9

Funding, Collaboration, and Coordination

This chapter reviews the current state of research funding, infrastructure, and coordination in biological physics and outlines opportunities to structure future investments for greatest impact. Funding touches nearly every aspect of the scientific endeavor. From a student’s earliest forays into a field through their emergence as an independent investigator; from the seed of an idea through the fits and starts of theory-building and experimentation; from an area of focus through the birth of a field, funding is essential. Consistent funding makes possible the time and tools to enable discovery, supports the environments for knowledge to flourish, and maintains the continuity that allows the best ideas to grow and bear fruit. Competitively awarded scientific funding both rewards past successes and recognizes the potential within people, groups, and ideas, with an eye toward cultivating fertile intellectual grounds that will enrich science and society for generations.

Biological physics is central to the missions of an astonishing array of research funders and stakeholders. Government agencies seeking to advance fundamental understanding of our world turn to biological physics for insights into the physical underpinnings of life. Others look to biological physics to elucidate processes that could form the basis for exciting new applications in medicine, energy, engineering, and more. Governments, foundations, and the private sector all have much to gain from the basic mechanisms uncovered and the ideas sparked by advances in the field. These opportunities exist across the full range of the field, along all axes: from the dynamics of single molecules to the collective behavior in large communities of organisms, from theory and experiment, from research by individual investigators and by larger groups. Many funding agencies have successfully targeted particular

parts of this multidimensional space, often through connections with topics nominally outside of biological physics.

The existence of multiple funding sources for biological physics lends a degree of robustness to the system, and gives the community an opportunity to observe the best practices of different agencies. On the other hand, the diversity of funding sources fragments the field, obscuring its coherence. Individual investigators have adapted to this funding landscape, but the analysis which follows argues that the time is right for the funding landscape to adapt to the field.

CURRENT FUNDING FOR RESEARCH AND EDUCATION

Overview and Methodology

The principal funding for research in biological physics comes from three federal agencies: the National Science Foundation (NSF), the Department of Energy (DOE), and the National Institutes of Health (NIH). Beyond this there is support from the Department of Defense (DoD) agencies through the Defense Advanced Research Projects Agency (DARPA), the Army Research Office (ARO), the Office of Naval Research (ONR), and the Air Force Office of Scientific Research (AFOSR). Furthermore, several philanthropic foundations are invested in the field, prominently the Alfred P. Sloan Foundation, the Burroughs Wellcome Fund (BWF), the Gordon and Betty Moore Foundation, the Howard Hughes Medical Institute (HHMI), the Simons Foundation, and the Kavli Foundation. The analysis here makes use both of publicly available data, and responses to queries from the committee as described in Appendix C.

The diversity of funding sources creates challenges in assembling a global view of support for the field, and it seems prudent to begin by enumerating some of the resulting caveats. First, there can be a challenge even in finding biological physics projects in an agency’s categorization of its own funding programs, and the committee adopted different approaches with different agencies, as described in detail below. Second, different agencies have different approaches to multiyear grants. At NIH, for example, these are listed in publicly available data as multiple annual grants, while analogous databases at NSF list a single grant. For these reasons, broad trends over multiple years are more instructive than year-by-year comparisons.

A third distinction is that support is provided in different ways. All the agencies support individual investigators and small groups, but DOE in particular plays an enormous role in supporting large infrastructure, often in the form of user facilities that are accessible by peer-reviewed proposal at no cost to the researcher. These facilities address the needs of the scientific community as a whole. Biologi-

cal physics is a fraction of this user base, sometimes highly visible but not easy to quantify. NSF, NIH, and others provide user facilities to a lesser extent, sometimes in partnership with DOE. User facilities are important enough to the community that they are discussed in a separate section below.

Figure 9.1 provides a somewhat crude summary of total spending over the past decade. As should be clear from the previous remarks, uncertainties are large, especially beyond NSF and NIH, where public databases make it possible to drill down to the level of individual grants to check on what is being included as support for biological physics. Exploring these issues involves looking more closely at what these numbers mean for each of the many agencies that support the field, and then stepping back for some perspective. This sets the stage for addressing the challenges which emerge from the analysis. Finally, the chapter concludes with a survey of the state of user facilities.

Agency by Agency Analysis

In fiscal year 2020, federal research and development funding in the United States reached an estimated $164 billion.¹ Congress appropriates this funding through 12 annual appropriations bills, supporting science and engineering re-

___________________

¹ Excluded from this total is research directed specifically at the SARS-CoV-2/COVID-19 crisis.

search that advances national objectives aligned with each agency’s mission. NSF has a uniquely broad mission—“to promote the progress of science; to advance the national progress of health, prosperity, and welfare; and to secure the national defense; and for other purposes”—while other agencies can be (much) more focused (Appendix D). Further subdivided, agency directorates and programs have missions and objectives that contribute specifically to the agency’s overarching mission, and funding is awarded accordingly.

National Science Foundation

NSF supports biological physics in part through the Physics of Living Systems (PoLS) program within the Physics Division (PHY) of the Mathematical and Physical Sciences (MPS) Directorate. This program has its origins in the early 2000s, and although it remains small—with a budget five times smaller than the NIH support for the field—it has played a key role in supporting the emergence of the field as a branch of physics. Biological physics also has been supported through the Physics Frontier Centers (PFC) program, again led by PHY but with significant contributions from other divisions and directorates. Uniquely among the funding programs surveyed here, NSF/PHY has supported the physics community’s exploration of life across all scales, from single molecules to populations of organisms, including both theoretical and experimental work, and has embraced the field as a part of physics more broadly.

There is a much longer history of supporting biophysics through NSF’s Biological Sciences Directorate (BIO); today much of this support is through the Molecular Biophysics (MBIO) cluster within the Molecular and Cellular Biosciences (MCB) division. As the name suggests, MCB is a large division that funds work across a broad range of molecular and cellular biology, with clusters focused on Cellular Dynamics and Function, Genetic Mechanisms, and Systems and Synthetic Biology, alongside Molecular Biophysics. Physicists working on the brain also are supported by the Neural Systems program within Integrated and Organismal Systems, and by the program on Collaborative Research in Computational Neuroscience (CRCNS), which is part of the Information and Intelligent Systems Division of the Computer and Information Science and Engineering Directorate and funded jointly by NIH; this is not included here due to the complexities of joint funding. Note that all NSF awards can be found at https://www.nsf.gov/awardsearch, which is the source for all data shown here.

In Figure 9.1, what is counted as total NSF funding for biological physics combines the PoLS program, the PFCs with a clear focus on the field, and MCB awards identified as “molecular biophysics.” This total for the decade is broken out year by year in Figure 9.2, and further divided into the regular awards from PoLS

and MCB and the PFCs.² The partnership between PHY and BIO in supporting biological physics has been a powerful catalyst for growth and played a critical role in establishing the United States as a world leader in the field.³ More generally, NSF has managed to provide much better support for the field by coordinating across even its largest administrative divisions.

Finding: The Physics of Living Systems program in the Physics Division of NSF is the only federal program that aims to match the breadth of biological physics as a subfield of physics.

