EXECUTIVE SUMMARY¹

The U.S. biomedical research enterprise—including discovery and translational research conducted by the federal government, pharmaceutical industry, health care, and public health—contributes significantly to America’s health and economy. It supports scientific progress nationally and globally, demonstrated by the large number of American-born and -trained scientists who have received the Nobel Prize and have made breakthrough achievements recognized by other accolades. Five of the 10 largest pharmaceutical companies are based in the United States, and America provides many talented global scholars with advanced biomedical training every year. Many international scientists who train in the United States remain in the country and contribute to growing America’s knowledge capital and gross domestic product (GDP)—further strengthening the U.S. biomedical research enterprise.

Despite these many positives, the biomedical research enterprise, in its current state, is not achieving all it can. The structure of the enterprise, established in the early 1940s, has not significantly changed since then. It has achieved much in the past 80 years, including reducing cancer mortality, developing medications to treat and prevent HIV/AIDS, sequencing the human genome, and developing and distributing vaccines that helped quell the COVID-19 pandemic—but the challenges facing Americans and, therefore, the enterprise have changed.

First, the health threats causing the highest levels of morbidity and mortality for Americans are increasingly complex, intertwined, and connected to the social determinants of health. These health threats are also almost unilaterally disproportionately impacting minoritized populations, resulting in inexcusable health inequities. For example, within the United States, maternal mortality rates for non-Hispanic Black women are 3.0 times that of Hispanic women and 2.5 times that of White women. Therefore, a single treatment, drug, or diagnostic

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¹ This Executive Summary does not include references. Citations for the discussion presented in the Executive Summary appear in the subsequent chapters.

will not be able to solve these health problems. A coordinated, transdisciplinary approach is necessary to understand, intervene, and alleviate these diseases—and the current structure of the U.S. biomedical research enterprise struggles to facilitate and fund such convergence science. The enterprise has also never explicitly focused on health equity, and the time for improving the health of all Americans is well overdue.

Second, America’s peer nations are beginning to invest more and more of their own GDP and person-power into biomedical research while America’s investments have remained relatively flat for the past two decades. These peer nations are also developing, implementing, and utilizing national-level strategic plans to guide their investments and areas of focus. The United States has long held a leadership position in biomedical research, but a lack of high-level national coordination results in inconsistent emphasis and growth. This lack of focus will likely put the United States at a disadvantage compared to its peer nations when health challenges are only growing.

Third, structural issues are standing in the way of the enterprise’s utmost efficiency and effectiveness—two of which are a lagging workforce and fragmented funding. The U.S. biomedical enterprise would not exist without the scientists, scholars, and related personnel who conduct and support the research that leads to breakthroughs, therapies, and diagnostics. However, the enterprise is not financially competitive when compared to industry and academia, female scientists and those from minoritized backgrounds compose an unacceptably small portion of the workforce, and international scholars who earn their degrees in America are increasingly exiting the U.S. biomedical workforce for employment elsewhere. Although the federal government drives most of America’s biomedical research funding, increasingly large contributions from industry, venture capital, and philanthropy bring conflicting agendas that can result in research focused on what is profitable rather than what is beneficial for most Americans.

Now is the time to take bold steps to structurally improve the U.S. biomedical research enterprise, implement efficiencies, increase the use of convergence science, and break down silos. Without these efforts, America risks harming the nation’s health and economy.

This National Academy of Medicine (NAM) Special Publication addresses each of these barriers in turn, spending a chapter focusing on the history and current challenges associated with a specific barrier and then proposing actions to address and eliminate it. This Special Publication aims to provide a roadmap for reimagining and reinvigorating the U.S. biomedical research enterprise before a time of dire crisis when all Americans and the world need it to be working at its full efficiency.

AUTHOR GROUP

The NAM appointed a committee to author this Special Publication composed of NAM members and other leaders who are dedicated to health and medical research, its promise, and its future. They have expertise in medicine, nursing, public health, population science, patient advocacy, basic science, academic leadership, education, policy, pharmaceuticals, federal government, and science advocacy. The authors met over a year and reviewed the nation’s progress in health and medical research since 1999 with a focus on its current state. They then developed and proposed solutions to ensure that future generations can reap the benefits of a nation that is an innovative leader in health science research.

