Summary

“… the action most worth watching is not at the center of things but where edges meet … shorelines, weather fronts, international borders …”


Anne Fadiman, The Spirit Catches You and You Fall Down


Almost since their inception, the natural sciences, those fields that use the scientific method to study nature, have been divided into two branches: the biological sciences and the physical sciences. In part, this division can be viewed as a convenient social contrivance. However, over time it has also served more functional purposes. Physical scientists, when seeking the fundamental laws, have found it necessary to focus on the simplest of systems—elementary particles, atoms, and molecules—items clearly not alive. It also has been convenient for biological scientists to investigate the immense diversity of living things and their elaborate inner workings without simultaneously accepting the burden of trying to follow these complexities down to their atomic level roots.

Today, while it still is convenient to classify most research in the natural sciences as either biological or physical, more and more scientists are quite deliberately and consciously addressing problems lying at the intersection of these traditional areas. This report focuses on their efforts. As directed by the charges in the statement of task (see Appendix A), the goals of the committee in preparing this report are several fold. The first goal is to provide a conceptual framework for assessing work in this area—that is, a sense of coherence for those not engaged in this research



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Summary “. . . the action most worth watching is not at the center of things but where edges meet . . . shorelines, weather fronts, international borders . . .” Anne Fadiman, The Spirit Catches You and You Fall Down Almost since their inception, the natural sciences, those fields that use the sci- entific method to study nature, have been divided into two branches: the biological sciences and the physical sciences. In part, this division can be viewed as a con- venient social contrivance. However, over time it has also served more functional purposes. Physical scientists, when seeking the fundamental laws, have found it necessary to focus on the simplest of systems—elementary particles, atoms, and molecules—items clearly not alive. It also has been convenient for biological scien- tists to investigate the immense diversity of living things and their elaborate inner workings without simultaneously accepting the burden of trying to follow these complexities down to their atomic level roots. Today, while it still is convenient to classify most research in the natural sciences as either biological or physical, more and more scientists are quite deliberately and consciously addressing problems lying at the intersection of these traditional areas. This report focuses on their efforts. As directed by the charges in the statement of task (see Appendix A), the goals of the committee in preparing this report are several fold. The first goal is to provide a conceptual framework for assessing work in this area—that is, a sense of coherence for those not engaged in this research 

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ReseARch inteRsection PhysicAl life sciences  At the of the And about the big objectives of the field and why it is worthy of attention from fellow scientists and programmatic focus by funding agencies. The second goal is to assess current work using that framework and to point out some of the more promising opportunities for future efforts, such as research that could significantly benefit society. The third and final goal of the report is to set out strategies for realizing those benefits—ways to enable and enhance collaboration so that the United States can take full advantage of the opportunities at this intersection. CONCEPTuAL FRAMEWORk FOR ASSESSING THIS INTERSECTION Any attempt to provide an all-inclusive framework for this work will inevitably leave out research that belongs within it. With that caveat, a good way to think of research at this intersection is that it turns ways of looking at things—both figu- ratively and literally—from their original purpose and uses them to tackle new problems, often in ways far removed from when they were first conceived. Most—but not all—of the new problems being addressed at this intersection are biological ones, largely because of the incredible richness of this field. The realm of biology is immense, involving complicated structures as small as molecules and as large as the biosphere and timescales that range from submicroseconds to eons. Answers to these problems seek not only to describe how the individual structures, in their immense complexity and diversity, work but also how they interplay. A very rich source of potential questions indeed. The ways of looking often come from the physical sciences. Those ways might be conceptual—approaches for looking at and solving problems—or analytical— methods for extracting understanding from data—or technical—tools for collect- ing information needed to address the problem at hand. But it is this intermingling of problems from one arena and ways of looking at them from another arena that makes this intersectional area between the biological and physical sciences so rich and offers many of the opportunities that reside there. The committee expects that ideas will emerge from such studies that will go well beyond the intersection and transform both the biological and physical sciences. CuRRENT WORk AT THE INTERSECTION What, then, are some of the areas being explored at this intersection? Interest- ingly, many share common conceptual themes, several of which are discussed in this report. Interactions appear in both branches, albeit with much different content and contexts. Describing how individual particles interact—what forces and energy exchanges cause crystalline materials to form, and matter in all phases to display characteristic behavior and to undergo phase changes—are mainstays of the world of physics. However, these ways of thinking about and discussing how inanimate

