grant questions - fbi inquiry - 1-r01ai110964-01 - 2-r01ai110964-06

140 messages over 4 months, 2020-05-13 – 2020-09-14.

2020-05-13 11:59 Ashley Sanders open PDF p.10

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: vt tes en at ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> 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 Date: Thu, 21 May 2020 11:22:11 -0400 Importance: Normal 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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-13 11:59 Ashley Sanders open PDF p.13

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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 ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? LiF
2020-05-13 11:59 Ashley Sanders open PDF p.19

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: vt tes en at ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNCCH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating C3b "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. On page 119 of AI110964-01 under "C3d) Humanized mouse in vivo infection experiments" it states
2020-05-13 11:59 Ashley Sanders open PDF p.29

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley y't tes ing rt (Db >E2 Expressing Mice with dn experiments as described this occurred? Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? We might also want to include OGC / Anna Jacobs in our .0964-06 1d just sent the following response to 0 AM
2020-05-13 11:59 Ashley Sanders open PDF p.36

2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have rt tes en at ing rt (Db ACE2 Expressing Mice with ction experiments as described Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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 this occurred? in the SF 424. This is more of less the same as the question above, but do you know where this occurred? I could ask Melanie to « this Sunday; I'd be .0964-06
2020-05-13 11:59 Ashley Sanders open PDF p.48

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. y't tes ing rt (Db -E2 Expressing Mice with dn experiments as described this occurred? Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? 0) (e)" > .0964-06 ed t's going on in this space
2020-05-13 11:59 Ashley Sanders open PDF p.56

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. yt tes ing rt (Db >E2 Expressing Mice with dn experiments as described this occurred? Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? wh.iov.cn> 20 6:30 AM EDT
2020-05-13 11:59 Ashley Sanders open PDF p.233

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: vt tes en at ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> 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 Date: Thu, 21 May 2020 11:22:11 -0400 Importance: Normal 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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-13 11:59 Ashley Sanders open PDF p.236

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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 ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? LiF
2020-05-13 11:59 Ashley Sanders open PDF p.242

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: vt tes en at ing ot (Db >E2 Expressing Mice with on experiments as described this occurred? 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNCCH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating C3b "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. On page 119 of AI110964-01 under "C3d) Humanized mouse in vivo infection experiments" it states
2020-05-13 11:59 Ashley Sanders open PDF p.252

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley y't tes ing rt (Db >E2 Expressing Mice with dn experiments as described this occurred? Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? We might also want to include OGC / Anna Jacobs in our .0964-06 1d just sent the following response to 0 AM
2020-05-13 11:59 Ashley Sanders open PDF p.259

2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have rt tes en at ing rt (Db ACE2 Expressing Mice with ction experiments as described Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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 this occurred? in the SF 424. This is more of less the same as the question above, but do you know where this occurred? I could ask Melanie to « this Sunday; I'd be .0964-06
2020-05-13 11:59 Ashley Sanders open PDF p.271

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. y't tes ing rt (Db -E2 Expressing Mice with dn experiments as described this occurred? Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? 0) (e)" > .0964-06 ed t's going on in this space
2020-05-13 11:59 Ashley Sanders open PDF p.279

Good afternoon Emily, OMA/DPI received questions related to an FBI inquiry for the following NIAID grants: 1R01AI110964-01 through 2R01AI110964-06. The agent is requesting clarification on the details of the study, where certain aspects were performed, and whether seamless cloning techniques were used. I note you were the last official to sign off on 4/27/20. Would you be able to provide a response to the below-captured questions and/or be available for a joint call with our office and the agent? If not, who would be the best SME on this matter? I'm sure you understand, since this is a sensitive matter, we need to maintain confidentiality and limit the touch-points within NIH. I'm happy to discuss further if you have any questions. yt tes ing rt (Db >E2 Expressing Mice with dn experiments as described this occurred? Thank you, Ashley Ashley M. Sanders, MPS Senior Program Investigations Officer NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: @nih.gov FBI Questions: 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. 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 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? 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. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. 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? 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? wh.iov.cn> 20 6:30 AM EDT
2020-05-20 13:00 Ashley Sanders open PDF p.10

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.12

let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have ite dn't cates hen it at Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.19

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.29

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.36

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.48

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.56

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.233

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.235

let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have ite dn't cates hen it at Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.242

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.252

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.259

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.271

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-20 13:00 Ashley Sanders open PDF p.279

