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I N T E R V I E W :
B A L T I M O R E & C U L L I T O N
16 May 2006
Science For Life: A Conversation With
Nobel Laureate David Baltimore
The biotechnology revolution and what innovation means to
science, health, and the economy.
by Barbara J. Culliton
ABSTRACT:
As a man with equal interests in science and science policy, David Baltimore has been at the forefront of many of the important debates that have shaped science since the 1970s. Very much engaged in the initial discussions about the use of recombinant DNA technology, Baltimore had a front-row seat as the biotechnology industry developed. He was also a major player in the decision that resulted in funding of the Human Genome Project by the National Institutes of Health (NIH). Baltimore discusses biotechnology, science education, and the need for a strong dialogue among scientists and scholars in the health policy community. [Health Affairs 25 (2006): w235–w240 (published online 16 May 2006; 10.1377/hlthaff.25.w235)]
Barbara Culliton: As you know, Health Affairs, which has been published for a quarter-century, devotes most of its coverage to papers in health policy and health services research. We think that it would be useful to create a dialogue between the health policy community and the leaders of the world in which you live—namely, biomedical and biotechnology research—where the policy concerns have a slightly different focus.
David Baltimore: That is an excellent idea. The two worlds do, in fact, have different goals, but they are not antithetical, and a dialogue could be very useful for research, medicine, and policy in the future.
Role Of The NIH
Culliton: We are all familiar with the role that the National Institutes of Health [NIH] plays in supporting basic biomedical research. Do you think that the new NIH Roadmap or, in general, the way in which NIH is making funding decisions is sound? Are there priorities you would add or change?
Baltimore: NIH is a huge enterprise. Only a rare person, aside from insiders, ever spent the time to really analyze its grant portfolio. The roadmap is an attempt to develop new funding priorities that cut across the institutes. The fragmented nature of NIH, with some twenty-five-odd separate institutes and centers, has made central planning difficult. As NIH director, Dr. [Elias] Zerhouni deserves credit for trying to develop funding themes. The particular themes—translational research in particular—are important ones. But I have no idea how this is working in practice.
Culliton: A good deal of NIH funding is decided by peer-review panels. Does this system foster innovative science?
Baltimore: Peer review is the only reliable way to judge science and, therefore, grant applications. Unfortunately, in tight times, peer reviewers become conservative, and bold science often suffers.
Conflict Of Interest
Culliton: I want to talk in some detail about the biotechnology industry, but first I’d like to broach the issue of conflict of interest that can arise when academic researchers work with colleagues in the private sector. Most universities today have conflict-of-interest policies. Have you instituted any special policies since you became president of Caltech? Do you see any new types of problems in the future?
Baltimore: This can be a sticky area, but I think most universities have handled it well. The major conflicts relate not to basic research but to clinical research. There, avoiding conflict is especially important because the health and well-being of patients is involved. We have not instituted new policies at Caltech, but we do monitor the situation closely.
Development Of Biotechnology
Culliton: During the past thirty years, since the biotechnology industry was “invented,” biotech has played an increasingly important role in research and medicine. You were there when what we now call biotechnology was invented. What were the most important elements to its development?
Baltimore: The major element was pregnant science—science ready to make a contribution to medicine but not yet exploited by the pharmaceutical industry. The second, related, element was the pharmaceutical industry, asleep at the wheel, unable to understand the profound opportunities provided by molecular biology and, therefore, unable to take advantage of them. In fact, the pharmaceutical companies were initially blind to the biotechnology revolution because drug companies were so based on making small-molecule drugs by traditional chemical means. The third was a developed venture capital industry, ready to fund the exploitation of the science in the emerging biotechnology sector. And the fourth was a cadre of highly trained people who could be the human capital of this nascent industry.
Culliton: Researchers in the biotech industry have developed some very useful and, in some cases, very expensive drugs. Can you say something about how these drugs differ from what we think of as traditional pharmaceuticals and about their importance to special groups of patients?
Baltimore: The biotech industry today does all types of drug development, but the classic companies early on focused on biologics: proteins that can provide therapeutic benefit. The pharmaceutical industry was really chemically based, with insulin being one of the few biologics made by a pharmaceutical company.
