Evolution,New Concepts,and Institutional Adaptation to the 2024 Dual-Use Research of Concern and Pathogens with Enhanced Pandemic Potential Policy

Introduction

The 2024 “United States Government Policy for Oversight of Dual-Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential” ¹ together with its Implementation Guidance ² represent a significant evolution in the governance of high-consequence biological research. This policy builds on the principles established by previous policies issued in 2012, ³ 2013, ⁴ 2014,^5,6 and 2017 ⁷ and directly addresses the evolving challenges posed by modern life sciences research, including the rapid advancements in biotechnology and synthetic biology that have introduced new risks associated with pathogens with pandemic potential and dual-use research.^8,9 Furthermore, it also considers the principles set out in the World Health Organization Global guidance framework for the responsible use of the life sciences. ¹⁰ While this policy is a U.S. initiative targeting U.S. federally funded research projects, its implications extend beyond American borders, influencing global research practices, international policy frameworks, and the global approach to biosafety and biosecurity in an increasingly interconnected world.

Historical Context and Policy Evolution

Research involving dual-use technologies and pathogens with enhanced pandemic potential (PEPP) is essential to advancing scientific understanding and developing critical countermeasures, such as vaccines and treatments for infectious diseases.^11,12 However, this research also carries inherent risks, such as the potential for accidental release or misuse, which make robust safety and security regimens essential to achieving these benefits responsibly.

The oversight of dual-use research in the United States has historically been shaped by reactive responses to specific biological threats, a pattern evident since the mid-20th century. This approach has led to policy development in response to particular incidents, such as the illegal acquisition of plague bacteria in the 1990s ¹³ and the anthrax mailings of 2001. ¹⁴ These events prompted significant adjustments, including the establishment of the Biological Select Agents and Toxins program ¹⁵ to regulate and secure dangerous pathogens and toxins. Despite such efforts, U.S. policies governing dual-use research have often been characterized by reactive updates following emerging threats rather than a proactive, cohesive strategy.

A pivotal moment in dual-use research oversight occurred with the 2011–2012 controversy surrounding H5N1 mammal-transmissible avian flu research. ¹⁶ In this case, scientists enhanced the transmissibility of the H5N1 virus among mammals to better understand its pandemic potential. The study raised substantial biosecurity concerns, sparking international debate over the risks and benefits of gain-of-function (GoF) research, which involves modifying pathogens to study potential threats. ¹⁷ As a result, the U.S. government introduced the 2012 Dual-Use Research of Concern (DURC) policy ³ to establish formal oversight mechanisms for research that could be misused, focusing particularly on select agents and toxins that pose significant public health risks.

In 2014, additional DURC guidance ⁵ was released to expand oversight responsibilities, delegating authority to institutions themselves to identify and manage dual-use research risks. However, that same year saw a series of high-profile biosafety incidents that underscored ongoing vulnerabilities in laboratory practices. In June 2014, approximately 75 Centers for Disease Control and Prevention (CDC) scientists were potentially exposed to live Bacillus anthracis (anthrax) due to improper inactivation protocols. ¹⁸ Shortly after, National Institute of Health (NIH) workers discovered six forgotten vials of live smallpox virus (Variola virus) in a storage room, exposing significant lapses in pathogen inventory management. ¹⁹ In a third incident, a low-pathogenic avian influenza virus was accidentally contaminated with the highly pathogenic H5N1 strain and then inadvertently sent to an external lab. ²⁰ These incidents prompted the establishment of the Federal Select Agent Program ²¹ and recommendations from the Federal Experts Security Advisory Panel ²² and the Federal Technical Advisory Committee on Select Agent Regulations. ²³ While these were significant reactive measures, their implementation was only moderately successful, underscoring the challenges of systemic reform in biosafety and biosecurity oversight.^24,25

In response to growing concerns about GoF research, the U.S. paused Federal funding for certain types of GoF studies in 2014. This pause gave agencies time to reassess risks and led to the creation of the 2017 Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (P3CO Framework). ⁷ The P3CO Framework, introduced by the White House Office of Science and Technology Policy, allowed high-risk research to continue but required rigorous oversight, including ethical reviews, risk–benefit assessments, and stringent safety protocols.

Despite these advancements, U.S. policies for overseeing dual-use research have continued to be critiqued for their reactive nature and fragmented implementation.^26,27 The 2024 DURC/PEPP policy seeks to adopt a more proactive and cohesive approach, consolidating oversight measures and addressing public concerns over laboratory safety, particularly in the post-COVID-19 context.

Key Aspects of the 2024 DURC and PEPP Policy

This policy represents a comprehensive and integrated approach to manage these ongoing challenges. This policy not only builds on the foundations laid by its predecessors but also addresses the gaps identified in previous analyses. ²⁸ It introduces new concepts and broadens the scope of oversight to include a wider array of pathogens and research practices, reflecting the evolving nature of biological threats and the increasing complexity of the biotechnology landscape.

This policy also emphasizes the importance of continuous risk management, ethical oversight, and public accountability. By incorporating these elements, the 2024 policy aims to provide a more robust and adaptive framework for governing high-consequence biological research, ensuring that the benefits of scientific advancements can be realized while minimizing potential risks to public health and national security.

Comprehensive Integration of DURC and PEPP Oversight

One significant improvement in the 2024 policy is the combination of DURC and PEPP oversight into a single, cohesive framework. This approach recognizes that the risks associated with dual-use research and PEPPs are interconnected and require coordinated management. The policy clearly defines the roles and responsibilities of researchers, their institutions, and Federal agencies, ensuring that all parties involved understand their duties and obligations. Institutions are required to establish or strengthen Institutional Review Entities (IRE) responsible for oversight, aiming to equip these entities with experts in biosafety, biosecurity, ethics, and relevant scientific fields.

