Part IV
Science Policy and Societal Impacts



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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Part IV Science Policy and Societal Impacts

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program This page in the original is blank.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Science Policy and Society: Current Challenges, Future Priorities Mina Bissell Director, Life Sciences Division Lawrence Berkeley National Laboratory Berkeley, California In the 21st century, biologic science will occupy the same role that physical science occupied in the early 20th century. In looking toward the 21st century, we have to address a number of important topics: Whether support of basic science should or can be viewed as a wise investment strategy. What the changing balance of private and public funding of science means. What the ethical, legal, and social issues in science are. How we will educate and inform the public about science. What the roles of basic and applied science in mission-oriented agencies will be. How R01 grants versus ''big science'' and team research will work out. What the role will be of the Biological and Environmental Research (BER) program in the Department of Energy (DOE). How the national laboratories will work in preserving the nation's scientific and technologic competitive edge. Should or can support of basic science be viewed as a wise investment strategy? An article in the New York Times ("Study finds publicly financed science is a pillar of industry," William J. Broad, May 13, 1997) describes a study that found that publicly financed science is the "pillar of industry." The study, conducted for the National Science Foundation by a private research group, found that 73% of the main science papers cited in American industrial patents in 2 recent years were based on domestic and foreign research financed by government or nonprofit agencies. Private companies paid for the rest. Thus, publicly financed science had turned into a "fundamental pillar" of industrial advance. That finding sharply contradicts the view that publicly financed research, which gave birth to high-technology industry, is no longer so important. The article quotes Charles F. Larson, executive director of the Industrial Research Institute, a nonprofit group in Washington that represents large companies: "[The report is] going to make people realize something that they should have known all along—that public investment in academic science through government-funded programs, pays dividends to society . . . that it pays off handsomely." I could not have said it better. I think that some of the members of this panel could also address this. But it seems that the case is very well made that it is singularly important for government and tax money to be used to develop fundamental knowledge because it pays back to society. As to the ethical, legal, and social issues in science, I am the president of the American Society for Cell Biology (ASCB), and we took our charge quite literally and went on record with a statement about the science of

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program cloning of sheep. It is important that scientists police themselves. ASCB went on record that, indeed, we do not approve of cloning of human beings and that we do not know enough to allow going forward in that direction. But we also have gone on record to make sure that the fear of cloning, which can be exaggerated, is not going to prevent the magnificent scientific advances that the scientific community is making, including the use of DNA-engineering and cloning techniques, which play an important role in scientific advance. David Cox addresses this issue with regard to the ethics of the Human Genome Project. Charles Shank addresses the role of basic versus applied science in mission-oriented agencies, but I want to address the question of R01 grants versus "big science" and team research. This theme has interested many of us in industry, in national laboratories, and in universities. There seems to be a question of individually driven science as opposed to team science. It should not be an either-or situation; it should not be one versus the other. Indeed, it is important to make smooth boundaries and connections between individually driven science and big science. The national laboratories and the Office of Biological and Environmental Research (OBER) are capable of advancing magnificent, team-driven big science. But it is important to recognize that it is individuals who actually do it. We need to bring multiple fields to bear on large problems, and we must use the best talents and the most-original intellects to achieve our goals. Few of us would question that it is important to have the best and the brightest in the national laboratories and in OBER-related science to achieve the goals that we want to achieve. I want to say a couple of words about the role of the OBER program in DOE and about the future role of the national laboratories in the nation's scientific and technologic competitive edge. This will be somewhat personal. In the early 1980s, I was doing a sabbatical in England, and I was asked to become a charter member of the secretary of energy's Health and Environmental Research Advisory Committee (HERAC). When we walked into the room, there were 10 or 12 university and industry people and 2 or 3 scientists from the national laboratories. The committee had been created to take a hard look at the quality of the science supported by the Office of Health and Environmental Research (OHER) of DOE. However a number of the members unofficially wanted to do away with the office. The questions always were, Why should biology be done in the national laboratories? Should they be allowed to do it? These members felt that we were going to look at the OHER program and would come to the conclusion that the science was not good and thus the program should be closed. I now would like to share with you an excerpt from the committee's report. This is about 10 yr old, but it is still relevant. I was delighted to be a member of HERAC and help to write it. "Throughout all of our discussions, the themes came up again and again about the unique role that OHER plays, about the breadth and the coherence of the Program, about the importance of the field laboratories as national resources, about the critical tightness of funding, and about the heavy losses to be expected if the pattern of diminishing funding continues. Regardless of discipline or distance from OHER, the members shared this common perception of OHER's role and its special value. We tried to write these perceptions into the document, but I wish we had some better way to transmit to the skeptics how a committee of virtual strangers came to such a common, strongly positive consensus. For those who control the future of OHER, we hope they can come to appreciate what we see in the Office's performance and style. Not only does the Office carry out its primary mandates effectively, but it has created, and is responsible for a very special national resource at its on-site laboratories. And perhaps most importantly, in its approach to problem-solving by supporting science broadly, OHER has come to play a critically important role in the cutting edge and even the survival of large pieces of relevant, modern, health and environmental research." That is the case even today. People should look at what the OBER program (the current name of OHER) has actually achieved—the accomplishments of this group, that it takes risks, that it supports science for an extended period, and that important biologic findings have come to pass because of this pattern of thinking and daring. A perfect example is the assay of Bruce Ames. The assay is now used everywhere and was funded by this office. He could not get National Institutes of Health (NIH) funding for it. Now it is established, and all government testing agencies use it. The field of DNA repair would not be on the map were it not for this office and its vision. Many of the technologies—the flow cytometer, comparative genomic hybridization, all sorts of other exciting technology—that we now use and take for granted were funded by this office.