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THE NEED FOR FEDERAL COORDINATION AND USE OF CONVERGENCE SCIENCE

When examining the work, strategy, and outcomes of the federal government, a common observation is that better coordination would reduce redundancies and increase efficiency. Although commonplace, this is a critical observation. Coordinating across federal agencies is a bedrock action for advancing the U.S. biomedical research enterprise. As mentioned in Chapter 2, improved and continuous coordination across federal agencies will both support and be driven by the development of a national strategic vision for the U.S. biomedical enterprise.

The need for federal coordination is so great for two reasons. First, the health challenges faced by America are complex, interdependent, and cannot be solved without collaboration between institutes and centers of the National Institutes of Health (NIH), other agencies of the federal government, and actors beyond. Addressing these challenges requires not only high-level coordination to ensure adequate funding, infrastructure, and person-power but also expertise from many fields of study as scientists, researchers, and clinicians work together to develop new therapies and treatments. The use of convergence science—or “an approach to problem-solving that integrates expertise from life sciences with physical, mathematical, and computational sciences, medicine, and engineering to form comprehensive synthetic frameworks that merge areas of knowledge from multiple fields to address specific challenges”—is no longer a value-add (NRC, 2014). It is required to address the diseases and threats facing the American public today.

Second, current methods for funding biomedical research result in fragmented areas of focus and often produce duplicative or conflicting efforts to achieve the same ends. Better coordination across the federal government—driven by the national strategic vision—will enable all players within the federal government

and external agencies to “pull in the same direction.” Breaking down siloes to facilitate collaboration and movement toward the national strategic vision will not eliminate current efforts or prevent future ones. Rather, the biomedical research enterprise will be better positioned to act more proactively, increase efficiencies and productivity, and make tangible progress toward reversing the health challenges and chronic diseases that currently impact many Americans.

COMPLEX HEALTH CHALLENGES AND PERSISTENT CHRONIC DISEASES

As outlined in Chapter 2, the obesity epidemic is one of the most pernicious, complex, and deadly health trends currently impacting Americans. By some estimates, 50% of the U.S. adult population will be obese by 2030 and 1 in 4 adults will be severely obese—defined by having a body mass index (BMI) greater than 40 (Ward et al., 2019). In addition to its own health impacts, rising rates of obesity and diabetes are likely also contributing to rising rates of mortality from cardiovascular disease (Akil and Ahmad, 2011). Obesity is also known to increase the risk of diabetes, making the two chronic diseases inextricable (Klein et al., 2022). The coupling of progress and reversal in obesity, diabetes, and cardiovascular disease, as well as the known—and unknown—causes of obesity illustrate that efforts to improve human health cannot exist in only one field of science or medicine. Instead, there is an urgent need to coordinate research to uncover the biological, social, economic, geographic, and other underpinnings of disease to enhance education, prevention, diagnostics, and treatments to improve care and treatment for all Americans and reduce existing health disparities.

For example, it is known that obesity and diabetes disproportionately impact minority and low-income populations, with non-Hispanic Black individuals experiencing higher rates of end-stage renal disease than their counterparts, and Hispanic and Asian individuals experiencing higher rates of end-stage renal disease complications (Thornton et al., 2020). To address the complex interplay of disease states as well as the clear health disparities in a manner that prioritizes convergence science, in the future envisioned by this Special Publication, the research agendas set by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the National Institute on Minority Health and Health Disparities would be coordinated to appropriately address the interplay between and disparities that arise from the intersection of obesity, diabetes, and cardiovascular disease. Perhaps more importantly, scientists from each institute would intentionally collaborate, share

information, and participate in studies together to ensure that the knowledge from each field is brought to bear in real time. Intentional coordination of this type will help address all aspects of a difficult problem and avoid unintended consequences.

In addition to better understanding the molecular underpinnings of obesity, diabetes, and cardiovascular disease and developing drugs and treatments to address these conditions, the United States will need to coordinate behavioral health, mental health, food science, nutrition education, and other experts. This new level of convergence science is required to address these complex health challenges. The authors of this Special Publication believe that the current structure of the U.S. biomedical research enterprise cannot effectively address the obesity epidemic—and similarly complex health challenges—so new and creative approaches and collaborations are required.

Two additional examples of complex problems that require convergence science to solve are existing and emerging infectious diseases and deaths of despair. As the global climate continues to change, animals, insects, and other disease vectors will expand into geographic regions in which they were not previously able to survive, leading to the emergence of new infectious diseases and broader spread of existing infectious diseases. For example, in 2022, the United States reported 2,000 cases of malaria due to travel to areas where malaria is endemic (Mitchell et al., 2024). However, in 2023, at least nine cases were contracted by people who had not traveled outside of the country, meaning that their infectious were locally acquired (Bagcchi, 2023). The World Health Organization classified America as malaria-free in 1970, but these locally acquired cases signal the need to prepare for malaria’s potential return (WHO, 2023b). Infectious disease experts, entomologists, climate scientists, civil engineers, and state and local health departments will need to collaborate to adequately prepare for potential increases in malaria and other infectious diseases.

