Reading Room Production — page 35

cation >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained ) te] > ne for _--_i > On page 119 of AI110964-01 under "C3d) Humanized mouse in vivo infection experiments" it states that humanized mouse in vivo experiments in humanized mice was occurring at the Wuhan Institute of Virology. I did not see the location where these gain of function experiments were being done but if the injections were occurring at WIV then was the recombinant DNA also generated at WIV? Was Seemless Cloning also being done? This is not GoF work. The humanized mouse experiments described in C3d refer to work with wild type viruses isolated from wild bats. Refer to the section stating: "We will passage isolated bat-CoVs in permissive cells twice..." This is a standard virological technique to create an inoculum to infect animals. In no portion of C3d do they describe any manipulation of isolated virus, therefore this does not describe any kind of gain-of-function studies, nor does it involve the creation of any recombinant DNA or viruses. Characterization of naturally occurring viruses was explicitly excluded from the GoF policy. Further, the USG P3CO Policy Guidance states that "Wild-type pathogens that are circulating in or have been recovered from nature are not enhanced PPPs, regardless of their pandemic potential." RPPR (AI110964-05) Finally, in the RPPR (6/1/2017-5/31/2018) on page 28 under "In Vivo Infection of Human ACE2 Expressing Mice with SARSr-Cov S Protein variants", it appears to be showing the results from their gain of function experiments as described in the SF 424. This is more of less the same as the question above, but do you know where this occurred? These are not the results of GoF experiments. The figure you reference (Fig 35) shows weight loss and lung viral titers of chimeric viruses with bat CoV (wild type WIV-1, SHC014, WIV16, and 4231) spike proteins expressed on the WIV-1 backbone. Weight loss and viral titers were comparable across all chimeras when compared to the wild type (Fig 35a, red series; Fig 35b small box pattern). There are no statistical differences reported, so the chimeric viruses have not gained any function/attribute they did not already exhibit. From: Sanders, Ashley (NIH/OD) [E] @nih.gov> Sent: Thursday, May 21, 2020 3:04 PM To: Stemmy, Erik (NIH/NIAID) [E] @nih.gov>; Linde, Emily (NIH/NIAID) [E] @mail.nih.gov> Cc: Shannon, Mike (NIH/OD) [E] @nih.gov> Subject: RE: Grant Questions - FBI Inquiry - 1-R01AI110964-01 - 2-R01AI110964-06 Hi Erik, Thank you for providing this information. We would like to set up a call with the agent as they may need additional context or have other questions. Would you be available next Tuesday around 11:30AM? I'll set up a conference line for us and send an invite. If that time doesn't work for you, please let me know alternative times you have available. Thank you, Ashley From: Stemmy, Erik (NIH/NIAID) [E] @nih.gov> Sent: Thursday, May 21, 2020 11:22 AM To: Linde, Emily (NIH/NIAID) [E] @mail.nih.gov>; Sanders, Ashley (NIH/OD) [E] @nih.gov> Cc: Shannon, Mike (NIH/OD) [E] @nih.gov> Subject: RE: Grant Questions - FBI Inquiry - 1-R01AI110964-01 - 2-R01AI110964-06 Hi Ashley, I would be happy to answer questions related to this award. Would it be best if I just addressed the comments at the end of this email thread? I'll say generally that NIAID has an extensive review process for P3CO (and formerly for GoF) and that all of this work was formally evaluated by the respective committees and determined not to be gain-of-function, nor