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Question: How does the NIH decide which medical research to fund?

Francis Collins: The process that NIH goes through to decide which research to fund is complex; there’s a lot of factors.  Certainly the burden of the disease has to be one of those, but if that was all you paid attention to, rare diseases would get neglected so that can’t be the only story.  

Scientific opportunity has to be a big part of it.  There’s no point throwing money at a problem if nobody had any ideas about how to move the ball forward.  And you can see then sometimes when a rare disease which may not affect that many people hits that moment of scientific opportunity, and oftentimes rare diseases teach you a thing about common diseases as well.  So, it’s a complicated mix.  

NIH depends very heavily on the scientific community to come forward with their best and brightest ideas, and they send us their grant proposals in an unsolicited way and that’s where the majority of our money goes.  But we also identify areas which are ripe for exploration, where something is really starting to go great guns and we don’t want to slow that down, in fact, we want to speed it up.  So in that situation, NIH would issue what’s called a "Request for Applications" saying, we think there’s opportunity here scientifically so we’re gonna set aside some money and we want people who have skills and interest in that area to come forward with some ideas and we’ll pay for the best in the group.  

Question:
Since becoming director, have you put a specific emphasis on addressing specific diseases?

Francis Collins: I think it’s hard to pick out individual diseases and say, "Well those are more important that the others." But I think one can look at circumstances where there are especially ripe opportunity.  Cancer certainly would be on that list because we are beginning to understand cancer on a detailed molecular level, in ways that we never dreamed possible.  So there’s a real potential there for moving forward in a new quantum leap into understanding.  

Autism is certainly something many people are now focused on as an area of very high priority disease that affects now one in 100 kids.  This seems to be more common all the time and we don’t understand it very well—a very high sort of public health significance.  But many other things would also sort of fit on my list, diabetes, heart disease. Alzheimer’s disease—good heavens, when you look at the burden that is going to place on individual’s families and our economy.  

It’s all a mix though, and frankly what I’ve tried to do since I became Director of NIH in August of 2009, is to identify specific areas that actually touch on multiple diseases that are ripe for investment, so I came up with a series of five themes that, if pursued vigorously, could really change the landscape, but they would really do that for lots of diseases not just a few that are specifically targeted.

Question:
How much is the NIH's funding process affected by politics?

Francis Collins: We’re fortunate at NIH, that the Congress has in general has adopted a view that making priority decisions about scientific research is best done by scientists.  People talk about areas in other parts of the government where there’s earmarking or sometimes in a less friendly way called "pork" funding; we are relatively free of that.  Congress will certainly indicate to us when they think there is an area that needs more attention, but rarely will they attach a specific dollar figure to that.  They’ll just ask us to look at that a little more carefully.  So we have a very good working relationship.  

Likewise with the administration.  The administration is interested in seeing NIH be very productive and they want to hear all the time about how we’re spending our money and have us defend why it’s the right way to go.  But they’re generally reluctant to say, “Well you should spend X dollars on Y disease.”  And that just doesn’t seem like the way to make the choices.

Question:
How much say should the public have about what federal research money is spent on?


Francis Collins: Well the public does have a lot of say.  We have many disease advocacy groups who are constantly putting forward their case for why more research needs to be done on their condition, and of course, I would love to meet all of those requests, but we are often stuck in a situation where we’re limited in resources, and so we can’t do everything.  

But certainly we work I think pretty effectively with a lot of those groups to identify where are the areas that are most ripe for investment.  And sometimes that means coming up with an RFA because something is about to break.  Sometimes it’s organizing a workshop and trying to survey the field of a disease that seems to have gotten stuck for a while and figure out how to get it unstuck, and figure out how to get some new ideas and new scientific minds working on the problem.  I would say, for the most part, we have very productive, synergistic, friendly relationships with disease advocates who understand how the process works, are anxious to see resources put into their disease, but want it to be done in a fashion that’s scientifically productive and not just throwing money at the problem.

Question:
Are there areas of medicine or technologies where research dollars go farther?

Francis Collins: Return on investment is always an interesting question when it comes to medical research.  Well, what would you call "return?"  Is it that you’ve published a certain number of papers?  Well, that is one metric I suppose and that they are in high-impact journals, that’s another metric.  But really what we’re about is trying to help people.  