APPROACH AND METHODOLOGY

The authors reviewed trends over time—including past, current, and growing health challenges, the research funding dedicated to select conditions, and associated mortality and incidence—using publicly available data and focusing primarily on 2000 to today. The authors also interviewed 10 leaders and experts in biomedical research, federal government, philanthropy, and venture capital funds to understand their experience since 2000 and where they believe the U.S. biomedical research enterprise needs attention. The data presented in this Special Publication and the input collected from the 10 interviews served as the basis for 9 months of analysis, discussion, and review, culminating in a hybrid retreat to formulate this Special Publication’s priorities for action.

PRIORITIES FOR A RENEWED AND REVITALIZED U.S. BIOMEDICAL RESEARCH ENTERPRISE

Biomedical Research Enterprise Advisory Body and National Strategic Vision

The U.S. biomedical research enterprise is a large and complex entity composed of many actors and serving many agendas. These often conflicting and numerous prerogatives and stakeholders result in a fragmented approach to prioritization and funding that may elevate areas of focus other than the emerging needs of the American people and the world. The National Institutes of Health (NIH) is the largest single funder of American federal biomedical research, but even within NIH—which is composed of 27 different institutes and centers—project and priority redundancy and fragmentation are likely, as every institute and center

receives its own funding and sets its own agenda. This fragmentation may lead to minimal strategy and coordination, increased redundancy, and prioritization of disease areas that are profitable rather than impactful. Strategic coordination across all aspects of the U.S. biomedical research enterprise is necessary to ensure that it is living up to its full potential. Furthermore, this Special Publication argues that dedicated federal funding can significantly impact how Americans are affected—or not—by a specific disease, so the issue of coordination and strategy is not only one of efficiency but also one that may determine the future health and wealth of the nation.

Many of America’s peer nations steer their funding and focus with the help of a national-level advisory body and subsequent national strategic vision. The United States currently has neither. Strategic planning at a national scale would enable the United States to be proactive against future health threats, create a communal direction toward achievable goals, improve operational efficiencies, increase productivity, and potentially advance cost-effective health care delivery.

Specifically, a national strategic vision and associated advisory body is necessary to address the increasingly complex health challenges facing Americans, including but not limited to:

• Decreasing life expectancy,
• Women’s health issues,
• Persistent health disparities,
• Deaths of despair,
• Obesity,
• Diseases of aging,
• Emerging diseases with pandemic potential, and
• Climate change.

A national strategic vision and advisory body would also enable the direct inclusion of members of the public in discussions about and priority setting for research. Providing opportunities for public input into priorities and execution can ensure that research is relevant to the American people’s needs and will help build trust and reassure individuals who are willing to engage directly with the U.S. biomedical research enterprise.

Given the urgency of the health threats facing Americans and the reality of current fragmentation across the biomedical research enterprise, the authors of this Special Publication propose the following:

Priority 1-1: A U.S. biomedical research enterprise advisory body, created by the President of the United States and Congress, to galvanize national leadership, develop a national strategic vision, and coordinate efforts and resources.

Priority 1-2: This advisory body could:

• Be composed of leading scientists from a wide variety of disciplines, such as life, physical, social, and behavioral sciences; engineering; economics; and the humanities to ensure a convergence science approach to addressing all emerging needs;
• Engage with multiple relevant federal agencies;
• Be established with long terms;
• Be empowered to set national goals and benchmarks;
• Provide input on resource allocation that matches strategy;
• Consider, examine, and utilize global best practices in all aspects of its work, but especially as guidance for developing the national strategic vision;
• Include patients, caregivers, and members of the public to provide transparency and public engagement;
• Have clear, measurable goals and timelines;
• Coordinate with the National Economic Policy Council and the Domestic Policy Council to ensure the engagement of all relevant stakeholders; and
• Monitor their progress and report to Congress and the American public annually on their work.