Department of Energy

Of the U.S. federal science and technology funding agencies, the DOE Office of Science provides the largest amount of funding for physical sciences research broadly, and is second to NSF in providing physical sciences research funding to universities and colleges. At DOE, the Basic Energy Sciences (BES) program

___________________

² The PFC competition happens only once every 3 years, but (as noted above) multiyear NSF awards are listed as belonging to a single year. If not separated, this would produce an artificial oscillation in apparent annual funding.

³ Many NSF awards are co-funded by different programs. In this accounting the full award amount is attached to the lead program, and there is no double counting.

provides the majority of physical sciences research funding, including funding for projects in condensed matter and materials physics, chemistry, geosciences, and the “physical biosciences,” which have substantial overlap with what we identify in this report as biological physics. A major component of the BES program are shared research facilities based at DOE national laboratories and open to researchers from all disciplines. These user facilities serve more than 16,000 scientists and engineers each year, and include X-ray, neutron, and electron beam scattering sources. The enormous impact of these facilities on biological physics is discussed more fully below, along with DOE support for advanced scientific computing.

The interaction between basic science and the agency mission has a long history at DOE and its precursor agencies; for example, the study of biological responses to radiation led to the discovery of very general DNA repair mechanisms; the pursuit of more efficient solar energy conversion led to many discoveries about the molecular events in photosynthesis; and more. DOE also supported “theoretical biology” at the Los Alamos National Laboratory at a time when those words were very unpopular, helping to advance research from protein dynamics to immunology and more; much of that work is connected directly to modern research in biological physics. The Human Genome Project began with DOE efforts in the mid-1980s, before being fully launched in 1990 through a memorandum of understanding between DOE and NIH. For some perspective on these efforts, a 2011 report estimated the $3.8 billion federal investment in the Human Genome Project generated $796 billion in economic impact, providing more than 300,000 jobs in the genome-driven industries that emerged.⁴

Beyond shared research facilities, the BES program provides funding for biological physics research through its Chemical Sciences, Geosciences, and Biosciences (CSGB) Division. Under CSGB, there are three foci for investment: Fundamental Interaction, Photochemistry and Biochemistry, and Chemical Transformations, each of which is further subdivided. Photochemistry and Biochemistry is focused on “research on molecular mechanisms involved in the capture of light energy and its conversion into chemical and electrical energy through biological and chemical pathways” and is furthered subdivided into Solar Photochemistry, Photosynthetic Systems, and Physical Biosciences. Significant parts of the work on photosynthesis described in Chapter 1 are supported by these programs, as are efforts to build artificial systems that mimic this and other biological functions. In addition to funding through BES, the DOE Biological Environmental Research (BER) program provides funding for biological physics research through its Biological Systems Science Division (BSSD). The BER mission is “to support transformative science and

___________________

⁴ S. Tripp and M. Grueber, Economic Impact of the Human Genome Project, 2011, Battelle Memorial Institute, Columbus, OH, https://www.battelle.org/docs/default-source/misc/battelle-2011-misceconomic-impact-human-genome-project.pdf.

scientific user facilities to achieve a predictive understanding of complex biological, Earth, and environmental systems for energy and infrastructure security, independence, and prosperity,” and BSSD is organized to support research that “integrate[s] discovery- and hypothesis-driven science with technology development on plant and microbial systems relevant to national priorities in energy security and resilience.” Through BSSD’s Biomolecular Characterization and Imaging Science effort, DOE funds efforts to study structural, spatial, and temporal relationships of metabolic processes to better understand environmental and biosystems design impacts on ecosystems from the atomic to the microbial and plant scales.

The funding reported for DOE in Figures 9.1 and 9.2 represent totals for CSBG and BSSD, and were obtained from congressional budget documents.⁵ These programs have strong overlap with biological physics, but also clearly support much work outside the field. Indeed, DOE has made substantial efforts to integrate different disciplines, and to create a continuum of support from basic science to applications, all in pursuit of its mission. The simple sums reported here thus substantially over-estimate the support for the field, but on the other hand leave out the support for shared facilities described later in the chapter (see “User Facilities”).

Rather than trying to dissect the budget, the committee asked DOE staff for their views (Appendix C). They responded that,

In a second direction, BES mission-directed programs draw from understanding of microscopic mechanisms of energy transduction but are increasingly looking at “using biology as a blueprint for the design and synthesis of self-regulating, resilient materials that incorporate predetermined functionality and information content approaching that of biological materials.”

The DOE Office of Science supports an Early Career Research Program (ECRP) for universities and national laboratories. Awardees are all within 10 years of receiving a PhD, and can receive $150,000 per year at universities and $500,000 per year at national laboratories for 5 years to launch their careers. A number of ECRP funding opportunities in BES and BER have focused on biological physics topics in recent years.

___________________

⁵ U.S. Government Publishing Office, “Budget of the United States Government,” https://www.govinfo.gov/app/collection/budget/2023.

Finding: The United States has had a long-standing role as a leader in the area of biological physics at the molecular scale. Crucial support for this effort comes from DOE investment in programs and user facilities.

DOE’s capabilities in “large project team science” are well known as essential to support of the U.S. effort in elementary particle physics. As particle physics began to connect with astrophysics and cosmology, these efforts expanded, including through partnerships with the National Aeronautics and Space Administration (NASA). As noted above, the Human Genome Project was joint effort of DOE and NIH, while the follow-up National Plant Genome Initiative has involved DOE, NSF, and the U.S. Department of Agriculture (USDA). More recently, DOE has explored bringing its team science expertise to bear on explorations of the brain, under the umbrella of the national BRAIN initiative, and this has involved connections with both NSF and NIH.⁶

National Institutes of Health

NIH has no single program geared specifically for supporting work in biological physics, but it has made substantial investments in the field. Funding comes from multiple Institutes and represents a major source of individual research support for the community. Using NIH’s RePORTer tool⁷ to search the term “physics” produced 572 funded projects totaling $234,958,323 for the 2019 fiscal year alone, though a closer inspection of the results for this and other fiscal years revealed that many of these projects did not appear related to biological physics. In contrast, searching for projects led by scientists whose primary departmental affiliation was physics or biophysics yielded results that were far more relevant and consistent. Thus, the committee tracked NIH support for biological physics based on departmental affiliation, while support from other agencies was tracked in other ways. This approach certainly undercounts biological physics researchers who do not have primary appointments in physics or biophysics departments, and may include some scientists who would not identify with the definition of the field adopted in this report, but seems a reasonable proxy.

Over the decade 2010–2019, NIH made approximately 170 awards per year to principal investigators (PIs) whose primary affiliations are in physics or biophysics departments, with a total budget of roughly $60 million annually. About 84 percent of these awards were single PI grants. The National Institute of General Medical Sciences (NIGMS) accounted for the largest share, about 40 percent of overall funding, but the National Cancer Institute (NCI); the National Heart, Lung,

___________________

⁶ National Institutes of Health, “Brain Research Through Advancing Innovative Neurotechnologies®,” https://braininitiative.nih.gov.

⁷ National Institutes of Health, “RePORTER Version 2020.9,” https://reporter.nih.gov.

and Blood Institute (NHLBI); the National Institute of Biomedical Imaging and Bioengineering (NIBIB); and the National Institute of Neurological Disorders and Stroke (NINDS) each awarded more than 100 grants over the decade, and awards from 17 other institutes form a long tail, as shown in Figure 9.3. While this funding has been a key contributor to biological physics, it represents only about 0.2 percent of all NIH awards.