So the real return you’re looking for is clinical benefits, diagnostics, therapeutics, preventive measures.  The lead time on those is often measured in years.  And so it maybe quite difficult to assess when you’re just looking at a program that’s been underway for three or four years, how does it measure up in terms of what you’re getting for your dollars compared to some other program that similarly is sort of in an early stage of moving into clinical benefits?  But we try to do that to the extent we can and I think we should.  This is taxpayers' money; the taxpayers believe in us as the place that is gonna make that next breakthrough.  They want to be assured that we’re using those dollars in the most effective way possible.  Sometimes people think NIH is just, you know, playing around in the lab.  I can assure that’s not the view of people here, but we need to be prepared at any moment to defend the choices we’ve made as having had the best chance of benefiting real people out there who are counting on us to use their money wisely.  It is their money. 

Question:
How has the recession affected the NIH's funding priorities?

Francis Collins: Having the economy struggling at the level that it is and having rising concerns, understandably so, about the federal deficit has certainly had an impact on funding for biomedical research through the National Institutes of Health.  When you look at the support we’ve had, we are grateful that even in tough economic times there has been a willingness to try to keep up at least with what we were doing before.  But we haven’t gained much in terms of buying power over the last 10 years, we’ve been pretty much flat—even though the dollars being put in medical research have gone up a big, inflation has eroded that.  The one exception was a $10 billion dollar increment as part of the Recovery Act, which needed to be spent in two years and which was invested in ways that I think are truly exciting. But science doesn’t operate on two-year cycles, so now that the Recovery Act money is running out, we are facing what could be very lean times indeed for medical research.  

That forces us to be even more specific about how we set priorities. It forces us to say, we can’t do everything.  It forces us in some instances to close down programs that have been reasonably productive, but compared to what we’d like to do now in terms of new an innovative projects aren’t quite as compelling as if we had unlimited resources.  It makes the job of a science manager a lot tougher, but is the reality of what we are currently living with.

Question:
Does the tight budget make it less likely that unorthodox or creative studies will get funding?

Francis Collins:
I think there’s been a lot of concern that when budgets get tight, the peer review process can tend to be a little more conservative.  And budgets are tight right now.  If you send a grant to the NIH that’s got your best ideas in it, the chances that you’ll get funded is less than 20%.  In some of our institutes, it’s down around 10%. That’s a terrible stress on the system. That means that investigators are having to write and rewrite grants over and over again in order to just keep their labs going.  That means that reviewers who come to look at those grants spend time going into the details of a big pile of exciting applications knowing that probably they’re only going to be able to fund a small number.  

And if you were a reviewer, and you’re looking at a pile of grants and amongst them are some very solid applications from very well-established investigators who have a really amazing track record.  And then there’s another pile of new investigators you haven’t heard of who are just getting into the scientific arena, and don’t have as much preliminary data and haven’t published as much.  There is a tendency, I think, to go with the proven entities and that may mean you are missing out on the innovative stuff from the new investigators.  

To try to counter that, NIH has established a number of programs which can only be applied to if you have a slightly wacky idea.  So those include things like the Pioneer Awards, and the New Innovator Awards, and the Transformative R01 Awards.  All of those have a pretty high bar for innovation and a pretty limited requirement for preliminary data.  And they are some of the most exciting science that we are currently supporting, but it’s a small fraction of the total.  But it is an effort to try to avoid the conservatism that might otherwise become more prominent in times of difficult budget support.

Question: What are the biggest health risks facing America?

Francis Collins: If you look at health in the United States, you could point to some really significant achievements and you could also point to the role that NIH has played in making those things happen; cardiovascular disease has dropped by more than 60% in mortality over the course of the last 30 to 40 years, much of it from insights derived from groups like the Framingham Study which pointed out what the risk factors were and what we could do about them.  Cancer is dropping in its frequency, finally, after many years of going up.  

But there are clouds on the horizon of public heath, obesity and it’s related disease, diabetes, probably is the one that causes the greatest concern when you see the way in which our population is growing more overweight almost year by year with no sign that we’ve managed to turn this around.  And that could, if not somehow addressed, result in an outcome where our grandchildren will not live as long as we do and we would therefore turn down what has been upward curve in longevity over many decades.  A critical need there through research, research that involves nutrition, research that involves understanding exercise, then understand the built environment and how to motivate health behaviors to try to turn around this obesity epidemic.  

