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A Decade on, Human Genome Research Yet to Directly Affect Many Patients

June 24, 2010 at 12:00 AM EST
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Ten years after the cracking of the human genetic code, Jeffrey Brown talks to a scientist about advancements and setbacks in using the research to pinpoint the causes of illnesses and craft individualized therapies.
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JEFFREY BROWN: And finally tonight: the impact of a revolution in genetic science. It was 10 years ago this week that researchers mapped out the basic sequence of the human genome, a working blueprint for human life comprised of the three billion pairs of DNA in the cells of our body. It was a heady time then, the reality now a bit more sobering.

FORMER U.S. PRESIDENT BILL CLINTON: With this profound new knowledge, humankind is on the verge of gaining immense new power to heal.

JEFFREY BROWN: It was a landmark moment in science celebrated at the White House in 2000: the decoding of the first draft of the human genome, the cracking of the genetic code.

BILL CLINTON: Genome science will have a real impact on all our lives and even more on the lives of our children. It will revolutionize the diagnosis, prevention, and treatment of most, if not a all, human diseases.

JEFFREY BROWN: The project, completed simultaneously in both the public and private sectors, raised the prospect of pinpointing the root causes of illnesses, eventually leading to so-called designer drugs and other therapies.

The decade since has seen a number of advances, and hundreds of sites on the human genome have been linked with diseases, including various kinds of cancer. But developing cures has proven difficult, and some researchers now believe that genetic mutations, or changes in our DNA, may not have a direct cause-and-effect relationship with disease.

I talked about all this recently with one of the leaders of the original decoding effort, Dr. Francis Collins, then head of the government’s Human Genome Project. He’s now director of the National Institutes of Health.

Francis Collins, welcome.

DR. FRANCIS COLLINS, director, National Institutes of Health: Nice to be with you.

JEFFREY BROWN: So, 10 years later, give me an overview. How far have we come?

FRANCIS COLLINS: We have learned a prodigious amount about our own DNA instruction book, the human genome, after revealing in draft form in 2000, getting a completed form in 2003, and then applying some of the best and brightest minds on the planet to try to figure out how it works.

We know about the variation in the genome, that half-a-percent that makes you different from me. We have cataloged most of that.

JEFFREY BROWN: Half-a-percent?

FRANCIS COLLINS: Half-a-percent, that’s all. And we have actually learned how a lot of those variations play a role in risks of disease, almost 1,000 of them that you can pinpoint and say, that one increases your diabetes risk. That one increases your cancer risk. The risks are modest, but those are really important insights.

JEFFREY BROWN: Let’s try to break it down a little bit. You — you wrote in a recent article, “Genome research has already had a profound impact on scientific progress.”

Now, what does that mean? In what ways?

FRANCIS COLLINS: A graduate student working in biology today cannot imagine how you did research without having access to the sequence of the human genome. It is so fundamental. It’s something you’re looking at on your computer many times a day to guide your experiments.

It is just the foundation of everything we do. And we have that information now. So, for a scientist, this is incredibly empowering.

JEFFREY BROWN: In what way? Give me an example.

FRANCIS COLLINS: OK.

Well, let’s suppose I’m interested in trying to understand autism. We know that autism has hereditary contributions. If a family has a child with that disease, the risk that the next child will have it goes up by almost a factor of 100. So, there’s something really significant going on there.

But how would you approach that? Without having the genome to sift through, to look for those places that might correlate with the illness, you really couldn’t even start to ask that question. Now, with sequencing technologies that allow you to sequence an entire genome for $10,000 in less than a week, you can really begin to see what’s there.

JEFFREY BROWN: But, in the same recent article, you wrote, “But it’s fair to say that the Human Genome Project has not yet directly affected the health care of most individuals.”

Why not?

FRANCIS COLLINS: Most of us, going to our regular physician, have not yet had the experience of having a recommendation placed in front of us that’s a direct consequence of the Genome Project, although some people have. If you’re somebody with a strong history of breast cancer or colon cancer, you probably have had an impact as a result of this.