While NIH grants are funded by institutes, they are reviewed by study sections, which are (largely) standing committees with responsibility for particular areas of science. There are roughly 200 of these study sections, on topics ranging from macromolecular structure to the organization and delivery of health services. It is remarkable that PIs whose primary affiliations are in physics or biophysics departments received their grants through 75 different study sections (Appendix E). On one hand, this means that the impact of the physicists’ approach to life is felt throughout a large part of the NIH portfolio. On the other hand, it means that biological physics proposals need to be tuned to the interests of these very different groups.

Finding: NIH provides strong support for many individual investigators in biological physics, through multiple institutes and funding mechanisms.

The committee notes, more explicitly, that there are several study sections traditionally thought of as “biophysics” study sections, but these only serve a rather narrow slice of the biological physics community. This includes traditional structural biology and single molecule research, some works on theories and models connected

very closely to experiments, and some neuroscience. This leaves large segments of the biological physics community having to navigate the study sections across many different subject areas to find which ones are friendly to their flavor of scientific approach. This has the effect of scattering the field and obscuring its coherence.

NIH awards grants in several broad categories, including research awards (R**), training grants (T**) that support stipends and tuition for students and postdoctoral fellows, and career development awards (K**) that include grants to aid the transition from postdoctoral fellow to independent investigator; for a complete list of relevant funding mechanisms see Appendix E. Of the 4,841 K awards (K01, K08, K22, K25, K99) NIH made across all institutes and disciplines in the past 10 years, about 2 percent (104 awards) went to PIs in physics or biophysics departments. Note that this is 10 times larger than the fraction of research awards flowing from NIH into the biological physics community. This is a strong endorsement of the idea that the community is producing young scientists who are exceptionally well prepared to meet the intellectual challenges posed by the phenomena of life, whether they end up identifying as biological physicists, physical biologists, biologists, or medical scientists.

Department of Defense

Biological physics researchers and projects also are supported by and integral to a variety of programs at DoD. This funding comes through DARPA, ARO, ONR, and AFOSR; where available, annual funding levels over the decade are included in Figure 9.4, while a broader set of DoD agencies contribute to the decadal total in Figure 9.1. These agencies’ engagement with the field—evident in both their funding allocations and in the thoughtful comments they provided to the committee—reflects the strong potential biological physics holds for advancing mission-driven basic science as well as practical applications in a variety of domains (for descriptions of these agencies’ missions, see Appendix D). Overall, the amount of support these agencies provide to biological physics research is substantial, though it is qualitatively different from the support provided by NIH and NSF. Most grants at the DoD agencies support biological physics as a part of larger, multidisciplinary collaborations, so that the budgets quoted in Figures 9.1 and 9.4 usually are shared across many disciplines. Nonetheless, DoD’s enthusiasm to bring biological physics researchers into these larger projects is a marker of the field’s impact.

Finding: DoD agencies have highlighted multiple areas where the interests of the biological physics community intersect their missions.

Concretely, in response to the committee’s request for data on the support for biological physics, representatives of several DoD agencies called out multiple

areas where the field intersects their mission: soft robotics; bio-inspired materials and autonomous systems; computational neuroscience and sensorimotor control; radio-bio; insect brains; soft-matter circuit design; locomotion; non-equilibrium active matter; physics-based models of stochasticity in populations; inter-cellular communication; agent-based models; and more. While distributed across many different funding programs in multiple DoD agencies, this broad spectrum of topics connects with a large swath of the biological physics community.

In the mid-2000s, the federal government created a new agency, the Intelligence Advanced Research Projects Agency (IARPA), parallel to DARPA but under the auspices of the Director of National Intelligence. Although not a part of our full survey, we note that IARPA supports a major project to uncover principles of data representation and computation in real brains, with the goal of exporting these principles to artificial systems. As part of this effort, IARPA contributed to one of the largest efforts to date in connectomics (Chapter 3).

Private Foundations

Beyond the federal funding agencies, several private foundations in the United States have made, and continue to make significant contributions to the support of biological physics and allied efforts. Examples include the Alfred P. Sloan Foundation, BWF, the Gordon and Betty Moore Foundation, HHMI, the Simons Foundation, and the Kavli Foundation. These different organizations have used a wide range of funding mechanisms. Starting in the mid-1990s, for example, the Sloan

Foundation supported the establishment of six centers for theory in neuroscience. As described in several sections of Part I, this was a moment when a new generation of ideas and methods from physics were having an impact on thinking about the brain, and the physics community was beginning to appreciate the challenges of real neural networks. The young people who passed through the Sloan centers formed an important part of the nucleus for a more quantitative, theoretically oriented exploration of the brain, with substantial connections to the biological physics community.

Not long after the Sloan initiative, BWF started a program to support centers for research and graduate education at the interface of the biological and physical sciences, and this evolved into the Career Awards at the Scientific Interface (CASI), which provides $500,000 grants to postdoctoral fellows, nominally for 5 years, with the intention that support is carried into the initial years of their junior faculty positions. While not aimed solely at biological physics, a number of young people in the field have been supported by the CASI program, which also provides community and mentorship for the grant recipients, who now number nearly 200. Importantly, the CASI program has taken a broad view of the field, and grant recipients have worked on problems ranging from the dynamics of single molecules to the behaviors of large populations of organisms.

The Gordon and Betty Moore Foundation has two major initiatives that overlap the biological physics community, in Marine Microbiology and Symbiosis, and in Aquatic Systems. Separately it makes grants not tied to specific initiatives. In response to the committee’s query, Moore Foundation staff identified 64 grants related to the physics of living systems during 2010–2019, including investigator awards, multidisciplinary awards, and support for postdoctoral scholars in larger research communities.

HHMI is a major supporter of biomedical research in the United States, both at the Janelia Research Campus and through the appointment of HHMI investigators based at universities and medical schools around the country; total expenditures in fiscal year 2020 were $822 million. In this broad portfolio, one can find many people and projects that connect strongly to the physics of living systems community. On the other hand, only a handful of the more than 250 HHMI investigators have appointments in physics or applied physics departments, which is roughly the same as the representation of biological physics among NIGMS grantees. There is stronger representation of physicists among the HHMI professors, who are selected for their integration of research with undergraduate teaching. HHMI also has supported fellowship programs for PhD students coming from abroad, and from underrepresented groups in the United States.

The Simons Foundation has multiple programs that overlap with the interests of the biological physics community. Since 2017, the foundation has partnered with the Division of Mathematical Sciences at NSF to support four NSF-Simons Research Centers for Mathematics of Complex Biological Systems. The Simons Foundation also supports several large-scale collaborations, including on the Origin of Life, the

Principles of Microbial Ecology, and the Global Brain, all of which have substantial participation from the biological physics community. These collaborations fund multiple investigators around the world, often with associated programs for postdoctoral fellows and to support the transition from fellow to independent investigator, similar to the BWF/CASI program. The Simons Investigator program provides stable, longer term support for faculty working in theoretical physics and astrophysics, theoretical computer science, and mathematics. For several years, there was a young investigator program for mathematical modeling of living systems, but now the theoretical physics program explicitly includes biological physics. At the recently established Flatiron Institute, two of the five centers—the Center for Computational Biology and the Center for Computational Neuroscience—have strong overlap with the physics of living systems.