Certainly other areas of concern... Alzheimer’s Disease comes to mind as a condition which as our population is aging and as the Boomers are coming into this phase of potentially higher risk of Alzheimer’s, that we are gong to see very large numbers of people affected by this heartbreaking disease with terrible consequences for themselves and their families and for our medical economics because of the cost of caring for them.  So this has to be a very high priority for our high intensity efforts to come up with new solutions about prevention and treatment.

Question:
How much of research should be focused on prevention, as opposed to treatments and cures?


Francis Collins: NIH is intensely interested in prevention.  I think everybody would agree that we haven’t paid enough attention to this approach to maintaining health, that we’ve not had a health care system in terms of medical care—we’ve had a "sick care" system where if you get sick there might be some help for you, but there’s been relatively little invested in terms of helping people stay well.  And maybe as a part of that we’ve had modest efforts, really, to try to invest in research on prevention.  That’s all changing.  Some of that’s coming about because of a better understanding of the environment and things that people should be careful about as far as bad influences on their future health, whether it’s smoking or diet or exercise.  We’re learning a lot about that.  

And some of it is the ability through personalized medicine to begin to identify individual risks for a future illness to get us beyond the one-size fits all approach to prevention, which has been not that effective.  People haven’t necessarily warmed to these recommendations about what you should do about diet, exercise, colonoscopies, mammograms and so on because it all sounds very much generic.  

But if you could provide people with information about their personal risks and allow them therefore to come up with a personalized plan for maintaining health that seems to inspire a lot more interest.  Genomics is moving us in the direction of being able to do that and I think that’s one of the more exciting developments in the prevention arena even though it’s early days yet, to see how that’s going to play out.

Question:
How is the NIH dealing with a recent court injunction against using federal funds for embryonic stem cell research?

Francis Collins:  The injunction that insisted that federal funds could not be used for human embryonic stem cell research came as a great surprise since it was based on a new interpretation of legislative language that’s been in place for 14 years.  It absolutely cast a cold chill through the field of human embryonic stem cell research with investigators who had banked a lot of their career in working in this area suddenly questioning whether they had a career at all.  This resulted here in our intramural program, scientists who work here on this campus in Bethesda, having to close down experiments immediately.  Individuals working in universities and medical centers who had grants from NIH were able to continue with the funds they’d already received, but were not going to be able to get renewed the next time they came back for an annual renewal under the conditions of this injunction.  

And we had other grants that had already been through the first level of peer review and were poised to get funded that had to be shelved because of the terms of the injunction.  I’m pleased and reassured and encouraged to say that that has over the course of two-and-a-half very tumultuous weeks now resulted in a stay of that injunction from the Court of Appeals.  But it’s a temporary stay and we don’t know in the longer term where this might go.  

That means that the field continues to be feeling very whipsawed and uncertain about its future.  I’ve spoken to many scientists involved in human embryonic stem cell research who are quite troubled about this and who, in many instances are questioning whether this is an area that they can continue to work without feeling as if their whole program could be pulled out from under them by another event of this sort.  

The promise of human embryonic stem cell research remains somewhat uncertain.  This is a very new field, but it is potentially one of the most exciting developments in many years and to have this after many years of being slowed down by this kind of intense scrutiny and oversight, and now maybe even stopped, is troubling indeed.  And it will certainly lead to a higher proportion of this work going on in other countries in which ought to be a concern to anybody who is worried about the American leadership in science and the economic consequences that flow from that.  It’s a very uncomfortable and unstable situation right now.

Question:
What are some of the main bioethical issues with this kind of stem cell research?

Francis Collins: Well first of all, I think the bioethical considerations about deriving stem cell lines have been worked out.  These are derived from excess embryos that are obtained during in vitro fertilization and that are otherwise doomed to be discarded, and if they’re derived with full consent of the donor couple and with no financial inducements, then the general consensus is that is a legitimate way to have these lines generated and that once generated they can be used for federal funding.  That’s what the Obama Executive Order said back in March of 2009.  So that part of the process I think has been well traveled.  

