NIH's Collins on Changing the Future of Medicine

Taking Health and Disease to the Next Level

Eric J. Topol, MD: Hello. I am Eric Topol, editor-in-chief of Medscape. I am thrilled to welcome Francis Collins, director of the National Institutes of Health (NIH), for a Medscape One-on-One discussion.

Not long after the President's announcement during the State of the Union address, the White House Precision Medicine Initiative was established. Let's start with that and your impressions of where it is headed.

Francis S. Collins, MD, PhD: I am enormously pleased with the President's enthusiasm and excited that this project is beginning to take shape and move forward. Precision medicine is an area that you have written a lot about, and those of us who are interested in trying to bring our understanding of health and disease to the next level can see the potential. This proposal from the President for significant new resources in the next fiscal year is quite a moment.

Dr Topol: You have been working on this for many years. What happened to finally move it in this direction?

Dr Collins: I published a paper in Nature^[1] in 2004, proposing a longitudinal large-scale cohort in the United States to try to track all of the factors involved in health and disease. It landed with a loud thud because, at that time, problems with practicality were identified: "How much is this going to cost? Do we actually have the ability to collect phenotype information on individuals in any kind of reasonable way?" A lot has happened in those 11 years. Now there is a perfect coming together of opportunities with electronic health records being a part of medical care. Genome sequencing costs have plummeted (down to a few thousand dollars for a complete genome), and now patients want to take part in initiatives of this sort.

Add to that something that you have written a lot about—the increasing availability of exciting, wearable sensors to keep track of an individual's physiology and environmental exposures—and this is starting to take shape in a very exciting way. The time is right, and the President realizes that. It's not just the President's enthusiasm that is driving this; both parties seem very excited about the potential of putting America onto an exciting path to understanding things that we have not had the power to discern before.

Knowledge From Big Data

Dr Topol: You recently had a 2-day workshop at NIH to try to work out some of the details. How do you feel that momentum is coming along to help the initiative take shape?

Dr Collins: It was a very exciting couple of days. We had 85 people in the room; it was a remarkable gathering of people with many different perspectives, including many patient advocates, people who knew a lot about technology that is going to be necessary for the initiative, privacy experts, genomics experts, epidemiologists, and those who are already running cohorts of various sizes that could potentially be brought together to create this planned American cohort study a million or more people strong. It was clear that although everyone identified that there was much work to be done and a lot of details to be sorted out, they said, "We had better get busy." The sense of the potential of this initiative, called Big Data to Knowledge (BD2K), was fairly universal, and that was very exciting to see.

Now what do we do? We have started to put together a process to add details to what is currently a fairly skeletal plan and a working group of my advisory committee that is going to be cochaired by Rick Lifton of Yale and Kathy Hudson of NIH. We are trying to identify the membership of that working group to ask them to come forward by September with a more detailed plan of what we might want to do beginning in October, when the new funds, we hope, will be available.

They will be asked to keep going, and maybe by the end of this year, we will have more details available. It is a lot of work. When you start identifying the number of questions, it is a long list, but everybody is ready to roll up their sleeves and make this happen. It is not just NIH. We are working with the White House, the US Food and Drug Administration, the Office of the National Coordinator for Health Information Technology, all of whom are partners in this effort and who have expertise to bring to it.

Dr Topol: That is fantastic. There are other initiatives around the globe, although they are perhaps not quite as ambitious. For example, there is a large initiative in the United Kingdom called Genomics England. Is there a sense that maybe over time there would be international cooperation to bring these together?

Dr Collins: Absolutely. We have a lot to learn from each other. In some ways, the United States is a little behind the curve compared with other countries such as the United Kingdom. Estonia has an interesting program, as well. And, of course, Iceland has been at this for a while, although those data are not accessible in the way that we hope ours will be.