The examples of biotech drugs are well known: erythropoietin to stimulate red blood cell production and cure anemia; interferon to treat cancer, infectious diseases, and multiple sclerosis; Ceredase to reverse an inherited enzyme deficiency; monoclonal antibodies to fight cancer through various routes; humanized insulin to replace the animal insulin originally used; growth hormone to treat growth deficiency; and anti-inflammatory proteins to counteract arthritis and psoriasis. These are all now basic tools in the modern fight against disease.
Calculating Costs And Benefits
Culliton: So, some of these drugs really prolong life, and others add significant quality of life. That matters a lot to individual patients and their families. Some economists argue that there is an important issue here regarding cost. These drugs are expensive and tend to serve a relatively small population of patients. Is it worth it?
Baltimore: Yes, it is. There’s no way to do the calculus, but the value is real. The problem is this: If a drug has a clear benefit, even if that benefit is relatively short-lived, people will want it. And they have every reason to want it. The more difficult issue is something that has benefit for only a small fraction of the public. For example, there is now a new class of anticancer agents that in some patients produce remarkable results—really, the next best thing to cures—for diseases for which we have no good treatment. At this point, the benefit is often short-lived, measured in months to a year or two. Should everybody be paying whatever the cost is—enormous amounts of money—to get this stuff? Should somebody insist that there be stratification to those who will benefit and those who won’t? The problem with that is that we don’t generally know enough to know how to do that stratification.
Culliton: But don’t you think we will? We have not talked about the insights that genomic science is bringing to medicine, but it seems likely that, in time, we will be able to know who will benefit from a certain new drug and who will not. We already stratify patients, if you will, who have breast cancer. Those whose tumors are estrogen-sensitive often get tamoxifen as follow-up therapy, often for years. But we don’t give tamoxifen to patients who are not likely to respond. That is already standard of care, although it is only one example.
Baltimore: I do think that we will become good at predicting who will benefit from new agents. When that is possible, with a high degree of accuracy, I think it will make sense, from both a medical and an economic point of view, to insist on it. But at present we’re not good enough. For example, take tamoxifen, which you mentioned. We understand well enough how it works that we can make a pretty good guess about which breast cancer patients it will help and who is unlikely to benefit. But in the case of the EGFR [epidermal growth factor receptor] inhibitors—Erbitux, Tarceva, Iressa—it’s still not clear. We thought that there was going to be a simple formula, but it’s not so simple. In any case, it will take a really serious clinical trial before we can stratify patients. So, meanwhile, lots of people are taking the drugs, and a small but real number are benefiting.
Culliton: Do you think that it would be worth paying for the drugs?
Baltimore: Well, the people who do benefit, benefit enormously. I would only support a system that enabled those people to get them. Now, the cost of their getting it could be very high. But we’re willing to pay enormous sums of money for people to get drugs that are worthwhile—the best case being Ceredase and Cerezyme, which treat a very small number of patients—the whole Genzyme Corporation is built on it. But they’ve been able to charge hundreds of thousands of dollars per patient per year for the drug because people believe that it’s important for it to be available. And it’s not because the drug is so expensive to make. It’s because there are so few patients who need it that to have a supply of it and therefore to make it valuable to the company to produce it, they’ve got to charge a lot for it.
Culliton: Does that give you any hesitation with respect to questions of fairness or distribution of expensive drugs?
Baltimore: If I were in an underdeveloped country where resources were a very limiting factor, I think that would be a very important question. But I’m not. We’re in a highly developed country where it’s a matter of, Do you spend the money to keep a few people alive, or do you spend the money on something crazy like the war in Iraq? In my opinion, it is much more important to keep those few people alive.
Growth Of The Biotech Industry
Culliton: Since the 1970s, biotechnology has grown from a handful of companies to an industry in and of itself. Do you think it has really changed the economics of medical research or medical care? It certainly seems to be an important element in the economics nationally, in terms not only of new drugs but also of employment. We often think in terms of cost. We’ve been discussing the fact that biotech drugs tend to be very expensive. But there is another side to the story. How has biotech contributed to the national economy?