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program My own research, being very basic, was alien to how people normally think, and was regarded initially as something that could not possibly become important. It would have not been possible to do it without the support and vision of OHER. I have said this in front of many audiences: my very beginning was in the National Science Foundation, where someone was willing to give these ideas a chance. NIH committees looked at my first 2 grant applications and said that they did not see how it could work. They were unwilling to take any chances within the science. But 15 yr later, this exciting field of extracellular matrix signaling is on the map. Think about it: Without that 15 yr of funding, this field would not be on the map now. I want to say that I vote with my feet, as well as the feet of my colleagues, who have been there to be beneficiaries of this. That is why I am here today. Where do we want to go in the 21st century? The ultimate mission of the health programs in OBER is related to risks to human health. Today, you have heard panels on global and atmospheric research, on the human genome, and on nuclear medicine; I am not going to reiterate them because they articulately discuss some of the exciting things that the science is going to bring. My field is health effects, and I thought that I would address that a little bit more. In the 21st century, the sequencing of the genome, which is already under way, will be a reality. What we must prepare for now is not only the structure-function relationship of proteins, but how they are regulated at the subcellular, cellular, and tissue levels. We need to understand function in the context of the organism. We need to address human biology and physiology and, most importantly, functional genomics and postgenomics; we need to address the complex problem of individual susceptibility and the cumulative effect of low-level environmental insults. These are very important challenges. We will meet these by bringing funding agencies together through the unique capabilities of academia and of the national laboratories, where many disciplines are brought to bear to answer such complex questions. That is why we need biology in the national laboratories—to bring many disciplines to bear on the complex problems of life and regulation of function and to use teamwork to answer the big questions.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Discussant Mary Clutter Assistant Director, National Science Foundation Washington, DC President Clinton made an important statement during his commencement address at Morgan State University in May 1997. He said that the 20th century was the age of physics and that the 21st century will be the age of biology. I would like to discuss why the 21st century will be the age of biology and how this came about. There can be little doubt that this country is first in the world in biomedical science. This has happened over the last 50 yr. Actually, the major growth has occurred over the last 30 yr and has made it possible to say that the 21st century will be the age of biology. A number of factors have contributed. A major one was that we placed emphasis on supporting individual investigators, especially young investigators, pursing their own ideas in competition with each other at the national level. (That has not been true in other countries, although the situation is changing somewhat.) One great benefit of our investment in biologic research over the last 50 yr is that we now have well-trained biologists everywhere in this country, not just at the top research universities. These scientists are also at the national laboratories, at so-called second-tier universities, at small colleges, and of course in industry. Thus, we have unsurpassed intellectual strength in biology everywhere in this country that can be tapped as we embark on the age of biology. We must note that as we embark on the age of biology, we are also living in the age of information. What does this mean for biologists? It means that scientists can now work with and analyze immense data sets that allow them to look at information both temporally and spatially in ways never before possible. The data can be shared with other scientists in this country and all over the world. This capability is changing how we think about biologic questions, and it will certainly change how biologic research is conducted in the 21st century. Let me give you a couple of examples. In January 1997, I had the good fortune to go to Antarctica and interact with scientists who are doing research there. They are in daily contact with their laboratories in the United States or whatever country they are from via the Internet. They can tap into any database available on the World Wide Web from that remote location. In May 1997, some visitors from the Mongolian Academy of Science visited me. They want to participate in leading-edge biotechnology research because they now have access to the Internet. It is increasingly possible for their scientists to work with our scientists. In fact, it is happening already. The National Science Foundation (NSF) supports a number of long-term ecologic research (LTER) sites throughout the United States and Antarctica. We are now connecting scientists around the world in an international network. Scientists in Mongolia have begun to collaborate with our LTER scientists in Colorado. Thus, biologic research is changing. One does not have to feel isolated at some remote location. One can be very much in contact with the mainstream of biologic thinking from anywhere, and this will be increasingly possible as we move into the next century. That also means that scientists anywhere can participate in large projects. Increasingly in biology, scientists will collaborate on large projects, such as genome projects, linked via the Internet. They will not need to work in teams at the same location as physicists who work with large accelerators need to do. They can work alone, but be connected with others anywhere in the world who are investigating the same problems. We will have to be prepared to support that mode of research. It is increasingly clear that the major unsolved problems in science require support through the cooperative efforts of more than a single agency. That is certainly true for the Human Genome Project, but it is also the case with other projects. For example, the Department of Energy (DOE), NSF, and the US Department of Agriculture are supporting the Arabidopsis Genome Project, one of the most-important collaborative efforts in plant biology today. It links scientists all over the world in a multinational project with milestones and goals established not by federal administrators but by the scientists themselves. They set the priorities, and government officials act as facilitators. So far, it is working marvelously. However, we must be aware that that might cease when genes with commercial value are sequenced. For the moment, the coordinated effort is working.