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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Suggested Citation:"Report." National Research Council. 2009. The Role of the Life Sciences in Transforming America's Future: Summary of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/12592.
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Prepublication Copy A Critical Time for the Life Sciences Speaker after speaker at the Summit agreed: the life sciences are poised to usher in a period of unprecedented health and prosperity. Basic scientific research into how living things function is producing new understanding of how living systems work and new ways of using biological processes to meet human needs. If current opportunities are grasped, the life sciences can help produce enough food for a growing population, cure chronic and acute diseases, meet future needs for energy, and manage the preservation of earth’s biological heritage for future generations. From the perspective of the life sciences, we live in the most exciting and promising period in human history. Yet even though the potential is enormous, speakers emphasized that the benefits will be achieved more quickly if financial and institutional barriers to newly emerging capabilities are reduced. The potential of the life sciences today has two roots. First, powerful tools are allowing biologists to collect and analyze vastly more information about complex systems, from single cells to global biogeochemical cycles, than has been possible before. This information is helping to uncover not just the molecular mechanisms that underlie biological processes but the ways that biological subsystems interact in whole organisms and in terrestrial and marine ecosystems. In this way, ongoing research is helping to unify biology by revealing the commonalities among organisms and by linking biological processes at different levels of organization. If current opportunities are grasped, Second, a profound reorganization within science is occurring. Important the life sciences can help produce segments of the life sciences are merging with the physical sciences and engineering enough food for a growing to create “transdisciplinary” scientific endeavors focused on pressing global population, cure chronic and acute problems. This blending of disciplines is diseases, meet future needs for leading to new insights into life processes and creating new opportunities to translate energy, and manage the preservation those insights into practical applications, just as the synthesis of the physical and of earth’s biological heritage for mathematical sciences with engineering in the 20th century created the electronics and future generations. information revolutions that have transformed our lives. Scientists, policymakers, and research administrators cannot predict which new technologies and industries will emerge from the unification of biology and the convergence of the life sciences, the physical sciences, and engineering. Yet steps can be taken now, multiple speakers pointed out, to ensure that the great potential of the life sciences bears fruit as quickly as possible, thereby giving rise to a steady stream of new ideas and new applications of science. Public and private funders can support the high- risk, transformational research that is commonly underfunded, especially during times of stagnant budgets. They can support younger researchers, who face daunting challenges in competing for scarce funds yet often have important insights that can spur progress. 1

Prepublication Copy They can help break down the barriers among disciplines that continue to inhibit transdisciplinary research. And they can foster educational programs that will produce the transdisciplinary scientists and engineers of the future. The Promise of the Biological Sciences Investments in the life sciences pay off in three broad areas, observed Massachusetts Institute of Technology (MIT) President Susan Hockfield. They improve human health. They foster industries that boost the economy while addressing a wide range of environmental, energy, health, and agricultural challenges. And they further human understanding of some of the most fascinating systems in the universe. Improving Human Health The biological sciences have enabled most of the world’s population to enjoy higher living standards and longer life spans than ever before, said National Academies President Ralph Cicerone. New understanding of the links between disease and sanitation, the role trace nutrients play in health, and the potential of vaccines and antibiotics, among many other research results, have improved the lives of people everywhere. The progress made in combating heart disease is a prime example of the payoffs from investment in the life sciences, said Hockfield. Over the past 30 years, the National Institutes of Health (NIH) has invested about $4 per American per year in cardiovascular research. That investment has helped reduce the rate of death from heart disease and stroke by more than half. Knowledge of cholesterol metabolism led to the development of the drugs known as statins, which have reduced heart attacks and strokes. The development of drug-eluting stents has enabled physicians to open occluded blood vessels. Study of receptors on the surface of nerve cells has led to new beta blockers that are being used to treat hypertension and heart disease. Similar advances have produced benefits throughout medicine, observed Thomas Cech, President of the Howard Hughes Medical Institute, and Harold Varmus, President of the Memorial Sloan-Kettering Cancer Center. Greater understanding of the role of tumor necrosis factor in inflammatory disease has led to antibody treatments that have changed the lives of many people with rheumatoid arthritis. Materials science is producing spare parts for bones, arteries, and other tissues and organs. The Artificial Retina The artificial retina is an implantable microelectronic device designed to restore useful vision in people blinded by retinal diseases like macular degeneration. It is being developed by six Department of Energy (DOE) national laboratories, four universities, and private industry. A camera mounted in eyeglasses sends a signal to a microprocessor worn on a belt that converts the camera’s image to an electronic signal. This signal is fed to an array of electrodes positioned on the retina of the eye. The electrodes are coated with diamonds so they do not decay in the salty environment inside the eye, and they are 2