Perhaps you are also asking though about the use of such stem cell lines when it comes to therapeutics.  And that really falls into the same kind of discussion you have whenever you are contemplating a new therapy that hasn’t really been done on humans before, what is the likelihood of effectiveness and what is the risk of danger of a bad outcome?  Those things, of course, have been getting debated now for several years with protocols that are proposed in the private sector and of course, the first one of those, the Geron trial for using human embryonic stem cells for spinal cord injury patients has been approved by the FDA and is about to enroll its first patients.  

So there are uncertainties there, there was a concern and there probably will be for quite a long time until we have more actual experience that human embryonic stem cells could in fact grow into tumors.  They are pluripotent which means they can make all different cell types and one of the ways you test to see if a cell line is pluripotent is that it’s capable of making tumors in an immune deficient mouse.  So that potential is there and great care has to be taken to be sure you have minimized that risk.  

But I see this very much in the long line of experiences of radically new therapies that reached the point that is it arguable appropriate to begin to try this and very carefully to find human situations with close oversight and a very rigorous informed consent so that those that are involved in the research know exactly what they are getting into and have a chance to say no if they don’t think it’s a good balance of benefits and risks.  

Question:
During your work on the human genome, you linked many genes to specific diseases. How are these links established?

Francis Collins:  It’s too bad you can’t actually see DNA easily under a microscope and scan across a double helix and read out the sequence of bases that amounts to the information content because it would be easier, I think, to explain then how a geneticist goes about tracking down the molecular basis of a disease at the molecular level.  Our methods are indirect—they’re very powerful, they’re really highly accurate, but they’re not as visual as you might like.  We do have methods though, now, that allow you to read out with high accuracy, all three billion of the letters of the DNA instruction book, those letters are actually these chemical bases.  The chemical language of a DNA is a simple one, there’s only four letters in the alphabet.  Those bases that we abbreviate A, C, G and T.  and we have methods of being able to compare then the DNA sequence of people who have a disease versus people who don’t and look for the critical differences in order to nail down something that might be the cause.  

Well since, however, we all differ in our DNA sequence by about a half of one percent, you wouldn’t get very far if you basically sequenced my DNA and the DNA of somebody with Parkinson’s Disease trying to figure out what the differences were because it would be way too many of them. But if you’re willing to do that for a large number of people, you kind of average out all the noise and the difference that matters begins to be more and more clear.  That’s an overly simplified description of how a geneticists goes about zeroing in on the actual molecular cause of a complex or a simple disease.  This works most readily for diseases that are highly heritable; cystic fibrosis, Huntington’s Disease—those are conditions where as single mutation very reproducibly results in the disease.  

It’s been a lot tougher for diseases where the inheritance is muddy.  If you take diabetes, for instance, which is what my lab primarily works on, or you take asthma or high blood pressure, that is not a set of conditions where one gene is involved in risk, there are dozens of genes involved in that and no single one of them contributes very much, but you put it all together and the consequence to that individual may tip them over the threshold into having the illness.  We’re in the throes right now trying to sort that part out for the common diseases that we know have hereditary influences because they run in families but they’re much more complicated than say, cystic fibrosis.

Question:
Was there anything that totally surprised you in your research on the genome?

Francis Collins: There were a lot of surprises a lot of times where you just marveled as what you had uncovered and felt like you must have really somehow missed it when you were making guesses about what would be there.  I guess the one that startled most us the most profoundly was how few protein coding genes there actually are in the genome.  The old paradigm about DNA-makes-RNA-makes-protein, well then a stretch of DNA is going to make a protein, how many genes does it take to specify a human being?  Hooh, you would think there would be an exorbitant number.  And various estimates have been put forward before we knew the answer that we’re in the neighborhood of 100,000 to 150,000. Ultimately, it turns out we only have about 20,000 protein coding genes.  A breathtakingly short list of instructions for an organism as complex as homo sapiens.  

There are other genes that don’t code for protein that are turning out to be pretty important, so in a certain way we’re rescuing our sense of complexity by discovering there are other categories or genes that don’t have to be of the protein coding sort, but it is still astounding to think that just 20,000 of these protein coding genes is enough to take a single cell, which we all once were and inspire this program of elaborate complex development into a human being, including a nervous which is beyond our ability at the present time to even quite contemplate because of its complexity.  