Good afternoon, We are following up on a time-sensitive request for information from the FBI. Please let us know if you are able to accommodate their request or if you can recommend a POC to address the concerns. Thank you, Ashley
2020-05-21 06:17 Emily Linde open PDF p.9

Hi Ashley, let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.12

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.18

Hi Ashley, let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.29

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.36

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.56

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.232

Hi Ashley, let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.235

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.241

Hi Ashley, let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.252

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.259

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 06:17 Emily Linde open PDF p.279

Hi Ashley, The Program Official for this grant, Dr. Stemmy, who is copied on this email, would be the most appropriate POC for these questions. Regards, Emily
2020-05-21 11:22 Erik Stemmy open PDF p.9

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.18

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.28

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov AID) [--] > let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have
2020-05-21 11:22 Erik Stemmy open PDF p.35

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 erminated) for evidence of AID) [--] > let us know if you are able to subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.47

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.55

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 AID) [--] > let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.232

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.241

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.251

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov AID) [--] > let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have
2020-05-21 11:22 Erik Stemmy open PDF p.258

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 erminated) for evidence of AID) [--] > let us know if you are able to subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.270

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 Phone: Email: @nih.gov
2020-05-21 11:22 Erik Stemmy open PDF p.278

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 subject to P3CO oversight. We also continually monitored the progress (until the award was terminated) for evidence of unexpected increases in viral replication. Erik Erik J. Stemmy, Ph.D. Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/HHS 5601 Fishers Lane, Room 8E18 Bethesda, MD 20892-9825 AID) [--] > let us know if you are able to 2rtain aspects were fficial to sign off on 4/27/20. you understand, since this is a sensitive I'm happy to discuss further if you have Phone: Email: @nih.gov
2020-05-21 15:04 Ashley Sanders open PDF p.9

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
2020-05-21 15:04 Ashley Sanders open PDF p.18

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
2020-05-21 15:04 Ashley Sanders open PDF p.28

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
2020-05-21 15:04 Ashley Sanders open PDF p.35

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
2020-05-21 15:04 Ashley Sanders open PDF p.47

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
2020-05-21 15:04 Ashley Sanders open PDF p.55

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
2020-05-21 15:04 Ashley Sanders open PDF p.232

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
2020-05-21 15:04 Ashley Sanders open PDF p.241

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
2020-05-21 15:04 Ashley Sanders open PDF p.251

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
2020-05-21 15:04 Ashley Sanders open PDF p.258

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
2020-05-21 15:04 Ashley Sanders open PDF p.270

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
2020-05-21 15:04 Ashley Sanders open PDF p.278

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
2020-05-21 17:50 Erik Stemmy open PDF p.26

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 know UNC-Chapel Hill you know where this was he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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) >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained te] > ne for _--_i > 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.
2020-05-21 17:50 Erik Stemmy open PDF p.33

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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. ated aring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he iuldn't jicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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
2020-05-21 17:50 Erik Stemmy open PDF p.45

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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? he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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? ters of 35a, red ained ) te] > ne for a > 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.
2020-05-21 17:50 Erik Stemmy open PDF p.53

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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 t are circulating in or >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained ) te] > ne for a > 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.
2020-05-21 17:50 Erik Stemmy open PDF p.249

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 know UNC-Chapel Hill you know where this was he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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) >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained te] > ne for _--_i > 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.
2020-05-21 17:50 Erik Stemmy open PDF p.256

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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. ated aring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he iuldn't jicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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
2020-05-21 17:50 Erik Stemmy open PDF p.268

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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? he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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? ters of 35a, red ained ) te] > ne for a > 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.
2020-05-21 17:50 Erik Stemmy open PDF p.276

Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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 t are circulating in or >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained ) te] > ne for a > 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.
2020-05-22 11:05 Ashley Sanders open PDF p.15

Sanders, Ashley (NIH/OD) [E] @nih.gov) has sent you a prot Read the message Learn about messages protected by Office 365 Message Encryption. Privacy Statement Email encryption powered by Office 365. Learn More Microsoft Corporation, One Microsoft Way, Redmond, WA 98052 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> To: "Sanders, Ashley (NIH/OD) [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 Date: Thu, 21 May 2020 17:49:51 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 manipulate CoV genomes or create iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. On page 119 of AI110964-01 under "C3d) Humanized mouse in vivo infection experiments" it states that humanized
2020-05-22 11:05 Ashley Sanders open PDF p.238

