Reading Room Production — page 159

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. 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 "high-consequence" 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 "wildtype or synthetic" pathogens already listed - what is meant by "synthetic construct" in addition to previous use of "synthetic" and does this mean that using only a piece of a "high-consequence pathogen" (e.g. synthesizing the receptorbinding site and studying receptor affinity in vitro, or synthesizing a viral or bacterial enzyme and studying inhibitors in vitro) would potentially still be considered "high-consequence"? o Subparagraph B is auto-referential creating an exclusion for seasonal influenza unless genetic sequences have been introduced from the list of pathogens that includes influenza A - does this mean that any introduction of genetic material from one seasonal influenza virus into another seasonal influenza virus would be considered "high-consequence"? o Some other included pathogens besides influenza may be commonly circulating in the population, and classifying them as automatically "high-consequence" could potentially delay or interfere with clinical diagnosis and care depending on how the other criteria for centralized Board review are interpreted (e.g. all sarbecoviruses, all mpox viruses).