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Another cooperative program is the one on bioremediation. The partners are DOE, the Environmental Protection Agency, the Office of Naval Research, and NSF. It is a joint peer-reviewed competition open to investigators anywhere in the country. It is still too early to announce any outcomes, but some very exciting research is being supported because agencies have joined in partnership to support large projects that would be difficult for a single agency to fund. A final example is the Protein Data Bank, supported by DOE, NSF, and the National Institutes of Health. It would certainly be too expensive for 1 agency alone to support. Yet the data are invaluable to scientists supported by the 3 agencies. As we move into the next century, I believe we will see an increase in the number of multiagency partnerships. The President said something else at Morgan State that has not been quoted widely. He proposed that this country join with other nations to solve environmental problems. I see that as a huge, compelling challenge for our agencies as partners. Successful scientific partnerships, such as the Arabidopsis Genome Project, might well be used as models. But it is essential that scientists identify the questions and set scientific priorities and goals to construct a roadmap to the future that can be used by agencies as they set their priorities. The 21st century will be the age of biology, but only if we use the talents of scientists from many disciplines, wherever they are, and the combined resources of agencies, public and private, in partnership.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Discussant David Cox Genetics Department Stanford University Palo Alto, California I do not have a long history with the Department of Energy (DOE), although I have been involved with it in many ways. But I want to be a part of this celebration because of the Human Genome Project. Throughout my scientific and medical career, I have been trying to figure out how to use genetics as a tool to monitor health effects. I do not believe that it is the answer to life, but I do believe that it can be an important tool. I remember being at the Lawrence Livermore National Laboratory in the mid-1980s, listening to Charles Cantor talk about some guy named DiLisi, who thought that the human genome could be sequenced. Interested as I was in genetics, I did not have the vision to see what would be possible, and Charles DiLisi did. That vision revolutionized my scientific career, and that is why I am so pleased to be here. Mina Bissell, our panel chair, gave us a charge, that is much broader than genetics and the genome project: science in the next millennium. Because I am a fairly narrow person, I am going to focus on that in the context of genetics. I too would like to refer, as Mary Clutter did, to President Clinton's May 1997 commencement speech at Morgan State University. The president stood up and said that the next age will be the age of biology. I do not know that much about Washington politics, but I do know that perception can lead to reality. If the president says that it is going to be biology, it is likely to be biology. How is biology going to go forward in the context of human health? I would like to use genetics as an example here and start with the Human Genome Project. For a long time, people talked about using human genes to get a better understanding of disease, particularly genes that caused diseases when mutated. In the early 1980s, when this was suggested, some thought that it would never happen. But, slowly but surely, individual disease genes were cloned. The cystic fibrosis gene—the gene that was necessary and sufficient for this relatively rare genetic disease—was cloned. It cost at least $200 million to do that. It was one thing to stand up and talk about using modem molecular biology and genetics for human health, but even those as naive as I am with respect to economics knew that this was not in the cards if it was going to cost $200 million for each disease. That is where DiLisi had great vision. The idea was that if one could get all of the genetic information in a rapid and cost-effective way, one could apply it to all the different diseases. The important insight was related to making that happen. Biology is as much of a nightmare as atmospheric science. Biology is difficult to model. I think that the whole world is difficult to model. But the advantage of genetics is that it is bounded by discrete chromosomes. The human genome has 3 billion base pairs. That is the bad news. The good news is that when you are up to 3 billion, you are finished. Even when we reach that point, it does not mean that we are going to understand everything, but we will have a completed tool for unraveling biology. The important vision of the genome project is not that it will stamp out disease, but that it is bounded, it is doable, and it will provide a resource that can be used into the next century. How does one sequence the genome? I do not believe that it will be done by individual small-laboratory investigators. We have tried that. That was the idea of cloning individual genes; it cost a fortune, and it was not efficient. But it does not require the same mass group of people that some of the very big, high-energy physics projects did. Since 1990, my colleague Rick Myers and I have managed one of the National Institutes of Health Genome Centers. The group numbers 30. Most of the genome centers are not bigger than 50—smaller than most major research laboratories. With respect to personnel, there are two ways to think about the genome project and big science. One is to assemble as many stupid people as you can so that they will not recognize how boring the task is. The other is to assemble few smart people. The latter is what has led to the success of the genome project. I agree with Mina Bissell that what we need—in the context of the genome project, in which only a small percentage of the human genome has been sequenced when the goal is to have it finished by the year 2005—is a

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program select group of smart people. We already have smart people at the DOE laboratories, and they can make a major dent in sequencing the human genome and in making the reagents and technologies available to us. This is an international collaborative effort, but not every laboratory in the world can put it together. It requires groups that are used to dealing with big projects, that are smart, and that know how to deliver the goods. This is one place where the Biological and Environmental Research (BER) program, in addition to having the vision, has the prospect of delivering the goods. The idea of a joint sequencing center, combining 3 of the national laboratories, is outstanding. It is timely, and it is necessary. How is the genome sequence going to be applied to human health? The common way that is talked about, which is reductionist, is that we are going to find the gene that causes a disease, figure out how it works, and come up with a therapy for the disease. That is not practical in a realistic period of time. I am not getting any younger, and it is certainly not practical for my scientific lifetime. It would be like trying to model and understand the whole environment. We will use the genetic information cost effectively by using the variation in the human genome as a way of satisfying human-health problems in terms of their common genetic cause. When I talk to physicians about this, they ask, Are you going to throw out all my diagnoses? When I talk to other groups, they ask, Do you think that genetics has the best answer? All genetics does is provide a type of information that enables one to take what looks like a single disease and group it into the 5 or 10 most-common forms on the basis of genotype. It is simple to think about that. A treatment that works on only 20% of patients with a particular disease is not going to be a very effective treatment. But genetics can be used to break that disease