Sanders, Ashley (NIH/OD) [E] @nih.gov) has sent you a prot Read the message Learn about messages protected by Office 365 Message Encryption. Privacy Statement Email encryption powered by Office 365. Learn More Microsoft Corporation, One Microsoft Way, Redmond, WA 98052 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> To: "Sanders, Ashley (NIH/OD) [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 Date: Thu, 21 May 2020 17:49:51 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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 manipulate CoV genomes or create iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? ters of 35a, red ained 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. On page 119 of AI110964-01 under "C3d) Humanized mouse in vivo infection experiments" it states that humanized
2020-05-22 15:17 Ashley Sanders open PDF p.2

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? he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? ters of 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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 'ig 35a, red rt gained backbone. Weight loss and viral titers were comparable across all chimeras when compared to the wild type (Fig 35a, red
2020-05-22 15:17 Ashley Sanders open PDF p.5

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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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. 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> To: "Sanders, Ashley (NIH/OD) [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 Date: Thu, 21 May 2020 17:49:51 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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
2020-05-22 15:17 Ashley Sanders open PDF p.225

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? he iuldn't jJicates Then ent at mice these molecular clones are used to grow id UNC-CH performed studies with molecular e "mation but tion describes animal work at work. I believe UNC mean to say C3a and C3b) although it does not use that cation >E2 Expressing Mice with on experiments as described this occurred? ters of 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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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 'ig 35a, red rt gained backbone. Weight loss and viral titers were comparable across all chimeras when compared to the wild type (Fig 35a, red
2020-05-22 15:17 Ashley Sanders open PDF p.228

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. Recombinant viral cDNA is not directly injected into humanized mice. Rather, these molecular clones are used to grow virus in culture to create an inoculum used in infectivity studies. Both WIV and UNC-CH performed studies with molecular clones, which included infecting mice with the resulting recombinant viruses. Under "UNC Facilities where selected agents to be used" it continues with all mouse studies at UNC-CH will be performed...." However, on page 200 of the same SF 424 there is a letter from UNC - CH stating "The work to be performed by UNC-CH does not include animal and/or human research subjects." I know that was a lot of information but where exactly was the experimentation of injecting the humanized mice with the recombinant DNA occurring? I believe this to be a typographical error on the part of UNC's business office. The application describes animal work at UNC. Budget justifications and the consortium agreement also include references to this work. I believe UNC mean to say that the work "... does not include human research subjects." SF 424 AI110964-01 (received date 06/05/2013) In this SF 424 Aim 3 seems indicative of gain of function experimentation (C3a and C3b) although it does not use that exact term. The receipt date of this application was June of 2013, and the term "gain-of-function" was not widely used before the USG funding pause was announced in 2014. C3a and C3b describe work using pseudovirus assays, which would not have been considered GoF as they do not involve creating full replicating viruses. 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. 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> To: "Sanders, Ashley (NIH/OD) [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 Date: Thu, 21 May 2020 17:49:51 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. 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
2020-09-09 15:15 Ashley Sanders open PDF p.25

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? ID) [E] i > 164-06 (received date ated 2ring for investigators in this field are to create cDNA 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:15 Ashley Sanders open PDF p.40

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov .0964-06 ed t's going on in this space We might also want to include OGC / Anna Jacobs in our
2020-09-09 15:15 Ashley Sanders open PDF p.44

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. ID) [E] i > 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:15 Ashley Sanders open PDF p.52

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: De) a 164-06 (received date ated 2ring 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:15 Ashley Sanders open PDF p.248

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? ID) [E] i > 164-06 (received date ated 2ring for investigators in this field are to create cDNA 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:15 Ashley Sanders open PDF p.263

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov .0964-06 ed t's going on in this space We might also want to include OGC / Anna Jacobs in our
2020-09-09 15:15 Ashley Sanders open PDF p.267

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. ID) [E] i > 164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:15 Ashley Sanders open PDF p.275