Prepublication Copy springloaded so they do not destroy the cells inside the eye that convey images to the brain. The first model consisted of 16 electrodes and was implanted in six patients between 2002 and 2004. A second, much smaller model consisting of 60 electrodes is currently being tested in humans, and a third model containing more than 200 electrodes is now being designed. “When you see a patient who has been blind for 30 to 40 years recognize objects and be able to read large-scale newsprint, you begin to appreciate the consequences of the convergence of the physical and life sciences,” said DOE’s Raymond Orbach. Basic research into retroviruses motivated by their role in some cancers built the base of understanding that proved critical in first identifying the cause of the AIDS epidemic and then developing drugs to control the disease. “If we as a country hadn’t made the investment in the basic science, in the understanding of retroviruses, we would probably still today have a rapidly expanding global AIDS epidemic,” Cech said. Continued basic research into fundamental biological processes could yield a wealth of new medical advances. A Genetic Fountain of Youth? Many biologists have assumed that living things inevitably age and die. But recent research has shown that the rate of aging in many animals is at least partially under genetic control, suggesting that many organisms may be able to live longer than they do normally. In the 1990s, Cynthia Kenyon and her colleagues at the University of California, San Francisco, began looking for genes that might control aging in the tiny worm C. elegans. They found a worm with a mutation in a gene called DAF-2, which encodes a hormone receptor, that had a healthy life span twice that of normal worms. Mutants found since then have lifespans up to ten times that of normal worms. Kenyon and her colleagues also found that another gene called DAF-16 is needed for DAF-2 mutations to extend the lifespan. DAF-16 encodes a protein that turns other genes on and off. When another technique called RNA interference was used to regulate these genes one by one, many turned out to have an effect on aging in C. elegans. Furthermore, many of these genes may be involved in disease processes, since long-lived mutants have a remarkable resistance to disease. Similar genetic pathways have been identified in flies, mice, and humans. Study of families and populations with unusual longevity also are beginning to turn up genetic variants associated with long life. “It is looking as though these variants can affect human lifespans, which means that we could potentially increase longevity and youthfulness in humans by modulating components of this pathway,” said Kenyon. Investigations of bacterial genetics could provide new treatments for infectious diseases, including diseases caused by microbes that have evolved mechanisms to evade existing treatments. Bioengineered stem cells could provide regulated insulin secretion in people with diabetes, for example, or repair severed spinal cord nerves. Study of chronic diseases such as cancer, heart disease, and mental illness, which now account for the bulk 3

Prepublication Copy of health care costs, could lead to personalized treatments that reflect a disease’s unique characteristics in each individual. However, the translation of basic research findings to applications is not always straightforward or quick, Cech observed. Even where understanding of biological processes is extensive, vast amounts of work must be done, often by people in different disciplines and sectors working collaboratively, to apply new knowledge in medicine. From Discovery to Treatment A combination of deep biological understanding and innovative biotechnology has dramatically changed outcomes for many women with breast cancer. In the 1980s, researchers discovered a gene in rats that is involved in the origin and spread of cancer. The products of this gene could be blocked using a monoclonal antibody – a special kind of protein made using the tools of biotechnology. Researchers also discovered that this gene is related to a human gene called HER2 that encodes a growth factor receptor on the surface of human cells. Further research showed that women with breast cancer who had extra copies of the HER2 receptor on tumor cells survived with the disease only about half as long, on average, as did women with the normal number of receptors. In 1991 the Food and Drug Administration (FDA) received an application requesting that a monoclonal antibody directed against the receptor called trastuzumab (or Herceptin) be studied in clinical trials. In 2006, FDA approved the drug for use in patients undergoing breast cancer treatment who test positive for elevated expression of the receptor. That is not fast enough, said Susan Desmond-Hellmann, President of Product Development for Genentech, Inc. The drug should have been available sooner, and far more drugs similar to Herceptin need to be in the drug development pipeline than is the case today. Many questions remain unanswered about Herceptin. Why do some patients relapse despite being treated with the antibody? Why does Herceptin cause cardiac problems in some of the women who receive it? As Desmond-Hellmann said, “We need more, more, more basic science.” Also, scientists from academia, industry, and government need to be able to interact extensively to answer such questions. For example, noninvasive ways approved by regulators to monitor and diagnose cancers would catalyze the development of new drugs. Fostering Industries to Counter Global Problems The life sciences have applications in areas that range far beyond human health. Life-science based approaches could contribute to advances in many industries, from energy production and pollution remediation, to clean manufacturing and the production of new biologically inspired materials. In fact, biological systems could provide the basis for new products, services and industries that we cannot yet imagine. Microbes are already producing biofuels and could, through further research, provide a major component of future energy supplies. Marine and terrestrial organisms extract carbon dioxide from the atmosphere, which suggests that biological systems could be used to help manage climate change. Study of the complex systems encountered in biology is 4