Finding: Private foundations have supported programs that engage the biological physics community, often before such programs become mainstream in federal agencies, and have explored different funding models.

Synthesis

Looking at funding agency by agency matches the way in which grants are awarded, and the way in which Congress supports science. But there are other axes along which to decompose the funding of biological physics that highlight the challenges of the current funding environment more clearly.

Scale of Support for Individual Investigators

The discussion above emphasized individual investigator grants because the majority of support for biological physics at both NSF and NIH is in this form (see Figure 9.5). But looking more closely at these individual awards uncovers dramatic differences. At NIH, single investigator and small group grants (R** research awards) typically have 3- to 5-year terms, with a median budget of roughly $300,000 per year, stably over the decade; roughly 10 percent of grants are early career awards. For NSF/PoLS, the median budget for individual investigators over this period was under $125,000 per year. Figure 9.6 shows the full range of award sizes to individual investigators in biological physics at both NSF and NIH.⁸

___________________

⁸ Echoes of these differences between NIH and NSF can be seen in the differential treatment of the physical and biological sciences within NSF itself. NSF’s major young investigator award, the CAREER, is a 5-year grant of $400,000 for proposals funded through the Physics Division (PHY), but $500,000 for those funded through the Biological Sciences Directorate (BIO). See National Science Foundation, Faculty Early Career Development Program (CAREER), NSF 20-525, https://www.nsf.gov/pubs/2020/nsf20525/nsf20525.htm.

The contrast between NSF and NIH award sizes is striking. The typical (median) NIH award has an annual budget larger than all but a few percent of NSF awards. It is important that the NSF grants in our field are not just smaller than NIH grants, but small in absolute terms. Appendix F estimates the bare minimum grant size needed to support a faculty member working with one PhD student;

this minimal budget is essentially equal to the median NSF annual award. While many members of the biological physics community manage to do outstanding science with less than this minimal budget, this low level of funding is not healthy for the field.

The small grant sizes at NSF hold back the development of biological physics in many ways, and generate hidden costs. NSF has been unique in embracing biological physics as a field of physics, in all its breadth. If individual investigators cannot support their research programs through NSF, they are driven to other funding agencies that fragment the field in various ways and de-emphasize connections to the rest of physics. Smaller grant sizes mean that many investigators need multiple grants to support their research programs, which require multiple reviewers and multiple reports, creating a cascade of burdens on the community that are largely unaccounted for. If particular grant programs cannot meet scientists’ needs, eventually they stop applying, giving the impression that community demand is shrinking, and making it more difficult for program officers to argue for greater resources.

Finding: NSF award sizes for individual investigators in biological physics have reached dangerously low levels, both in contrast to NIH and in absolute terms.

The committee emphasizes that this is not a criticism of NSF, which in fact has done a commendable job of stretching limited resources through partnerships across programs and divisions. Rather, NSF is caught between its budgetary constraints and its goal of supporting the field in its full breadth.

Centers and Research Communities

In many areas of science, from elementary particle physics to global climate, there are crucial projects that require large teams of investigators. These big efforts capture the public imagination, as did their historical precursors. There is a sense that progress more generally depends on supporting a “moonshot for X,” with argument more about the correct X than about the moonshot model. It is worth remembering that the most successful examples of “big science” did not start big, and for most of their history were as small as they could possibly be. The search for gravitational waves, for example, began with individual investigators, and grew only gradually to the point where the eventual discovery was reported by more than 1,000 authors.

Even when a single project does not require a large team, however, there can be benefits from more collective support for groups of investigators. In condensed matter physics and atomic physics, for example, “table top” experiments benefit enormously from shared resources in local communities, and the same is true for

biological physics. Theorists seldom write papers with large numbers of authors, but nonetheless congregate to share ideas, and communal mentorship of junior theorists is common. These research communities enhance the productivity of their individual members. Support for such research communities thus is important, not as an alternative to individual investigator grants but as a complement to them. Mechanisms for funding these groups need to support intellectual infrastructure as well as laboratory infrastructure.

There are several current models for support of biological physics research communities. At NSF, of the 17 PFCs that have been launched since the program began in 2001, three are focused on problems in biological physics, and several others have overlap with the field. Also at NSF, of the 19 currently active Materials Research Science and Engineering Centers (MRSEC), more than one-third host interdisciplinary research groups working on living or biomimetic systems. These examples are important in part because they demonstrate the ability of biological physics programs to succeed in open competition across all areas supported by the NSF Divisions of Physics and Materials Research. NSF and the Simons Foundation also have partnered to support four Centers for the Mathematics of Complex Biological Systems, as noted above, all of which have substantial participation from the biological physics community. Many of the institutions that host these different Centers are linked through NSF’s Physics of Living Systems Student Research Network, which also connects to a number of institutions internationally. Although this network has not yet reached all relevant U.S. institutions, it provides a model for how to share the benefits of strong local community support much more widely. More generally, Center grants often have a strong mandate for the integration of research and education, including reaching students outside the host institution.

NIH also supports centers and larger collaborations. There are Program Project/Center grants (P01, P30, and P50), but these now tend to be more specialized and are not offered across the full range of topics supported by NIH. There are cooperative agreements (U01) to support larger group efforts, and a number of biological physics projects can be found inside these agreements. As discussed below, the NIH training grant programs provide for institutional support of doctoral students, and in some cases postdoctoral fellows, working in a broad area, and as such serve some of the same functions as Centers in the NSF model. Perhaps the most radical experiment undertaken by NIH was the establishment of 12 Physical Sciences in Oncology Centers. Run through NCI, these centers incorporate the physical sciences into cancer research and have been quite successful in combining biological and physical sciences. Their focus has largely shifted, however, toward tool building and engineering and away from the search for deeper physical and mathematical principles.

Conclusion: As in many areas of science, there is a challenge in maintaining a portfolio of mechanisms to fund the spontaneity of individual investigators,

the supportive mentoring environments of research centers, and the ambitious projects requiring larger collaborations.

Support for Education and Workforce Development

Both NSF and NIH provide direct support for graduate education, through different mechanisms. The Graduate Research Fellowship Program (GRFP) was the first program established by NSF and now appoints just over 2,000 new fellows each year, across all fields of science. In 2020, 136 new fellows were appointed in physics and astronomy, with a distribution across subfields, including the Physics of Living Systems, that roughly mirrors the distribution of PhDs (see Figure 8.1). The GRFP also provides a model in which individual students are given considerable freedom and agency, with fellowship support attached to them as individuals rather than to their mentors or their doctoral program.

The NSF PoLS program has established a student research network connecting multiple institutions both within the United States and internationally. These grants (included in the analysis above) aim not at core funding but rather provide supplementary funding to enable student exchanges, summer schools, conference attendance, and other activities that enrich the experience of doctoral students. There are smaller and more focused fellowship programs sponsored by DoD (National Defense Science and Engineering Graduate Fellowship Program) and DOE (Office of Science Graduate Student Research Program), and both have some overlap with biological physics. As found in Chapter 8, however, there are some sharp distinctions between support for education and research that limit these agencies.

