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Angie Drakulich was editorial director of BioPharm International.
Inside the National Institutes of Health
Francis S. Collins, director of the National Institutes of Health, talks about the institutes' global partnerships, innovation strategies, small-business funding, and plans for personalized medicine.
Editor's Note:The following is an excerpted transcript of an interview that took place in June 2011 between Francis S. Collins, director of the National Institutes of Health (NIH), and BioPharm International's Senior Managing Editor Angie Drakulich, in preparation for the Biotechnology Industry Organization's (BIO) annual convention and Partnering for Global Health Forum, which was cosponsored by BioVentures for Global Health. Dr. Collins is noted for his landmark discoveries of disease genes and his leadership of the international Human Genome Project. The full recorded interview can be listened to at BioPharmInternational.com.multimedia.
BioPharm: Since you became director of NIH in 2009, you made it clear that you wanted to make global health a top priority. Could you summarize the role you saw then for NIH in global health and whether you feel that major strides have been made thus far?
Francis S. Collins
Collins: Yes, in figuring out what were the themes that offered the greatest opportunity for progress in term of NIH research, I spent a lot of time speaking with experts, seeking advice, and trying to identify areas that would fit as being exceptional opportunities. Global health clearly emerged as one of them and certainly resonated with my own desires to see advances in medical research benefit not only people in high income countries but also throughout the world.
I do think, scientifically, the arguments are pretty compelling that this is a unique time for assisting that process through NIH research. After all, we're making discoveries about the nature of pathogens that cause infectious diseases, that suggest new ideas about vaccines and therapeutics. And I think we have increasing abilities also to look at noncommunicable diseases in new ways and try to interrupt what otherwise is going to be a cycle in which those cause an increasing amount of morbidity and mortality throughout the world.
When I came to this position in August 2009, I convened almost right away a major gathering of organizations that fund global health research to try to get a better handle on who's doing what and where the gaps might be. And that was quite instructive because there are a lot of players doing a lot of interesting things, and it's not trivial to figure out exactly where the opportunities lie.
There are two projects that have come out of that discussion that are now underway and that ... I think are going to be interesting. One of those is what's called the Medical Education Partnership Initiative [MEPI], which is now funding academic institutions in 12 countries, a total of 30 institutions, to build capacity, both for medical education and for research. We're doing this jointly with [the US President's Emergency Plan for AIDS Relief], PEPFAR.
Eric Goosby [the US Global AIDS Coordinator] and I have agreed that this is a shared area of real importance for that part of the world, and the kickoff of the MEPI program occurred in March  in Johannesburg. It was very exciting to see how all of these investigators coming from institutions all over the continent—many of whom have never really been invited to come to the same meeting together and learn from each other—are really now going to be given a chance, with NIH support and support from PEPFAR, to build that kind of capacity.
The old model in which global health research is done by institutions in high-income countries and then sort of offered up to low-income countries has done good things. But in the future, we'd like to see that research capacity built in the countries where the medical needs are great, and I think we have a chance to do that through programs like MEPI.
BioPharm: And what is the second project underway?
Collins: The other program, which is going to be sponsored jointly by NIH and the Wellcome Trust, is called Human Health and Heredity in Africa, otherwise known as H3Africa. This is a bold effort to create a network of research activities that will look at environmental and genetic risk factors for both infectious and noninfectious diseases in the continent. It will adopt some of the same strategies that have been carried out more recently here in the US and other developed nations, but try to find out—in the cradle of humanity—how can we make the most of some of the new technologies that allow us to do genomics and environmental science and understand the causes of illness.
This will mean building capacity to do that kind of research, including information networks to share data and to carry out computational analyses. It will include setting up phenotyping capabilities to look at clinical consequences of various exposures and genetic risk factors. It will also mean establishing biorepositories to be able to store the samples that will be collected on what we expect will be thousands of individuals in Africa who will be the research participants in this bold new effort that will undoubtedly stretch over many years.
BioPharm: Have you found that countries and other groups are more willing to collaborate in recent years, and, if so, what do you think has led to that change?
Collins: I certainly do think that collaborative spirit is expanding in a wonderful way and it's driven, in part, by scientific opportunities. [For example, with our new consortium for rare-disease research], we are discovering the molecular causes at a prodigious rate. There are now some 4000 rare diseases for which we know, at a pretty detailed level, what the actual molecular problem is that leads to that illness, many of these being genetic diseases caused by mutations in the genome.
And, so, if you want to see that knowledge applied in terms of developing new therapeutics, that is something that is not trivial. You certainly don't want to waste the opportunity to bring groups together that might be able to do this faster, and you don't want to duplicate efforts and waste resources.
BioPharm: In previous statements you've mentioned that innovation should not be limited to the work that's done for developing nations. How can we best capture the technology and knowledge that's used for developing-nation treatments and apply them to drug development and discovery in every region of the world?
Collins: I think of innovation very much as a two-way street. We shouldn't think that new inventions or new creative ideas come forth only in the US or in Europe. We can also learn, in what's being called 'reverse innovation', about how to adopt new ideas that are being developed in low-income countries. A particularly good example is the use of cellphone technologies for medical purposes....
For instance, we have a technology that's being developed and tested in Africa which is a simple method of assessing whether, in fact, individuals who are being treated for tuberculosis or HIV/AIDS are compliant with the therapy. So, you have a pill box which essentially is hooked up to the cellphone network, and every time the pill box gets opened, it sends a signal to the clinic where that patient is being cared for so that you can tell, was it, in fact, opened, and was it at the appropriate time of day?