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summARy  objects interact have been found useful to scientists attempting to answer questions about the interplay of biological matter at many different levels. Another area finding fertile ground and producing fruitful cross-research opportunities centers on the dynamics of systems. Equilibrium, multistability, and stochastic behavior—concepts familiar to physicists and chemists—are now being used to tackle issues involved in living systems such as adaptation, feedback, and emergent behavior. Ideas of pattern formation that are at the heart of condensed matter physics now help us to understand biological self-assembly and the devel- opment of biological systems. This report also discusses how some of the mysteries of the biological world have been unraveled using tools and techniques developed in the physical sciences. These tools include not only imaging devices, both photon- and matter-based, but also computational models and algorithms. While many of them are used interchangeably by the two fields, others must be modified. However, to reach the heart of biological systems, even more sophisticated investigatory technologies and tools will be needed, many of which have not even been imagined much less developed. In preparing this report, the committee was mindful of the vastness of the number of topics that arguably comes within the ambit of this report’s subject matter. Work taking place at the intersections of engineering and the life sciences and of materials development and the life sciences covers but two of such topics. Both are fascinating examples of where the meshing of different cultures and sets of ideas can produce much fruitful discussion and advancement.1 However, the statement of task for this committee focuses on research, limiting this report to more basic activities than those typically involved in engineering and materials development. Further, the committee acknowledges that the research that is the subject matter of this report both arises from and depends upon the rich, ongoing efforts taking place within the core disciplines of the physical and life sciences. Such intersectional research serves to supplement rather than to supplant the scientific advances being made in the more traditional fields. PROMISING OPPORTuNITIES FOR FuTuRE EFFORTS Some of the most fundamental challenges in this area and near-term pros- pects for successfully meeting them are discussed in the form of five Grand Challenges: 1Some have been covered in other NRC reports. See, for example, Inspired by Biology: From Molecules to Materials to Machines, Washington, D.C.: The National Academies Press (2008) and A New Biology for the st Century, Washington, D.C.: The National Academies Press (2009). Others might be the focus of future reports.

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ReseARch inteRsection PhysicAl life sciences  At the of the And • Grand Challenge . Natural substances display remarkable architecture, demonstrating the immense breadth of what can be achieved in developing structures and systems. Can the skills and knowledge-sets of biological and physical scientists be combined to provide greater insight into identifying those structures, capabilities, and processes that form the basis for living systems, and then to use that insight to construct systems with some of the characteristics of life that are capable, for example, of synthesizing materials or carrying out functions as yet unseen in natural biology? • Grand Challenge . The human brain may be nature’s most complex sys- tem. Can we understand how it works and build on that understanding to predict brain function? Addressing this challenge will require drawing on the resources of the physical sciences, both existing and to be developed, from imaging techniques to modeling capabilities. • Grand Challenge . Genes and the environment interact to produce living organisms. Can we deepen our understanding of those interactions to begin to comprehend how organisms change over time—how they age and heal, for example—and from that understanding realize the promise of personal- ized medicine and access to better health care? • Grand Challenge . Earth interacts with its climate and the biosphere through strikingly different yet intertwined mechanisms that operate over vast ranges of time and space. Can life and physical scientists develop an effective approach for understanding how these mechanisms interplay and use that understanding to develop strategies that will preserve this heritage? • Grand Challenge 5. Living systems display remarkable diversity, serving to protect communities from harm. This diversity is declining, however, as the result of human activities, yet efforts to understand its role in the health of a species or an ecosystem have only recently been undertaken. Can knowledge gained at the intersection of the life and physical sciences teach us how to prosper while sustaining the diversity that allows life to flourish? Further research at this intersection not only will advance our understanding of the fundamental questions of science, but will also significantly impact public health, technology, and stewardship of the environment for the benefit of society. In the world of technology, our economy clearly is based on materials, but no synthetic material in use today is as complex as a dead piece of wood, let alone a living organism. Prospects for a material world as adaptive and robust as living things have been the stuff of science fiction for decades. To achieve these dreams requires a greater understanding of the organizing principles of life. For public

