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SHARP: I’m enough of a realist to know that in the private sector, if you can’t develop the revenues to support the technology, the technology is not going to grow. Second, you really don’t bring technology to fruition, in this country and almost anywhere in the world, unless the private sector does it-because it is so difficult in large, federally sponsored programs to have the focus, the sustained attack that you need to develop a new pharmaceutical.

Those are constraints of the real world. There is, on the other hand, a significant amount of research being done on worldwide infectious disease problems. I suspect that commitment will grow as we increasingly learn that these diseases are very transportable. As people travel in various parts of the world and come home with the “local disease,” the U.S. medical community is going to need to be able to treat them, both here and at the source, in order to control those diseases, and that in time will bring benefits.

Let me add a third point. In a recent issue of Nature, the British scientist Max Perutz wrote an article in which he showed that the fraction of gross domestic product being spent on biomedical research grew 10 times in the United States over the last 15 years, while growing only twofold in England and the other European countries. We have the biggest gross domestic product, and we are really dominating the biomedical research community. And as the world leaders, I think we would benefit-and benefit the world-by extending our interests a little more globally. In addition to helping people in developing places for humanitarian reasons, there are good pragmatic reasons that the government should encourage international collaborations, investments in problems and people elsewhere in the world to augment this leadership position we have. But if anything, as we’ve gotten more successful as a scientific community and as a pharmaceutical community, we’ve become more inward-looking.

TR: Given the biotech industry’s historic tendency to oversell a new technology, could you provide some perspective on two of the most highly publicized recent developments, gene therapy and anti-angiogenesis as a treatment for cancer?

SHARP: I’m still very optimistic that gene therapy will emerge as a therapeutic. But it’s going to take a while to learn how to use it in a clinically important way. Throwing a few genes into a patient and saying that’s going to help a cancer has just not been very useful.

But there is serious work going on. I expect the first applications to emerge as vaccines, where delivering a vaccine by DNA is liable to be more efficacious than by conventional ways, and safer. That could play a role in the HIV story. And I also think that as we become capable of regulating gene activity as well as inserting genes, we’re going to see gene therapy used with therapeutic genes. In other words, you’ll be able to insert the gene for erythropoietin, which tells the body to make red blood cells, into the appropriate cells of a patient. And once these cells take up the gene and aren’t rejected, you can essentially turn the gene on and off over long periods of time, producing a source of therapeutic protein that controls a disease state.

As for angiogenesis, my guess is that we’re going to find that it’s going to take four, five, maybe 10 years in the clinic to learn how to use this. And even with well-controlled experiments, you’re going to step back and scratch your head and say, “Why didn’t that work?!?” Or, “Why didn’t it work better?” You know, like everybody else, I’d love to have it available today. But these are complicated biological processes.

TR: Do you see any danger of a public backlash against biology because of the promise of success-the familiar drumbeat of hype which creates the expectation that some newly discovered drug or process is going to cure disease?

SHARP: I don’t underestimate the intelligence of the public. I come from Kentucky, and not from an academic family. My father was a manual laborer. I keep in pretty close contact with that community, and they understand now, given 20 years of intense press coverage of science, that there is always a time between discovery and delivery.

But they also, and this is very important to point out, hope that the world in the future will be better than the world in the past. And if they can’t benefit from a drug, they certainly would like to see somebody else ultimately benefit from the drug. The promise that progress is being made-and historically, progress has been made-is something that they enjoy, appreciate and are interested in learning about. So they can dream of the day when they don’t have loved ones who died of cancer. It’s not going to hurt them.

It’s not clear we will get there. We can’t say from our technology that we’re going to get there. All we can say is that we’re making incremental improvements, and we would hope-and underline “hope”-that we’ll get better at that.

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