Gregory D. Koblentz, David Gillum, and Rebecca Moritz
October 15, 2024
On September 25, 2024, Senator Rand Paul introduced a revised version of the Risky Research Review Act (S. 4667) which was voted out of the Senate Homeland Security and Government Affairs Committee by a vote of 8-1. In a recent OpEd in STATNews, we wrote of the original bill: “this legislation threatens to cast a shadow over the future of life sciences research and slow it down.” While this revised bill contains some positive changes, it remains deeply flawed and does not represent a viable solution to the challenges posed by dual-use research. This article analyzes the good, the bad, and the ugly of the revised Risky Research Review Act and finds that the negative features outweigh the positive ones.
The Good
The revised bill contains three positive additions compared to the original: the inclusion of a biosafety expert on the Life Sciences Research Security Board, the provision for expedited review of high-risk life sciences during an emergency, and a clearer definition of high-risk research that is more closely aligned with current U.S. government policy.
The composition of the Life Sciences Research Security Board has improved slightly. In our OpEd, we wrote, “The composition of the proposed board also raises serious concerns about its ability to effectively oversee high-risk research. The board would consist of political appointees, including life scientists and national security experts, but lacks a requirement for members to have expertise in biosafety and biosecurity. This omission is critical, as effective oversight of high-risk research requires nuanced understanding and practical, hands-on experience in these areas.” The revised bill now includes one biosafety expert on the Board, in addition to the executive director, five non-governmental life scientists, and two non-governmental experts in national security. Ideally, this expert should have practical hands-on biosafety experience both implementing research policy on a daily basis as well as reviewing life science research for potential misuse and developing risk mitigation measures. The new composition of the Board is one step closer to the long-recognized and widely supported need for a multidisciplinary approach to oversight of dual-use research. For example, current guidance from Office of Science and Technology Policy is that committees at Federal funding agencies conducting reviews of dual-use research should include representatives with experience in scientific research, biosafety, biosecurity, national security, and ethics, and other relevant areas.
The revised bill, however, does not address a problem we raised regarding how the bill’s conflict of interest provisions could affect the composition of the board: “The bill’s provisions regarding conflicts of interest defined too broadly could also disqualify many well-qualified individuals from serving on the board. It would exclude scientists with experience conducting high-risk research, which could result in a board lacking the necessary knowledge, expertise, and skills to make informed decisions about the risks and benefits of life sciences research, thereby undermining its effectiveness and credibility.”
Another good addition to the bill is a provision, in section 7906(d), for expedited review of high-risk life sciences research during a public health emergency or to address a specific national security concern. This was a necessary addition given the legislation’s 120-day timeline for reviewing and approving research proposals involving high risk life sciences research.
The revised bill also more clearly defines the scope of what it considers “high risk life sciences research” and this definition is in closer alignment with the 2024 United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (also known as the 2024 DURC/PEPP Policy), but the scope of high-risk research still has important ambiguities. The definition of high-risk life science research includes “gain of function” research and dual-use research of concern (DURC) involving a high-consequence pathogen (HCP), a new term of art introduced by this bill. However, the overall scope of the Risky Research Review Act is actually narrower than the 2024 DURC/PEPP Policy.
The definition of dual-use research of concern in section 7901(4) is mostly aligned with the definition of Category 1 Research in the 2024 DURC/PEPP Policy, with a few minor exceptions. The bill adds two additional experiments of concern to what constitutes DURC under the 2024 Policy: enhancing the transmissibility of a pathogen in humans (7901(4)(B)(i)(X)) and enhancing the virulence of a pathogen in humans (7901(4)(B)(i)(XI)). Since enhancing the transmissibility and virulence of pathogens are already covered under 7901(4)(B)(i)(I) and (7901(4)(B)(i)(II), respectively, it is not clear what the purpose of including these additional experiments are.
In addition, the bill includes “generate, use, reconstitute, or transfer an eradicated or extinct high-consequence pathogen” which is broader than the 2024 DURC/PEPP Policy which specifies such research with a pathogen with pandemic potential (PPP) or a previously identified pathogen with enhanced pandemic potential (PEPP). There are only three eradicated or extinct pathogens of concern—variola major, variola minor, and rinderpest. Since the generation, use, reconstitution, or transfer of variola major and variola minor are already covered by 18 US Code 175c, the 2024 DURC/PEPP Policy, and the Select Agent Regulations, the only impact of this provision is to apply the same restrictions to rinderpest, which is not considered a PPP since it does not affect humans.
