BAZELL: Shouldn't we look at precisely why we are here? Because, as Barry said, it's hope; it's something different. Do we have the right to expect it to be better in any way than, say, the steel industry or the oil industry?

BLOOM: It would seem to me that there is a continuity in science. Even if it's not all good. A profound testimony to science is reflected in a graph1 put out by the World Bank from the best demographic data available in the world, by the dean of arts and sciences at the University of Pennsylvania, Sam Preston. It addresses the following question: Is there a relationship between per capita income and life expectancy? It doesn't sound like a scientific question, but if you'll bear with it, I think it has a profound application to one's thinking about science. There's a set of four sweeping curves for 1990, 1960, 1930, and 1900. In life expectancy, if you took per capita income normalized to 1991 dollars, what you would find is that people with as little as $4,000 had an increase of 15 years (or approximately that) in life expectancy. So that's obvious. It says that if people are really poor, they can't buy food, they can't buy health, they can't have a decent living environment, and they are going to die young. The other half of that curve is, What happens if people had vast amounts of money, 20,000 take-home dollars purchasing power a year in 1900? They still died on average 25 years earlier than people with $4,000 income in 1990. What is it that with all the money in the world, you couldn't buy in 1900 but can buy in 1990? I would submit that a good part of that is knowledge--knowledge about health. A good part of that knowledge derives from science: antibiotics, drugs, public health, prevention of disease, ventilation, requirements for housing, occupational health. That is knowledge that you could not buy with money, and that's what science I believe has contributed to life expectancy in the modern era.

POLLACK: Barry, every one of those things you mentioned peaked before or around 1950. Name something from the second half of the 20th century which contributes to the same extent to an increase in life expectancy.

GRIFFIN: Early retirement.

BLOOM: The first real antibiotics were available in 1952. We have a lot more than penicillin now, and if you have a hospital infection in this modern world, with antibiotic resistance from many things, penicillin isn't going to get you through. We have a lot more vaccines; let me give you the numbers. Nine million kids that would have died in 1974 from vaccine-preventable diseases--when only 5 percent of the world's kids got the six vaccines--75 to 80 percent of those kids now get vaccinated, and 9 million don't die. That's knowledge.

POLLACK: You are making my argument. That is the expansion out of earlier ideas in basic science, and you're absolutely right: We should only have more of them. But I think the question we're being asked is, Will there be a qualitative new set of ideas from which applied biology and biotechnology can build, the way biotechnology is still building from the first half of the 20th century's notions of antibiotics, vaccines, public health, and clean water? Is there something out of DNA of equal power to a vaccine?

BLOOM: Sure. It's a fair question, and it's a common argument that all the ideas and fundamental advances were made in the past and now we're only cashing in on old investments in science, not the new science. Let's take the first exception. AIDS is a lethal disease; AZT came out of an ordinary drug screen, and it was pretty good, except that resistance developed quickly. We're going to have about 40 million people infected with AIDS by the end of this decade, and in the vast majority, 90 percent of whom live in developed countries, they are mostly going to die. What do we do for people here? Well, with protease inhibitors we saw the first example of rational drug design that I'm aware of: identifying a target for a drug, isolating the protein, making the crystal structure, modeling with the computer to get something that fits in the crystal structure. And then somebody--lots of somebodies--went out and made that. What's great is not that there was one drug, like penicillin, but there are eight or nine drugs, because they're all going to wear out sooner or later. That is the new paradigm. This didn't take 50 years from the idea to the product; it took more like five.

BAZELL: And you're saying, to extrapolate this, that there's going to be lots of those in the next years.

BLOOM: There's going to be enough to make it wonderful, and an awful lot are never going to make it.

BAZELL: But the premise of this entire industry is exactly that: that all these targets can be so significant that they can be exploited.

GRIFFIN: I think there will be fragmentation. There's a vaccination policy to vaccinate the whole of the population, for example, against poliomyelitis. I come from a period in the U.K. where I benefited directly from that, and I had relatives that did suffer from polio, and it was an awful disease. I don't think we're going to see anything as quite as dramatic or radical as that unless we get new diseases. I think there will be a fragmentation of the effort in biotechnology across a wide range of different issues, from environmental pollution through better veterinary care through treatment of very specific diseases. One of the problems that will have to be addressed is that if the market is fragmented into smaller sections, is there enough finance there available for companies to pursue relatively small markets? There are schemes by which, for example, drug companies or the first producers of products will get Orphan Drug status, and that benefits their position financially. In the Third World, perhaps it should be part of the aid programs to address issues which are relevant to people [there]. But the technology tends to be expensive, and we will have to find different ways of financing it with relatively small markets for each segment.

POLLACK: Since you talk about financing, and since I find Barry's answer compelling, I guess it makes me wonder whether we can, as a country, continue on what I see as two divergent paths. To the extent Barry is correct, and this technology throws off novel pharmaceutical interventions which could have not existed by a random walk but required a logical database of 3-dimensional crystalline structure of proteins--when that happens in a country where one person in seven has no medical insurance and no access to any medical diagnostic or treatment facilities, except in an emergency or in a prison--at what point does the corporate world that produces those compounds have some obligation to help move the politics of the country to a place where everyone has roughly equal access, depending on their need for these kinds of compounds?

