Modernizing Biosecurity and Biosafety in the U.S.: Key Lessons Learned

Research in the biological sciences enables significant advancements in areas as broad as agriculture, manufacturing, environment, and health, but can also pose serious risks. In particular, research with pathogens and toxins is particularly critical for combatting disease, creating new medicines, and improving health outcomes, while accidents or misuse could harm human health, the environment, and national security. The United States has established biosafety and biosecurity policies to guard against these risks. But advances in technology, the growing research sector, and a changing threat landscape demonstrate the need for these policies to be continually evaluated and calibrated. This article outlines current U.S. government processes to bolster biosecurity and biosafety measures, and summarizes five key findings from biosecurity experts, namely:

1. The threat landscape is becoming more challenging

2. Defense in depth is key to resilience

3. Clarity and transparency should be enhanced

4. Clearer leadership and policy coordination is sorely needed

5. International alignment is increasingly vital 

The U.S. Government is reviewing its biosecurity measures

The United States has several policies already in place to address biosecurity risks associated with research, including Policies for Federal and Institutional Oversight of Life Sciences Dual Use Research of Concern (DURC), and the Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO), which mandate risk-benefit assessments, oversight mechanisms, transparency, and collaborative efforts among federal entities and research institutions to ensure the responsible conduct of high-risk research. Together, these policies form part of the U.S.’s broader biosafety and biosecurity system, seeking to mitigate risks while enabling vital research. 

Reviews of these biosafety and biosecurity frameworks are currently underway. In March 2023, the National Science Advisory Board for Biosecurity (NSABB), a multidisciplinary group of experts who advise the Department of Health and Human Services, released its report on Proposed Biosecurity Oversight Framework for the Future of Science, which recommended a more integrated approach to research oversight. The report also recommended more clearly articulated responsibilities, alongside updated requirements that better capture current and anticipated risks. Informed by this report, the White House’s Office of Science and Technology Policy (OSTP) released a Request For Information in September 2023, seeking input on the NSABB’s proposed changes to the DURC and P3CO policies. 

Engaging public, private and academic stakeholders is key

Managing the safety and security risks of biological research requires participation and expertise from practitioners, industry leaders, policymakers and researchers. On October 6, 2023, the Belfer Center's Defense, Emerging Technology, and Strategy Program hosted “Advancements and Challenges in Biosafety and Biosecurity Oversight in the United States” to bring experts together to explore the nuances of U.S. biosecurity and research oversight policies. The panel featured Dr. Rajeev Venkayya, CEO of Aerium Therapeutics and an independent member of the board of the Coalition for Epidemic Preparedness Innovations; Dr. Gregory Koblentz, Associate Professor and Director of the Biodefense Graduate Program at George Mason University's Schar School of Policy and Government; Dr. Larry Kerr, Deputy Vice President of Global Health & Multilateral Affairs at the Pharmaceutical Research and Manufacturers of America; and Dr. Angie Rasmussen, virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan.  The session was chaired by Dr. Syra Madad, Belfer Fellow and Senior Director of System-wide Special Pathogens Program at New York City Health and Hospitals.

Key Lessons Learned

Below are five key lessons learned from the panel that could help inform consideration of updates to U.S. biosecurity and biosafety policies.

Lesson 1: The threat landscape is becoming more challenging

“The global virus landscape has really become much more complicated and challenging over the last several years due to several trends.” - Dr. Koblentz

According to Dr. Koblentz, threats are being exacerbated by trends that were underway before the pandemic, but have been accelerated by COVID-19. These include the growth in maximum containment laboratories, the rise of pre-print servers, the growing investment of the private sector in biological research, the growth in virus-hunting, and developments such as new biotechnologies and artificial intelligence (AI).

Dr. Koblentz’s work with the Global Biolabs Initiative (GBI) has tracked the growing number of maximum containment labs, ‘where work takes place with lethal and contagious pathogens for which there are few or no effective treatments,’ around the world since the COVID-19 pandemic, flagging the increasing interest in high-risk pathogen research. According to GBI’s latest analysis, there are currently 69 of these Biosecurity Level 4 (BSL4) labs in operation, planned, or under construction in 27 countries. While the United States still maintains its position as the country with the largest number of BSL4 labs, many of the new facilities are being set up in developing countries. In the absence of strong international biosecurity and biosafety standards, a growing number of facilities may increase risk of accidents or misuse.

The rise of pre-print servers - online repositories which enable researchers to publish research without peer review - is also increasing biosecurity risks. Peer review can be an avenue through which dual use risks are identified and mitigated. Publishing early-stage research without the usual checks may increase the risks of sensitive research being disclosed and misused.

The growth in private sector investment in biological research is also leading to an increasing proportion of research being undertaken with little government oversight or control. Requirements attached to U.S. government funding have previously been a key lever for enforcing desired biosecurity and biosafety standards. With industry now leading the way on many kinds of pathogen research, this diminishes the impact of existing, funding-related oversight policies.

