4
Putting the New Biology to Work

The New Biology approach has the potential to meet critical societal goals in food, the environment, energy, and health, but taking a “business-as-usual” approach to supporting the emerging field will delay achieving its full potential. Success depends on new kinds of investments to enable and drive new, broadly integrated approaches.

SETTING BIG GOALS: LETTING THE PROBLEMS DRIVE THE SCIENCE

Responses to great challenges often must be enunciated, formulated, and launched before the capabilities to meet those challenges are in place. In this way, the response often motivates the creation of the necessary capabilities. The decisions to send humans to the moon and to sequence the human genome were both made when the relevant technologies were far from being up to the job. In each case, establishing a bold and specific target created unforeseen routes to solutions.

Recent technological and scientific advances have brought the life sciences to a point where rapid progress toward understanding complex biological systems is possible. Many of the essential ingredients are already in place. The New Biology is already emerging, but the interdisciplinary, system-level, computationally intensive projects it encompasses fit uneasily within traditional funding opportunities and institutional structures. A piecemeal strategy, with many different agencies funding interdisciplinary projects and investing in various technologies would continue to advance the efforts of some pioneer researchers whose work has enormous promise. But the cross-cutting technologies and tools that would genuinely empower the New Biology will require significant investment and advance planning. Currently, no mechanism exists



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4 Putting the New Biology to Work The New Biology approach has the potential to meet critical societal goals in food, the environment, energy, and health, but taking a “business-as-usual” approach to supporting the emerging field will delay achieving its full potential. Success depends on new kinds of investments to enable and drive new, broadly integrated approaches. SETTING BIG GOALS: LETTING THE PROBLEMS DRIVE THE SCIENCE Responses to great challenges often must be enunciated, formulated, and launched before the capabilities to meet those challenges are in place. In this way, the response often motivates the creation of the necessary capabilities. The decisions to send humans to the moon and to sequence the human genome were both made when the relevant technologies were far from being up to the job. In each case, establishing a bold and specific target created unforeseen routes to solutions. Recent technological and scientific advances have brought the life sciences to a point where rapid progress toward understanding complex biological systems is possible. Many of the essential ingredients are already in place. The New Biology is already emerging, but the interdisciplinary, system-level, computationally intensive projects it encompasses fit uneasily within traditional funding opportunities and institutional structures. A piecemeal strategy, with many different agencies funding interdisciplinary projects and investing in various technologies would continue to advance the efforts of some pioneer researchers whose work has enormous promise. But the cross-cutting technolo- gies and tools that would genuinely empower the New Biology will require significant investment and advance planning. Currently, no mechanism exists 

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66 A NEW BIOLOGY FOR THE 21ST CENTURY for the extremely diverse community of current and future New Biologists to identify, prioritize, and advocate for the investments that would have the big - gest impact on the most sectors. An alternative approach is to set an ambitious goal and invest in the research and technology development needed to meet it. This approach has led to some of America’s most spectacular scientific achievements. The committee believes that the best way to capitalize on the unique opportunity presented by emerging capabilities in the life sciences is to undertake a bold national program to apply the New Biology to the solution of major societal problems. The call for a large commitment to applying the New Biology to big goals is not meant to imply that such a program would consist only of “big science” collaborative projects. The enunciation of big goals is important because it invites the participation of both collaborative groups and individuals from a broad spectrum of disciplines. Solutions to large-scale problems demand con - tributions from investigators operating both individually and together. Given the need to stimulate both conceptual and technological advances to fulfill the promise of the New Biology, a mixture of both individual and large-scale proj - ects will be necessary. The Institute of Medicine and National Research Coun - cil addressed this question in the 2003 report Large-Scale Biomedical Science (National Research Council, 2003c). That report states that “the objective of a large-scale project should be to produce a public good—an end project that is valuable for society and is useful to many or all investigators in the field.” The report goes on to point out that “large-scale collaborative projects may also complement smaller projects by achieving an important, complex goal that could not be accomplished through the traditional model of single-investigator, small-scale research.” The report lists several criteria that characterize projects that are best carried out on a large scale, including external coordination and management, a required budget larger than can be met under traditional funding mechanisms, a time frame longer than that of smaller projects, and strategic planning with intermediate goals and endpoints as well as a phase-out strategy. The committee chose to focus on four areas of societal need because the benefits of achieving these goals would be large, progress would be assessable, and both the scientific community and the public would find such goals inspi - rational. Each challenge will require technological and conceptual advances that are not now at hand, across a disciplinary spectrum that is not now encom- passed by the field. Achieving these goals will demand, in each case, transfor- mative advances. It can be argued, however, that other challenges could serve the same purpose. Large-scale efforts to understand how the first cell came to be, how the human brain works, or how living organisms affect the cycling of carbon in the ocean could also drive the development of the New Biology and of the technologies and sciences necessary to advance the entire field. In the