NIH has a very different approach to the support of graduate education, with a large program of “training grants” that fund multiple students at single institutions. For many doctoral programs in the biomedical sciences, broadly defined, these training grants are a major pillar of support. Perhaps surprisingly, fully 14 percent of NIH grants awarded to physics and biophysics departments over the past decade have been training grants, but this represents only 0.5 percent of the more than 35,000 NIH training grants in total. The tiny fraction of NIH training grants that support doctoral education in biological physics is not commensurate with the impact that physics has had on the biomedical sciences. It is even inconsistent with the larger fraction of NIH career development (K) awards to physicists, as described above. This would not be a problem if NSF had analogous programs for the support of physics students more generally, but in the absence of such programs this represents a significant gap.

Finding: Physics programs do not have the stable, programmatic support for PhD students that is the norm in the biomedical sciences.

Theory as an Independent Activity

In physics, theory and experiment are partners in exploring the world. The relationship between theoretical and experimental physics is complex, but there is little doubt that theoretical physics has an independent identity. Correspondingly, there is a long tradition of federal agencies supporting theory as an independent activity. At NSF, for example, in the Division of Physics there are separate, parallel programs for theory and experiment in atomic, molecular, and optical physics; elementary particle physics; gravitational physics; nuclear physics; and particle astrophysics and cosmology. Also at NSF, in the Division of Materials Research the condensed matter physics program supports experimental condensed matter physics while the materials theory program supports theoretical condensed matter. One can find similar structures at DOE, and to a lesser extent in the DoD agencies. Importantly, independent funding for theory has never inhibited theory/experiment interaction.

Finding: Physics has a unique view of the relationship between theory and experiment, and in many fields of physics this is supported by separate programs funding theorists and experimentalists. This structure does not exist in biological physics.

Adding Things Up

The physicists’ view is that the numbers describing the world fit together into some coherent framework. It seems natural, in this spirit, to ask if the total funding for biological physics, across all the sources discussed here, fits together with other measures of the activity and vitality of the field. But what sets this scale? One well-defined anchor is the number of students each year who receive their PhD for research in the field, as described in Chapter 8 (see Figure 8.1). At a minimum, supporting the field means supporting these students during their thesis research, continuing to support the fraction who move on to postdoctoral positions, and supporting the community of university faculty and professional researchers who provide mentorship for these young scientists. Appendix F provides estimates for this minimal level of support.

Taking a very strict view of the field’s boundaries, corresponding to research that would be carried out by students receiving their PhDs in Physics, minimal support is in the range of $83 to $92 million per year. This is vastly larger than what is available, for example, through programs in the Physics Division of NSF. With a slightly broader view of the field, the minimum level of support comes close to the total expenditures of all relevant agencies (see Figure 9.4). These minimal levels do not include the costs of research facilities, equipment and supplies, technical or administrative support staff, travel for collaboration, and so forth.

Finding: Total support for biological physics is barely consistent with the minimum needed to maintain the current flow of young people into the field. This approximate balance of needs and support leaves significant gaps, and provides little room for new initiatives.

Conclusion: Biological physics is supported by multiple agencies and foundations, but this support is fragmented, obscuring the breadth and coherence of the field. It is precariously close to the minimum needed for the health of the field.

RESPONDING TO CHALLENGES AND OPPORTUNITIES

One of the major challenges facing the biological physics community is the substantial mismatch between the community’s intellectual activity and the structure of current funding programs. This should be understood in the context provided by the initial conclusion from Part I of this report:

Conclusion: Biological physics, or the physics of living systems, now has emerged fully as a field of physics, alongside more traditional fields of astrophysics and cosmology; atomic, molecular, and optical physics; condensed matter physics; nuclear physics; particle physics; and plasma physics.

In contrast, much of the support for the field continues to follow a model of biophysics as only the application of physics to biology. This perspective constrains what the funding agencies perceive as relevant, and reinforces an organization of the field around the classical subdivisions of the biological sciences. The biological physics community has been successful in adapting to this funding environment, but it now is time for the funding environment to respond more fully to the community.

General Recommendation: Funding agencies, including the National Institutes of Health, the National Science Foundation, the Department of Energy, and the Department of Defense, as well as private foundations, should develop and expand programs that match the breadth of biological physics as a coherent field.

This section explores how this broad recommendation can be implemented across the many relevant agencies and across other dimensions of research support. Discussion on major user facilities is deferred to the “User Facilities” section below.

It is important that the current funding structures are not only mismatched to the state of the field, but also fail to maximize the opportunities for agencies

to advance their missions. As an example, there is a set of interlocking questions about collective behavior in groups of organisms, the emergence and persistence of ecological diversity in multispecies groups, and, on longer time scales, the evolution of these populations. Taken together these questions are crucial for the missions of multiple agencies. The biological physics community has sharpened these questions and made progress toward answers by adopting the unifying language of statistical mechanics and dynamical systems, both in theoretical work and in the design and analysis of new experiments, as described in Part I. But mapping these questions into the current funding programs fragments the community: If the multispecies groups are bacteria living inside the human gut, then the problem is relevant for NIH, while bacteria living in soil are relevant for DOE; if the question asked is not about bacteria but about plants in the rainforest, then connections are drawn to climate science and the mission of the National Oceanic and Atmospheric Administration or the ecology programs of NSF, while interest in cooperative behaviors is a basic science problem connected to the practical problem of coordinating multiple autonomous vehicles and the mission of DoD. All of these agency missions would be advanced by more coherent and coordinated support for the biological physics community’s attack on these problems. More deeply, the community’s discovery of conceptual connections among these seemingly different problems offers opportunities for each of these agencies to benefit by seeing its mission in the broadest possible terms.

National Science Foundation

The committee’s concerns about support for biological physics at NSF can be stated simply: NSF does not have enough resources to accomplish a mission that includes biological physics. As emphasized above, NSF is the only agency to recognize biological physics in all its breadth, as a field of physics. The launch of a Biological Physics program within the Physics Division, a program that evolved into the current Physics of Living Systems program, not only provided an important source of support but also a marker that there is new physics to be found in the phenomena of life. But, as noted above, the level of funding for these programs has not kept pace with the growth of the field.

Specific Recommendation: The federal government should provide the National Science Foundation with substantially more resources to fulfill its mission, allowing a much needed increase in the size of individual grant awards without compromising the breadth of its activities.

National Institutes of Health

A substantial component of support for biological physics research in the United States comes from NIH. As emphasized above, these grants derive from a wide range of different institutes and 75 different study sections, testimony to the breadth of the field. None of these study sections, however, is devoted to biological physics itself. This fragments the field, and misses intellectual opportunities that cut across the historical sub-divisions of biology, as described in Part I of this report. More subtly, young investigators especially are pushed toward defining their work in relation to the communities represented by the study sections, thus working against the emergence of biological physics as a field of physics.

Finding: Support for the physics of living systems is scattered widely across NIH, making it difficult for investigators to find their way and obscuring the coherence of the field.

Specific Recommendation: The National Institutes of Health should form study sections devoted to biological physics, in its full breadth.