In addition, the growth in virus discovery - field research to uncover and understand new viruses - also presents real risks in the absence of national or international guidance for field biosafety.

Outside of pathogen research, broader technology developments could also increase the risk of a biosecurity event. In particular, increasingly accessible gene modifying technologies and future developments in artificial intelligence could increase the risks of an accident or misuse.

The panel agreed that existing safeguards require updating to remain calibrated to changing risks.

“There are stronger regulations governing the use of lab animals in experiments than there are conducting research with potential pandemic pathogens.” - Dr. Koblentz

Lesson 2: Defense in depth is key to biosecurity and safety

“There is no silver bullet for this problem. You need to have a series of imperfect layers of protection” - Dr. Venkayya

Defense in depth refers to the use of multiple, layered security measures to guard against threats. In the context of biosecurity and biosafety, it entails the integration of physical, technological, and procedural measures to safeguard against accident or misuse of biological agents and toxins, as well as public health capacity, surveillance, and response capabilities. Key to this approach is ensuring that when one layer is compromised, other safeguards exist to pick up and mitigate risks, and protect public health, the environment, and national security. In addition to addressing key emerging gaps, policymakers should consider how safeguards are integrated, and how they work together to reduce overall risk.

Lesson 3: There is a need to improve clarity and transparency

“Virologists … are often confused about how to actually comply with the framework.” - Dr. Rasmussen

While panel members agreed with the NSABB’s proposal to integrate and streamline the currently ‘patchwork frameworks’, they flagged that any ambiguity in definitions creates confusion. For example, both Dr. Kerr and Dr. Rasmussen flagged the terms ‘likely, moderate or highly virulent’ as highly subjective, and difficult to define. Centering new rules around clear examples could be useful in helping bridge the divide between policy ambitions and technical assessments. There is also a risk that ambiguity could dampen investment in much-needed research and development in the life sciences.

“Because what will happen in industry in the setting of ambiguity is that senior management - those that deploy capital - are going to adopt a more conservative posture.  They're less likely to fund R&D in critical areas if they believe that they're putting their company and their investors and stockholders at risk.” - Dr. Venkayya

Achieving greater transparency was also highlighted as a key requirement for improving biosafety and biosecurity practices throughout the research cycle. It is essential for increasing buy-in from the research community, strengthening their understanding of these policies, and bolstering public trust.

“We do need to have more transparency both on the side of regulation, as well as on the side of the investigators who are trying to comply with those regulations.”  - Dr. Rasmussen

According to Dr. Venkayya, more work could also be done to build maturity in biosecurity culture and awareness amongst researchers. In particular, it would be valuable to establish a culture where primary investigators are aware of the potential misuse of the research they are doing, and an environment where people feel empowered to raise questions about potentially problematic research. This need is already recognized in the current DURC policy, which states that ‘motivation, awareness of the dual use issue, and good judgment are key considerations in the responsible evaluation of research for dual use potential.’ Yet there are difficulties in translating this into practice. In updating these policies, the U.S. government should consider how it can better partner with industry and academia to build this culture of responsibility.

Lesson 4: There is demand for clearer leadership and policy coordination

The panel raised concerns that oversight of biosecurity and biosafety issues is fragmented, and proposed clearer government leadership of biosecurity and biosafety policies. Proposed options to achieve this objective ranged from a national agency administering national legislation to a dedicated federal office that coordinates efforts amongst existing agencies. The panel agreed that regardless of its form, it would be essential to ensure the maintenance of a risk mindset across the entire research enterprise. The possibility of leveraging existing networks and mechanisms was also raised.

“There's already a working relationship between the local and the Federal government that could facilitate questions and information exchange.” - Dr. Kerr

Lesson 5: International alignment is increasingly vital          

The global nature of biological hazards necessitates a harmonized and cohesive policy approach to managing biosafety and biosecurity risks. 

“A threat anywhere is potentially a threat everywhere.” - Dr. Venkayya

This is of growing importance in the context of developing countries with less experience in biosafety and biosecurity practices investing in BSL4 laboratories and pathogen research, as well as increasing global efforts in virus discovery. As home to leading global companies in biological research and a leader in biosafety and biosecurity, the United States should play a key role in promoting responsible biosafety and biosecurity practices around the world. This could be done through support of the World Health Organization, as well as more targeted outreach and engagement with key countries with growing bioeconomies.

Conclusion

The ongoing review of U.S. biosecurity and research oversight policies provides a valuable opportunity to reform these policies in light of the evolving biorisk landscape. The updated policies should adopt a defense in depth approach, improve the clarity and transparency of research oversight mechanisms, of the policy, provide stronger leadership and policy coordination, and promote the safe, secure, and responsible conduct of research around the world.

These topics and others were discussed at an October 5th Defense, Emerging Technology, and Strategy Event, "Advancements and Challenges in Biosafety and Biosecurity Oversight in the United States."