Contrary to prevailing belief, an evolutionary analysis finds no evidence that most viruses with epidemic or pandemic potential that jumped from animals to people were shaped by selection in a lab or prolonged evolution in an intermediate host—challenging claims that SARS-CoV-2, the virus that causes COVID-19, was engineered in a lab. 

A University of California (UC) San Diego–led research team analyzed viral genomes to characterize natural selection under the hypothesis that zoonotic viruses (Ebola, Marburg, mpox, influenza A, and SARS-CoV-2) need to adapt before infecting people and achieving sustained human-to-human spread. They focused on the evolutionary period right before outbreaks, when viruses would be expected to leave detectable traces of any substantial adaptation.

The researchers validated their approach using known examples of artificially selected viruses grown in cell culture or lab animals, which showed clear and reproducible evolutionary footprints distinct from natural transmission.

The findings were published late last week in Cell.

The investigators uncovered no evidence of a change in selection intensity right before viral outbreaks in humans compared with typical selection within reservoir hosts. Rather, measurable changes in selection usually appeared only after the virus sustained transmission in people. 

The analysis did identify a change in selection on SARS-CoV—which causes SARS (severe acute respiratory syndrome)—in an intermediate host (palm civets) and, in the case of the 1977 reemergence of H1N1 influenza A virus after 20 years of extinction, they detected a preceding shift in selection intensity (accelerated genetic gain), consistent with passage in a lab. Passage is repeated transfer of a virus from one host environment, such as cell culture, egg, or animal, to another to grow, maintain, or study it.

“The 1977 influenza story is, in many ways, even more compelling than what we found for COVID-19,” senior author Joel Wertheim, PhD, of UC San Diego School of Medicine, said in a university news release. “Our results provide new molecular evidence supporting the long-suspected idea that the H1N1 pandemic was sparked by a laboratory strain—possibly in the context of a failed vaccine trial.”