Prepublication Copy producing insights into similarly interconnected networks encountered in many other areas of science – and vice versa. Take agriculture as an example. The agricultural biotechnology industry is just a little more than a decade old, said Robert Fraley, Executive Vice President and Chief Technology Officer at Monsanto – the first bioengineered crop, a soybean seed with a gene providing tolerance for a common herbicide, was launched in 1996. Yet biotechnology crops are today being planted on 20 percent of the world’s farmland, and the percentage is projected to double as new crops are introduced and countries like India and China move toward full adoption of the technology. “This is the most rapidly adopted new technology in the history of agriculture,” Fraley said. The ability to introduce multiple genes into an ever-expanding array of crops has not only increased yields but has produced significant environmental benefits. By altering the characteristics of crops, agricultural biotechnology has made it possible for farmers to use fewer pesticides and other chemicals. Fewer trips through the fields on tractors mean less greenhouse gas emissions and reduced compaction of soils. Furthermore, the revolution in agricultural biotechnology has just begun, Fraley said. Within a few years, agricultural companies will be selling seeds with ten or more introduced genes. Crops can be modified to improve human health; for example, soybeans have been genetically modified to produce healthy rather than unhealthy fatty acids. Future crops will need far less water, a crucial consideration as climate change alters rainfall patterns and groundwater aquifers are depleted. As Fraley said, “As much as we have seen happen in the last decade, it is really just the beginning.” Advances in the underlying science of plant and animal breeding have been just as dramatic as the advances in genetic engineering. Results from basic research have allowed plant and animal breeders to produce organisms with desired combinations of genetic traits. Say, for example, that a breeder wants to assemble 20 desirable genetic traits in the same plant. Using traditional breeding methods, the odds of achieving exactly that combination of traits in a single plant would have been one in a trillion – essentially zero. Using the new techniques made possible through genetic research, the odds are one in five. Over the last half century, plant breeders have been able to achieve a nearly one percent annual increase in corn yields using traditional breeding techniques. With the new techniques, yields are now going up by two to three percent annually. “We can now pick traits and combinations of genes that it never would have been possible to produce in the history of agriculture,” said Fraley. “That says a lot when you consider that humans have been trying to do this for 8,000 years.” Many other technologies derived from basic scientific research are boosting agricultural yields. Automated gene sequencers test genetic markers in thousands of individual seeds per day. Magnetic resonance imaging can look inside plants and animals to characterize traits. Using tractors equipped with global positioning system devices, farmers can put down a band of fertilizer, come back six months later, and plant seeds exactly on that row, reducing the need for fertilizer, pesticides, and other agricultural inputs. 5

