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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research 11 Findings and Recommendations Finding 1 Biological science can contribute to solving societal problems and to economic competitiveness. Basic and applied research targeted toward a particular mission is one way to accomplish this important goal. However, increased investment in the development of biology’s fundamental theoretical and conceptual basis is another way to reap practical benefits from basic biological research. Theory is an integral part of all biological research, but its role is rarely explicitly recognized. The living world presents a vast reservoir of biological solutions to many practical challenges, and biological systems can inspire innovation in many fields. The many ways that basic biological research contributes to medicine are very familiar, but basic biology can also contribute to advances in fields as diverse as food, fishery, and forest production, pest management, resource management, conservation, transportation, information processing, materials science, and engineering. Biological research breakthroughs, therefore, have the potential to contribute to the solution of many pressing problems, including global warming, pollution, loss of biodiversity, fossil fuel dependence, and emerging infectious diseases. As the many examples in this report attest, biology is characterized by unity and diversity. There is unity because many biological processes have been preserved through evolution. There is also diversity because natural selection has led to many innovative solutions to the practical problems that living organisms have encountered over billions of years. Therefore, discoveries about a particular organism, sensory pathway, or regulatory network
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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research can have immediate applications throughout biology, and the transformative insight that provides the most direct path to a practical solution may arise in a seemingly unrelated research area. Giving explicit recognition to the role of theory in the practice of biology and increasing support for the theoretical component of biology research are ways to help make such connections and thus leverage the value of basic biological research. The extent of life’s diversity has not yet been plumbed, and many biological processes are understood only imperfectly. New tools and computational capabilities are improving biologists’ ability to study complex phenomena. Tying together the results of research in the many diverse areas of biology requires a robust theoretical and conceptual framework, upon which a broad and diverse research portfolio of basic biological investigations can be based. The impact of biology on society could be enhanced if discovery and experimentation are complemented by efforts to continuously enrich biology’s fundamental theoretical and conceptual basis. Recommendation 1 Theory, as an important but underappreciated component of biology, should be given a measure of attention commensurate with that given other components of biological research (such as observation and experiment). Theoretical approaches to biological problems should be explicitly recognized as an important and integral component of funding agencies’ research portfolios. Increased attention to the theoretical and conceptual components of basic biology research has the potential to leverage the results of basic biology research and should be considered as a balance to programs that focus on mission-oriented research. Finding 2 Biologists in all subdisciplines use theory but rarely recognize the integral and multifaceted role that theory plays in their research and therefore devote little explicit attention to examining their theoretical and conceptual assumptions. Major advances in biological knowledge come about through the interplay of theoretical insights, observations, and key experimental results and by improvements in technology that make new observations, experiments, and insights possible. The fragmentation of biology into many subdisciplines means both that the mix of these components can differ dramatically from one area to another and that the development of theoretical insights that cut across subdisciplines can be difficult. It is the committee’s opinion that all subdisciplines of biology would benefit from an explicit examination of the theoretical and conceptual framework that characterizes their discipline.
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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research Recommendation 2 Biology research funding portfolios should embrace an integrated variety of approaches, including theory along with experiment, observation, and tool development. Biologists in all subdisciplines should be encouraged to examine the theoretical and conceptual framework that underlies their work and identify areas where theoretical advances would most likely lead to breakthroughs in our understanding of life. Workshops sponsored by funding agencies or scientific societies would be one way to facilitate such discussions. The theoretical and conceptual needs identified by such subdisciplinary workshops should then be integrated into the funding programs for those subdisciplines. It would also be worthwhile to sponsor interdisciplinary workshops to identify theoretical and conceptual approaches that would benefit several subdisciplines. Finding 3 New ways of looking at the natural world often face difficulty in acceptance. Challenges to long-held theories and concepts are likely to be held to a higher standard of evidence than more conventional proposals. Proposals that break new ground can face difficulty in attracting funding, for example, those that cross traditional subdisciplinary boundaries, take a purely theoretical approach, or have the potential to destabilize a field by challenging conventional wisdom. Such proposals are likely to be perceived as “high risk” in that they are likely to fail. However, their potential for high impact warrants special attention. Successfully determining which of them deserve funding will require input from an unusually diverse group of reviewers. Recommendation 3 Some portion of the basic research budget should be devoted to supporting proposals that are high risk and do not fall obviously into present funding frameworks. One possibility is to initiate a program specifically for such “high-risk/high-impact” proposals—whether they are purely theoretical, cross-disciplinary, or unconventional. Another is to encourage program officers to include some proportion of such proposals in their portfolios. A third is to provide unrestricted support to individuals or teams of scientists who have been identified as particularly innovative. Evaluation of these proposals should be carefully designed to ensure that reviewers with the requisite technical, disciplinary, and theoretical expertise are involved and that they are aware of the