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 PUTTING THE NEW BIOLOGY TO WORK committee’s view, one of the most exciting aspects of the New Biology Initiative is that success in achieving the four goals chosen here as examples will propel advances in fundamental understanding throughout the life sciences. Because biological systems have so many fundamental similarities, the same technolo - gies and sciences developed to address these four challenges will expand the capabilities of all biologists. The committee suggests that a New Biology approach to the areas of food, the environment, energy, and health will require support for work at different scales, and from basic science to industrial application. As described in chap - ter 2, the New Biology has the potential to make significant contributions to addressing problems in each of these areas. In each area, the committee has suggested a challenge that is beyond the scope of any one scientific community or federal agency: for food, to generate food plants to adapt and grow sustain - ably in changing environments; for the environment, to understand and sustain ecosystem function and biodiversity in the face of rapid change; for energy, to expand sustainable alternatives to fossil fuels; and for health, to achieve individualized surveillance and care. The committee’s descriptions are meant to be evocative, not prescriptive. The first, and critical, step in designing New Biology programs in these four areas would be to bring to the table all of the stakeholders who could contribute, including scientists and engineers from many different communities, representatives of the relevant federal agencies, and private sector participants from both the commercial and non-profit sector. This step alone––bringing together the diverse talent and resources that already exist and giving them a mandate to plan a long-term, coordinated strategy for solving concrete problems––will already provide significant momentum to the emergence of the New Biology. The committee does not provide a detailed plan for implementation of such a national initiative, which would depend strongly on where administrative responsibility for the initiative is placed. Should the concept of an initiative be adopted, the next step would be careful development of strategic visions for the programs and a tactical plan with goals. It would be necessary to identify imaginative leaders, carefully map the route from ‘grand visions’ to specific programs, and develop ambitious, but measurable milestones, ensuring that each step involves activities that result in new knowledge and facilitates the smooth integration of cooperative interdisciplinary research into the traditional research culture. Implementation of a national New Biology Initiative project does not require creation of a new agency; coordination of the resources already existing in the academic, public, and private sectors is the goal. Estimating the cost of such an Initiative is beyond the scope of this committee, but for the purpose of providing a relative scale, the Interagency Working Group overseeing the National Plant Genome Initiative estimated that the program would require $1.3 billion to fund its programs from 2003 to 2008 ($260 million/year)(NSTC,

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 A NEW BIOLOGY FOR THE ST CENTURY 2003). The Common Fund, which funds the NIH Roadmap for Biomedical Research, had a budget of $480 million in 2008. Each of these programs has a more limited scope than any of the four proposed New Biology Initiative pro- grams in food, energy, environment and health, so the cost will be too large to be extracted from current research budgets. Whatever the budget, the timeline for such an Initiative must be long enough to justify investing in projects and technologies that will take time to bear fruit—at least ten years. As President Obama said in his address to the annual meeting of the National Academy of Sciences on April 28, 2009: As Vannevar Bush, who served as scientific advisor to President Franklin Roosevelt, famously said: “Basic scientific research is scientific capital.” An investigation . . . might not pay off for a year, or a decade, or at all. And when it does, the rewards are . . . enjoyed by those who bore its costs, but also by those who did not. That’s why the private sector under-invests in basic science—and why the public sector must invest in this kind of research (The White House, 2009). CROSS-CUTTING TECHNOLOGIES AND FOUNDATIONAL LIFE SCIENCES A quantum jump in the level at which we understand biological systems will be required to solve these grand challenges. Although there are increasing efforts to apply quantitative approaches to biological questions, more must be done to transform biology from its origins as a descriptive science to a predic - tive science. We will ultimately be limited in our ability to deploy biological systems to solve large-scale problems unless we significantly deepen our fun - damental understanding of the organizational principles of complex biological systems, a staggeringly difficult challenge. The growth of the New Biology will be dramatically accelerated by developing frameworks for systematically analyzing, predicting, and modulating the behavior of complex biological sys - tems. Only with powerful tools to interface with biological systems, accessible to diverse researchers, will it be possible to effectively generate biology-based solutions to the diverse problem areas described in chapter 2. Many of the foundational technologies and sciences identified as central to New Biology contribute to meeting all four of the critical societal goals. The case for informational technologies is obvious; they will provide the means of disseminating discoveries whether they arise out of research focused on energy, food, environment, or health. Perhaps less obvious is systems biology. Discovering the general principles of dynamic control of the flow of energy, chemicals, and organisms through units spanning from cells to ecosystems is critical for all four societal challenges. The advances in systems biological research will come from insights of computational and physical scientists and engineers as well as cell and molecular biologists. For example, to model the flow of information from the surface of a cell when a hormone

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 PUTTING THE NEW BIOLOGY TO WORK stimulates a receptor, to the activation of a set of genes, and, ultimately, cell division requires biologists to establish the experimental system, engineers to measure the time course of changes in thousands of molecules, computa - tional scientists to analyze the data, and all three to integrate the results into a cohesive, testable model. The tools and concepts for each of these steps also have to be created. The technologies and sciences are highly interconnected. Progress in any of them will support and advance all the others, leading to faster progress in meet- ing all four goals. Take, for example, the role of synthetic biology in improving pharmaceuticals. Synthetic biologists have already transferred into bacteria all of the necessary molecular machinery to synthesize artemisinin (Martin et al., 2003). This potent anti-malaria compound is naturally produced in small amounts in the leaves of the wormwood tree. Through synthetic biology, the compound can be produced in greater quantity and at lower cost. Clearly synthetic biology has great promise in the area of improving therapeutics and thereby human health. But synthetic biology also has the potential to engineer bacteria that produce high-energy biofuels, thus contributing to the energy challenge; bacterial communities that digest pollutants, thus cleaning the envi - ronment; or even sentinel plants that signal the presence of invasive species or crop pests. The field of synthetic biology, however, does not exist in a vacuum; to reach its greatest potential it will require imaging technology to watch indi - vidual proteins at work in cells, high throughput technology to measure the output of individual bacteria, engineered biological systems to support high yields of desired products, and information technologies to analyze and model complex metabolic networks. The foundational sciences and technologies described here are by no means a complete list. In fact, the emergence of new technologies and fields of science as a result of the interdisciplinary collaborations in New Biology is another likely benefit of a major interagency initiative. What is clear is that there are certain technologies and sciences that are of cross-cutting importance and will support communities of researchers whether they are working on food, the environment, energy, or health. Therefore, an interagency initiative will benefit from a mechanism for planning investments in these and other cross-cutting areas. These investments will drive progress in all four problem areas. But advances in these foundational sciences and technologies will not only advance the work of the communities working directly on the New Biology Initiative. The lesson of the Human Genome Project is that these advances will spread into the wider scientific community, multiplying the value and increasing the productivity of researchers throughout the life sciences community. Investment in cross-cutting technologies will make it likely that the United States will be the leader in the resulting new industries with all the attendant economic and job creation benefits.