NIH study sections are established via a process called ENQUIRE, through the Center for Scientific Review (CSR). ENQUIRE integrates data and input from stakeholders to determine whether changes in study section focus or scope are needed to facilitate the identification of high impact science, with special consideration of emerging science. Clusters of study sections are formed based on scientific topics (instead of CSR managerial units); review via the ENQUIRE process is systematic, data-driven, and continuous—roughly 20 percent of CSR study sections are evaluated each year, and every study section is evaluated every 5 years.

Department of Energy and Other Agencies

DOE, along with most of the federal agencies involved in the support of science, has a concrete mission (see Appendix D), and there is an important challenge in connecting the frontiers of biological physics research with these different missions. Importantly, DOE often views its mission not only in terms of particular domains of science and technology, but also in bringing its expertise in “big science” to bear on problems well outside of energy. An example of this is the recent series of workshops sponsored jointly by DOE and NIH addressing the feasibility of larger scale projects in connectomics, mapping the synaptic connections among neurons, perhaps even in entire brains. Several imaging modalities, including various forms of electron microscopy, synchrotron X-ray computed nano-CT or pytchography,

and various forms of optical microscopy, are under evaluation as foundational technologies, and this effort could require investments on the order of several hundred million dollars. Such maps would provide a structural scaffolding on which to place the growing body of experiments that monitor the electrical activity of many neurons simultaneously, also a problem where measurement technologies are advancing rapidly. These efforts have had substantial input from the biological physics community, both in the development of experimental methods and in the articulation of theories within which one might make sense out of such large data sets. More broadly, the physics community has tremendous experience with projects on this scale, from the construction of large instruments to making the data accessible and integrating experiment with theory. If DOE is to be the path for large-scale brain projects in the physics tradition, it will be important to engage the broader biological physics community from the very start.

As DOE looks to partnerships with other agencies to explore a broader view of its mission, it is important to have successful models for such partnerships in support of biological physics. An example is the program for Collaborative Research in Computational Neuroscience (CRCNS), funded jointly by NSF and NIH, which has supported a number of groups in the biological physics community. In this program, NSF takes the lead in soliciting and managing the review of proposals, while representatives of several participating NIH Institutes engage with the process to identify proposals recommended for funding that would fit in their larger programs. Since its inception as an NSF/NIH effort, CRCNS has expanded to include partnerships with DOE and with agencies in France, Germany, Israel, Japan, and Spain; the procedures leading to joint funding necessarily have become more complex, but are well managed. The joint support of the Center for Quantitative Biology by NSF and the Simons Foundation provides a related but very different model.

Finding: Biological physics has benefited from funding programs that are shared across divisions within individual federal funding agencies, between agencies, and between federal agencies and private foundations.

The problem of connecting biological physics to agency missions also exists in the DoD agencies. In these agencies, the individual programs and program officers have considerable autonomy, however. Furthermore, there is a tradition of DoD agencies, at various times, seeing their mission in the broadest possible terms. As described above, DoD officials see a wide range of connections to topics being explored by the biological physics community. Importantly, many of these connections involve not a simple translation of biological mechanisms into engineering contexts, but rather the emulation of deeper physical principles that enable the extraordinary functionality of living systems.

Specific Recommendation: The Department of Defense should support research in biological physics research that aims to discover broad principles that can be emulated in engineered systems of relevance to its mission.

In addition to supporting a broad spectrum of activities that engage the biological physics community, DoD agencies also offer models of different funding structures. In particular, the Multidisciplinary University Research Initiatives (MURI) Program can support mid-sized collaborations of five to seven PIs with budgets of $3−$5 million over several years. Work on this scale is becoming increasingly important in biological physics, as frontier experiments often require combinations of new technologies and produce data on a scale where strong integration with theory and analysis is necessary starting from the design of the experiments. A similar scale of project can be supported through the U01 and U19 mechanisms of NIH, but these are less common, making them something of a rarity in the biological physics community.

Conclusion: There is an opportunity for DoD agencies to use the MURI Program to support biological physics, and for NSF and NIH to expand their support of these mid-sized collaborations.

Industrial Research Laboratories

As described in Part II of this report, biological physics has strong overlap and interaction with many fields that are relevant for the pharmaceutical and biotechnology industries—structural biology, systems biology, molecular design, synthetic biology, and more. At various times, research laboratories sponsored by these industries have thus been very supportive of the field.

In the 1980s and 1990s, a very different set of industrial research laboratories provided strong support for the emergence of biological physics as a part of physics. AT&T Bell Laboratories, IBM Research, the NEC Research Institute, and others did not have biology programs in their research laboratories, simply because biology was irrelevant to their business. But all of these companies had biological physics groups that grew out of their basic physics efforts, looking at problems ranging from cooperativity in hemoglobin to neural coding and computation and collective behavior in flocks and swarms. In parallel, Exxon Research supported a large effort in soft matter physics, and many of the scientists from this group would move into biological physics. All these laboratories offered investigators the opportunity to explore the physics of living systems at a time when very few academic physics departments in the United States had identifiable groups in the field. There were paths from this basic scientific work into more applicable results, including

foundational work on neural networks, but—as with much of the work in these laboratories—the support for science was not tied to immediate application.

Pharmaceutical and biotechnology research has grown, but from the point of view of the physics community as a whole, the perceived golden age of industrial research labs is over. What has emerged instead are research laboratories supported by new industries such as Microsoft, Google, and Facebook. There also are new structures, intermediate between industrial research and private foundations, such as the Chan-Zuckerberg Initiative and Open AI, as well as new non-profit institutes such as the Chan-Zuckerberg Biohub and the Allen Institutes. There are many connections between the activities of these laboratories and the interests of the biological physics community, from understanding how the identities of cells emerge from patterns of gene expression to the physics of behavior, and this landscape continues to evolve rapidly. There are many opportunities both for technological progress and for fundamental discovery.

Specific Recommendation: Industrial research laboratories should reinvest in biological physics, embracing their historic role in nurturing the field.

Support for Education and Workforce Development

One advantage of support being so widely distributed is that the biological physics community samples the different approaches adopted by the different agencies. Nowhere are these differences more apparent than in the support for graduate education. As noted above, NSF, DOE, and DoD all have graduate fellowship programs, but these are individual fellowships and support only a tiny fraction of the PhD students who are funded through research grants by these agencies. NIH, in contrast, has a very large program of “training grants” that provide substantial support for the infrastructure of graduate education in the biomedical sciences. In the current fiscal year, these T32 grants are active at 150 institutions across the country, with a total budget of roughly $750 million per year. While there is widespread appreciation of the impact that physics has had on the mission of NIH, only 0.5 percent of training grant funds go to the biological physics community. To put this in perspective, a 3.5 percent increase in the T32 budget would provide enough funds to support all physics PhD students currently working on biological physics (Appendix F).

The training grant model has many advantages, not just for biological physics. Support is collective, and thus encourages the building of local communities, whose importance is emphasized above. With training grant support, students are empowered to pursue new and exciting directions. Programs can be judged not only on the collection of research directions available to students, but on their effectiveness in mentoring and placement of students after their degrees.

Specific Recommendation: Federal funding agencies should establish grant program(s) for the direct, institutional support of graduate education in biological physics.

It is important that programs for the support of graduate education in biological physics be matched to the culture of physics education more broadly. A number of T32 requirements, for example, are not well aligned with the typical structure of physics doctoral programs. More subtly, training grants typically impose significant restrictions on the support of international students. As discussed in Chapter 10, for the United States to maintain its position of scientific leadership will require renewed commitment to welcoming talented students from all over the world.