Question:
Some people have expressed disappointment that the decoding of the human genome has not yielded more. How do you feel about this?

Francis Collins: I’ve been a little disturbed about a wave of cynicism that seemed to emerge in the summer of 2010 at the time of the 10th anniversary of the original announcement of the draft sequence of the human genome.  There may have been those who claimed that that draft sequence was going to result of a complete overturning of everything in clinical medicine in the space of a year or two. But I don’t think anybody who understood the process of going from a basic discovery to clinical implications could have said those things and I certainly hope I never did.  

But 10 years after the fact it is fair to say that most of us have probably not had obvious evidence in a change in our medical care because of the fact that the genome sequence has been derived.  Certainly however, if you walk into a laboratory where people are working on any aspect of human biology, it is utterly different now because of the availability of that sequence, and graduate students cannot even imagine how anything was possible before that information was accessible with a click of a mouse.  So the scientific enterprise is revolutionized, the clinical consequences are lagging behind.  But even there, I must say, after sort of encountering some of the cynical views about the clinical benefits of genomics, I tried to sit down in a brief period and just write down the things that I thought had been significant as far as implications that were already affecting real people and it’s a long list.  More than two dozen examples came to mind in the space of about 10 minutes.  So while they are, for the most part, applied to relatively rare conditions, if you’re one of those people with those rare conditions, they’re pretty significant.

Question:
How close are we to creating personalized medicines?

Francis Collins: Personalized medicine is a term that gets used differently by different people.  In my view this is an effort to try to take diagnosis, prevention and treatment, and when possible factor into that individual information about that person in order to optimize the outcome.  I think in some instances, we’re not very far along with that and in others we’re making real progress.  

Take for instance the effort to try to choose the right drug at the right dose for the right person, what we call pharmacogenomics.  There are now more than 10% of FDA approved drugs that have some mention in the label about the importance of paying attention to genetic differences in order to optimize the outcome.  Take for instance, the drug Abacavir, which his used to treat HIV/AIDS.  A very powerful antiretroviral, but a drug that caused a pretty serious hypersensitivity reaction in about six or seven percent of those who took it.  We now know exactly how to predict that on the basis of a genetic test and so there is not what is called a "black box label" on the FDA label on this drug that says you must do that genetic test before you prescribe this drug in order to avoid that outcome.  That was unimaginable a few years ago that you would have that kind of precision in making that choice on the drug.  

Therapeutics, particularly in cancer.  We’re getting closer to the point where somebody’s tumor is going to be analyzed routinely to look for a variety of specific mutations that would predict response to one of the new targeted therapies as opposed to the broad-based chemotherapy.  Some people have compared broad-based chemotherapy to trying to turn off the lights in your kitchen by nuking your house.  The idea is to try to move more in the direction of turning off the lights by flipping the switch, and that’s what the targeted therapies are aiming to do.  And you can point to specific examples for people with lung cancer or leukemia where that is a dream that is not a pipe dream, it has come true for them and they are benefiting hugely from this kind of personalized approach to their disease.  

Unfortunately, that doesn’t work so far for the majority of cases where we haven’t yet found the Achilles' heel for the tumor to go after it or we don’t have yet the right weapon to attack the Achilles' heel that we know is there.  But it’s coming.

Question:
Why is it so difficult for scientists to believe in a higher power?

Francis Collins: Science is about trying to get rigorous answers to questions about how nature works.  And it’s a very important process that’s actually quite reliable if carried out correctly with generation of hypotheses and testing of those by accumulation of data and then drawing conclusions that are continually revisited to be sure they are right.  So if you want to answer questions about how nature works, how biology works, for instance, science is the way to get there.  Scientists believe in that they are very troubled by a suggestion that other kinds of approaches can be taken to derive truth about nature.  And some I think have seen faith as therefore a threat to the scientific method and therefore it to be resisted.  