Deaths of despair—or early deaths due to suicide, drug overdose, or alcohol consumption—are another example of a serious and complex health challenge that will require convergence science to address (Beseran et al., 2022). Experts in mental health, addiction science, neurologists, behavioral scientists, and social scientists will need to share information and expertise in new ways to combat these deadly trends. In addition, coordinated federal funding that cuts across agencies and NIH institutes could support real progress toward ameliorating these challenges. Such coordination—of expertise, information, people, and funding—will not only provide a solid foundation for research but also signal that these issues are a national priority.

COORDINATED FUNDING WILL LEAD TO COORDINATED SOLUTIONS

As mentioned in Chapter 2, the national strategic vision will drive coordination in both funding and new approaches to science. Coordinated funding will allow the convergence science necessary to solve these challenging issues to occur—one is not possible without the other.

The current biomedical research enterprise has not evolved to adjust for its own success and growth. Without clear, overarching goals, too many priorities compete for insufficient funds, which results in projects with similar objectives launching in parallel rather than in concert and leads to siloed research focused on only one or two areas of expertise, rather than the broad swath of expertise needed to solve many of the health challenges detailed above and in Chapter 2. Research expenditures across all sectors must be driven by a national mission to improve health, rather than individual agendas or motivations such as profit margins.

THE PROMISE OF PUBLIC–PRIVATE PARTNERSHIPS

Public–private partnerships (PPPs) provide tremendous opportunities to enable and encourage collaboration and convergence science and to accelerate discovery and development to improve human health. These joint ventures should not be reserved for public health crises but should be strategically deployed to advance health and health equity where and when most needed. Three impactful examples are provided below to share best practices and opportunities for how PPPs can help accelerate the use of convergence science across the U.S. biomedical research enterprise.

Foundation for the National Institutes of Health Accelerating Medicines Partnership^®

Launched in 2014 by the Foundation for the National Institutes of Health (FNIH), the Accelerating Medicines Partnership (AMP) aims to “improve understanding of disease pathways, facilitate better selection of targets for treatment and identify platforms and processes to accelerate new and effective therapies to patients” (FNIH, 2023a). Every AMP project is a PPP, and AMP currently includes 10 projects, 34 industry partners, 37 nonprofit partners, 16 NIH institutes and cross-institute programs, the U.S. Food and Drug Administration (FDA), and $834 million in funding (FNIH, 2023a). The AMP concept emerged

from a meeting with leaders of major pharmaceutical company research and development (R&D) branches who were collectively concerned with lagging productivity in drug development pipelines (FNIH, 2023a). Coalescing around a shared interest in accelerating timelines, reducing costs, and increasing success rates of new therapies, AMP supports PPPs that focus on the rapid development of basic tools that benefit all investors as well as the public and private sectors (FNIH, 2023a). AMP projects include:

• Identifying new, clinically relevant therapeutic targets for Alzheimer’s disease and improving validation of identified targets and biomarkers (FNIH, 2023b);
• Developing gene therapies for rare genetic diseases that otherwise would not have commercially viable treatments (FNIH, 2023c);
• Using new data and artificial intelligence to better define the symptoms and characteristics of heart failure with preserved ejection fraction—or diastolic heart failure—which occurs when the left side of the heart cannot fill or pump properly (FNIH, 2023d); and
• Validating biomarkers to better understand the early stages of schizophrenia and predict its progression into psychosis and other outcomes (FNIH, 2023e).

One of AMP’s completed projects, Phase 1 of the AMP Lupus Network, has established a nationwide network of clinical sites; optimized high-throughput protocols; and amassed a large sum of data from the analysis of renal tissue, urine, and blood from patients with lupus nephritis (LN) (FNIH, 2023f; NIH NIAMSD, 2024a). LN affects up to 40% of people with systemic lupus erythematosus and often results in end-stage renal disease and death—especially among individuals from racial and ethnic minorities (Pryor et al., 2021). Upon completion of the Phase 1 project, researchers are now beginning to identify biomarkers for LN. The newly established network of clinical sites and protocols will assist in learning more about how the kidneys change as LN progresses, providing a clearer understanding of how patients respond to treatments. The Phase 1 project was such a success that it has been expanded into a follow-up program for the Autoimmune and Immune-Mediated Diseases branch of AMP (NIH NIAMSD, 2024b).