Specific Recommendation: Federal agencies and private foundations should establish programs for the support of international students in U.S. PhD programs, in biological physics and more generally.

NIH has multiple funding mechanisms that emphasize career development beyond graduate education. The same T32 training grant programs that fund PhD students also can fund postdoctoral fellows; there are Institutional Research and Academic Career Development Awards that support communities of postdoctoral fellows engaged with modest amounts of teaching at minority serving institutions alongside their research activities; and there are Pathway to Independence programs to support individuals in the transition from postdoctoral fellow to independent investigator (K99/R00). As noted above, the biological physics community has done very well in the competition for these individual fellowships, but there is room for improvement of the community’s representation in the institutional grants. NIH also supports postdoctoral fellows through the Kirschstein National Research Service Awards, but these are not focused as explicitly on the independence of the fellows.

Many NSF divisions have programs for the direct support of individual postdoctoral fellows, for example in Mathematical Sciences, Astronomy and Astrophysics, Earth Sciences, and Biology. Similarly, NASA supports the Hubble Postdoctoral Fellows. As an example, the NSF Astronomy and Astrophysics Fellows, together with the NASA Hubble Fellows, support a bit less than 10 percent of the new PhDs awarded each year in astronomy and astrophysics. While these programs are small in comparison to the total budget for the field, the fact that fellows are appointed through a national competition attaches considerable prestige to the awards, and the impact on the community extends beyond the direct financial support. Perhaps more importantly, individual fellowships give the fellows a significant degree of independence, while the selection process allows judgements to be made about the quality of the mentoring environment in which they will be immersed. As explained in Chapter 8, this balance is especially important for young scientists

developing their own perspectives on the next generation of challenging problems in biological physics.

Conclusion: Accelerating young researchers to independence is critical to empowering the next generation of biological physicists. As in other fields of physics, independent, individual fellowships are an effective mechanism.

In addition to examples of how such fellowships are implemented at NSF and NIH, there are examples such as the BWF Career Awards at the Scientific Interface, which has had substantial engagement with the biological physics community, as discussed above.

Support for Theory

As more and more of the living world becomes accessible to large-scale, quantitative experiments, the biology community and the agencies that support research in the biological sciences have understood the need to support new approaches to data analysis. For the physics community, however, theory is more than data analysis (see also Chapter 8). The history of physics shows that the most compelling data analysis methods often are grounded in more general theoretical principles, sometimes articulated long before the relevant experiments were possible. Theory thus engages productively with questions that may not be relevant for today’s experiments, but help to set the agenda for the next generation of experiments. Conversely, a compelling analysis of today’s experiments can raise new theoretical questions, not about how best to fit the data but whether these data provide hints of new principles. Close examination of the examples presented in Part I of this report shows that biological physics has made substantial progress through this more subtle interplay between theory and experiment. Nonetheless, many members of the community report that finding funding for theoretical work that reaches beyond today’s experiments remains challenging.

The agencies responsible for support of physics more generally have established mechanisms for the support of theory as an independent activity, as noted above. Much could be gained by extending these mechanisms to encompass biological physics, or the physics of living systems. Not only would it be easier to support forward-looking theoretical research, but independent funding mechanisms would play a role in unifying the community of theorists and highlighting the role of theory in the search for a physicist’s understanding of life.

Specific Recommendation: Federal agencies and private foundations should develop funding programs that recognize and support theory as an independent activity in biological physics, as in other fields of physics.

Coda: The Usefulness of Basic Science

In October 1939, just after the start of World War II, Harper’s magazine published an essay on the usefulness of useless knowledge.⁹ It was an astonishing moment at which to offer a vigorous defense of human curiosity and intellectual exploration as the engines of progress. But the argument was prescient. Although the pre-war world had been transformed by automobiles, airplanes, and radio, the pace of change would accelerate dramatically during and after the war. In the industrialized world today, our lives are noticeably more dependent on advanced technologies than even a decade ago, and there is no end in sight.

Every piece of technology in the modern world has at its foundation remarkable developments in basic science. The path from science to useful technology can be long, and requires its own unique innovations, but without the scientific foundation, none of this is possible. An example from 1939 was that radios required the 19th-century unification of electricity and magnetism, and the resulting prediction of electromagnetic waves. Today, computer chips would not exist without quantum mechanics to describe the behavior of electrons in semiconductors. It would not have been possible to make effective vaccines against COVID-19 so rapidly without a generation of work on protein structure and on the basic mechanisms of gene expression and replication in cells.

While it is not so difficult to trace back in time from useful technology to foundational scientific discoveries, it is much harder to predict which discoveries or even which areas of research will lead to useful technology. Investments in microwave spectroscopy around 1950 led to the maser, which led to lasers, which led to dramatic improvements in eye surgery (Chapter 7), among other medical applications. But who would have argued, in 1950, that support for a small group of microwave spectroscopists was important for the future of ophthalmology?

All of this matters because much of the justification for substantial government spending on science is that these investments will have impact on our lives. More concretely, NIH support for research on biological physics ultimately is justified by the fact that physicists’ explorations of the phenomena of life have a profound impact on human health. As emphasized throughout this report, this is not merely “physics applied to medicine.” Similarly, DoD support for the field is justified by the impact that biological physics has on relevant technology. Again this impact comes in large part not from the application of physics to well-posed problems outside the field, but from the discovery of basic physical principles that govern living systems and can be emulated in engineered systems. These paths for impact are reviewed in detail in Chapter 7.

___________________

⁹ A. Flexner, 1939, “The Usefulness of Useless Knowledge,” Harper’s (179):544–552, reprinted with a companion essay by R. Dijkgraaf, 2017, Princeton University Press.

General Recommendation: To maintain the flow of concepts and methods from biological physics into medicine and technology, the federal government should recommit to the vigorous support of basic science, including theory and the development of new technologies for experiments.

To implement this recommendation it is essential that not only NSF but also the mission-driven agencies contribute to the support of basic science. Existing funding mechanisms often follow a pattern of siloed utilitarianism, focusing only on areas of funding where single agencies and even individual programs within these agencies are confident of their expertise or sovereignty. This style of funding can lead to the premature drawing of boundaries between what is relevant and what is not, limits the ability of agencies to advance their missions, and in the end can even inhibit the progress of basic science by fragmenting the field along these boundaries. History teaches us that the best investments in society’s future often involve trying to answer today’s most basic scientific questions.

USER FACILITIES

User facilities are substantial pieces of research infrastructure that are too large, too complex, or too costly for a single university or company to maintain. Examples relevant to biological physics research include synchrotron light sources; cryogenic electron microscopes; high-performance computing facilities; neutron-scattering sources; high magnetic fields; and specialized facilities for nanoscience, imaging, and genomics. These facilities and resources are generally available for research access on the basis of competitive peer review.