Baltimore: I am not an economist, so I’m the wrong one to ask that question of. But I can make some observations. That industry has provided expensive treatments for life-threatening diseases. It’s clearly met previously unmet medical needs. And the overall financial burden on the health care system, as I understand it, is not enormous because drugs are still 10–15 percent of medical costs. So for all the development of biotechnology, it has not overwhelmed the health care industry.
Culliton: Do you have any sense of what the biotechnology industry has done to generate revenues for the economy? This is something that interests me. A whole new industry not only produces products that cost money but generates all sorts of jobs.
Baltimore: Absolutely. I don’t know national data. I do know that the number of people employed in California in biotechnology is pretty immense—some 250,000 people. That number may be dead wrong, but I’ve seen the number in front of me; it’s got a lot of zeroes in it. And the amount of revenue that comes to the state of California is clearly in the billions of dollars. You know, a company like Amgen—one of the early biotech companies—probably employs 15,000 researchers and other workers. So, sure, these are big companies. Amgen is the cornerstone of the wealth of Thousand Oaks. And that’s also true in South San Francisco, previously a working-class environment. Genetech now has its headquarters there, and many other companies, often Genentech spin-offs, are located there. Amgen has bought one of those spin-offs, Tularik, and is now a visible presence in South San Francisco. It’s a whole new place. Biotechnology has had an enormous impact. It’s a real industry. And it’s an industry that doesn’t outsource much, so the jobs stay in the U.S.
Culliton: That’s an interesting point.
Baltimore: A lot of the particularly high-tech stuff stays in the United States, although that may be beginning to change. Of course, there are tax advantages to working offshore, so a lot the pharmaceutical industry does work in other countries. The biotech industry is a harder case. We don’t know whether it will change or not, but other nations are graduating large numbers of skilled scientists and technicians. I know that the biotech companies here in California would like to keep their workforce right here, if they can. Amgen, which I do know very well because I’m on its board, has outsourced a lot to Puerto Rico, but that’s still in the United States.
U.S. Science Education
Culliton: Outsourcing brings up the subject of science education.
Baltimore: It does.
Culliton: It’s a subject that lots of institutions from the National Academies to the American Association for the Advancement of Science and others have spent a lot of time thinking about. Do you think there’s a way to get more American-born kids into science? Do you think it matters?
Baltimore: Absolutely. I think it matters for the health and well-being of the next generation, because increasingly the available jobs in the United States are either minimum-wage jobs for which you don’t need any special skills or high-paying jobs for which you do need special skills and education, particularly in science and technology. And I think that children who are brought up today without a strong technical background are going to have difficulty in the future. Some of them will go to business school and law school and end up in managerial and professional service careers and will do fine. But you can’t run a whole nation on lawyers, even though we seem to try.
So, I think we need more and better students who are literate in science. But I must say, I don’t completely agree with most of my brethren who comment about these issues by pointing to the paucity of good K–12 education. That clearly is a problem. But I don’t think that the core of the problem lies there.
Culliton: Where does it lie, then?
Baltimore: I think that it lies in parenting—parents insisting that children get a good education, which means that the children have to pay attention to it. It’s not just a matter of having a good mathematics teacher. Parents have got to want it, and students need to learn to want it. And maybe the reason they have to want to learn is that their parents insist on it. That’s fine with me. I see kids here at Caltech who clearly have been raised by parents who cared enormously about education and about how their futures will depend on it, and those parents prepared them very well. Every year when I meet the new freshmen’s parents and every year when I graduate a senior class, I make it a point to congratulate the parents.
Culliton: Do you think there’s a way to make more parents like those?
Baltimore: It’s pretty hard. It’s cultural. We import a lot of the best parents. Caltech is a school where, if you look around, you’d say that it is Asian-dominated among the undergraduate population—and it is about 30 percent Asian. But few are from Asia. They’re mainly American. They’re the next generation. And so you’ve really got to ask, What is these parents’ secret? They were immigrants who brought over a culture that was and is different from the dominant American culture, and they managed to insulate their kids enough from that dominant culture. So instead of the kids spending their time watching television and being focused on the mall or whatever else, they’re actually focused on learning something.
Culliton: If I remember correctly, you talked about your own parents that way.