Priority 1-3: The advisory body’s national strategic vision could:

• Directly address the current fragmentation in funding and agenda-setting present in the U.S. biomedical research enterprise, in concert with the efforts proposed in Priorities 4-1 and 4-2. The national strategic vision cannot succeed without coordination and alignment of funding and agenda-setting, which, conversely, cannot be coordinated and aligned without the guidance of a national strategic vision. These priorities cannot be separated.
• Set priorities for the use of convergence science and implement a roadmap for bringing together relevant agencies and scientific disciplines to achieve this collaborative approach (see also Priority 4-2).
• Consider and propose funding to address:
  • Existing and emerging health challenges, including but not limited to infant and maternal mortality, women’s health concerns, deaths of despair, obesity, climate change, health disparities, diseases with pandemic potential, and diseases of aging;

• Future health threats such as increasing risks of extreme heat and other natural disasters due to climate change and emerging or existing infectious diseases;
• Public engagement in the entire U.S. biomedical research enterprise, but especially focused on increased participation in clinical trials;
• Deteriorating public trust in science and medicine;
• Prioritization and development of new and innovative research approaches to reduce and eliminate health disparities; and
• The needs of the U.S. biomedical research enterprise workforce, including adjusting historical pathways to employment or tenure as emerging health challenges, approaches to science, or the needs of the American public change.

Streamlined and Coordinated Funding

The United States currently spends the most of any country on research and development, but peer nations are increasingly dedicating a higher percentage of their GDP to funding biomedical research. Funding is not everything, but it does enable research to proceed in a focused, stable, and uninterrupted manner. A more streamlined approach to funding research and development, guided by a national body, will help ensure that the U.S. biomedical research enterprise can reach its full potential.

A variety of funding streams flow into U.S. biomedical research, including federal, industry, venture capital, and philanthropy—none of which arrives with “no strings attached.” Industry and venture capital funders are driven primarily by returns on investments required by their shareholders. Therefore, they will not or cannot fund a significant portion of biomedical research—particularly early-stage, curiosity-driven discovery research that is critical for advancing science but may have a high likelihood of failure or lack the potential for immediate profits. Alternatively, philanthropy often comes with personal directives that may be limited in scope. This piecemeal funding, driven by a variety of often conflicting agendas, makes it difficult to cobble together sufficient capital to comprehensively address the issues that are most directly impacting Americans.

Relatedly, funding for translating promising basic science into actionable therapeutics, drugs, or diagnostics is often extremely difficult to secure—leading to the funding “valley of death.” Many promising breakthroughs often languish between discovery and translation until their promise is recognized—which could be years or decades, if at all. The funding valley of death results in significant waste, because funding and person-power were used to make the discovery,

but the discovery is not translated into better health for Americans—or is significantly delayed. Addressing the funding valley of death is critical to ensuring the continuous improvement of the nation’s health and will add significant value to what the U.S. biomedical research enterprise is already producing.

To ensure that funding supports the health issues that affect the most Americans and is used to bridge the funding valley of death, the authors of this Special Publication propose the following:

Priority 2-1: A federally established national biomedical research funding collaborative, guided by best practices from existing international models, and federal determinations of how best to organize and allocate shared investments from the government, private sector, and philanthropy. The funding collaborative could be empowered to:

• Analyze successful existing models to develop best practices for the implementation of new methods for financing and accelerating biomedical research;
• Create a large-scale funding model to address the health challenges identified in the national strategic vision; and
• Develop new philanthropic collectives to encourage pooled, strategic gifts that can make a large impact.

Priority 2-2: Federally developed initiatives and funding strategies to specifically address the issue of the “funding valley of death” to translate promising basic research into breakthrough therapies, diagnostics, and treatments—helping to ensure that the full value of the U.S. biomedical research enterprise reaches all patients equitably.

Focus on Health Equity

The successes of the U.S. biomedical research enterprise have not reached all Americans. In fact, some are experiencing increasingly severe health disparities even while others are enjoying improved health. It is time for the U.S. biomedical research enterprise to realize its goal of improving health for all Americans and center health equity in its work.

Racial and ethnic minority groups in the United States experience worse outcomes in almost every measure of health and wellness compared to their White counterparts, and women or individuals who identify as women also experience disproportionate health disparities compared to men or individuals who identify as men. These disparities are due to a complex web of factors and are difficult to

untangle, understand, and treat. Research focused on reducing health disparities is necessary to better understand how to design and test interventions that can reduce morbidity and mortality for all Americans.

