In contrast, the reemergence of H1N1 influenza A virus in 1977 was preceded by a shift in selection intensity, consistent with the hypothesis of passage in a laboratory setting.

In 1977, the H1N1 influenza A virus reemerged in humans after going extinct 20 years prior. The re-emergent virus was closely related to a strain that had been circulating in the 1950s. Unlike other analysed zoonotic events, the 1977 H1N1 strain showed both unusually limited genetic divergence from 1950s viruses and a clear shift in selection consistent with viruses propagated in cell culture or laboratory animals. 

It has been proposed that H1N1 reemerged in 1977 without expected evolution because it was frozen in a laboratory before it was accidentally allowed to re-establish “wild” human-to-human transmission, perhaps involving a live-attenuated viral vaccine or a laboratory-adapted virus used as a challenge virus during an influenza vaccine trial.

Holistic phylogenetic analysis of selection regimes can be used to detect evolutionary signals of host switching or laboratory passage, providing insight into the circumstances of past and future viral emergence, the study suggested.

“Our goal is not just to understand the past, but to be better prepared for the future,” Wertheim said. “By clarifying how pandemics actually begin, we can focus attention where it belongs — on surveillance, prevention and reducing the opportunities for the constant barrage of viral spillover.”