Good afternoon Emily, I'm following-up on this inquiry - originally the questions circled around the scientific terms of the grant and Erik Stemmy provided the context to the FBI. In a recent discussion with HHS OIG and the FBI, they noted they received information that the below-grant with Ecohealth Alliance was "suspended" or "terminated". I've reviewed QVR and do not see an indication of that action other than the attached "Closeout of Award" email stating the end of the grant was 4/24/20 with a request for the FFR and FRPPR. Was this just a typical end of term closeout, or was it terminated early? If terminated/suspended, the OIG has the following questions: De) a 164-06 (received date ated 2ring 1. What information did NIH/NIAID receive, and from whom, that noted a concern for continuing to fund this research? 2. What was the reasoning for NIAID ending the grant and/or collaboration with Ecohealth Alliance? 3. What was communicated to the PI (Dr. Daszak) and/or Ecohealth? Please let me know if you're able to provide this information. Thank you, Ashley Ashley M. Sanders, MPS Supervisor, DPI Program Investigations NIH, OMA, Division Program Integrity 6011 Executive Blvd. Rockville, Maryland 20852 Office: Cell: @nih.gov
2020-09-09 15:26 Emily Linde open PDF p.25

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.32

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.40

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.44

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.52

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.248

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.255

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.263

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.267

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-09 15:26 Emily Linde open PDF p.275

Hi Ashley, Questions for that nature on this award should be referred to Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-10 10:40 Ashley Sanders open PDF p.32

Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 10:40 Ashley Sanders open PDF p.43

/0)) cE) as /0)) (] as Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 10:40 Ashley Sanders open PDF p.52

Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 10:40 Ashley Sanders open PDF p.255

Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 10:40 Ashley Sanders open PDF p.266

/0)) cE) as /0)) (] as Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 10:40 Ashley Sanders open PDF p.275

Hi Emily, These questions are specific to whether or not this particular NIAID grant was terminated early or ended as per a usual course of action. I'm not clear as to why I would need to go to the Deputy Director of NIH for OER for a response to a question on decisions and grant determinations made by NIAID. OMA properly and routinely seeks and receives information from IC's on grants and grant activity in support of audits and investigations, in accordance with Manual Chapter 1754 and 1752, as we are responsible to fully coordinate responses to OIG/FBI/DOJ etc. to support ongoing investigations. I must ensure our response is from the most relevant and accurate source of information, and answered in a timely manner. Is there a reason these inquiries are being directed outside of the IC? Thanks for your help, Ashley
2020-09-10 11:40 Emily Linde open PDF p.24

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-10 11:40 Emily Linde open PDF p.43

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-10 11:40 Emily Linde open PDF p.51

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily /0)) cE as /0)) (] as 1/0) cE] as
2020-09-10 11:40 Emily Linde open PDF p.247

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-10 11:40 Emily Linde open PDF p.266

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily
2020-09-10 11:40 Emily Linde open PDF p.274

Hi Ashley, For this award the most relevant and accurate source of information is Dr. Mike Lauer, Deputy Director for Extramural Research. Thanks, Emily /0)) cE as /0)) (] as 1/0) cE] as
2020-09-10 11:44 Emily Linde open PDF p.24

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.31

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.43

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.51

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.247

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.254

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.266

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 11:44 Emily Linde open PDF p.274

Good morning, I wanted to alert you to this request. I referred them to Mike as we have discussed and just sent the following response to their latest inquiry and will let you know if I hear more. Thanks, Emily
2020-09-10 12:43 Michelle G Bulls open PDF p.31

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.43

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.51

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.254

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.266

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.274

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.24

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-10 12:43 Michelle G Bulls open PDF p.247

Hi Mike, See way down below where OMA asks for information for the OIG and FBI regarding Eco Health Alliance. Emily referred them back to you, based on the nature of their questions. This is a sticky one--and from the beginning, NIAID were told to refer these detailed questions to you given the situation. Is it okay for us to provide her with a response to send that is accurate so that OMA does not have to translate? Or would you like for her to just respond and without context, that will be tricky for OMA and will cause more questions. Let me know... Michelle
2020-09-11 04:36 Michael Lauer open PDF p.31

Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-11 04:36 Michael Lauer open PDF p.254

Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-11 04:37 Michael Lauer open PDF p.42

Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people. 00) (e)" i > .0964-06 (E] > 1d just sent the following response to /0) ct is /o) ck is
2020-09-11 04:37 Michael Lauer open PDF p.50

We might also want to include OGC / Anna Jacobs in our 50) (e)" > .0964-06 (E] > 1d just sent the following response to /o) ck is Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-11 04:37 Michael Lauer open PDF p.265

Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people. 00) (e)" i > .0964-06 (E] > 1d just sent the following response to /0) ct is /o) ck is
2020-09-11 04:37 Michael Lauer open PDF p.273