The bill defines gain of function under section 7901(7) as “a research experiment that may enhance the transmissibility or virulence of a high-consequence pathogen.” The inclusion of gain of function as a separate category is redundant since the revised bill’s definition of dual-use research of concern also includes research involving the enhancement of transmissibility under 7901(4)(B)(i)(I) and 7901(4)(B)(i)(X) and enhancement of virulence in 7901(4)(B)(i)(II) and 7901(4)(B)(i)(XI).
This bill, like the 2024 DURC/PEPP Policy, covers these specified research activities when conducted in conjunction with certain pathogens. Like the 2024 DURC/PEPP Policy, the bill uses list-based and risk-based approaches to define what it considers to be a high consequence pathogen. The risk-based approach is identical to that used by the 2024 DURC/PEPP Policy to identify a PPP, namely a “pathogen that is likely capable of wide and uncontrollable spread in a human population and would likely cause moderate to severe disease and/or mortality in humans.” The list-based approach used by the bill (which is shorter than the original bill) yields a narrower list of agents subject to oversight compared to the 2024 DURC/PEPP Policy.
The list used by the revised bill includes wild-type or synthetic versions of influenza A viruses (excluding seasonal strains); sarbecoviruses, a subgenus comprised of 1 species; merbecoviruses, a subgenus comprised of four species; 11 other specific viruses; Yersinia pestis; and “a select agent or toxin, work with which poses a significant risk of deliberate misuse.” There are currently 68 agents and toxins under the Federal Select Agent Program. It is unclear what the bill means by “work with which poses a significant risk of deliberate misuse,” under what conditions research with a select agent and toxin would be trigger this provision and be considered a high-consequence pathogen, and how this definition relates to how the bill defines dual-use research of concern. If this provision is intended to subject all research with select agents, even with unmodified wild-type strains, to approval by the Board, then it belongs in the category of bad features of the bill.
Overall, the revised bill is an improvement over the original. However, the improvement is marginal and the bill is still plagued with definitional ambiguities. Overall, these positive changes are outweighed by the continued negative aspects that are retained from the original bill and are detailed in the next section.
The Bad
At its heart, this bill contains the same flawed process for reviewing high-risk life sciences research and the same excessive overreach we criticized in the original bill. As we wrote in STAT News,
“The proposed Life Sciences Research Security Board would have the unprecedented authority to veto funding for life sciences research, regardless of whether it is deemed high risk. This authority would effectively place the entire federally funded life sciences research enterprise under the board’s jurisdiction. This provision is particularly worrisome because it would allow the board to overrule agency decisions on a wide range of life sciences research, potentially including projects with minimal, or even no significant risk. Such extensive veto power could disrupt the research funding process, causing extensive delays that hamper scientific progress. This broad oversight could lead to a significant increase in the volume of research proposals subject to review by the board, further slowing down the funding process and creating bottlenecks that impede timely scientific advancements.”
Under the original and revised bills, entities that apply for Federal life sciences research funding must attest to whether their research falls into the category of “high-risk life sciences research” or not (section 7905(b)). The Federal funding agency receiving the proposal must then review these attestations and forward positive attestations to the Board for review. However, the funding agencies must also review negative attestations and “certify” that these attestations are valid. While the enforcement provisions in section 7905(g) of the revised bill are less draconian than those in the original bill, they are stiff enough that they will create a strong incentive for agencies to scrutinize every life sciences research proposal submitted to ensure that the offered attestation, positive or negative, is correct. In addition, the need to review and certify life science research proposals that are not deemed to be high risk will absorb additional resources within funding agencies. This will inevitably slow down the review and approval of all proposed life sciences research, even if it is declared not to pose a high risk.
The Board can take up to 150 days (an agency submits notification 30 days before award and the Board has 120 days to review) to render their determination on proposed high-risk research. Therefore, proposed high-risk life sciences research could be delayed for up to five months beyond the current process, assuming this new review process runs smoothly. If proposers or funding agencies categorize a broad range of life sciences research as high-risk to avoid being accused of not following the legislation, then this lengthy review process could affect a much larger volume of research beyond that which is genuinely high-risk, and it will be more difficult for the Board to review proposals based on this timeline.