down into, say, 5 homogeneous entities, then perhaps 5 treatments would take care of everyone. This does not have anything to do with gene therapy. It does not have anything to do with understanding how a particular gene works. What it has to do with is that the genome is bounded and that 1 in 1,000 base pairs in the DNA is variable, and you can use that information for a mix-and-match—a correlation. I am absolutely sure that the genome will be sequenced, that we will have the variations, and that we will have the technologies and the chip arrays that are going to identify the variations. But I do not think that our society is set up to use the information. The DOE laboratories can play a major role in providing the information, but I suggest that the BER program could play a major role in making use of it with respect to human-health effects. I am on 2 government groups. The Task Force on Genetic Testing has just finished its work. It was a task force of mixed public and private people—lawyers, economists, health-maintenance organization people, and ethicists—who tried to figure out how to deliver safe and effective genetic tests. The task force asked several questions: How do you decide whether a particular test is safe or effective? Do we need to have laws and regulations to protect individuals' autonomy and individual freedoms? How can scientists use genetic information to make sure that people are helped more than they are hurt? President Clinton, in his Morgan State speech, talked about ethics, particularly biologic ethics and how this biologic work was going to be for society. The president said that, if we axe going to have this new technology, it should extend to all people in the United States, not just to a few rich people. It should be fair under law so that it does not discriminate against some people. It should help people more than it hurts them. This should sound familiar to physicians. Are we in a position now, using genetic tests as an example, in which more people will be helped than hurt? Absolutely not. In fact, one way in which people can be hurt the most is in the inability to get health insurance. Much to my surprise, the president suggested that there be legislation to ensure that genetic information is not used to discriminate unfairly against people with respect to health insurance. I applaud that statement. What the Task Force on Genetic Testing, much to its surprise recognized, is that the missing component is the continuing collection of the data needed to figure out whether a test is useful or harmful and which therapies work with what test results, and which do not. This is not done in our country now. We pretend that we use science to make policy decisions; in fact, we make policy decisions on the basis of our preconceived notions. If science helps to support those preconceived notions, we use it; if it does not, we say that it is bad science.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program I would hope that in the 21st century we can use genetics as the paradigm and have all science policy be more evidence-based. If that is to be the case, at least with respect to human-health effects, the public will have the scientific facts and other information needed to decide whether it wants to use a test or not. The President's Bioethics Commission, which ! am also involved with, feels exactly the same way. That commission is dealing with the cloning of human beings. Rather than making moral statements, we are focusing on our lack of scientific information on this complex technology; we think that it would be a good idea to have a substantial knowledge base before generating human beings with this technology. The BER program should be involved not only in sequencing DNA to drive biology but also in collecting information with respect to the human population to see how the genome sequence can be used to help and not harm. DOE can play an important role in filling that information gap.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Discussant Charles V. Shank Director, Lawrence Berkeley Laboratory Berkeley, California From my days in industry at Bell Laboratories, I know that a company like AT&T was able to invest in basic research as well as applied research, with the idea that it could capture the value of its investment because it essentially had a monopoly on telecommunications. Today, very few businesses can own all of the investment in basic research in their fields. A country needs to build a foundation for doing basic research, as opposed to providing a financial driver for industries to be able both to invest and to recover their investments. In the United States, 73% of the applied industrial research has had some basis in or connection with federally funded basic research in universities and in national laboratories. The United States has had a 50-year legacy of investment in research, and the technologic progress that has been made as a result of it is amazing. We are able to form businesses that cannot be found anywhere else in the world. Investing in research will probably be even more important in the next 50 years than it has been in the last 50. As we look at the kinds of basic research that are going to go on, one question that arises is, What is the role of the Biological and Environmental Research program in the Department of Energy (DOE)? DOE is different from other funding agencies in that it is driven by problems—problems in energy and problems left by the legacy of wastes that have accumulated as a result of the Cold War. It is going to be more important than ever to apply biology and environmental-effects research for the technologies that will be developed to clean up this multi-hundred-billion-dollar mess that the country is involved in. Having biologists work in close connection with researchers in energy and in cleanup will be crucial for the effective and cost-effective kind of cleanup that will be needed. The multidisciplinary laboratories, now called "multiprogram laboratories, have the capability of assembling expertise in a wide variety of scientific fields. We are often asked, How can you be a multiprogram laboratory if you do not have a sharp center of focus? I think that our focus needs to be to assemble teams to attack problems. Problems are seldom defined by a discipline or a focus. They are defined by a national need. The laboratories have shown themselves to be extraordinarily adept at building multidisciplinary efforts. We can look at the sequencing of the human genome as an example of the problems facing DOE today. In the laboratories we have the skill and capability to bring engineers, physicists, and biologists together to invent a new kind of biology that is going to take advantage of advances in automation and informatics. Structural biology is another example. We are going to have biologists taking advantage of the new synchrotrons, the advanced photon source, and the advanced light source. The synchrotrons produce unique kinds of X-rays for doing structural determinations. It has taken, in many cases, months, sometimes years, to solve the structure of a complex protein. I predict that within the next 5 years we will be determining structures in fractions of a day, maybe even in minutes, as we begin to marry state-of-the-art computation, biologic needs, and advances in third-generation light sources. As to the cleanup program, large areas in this county are carrying a load from previous use for nuclear materials. The legacy of that work is going to require not only an understanding of the chemistry and environmental effects under the earth, but also a bringing together of a biologic perspective, a computational perspective, a chemical perspective, and a physical perspective. Multiprogram laboratories can do that.

