Comment by Arturo Casadevall

The genomic sequence of SARS-CoV-2 offers a means of testing the laboratory-origin hypothesis. Namely, if the virus had a laboratory origin, we would expect the viral genome to carry signatures resulting from the propagation of the biological isolate in the lab. [...] Over the past 3 years, hundreds of research groups around the world have cultured human isolates of SARS-CoV-2 in cell lines. This collective experience has revealed a highly reproducible consequence of viral propagation in culture: the deletion of the portion of the spike gene encoding the furin cleavage site. If SARS-CoV-2 had a laboratory origin, it would have been amplified in a laboratory through a process of serial passage typically needed to recover high-titer stocks from environmental samples. In this process, the deletion of the furin cleavage site is expected, offering a signature of laboratory handling. However, early isolates of SARS-CoV-2 show the furin cleavage site to be intact, arguing against introduction into humans after laboratory cell culture.