But faith in its perspective is really asking a different set of questions.  And that’s why I don’t think there needs to be a conflict here.  The kinds of questions that faith can help one address are more in the philosophical realm.  Why are we all here?  Why is there something instead of nothing?  Is there a God?  Isn’t it clear that those aren't scientific questions and that science doesn’t have much to say about them?  But you either have to say, well those are inappropriate questions and we can’t discuss them or you have to say, we need something besides science to pursue some of the things that humans are curious about.  For me, that makes perfect sense.  But I think for many scientists, particularly for those who have seen the shrill pronouncements from extreme views that threaten what they’re doing scientifically and feel therefore they can’t really include those thoughts into their own worldview, faith can be seen as an enemy.  

And similarly, on the other side, some of my scientific colleagues who are of an atheist persuasion are sometimes using science as a club over the head of believers basically suggesting that anything that can’t be reduced to a scientific question isn’t important and just represents superstition that should be gotten rid of.  

Part of the problem is, I think the extremists have occupied the stage.  Those voices are the ones we hear.  I think most people are actually kind of comfortable with the idea that science is a reliable way to learn about nature, but it’s not the whole story and there’s a place also for religion, for faith, for theology, for philosophy.  But that harmony perspective does not get as much attention, nobody’s as interested in harmony as they are in conflict, I’m afraid.  

Question:
How has your study of genetics influenced your faith?

Francis Collins: My study of genetics certainly tells me, incontrovertibly that Darwin was right about the nature of how living things have arrived on the scene, by descent from a common ancestor under the influence of natural selection over very long periods of time.  Darwin was amazingly insightful given how limited the molecular information he had was; essentially it didn’t exist.  And now with the digital code of the DNA, we have the best possible proof of Darwin’s theory that he could have imagined.  

So that certainly tells me something about the nature of living things.  But it actually adds to my sense that this is an answer to a "how?" question and it leaves the "why?" question still hanging in the air.  

Other aspects of our universe I think also for me as for Einstein raised questions about the possibility of intelligence behind all of this.  Why is it that, for instance, that the constance that determines the behavior of matter and energy, like the gravitational constant, for instance, have precisely the value that they have to in order for there to be any complexity at all in the Universe.  That is fairly breathtaking in its lack of probability of ever having happened.  And it does make you think that a mind might have been involved in setting the stage.  At the same time that does not imply necessarily that that mind is controlling the specific manipulations of things that are going on in the natural world.  In fact, I would very much resist that idea.  I think the laws of nature potentially could be the product of a mind.  I think that’s a defensible perspective.  But once those laws are in place, then I think nature goes on and science has the chance to be able to perceive how that works and what its consequences are. 

Question:
How would it affect scientific research if more scientists believed in God?

Francis Collins: Oh actually in surveys I have seen, indicate about 40% of scientists believe in a God to whom one may pray in expectation of an answer.  That’s not a God who went off after creating a universe and did something else.  That’s a God who is interested in human beings.  Forty percent would adhere to that statement.  The numbers are smaller when you ask members of the National Academy of Sciences and there’s various reasons people have proposed why so-called, "elite" scientists have an even lower proportion of believers.  But it’s not as devastatingly absent from the scientific community as people might assume based on the fact that the pronouncements that the hear coming from scientists are usually more in the skeptical or even the atheistic perspective.  

I think whether or not scientists are believers should not have a whole lot to do with how the conduct science.  The fact that I am a believer, as far as I am aware of, has had very little influence on my scientific work.  And I think that’s important to keep that distinction.  If I am asking a scientific question, it’s the tools of the science I should be using and not assuming something supernatural happened in the test tube at that moment and that would explain my data point.  So I do think people of faith and people who don’t have faith are capable of thoughtful, ethical decision-making.  So any notion that we are becoming less ethical as scientists because of a diminution I think has to be actually countered by arguments to say that a sense of ethical behavior is not distributed to just the people who are in fact interested in spiritual matters.  

So I’m not sure.  I think it would diminish the hostilities, which are bad for our culture, if more scientists were, in fact, willing to stand up and say that faith and science need not be in conflict—because right now that’s a minority view that doesn’t get heard very much and it’s apparent to some people that we are having more of a cultural war; a war that seems to imply that some world view needs to win and some world view needs to lose.  I would not want to look forward to a culture where science lost and religious faith became the dominating force for truth.  I would not want to live in a culture where faith lost and science, with all of its reductionism and its materialism became the sole source of truth.  I think we need both kinds of truth.  I think we need both kinds of worldviews. To the extent that scientists can help with that realization of the dual ways of finding answers to the appropriate kinds of questions that each worldview can ask, then I think that would be a good thing.