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program Discussant Daniel Goldin Administrator National Aeronautics and Space Administration Washington, DC When I travel around the country, I ask executives and others, "Do you believe in the future dream of America? Do you believe that America is going to be a great country in the year 2025?" Almost invariably, they will think about it and make a little sarcastic comment, but eventually, they will say, of course we are going to be a great country. Then I say, "Who is responsible? Are you?" People have a very hard time in answering because, in the corporate world, you cannot go beyond 5 yr in your thought process. I have yet to see a corporate strategic plan that goes beyond 5 yr. Of the basic research in this country, 8% is paid for by corporate America, and the lion's share is being left to the federal government that everyone talks about and wants to cut the budget of—they all go to the polls and vote for deficit reduction. But without federal funding for long-term research, cutting-edge research, it would be almost nonexistent in this country. The federal budget is around $1.6 or $1.7 trillion, and $30 billion of it goes into nondefense R&D. Even adding all defense-related R&D takes it up to $70 billion a year, not a huge amount on a national scale. More and more, when one goes to Congress to testify, one hears, "What is it going to do for my constituents today?" The answer is probably very little. It will do something for their children. That is the timeframe we have to use because if you are doing long-term basic research and getting results in 2-3 yr that have an effect, you should not be doing it. At least this is one government bureaucrat' s view of the situation. American industry does a wonderful job in near-term product development in the 2-to 4-yr timeframe. But the timeframe that one has to think about is the 10-30 yr. The National Aeronautics and Space Administration (NASA), the national laboratories, the National Institutes of Health (NIH), and the National Science Foundation (NSF) are probably the only organizations in the country that deal with that. It is important not to apologize and reduce the reason for the existence of the national laboratories, NASA, and NSF to near-term technology transfer and things that we send to industry. It must be resisted. If we do that, we will be measuring our success by the yard—we do this little widget and that little widget—and be wasting the taxpayers' money. What we really do is rewrite chemistry, physics, and biology textbooks. We develop fundamental understanding of the laws of nature in the physical sciences and the biologic sciences so that corporations years from now can deal with them. We inspire young people to learn the scientific process and to become part of society. The world economy today is $30 trillion a year, of which about 75% is represented by countries that can be counted on the fingers of 2 hands. The world economy is going to be $100 trillion some decades from now, and the growth is going to be in the developing countries. George David, CEO of United Technologies, in a recent speech to NASA calculated exports from the United States at $24 per hour; for imports, it is $3 per hour. If America thinks that it is going to put up big boundaries at its borders, continue to make sneakers and other low-end technology products, and assemble the products of yesteryear, the message is that it is hopeless at an average of $24 an hour. America has to drive up the food chain, be at the intellectual top, and add the value that will protect the economy, lead to sustainable development for the world, and provide national security, which is absolutely essential. The General Electric corporation, a decade or two ago, got 75% of its jet-engine business from the federal government, and 25% from the commercial sector. Today, it is reversed. If America does not lead the world in the technology of materials, fluid flow, and computational fluid dynamics, not only will it have economic problems, but its national security will be at stake. General Electric lacks the resources to do that. Suppose that the chairman, Jack Welsh, went to the bank and said, "I would like for you to give me a loan because in 15 yr I would like to build a hypersonic engine. I do not know whether it will work, and the engine might be built of ceramic matrix instead of metal so that it will have much higher combustion efficiency, and maybe in 5 or 10 yr I will know whether I even have a chance of doing it. I need a few billion dollars." They would throw him out on his head. How else

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program does it get done but by the federal government? We do high-risk, high-potential-payoff research that will affect the future of this country in the long term. When I go to Congress to testify, I refuse to explain the reason for NASA as Teflon, Velcro, and Tang. First of all, we did not invent any of it. And I cannot say, if you put a dollar into NASA today, a product will come out the back end. What I do say is that NASA tackles 7 basic questions. I think that this is a problem of communication for the Department of Energy (DOE) also, because no one knows what it is and what it will be in the country of the future. We have developed a strategic plan at NASA. It says exactly what we do. The new issue has 7 questions in it. Someone who does not work on these 7 questions should not be at NASA. How did the galaxies, stars, solar system, and planetary bodies form and evolve, and how does this knowledge help us to rewrite chemistry, physics, and biology textbooks? Is life of any form, single-cell or higher, carbon-based or not, peculiar to Earth? How does knowledge of the planets and the stars help us to build predictive environmental, climate, and resource models to explain the interaction of the oceans, the atmosphere, the biomass, and the land and to separate out the effect of the human species? How do we use the uniqueness of space—that is, the absence of gravity, the presence of partial gravity—to understand the laws of nature, and how do we open the space frontier by understanding how we could put people and robots into that environment? How do we develop revolutionary technologies to make transportation in air and space—anywhere, any time, for anyone—safer, more economical, and more environment-friendly? What tools do we need to answer questions 1-5, which are fundamental scientific questions, and how do we transfer these tools to enrich the American economy? (This question deals with technology transfer.) How do we communicate this knowledge to the American people, especially