Reading Room Production — page 228

From: "Sanders, Ashley (NIH/OD) [E]" < @nih.gov> To: "Miller, David A. (NK) (FBI)" < @fbi.gov> Cc: "Stemmy, Erik (NIH/NIAID) [E]" < @nih.gov>, "Shannon, Mike (NIH/OD) [E]" < @nih.gov> Subject: FW: Grant Questions - FBI Inquiry - 1-R01AI110964-01 - 2-R01AI110964-06 Date: Fri, 22 May 2020 15:17:48 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi David, In preparation for our call on Tuesday, Erik (cc'd) has provided responses to your initial questions below (also attached). Hope you have a great holiday weekend! Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov SF 424 AI110964-06 (received date 11/05/2018) Both SF 424s seem to be describing "gain of function" experiments. On page 192 of SF 424 AI110964-06 (received date 11/05/2018) under P3CO Research, it indicates they are conducting gain of function of SARSr-CoV. The funding pause on gain-of-function (GoF) experiments was in place from 2014-2017, and explicitly involved work reasonably anticipated to enhance the transmissibility or pathogenicity of influenza, MERS-CoV, or SARS-CoV. As such, that policy would not have applied to SARS-related coronaviruses (SARSr-CoV). The replacement policy, Potential Pandemic Pathogen Care and Oversight (P3CO), requires additional review and oversight of experiments that are anticipated to increase a potential pandemic pathogen's transmissibility or pathogenicity in humans. The viruses created under this award are chimeric bat viruses, which generally would not be anticipated to cause enhanced disease or transmission in people. When evaluating experiments for potential GoF or P3CO we determine the likelihood of altering one of these attributes compared to the wild-type or circulating viral strain. Were they also conducting Seemless Cloining and Assembly? From a review of their experimental details, it looks as if they were generating recombinant DNA of the viruses using WIV1 as the backbone but I could not determine if they were using Seemless Cloning techniques. I'm not aware of them using seamless cloning. Standard techniques for investigators in this field are to create cDNA molecular clones, which are then expressed in cull culture. I could not determine exactly where they were conducting these gain of function experiments. I know UNC-Chapel Hill has done these but within the document, I could not determine where this was occurring. Do you know where this was occurring? GoF experiments were not conducted as part of this award. While chimeric viruses were created via this award, they would not be considered GoF since the results did not confer attributes that were not already exhibited by the wild type versions of the viruses. For example, expressing the spike protein of SARS-CoV in the WIV-1 backbone did not increase the pathogenicity of WIV-1 beyond that of SARS-CoV. This award did not support work to manipulate CoV genomes or create chimeric viruses at Wuhan Institute of Virology; such work was performed at UNC-CH. It then appears that the recombinant DNA of the virus was then injected into humanized mice. However, again I couldn't determine where this occurred or was to occur. On page 187 of the same SF 424 under "Vertebrate Animals" it indicates that work with vertebrate animals will be conducted at Wuhan University at the School of Medicine and UNC - CH. Then under "Laboratory Mice" it states that lab mice will be sourced commercially by Wuhan Center for Animal Experiment at Wuhan University and that humanized mice will be bread at University of Wuhan and UNC - CH. Furthermore, the mice will be inoculated with the virus.