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0 A NEW BIOLOGY FOR THE ST CENTURY NECESSITY FOR INTERAGENCY COLLABORATION Biology-based solutions to major societal problems will not come exclu - sively from any one area of research. Many federal agencies already support researchers who are pioneers in the development of the New Biology and invest in the cross-cutting technologies and sciences discussed above. But current institutional and disciplinary fragmentation has two consequences. First, tradi - tionally separate research communities often are not aware of the significance of––and therefore do not quickly capitalize upon––advances made in other communities, and second, the multiplying value of investments in cross-cutting technologies and foundational sciences that would benefit all the different kinds of biological research is not readily recognized. Fragmentation within and across institutional structures poses a significant barrier to realizing the full potential of the New Biology. Interagency collaboration will be critical for accel- erating the emergence of the New Biology. Through collaboration, the unique strengths of each agency––for example, in technology development, shared facility management, basic and applied research support, or grant review and administration––can be combined to the benefit of all and needless redundancy can be minimized. Most importantly, synergies and entirely new approaches will emerge that would otherwise never have been realized. Interdisciplinary programs either within or across agencies do exist and some can provide valuable insight into what makes such programs succeed. For example, the Ecology of Infectious Diseases (EID) initiative began in 1999 as a joint program of the National Science Foundation (NSF) and the Fogarty International Center (FIC) of the National Institutes of Health (NIH). The jointly administered program solicits competitive research grants for research on relationships between environmental change and the spread of infectious agents. A 2005 review (Burke et al., 2005) concluded that the program “suc- cessfully bridged disparate scientific disciplines and institutional cultures to develop new approaches to critical environmental and health challenges. It has also played an important role in building a cadre of interdisciplinary sci - entists” and that “the first five years of the EID program have been successful and productive. A total of 34 projects have been funded, and all of them have been both interdisciplinary and appropriately targeted.” The review went on to note that— The EID program mission overlaps with the missions of several of the NIH Institutes and NSF Directorates. As one of the few joint NIH-NSF programs, the EID program is also a valuable example of effective interagency cooperation. It is to the credit of the program officers and the original partner agencies that the need was recognized and the gap was effectively bridged. It is hoped that the lessons learned from the EID program can help encourage and inform future intra-agency and interagency cooperation. The report points out management issues that arose from the interagency nature of the program, and made several recommendations that will be even

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 PUTTING THE NEW BIOLOGY TO WORK more critical for enabling the larger scale interagency cooperation needed to implement the New Biology. For example, the report recommended that pro - posal application and reporting processes be streamlined into a single process and that data and sample sharing be promoted. Because of the many lessons learned in implementing this inherently interdisciplinary program, the review suggested that the EID program continue to evolve as a model for interagency cooperation and to strive to include other institutes at NIH and other divisions of NSF. Another successful interagency program is the National Plant Genome Initiative (NPGI), established in 1998. The NPGI is overseen by the Inter- agency Working Group (IWG) on Plant Genomes, which includes representa - tives from NSF, NIH, the Department of Agriculture (USDA), Department of Energy (DOE), Office of Science and Technology Policy (OSTP), Office of Management and Budget (OMB), and, since 2003, the Agency for Interna - tional Development (USAID). The IWG coordinates all plant genome research activities supported by the participating agencies. In 2008 the NRC issued the report Achieements of the National Plant Genome Initiatie and New Hori- zons in Plant Biology (National Research Council, 2008), which evaluated the first five years of the NPGI and made recommendations for the next five-year effort. The report concluded that “NPGI has been very successful by all mea- sures applied in this study” and that “plant genome scientists, as a community, have . . . elucidate[d] basic biological principles that are likely to be broadly operative across plant biology and can thus facilitate rapid applications to crop genomics and improvement.” The report also noted that “basic research funded by NPGI to date has served as the springboard for several applied, agency- specific, mission-oriented programs” and that “NPGI principal investigators also reported diverse and substantive translational activities . . . rang[ing] from starting their own companies on the basis of research results to patent filings and licensing arrangements with a variety of plant biotechnology entities.” The NIH Roadmap for Medical Research, which began in 2004, shares many characteristics of an interagency program, although it is confined to NIH. Its goal is to support research that crosses individual Institute and Center missions and to— address roadblocks to research . . . by overcoming specific hurdles or filling defined knowledge gaps. Roadmap programs span all areas of health and disease research and boundaries of NIH Institutes and Centers (ICs). These are programs that might not otherwise be supported by the NIH ICs because of their scope or because they are inherently risky. Roadmap Programs are expected to have exceptionally high potential to transform the manner in which biomedical research is conducted (NIH, 2009). The first round of funding included support for Interdisciplinary Research consortia, Clinical and Translational Science awards, projects in nanomedicine and structural biology, and centers for biomedical computing, and networks