We might also want to include OGC / Anna Jacobs in our 50) (e)" > .0964-06 (E] > 1d just sent the following response to /o) ck is Thanks Michelle - I agree with your plan we should handle this. We might also want to include OGC / Anna Jacobs in our conversations with OMA. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-11 09:23 Michelle G Bulls open PDF p.42

Mike, Just to provide you with an update on this one. Mike Shannon went to NIAIDs Deputy Director last evening to note that Emily was being "non-responsive" so the issue would be escalated. Emily said that as soon as the Deputy Director figured out which grant was involved, they knew that Emily had acted appropriately, and that OMA should be trusting her professional judgement. The Deputy Director is meeting with Mike Shannon today to discuss. You were not included in the emails from Mike Shannon at any point, not even as a FYI. Really happy that NIAID leadership supported Emily--huge in this case. Just want you know what's going on in this space and the fact that Mike is meeting w/the Deputy Director today. Thanks, Michelle
2020-09-11 09:23 Michelle G Bulls open PDF p.50

Mike, Just to provide you with an update on this one. Mike Shannon went to NIAIDs Deputy Director last evening to note that Emily was being "non-responsive" so the issue would be escalated. Emily said that as soon as the Deputy Director figured out which grant was involved, they knew that Emily had acted appropriately, and that OMA should be trusting her professional judgement. The Deputy Director is meeting with Mike Shannon today to discuss. You were not included in the emails from Mike Shannon at any point, not even as a FYI. Really happy that NIAID leadership supported Emily--huge in this case. Just want you know what's going on in this space and the fact that Mike is meeting w/the Deputy Director today. Thanks, Michelle
2020-09-11 09:23 Michelle G Bulls open PDF p.265

Mike, Just to provide you with an update on this one. Mike Shannon went to NIAIDs Deputy Director last evening to note that Emily was being "non-responsive" so the issue would be escalated. Emily said that as soon as the Deputy Director figured out which grant was involved, they knew that Emily had acted appropriately, and that OMA should be trusting her professional judgement. The Deputy Director is meeting with Mike Shannon today to discuss. You were not included in the emails from Mike Shannon at any point, not even as a FYI. Really happy that NIAID leadership supported Emily--huge in this case. Just want you know what's going on in this space and the fact that Mike is meeting w/the Deputy Director today. Thanks, Michelle
2020-09-11 09:23 Michelle G Bulls open PDF p.273

Mike, Just to provide you with an update on this one. Mike Shannon went to NIAIDs Deputy Director last evening to note that Emily was being "non-responsive" so the issue would be escalated. Emily said that as soon as the Deputy Director figured out which grant was involved, they knew that Emily had acted appropriately, and that OMA should be trusting her professional judgement. The Deputy Director is meeting with Mike Shannon today to discuss. You were not included in the emails from Mike Shannon at any point, not even as a FYI. Really happy that NIAID leadership supported Emily--huge in this case. Just want you know what's going on in this space and the fact that Mike is meeting w/the Deputy Director today. Thanks, Michelle
2020-09-13 13:23 Michael Lauer open PDF p.42

Thanks Michelle for the update and good to hear that NIAID backed up Emily. I'll be talking with Ashley Sanders (OMA) from 8:30 AM to 9:00 to tell her the story behind the case. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-13 13:23 Michael Lauer open PDF p.265

Thanks Michelle for the update and good to hear that NIAID backed up Emily. I'll be talking with Ashley Sanders (OMA) from 8:30 AM to 9:00 to tell her the story behind the case. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-13 13:24 Michael Lauer open PDF p.50

Thanks Michelle for the update and good to hear that NIAID backed up Emily. I'll be talking with Ashley Sanders (OMA) from 8:30 AM to 9:00 to tell her the story behind the case. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-13 13:24 Michael Lauer open PDF p.273

Thanks Michelle for the update and good to hear that NIAID backed up Emily. I'll be talking with Ashley Sanders (OMA) from 8:30 AM to 9:00 to tell her the story behind the case. Best, Mike Note: This conversation is restricted, so you might not be able to cut or copy from it. See the information above the To line for more details. Also, while the conversation is restricted, the conversation owner can send the message to other people.
2020-09-14 16:42 Michelle G Bulls open PDF p.50

Perfect! Thanks so much, Mike.
2020-09-14 16:42 Michelle G Bulls open PDF p.273

Perfect! Thanks so much, Mike.