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The re-creation of horsepox virus, an extinct orthopoxvirus with similarity to smallpox virus, has caused concerns in the biosecurity and biodefense communities that the technical capabilities achieved could advance the re-creation of smallpox virus by nefarious actors. The work is now published. While the authors went through due biosecurity diligence at their research institution and with the proper Canadian federal authorities, now that the experiments have been published, there is an opportunity to discuss the dual use risks and benefits of the research itself, as well as those associated with publication of such research—all of which challenge current policies. Here, an analytical framework is used to assess the risks and benefits of such dual use research, and relevant components of biosecurity policy and the biodefense enterprise (including the acquisition of medical countermeasures) in the United States are discussed. The authors emphasize the need to use such risk/benefit assessments at the onset of research and throughout its development, followed by an assessment for its responsible communication.