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 A NEW BIOLOGY FOR THE ST CENTURY and pathways, among others. The second round of funding, in 2008, added epigenomics and analysis of the human microbiome. No external review of the program has taken place comparable to the NRC review of the NPGI, but many of the projects funded in the first round of funding were given renewed support for a second term, and internal evaluation of the effectiveness of the programs is built into the program. The joint effort between DOE and NIH to make synchrotron resources available to the life sciences research community is another example of suc - cessful interagency collaboration. The DOE funds the building and operation of the synchrotron facilities and NIH funds the building and operation of beamlines and experimental stations specifically designed for life sciences applications. These collaborations have been especially important for struc - tural biology and support for life sciences research is an increasingly important part of DOE’s portfolio. Currently “>40% of all research done at synchrotrons is in the biomedical sciences, although synchrotrons were originally devel - oped for high energy physics experiments” (National Center for Research Resources, 2009). The effort required for success in meeting the four major societal goals is different in scale from NPGI, EID, or the NIH Roadmap: it will need to involve more agencies, a larger investment and a long-term commitment. True interagency collaboration will demand interagency strategic planning (including a commitment to supporting the development of novel, integrated approaches to education), interagency funding, and interagency evaluation and review. Such an infrastructure for interagency collaboration will empower and enable the joint efforts of individuals and groups who are currently insulated from one another by bureaucratic barriers. Importantly, the need is not for a new agency, which would merely establish another silo, or even for a reorganization of existing agencies, but rather for mechanisms that actively permeate their current boundaries. Successful “permeation” would bring together scientists with different backgrounds, expertise, and goals, sparking new shared visions and synergies that could not have been realized separately, new ways of conceiv- ing and addressing major societal challenges, and eventually, transformational advances (Box 4.1). It is worth emphasizing explicitly three elements essential for achieving these ends. First, availability of dedicated interagency funds, outside of each agency’s individual budget needs, will motivate their involvement. Second, interagency strategic planning will place the focus of a broad spectrum of scien- tists and engineers on discovering novel, shared, life sciences-based approaches to these societal goals. Inclusion of some private sector scientists in this inte - grated planning effort might evolve novel public-private partnerships that could help drive late-stage efforts. And finally, given the cross-cutting and interdisci - plinary nature of the science that will be needed, establishment of a common interagency peer-review and evaluation process will set shared standards of

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 PUTTING THE NEW BIOLOGY TO WORK BOX 4.1 How Might Interagency Programs Catalyze the New Biology? Most key scientific advances to date have been funded by disciplinary funding programs. Advances in the New Biology will require programs that compel integration across disciplines, and synthesis that allows fundamental biology to be applied to key social challenges. One example of a funding program that stimulates such integration of computer science, informatics, and biology is the National Science Foundation– supported National Center for Ecological Analysis and Synthesis (NCEAS), located at the University of California-Santa Barbara. NCEAS provides long-term support in ecoinformatics, with on-site expertise in mathematics and geospatial modeling, visu- alization, and data synthesis, and invites individuals and teams to assemble at the center to conduct new kinds of research (NCEAS, 2009). The United Kingdom’s Engineering and Physical Sciences Research Program provides another approach to stimulating interdisciplinary scientific research through “sandpits.” Sandpits are residential workshops that include 20–30 participants from multiple disciplines, who work together to develop new research projects. By provid- ing an opportunity for exploring possible collaborations and immediate feedback on proposals, sandpits aim to “drive lateral thinking and radical approaches to addressing particular research challenges” (EPSRC, 2009). These efforts are resulting in dramatic advances. Similar efforts by interagency programs could launch the New Biology in the United States. excellence and drive periodic assessments of progress. A national New Biology Initiative would provide all three of these elements. There is every reason to expect that just as the Human Genome Project (HGP) had an impact across the life sciences far beyond the sequence data generated, investments in problem-focused projects and foundational tech- nologies and sciences will have similarly profound effects. The HGP had the advantage of a clear and definable endpoint––the complete sequence of the human genome––and a similar endpoint for some of these interdisciplinary and cross-cutting projects may be more difficult to define. However, the success of the HGP justifies community-wide efforts to plan and implement strategies to address challenges in the areas of food, the environment, energy, and health, and to invest in those technologies whose development would most significantly contribute to the success of those programs. THE ESSENTIALITY OF INTERDISCIPLINARY COLLABORATION The New Biology depends on interdisciplinary collaborations among scien- tists and engineers who share sufficient common language and understanding to

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 A NEW BIOLOGY FOR THE ST CENTURY envision and embrace common goals. To expand the pool of such individuals, it will be important to educate students in new ways. Interagency funding mechanisms could give universities incentives to create novel interdisciplinary entities that provide the basis both for new research approaches and for new educational strategies. Research universities and academic medical centers have for hundreds of years been structured around departments and colleges that circumscribe spe - cific disciplines and intellectual approaches (National Academies, 2004). These structures have had enormous value in encouraging discovery, establishing suf - ficient focus to virtually define whole fields, and imparting increasingly refined expertise to successive generations of trainees. Indeed, it is in many ways due to the success of these delineated departmental structures that the base of knowledge in each field has advanced sufficiently to make each relevant and potentially contributory to the others. Analogous to the separate government agencies, however, traditional department structures also serve as bureaucratic barriers that inhibit communication and productive interaction. Traditional metrics of success are accomplishments that can be ascribed to individual units, including grant generation, buildings, laboratory equipment acquisition, and financial support for faculty. Faculty within these units being considered for tenure and promotion are reviewed within the department structure, leav - ing them vulnerable if their focus is interdisciplinary. Certain institutions have recognized these limitations of traditional departments for establishing the New Biology, and have responded not by eliminating departmental structures, but rather by supplementing or overlaying them with interdisciplinary programs or institutes that have both research and educational objectives. Examples include the QB3 Institute at the University of California, Berkeley and the Institute for Bioengineering and Bioscience at the Georgia Institute of Technology. 1 The availability of interagency funds targeted to foster and nurture such integrative programs and institutes would strongly incentivize universities to establish and maintain them, and could prompt a reframing of promotion standards that rec - ognizes the value of collaborative and interdisciplinary education and research in the life sciences. THE CENTRAL IMPORTANCE OF INFORMATIONAL TECHNOLOGIES IN ENABLING THE NEW BIOLOGY Information is the fundamental currency of the New Biology. Interagency collaboration to develop the information sciences and technologies necessary to handle biological data would make the single largest contribution to future 1 For more information, see the websites of the California Institute for Quantitative Biosciences (http://research.chance.berkeley.edu/page.cfm?id=56) and the Parker H. Petit Institute for Bio- engineering and Bioscience at Georgia Tech (http://www.ibb.gatech.edu/).