Prepublication Copy Fraley said that the global agricultural system needs to adopt “Just as the basic biomedical research in the the goal of doubling the current yield of crops while reducing key future is not going to be done by the inputs like pesticides, fertilizers, and water by one third. “It is more pharmaceutical companies, [oil companies and important than putting a man on agribusinesses] aren't going to do the the moon,” he said. Doubling agricultural yields would “change fundamental research in photosynthesis and the world.” Another billion people will join the middle class over the plant development and plant hormones that is next decade just in India and China as economies continue to grow. going to lay the groundwork for a future And all people need and deserve understanding of how plants work,” said Cech. secure access to food supplies. Continued progress will For the life sciences to have a dramatic effect require both basic and applied research, as scientists learn more on nutrition, the world’s food supply, and the about the fundamental biology of plants and collaborate with others renewable energy problem, “we need to keep in putting that knowledge to work. reinvesting in understanding the biology.” “Just as the basic biomedical research in the future is not going to be done by the pharmaceutical companies, [oil companies and agribusinesses] aren't going to do the fundamental research in photosynthesis and plant development and plant hormones that is going to lay the groundwork for a future understanding of how plants work,” said Cech. For the life sciences to have a dramatic effect on nutrition, the world’s food supply, and the renewable energy problem, “we need to keep reinvesting in understanding the biology.” Answering Fundamental Questions The life sciences can answer some of the most fundamental, interesting, and difficult questions that human beings can ask. How did the great diversity of living things come to be? How do cells function on a molecular level? What is the role of life in changing the surface of the earth? Consider this last question, The evolution of life “put earth under new said James Collins, who is currently on leave from Arizona State management,” Collins said. Understanding University to serve as Assistant Director for Biological Sciences at the future state of the planet will require the National Science Foundation. According to a recent estimate, of understanding the biological systems that the approximately 4,300 types of have shaped the planet. minerals on the earth, about 3,000 are the products of biological 6

Prepublication Copy processes. The evolution of life “put earth under new management,” Collins said. Understanding the future state of the planet will require understanding the biological systems that have shaped the planet. Many of these biological systems are found in the oceans, which cover 70 percent of the earth’s surface and have a crucial impact on weather, climate, and the composition of the atmosphere. In the past decade, new tools have become available to explore the microbial processes that drive the chemistry of the oceans, observed David Kingsbury, Chief Program Officer for Science at the Gordon and Betty Moore Foundation. These technologies have revealed that a large proportion of the planet’s genetic diversity resides in the oceans. In addition, many organisms in the oceans readily exchange genes, creating evolutionary forces that can have global effects. The oceans are currently under great stress, Kingsbury pointed out. Nutrient runoff from agriculture is helping to create huge and expanding “dead zones” where oxygen levels are too low to sustain life. Toxic algal blooms are occurring with higher frequency in areas where they have not been seen in the past. Exploitation of ocean resources is disrupting ecological balances that have formed over many millions of years. Human-induced changes in the chemistry of the atmosphere are changing the chemistry of the oceans, with potentially catastrophic consequences. “If we are not careful, we are not going to have a sustainable planet to live on,” said Kingsbury. Only by understanding the basic biological processes at work in the oceans can humans live sustainably on earth. The prospect of answering basic questions about the nature and history of life attracts many students to the life sciences, especially when they see that putting that knowledge to work can contribute to building a cleaner and healthier world, said several speakers at the meeting. How did the first living organisms arise from the inanimate compounds present on the earth? What biological mechanisms give rise to consciousness? Have living things evolved on other planets in our solar system or elsewhere in the universe? These are the kinds of questions that can spark the imaginations and convictions of students and researchers alike. The Rise of Transdisciplinary Science The way that biological research is being done “is changing right in front of our eyes,” according to Collins. Researchers from different fields of biology are working together on projects that transcend divisions within the discipline. Similarly, life scientists are increasingly working in partnerships with physical scientists and engineers on problems that no one discipline could solve on its own. The Unification of the Life Sciences Since the emergence of biology as a profession in the 19th century, the discipline has included two major intellectual strands, said Collins. One strand focused on understanding life, as exemplified by Charles Darwin’s identification of natural selection as the explanation for the diversity and distribution of living things. The other strand focused on controlling life, as exemplified by the work of Jacques Loeb, a German biologist who worked at the University of Berlin and the University of Chicago in the late 7