China is also invested in this kind of effort. We need to learn more about that. There is a great opportunity to develop an international network so that the whole becomes greater than the sum of the parts. You understand the kind of insights we want to derive here. They depend on having very large numbers. We need big data because we are looking for correlations that will be discernible only if we have many events to learn from.

Road to the White House

Dr Topol: I am going to move from the globe to your origins in Staunton, Virginia. You have come a long way from Staunton, Virginia. You went to the University of Virginia, so we share a common thread there. The other thread we share is that we joined the faculty at the University of Michigan right around the same time, in the mid-1980s. I will never forget grand rounds or your discovery of cystic fibrosis. Was that in 1988 or 1989?

Dr Collins: It was August of 1989.

Dr Topol: I have never been to a grand rounds that was more invigorating than when you talked us through chromosome jumping. Then in 1993, you went to NIH to run the Genome Institute. You took a break from running it. What did you do during that time?

Dr Collins: I wrote a book about personalized medicine, which I had wanted to do. As the person running the Genome Institute, it would have been a conflict of interest, so I had to step away from that to be able to write it. I quickly got pulled into science advisory to the Obama campaign; and then when Obama was elected, I was asked to serve on the transition team, along with (former director of the National Cancer Institute) Harold Varmus, to help figure out what might be done at NIH during this administration. I do not remember much about Thanksgiving or Christmas of that year because it was extremely intense trying to pull all of this together.

Although I was not expecting it, I got a call to come back to NIH in a different role to serve the President in this administration, to lead NIH in an exciting although stressful time, given the budgetary situation and our nation's fiscal dilemmas.

Medical Research: A Victim of Budget Cuts

Dr Topol: You have been quite a champion for trying to get the budget improved at a very tough time. Is that the toughest frustration you have had to deal with?

Dr Collins: My daily experience is paradoxical. Science right now is exhilarating. I write a blog twice a week, and I get to pick topics from everything that is happening. It is hard to decide what to focus on because so many things are bursting with potential. That is one side of the NIH director's experience; the other is facing tight resources. Many scientists with great ideas are missing the cut when it comes to peer review and our funding decisions. Funding is the worst it has been in 50 years, particularly for early-stage investigators who are just getting started. We are very worried about the future of our enterprise in this country. If we do not turn that corner soon, we are going to lose a significant fraction of those investigators who will just give up after a while. That will be a terrible and irreversible tragedy for our future.

Dr Topol: It would be hard to imagine someone having as much infectious enthusiasm as you do to explain to Congress and the people who come up with funding to take NIH to the next level. Hopefully, the precision medicine initiative will jump-start this. What do you think?

Dr Collins: It has captured much imagination. Besides the million strong cohort, precision medicine has another very significant component focused on cancer, which is much more immediate and short term. We basically take what we are learning about the ability to dissect individual cancer genomes and understand what that means about the kind of therapeutics that we choose. This is going to roll out rather quickly next year, expanding those efforts by looking at combination therapies to understand when resistance occurs and looking at liquid biopsies as a way of assessing response to therapy for people with cancer. All of that has immediate potential, and Congress is also very excited when they hear about that. In 5 years as NIH Director, I do not remember a meeting with a member of Congress that I felt went badly. The evidence is so compelling for the value of what we are doing, for medical benefits, for the economy, for American competitiveness. For every theme, we have a great story to tell.

Dr Topol: The return on investment is staggering in a positive way.

Dr Collins: There is no question about bipartisan enthusiasm. The problem is that medical research has been caught as an innocent bystander in this unresolved national debate about what we are doing with federal funding. Medical research, oddly enough, is part of the discretionary budget, although it does not seem, from many people's perspectives, that it ought to be discretionary. It is. Over the past 12 years, whenever we got into a pickle, the discretionary budget got whacked. We have lost 22% of our purchasing power for research since 2003, just at the point where all of this potential is just emerging. It is so compelling.