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 PUTTING THE NEW BIOLOGY TO WORK life sciences research productivity. Provision of resources for the transmission, exchange, storage, security, analysis, and visualization of biological information will be essential. Biological research is increasingly supported by large-scale information resources available over computer networks. The development of these resources is a community effort. Researchers provide data acquired in their own laboratories, and data management systems organize the shared data and provide software tools for accessing, displaying, and interpreting parts of the data. Traditional dissemination of results through publications in journals can convey only a fraction of the information that is generated in most experiments. To capture the full benefit of funded scientific work, one must maximize the ability to share that information. Information about research results that is not made accessible is lost to the rest of the research community and thus can be considered a hidden tax on scientific research funding. Ongoing support for the storage, curation, and accessibility of data is critical, but it is also exceed - ingly expensive and, for funding agencies, comes at the expense of funding new research. Many specialized communities already exist to support database resources, for example, those focused on model organisms, such as Fly Base for the Drosophila community and TAIR for the Arabidopsis community. There will be increasing demand for resources to support these efforts, especially to support coordination among these specialized communities. Because so much can be learned in biology by comparing results across different organisms and systems, biological data have more value if made avail - able in a form that can be easily shared, meaning that measurements from one laboratory to another need to be clearly defined. Ideally, biological and biomedical experiments should adhere to nomenclatures and protocols speci - fied by standards bodies in consultation with communities of researchers. As much as possible, data should be reproducible, with no ambiguity as to their meaning and the experimental conditions under which they were acquired. However, rigid application of standards can hold back the introduction of new technologies and their application to a widening range of environments and conditions. Innovation in experimental technologies and their application will inevitably outpace efforts at standardization. Thus, while enforcing stan - dards for mature technologies, data management systems must also incorporate diverse types of ad hoc experimental measurements that are informative even if loosely characterized. A more recent development in the life sciences is the potential to derive new information from existing collections of data. Hypotheses can be tested and connections across different biological systems discovered using data acquired from the published literature by curation or automated search, transferred from other databases, or inferred from experimental data by various forms of aggre - gation, classification, clustering, comparison, annotation, or even analogical rea - soning. For example, most of the reported assignments of proteins to functional

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 A NEW BIOLOGY FOR THE ST CENTURY categories are derived not by biochemical experiments, but by imputation from the functional classification of similar proteins, often from a different species. The value of existing data can be multiplied by these approaches, but the basic scientific requirement of reproducibility requires that database management systems provide tools enabling researchers to trace the origins of such indirect inferences and assess the supporting evidence. The study of complex biological problems typically requires the integra - tion of diverse data sources (Box 4.2). For example, understanding the possible BOX 4.2 The Critical Role of an Information Infrastructure: Two Examples Electronic Medical Records The revolution in information technology has provided an enormous opportunity to make electronic medical records (EMR) a reality. These records not only have the potential to improve the quality of health care, but also could contribute substantially to basic biomedical research. In his speech to the annual meeting of the National Academy of Sciences, President Obama noted that EMRs offer “the opportunity to offer billions and billions of anonymous data points to medical researchers who may find in this information evidence that can help us better understand disease” (The White House, 2009). The great potential of an EMR for biomedical research is that it provides integrated health information, demographic data, imaging, and laboratory results for each indi- vidual. Currently, all the information that resides in each individual’s medical records is essentially invisible to researchers. The ability to search this massive data source would allow researchers to detect patterns in drug side effects, relationships between genomic information and disease incidence, spread of infectious diseases, and many others. However, the power of this resource to drive discovery and improve health has yet to be realized. This tremendous opportunity depends on developing an adequate information infrastructure. Turning all of the information in patients’ medical records into a form that can be standardized, digitized, secure, and anonymous is a major challenge and will require developing adequate network and analysis capabilities so that researchers can make full use of the data. The range of useful information that could be included is already vast and will only grow with time as the affordable genome, high-throughput pro- teomics and metabolomics technologies, and ever more sophisticated imaging are just over the horizon. A major effort to standardize (and anonymize) an EMR that provides the full complement of patient information, and to develop the resources to make those anonymized records fully accessible to researchers, would be an enormous boon to clinical research.

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 PUTTING THE NEW BIOLOGY TO WORK impact of a new cancer drug might involve data from human genome-wide asso- ciation studies, experiments with mice, characterizations of known molecular pathways and metabolic processes in yeast, and clinical experience with related drugs. A database on biodiversity might contain genetic sequence, photographs, movies, museum catalogues and digital representations of samples, geospatial coordinates, satellite images of collection sites over time, and detailed informa - tion about range, habitat, or behavior; ideally all of these kinds of data would be cross-referenced. Statistics, machine learning, and data mining, supported by The National Ecological Observatory Network It has become increasingly evident that long-term measurements of ecological function are key to sensing critical changes in the environment. Many studies are now revealing that short-term assessments are not capable of revealing such diagnostic and critical trends as changes in lake ice-melt, glacial melting, or changes in seasonal behavior that signal biological responses to climate change. Research platforms that allow early detection of changes in biological functioning over continental scales are necessary not only for understanding the interactions of climatic change and land use with ecological processes, but also for anticipating threshold responses that could occur during rapid environmental change. Similar to monitoring human health over broad scales to assess trends in risk and improvement, regular collection of data on ecosystem carbon dioxide exchange, land use change, and invasive and other species distributions is critical for understanding and predicting future conditions that influence human well- being. The currently planned NEON research platform represents such an initiative.a Just as with EMRs, the kinds of data researchers will need to share, compare, and ana- lyze are exceedingly diverse: satellite images; air, water and soil characteristics; mea- surements of species diversity and population sizes; changes in the genomes, health, and behavior of organisms; and many others. The benefits of such a data resource to understand, monitor, and predict environmental conditions would be great. Achieving either of these goals––making the information collected in EMRs avail- able to clinical researchers or the environmental information provided by NEON and many other sources to ecologists––will require a concerted effort. Ideally, even those two very different sets of data would benefit from being inter-operable; understanding the impact of the environment on human health, or how infectious agents pass between animals and humans would be just two possible applications. The full benefit of the impending revolutions in the life sciences discussed in this report will require a national effort to develop an information infrastructure that would support these applications. aFor more information, see the National Science Foundation report, The NEON Strategy (http:// www.neoninc.org/sites/default/files/NEON.Strategy.July2009.Release2_2_0.pdf).