Prepublication Copy 19th and early 20th centuries, to understand and modify the physiological mechanisms responsible for biological processes. Over the course of the 20th century, these two streams of scholarship blended. The effort to understand organisms led to the study of biological processes on progressively smaller scales. As former NIH Director Elias Zerhouni put it, “Just as physicists went from gross phenomena to atomic structure to subatomic particles, we have gone from understanding organs and their general functions to trying to understand molecular events.” This research led to the discovery that all organisms rely on essentially the same basic molecular mechanisms, so investigations of one organism can yield insights that apply throughout biology. It turn, new understandings of the molecular constituents of organisms have made it possible to adapt biological mechanisms for specific purposes. Today, the ongoing unification of the life sciences is also evident in a contrasting endeavor: the effort to build upward in scale from an understanding of molecular mechanisms to an understanding of entire organisms and ecosystems. Living things, from “The generation of data is not equal bacteria to humans, consist of biological to the generation of knowledge,” said subsystems that are connected in complex, interacting networks. Biologists now have a Zerhouni. Understanding the fairly good understanding of many of these complexity inherent in organisms is subsystems, said Zerhouni. But they need to develop ways of integrating their knowledge of another grand challenge that could subsystems to understand the behavior of inspire the best efforts of students organisms and assemblies of organisms. Computing, robotics, and other technologies and scientists. allow life scientists to generate immense amounts of data. But “the generation of data is not equal to the generation of knowledge,” said Zerhouni. Understanding the complexity “We have to encourage young people inherent in organisms is another grand challenge that could inspire the best efforts of students and to take up this next challenge,” scientists. Hockfield said. “[We need] to grab The Rise of Transdisciplinary Research the attention of kids from K to 12 to say, ‘wow, this is cool stuff, I want to To continue to make progress on basic scientific questions and on the application of be doing science and engineering and new knowledge to human needs, life scientists math.” are discovering that they must join in partnerships with physical scientists and engineers. This convergence of disciplines is “the defining intellectual movement of our time,” according to Hockfield. In crucial respects, the life sciences are undergoing a transition analogous to a transition that the physical sciences underwent at the beginning of the 20th century. Basic research in the physical sciences at the end of the 19th century and the beginning of the 20th produced a deep understanding of the physical world. This fundamental scientific 8

Prepublication Copy research revealed the structure and nature of matter. It demonstrated the nature of the cosmos and our place within the cosmos. It was a triumph of knowledge for knowledge’s sake. This new understanding of the physical world also yielded what Hockfield called a “parts list” for the physical world – a basic understanding of the constituents and interactions of physical objects. Having this parts list enabled scientists and engineers to incorporate the insights of physics into a wide array of practical applications. The resulting convergence of the physical sciences and engineering spawned the electronics industry, the computer industry, and the information industry. “If you contrast daily life today with what it was like a century ago, you would be hard-pressed to name a set of technologies and industries that have had a more transformative impact on our lives and on how we do our work,” Hockfield said. The biological sciences are poised on the brink of a comparable transformation. The discovery of the structure of DNA in the middle of the 20th century drove a worldwide effort to construct the parts list of biological organisms. The construction of this list, which has been a tremendously exciting intellectual adventure in its own right, is also having revolutionary practical outcomes, such as the biotechnology revolution in medicine and agriculture and the application of knowledge from the life sciences to energy and environmental issues. From Genetics to Genomics to Metagenomics The first large-scale transdisciplinary project centered on the life sciences was the Human Genome Project (HGP). It drew on concepts and technologies from many disciplines, including physics, engineering, computer science, and mathematics. Many of the technologies needed for ultrafast genetic sequencing were not available when the HGP started in 1990, and some biologists wondered if the data generated by the project would ever have broad applications. In fact, the HGP greatly accelerated the development of many new technologies, and the data and techniques generated by the project have had revolutionary effects throughout biology. For example, said Sloan-Kettering’s Harold Varmus, the availability of the human genome has “completely changed our approach to cancer,” including diagnostics, classification, prevention, and treatment. The HGP marked the transition from genetics – the study of the DNA sequences that constitute genes – to genomics – the study of the complete DNA sequences of organisms. Now the continued development of sequencing technologies is giving rise to metagenomics – in which the collective ‘genome’ of entire communities of microorganisms is studied. Metagenomics reveals the characteristics of organisms that cannot be cultured in the laboratory, and it helps show how organisms relate to each other in natural environments. It also has revealed a range and diversity of DNA sequences -- and even organisms -- previously unknown to science. In the past, biologists simply borrowed tools from the physical sciences and engineering to solve problems within their own discipline. Today, biological and 9