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summARy 5 health, the complexity of molecular recognition and the emergent regulation of physiology must be better understood if drug design is to progress from the art it is to engineering science. Without understanding the diversity encompassed in human biology, personalized medicine will remain more a hope than a reality. We often think of environmental challenges as being biological (“Save the whales!”) or physical (“Limit greenhouse gases!”) but, again, this distinction between the disciplines is a distortion. The constant interplay between the bio- logical sciences and the physical sciences is profound when Earth is viewed as an entire system. STRATEGIES FOR ENABLING AND ENHANCING WORk AT THE INTERSECTION Throughout the report, the committee recommends ways to accelerate progress in this field. Some of these recommendations are implicit. By describing the vast array of outstanding questions at this intersection, it hopes to intrigue some of its fellow scientists to venture into this area and perhaps find interesting questions to address. Of the report’s explicit recommendations, several are directed to those administering the faculties and resources of our great research institutions. In both the academic and business world, the cultures of the biological and physical sci- ences have evolved separately. Indeed both of these broad areas maintain numerous subcultures within themselves. It might seem that the daily life of a physician and that of a professor of theoretical physics would have nothing in common, but they must appreciate each other’s insights if the scientific challenges at this interface are to be met and the societal benefits realized. Just as important, educational institu- tions need to develop multidisciplinary research and education opportunities that transcend the traditional departmental structure. They need to establish curricula and training opportunities to prepare the next generation of scientists to grapple with the questions posed at this intersection. The committee recognizes that the needed changes will not come about just because of this report. Federal and private funding agencies will have to estab- lish policies and programs that provide the appropriate incentives. Professional societies will need to break down disciplinary barriers and promote scholarships at the intersection of disciplines. And academic leaders will need to take what steps they can to facilitate the changes. This report describes the many profound and societally important scientific issues yet to be explored in this area. In it, the committee hopes to make the case that inertia and the understandable resistance to change must be overcome and that necessary structural changes in academic departments and curricula need to be undertaken.

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ReseARch inteRsection PhysicAl life sciences  At the of the And RECOMMENDATIONS • universities should establish science curriculum committees that include both life scientists and physical scientists to coordinate curricula between science departments and to plan introductory courses that prepare both those who would major in the life sciences and those who would enter the physical sciences. • Professional scientific societies should partner with peer societies across the life and physical sciences to organize workshops and provide resources that will facilitate multidisciplinary education for undergraduates. • Federal and private funding agencies should offer seed grants to academic institutions to develop new introductory courses that incorporate both the physical and life sciences and to professional societies for organiz- ing workshops and developing resources for multidisciplinary educa- tion. They should also support research to identify best practices in such education. • Federal and private funding agencies should offer expanded train - ing grants that explicitly include graduate students and postdoctoral researchers from fields across the life and physical sciences and that require the involvement of academic departments from both the physi- cal and life sciences. Funding agencies should also offer administrative supplements to existing research grants that would enable a principal investigator in the life sciences to support a postdoctoral researcher with a background in the physical sciences, or vice versa. The report also makes recommendations to help provide better support and guidance for research in these areas. The committee hopes that this report makes the case that much of the best science at this intersection has difficulty finding a financial home and resources. All too often, the most interesting questions that researchers seek to address here do not readily fall within the purview of a particular agency program or review structure. Accordingly, the committee calls for changes in funding mechanisms that will produce effective collaboration and cooperation among federal agencies that support research in the physical and life sciences.2 Established investigators trained in one discipline should have the opportunity to receive training in another, so they may apply their experience to multidisciplinary problems. Mechanisms need to be put in place to support investigator-initiated multidisciplinary research where review of the proposal assesses the candidate’s previous work rather than just the research being proposed. 2 See also the discussion in the NRC report A New Biology for the st Century, Washington, D.C.: The National Academies Press (2009).

