Attachment

The 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. 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. The list of "high-consequence pathogens" is concerning and would have an immediate negative impact to science and public health. The mention of Influenza A viruses, for example, would include all work with H5N1 viruses which are having a significant impact on our poultry and dairy farms. Research into vaccines, treatment, spread and evolution of these viruses is critical to ensure to curb this outbreak and to prevent those in the future. The same could be said for the inclusion of all mpox. The current outbreak and identification of Clade I is highly concerning and without scientists able to pivot nimbly, the outcome is concerning. We are also concerned with the catchall language that could expand the scope of pathogens and categories the board reviews simply by a majority vote from the board.of our concerns with the bill are: • Scope: The legislation continues to codify a list of pathogens, which would reduce the flexibility of funding agencies to adapt to changes from natural and anthropogenic evolution. It also continues to enable the board to review routine life science research outside of the "high risk" definition on a case-by-case basis, and it is unclear how this would be implemented in practice without significantly impacting research review timelines. • Board processes and makeup: The o Given that certain types of research with any "wild-type or synthetic" pathogen among the listed species would apparently require review by the new Board, this appears to suggest that research with viruses engineered or adapted for decreased pathogenicity (e.g. certain mouse-adapted or tissue-culture-adapted strains) would be considered "highconsequence" even if they have been deliberately altered to decrease the research risk, e.g. for exploration of drug-resistance mechanisms at lower BSL levels. o Category XVIII "any synthetic construct of a pathogen or category of pathogen described in this clause" may be confusing regarding what it adds to the "wild-type or synthetic"