BioPharm: That technology provides a great way for doctors to follow through when they're not close by.
Collins: Exactly, and that, already, has spurred ideas about how we might adopt those same approaches here in the US for people who have, for instance, diabetes or hypertension. Medical compliance, we know, is critical for success in treating many conditions, and yet we haven't really had a good way of monitoring it.
BioPharm: Some other conversations going on in the pharmaceutical industry right now have to do with translational research, and NIH is a big supporter of that. How is NIH selecting projects to pursue in this area and how far can it take the projects, for example, through proof of concept in animals or Phase I clinical trials?
Collins: This ties into the conversation we were having about rare diseases [as part of the new consortium's goals to find treatments for 200 diseases by the year 2020] and the goal of having new therapeutics in a reasonable time. As you know, the current situation is a little scary when it comes to making such promises because, after all, the average time it takes from identification of a potential drug target to ultimate approval of that therapy is about 14 years, and the failure rate is about 98%. We think the time has come to look at that process the way that an engineer would and see if there are ways that we could optimize some of the steps that currently are slow, expensive, and likely to fail. That is part of NIH's effort now in putting together a new entity called the National Center for Advancing Translational Sciences.
We certainly will do this in a way that is complementary, and not competitive, with what the private sector would like to do, but we do expect that this kind of initiative may make projects that previously appeared too risky start to look attractive. So some of this is the idea of derisking projects which the private sector might otherwise not feel were economically attractive.
And certainly, when NIH sees opportunities for therapeutic development, working through the 27 institutes and centers that have a lot of knowledge about these areas, we will try to move projects forward to the point where they've become commercially viable and then license them out as quickly as possible in order to get them over the finish line.
Again, the goal here is to try to take advantage of remarkable scientific opportunities that might otherwise lie untouched but also to recognize the economic realities which means that companies, in general, are not going to go after projects that they don't think ultimately will become profitable.
BioPharm: Do you think at some point you'll be able to recruit development partners in industry, such as any Big Pharma companies?
Collins: Oh, absolutely! I think already we're having some pretty interesting conversations with leaders of big companies about ways that we could work together in some areas that currently tend to be slow and inefficient.
One example is, how do we actually determine whether a new potential drug is safe to give to humans? Right now the way that that is done, as a sort of preclinical toxicology, depends upon the use of animal testing which is expensive, slow, and often not very reliable. We have a program already underway called Tox21, with 21 representing the 21st century, that is jointly done with FDA and EPA [the Environmental Protection Agency]. We're looking at potential environmental toxins and also with drugs to see if there are better ways that are higher throughput, depend upon human cells as opposed to other animals, and give a reliable signal about whether a compound is safe or not.
The Tox21 project is, I think, a good start in the direction of what could be a totally new science of doing preclinical toxicology in the era of having human cells that could be engineered into three-dimensional organoids.
BioPharm: You mentioned funding, and there has been some debate recently regarding the NIH grant program for small businesses. The Small Business Innovation Research (SBIR) program has been authorized by Congress until Sept. 30, 2011, but there are still disagreements in Congress about how venture capital affects those grants and the qualification of companies. In your opinion, what is best in that regard for drug discovery and development? Are there certain things you'd like to see happen with that particular bill and the program?
Collins: NIH has a long track record of supporting small businesses in a very productive fashion. We can point to some fairly major successes there that have resulted from that kind of starting support for the early phase of a company's development. Take the company Affymetrix, which has been a leader in the area of microarrays. That whole company was started on an SBIR grant and is now valued at quite a lot of money.
We could point to other examples as well. NIH's perspective is that we would like our SBIR dollars be used for projects that have the greatest chance of ultimately resulting in public benefit. Consequently, to have companies excluded on the basis of the amount of venture capital involved in their startup doesn't always make sense. So we are looking forward to seeing that limitation relaxed a bit because I think it has excluded some companies that might have been really good grantees. Obviously, that's a topic that's on an ongoing discussion on the Hill.
BioPharm: Another area of leadership and research for NIH is the Genome Project, which is supposed to provide the foundation for personalized medicine. How close do you think we are to truly having personalized medicine, and what do you think needs to happen to make it a reality?
Collins: I think we're there in some instances. It isn't one of those things where you don't have it one day and the next day you do. It comes along in various applications bit by bit. If you consider, for instance, a woman who's diagnosed today with breast cancer and has negative lymph nodes at the time of surgery, the question is, is the surgery she just had, the lumpectomy and the radiation that will follow, is that sufficient? Is she cured or does she also need adjuvant chemotherapy?
Well, personalized medicine is here because about half of the women in the US who are in that situation this year will have their breast-cancer cells analyzed to see whether there is a signature at the genetic level that would indicate that they are at a higher likelihood of recurrence and, therefore, need the chemotherapy or whether they're at low risk and can be spared the cost and the side effects of what can be a pretty unpleasant experience. That personalized medicine intervention right now is saving our healthcare system this year about $100 million in terms of the women who won't end up needing chemotherapy who otherwise would go through it. So it's a pretty good example.
Pharmacogenomics is another frontier. One example is abacavir for HIV, where it's now required on the label to do a genetic test before prescribing the drug for hypersensitivity. Or Plavix, which is one of the most highly prescribed drugs and where there's now an FDA label saying physicians should be aware that about one-third of the people given that drug will not benefit from it because of their genetics and should be offered some other alternative.
So, in those instances, I would say personalized medicine isn't the future, it's the present! It's here.