But that’s coming. And, frankly, I think predictions made in 2000 that that was going to happen overnight were probably not very realistic. I hope I didn’t make too many of those. I think there were some expectations, though, on the part of the public, and maybe revved up a bit by efforts in the private sector in a few places to try to improve stock values that made it sound as if it was going to be so easy now; as soon as we have got the genome, we will cure everything next week.

JEFFREY BROWN: As I read the literature, as I read reports about this, there’s some sense of disappointment about being able to translate the scientific advances into clinical advances.

FRANCIS COLLINS: Well, I understand that impatience. But this is a long and complicated pathway, especially if you’re talking about therapeutics.

It’s one thing to scan through the genome and identify a pathway that seems to be involved in cancer. It’s another to take that information and come up with a magic bullet that you could give to a patient with leukemia or lung cancer to try to turn that around.

JEFFREY BROWN: What did you and others not quite grasp or understand in terms of how complex this or difficult this would all be?

FRANCIS COLLINS: I think we underestimated the contribution of the parts of the genome that don’t code for protein. And the part that codes for protein is only about 1.5 percent, and we figured, if we understood that part, then we would be very far along in understanding risks of disease.

It turns out, the other 98.5 percent is incredibly complicated, but incredibly important in terms of the way it regulates how those genes function. And we probably should have known that there must be a lot going on there.

JEFFREY BROWN: Well, so, what’s next? Do you want to try to predict the next 10 years…

FRANCIS COLLINS: I will try.

JEFFREY BROWN: … in terms of making those clinical advances?

FRANCIS COLLINS: We are still not able to identify the heritability for common diseases like diabetes and heart disease in its entirety. We have now identified a lot of interesting pointers to that. But there’s some missing parts here.

The dark matter of the genome, as people refer to it, is still dark matter. We haven’t discovered what is the cause of those risks. If we could do that in the next three to five years, now that we can sequence an entire human genome so quickly, and we can do so many of them, I think that will greatly increase the ability to make accurate predictions about individual risks for the future.

So, that’s going to be a growing area over the next 10 years. More and more people will have their genomes sequenced, placed in their medical record, have that information available to predict what they might be at risk for and what they can do about it.

On top of that, that same information will be very valuable for individual choices about what drug is going to work for you if you need one for an illness, this variability in drug response. A lot of that comes from your genome. We are learning a lot about that. There are already about 10 percent of drug for which we have good evidence that using genetic information will result in a better outcome.

The longest term, but probably the most significant, will be the development of these completely new therapeutics. And that’s probably for many diseases another 10 years off. For cancer, for heart disease, for Alzheimer’s disease, for Parkinson’s, it’s going to take a little longer because of those long steps of going from discovery, to an idea about a compound that might work, to animal testing, to clinical trials, to approval.

JEFFREY BROWN: How close are we to where this is just sort of the norm for people for affordable, readily available, personal genome sequencing?

FRANCIS COLLINS: Well, the technology for sequencing DNA has just been moving forward at a remarkable pace.

People often talk about Moore’s law for computers as an example of an unbelievable pace of acceleration, where computer power gets better by a factor of two every two years. DNA sequencing is going much faster than that. We now can see, within three to four years, the reality that your complete genome can be sequenced for less than $1,000.

That will become, then, a very appealing opportunity, because it is your genome. It’s not going to change. For the most part, it is what it is. So, why not get that information once and for all, do it accurately, put it into your medical record, and then begin to utilize that for a host of decisions about your medical care?

JEFFREY BROWN: Of course, that will also raise questions you were talking about 10 years ago about the — about privacy issues, about what we even do with all this information once we have it.

FRANCIS COLLINS: Interpretation is going to be a moving target. If I gave you your complete genome sequence today, would you know exactly what to make of it? Well, you would have some ideas, but a lot of it would still be pretty foggy.

It’s going to get stronger over the course of time, which is to say that all of us, once we have our genome sequenced, are going to want to be connected with the process of interpretation, which is going to get gradually better over time, so that if somebody makes a discovery that happens to be relevant to you, you learn about it.

JEFFREY BROWN: Francis Collins, thanks for talking to us.

FRANCIS COLLINS: Great to be here.