Reading Room Production — page 140

Pp uld or writ large (including research that is not associated with pathogens or toxins and raises no identified national security threats, such as cancer research). o If the statute only provided the board the responsibility to review federally-funded research involving DURC and PEPP, as defined in the DURC/PEPP policy, it would ensure oversight resources are used most efficiently to assess and mitigate risks to the public while avoiding unintended negative consequences for the nation's biomedical enterprise. We believe this is the intent of the bill but as written the definitions are not harmonized. (We recommend other definitions in the text be aligned to current U.S. Government policy, including "life sciences research.") o We recommend that the definitions and scope of review be fully harmonized with the DURC/PEPP policy and not include a separate list of pathogens. o A large amount of scientific research involves gain or loss of function; it's a fundamental process in science. For example, some types of immune therapy cause the immune system to gain function to fight against a disease. Unfortunately, the term "gain of function" has often being misconstrued to suggest all research that causes a gain of function is highly risky, which is inaccurate. In fact, most research involving a GOF does not confer significant additional risk or require additional oversight. NIH does not define the term GOF and current federal policy does not define or operationalize the term. The research that requires strict oversight involves enhancing the transmissibility and/or virulence of a pathogen such that it would pose an increased pandemic potential in humans. The USG policy on oversight of DURC and PEPP (effective May 2025) also does not use the term GOF when describing research that requires additional oversight because of its higher risk. As it appears the intent of the term "GOF" in this bill is to refer specially to research that has the potential to enhance the transmissibility or virulence of a potential pandemic pathogen, for clarity we would recommend the use of the term "pathogen with enhanced pandemic potential" in the 2024 OSTP policy that addresses this type of research, as well as it's associated definition. This would help to avoid the ongoing confusion surrounding the term GOF. · Board processes and makeup: While biosafety expertise is now included, the makeup and processes of the board could introduce a number of issues. For example, the limitations on prior federal service and designation of participation in high-risk research as a "conflict of interest" could limit the board from accessing relevant national security and life sciences expertise. The exclusion of those involved in high-risk research, based on the definition in the draft legislation, could exclude anyone with a current BSL3 or BSL4 program, excluding individuals with key expertise on how to conduct work safely. These limitations may also exclude individuals who work in government with relevant knowledge of intelligence and threat assessments. We also recommend relaxing the limitations on membership of the board and note that a number of the timelines are untenable (e.g., Congressional notification requirements within 3 days of identifying a potential conflict of interest; publishing procedures in the Federal Register within 90 days of the appointment of initial members; etc.). We note that several provisions relating to the membership of the Board or its support staff are vague, including the requirement that Board members be "impartial" and that support staff be prohibited from "directly or indirectly influenc[ing]" the Board. The proposed legislation would also politicize independent peer review by making the constituent members presidential appointees. · Review process: While a path for expedited review has been added, there could still be major issues with continuity of science due to delays of reviews or membership being confirmed. Among other concerns, in particular, this will significantly impede the USG's ability to prepare for and detect emerging infectious diseases/epidemics/pandemics and will also significantly impede the USG's research response to an epidemic/pandemic. We recommend establishing a default rule that research may proceed if a decision is not made within a fixed timeframe to ensure that any lapse in function by the Board (e.g., delays in confirmation) do not result in life sciences research grinding to a halt. We also recommend a formal appeals process and an exemption to public reporting requirements if the information could pose national security risks. · Review criteria: The bill does not articulate a principle or threshold that guides whether the board should or should not approve a study for funding - for example, should the Board approve research where it determines that the potential public health benefits of the research outweigh the potential risks to U.S.