There are precedents for laboratory incidents leading to isolated infections and transient transmission chains, including SARS-CoV (Parry, 2004). However, with the exception of Marburg virus (Ristanović et al., 2020), all documented laboratory escapes have been of readily identifiable viruses capable of human infection and associated with sustained work in high titer cultures (Geddes, 2006; Lim et al., 2004; Senio, 2003). The 1977 A/H1N1 influenza pandemic, that most likely originated from a large-scale vaccine challenge trial (Rozo and Gronvall, 2015), is the only documented example of a human epidemic or pandemic resulting from research activity. No epidemic has been caused by the escape of a novel virus and there is no data to suggest that the WIV—or any other laboratory—was working on SARS-CoV-2, or any virus close enough to be the progenitor, prior to the COVID-19 pandemic. Viral genomic sequencing without cell culture, which was routinely performed at the WIV, represents a negligible risk as viruses are inactivated during RNA extraction (Blow et al., 2004). No case of laboratory escape has been documented following the sequencing of viral samples.
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The WIV possesses an extensive catalogue of samples derived from bats (Latinne et al., 2020) and has reportedly successfully cultured three SARSr-CoVs from bats – WIV1, WIV16 and Rs4874 (Ge et al., 2013; Hu et al., 2017; Yang et al., 2015). Importantly, all three viruses are more closely related to SARS-CoV than to SARS-CoV-2 (Ge et al., 2013; Hu et al., 2017; Yang et al., 2015). In contrast, bat virus RaTG13 from the WIV has reportedly never been isolated nor cultured and only exists as a nucleotide sequence assembled from short sequencing reads (Cohen, 2020). The three cultured viruses were isolated from fecal samples through serial amplification in Vero E6 cells, a process that consistently results in the loss of the SARS-CoV-2 furin cleavage site (Davidson et al., 2020; Klimstra et al., 2020; Liu et al., 2020b; Ogando et al., 2020; Sasaki et al., 2021; Wong et al., 2020; Zhu et al., 2021b). It is therefore highly unlikely that these techniques would result in the isolation of a SARS-CoV-2 progenitor with an intact furin cleavage site. No published work indicates that other methods, including the generation of novel reverse genetics systems, were used at the WIV to propagate infectious SARSr-CoVs based on sequence data from bats. Gain-of-function research would be expected to utilize an established SARSr-CoV genomic backbone, or at a minimum a virus previously identified via sequencing. However, past experimental research using recombinant coronaviruses at the WIV has used a genetic backbone (WIV1) unrelated to SARS-CoV-2 (Hu et al., 2017) and SARSCoV-2 carries no evidence of genetic markers one might expect from laboratory experiments (Andersen et al., 2020). There is no rational experimental reason why a new genetic system would be developed using an unknown and unpublished virus, with no evidence nor mention of a SARS-CoV-2-like virus in any prior publication or study from the WIV (Ge et al., 2012; Hu et al., 2017; Menachery et al., 2015), no evidence that the WIV sequenced a virus that is closer to Journal Pre-proof 8 SARS-CoV-2 than RaTG13, and no reason to hide research on a SARS-CoV-2-like virus prior to the COVID-19 pandemic. Under any laboratory escape scenario SARS-CoV-2 would have to have been present in a laboratory prior to the pandemic, yet no evidence exists to support such a notion and no sequence has been identified that could have served as a precursor.