to children to tell them that adults care about their future? NASA is a science-driven agency that develops technology to support the science mission. Unless people can explain their relationship to those 7 questions and prove that they are the best in the world at it, we shut down their program. That might be shocking in light of the jobs that are put into specific congressional districts. We are setting up centers of excellence because we had tremendous overlap. We found that at NASA we had 10 centers with marketing teams that were trying to justify their existence. Now, we are stopping that activity. We only justify what we do on the basis of answering the 7 questions. I went down to the NASA establishment in Mississippi, where they test rocket engines. I said, ''Do you have the best rocket-engine testing facility in the world?'' They said no. I said, "Where does it exist?" They said nowhere. I said, "How many rocket test facilities does America have?" They said 7. I said, "Why is that the case?" Because we cannot figure out the politics of shutting down 6 of the 7. Think about that and see whether it applies to what you do. This is killing science in America. The Cold War is over. We are not going to spend whatever it takes to answer fundamental questions. Egos have to be set aside. We have to give young experimenters room to break through the system, not lock them out. The peer-review system is wonderful, but the peer-review system maintains the status quo. For example, NASA was given the job of Mission to Planet Earth to answer question 3. We set up a team of people in the late 1980s and gave them multidecade grants. That is very bad. The team set up a system of building 3 generations of spacecraft that would be launched every 5 yr and that would cover a 15-yr period. The spacecraft had 24 sensors. They weighed 40,000 lb, were 15 ft in diameter, were 40 ft long, and cost billions of dollars. If a single sensor failed, they would have to be replaced. Before you launched the second, you would be building the third. We had a nice white-collar jobs program. You should have seen the intellectual outpouring when we announced that we were killing it. A total of $18 billion was allotted in this decade, and we now have it down to $6 billion. We had 2 spacecraft with 24 sensors launched: an a.m.-crossing spacecraft and a p.m.-crossing spacecraft. We would have launched these every 5 yr. Now we have about 16 or 18 spacecraft. What we say now is that you cannot build a spacecraft in more than 3 yr. We do not even specify the science on the spacecraft when we go out for peer review. It is called the Earth-Space Science Systems Probe. Anyone in America can bid. They have to form a team and figure out the science

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program question that feeds into the broader question. They propose the science, the scientific team, and what they are going to build. The principal investigator dominates it. Every other year, we award 3 contracts. The total cannot be more than $240 million, and launch has to take place within 3 yr. We give 2 prime contracts, and we hold back a third. If one of the 2 teams does not do what it says it is going to do, we cancel the contract and give it to the third one. That is what I call peer review. It is a lot different from ordinary peer review. Young people are actually winning some of these things. We are trying to change NASA, but it is difficult. People speak with tremendous passion to hold onto the past, but the past is not there. We were finding ourselves doing near-term work, and it raised the question of applied research versus basic research. I view it differently. It is near-term (0-5 yr), as industry handles product development, versus wide-open research, which can be in science or technology. We are forcing our budget more and more into high-risk, high payoff research. Instead of building multibillion-dollar platforms, we are building much smaller sizes and in much higher quantity, so we are allowed to fail. In fact, we reward people when they fail. They cannot be incompetent or malicious, but we want people to take risks. We think that we can build some spacecraft in 1-5 yr from start to launch—and we are developing launch vehicles that cost $1.5 million, which is quite interesting. I have been appalled by the scientific cannibalism in this country, a problem of the Cold War era: people somehow believe that if someone else's project is canceled, their own research will be covered. But the scientists of America are like sheep going to slaughter. Members of Congress love it when scientists attack each other's projects because once they are canceled, the money for them does not go into science, but goes into the survival portion of the American budget. I am proud to say that I was a major supporter of the Superconducting Super-Collider, and my people said, "How can you support it? If you support that, we will lose the space station." I said, "How can I not support it? We have to study inner space while we study outer space because when we have telescopes powerful enough to look at some of the high-energy objects at the outer bounds of the universe, we are going to need Superconducting Super-Collider data on fundamental interactions of matter in inner space. It hurt when we lost the Superconducting Super-Collider. Scientific cannibalism better stop, and we ought to go to real peer review, not nonsensical peer review of survival. It is killing American science, and it is killing our credibility; the scientific community is doing it to itself, and it grieves me. After we developed the 7 questions at NASA, we developed 4 enterprises to address them: space science, earth science, humans in space, and aeronautics. Each enterprise gets questions to answer. For example, the space-science enterprise answers questions 1 and 2. And I asked the program people to set up long-term goals so that the American public has a score sheet and knows what the enterprises are going to do. One of the goals is, within 10-15 yr, to detect Earth-size planets within 100 light-years of Earth, if they exist; and if they have an atmosphere, determine whether that atmosphere has oxygen and carbon dioxide in a chemical equilibrium with water vapor. If that is the case, we can infer photosynthesis. That is a goal; the American public has a score sheet and understands that. In the aeronautics enterprise, we adopted goals of reducing the crash rate of planes by a factor of 5 in 10 yr and by a factor of 10 in 20 yr, and so on. By next year, each of our enterprises is going to have a set of specific goals for 10 yr and 25 yr that are related to the 7 basic