The bill also gives the Board the ability to expand its jurisdiction unilaterally by changing the definition of dual-use research of concern (under section 7901(4)(B)(ii)) and expand the list of HCPs (under section 7901(8)(A)(ii)(XVII). Coupled with the lack of provisions requiring the Board to solicit public comment on proposed procedures for the high-risk life sciences proposal review process (under section 7904(c)), there is a significant risk that the Board could engage in regulatory overkill that fails to balance the risks and benefits of the dual-use research it is charged with overseeing.
A highly problematic provision of the original bill retained in the revised bill extends the jurisdiction of the Board to all life sciences research, even if it is not considered high-risk. Under section 7906(a)(2), the Board will have the authority to review all proposed research in the field of the life sciences, even if it is not designated as high-risk and determine if it should be funded or not. In section 7901(10), the revised bill defines life sciences research as the study or use of a living organism, virus, or product of a living organism, and “each discipline, methodology, and application of biology, including biotechnology, genomics, proteomics, bioinformatics, and pharmaceutical and biomedical research and techniques.” While this is a narrower definition than found the original version, it is still broad enough to provide the Board with unfettered control over the entire Federally funded life sciences research enterprise. Federal agencies spent $42.5 billion on life sciences research in 2020. In 2022, Federal agencies awarded approximately $30 billion to academic institutions for life sciences research.
The Ugly
Several features of the bill make the Board vulnerable to abuse which could have a chilling effect on a wide swathe of life sciences research that includes work on infectious diseases and the development of medical countermeasures.
Under section 7906(a)(3), the Board will have the authority to audit previously funded life sciences research that was determined not to be high-risk. The bill, under section 7905(e), also gives the Board the power to demand “any information relating to Federal funding awards for life sciences research determined necessary by the Board to provide oversight of the agency.” In addition, under 7905(h)(3), the Board may request additional information directly from an entity that has proposed or is receiving Federal funding and uses subawards or subcontractors to conduct its research. These provisions appear designed specifically to empower the Board to investigate the National Institutes of Health’s (NIH) previous decision to fund research on chimeric coronaviruses by EcoHealth Alliance at the Wuhan Institute of Virology, which was deemed by NIH not to fall within the scope of the Office of Science and Technology Policy’s Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (or P3CO Policy). Senator Paul has been one of the leading voices linking this research to the origin of SARS-CoV-2 and the COVID-19 pandemic.
The partisan nature of the bill is reinforced by several provisions that grant Congressional members and committees’ extensive access to the inner workings of the Board, Federal funding agencies, and research institutions that conduct life sciences research. Under section 7902(g), the Senate Homeland Security and Government Affairs Committee and the House Committee on Oversight and Accountability shall “have access to any records provided to or created by the Board.” The Board must respond to requests for information from a member of Congress within 30 days and the Board must brief the appropriate Congressional committees at least quarterly. While congressional oversight of executive agencies is both proper and necessary, the degree of congressional access and influence hardwired into the Board makes it more vulnerable to political pressure. The perception that the Board is being used as a stalking horse by political actors will undermine its legitimacy, credibility, and effectiveness.
Conclusion
Although this legislation is touted as focusing on the review of high-risk life sciences research, the Board’s authority to review all life sciences research, regardless of risk level, and veto funding agency decisions, will result in the close scrutiny of a much wider swathe of life sciences research which will likely lead to significant delays in the funding of this research. In addition, the ambiguities in its definition of high-risk life sciences research, the additional scrutiny of life sciences research that is not deemed high-risk, and the broad authority to investigate how funding agencies and institutions conduct research has the potential to have a chilling effect on the willingness of U.S. scientists to seek Federal funding for research with dangerous pathogens and for Federal agencies to fund such research. This could, paradoxically, incentivize researchers to seek funding from the private sector or foreign sources, which will exercise little to no oversight for biosafety or biosecurity. The end result could be a less dynamic, innovative, and competitive life sciences research enterprise in the United States and riskier research being conducted with less oversight.
Gregory D. Koblentz is director of the Biodefense Graduate Program at George Mason’s Schar School of Policy and Government and co-director of the Global BioLabs Initiative. David Gillum is associate vice president of compliance and research administration at the University of Nevada, Reno, an associate editor of Applied Biosafety, and co-founder of Tutela Strategies. Rebecca Moritz is co-founder of Tutela Strategies and is the immediate past president of ABSA International.
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