The workforce of the U.S. biomedical research enterprise is also in need of attention as it remains majority White and male. Increasing the diversity of the workforce is not only morally right but also will likely improve outcomes for patients and ensure that research focused on ameliorating health disparities is conducted comprehensively and respectfully. Just as public input is necessary to ensure the success of the national strategic vision, researchers who deeply understand how health and health care are prioritized, viewed, and addressed in their own communities should be involved in developing successful interventions and therapeutics.

The U.S. biomedical research enterprise itself also needs to be examined for issues of equity—specifically regarding the data it collects, aggregates, and uses for research. These data, which are increasingly used to train artificial intelligence models and tools, are not diverse, not representative, and may be race insensitive. Data used throughout the enterprise must represent the actual American populace to advance health equity, reduce health disparities, and design interventions that can successfully address the issues of all Americans.

Lastly, the U.S. biomedical research enterprise must invest in understanding and closing “the last mile”—a critical issue that the authors of this Special Publication have dubbed the “health equity valley of death.” Closing the last mile is of equal importance to addressing the funding valley of death because it prevents America’s most vulnerable populations from accessing care and the fruits of the U.S. biomedical research enterprise itself. Until the U.S. biomedical research enterprise can address all Americans’ unique needs and ensure that the research and products it advances are accessible, it will not have achieved its goal of improving health for all.

To center health equity in all operations of the U.S. biomedical research enterprise and make strides to close the health equity valley of death, the authors of this Special Publication propose the following:

Priority 3-1: Federal prioritization of research that informs solutions for achieving health equity in the United States, including those focused on the social determinants of health, diversifying the workforce, and the U.S. biomedical research enterprise itself. These research areas could include:

• Increasing trust in medicine, science, and the U.S. biomedical research enterprise itself;

• Mitigating structural and systemic discrimination;
• Delivering care to patients and the communities where they reside, using advances in implementation science to guide these solutions;
• Improving the communication of scientific and medical information; and
• Bolstering community engagement and effective bidirectional dialogue.

Priority 3-2: Federal prioritization of research on the “health equity valley of death”—closing the last mile—to understand and eliminate barriers that are preventing the most vulnerable populations in the United States from receiving and accessing comprehensive, high-quality, culturally appropriate care. Specific research areas could include:

• The digital divide;
• Improving access to health care, specifically for individuals who cannot afford adequate or any insurance coverage;
• Transportation barriers;
• “Health care deserts,” or a lack of health care providers—primary and specialty—in a given geographic area;
• Improving trust in science, medicine, and practitioners of both;
• Providing care outside of clinics and hospitals to meet individuals where they are; and
• Reducing racism, sexism, and other discriminatory practices that may keep individuals from seeking care.

Improved Federal Coordination and Use of Convergence Science

Suggesting that the federal government needs to coordinate better is an often-recommended improvement; however, for advancing the U.S. biomedical research enterprise, it is a bedrock action. Improved federal coordination is critically necessary for the operation and success of the advisory body and national strategic vision proposed in Priorities 1-1, 1-2, and 1-3 as well as the success of the funding collaborative proposed in Priority 2-1. Implementing these priorities will also ensure more effective and cohesive functioning of all aspects of the U.S. biomedical research enterprise.

Improved federal coordination will also enable the deployment of convergence science to solve the pernicious health challenges currently facing the American public. A National Research Council report defined convergence science as “an approach to problem-solving that integrates expertise from life sciences with physical, mathematical, and computational sciences, medicine, and engineering”

as well as social, behavioral, and economic sciences “to form comprehensive synthetic frameworks that merge areas of knowledge from multiple fields to address specific challenges” (NRC, 2014). The report specifically notes that “[a]n enhanced and expanded partnership among convergence practitioners … in the life, physical, and engineering sciences, the economic, social, and behavioral science and humanities research communities, and institutional leaders could be invaluable” (NRC, 2014). The authors of this Special Publication agree. Siloed funding and research agendas, by their nature, prohibit collaboration across federal agencies and areas of expertise—both of which are necessary to solve increasingly complex health issues such as obesity, deaths of despair, and the health impacts of climate change.

Federal coordination and advancement of convergence science will also facilitate the use of public–private partnerships, which provide tremendous opportunities to accelerate discovery and development. Public–private partnerships were implemented during the COVID-19 pandemic, often to great success, but should not be relegated to times of crisis. They should be thoughtfully deployed to address emerging and chronic diseases as well.

