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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.

Recorded September 13, 2010
Interviewed by David Hirschman

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