Baltimore: I certainly could talk about my own parents that way. Although they weren’t immigrants, they were brought up in an immigrant culture because their parents were immigrants, and they grew up in the ferment of the New York immigrant community.
Dialogue Between Science And Health Policy
Culliton: One of the things, as I told you earlier, that Health Affairs is thinking about is the need to create a dialogue between people such as yourself in the scientific community or the biotech community and people in the health care and health policy world. Do you see value in that, and do you see any ways in which it could be accomplished? Or do you think that it’s just wishful thinking?
Baltimore: No. I think there’s value in having serious conversations about where we’re going. What I don’t know is whether you can affect where we’re going scientifically or medically or in terms of devices. I don’t think we can. I don’t think we want to. But we can discuss how the medical health care establishment will adapt itself to changing circumstances and how all of this can be affordable, because the industry’s going to produce more and more opportunity at higher and higher prices. And I’m worried that sooner or later we will run into the inability to pay.
Culliton: Unless we can create a whole new system somehow.
Baltimore: Right.
Reasons For Universal Coverage
Culliton: One of the questions is this: If the economists, the health policy people, and the health services research people could talk to the scientists, might we devise entirely new ways of approaching projects and problems?
Baltimore: We might. It’s worth trying. Let me comment on one place where I think this is critical. We talk about universally available health insurance that would not depend on a person’s particular history but would provide health care coverage for everyone—the arguments that are made about this are arguments about availability, about cost. There’s another argument, which overwhelms all of those; it has to do with what the genomics revolution will produce in the future. The genomics revolution that we’re just living through is making it clear that we are all genetically hamstrung in one way or another. And the only way to treat people who have genetic diseases, and we all do, is to think about universal coverage. We can’t hold individuals responsible for their genetics. We must insure them nationally. If we do hold people responsible for their individual genetics, then we will have a completely unacceptable level of discrimination. It’s inevitable, because insurance companies will say, I need to know your genetic constitution before I insure you. And they’re right.
Culliton: That is what the insurance industry does.
Baltimore: That’s what they’re about. That’s what they’re trying to do. That’s what they’ve always tried to do. And now we’ve given them this very powerful tool that could enable them to really discriminate. I think the implications of that powerful tool are that there should no longer be an insurance system that holds people responsible for inherited diseases, whether they be so-called Mendelian diseases, such as sickle cell or cystic fibrosis or Tay-Sachs, or complex diseases, such as cancer or heart disease.
Culliton: So that means you’d go to universal health insurance?
Baltimore: Absolutely, I think that it does.
Culliton: Well, that may be a very good place to begin a dialogue. The scientific community—particularly people who work in genetics and genomics—has a lot to say about the nature of disease and the nature of risk. Obviously, health policy leaders are aware of this, but there could be real value in bringing representatives of the two groups together to talk about solutions based on science rather than politics.
Baltimore: That’s for sure.
Concluding Comment
Culliton: For more than forty years you have been deeply engaged in scientific research, university administration, and national science policy. What do you do to relax?
Baltimore: “Relax” is not a word in my vocabulary. I do alternative things to provide variety in my life, like fly fishing, sailing, and skiing. But between science and administration, I have most of every day more than occupied.
This interview is the third in a series of interviews with leaders in the biomedical sector, sponsored by the nonprofit Institute for Health Technology Studies, or InHealth, which recognizes that innovation in medical technology plays a vital role in better and more cost-effective health care. The series focuses on individuals who are either innovators in their own right or in a position to foster novel research.
David Baltimore (baltimo{at}caltech.edu), president of the California Institute of Technology, former president of Rockefeller University, and founding head of the Whitehead Institute at the Massachusetts Institute of Technology, is one of the leading statesman for basic science and science education in the United States. Baltimore, now age sixty-seven and soon to step down as president of Caltech, is the new president of the American Association for the Advancement of Science. Baltimore shared the Nobel Prize in Medicine in 1975 for the discovery of an enzyme called reverse transcriptase, an important element in retroviruses such as HIV, which causes AIDS. Barbara Culliton is a Health Affairs deputy editor.
DOI: 10.1377/hlthaff.25.w235
©2006 Project HOPE–The People-to-People Health
Foundation, Inc.
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