Prepublication Copy physical scientists and engineers are working as equal partners on problems. In the process, they are forging a “strong and fruitful new synthesis,” said Hockfield. This work represents a step beyond interdisciplinary research, in which researchers from different disciplines contribute elements to a common problem, or multidisciplinary research, where disciplines overlap. The convergence of the life sciences, the physical sciences, and engineering has the potential to produce a transdisciplinary science in which separate disciplines merge into something new. In laboratories such as that of Stanford’s Lucy Shapiro (see sidebar), this convergence is generating not just new results but new approaches to research. As Keith Yamomoto, Professor and Executive Vice Dean of the School of Medicine at the University of California, San Francisco, put it, “disciplines that were thought to be distinct begin to melt together and be able to contribute different kinds of expertise and thought processes to solving problems.” A Wiring Diagram for Cells Cellular systems can be represented in “wiring diagrams” analogous to those of electronic circuits. But the components in the diagram are proteins, nucleic acids, and other biologically active molecules while the wires are interactions among those components. Lucy Shapiro’s laboratory at the Stanford University School of Medicine chose a simple organism -- a bacterium called Caulobacter crescentus -- and set out to understand all the integrated processes that this organism needs to function as a living cell. Among these processes are the biochemical circuits that control cell division and differentiation. Four proteins serve as master regulators of these processes, Shapiro and her colleagues have found. Rising and falling quantities of these proteins in in particular parts of the cell produce “an exquisite coordination of events in a three-dimensional grid.” Building these circuit diagrams has allowed researchers to identify nodes that control cellular functions and are attractive targets for drugs designed to alter the functioning of cells. Research in Shapiro’s lab, for example, has led to drug development projects for two new antibiotics and an antifungal agent. Shapiro’s lab members are about half biologists and half physicists and engineers. Each has had to learn the language of the others so that they can work together. “You put all these people together and amazing things happen,” Shapiro said. “Now we understand in a completely different way how this bacterial cell works.” Maximizing the Return on our Life Sciences Research Investment In many places, life sciences research is already being done in new ways, but several speakers emphasized that changes in how life sciences research is funded, how students are educated, and how academic institutions are organized could speed the emergence of new ideas and applications from the life sciences research community. The tremendous potential of the life sciences demands new approaches not just by researchers but by the policymakers and administrators who fund and oversee scientific research. While many steps can be taken to strengthen the scientific enterprise, speakers at the meeting emphasized two in particular: supporting high-risk, high-payoff science, and educational initiatives at all levels to prepare the scientists and engineers of the future. 10

Prepublication Copy Taking Risks Stagnant funding for the life sciences over the past five years has had major consequences for research. When funding is tight, science almost always becomes more conservative. Funders focus on projects that have a high likelihood of succeeding, not on projects that could have great payoffs but may be less likely to succeed. “Potentially transformative or high-risk, high-reward research is discouraged,” said Cech. At the same time, younger scientists tend to have a harder time getting research grants––especially when funding is constrained. They have less of a track record, so their proposals tend not to score as highly in reviews of their proposals. Also, because of the shift in science toward work that combines disciplines, many projects tend not to fall neatly within disciplinary boundaries, even though the panels set up to review proposals tend to be organized by discipline. Today, the average age at which biologists get their first R01 grants as independent investigators from NIH is 43. “I find this astonishing,” said Hockfield. “I got my first NIH R01 when I was 30, and I was not considered to be a young receiver of an award.” According to Zerhouni, “The greatest risk in periods of tight economic times and tight budgets is to stop taking risks.” Funding mechanisms need to cut across different institutes within NIH and across federal agencies. While the principles of peer review need to be maintained to ensure the quality of the research that is funded, several speakers suggested that a new kind of proposal review mechanism may be needed that has a multidisciplinary foundation. “Our funding agencies and not just our scientists need to be collaborators,” said Hockfield. Zerhouni suggested several ways that more adventurous science could be encouraged. For example, a small percentage of support could be set aside at each research- funding agency as a “venture budget.” These funds could be used to take advantage of fast- emerging opportunities and to support small-scale projects to gauge the likelihood of success for a larger project. Also, program officers could be given some authority to override study sections to support innovative projects with the potential for important advances, allowing researchers to spend their time doing science instead of writing grant applications. Finally, it is important for federal agencies to have “flexible funding mechanisms to support unconventional self-assemblies of scientists with ideas beyond the typical framework of grants.” Zerhouni – along with several other speakers - further asserted that federal agencies need to find ways of supporting younger scientists. The panels that review grant proposals could be organized in such a way that expectations are appropriate for the career stages of applicants. Programs may also be needed that move promising young researchers from initial, small-scale grants into mainstream funding mechanisms. Steps in these directions have occurred in both the public and private sectors. NIH, NSF, and the Department of Defense have new grant programs to support younger researchers. Private philanthropies like the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation have instituted programs that essentially fund people rather than projects. “We identify the best people that we see coming up and invest in them,” said Kingsbury. “It has been incredibly powerful and transformative in our view.” The Bill & Melinda Gates Foundation has been supporting small-scale explorations of 11