Global Health Innovative Technology Fund

Japan’s Global Health Innovative Technology Fund (GHIT) is the first PPP of its kind in Japan (GHP and IFPMA, 2024). GHIT’s partners include the government of Japan, the Bill & Melinda Gates Foundation, the Wellcome Trust,

and assorted global life sciences companies (GHP and IFPMA, 2024). GHIT invests and manages an R&D portfolio aimed at addressing neglected diseases such as malaria, tuberculosis, and other tropical diseases that afflict the world’s underserved populations (GHP and IFPMA, 2024).

To date, the GHIT Fund has invested approximately ¥29.1 billion ($202 million USD) in 118 projects (GHIT Fund, 2023). Fifty-three projects are under way, including “26 targeted and exploratory research projects, 15 non-clinical trials and 12 clinical trials” (GHIT Fund, 2023). Demonstrating the GHIT Fund’s partnership strength, “170 partners (59 domestic and 111 global groups) have participated in product development thus far, and the number of Japanese institutions and partnering global institutions has increased dramatically over the past 10 years” as of May 25, 2023 (GHIT Fund, 2023).

The GHIT Fund requires that products resulting from research it funds be appropriate, effective, affordable, and accessible to all, regardless of socioeconomic status. In fact, all grant investment proposals must prioritize open innovation and guarantee that products will be developed on a “no gain, no loss” basis (Slingsby and Kurokawa, 2013); that is, in low-income countries, these drugs will be licensed without royalties, but in middle- or high-income countries, they will be licensed at cost (Slingsby and Kurokawa, 2013).

Operation Warp Speed

The U.S. government launched the PPP Operation Warp Speed (OWS) in May 2020 with $18 billion in federal funding to accelerate the development, manufacturing, and distribution of COVID-19 vaccines (GAO, 2021; Tozzi et al., 2020). OWS involved agencies within the Department of Health and Human Services—the Centers for Disease Control and Prevention, FDA, NIH, and the Biomedical Advanced Research and Development Authority—the Department of Defense, the Department of Agriculture, the Department of Energy, and the Department of Veterans Affairs (NIHB, 2020). The primary function of OWS was to provide private companies, which sometimes partnered with federal agencies or scientists, with funding to develop vaccines and treatments. Several companies received funding—Moderna and Pfizer/BioNTech on an mRNA platform; Janssen and AstraZeneca on a replication-defective, live-vector platform; and Sanofi/GlaxoSmithKline and Novavax on a recombinant-subunit-adjuvanted protein platform (GAO, 2021).

OWS’s public financing was critical in developing these desperately needed vaccines, as the federal government took on the financial risk for their development, enabling the private companies to focus not on market profitability but on high-

volume production. An article from 2023 said, of OWS, “[i]t’s a case study in how the U.S. government can solve complex, urgent problems, and it challenges the narrative that public institutions have lost their ability to dream big and move fast” (Hamel and Zanini, 2023).

CALL TO ACTION

The U.S. biomedical research enterprise has produced an overwhelming number of scientific advances and discoveries since its inception. However, the needs of the American people and the health challenges facing them have changed, and the enterprise needs to change as well. The health challenges causing the most mortality and morbidity among the American public are increasingly complex and varied, and cannot be disconnected from pervasive and deadly health inequities and impacts of the social determinants of health. Initiatives to address these challenges require coordination at both the macro and micro levels.

At a macro level, increased coordination among the federal government and specifically the agencies responsible for biomedical research—notably, institutes of the NIH—is vital. Increased coordination will help eliminate siloed approaches to complex health problems, which divide pools of funding and necessary expertise, putting research projects at an immediate disadvantage. It will also produce funding and workforce efficiencies, remove barriers, and hopefully lead to a new series of breakthroughs to improve the health of the American people.

At a micro level, convergence science is no longer a bonus—it is required to solve 21st-century health problems. The health issues outlined to date in this Special Publication—notably, the complex interplay between obesity, diabetes, and cardiovascular disease—by their very nature require a transdisciplinary understanding and approach to solve. Addressing only the biological aspect of any disease is no longer sufficient to appropriately reduce or eradicate it—expertise from other scientific fields, especially behavioral and social sciences, will be imperative to improving health in the long term. Coordination among federal agencies will support the need for convergence science, and both are necessary to achieve the full possibility of the U.S. biomedical research enterprise.

To achieve this vision, the authors of this Special Publication propose the following:

Priority 4-1: Federal requirement and facilitation of necessary and essential coordination across government agencies, especially the National Institutes of Health and the National Science Foundation, as well as external parties, to enable the use of convergence science,

coordinate funding and strategy, adequately address the increasingly complex and interconnected health challenges facing the nation, and promote information sharing.

Priority 4-2: Federal promotion and use of convergence science in all appropriate projects receiving federal funding.