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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research goal of supporting potentially consensus-changing research. Proposals that challenge conventional theory require not only that the originality and soundness of the theoretical approach be evaluated but also that the biological data being used are appropriate and the question being asked is significant. Finding 4 Technological advances in arrays, high-throughput sequencing, remote sensing, miniaturization, wireless communication, high-resolution imaging, and other areas, combined with increasingly powerful computing resources and data analysis techniques, are dramatically expanding biologists’ observational, experimental, and quantitative capabilities. Questions can be asked, and answered, that were well beyond our grasp only a few years ago. It is the committee’s contention that an increased focus on the theoretical and conceptual basis of biology will lead to the identification of even more complex and interesting questions and will help biologists conceive of crucial experiments that cannot yet be conducted. Biologists’ theoretical framework profoundly affects which tools and techniques they use in their work. All too frequently, experimental and observational horizons are unconsciously limited by the technology that is currently available. Advances in technology and computing can provide biologists with many new opportunities for experimentation and observation. For many of the multiscale questions raised in this report, there is a strong need for teams of biologists, engineers, physicists, statisticians, and others to work together to solve cross-disciplinary problems. The interaction and collaboration of biologists with physicists, engineers, computer scientists, mathematicians, and software designers can lead to a dynamic cycle of developing new tools specifically to answer new questions, rather than limiting questions to those that can be addressed with current technology. The growing role and shortening life cycle of technology mean that biologists will have to become ever more adept in the use of new equipment and analysis techniques. Understanding the capabilities, and especially the limitations, of new instruments so that experiments are designed properly and results interpreted appropriately will be important in more and more areas of biology. Because the potential benefits of more precise and rapid measurements of biological phenomena are so high, it will be important for biologists to be aware of both instrumentation capabilities in the physical and engineering sciences and theoretical advances in physics, chemistry, and mathematics that could be integrated into biological research. Conversely, if researchers outside biology are aware of the kinds of questions biologists are now asking, they can use their techniques, instruments, and approaches to advance
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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research biological research. Close collaboration between biologists and researchers in other fields has great promise for leveraging the value of discoveries and theoretical insights arising from basic biological research. Recommendation 4 In order to gain the greatest possible benefit both from discoveries in the biological sciences and from new technological capabilities, biologists should look for opportunities to work with engineers, physical scientists, and others. Funding agencies should consider sponsoring interdisciplinary workshops focused on major questions or challenges (such as understanding the consequences of climate change, addressing needs for clean water, sustainable agriculture, or pollution remediation) to allow biologists, scientists from other disciplines, and engineers to learn from each other and identify collaborative opportunities. Such workshops should be designed to consider not just what is possible with current technology but also what experiments or observations could be done if technology were not an obstacle. Opportunities for biologists to learn about new instrumentation and to interact with technology developers to create new tools should be strongly supported. One possible approach would be the creation of an integrative institute focused on bioinstrumentation, where biologists could work in interdisciplinary teams to conceive of and develop new instrumentation. The National Center for Ecological Analysis and Synthesis and the National Evolutionary Synthesis Center could serve as models for the development of such an institute. Finding 5 To get the most out of large and diverse data sets, they will need to be accessible and biologists will have to learn how to use them. While technology is making it increasingly cost-effective to collect huge volumes of data, the process of extracting meaningful conclusions from those data remains difficult, time-consuming, and expensive. Theoretical approaches show great promise for identifying patterns and testing hypotheses in large data sets. It is increasingly likely that data collected for one purpose will have relevance for other researchers. Therefore, the value of the data collected will be multiplied if the data are accessible, organized, and annotated in a standardized way. While it is somewhat new to many areas of biology, other fields that create massive data sets, like astronomy and seismology, rely on theory to guide pattern detection and to direct in silico experimentation and modeling. Getting the most out of the extensive biological data that can now be collected will increasingly require that biologists broadly develop
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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research those skills and collaborate with mathematicians, computer scientists, statisticians, and others. This process of building community databases is well underway in many areas of biology, genomics being a prominent example, but the specialized databases developed by one research community may be unknown or inaccessible to researchers in other fields. Significant resources are needed to maintain, curate, and interconnect biological databases. Recommendation 5 Attention should be devoted to ensuring that biological data sets are stored and curated to be accessible to the widest possible population of researchers. In many cases, this will require standardization. Providing opportunities for biologists to learn from other disciplines that routinely carry out theoretical research on diverse data sets should also be explicitly encouraged.