Prepublication Copy promising but high-risk ideas. The federal government’s support of the life sciences would benefit by incorporating more of this spirit of innovation, said Zerhouni. At the same time, research administrators need the tools to do their jobs more effectively. Today it can be difficult to determine what kinds of science are being funded even within a single agency such as NIH. The diversity of funding sources is a strength rather than a weakness of the U.S. research system, said Kingsbury, but program officers need some way of knowing whether important research is being overlooked. New policies also are needed to promote efforts designed to move discoveries from the laboratory to the marketplace. For example, some work progresses best in an academic environment and some progresses best in an industrial setting, said Hockfield. Researchers from both settings need to be able to work together with clearly spelled out policies on conflict of interest that facilitate research without compromising its integrity. Producing the Scientists and Engineers of the Future Fifty years ago, the challenge posed by the Soviet Union’s launch of Sputnik helped generate a response in the Unites States that caused a generation of students to become excited about science and engineering. The potential of the life sciences to address major global problems could create a similar level of enthusiasm for science, technology, engineering, and mathematics (STEM) subjects today, said Hockfield. “We have to encourage young people to take up this next challenge,” she said. “[We need] to grab the attention of kids from K to 12 to say, ‘wow, this is cool stuff, I want to be doing science and engineering and math.’” Education in STEM subjects needs to reflect the changing nature of science. The disciplinary structure of university departments organizes knowledge in a coherent way for teaching and research. But it also erects barriers to the kind of across-discipline research and education needed to address many of today’s major challenges. Universities need to find ways to reduce the institutional, physical, and attitudinal barriers between departments, said several speakers at the meeting. Students throughout the sciences and engineering need a “broad education,” said Hockfield, “so that the material they study has a common element that equips them to cross talk.” Education in the life sciences also needs to be more quantitative, more analytic, and more computationally oriented, said Kingsbury. This emphasis needs to be in place both at the molecular level and at the organismal and ecological levels so that data and insights travel freely and quickly within the life sciences and between the life sciences and other disciplines. In addition, STEM education needs to reflect the changing nature of students. Young people are growing up in a world saturated with information technologies. They interact electronically with social networks, contribute to wikis and other distributed collaborations, and receive information in ways different from those of previous generations. Students themselves are more multidisciplinary than in the past and recognize the importance of working on problems that transcend disciplinary boundaries. Before graduate school, and even before college, the groundwork needs to be laid for the integration of the life sciences, the physical sciences, and engineering. “We need to find more and more ways, . . . starting at least at the high school level, to teach topics from a multidisciplinary point of view,” said Cech. According to Varmus, changes at the 12

Prepublication Copy precollege level require “high school teachers who are better paid and who approach science not from textbooks but from experiential approaches.” College instructors also need more funding and support to develop the kinds of innovative classes that combine elements from different disciplines. The life sciences have an intrinsic advantage in education because of the innate interest students have in learning about things that are alive, said Cicerone. “That sense of wonder and curiosity . . . is what drives so many students.” Conclusion One hundred years ago, the airplane and the tungsten filament light bulb were five-year-old inventions. “No one could have predicted where those inventions would have taken us,” said Yamamoto. Today the life sciences are in a comparable position. It is impossible to predict what new technologies and new industries will arise from today’s basic research. What can be predicted is that the world will undergo dramatic changes in the next one hundred years, and that the life sciences can help ensure that those changes produce a better life for people everywhere. While the potential for significant advances is enormous, many challenges need to be to overcome. Achieving the promise of the life sciences articulated by the Summit speakers will require investment, creative approaches to how life sciences research is organized and funded, and attention to improving science education at all levels. The Summit demonstrated that many of the ingredients for success are already in place. Many policy-makers, university officials, and scientists have begun to implement the changes that will allow the life sciences to transform America’s––and the world’s–– future. Expanding these initiatives to a broader set of funding agencies, universities, and industrial entities will help ensure that the 21st century will be, as many have predicted, the century of biology. 13

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