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 A NEW BIOLOGY FOR THE ST CENTURY advances in probabilistic modeling, computational simulation, discrete math - ematics, algorithms, and data structures, are rapidly advancing in their ability to extract more information from such complex data sets. Innovative methods of information display, based on advanced graphics capabilities including anima - tion and virtual reality, will be essential for biological researchers to visualize such complex models. As argued throughout this report, the fundamental unity of biology means that data generated to develop biofuels are relevant to biomedical researchers and vice versa. Thus, building a system that captures the most possible value from ongoing research is a challenge that must be addressed above the level of any single biological subdiscipline or any one funding agency. The value of pro- viding a standardized, shared database with a user-friendly interface is exempli- fied by Genbank (National Center for Biotechnology Information, 2009), which provides researchers with a steadily increasing database of sequence informa - tion and standardized tools such as BLAST with which to analyze it. Genbank is housed within NIH, but its use is cross-agency. Every biology-related publi - cation is required to deposit any sequence generated into this central sequence database, and biologists funded by every agency make use of it. The Genbank model has not been achieved for other types of data that may not be as easy to share and standardize as sequence information. But this does not make such data less important. There is no single, obvious solution to the challenge of providing a flexible, efficient, and high-performance information infrastructure for the data that will power the New Biology. As technology and biological knowledge advance, both requirements and capabilities will shift. But explicitly acknowledging the essen- tial role of information to the life sciences and investing the effort and resources necessary to develop robust informational technologies and sciences would have an enormous pay-off in capturing the full value of life sciences research results. An immediate, interdisciplinary, and interagency effort to address the information requirements of the New Biology would provide a system-wide solution to a problem that is imposing greater and greater costs on the life sci - ences research establishment. ENGAGING THE PRIVATE SECTOR IN THE NEW BIOLOGY The private sector has a great deal to contribute to the proposed New Biology Initiative and should be engaged in the review and assessment of these interdisciplinary projects. Both commercial and non-profit entities will be help - ful in assessing knowledge in the field, helping to set objectives and evaluating progress. In some areas, the private sector has capabilities more advanced than the public sector, and is setting the standards for the field (e.g., handling of data for use by web-based search engines). In such cases, interdisciplinary projects would benefit from involving the private sector not only in review and assess -

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 PUTTING THE NEW BIOLOGY TO WORK ment, but also as explicit participants in the projects. In other areas, the private sector has data that are not readily available in the public domain that could be included in the projects. For example, efforts in the analysis of biological signal- ing pathways and networks rely on the compilation of extensive experiments involving manipulation of gene expression. The pharmaceutical industry has a large amount of such data, based on small-molecule drug manipulation, that is not readily available in the public domain. Similarly, there is a large amount of data from genetically informed breeding experiments in the agriculture indus - try. Such data would greatly facilitate the advancement of these pre-competitive opportunities, which would serve to benefit all stakeholders. EDUCATING THE NEW BIOLOGIST To thrive, the New Biology will require researchers with both depth of knowledge in a specific discipline and highly developed computational and quantitative skills. In addition, the New Biology will require these investigators to be well versed enough in varied disciplines and technologies to facilitate dialogue with other researchers and participate in integrated research. The emergence of the New Biology signals the need for changes in how scientists are educated and trained. A highly visible science program like a New Biology Initiative could inspire a new generation of students to see becoming a scientist or engineer as a way to contribute to solving important societal prob - lems. The Initiative itself would provide the opportunity to put in place and evaluate new educational and training opportunities. Thousands of reports, surveys, public speeches, articles, and television shows have bemoaned the quality of science education in the United States and numerous solutions to poor performance have been proposed. Many of these solutions would contribute to preparing students for careers as New Biologists. Implementing these solutions will require investment in human resources and materials and interaction among educators and researchers from a broad spec - trum of disciplines. The New Biology represents an integrated, problem-focused approach to science that is entirely consistent with research on how students learn best. Just as the goal of landing on the moon inspired a generation of students, high visibility projects using biology to solve important problems could provide a platform to engage all students in the process of science, and illustrate the excitement and benefits of using science and engineering to solve problems. An ambitious, high visibility program would demonstrate that basic science research is not distinct from society but is a critical ingredient in developing innovative solutions to societal problems. Integrating information from several disciplines to study practical ques - tions is a valuable approach at any educational level from kindergarten on. But it is at the undergraduate and graduate levels that the New Biology both

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0 A NEW BIOLOGY FOR THE ST CENTURY demands and presents an opportunity for new approaches. The New Biology makes it clear that biology is not only about observing and describing natural history and phenomena. Rather than teaching each level of biological organiza - tion separately––from molecules to cells to organs, etc., and on to ecosystems (if time allows)––a New Biology curriculum would emphasize the intercon - nections among those levels to understand system-level phenomena. Harvard University, for example, has recently introduced introductory courses that teach basic science material in the context of understanding AIDS treatment, or the possibility of synthetic life (Box 4.3). Such an approach makes it clear that quantitative analysis, physics, and chemistry are necessary to understand complex issues, along with biology. As BOX 4.3 Connecting Bio 101 to Real-World Issues: An Interdisciplinary Approach In 2005–2006, Harvard University launched two semester-long introductory courses that provide an interdisciplinary introduction to biology and chemistry. The first course synthesizes essential topics in chemistry, molecular biology, and cell biology and the second synthesizes essential topics in genetics, genomics, probability, and evolutionary biology. Scientific facts and concepts are introduced in the context of exciting and interdisciplinary questions, such as understanding the possibility of syn- thetic life, the biology and treatment of AIDS and cancer, human population genetics, and malaria. Through interdisciplinary teaching, students’ grasp of fundamental con- cepts is reinforced as they encounter the same principles in multiple situations. Each course is taught by a small team of faculty from multiple departments. Members of each teaching team attend all lectures and participate for the entire term. The preparation for and teaching effort in each course offering is integrated. Teaching assistants are also drawn from different departments and work in small interdepart- mental teams. Development of these courses required institutional support. The President, Dean of the Faculty, and the Chair of the Life Sciences Council all provided funds to support a one-year curriculum development effort, lab renovations, lower teach- ing fellow-student ratios, equipment, and development of teaching materials. One of the founding faculty member’s HHMI undergraduate education award contributed to developing specific sets of teaching materials. Success depended on finding faculty members with personal commitments to the principles of the courses and willingness to work as a team to build the new courses from scratch. This effort was rewarded as individual departments agreed to count these interdepartmental and interdisciplinary courses toward their respective departmental teaching expectations. Since the courses were implemented, undergraduate enrollment in introductory life sciences courses is up more than 30 percent and the number of life sciences majors has risen 18 percent.