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summARy  RECOMMENDATION The Office of Science and Technology Policy (OSTP) and the Office of Man- agement and Budget (OMB) should develop mechanisms to ensure effec- tive collaboration and cooperation among federal agencies that support research at the nexus of the physical and life sciences. In particular, OSTP and OMB should work with federal science agencies to establish stand- ing mechanisms that facilitate the funding of interagency programs and coordinate the application and review procedures for such joint programs. Moreover, the National Science and Technology Council should establish a standing interagency working group on multidisciplinary research within its Committee on Science, with focus on the intersection of the physical and life sciences. RECOMMENDATION Federal and private funding agencies should offer opportunities for both early-career and established investigators trained in one discipline to receive training in another and apply their experience and training to interdis- ciplinary problems. In particular, postdoctoral career awards should be established that facilitate the transition of a candidate prepared in a physical science field to apply that training to important questions in the life sciences and vice versa. Funding agencies should also provide expanded support for experienced investigators to receive training in a new field, perhaps in the form of sabbatical fellowships. RECOMMENDATION Federal and private funding agencies should enhance the ability of more than one researcher to serve as principal investigator (PI) on research projects. Each PI should receive full credit for participation on the grant, with the lead PI serving as the administrative contact. RECOMMENDATION Federal and private finding agencies should devote a portion of their resources to support potentially transformative research, including opportunities at the intersection of the physical and life sciences. These sponsors should have peer review procedures that incorporate the viewpoints of scientists from a variety of disciplines. Moreover, they should continually assess the effective- ness of these grant programs and the review procedures to ensure that they are meeting the desired aims.

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ReseARch inteRsection PhysicAl life sciences  At the of the And RECOMMENDATION Federal and private funding agencies should expand support for interdisci- plinary and multidisciplinary research and education centers. In particular, extramural funding should be provided to establish and maintain center infrastructure and research expenses. Initial (e.g., 5-year) salary support for investigators performing research that spans disciplines should also be included, with continuing salary support for faculty associated with the center provided by the host institution(s) or department(s). To support these centers, universities will need to implement multidepartment hiring practices and tenure policies that support faculty working collaboratively within and across multiple disciplines, establish shared resources, and pro- vide incentives for departments to promote multidepartmental research and cross-disciplinary teaching opportunities. Many of these recommendations are not new, but instead resemble those rendered by previous committees about the need to break away from “stove piping”—narrowly focused and isolated funding programs—and to implement new ways for evaluating funding opportunities and prioritizing funding for the most promising research. These resemblances should be seen as a renewed acknowl- edgement by this committee that such changes remain important and continue to be necessary to take full advantage of the research opportunities at this interface. As noted by President Obama in his remarks to the National Academy of Sciences in April 2009, change and convergence are key to fully meeting the chal- lenges and opportunities at this intersection: In biomedicine . . . we can harness the historic convergence between life sciences and physical sciences that’s underway today [by] undertaking public projects—in the spirit of the Human Genome Project—to create data and capabilities that fuel discoveries in tens of thousands of laboratories and identifying and overcoming scientific and bureaucratic barriers to rapidly translate scientific breakthroughs into diagnostics and therapeutics that serve patients.3 New cultures must be forged and scientists must grow as comfortable in them as they are in their existing subcultures. There must be funding for work in those new cultures that extends beyond existing-culture “stove pipes.” Most important, they must prepare the rising generation to mine new-culture opportunities without losing touch with scientists in the traditional disciplines or the principles of such disciplines. The future will be driven by progress at this intersection. 3 Remarks by the President at the National Academy of Sciences Annual Meeting on April 27, 2009; available at http://www.whitehouse.gov/the_press_office/Remarks-by-the-President-at-the-National- Academy-of-Sciences-Annual-Meeting/. Last accessed September 3, 2009.