Question:
What do you think of the suggestion that there is a biological component to religion and that belief is an evolutionary trait?

Francis Collins: Certainly the social biologists have put forward arguments that religion could have an evolutionary basis that we humans are designed in a certain way to look for agency behind actions that we don’t understand and that may then relate to why various cultures over time have identified something mysterious and supernatural outside of their own experience to try to explain things that didn’t otherwise have an explanation.  

I think it’s too simple to basically say, well that does it.  Either god is true or god is not true.  Either God is real or god is not real.  It’s not a matter of whether you can explain it away by hypothesis.  The question is what’s the real answer?  And I think far too few people have kind of looked at the question from that perspective.  What’s the evidence for the idea that god exists or doesn’t exist.  I think anyone who’s looked at that would conclude that the strong atheist position of saying, "I know there is not God," is not an easy one to sustain.  It basically implies a certain degree of hubris and arrogance to say that I know so much that I could exclude any possibility of there being a God.  

On the other hand, the evidence will never draw people to the conclusion of saying; I know confidently there is a God.  Maybe God didn’t intend it to be that easy.  

Question:
What is some of the most exciting research the NIH is currently working on?

Francis Collins:
We are experiencing right now a remarkable deluge of discovery in terms of the causes of disease, much of it coming out of genomics, the ability to pinpoint at the molecular level what pathway has gone awry in causing a particular medical condition.  And that in itself is exciting because it’s new information, but what you really want to do is to take that and push that forward into clinical benefit.  

Some of that could be in prevention by identifying people at highest risk and trying to be sure they are having the right preventive strategy.  But people are still gonna get sick, and so you want to come up with also, better treatments than what we have now.  How to do that has largely been left to the private sector in the past, basically private sector has made their whole business out of identifying possible ways of coming up with a therapeutic, which is often a small molecule an organic compound that would have just the right properties to improve the situation.  

In the past, those were derived rather empirically, just trying thing to see what worked and not always knowing why it worked.  More recently because we do have a better handle on what’s going on inside a cell and how a disease affects that, there are rational strategies for screening a very large library of chemical shapes trying to find the one that’s got the right properties.  This is a high throughput screening approach.  

NIH has gotten much more involved in that in the last six or seven years and many academic investigators who are really unfamiliar with these steps towards therapy have gotten pretty excited about being able to take their basic discovery and move it in the direction of a therapeutic.  But it’s a long path, it’s one thing to have a compound that works in a petri dish, that looks like it might potentially have the right properties to treat a disease.  The idea of actually giving that to a patient means you’ve got a lot more work to do in terms of testing its toxicity in an animal, its ability to be metabolized and absorbed.  All of those which are long, expensive processes.  And in that degree, that’s called ‘The Valley of Death’ and that’s where a lot of projects die.  

NIH is now pushing very hard to provide bridges across that “Valley of Death” for carefully chosen project so they don’t stop at that point.  Not that we’re competing with the private sector.  We wouldn’t undertake projects of that sort that the private sector is already going after, but for diseases that are relatively less common; the economic incentive is just not there to push these things closer to the clinic.  

So through new programs, particular one called The Cure is Acceleration Network, we are investing in that process and making it possible for academic investigators to go much further down that pipeline towards a therapeutic, and we have clinical centers scattered all over the country; about 60 of them, plus the largest of them right here at NIH with 240 research beds that are set up to do those initial clinical trials to see if the drugs work.  We built a much stronger relationship with the FDA than has ever been in place before to try to be sure there’s a synergism there between the development of these compounds and their oversight.  And we’re optimistic.  This is gonna change the paradigm in partnership with the private sector to get more effective treatments out through this pipeline and approved by the FDA and into the hands of the public even for conditions that are not that common.  

We can’t wait for the next blockbuster, there aren’t going to be very many blockbusters.  Diseases are actually being broken apart into subsets by molecular understanding, which means that the block buster model is getting less and less viable.  But if we want to see program in therapeutics, NIH has to play a larger role.  And we embrace that.  And that for me is one of my highest priorities while I am the director.


Recorded September 13, 2010
Interviewed by David Hirschman

 

Big Think Interview With Fr...

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