Many are physically located at the DOE National Laboratories and are supported directly by the DOE Office of Science. Other facilities and funders relevant to the biological physics community include, among others:

• The Advanced Imaging Center at Janelia Research Campus of HHMI, supported in part by the Gordon and Betty Moore Foundation;
• The New York Structural Biology Center, supported by a consortium of New York–based universities, the Simons Foundation, and NIH;
• The National High Magnetic Field Laboratory at Florida State University, supported by NSF along with DOE through facilities at Los Alamos National Laboratory; and
• The Pacific Northwest Center for Cryo-EM (PNCC), supported by NIH along with DOE through the Pacific Northwest National Laboratory.

The federal facilities are a huge national investment in science that support tens of thousands of research projects each year. As technologies evolve, evolution of the facilities can provide a dramatic democratization of frontier science.^10,11

To gauge trends and needs with regard to the use of such facilities for biological physics research, the committee solicited information via a questionnaire distributed both to facilities directly and also to the DOE Office of Science (Appendix C). The responses reflect the key role of user facilities in enabling cutting-edge biological physics work and also suggest some important opportunities for improvement.

The facilities reviewed here categorize their users as belonging to Biology and Life Science, Chemistry, Earth and Environmental Science, Engineering, Materials, or Physics. Figure 9.7 shows the proportion of users identified as Biology and Life Science at each of the facilities. Three centers primarily support the life sciences, but several other user facilities that might have been seen as giving primary support to the physical sciences in fact support much broader communities. The four X-ray sources report biology and life science use ranging from 25 to 40 percent; the high magnetic field laboratory 24 percent, the three advanced computing centers 5 to 13 percent. The Environmental Molecular Sciences Laboratory (EMSL) has a quarter of its users in biology, and more than a third in environmental sciences. A common thread is that the genesis of these powerful tools has come from decades of investment in physics-based technologies, often without a particular vision that they would impact our exploration of the living world. When these tools are found to be useful in a new field, a community of users learns to exploit them.

Finding: Large-scale physical tools, particularly those for imaging and advanced computing and data, are an important part of the infrastructure supporting thousands of researchers exploring the living world.

Engagement of the biological physics community with user facilities goes beyond instruments to include high-performance computing. As an example, of the approximately 60 peer-reviewed Innovative and Novel Computational Impact on Theory and Experiment (INCITE) awards supported annually by the Argonne and Oak Ridge Leadership Computing Facilities, there have annually been 5 to 10 in the category “Biological Sciences: Biophysics.”

___________________

¹⁰ E. Hand, 2020, “Cheap Shots,” Science 367(6476):354–358, https://www.science.org/doi/10.1126/science.367.6476.354.

¹¹ C. Tachibana, 2020, “Democratizing Cryo-EM: Broadening Access to an Expanding Field,” Technology Feature, Science.com, https://www.science.org/content/article/democratizing-cryoem-broadening-access-expanding-field.

The facilities report generally standardized methods of access (application and peer review), and each has multiple ways of getting community input for facility development. Most of them provide a “concierge service” for new users and they are incentivized to get this right. They invariably offer specialized training, courses and summer schools, run conferences bringing together their user communities, and host student interns. PNCC notes the centrality of training, “One of our center goals is to train cryo-EM researchers toward independence, with a focus of providing hands-on training opportunities, that are in short supply amongst many existing cryo-EM workshops.”

Although the raw data do not offer a detailed accounting of facility use by biological physics researchers, respondents offered insightful comments on the role of biological physics in the evolving interests and needs they are seeing among their user communities. Of growing interest, for example, is the ability to image with high resolution over large fields of view and to perform multi-modal studies. EMSL noted its investments “in the development of multi-modal analytical capabilities to enable the spatio-temporal imaging of cellular, communal, and systems level organisms (microbial, fungal, plant, for example) to facilitate the prediction

and control of biological systems for beneficial purposes.” This highlights an opportunity for the intersection of the biological physics community’s approach to collective behavior and ecological diversity (Chapter 3) with approaches to related problems in the environmental sciences community. As noted elsewhere, partnerships between funding bodies will be instrumental in advancing this exchange.

Often the large facilities themselves act as agents to bring research communities together and help those partnerships. For example, past partnerships between DOE and NIH to make dedicated beam-lines and support protein characterization played an important role in advancing structural biology. Advanced Photon Source (APS) users deposit more protein structures into the Protein Data Bank than any other facility in the world. APS noted:

User facilities are not always based around large instruments. The five DOE nanoscience centers, for example, provide advanced instrumentation to a very wide research community, though the individual instruments might not be beyond the financial reach of some university laboratories. Their value is often in providing a professional concierge service to a science user who wants the tool without the overhead of managing it, and may also need a few weeks of access rather than full-time ownership. Sometimes the proximity of multiple tools matters, and perhaps also a straightforward connection to large-scale data analysis and computing. This model offers an opportunity to rapidly democratize advances in, for example, optical imaging, NMR imaging, force microscopies, and electron diffractive imaging. These tools are often of interest to many disciplines, of course, but most facilities are managed by organizations that have a predominantly physical sciences agenda, especially DOE. It also is critically important to invest in the development of next generation technologies (see Box 9.1).

While DOE facilities are generous in welcoming users from many different communities, the process of commissioning new facilities and upgrades is strongly confined by agency mission need. As an example, when modern synchrotrons were developed in the 1990s the case for them barely mentioned what has been one of their most productive contribution to science, medicine, and the economy: protein structure.

Finding: DOE has become a major sponsor of research in biological physics, especially through facilities, without acknowledging the field’s supporting contribution to the DOE mission.

Specific Recommendation: Congress should expand the Department of Energy mission to partner with the National Institutes of Health and the National Science Foundation to construct and manage user facilities and infrastructure in order to advance the field of biological physics more broadly.

A challenge in implementing this recommendation is that, in the language that DOE uses to describe users of its facilities, biological physics simply does not exist. If you are studying the structure of a protein, for example, you are a “biology or life sciences” user, no matter what question you are asking. This enforces the view that physics provides tools, but the phenomena being studied are outside of physics, belonging to another discipline. Obviously, this view has not stopped DOE from making enormous contributions to our exploration of life, and to many problems that fit squarely under the umbrella of biological physics as defined in this report. Nonetheless, it is worrisome that the nation’s largest source of funding for the physical sciences does not recognize more explicitly that the living world is a source of profound physics problems.

Finally, one major user facility does not fit the usual model, but has had a substantial impact nonetheless: the Kavli Institute for Theoretical Physics (KITP), which describes itself as a “user facility for theorists.” KITP was founded in 1979 (as ITP), supported by NSF and housed at the University of California, Santa Barbara. The model was to have a small permanent faculty, a community of postdoctoral fellows, and a steady stream of visitors. This model was common to many centers for theoretical research, both in the United States and around the world, but what made ITP a user facility was that it solicited proposals from the community for programs that would organize larger groups of visitors for extended periods. By any measure, this has been very successful, and is widely emulated. Now in its fifth decade, KITP efforts have expanded, and to keep pace with this expansion funding for its core programs now comes not just from NSF but from the Kavli Foundation, NASA, NIH, the Gordon and Betty Moore Foundation, and other sources. ITP’s first forays into biological physics were in the mid-1980s, and accelerated in the 21st century. An important component of these programs has been that they highlight, for the physics community as a whole, that biological physics has a place alongside other subfields as part of an integrated effort in theoretical physics. As the field grows, there is room for more experimentation with support for theory communities, where considerable impact is possible at relatively low cost.