Expansion of Pathogen Scope

A notable change in the 2024 policy is the expansion of the types of pathogens and research practices that fall under its scope. This is operationalized through a two-category classification system, with one extra layer of agency oversight required for Category 2. •

Category 1 research applies to Biological Select Agents and Toxins ²⁹ and to a list of risk group 3 and risk group 4 pathogens reflecting the current guidance from the NIH, with experimental outcomes that would increase the virulence, toxicity, or transmissibility of the pathogen. However, select categories of viruses, bacteria, and fungi are exempted from Category 1 oversight. For example, pathogens integral to addressing ongoing public health crises, such as HIV, are excluded due to their foundational role in current therapeutic and vaccine development efforts.

While Category 2 broadens the scope of research under review, it leaves a critical gap by excluding animal epizootics, plant pathogens, and research with potential widespread environmental impacts. ³⁰ These areas pose significant global threats, as disruptions to animal health, agriculture, and ecosystems can indirectly affect human health while undermining food security, environmental stability, and biodiversity. This narrow focus on human health overlooks the interconnectedness of human, animal, and environmental health—a principle central to the One Health approach. Expanding Category 2 to incorporate these broader considerations would create a more comprehensive framework for addressing biosecurity challenges on a global scale. The need for a broader scope is underscored by the U.S. Department of Health and Human Services (HHS) Screening Framework Guidance for Providers and Users of Synthetic Nucleic Acids, ³¹ which applies to pathogenicity or toxicity threatening not only public health but also agriculture, plants, animals, animal or plant products, and the environment.

The flexibility of this classification system allows the policy to adapt to new and emerging threats, representing a more evolutionary approach compared with previous policies that relied on predefined lists. However, this flexibility also presents challenges, as the criteria for Category 2 could lead to varying interpretations and implementations across institutions, potentially resulting in uneven application of the policy.

Dynamic Risk Management

The 2024 policy places a strong emphasis on dynamic risk management, recognizing that the risks associated with biological research are not static and can evolve over time as research progresses and new information emerges. While the 2014 policy required annual reviews of risk mitigation plans, ⁵ the 2024 policy goes further by embedding continuous and adaptive risk assessment throughout the entire research lifecycle. This shift ensures oversight is not limited to periodic evaluations but remains proactive and responsive to emerging risks, enabling a more comprehensive and flexible approach to managing high-consequence research. •

Continuous Risk Assessment: Institutions are now required to implement systems that facilitate ongoing risk assessment throughout the entire research lifecycle. This means that rather than a one-time evaluation at the outset of a project, risk assessments must be revisited and updated regularly to account for changes in the research, such as new findings, technological advancements, or shifts in the project’s scope.

Ethical Oversight and Public Accountability

In addition to dynamic risk management, the 2024 policy incorporates elements of ethical oversight and public accountability, addressing concerns about the risks and transparency of research involving PEPP and GoF studies. ³² •

Ethical Oversight: For Category 2 research reviewed by Federal funding agencies, the policy emphasizes the inclusion of ethical considerations, such as nonmaleficence, beneficence, and justice, to ensure that potential risks are balanced against societal benefits. However, this approach aligns closely with prior frameworks, such as the 2017 HHS P3CO Framework, and does not explicitly extend to Category 1 research.

Communication and Publication Controls

The 2024 DURC and PEPP Policy emphasizes the responsible communication of research findings to minimize risks associated with dual-use research. Institutions are required to ensure that all research findings involving DURC or PEPPs are disseminated in accordance with the risk mitigation plan approved by the IRE. These plans must address how sensitive information will be managed to prevent misuse while enabling the appropriate sharing of scientific knowledge. By following these guidelines, institutions can ensure that communication is aligned with biosafety and biosecurity principles, although the specific approaches may vary between institutions.

Concretely Adapting to the 2024 Policy

To adapt to and comply with the 2024 DURC and PEPP Policy, institutions need to implement several concrete measures:

Establish or Strengthen IRE: Ensure the IRE is equipped with the necessary expertise and training to manage DURC and PEPP-related research effectively.

The implementation guidance [2] provides further information and concrete examples to assist the user in the implementation of the policy.

Conclusion

The 2024 DURC and PEPP Policy represents a major step forward in the governance of high-consequence biological research, integrating and expanding upon the principles established by earlier U.S. policies. By broadening the scope of pathogens and research practices covered, enhancing public accountability, emphasizing dynamic risk management, and implementing concrete measures for compliance, the policy sets a new standard for biosafety and biosecurity. While its focus on federally funded research marks a key limitation, the same principles could serve as best practices for nonfederally funded projects to promote a more unified global approach. This evolution not only is critical for safeguarding public health and national security within the United States but also has significant implications for international policies and practices.

The United States is a global leader in scientific research and policy development, particularly in the life sciences. In 2021, U.S. research and development (R&D) expenditures accounted for 27% of global R&D investments, with funding in the life sciences alone surpassing the total R&D budgets of many other nations. ³⁴ This substantial investment empowers the United States to set benchmarks in research practices and policy frameworks, including the 2024 DURC and PEPP Policy, which is poised to shape global standards in biosafety and biosecurity.

The policy’s emphasis on dynamic risk management, public accountability, and ethical oversight reflects a forward-looking approach that aligns with international guidelines, including the World Health Organization’s Laboratory Biosecurity Guidance, ³⁵ which highlights risk assessment as a core element in managing high-consequence research. As countries worldwide grapple with balancing scientific progress and biosecurity risks, the U.S. framework may serve as a model for developing or refining regulations, particularly in areas like dual-use research and the oversight of PEPP. By strengthening oversight and emphasizing transparency, the U.S. policy could encourage a more unified, globally consistent approach to managing the risks associated with high-consequence research.