Long-term Impact of Precision Medicine

Dr Topol: You have emphasized that this is the most exciting time in science and medicine, and you would hope that we will leverage that opportunity more. Let us fast forward, and say that we can, through your leadership, continue to get the support that is needed. Where do you see medicine in the year 2020? What changes will we see in 5 years?

Dr Collins: It is tough to make predictions, and you have stuck your neck out a few times. I have too; sometimes I am right on the money, and sometimes I have underestimated the pace. The first law of technology says that when something emerges that has potential—a groundbreaking opportunity—we tend to overestimate the immediate impact and underestimate the long-term impact. Precision medicine is probably in that category. The question is: Where are we? Are we talking about the short or the long term? Over the course of 5 years, particularly for such areas as cancer, we are going to see a complete transformation in the way disease is diagnosed and treated, and that is good. This will disseminate widely across many different medical centers, not just those that are doing high-tech research.

In terms of the precision medicine approach to monitoring health, you have written cogently about the remarkable curve we are on in terms of the number of gadgets available to tap into, and the momentum for applying them to medical care is unstoppable. We have to be sure (and I am sure you would agree) that we do not just get excited about apps. We must demonstrate in a rigorous way that they improve outcomes.

Dr Topol: You have done a great thing with this data-to-knowledge initiative because we are going to be generating data. In fact, the data seem homeless because there isn't going to be an electronic medical record. You have terabytes coming from not only sequencing but sensors and everything else. Is the rate-limiting step (besides finding) being able to deal with this massive outpouring of data?

Dr Collins: That is certainly one of them. Having now recruited Phil Bourne, from the University of California at San Diego, to serve as my new associate director for data science, it is great to see the way we are now tackling that in a substantive way, whereas maybe 2 or 3 years ago, people worried, "Do we have a plan here?" Now, we can see what needs to be done. We have to get it done, and Phil's idea is to generate a mechanism to format the data and the metadata in a format that we can compute, which will be critical. However, that is not a substitute for having smart people who know what to do with the data. Another part of BD2K is to nurture the training process. There is a lot of talent out there, but we have to be sure that we give people the right skill set. It will be interesting to see how that plays out.

Will Medical Practice Keep Up?

Dr Topol: Do you think medicine will evolve as a data science?

Dr Collins: Biomedical research as a whole is increasingly in that space, and the practice of medicine needs to do so. We all want to get to a place where patients are fully engaged in their own care. They are going to be dependent on data science that is accessible and understandable. Physicians basically want to deliver evidence-based medicine whenever they can, and to do so is going to depend on datasets. I worry about how quickly the practice of medicine will be able to change because we have a long tradition of being slow to change, but patients will drive the process, and physicians who are not up to that kind of interaction are going to find it increasingly harder to have a satisfying practice.

Dr Topol: When you were back at Michigan in 1989 studying cystic fibrosis and then neurofibromatosis, multiple endocrine neoplasia, and progeria, did you ever think that 25 years in the future, we would be where we are today?

Dr Collins: Absolutely not. I had a great time at Michigan. It is a wonderful place. I was there doing research, teaching medical students, and taking care of patients with genetic diseases. I figured that was kind of the path I would be on for my whole career. Then I got that call to come to NIH to become a federal employee and manage a huge, sprawling, and at that time very risky enterprise, The Human Genome Project. It was really quite breathtaking. It was a hard decision. Anyone reading this who has their own dreams about their career path, these days no one can plan what that is going to look like. You have to keep your eyes open. You have to be prepared for doors to close and open that you did not quite expect and go with it. What an amazing ride it has been, and what a time it is to be involved in biomedical research. We are able to ask and answer questions that I would not have dreamed, even a decade ago, were even possible to consider.

Dr Topol: You are a phenomenal inspiration, and it is wonderful to get your perspective on this exciting time in precision medicine and also learn about your background and how you got on this path. Thanks for joining us. We will be cheering for you so that we can jump forward and actualize the excitement that is out there in biomedicine.