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 PUTTING THE NEW BIOLOGY TO WORK students are taught to approach science as an exercise that solves a problem, they will recognize how mathematics, physics, chemistry, computational sci - ence, and engineering contribute to the problem-solving process and therefore see the relevance of and be more motivated to master these other disciplines. Students and teachers alike will recognize that memorization of observations and facts do not allow one to understand or predict how complicated bio- logical systems behave—and without that ability one will not be able to solve problems. Engaging students in the New Biology will require science teachers who understand and can pass on the interdisciplinary nature of science problem- solving. Exciting undergraduate experiences that are science based will not only help attract students into research careers, but also equip those life science majors who choose teaching careers with the disciplinary knowledge and hands- on experience to teach the New Biology. Many of the changes that would help prepare students to practice the New Biology have been recommended in several previous reports (Box 4.4), especially a 2003 NRC report, Bio 00: Transforming Undergraduate Education for Future Research Biologists (National Research Council, 2003a). Bio 2010 recommended that each institution of higher education reexamine its current curricula and ensure that biology students gain a strong foundation in mathematics, physical BOX 4.4 Previous Reports Evaluating Science Education 1. Transforming Undergraduate Education in Science, Mathematics, Engineering, and Technology (National Research Council, 1999) 2. Evaluating, and Improving Undergraduate Teaching in Science, Technology, Engineering, and Mathematics (National Research Council, 2003b) 3. Learning and Understanding: Improving Advanced Study of Mathematics and Science in U.S. High Schools (National Research Council, 2002) 4. America’s Lab Report: Investigators in High School Science (National Research Council, 2006) 5. How People Learn: Mind, Brain, Experience, and School (National Research Council, 2000b) 6. How Students Learn: Mathematics in the Classroom (National Research Council, 2005) 7. Bio 2010: Transforming Undergraduate Education for Future Research Biologists (National Research Council, 2003a) 8. Fulfilling the Promise: Biology Education in the Nation’s Schools (National Research Council, 1990) 9. Educating the Engineer of 2020: Adapting Engineering Education to the New Century (National Academy of Engineering, 2005) 10. Math and Bio 2010: Linking Undergraduate Disciplines (Steen, 2005)

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 A NEW BIOLOGY FOR THE ST CENTURY and chemical sciences, and engineering as biology research becomes increas - ingly interdisciplinary. Concepts, examples, and techniques from mathematics, and the physical/chemical sciences should be included in biology courses, and biological concepts and examples should be included in other science courses. College and university administrators, as well as funding agencies, should sup - port mathematics and science faculty in the development or adaptation of tech - niques that improve interdisciplinary education for biologists. Bio 2010 also called for laboratory courses to be as interdisciplinary as possible, and for all students to be encouraged to pursue independent research as early as is practical in their education. Finally, the report recognized that faculty development is a crucial component to improving undergraduate biology education and called for efforts to provide faculty the time necessary to refine their own understanding of how the integrative relationships of biology, mathematics, the physical/chemical sciences, and engineering can be best melded into either existing courses or new courses in the particular areas of science in which they teach. Implementing the recommendations of the Bio 2010 report would go a long way toward preparing the biology students of the future to practice the New Biology. The advances in life sciences research described in this report will cre - ate tremendous opportunities for students in the coming decades. Both at the undergraduate and graduate level, a new generation of students could learn in different ways, be challenged by new curricula and approaches, and contribute to breakthroughs that can barely be imagined today. Implementation, however, requires resources, time, and flexibility on the part of university administra - tors, faculty, and even students, who must be convinced that interdisciplinary courses will satisfy graduate school or medical school admissions requirements. A national New Biology Initiative could have a lasting impact by devoting some of its resources to providing incentives for universities and researchers to find innovative ways to implement recommendations like those in Bio 2010, and to identifying and disseminating best practices. Grants programs could support development of interdisciplinary courses like Harvard’s introductory biology courses, or Princeton’s integrated science curriculum2 at other institutions. The National Academies Summer Institute on Undergraduate Education in Biology, created in direct response to a Bio 00 recommendation, is another approach that could be expanded with additional funding (Box 4.5). A national New Biology Initiative could also support graduate training programs designed to prepare researchers for careers as New Biologists. The Integrative Graduate Education and Research Traineeship (IGERT) program is an example of such a program (Box 4.6). The new biology will be most successful if it attracts the best students from a wide range of backgrounds. Communicating the excitement of biological 2 More information can be found at http://www.princeton.edu/integratedscience/.

