By CRG staff - interview with James Evans

James EvansDr. James Evans, MD, PhD, is Bryson Distinguished Professor of Genetics and Medicine at the University of North Carolina School of Medicine. He co-authored an article appearing in a February issue of Science (vol. 331), titled "Deflating the Genomic Bubble," warning against perpetrating unrealistic expectations of genetic research.

What sort of response have you been getting to the Science article?

It's interesting: I've received a number of emails-especially from social scientists, people who study behavior and some epidemiology people-that were very laudatory in their response. I have not had a lot of reaction from the genetics and genomics community, and can't really say why that is.

I must admit that I was frankly a bit nervous about publishing this. What I worry about is that our message will be misconstrued as some kind of call to gut genomics research. That's not at all what we were trying to do. I hasten to add that I have not heard that response; but it worried me, and still does to some extent.

The reason I went ahead and published it is that I feel that in the end, we really are all in the same business: we want to decrease human suffering and disease. I think what that mandates is that regardless of your particular turf, one has to try to be logical and fair as we think about allocating resources.

The real impetus for this article came when I was at a public health and genomics meeting in England this spring, and one of the presenters put a slide up that was from a Science paper several years ago by Walter Willit. It was just a simple bar graph demonstrating the large attributable component of most common diseases in the U.S. to behavior. It is absolutely striking how important behavior is. And I got to thinking: I'm a huge believer in genomics. I'm a huge booster of genomics and genomic research, and I firmly support the investment that's being made in genomics. But I do think that if our ultimate goal is to reduce disease, we need to be doing more with regard to behavioral research, because human behavior accounts for so much human suffering.

Is the emphasis on genomics partly a matter of researchers talking up their own research?

Sure, and we explore that to some extent in our piece. I think there are many things that contribute to, I guess it's fair to say, overly optimistic expectations. And I think it's fair to include the natural and understandable enthusiasm of the "converted," of scientists working on a particular problem. I mean, we go into a field because we love it. Of course we're enthusiastic!

Secondly, there are certainly tremendous pressures in regard to promotion and career advancement that make one want to talk up one's field. The press is also certainly complicit, because they want breakthroughs; they want someone to say "This is the greatest thing since sliced bread!" as opposed to, perhaps, people who take a more sober and realistic attitude.

And I think, finally, part of the blame rests at the feet of the poor scientific literacy and understanding of the general public. People do not understand-and we don't do a good enough job of emphasizing-the incremental nature of science; the fact that something like the human genome project, while it will pay tremendous dividends, is simply going to take a long time to pay off in dramatic terms. People don't have a good understanding of the way science works, and I think that also contributes to misinterpretations.

Can you think of any especially egregious overstatements, in genomics or more generally?

Generally, a really nice example of this is gene therapy. When I was a genetic fellow, one saw rampant predictions about how gene therapy was going to revolutionize the treatment of human disease. Predictably, that did not occur. We are now beginning to see real glimmers of utility and hope for its application, but it was really rather predictable that it was going to take a long time and wasn't going to revolutionize medicine overnight.

You have to navigate a responsible middle ground. You have to advocate the fact that these advances are going to be important; they are ultimately going to be of benefit, but that we shouldn't expect them to be revolutionary in the short term.

There are very few technologies that are truly revolutionary in the near-term. Going back to 1895, when Wilhelm Röntgen discovered X-rays, that had immediate revolutionary and practical benefits in medicine. And the discovery of antibiotics-well, the discovery of antibiotics in some ways actually makes my point. When Alexander Fleming discovered penicillin, it was many years before that discovery in the Petri dish on his windowsill actually became practical in its application.

Science is incremental. It's slow. And if we fail to recognize that, we run the risk of a backlash that not only disappoints people, but hurts our field in the long run.

There has been an upswing in talk about advancements in genomics because of the ten year anniversary of sequencing the human genome. Are there any big successes from the human genome project with near-term benefits that you think are worth talking about?

I think that there are near-term benefits, as we articulate in the article. Firstly, we are already beginning to see certain specific applications in the realm of pharmacogenomics that will improve medical treatment. And that's a big deal. As we say, pharmacogenomics is not going to guide the use of every drug, but is going to be a near-term success with some.

Number two, I think that the tailoring of cancer therapy based on tumor expression and mutational analysis will likely be a near-term success. We're already seeing some clinical utility to such expression analyses, and that was certainly an outgrowth of the genome project.

Also, I'm quite convinced that diagnosis of genetic disease-which, while individually rare, are not trivial in aggregate-will be revolutionized in the near term by things like next generation sequencing.

Where I think the hype is just that, and not justified, is in claims that fine-tuning an individual's risk for common diseases will be clinically meaningful. I think this has been grossly exaggerated and is basically based on a naïve view of how clinical medicine works. Fine-tuning individuals' risk for common disease based on genetics is unlikely to be significant for their care.

And I think that while the application of next generation sequencing technology will be extremely important for the diagnosis of genetic disease, I doubt that sequencing technology will greatly advance our treatment and our management of common diseases anytime soon, for the very simple reason that common diseases have many etiologies of which genetics is only one, usually fairly minor, component.

You mention in the article the need to revisit funding priorities. How imbalanced, currently, is funding for genomics versus, say, behavioral research?

As a geneticist, as a scientist, and as a doctor, what I would argue to the people who make those funding decisions is that we should not cannibalize one particular field-especially one like genomics, that is promising and in which great progress is being made. We need to expand the pie instead of cutting it up more finely, and it seems to me that we definitely need to support behavioral research so we can figure out better ways of changing human behavior, which is so important in disease.

I can't really give you a quantitative figure for what the proportions should be, but my bottom line would be that behavioral research demands more investment. I would also add that we can't rigidly tie funding of scientific endeavors to some simple equation that, for example, correlates directly with burden of disease; science is always a question of what is doable and what is tractable. While there are questions that we may want to answer, the reality is that there is only a subset of questions we can answer, and we do need to address those.

Science is quirky and idiosyncratic in its trajectory. We have to be cognizant of that, and that's why it is very important for the public to understand that we do need to fund things that don't necessarily have immediate, obvious benefits. We can't go the other way, either, and not pay sufficient attention to where our major practical problems lie. It's a very nuanced set of decisions, and unfortunately, with the current state of science literacy in the population and probably in policy circles, I think nuanced decisions like that are difficult.

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