To encourage federal coordination and deploy convergence science across all areas of need, 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.

21st-Century Workforce

To ensure that the U.S. biomedical research enterprise can continue to produce effective therapeutics, drugs, and diagnostics, it must attract the smartest and most dedicated scientists, researchers, and support staff. However, growth in the biomedical workforce has slowed compared to America’s peer nations. Structural compensation, education, and training issues have reached a tipping point and

must be addressed before the United States loses competitive applicants to other fields or nations.

International students, scientists, and scholars have contributed significantly to the U.S. biomedical research enterprise. In 2019, more than 4,000 individuals holding temporary visas in the United States were awarded bachelor’s degrees in biological sciences; more than 2,500 were awarded master’s degrees; and almost 2,000 were awarded doctoral degrees (Trapani and Hale, 2022). Many of these graduates remain in the country for the rest of their professional careers. The biomedical research enterprise must ensure that the United States remains a welcoming and accessible country for international scholars to live, learn, and work.

Fragmented and flat funding for biomedical research also directly impacts the workforce and may influence scientists who are considering careers in biomedical research. The static availability of federal funding may lead to a more cautious approach toward awards, likely harming early-career scientists the most. A coordinated and strategic approach to funding would enable prospective members of the workforce to clearly understand where priorities lie and tailor their research and proposals, if possible.

Lastly, compensation and benefits for entering biomedical research must be raised to parity with similar positions, or the United States will risk losing qualified applicants to industry or academia. Postdoctoral positions regularly pay $15,000 less than comparative positions. Postdoctoral positions—depending on the source of funding—can also vary in access to standard benefits. While most offer health insurance, other benefits such as disability, retirement, or paid leave are not as common. The math here is simple—pay and benefits for these positions must be equivalent to their peer positions, or qualified individuals will move to where the money is.

To ensure a competitive, committed, and well-compensated U.S. biomedical research workforce, the authors of this Special Publication propose the following:

Priority 5: Steps by the federal government and Congress to increase the competitiveness of the U.S. biomedical research enterprise workforce, including the following key priorities:

• Align the U.S. biomedical research enterprise’s national strategic vision with the needs of its workforce and set goals to meet those needs;
• Incentivize and implement appropriate, specialized, and necessary education and training for all levels of the U.S. biomedical research workforce—including a reinvigorated focus on K–12 science, technology, engineering, and mathematics education to reinforce the pipeline at its earliest stages;

• Remove barriers that may prevent full accommodation and integration of international scientists into the U.S. biomedical research enterprise workforce, including expanding eligibility for federal research funding to temporary visa holders;
• Expand Early-Stage Investigator funding opportunities, particularly for physician-scientists, to help stabilize the career-launch phase of becoming an independent investigator;
• Reclassify federally funded postdoctoral scholars as employees and provide full benefits to remove unpredictability and make these positions more attractive, including the following potential approaches:
  • Significantly shortening the duration of postdoctoral training so that scholars gain independence faster,
  • Allowing postdoctoral scholars to apply for their own federal funding, and
  • Creating PhD-to-faculty positions, which would provide new pathways to stable employment;
• Promote the importance of physician-scientists to the biomedical research enterprise and support their training, education, and professional work, including the following potential approaches:
  • Expanding and increasing scholarships specifically for physician-scientists,
  • Protecting research time and salary support,
  • Connecting postdoctoral scholars with mentors, and
  • Employing innovative and immersive training and research programs; and
• Prioritize and implement innovative approaches to recruiting and retaining the specialized workforce, including by expanding student loan forgiveness, providing new funding modalities for postdoctoral trainees, and creating early career development awards for new investigators seeking to pursue research fields prioritized by the national strategic vision.

The authors of this Special Publication believe in the strength, power, and impact of the U.S. biomedical research enterprise to support the economy and improve health for all. The actions laid out in this Special Publication, when taken together, will provide the foundation for the U.S. biomedical research enterprise of the future. As a nation, we have already contributed so much—financially, professionally, and personally—to support and advance the enterprise. We owe it to ourselves—and our children and grandchildren—to ensure that biomedical research, conducted effectively, efficiently, and strategically, is benefiting all of America.