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 PUTTING THE NEW BIOLOGY TO WORK BOX 4.5 National Academies Summer Institute on Undergraduate Education in Biology The National Academies Summer Institute seeks to transform undergraduate biology education at research universities nationwide by improving classroom teach- ing and attracting diverse students to science (Handelsman et al., 2004; Pfund et al., 2009). Teams of two or three faculty members, most of whom teach introductory courses, learn about and implement the themes of “scientific teaching” (Handelsman, et al., 2004)—active learning, assessment, and diversity—during a week-long workshop dedicated to teaching and learning. Participants work together to develop materials and lessons that they agree to implement in their courses in the following year. The impact of the Summer Institute is far greater than the individual teaching materials; it transforms how individual faculty members view their teaching and, by extension, influence other members of their departments and their disciplines to make similar transformations (Pfund et al., 2009). Participants are asked to disseminate what they learn at the Institute with colleagues on their campuses, and university administrators commit to support participants in tangible ways upon their return to campus. Participants are named National Academies Education Fellows in the Life Sciences and are encouraged to become ambassadors for education reform on their campuses and throughout their professional communities. The aim is, therefore, to leverage a program that directly reaches 40–50 faculty per year—who themselves teach 15,000–25,000 students per year—into one that reaches hundreds of thousands of students. Since 2004, more than 250 instructors from 82 institutions in 40 states have participated in the Summer Institute including a broad cross-section of faculty from throughout all of biology—anatomy to zoology—as well as deans and department chairs, curriculum and laboratory coordinators, lecturers to postdocs. The Summer Institute is supported by the Howard Hughes Medical Institute, the Research Corporation for Science Advancement, the Burroughs Wellcome Fund, the Presidents’ Committee of the National Research Council, and the University of Wisconsin–Madison. research is crucial to attracting, retaining, and sustaining a greater diversity of students to the field (Box 4.7). All of the agencies that support life sciences research have implemented programs to attract participants from underrepresented groups. Some groups remain underrepresented––in 2005, African Americans received 3.6 percent and Hispanics 5.2 percent of doctorates in the biological sciences (Hill, 2006)— it is certain that there is much to be learned by studying the effectiveness of these different programs. A recent NRC workshop summary Understanding Interentions that Encourage Minorities to Pursue Research Careers (National Research Council, 2007a) discussed the need for research efforts to identify the

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 A NEW BIOLOGY FOR THE ST CENTURY BOX 4.6 The Integrative Graduate Education and Research Traineeship Program Federal agency funding programs can be very effective at stimulating entre- preneurship and change at academic institutions. For example, the National Sci- ence Foundation supports large grants through its Integrative Graduate Education and Research Traineeship (IGERT) program. This program has catalyzed numerous universities (currently 125) to advance interdisciplinary education. According to the program website— the IGERT program was developed to meet the challenges of educating U.S. Ph.D. scientists, engineers, and educators with the interdisciplinary back- grounds, deep knowledge in chosen disciplines, and technical, professional, and personal skills to become in their own careers the leaders and creative agents for change. The program is intended to catalyze a cultural change in graduate education, for students, faculty, and institutions, by establishing inno- vative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. The IGERT program, which has supported almost 5,000 students since its incep- tion in 1998, is an example of how federal agencies can catalyze change within U.S. institutions to reach true interdisciplinarity. elements that characterize programs that are successful in increasing minority participation. Including resources in a New Biology Initiative to encourage minority participation and, importantly, to evaluate the success of those efforts, will have an important pay-off in ensuring that the new biology benefits from all of the talent this diverse country has to offer. CONCLUSION Many intellectual, technological, and institutional challenges will need to be met in order for the New Biology to reach its full potential. Perhaps the most challenging step will be achieving widespread recognition that an inte - grated approach to solving problems with the life sciences is important and worthwhile. Some portion of the life sciences research enterprise will need to be devoted to approaching the science in this new way. Empowering the New Biology means adding a new layer to the traditional approach; an approach that is purposefully organized around problem-solving; marshalling the basic science, teams of researchers, technologies, and foundational sciences required for the task; and coordinating efforts to ensure that gaps are filled, problems

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 PUTTING THE NEW BIOLOGY TO WORK BOX 4.7 The International Genetically Engineered Machine (iGEM) Competition Every November for the last five years, hundreds of dedicated young synthetic biologists from around the world have gathered at MIT for the annual iGEM com- petition. Modeled after popular robotic design competitions, iGEM brings together teams of students whose challenge is to use standard biological parts to design and build a novel genetic-encoded machine that carries out an interesting or useful function. In 2008, 84 teams from over 20 countries participated. Most teams are from undergraduate colleges and universities, but more recently, high school teams have also begun to participate. The iGEM competition has become a major force in both education and innova- tion. Scores of top students are drawn to the excitement of the new field of synthetic biology, a field that is revolutionizing how biological systems are viewed and has the potential to solve many societal problems. Students come from biology, computer science, engineering, and many other fields, but work together to formulate their own projects. All the standard biological parts they design are submitted to the iGEM parts registry and projects are described on open websites. The teams gather at MIT to present their work to a panel of judges. iGEM projects rival those of professional research laboratories and biotech com- panies in sophistication, and frequently exceed them in innovative thinking. Projects have included design of bacteria that sense arsenic, a bacterial replacement for blood, and a synthetic cellular organelle that could be used to house biofuel pathways. The iGEM competition provides a model for future modes of education in biology. Unlike many summer research projects, iGEM projects are emergent—students come up with their own ideas and work as a team to develop and execute them. The creative challenge, competitive framework, and required self-investment results in extraordi- nary levels of motivation and innovation. The forward-looking iGEM team projects may foreshadow how biology will be practiced and applied in the future. solved, and resources brought to bear at the right time to keep the project mov- ing forward. Close interaction between larger, problem-oriented projects and the more decentralized basic research enterprise will be critical––and mutually beneficial––as discoveries will continue to emerge from traditional approaches, and advances that benefit all researchers will emerge from the large projects. The New Biology Initiative would represent a daring addition to the nation’s research portfolio, but the potential benefits are considerable: an immensely more productive life sciences research community; new bio-based industries; and, most importantly, innovative means to produce food and biofuels sustain- ably, monitor and restore ecosystems, and improve human health.

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