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Reflections On Human Genome Project A Decade Later: NIH Director Visits KC

http://stream.publicbroadcasting.net/production/mp3/kcur/local-kcur-913528.mp3

Kansas City, MO – Researchers, drug makers and regulators convened in Kansas City earlier this week to address some of the challenges of developing new cancer therapies. National Institutes of Health Director, Francis Collins, was among the featured participants. Though Dr. Collins now manages the world's largest source of biomedical research funding, he's also widely noted for having led the Human Genome Project, which successfully mapped out the entire human DNA.

KCUR's Elana Gordon caught up with Dr. Collins just outside the conference to discuss how science has been impacted by an increased knowledge of the human genome since it was first sequenced a decade ago.

Extended Interview:

GORDON: In a recent article you described it [the impact of the human genome project] as an 'epic drama.' I'm wondering if there's more hype than what's developed. What are your thoughts on this?

COLLINS: Oh I think it's been a fundamental translational revolution in our understanding of how life works. We've actually been able to read the script for biology - both other organisms and ourselves. And it's completely changed our view of how the cell is able to do what it does. And so in that regard, it's certainly been anything but a disappointment. It's been a revolution. Students today can't imagine how we did medical research without having the human genome to guide that effort. In terms of its medical benefits, those were predicted to come along more slowly, except for a few overblown predictions that were made right at the time of the genome announcement. And they are coming along, but it is a long slog to go from uncovering a genetic variant that you know is associated with a risk for diabetes or Alzheimer's disease and then turning that into an actual preventive or therapeutic measure. The genome project sped up the discovery of new targets, but it didn't necessarily speed up the subsequent steps of getting that all the way through the regulatory process and approved as part of the practice of medicine. Today at this meeting here in Kansas City, we're talking about how to speed up those other steps, too, by new partnerships between government, academia, and the private sector.

GORDON: What do you mean by targets?

COLLINS: Well if you want to make a drug for cancer or heart disease or diabetes, you want to know what that drug should go after, what step in biology is it supposed to effect. That really is 'what's the target.' Because drugs are essentially shapes. Small chemicals. They need to bind to something. Whatever it binds to, that's the target. And so if you're trying to develop a drug for cancer, you want to know what would be the right thing to target it toward. You want to know what's wrong in the cancer cell. Genomics is teaching us those things in a much more rapid way than we were able to in the past - in a more comprehensive way. But it doesn't mean that knowing the target means that you have the answer about what to do about it. That's the long, slow, painful, failure-prone process that needs now to be optimized.

GORDON: What are your hopes or predictions for the coming decade?

COLLINS: Science is moving so fast right now that it's somewhat risky to make predictions more than sort of a month or two ahead. Ten years is a stretch, but I do believe in the next ten years we will build upon this foundation of information about the basic causes of disease, which are pouring out of laboratories right now, and bring that to the bedside in terms of new treatments for cancer, for heart disease, for diabetes, for mental illness. And I think we will also come up with better means of prevention, and prevention that's individualized instead of one size fits all.

GORDON: Biggest frustrations with genetic research?

Oh my frustration is the impatience part. I just want it to go faster. And yet research, if you're doing anything interesting, your experiments fail a lot of the time. Your hypotheses are wrong. You go down a pathway thinking it's the answer and then you hit a dead end and realize you have to recoup and back up. That's the nature of science. I'm not sure that's well understood. It's not turning a crank. It's not like you have a linear pathway from A to B and you just have to walk that path and you'll get there. There are all these branching decision points that you have to use your best data, your best intuition. And you have to convince really smart people to come and work on those problems, many of whom could probably be better off financially if they did something else. Cause science is not all that profitable for most of us who do it. But the payoff - to learn something that wasn't known before by anyone and then to see that applied for the benefit of human health, to reduce suffering, to prevent deaths that otherwise would occur needlessly, that makes it all worthwhile.

GORDON: Recently, the National Institutes of Health rejected the use of several stem cell lines. And when President Obama came into office he talked about lifting several restrictions that had been on this research from the previous administration. So, in establishing these new restrictions, why? Many researchers are saying that this is creating a lot of barriers.

COLLINS: President Obama I think wisely concluded that it was appropriate to lift the barriers that had prevented federal funds from being used for human embryonic stem cell lines that had been developed after August of 2001 and charged the NIH with coming up with specifics about how to review new stem cell lines to see if they could be approved. That we did after much public comment. And that we have used now to approve 75 human embryonic stem cell lines just in the last few months that are now available for use with federal funds. There was this set of lines that recently came forward for approval. The problem was the informed consent that had been used with the donors who donated those particular embryos for the development of stem cell lines, did not measure up to federal standards for what informed consent should say. So although it was very painful not to approve those lines because they probably could have been quite useful scientifically, we didn't see how we could violate our own ethical standards in this instance and approve lines where the informed consent basically fell short.

GORDON: It seems that science and religion can be at odds with one another. You've spoken and written a lot about your own religious background [as an Evangelical Christian] - how do you reconcile that with being a scientist and being so focused on the natural world and natural explanations? How do you reconcile that with spirituality?

COLLINS: Science is the best way, maybe the only way, to ask questions about the natural world and get answers that you can trust. Science has been very successful in that regard. But is that all that we care about? Science is pretty much powerless to answer some other large questions like why are we all here anyway, and what was there before there was a universe and is there a God. If you think those are interesting questions, then you have to have some other way of approaching them. And that's where spirituality and faith come in. I find no conflict between a person who when asking a question about the natural world, insists on scientific data before accepting the conclusion. And also being a person of faith, I think if God intended to have this amazingly complicated universe and even to have it result in creatures like ourselves and used natural processes to make it so, who are we to say that wasn't pretty elegant? It's amazing.

GORDON: Is there any particular research going on right now, some specific study, that you have your eye on and think is just fascinating?

COLLINS: I guess I'd have to point to this new development in stem cells called induced pluripotent stem cells, or IPS cells, where you can take a skin cell from an individual and by just putting four specific genes into it, convince that cell to become pluripotent - that is, capable of turning into virtually any other cell that person might need - a liver cell, a muscle cell, a brain cell. This, if we can move it to the point of clinical applications is enormously exciting because it would get beyond the problem of transplantation rejections. Because it would be your cells engineered to be the kind of cells you need at that point if you had liver failure or diabetes or Parkinson disease or spinal chord injury - that could be brought to help you. I don't know whether that will work. There're all kinds of issues to deal with as far as effectiveness and even risks of toxicity. But this is probably one of the most exciting scientific developments in the last two or three years, and it was utterly unanticipated. People just didn't believe that our cells had that kind of plasticity.

GORDON: Dr. Francis Collins, Director of the National Institutes of Health, thanks for speaking with me.

COLLINS: Thanks, it's been a pleasure.

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