questions. We will reach some and we will fail to make some, but the goals will be clear. That will be our communication tool, so America will understand what we are doing and we will not apologize that we exist for Tang, Teflon, and Velcro. It is deadly and it is insulting to our scientists who try to justify their existence on the basis of near-term benefits to America. We in government have not undergone the revolution that American industry has undergone through reinvention and continuous improvement. Industry's pace of doing things is lickety-split. Ed McCracken, the CEO of Silicon Graphics, told me that its oldest product is 5 months old. Compare that with the pace of government in putting in a major engineering or scientific facility. We allow the bureaucracy to get in our way, and it is shameful. The problem is not in Congress; it is in the agencies and how they hide behind paperwork and have not dealt with the tough issues that have to be dealt with. We must get the bureaucracy out, and we must put the scientists and engineers back to work and not have them pushing paper and managing

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program contracts. When I came to NASA, NASA called them contract managers. These are people with doctorates from the best schools in the country—and even they could not get the development time down. In 1992, the average time for developing a spacecraft was 8 yr. Today, it is 4.5 yr. Our goal is an average of 3 yr by the end of the decade and about 2 yr, with a maximum of 3 yr, somewhere around 2005. We are concerned with how much an average spacecraft costs to build and to launch, and we are not the only ones. It is time for some of the other science organizations to practice more openness because the American public is demanding it; it will allow us to have much better facilities. In the end, no corporation could afford to put in the kind of scientific and engineering facilities that the national laboratories have. They look on those facilities as a resource. The Boeing Corporation and McDonnell-Douglas tell me that without NASA—our computational fluid dynamics and our wind tunnels—they could not do their job. Many American corporations rely on the national laboratories, including the DOE facilities, but our infrastructure is rotting. We are not maintaining the infrastructure, and we are accepting the nonsense that it is socially unacceptable to invest 20-30 yr out into the future. We are part of the problem because our development time for major new facilities is much too long, and we are not matching Silicon Graphics and turning them around in 5 months. The public-private issue is also of concern. It is crucial that the government get out of the operations business and hand it over to industry. We intend to hand the keys of the shuttle over to a private corporation. We started the process. The amazing thing is that we are saving billions of dollars. Many people who have jobs on the shuttle are upset, so they hide behind the safety. You will see me getting beaten in Congress over this, but we took $1 billion a year out of the shuttle, and the reliability is 3 times what it was before, and 8,000 fewer people are working on it. It is not the goal of the federal government to support people in luxury through the year 2030 because they are working on the shuttle; it is the role of the federal government and NASA to answer the 7 questions that we developed. I love people, and I do not want to come across as harsh, but I put my hand on the Bible and swore to do the right thing for NASA. The right thing is not to hug the shuttle. Everyone is saying, "How could you hand the shuttle over to a private company?" I say, "How would you like to fly on American Airlines managed by the federal government?" We laugh, but the very same people are trying to tell the American public that you have to protect jobs by having people work on the shuttle so that we will have people who watch people who watch people. And then, if the shuttle crashes, we will have all sorts of documentation so that we will say it is okay. When I arrived at NASA, that shuttle would shut off at the Cape within milliseconds of launch. Here is how they fixed it: our prime contractor, Rocket-Dyne, added 8 more inspectors to look at something for which we did not have the fundamental process under control, to document it so that if we had a crash, they could say, by God, we are safe. In space, people could die. I repeat: in space, people could die, because it is tough and it is rough. You do everything you can do to make it safe, but it is not our job, for job security, to hide behind safety for the shuttle. We are going to hand the space station over to a private corporation and hand mission control over to private corporations because there is no need to have people with doctorates in physics, chemistry, and biology operating consoles where they look at analogue dials and turn knobs and are contract monitors. I think there are parallels in DOE. I have dealt a little bit with ethics. I feel personally responsible for the lives of the astronauts. I feel that because of total quality management, continuous improvement, and re-engineering, the shuttle is a safer machine. Some 10 yr ago, America believed that the probability that the shuttle would blow up was 1 in 1 million. In 1992, the probability was 1 in 78. We have now worked our way back up to 1 in 248. I have an ethical responsibility to tell the American public that the space frontier is dangerous and that people might die. The head of public affairs at NASA dies whenever I say that emotionally. But there are other cases in which the ethical problem with respect to the American public is not that we do the wrong thing, but that we do not openly talk to the American public as though they are adults. We are so afraid of telling them the truth in the news media that we do stupid things. That is where we ran into the ethical problem of using people in nuclear experiments. In itself, it might not have been wrong, but that the American public was not told in advance was wrong. How does that apply to NASA? We are going to send people out of Earth's orbit. When you leave Earth's orbit, you encounter cosmic radiation. The reason we have life on this planet is that these magnetic fields protect