Right now, in a sense, the greater the success, the more the class difference between those who can buy and those who cannot buy makes this country look quite irrational in its investment policy. What is the point of not at some point having medical care be in some way a right, as it is in the U.K. and in most of the industrialized world, so that the fruits of this product are seen as available by right--even if that were to perturb the market that right now drives the production of these compounds?

BAZELL: Isn't that just a socialistic argument, that everybody should be for free medical care, or even access to medical care? What's that got to do with biotechnology?

BLOOM: It's going to be a roundabout answer, but I will give it the following try. We are dealing with diagnostics and cures for diseases. That is why I went into biomedical research: I cared about understanding diseases and finding interventions to treat them. I think we're in a new paradigm shift--prevention of disease; I hope biotechnology helps in that. I think we're going to come reasonably close in the next decade or two to how long people can live, functionally and usefully. And I gave you some figures on life expectancy; I would be able to give you some more on the equity question that Bob raised, if you wished. But I think that's not where we are going. I think we are going to a different world where life expectancy is not the measure, and I point out to you that in the health statistics in the United States, up until two years ago, the only index of health was how long you lived. Whether you were unable to function, in mortal pain, and destitute, was not part of those figures.

What one wants to do, and it seems to me the object of this paradigm shift basically is to prevent disease and disability to keep people alive, well, and functional to the day before they die. That is a paradigm shift, and when Bob talks about boutique medicine, I think that is correct; that is how we do it, and there will be an extent to which we'll have to do it. But there are also possibilities for prevention, and I'd to give you one, which again he alluded to. I think it's a profound change, and I confess the media has not missed it. It's a drug called tamoxifen. We all know tamoxifen as an inhibitor of the estrogen receptor, which is a major treatment in breast cancer. But if you remember about two months ago in the newspapers there was a study indicating that people who had high risk but not breast cancer were treated with this drug, which was invented as a curative drug.

BAZELL: It was actually invented as a birth control pill by the company that is now Zeneca, and this is an interesting saga. It was a lousy birth control pill; in fact, it caused multiple births, and it was put on the shelf. A guy named Arthur Walpole saw its potential, and he had a young graduate student at the University of Leeds named Craig Jordan. He thought about the breast cancer problem and he said to Jordan, "Well, why don't you look at this as a potential for treating breast cancer?" and he used mammary cancer in rats as a model. So continue with your story.

BLOOM: In any case, what the article in the Times did was to show that this is now the first new cancer preventive that I'm aware of. If you talk to Harold Varmus, director at NIH, he will tell you it's not a fluke. There are 70 trials now using anti-cancer drugs to prevent cancer at high risk. Then, how do you make new drugs, derivatives of drugs? I will tell you that combinatorial chemistry, which is related to biotechnology, is a way to make 50,000 compounds a week in a small one-floor biotech rented space in Cambridge or in Palo Alto--

POLLACK: Or Washington Heights.

BLOOM: Washington Heights, even. Whereas it would be five years before a major pharmaceutical company 10 years ago could make 50,000 derivatives of a lead-off compound that might work. I think that what we're seeing now is potentially a shift--one that could not be done by old-fashioned random screening--to create things that say, "We know what the tumor suppressor gene that's mutated in this kind of cancer; we can now make a crystal and design a drug." And not just give it to people with cancer and make a lot of money. If you had your genome analyzed to see that you had the wrong p53 mutations, would you pay to have a drug to prevent colon cancer, even though it won't work 100 percent of the time? And you might never get colon cancer? I sure as hell would.

BAZELL: Well, that wasn't missed. Eli Lilly then made a derivative drug, raloxifene. These drugs are called selective estrogen receptor inhibitors; there are probably about 30 of them in the pipeline because of the tamoxifen success. What's interesting is that so far the market hasn't been there as a preventive. Tamoxifen has some side effects that causes some increases in uterine cancer and blood clots in the veins; raloxifene hasn't been tested long enough, and neither one is a treatment for osteoporosis. But that particular area, understanding the estrogen receptor in all its ways and turning out molecules, has been one of the most exciting areas of biotechnology, and we include in biotechnology big drug companies adopting the technology that we ascribe to small companies as well.

POLLACK: I think that's a comprehensive and good counter example. My contribution to this discussion, then, remains the wish to set a frame around such a positive answer, and that frame, I would argue, is political. It is a matter of equity. It's a matter of boundary conditions so that when we know from the data Barry speaks of that there is an interventionary preventive way to keep tens of thousands of cancers from ever appearing, and the market does not see that as a thing to go for, nevertheless that's available. Now that is, you can say, socialism. Well, in this country, when you count federal, state, local employees, and the military, and veterans, half the people are on government medical insurance anyway. It's the other half that includes the one in seven that don't have anything. It's a crazy and irrational situation, and it prevents rational politics from accompanying rational drug design. A national DNA databank, to contain the kind of information you need to know whether you are eligible for such a drug, makes no sense when there's no national health service. So I would agree with you; I hope you're right. I hope to see how Varmus' combinametrics produced a thousand drugs. But we as a society are not prepared to distribute them equitably by biotechnology.

1. World Bank: World Development Report 1993: Investing in Health. NY: Oxford University Press, 1993. Figure 1.9. Adapted from Preston SH, Keyfitz N, Schoen R: Causes of Death: Life Tables for National Populations. NY: Seminar Press, 1972.

Photo Credits:
Chart: World Bank1, adapted by Howard Roberts; crowd; Photos Etc; stock photo: Crowd/Photos Etc.
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