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program us; the incoming cosmic particles are trapped in the Van Allen belts. When you go out there, you cannot put enough shielding in the spacecraft. The question is, How are we going to open the space frontier? We will have to pick some level of exposure above normal working levels. Could we go 3% more? 2% more? 1% more? We will have to talk openly about that. We are going to have to deal with the ethics of the search for life. Right now, we are having open discussions with the religious community because we are using federal money and we do not want to offend people who have religious beliefs on this issue. We are going to have to screen people on the basis of new knowledge about ourselves. We are still using very rudimentary techniques, but as genetic information increases, we will have to screen people genetically. There are going to be some interesting ethical questions. How do we deal with death in space? How do we deal with animals in space? At NASA, we are trying to understand the relationships of the muscular, structural, and neurological systems. In a program called Bione, we were using primates. Some people feel animals should not be used in research. But I have a responsibility to make sure that astronauts will be healthy and safe when they go into space. A person who goes into space loses bone mass and muscle mass. If problems occur, we do not know whether bones will heal. So we used primates to try to find out, and we did not lose any primates until the last mission. We had to do a biopsy on a primate when it came back. In the absence of gravity, everything in the body changes: the rate at which white and red blood cells are made changes, the immune system is depressed, fluids shift, bones decompose, muscles vaporize away, the vestibular system is lost, and so on. Unfortunately, with Bione, the scientists did biopsies on the primates 7 days after the mission. That is just the way they were doing it, as Tevye says, by tradition. We had to take the biopsies 1 day after they came back. But the primate did not adapt from zero gravity to 1 g, and it died. We had an ethical dilemma: we said we needed the data, but we would not take the data if doing so would put the primate at risk. It was a catch 22. So we said that we would stop the primate research at once because trying to obtain the needed data would cause us to kill the monkey, and then we would not be able to get the data. We try to deal with the ethics as well as we can. Now we are going to look for other methods of getting the needed information. We might find nonintrusive methods, and we might not. What happens if an astronaut has appendicitis in space? What if you bring him or her back from space very quickly, roll up the ambulance, and take the astronaut to the hospital? Could you give an anesthetic? How do you handle medicine in space under zero gravity? We have a whole new set of issues. How do we determine what to do? We cannot just go at it scientifically. We have to look at the ethical boundaries. We have an ethics board to help us to make these decisions, but the key is that we are open with the American public. NASA is probably one of the most open agencies. In effect, we have 2 billion people in our laboratories day and night. That is a strength. I do not know as much about DOE as I should, but I have tried to share my own experiences. I encourage you to go back to your laboratories and start a revolution—try to repeat the lessons that American industry learned in the last 10 yr to change your processes, but never give up on long-term basic research, because the national laboratories are a jewel of this country. If we lose the national laboratories, I will worry about the future of our country. But we could lose the national laboratories unless they get focused and have a specific set of goals and questions that they can communicate to the American public so that the public can understand what they are doing. I would like to leave you with one more thought. I have an engineering and physical-science background, and I am now seeing the error of my ways. When I went to school, biology was an art, not a science, in my mind. But the life sciences are becoming much more analytic. I see a major problem at NASA. Just after we discovered what we think are signs of fossilized life on Mars, we had a meeting of the Mars Working Group, 50 of the smartest scientists from academic institutions around the country. I asked, "How many life scientists are in the room?" Two hands went up. Mind you, we are searching for life. We just held our 5-yr review in Boulder, Colorado, with 75 people who are looking at the origins, evolution, and destiny of life. We have improved: we had 6 biologists. One of the problems in American science is that we train people through smokestacks. I do not propose that people lose their sharp skills by acquiring multidisciplinary skills, but they have to be able to talk across disciplinary lines. To prove my credibility, I went to the American Physical Society and lectured them that they are not

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Serving Science and Society in the New Millenium: DOE’s Biological and Environmental Research Program training physicists with a fundamental background in biology, although physics and biology are going to come together. Biologists do a better job with the physical sciences, but still not good enough. The next 10-15 yr will see an integration of physics, chemistry, and biology. For NASA, it is essential. To that end, we are opening the Astrobiology Institute, in Sunnyvale, California. We want to understand the origin of life. We want to learn whether life is ubiquitous in the universe. This is getting down to the fundamentals of science, but I do not see young people being trained to have the capacity to design the instruments that we are going to send into orbit and to other celestial bodies. In engineering, we are concerned about how little work is being done in self-assembling biologic systems, where we either mimic biology or use biology to build both living and inorganic systems. This is really the future of engineering. Engineers are ignorant on this subject. Biologists have an opportunity to be on the cutting edge and are not doing enough, are not communicating with physical scientists and engineers to bring this marriage about. At NASA, we are going to try our best. I have to appoint a chief scientist, and I have waited a year. But I will not appoint a chief scientist who is not a biologist or other kind of life scientist, because we must restructure the agency. We must be more forceful in helping people to understand that a crisis looms in our country. Very few people understand—although they hear about the Genome Project and drags—that biology is going to affect everything we do. Almost no thought is going into bringing together the biologists, the engineers, the physicists, and the chemists.

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