Recent Pandemic Viruses Jumped to Humans Without Prior Adaptation, UC San Diego Study Finds

“The 1977 influenza story is, in many ways, even more compelling than what we found for COVID-19,” Wertheim said. “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.”

Historical records and prior genetic analyses have suggested that the 1977 H1N1 virus appeared almost unchanged after a 20-year absence, a pattern difficult to reconcile with natural evolution. The new findings add another layer, showing that the virus also experienced selection similar to that seen in laboratory-adapted influenza strains and live-attenuated vaccines.

Beyond settling historical debates, the authors argue that their work has important implications for how scientists interpret future outbreaks. By establishing what “normal” zoonotic emergence looks like at the genomic level, the framework provides a benchmark for distinguishing natural spillovers from scenarios involving laboratory handling or prolonged artificial selection.

“This doesn’t mean lab accidents don’t happen,” Wertheim emphasized. “But it does mean that if a virus had been extensively passaged in a lab before an outbreak, we would expect to see it in the evolutionary record. In nearly all pandemics we’ve studied, that signal simply isn’t there.”

Looking ahead, the researchers see potential applications in outbreak forensics, viral surveillance and pandemic preparedness.

“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.”

Read the full study.

Additional co-authors on the study include: Jennifer L. Havens and Jonathan E. Pekar from UC San Diego; Sergei L. Kosakovsky Pond and Jordan D. Zehr from Temple University; Edyth Parker and Kristian G. Andersen from Scripps Research Institute; and, Michael Worobey from the University of Arizona.

The study was funded, in part, with federal funds from the National Institute of Allergy and Infectious Diseases National Institutes of Health, National Institutes of Health (NIH-NIAID) and National Science Foundation (NSF). Jennifer L. Havens acknowledges support from NIH (grant R01AI153044). Sergei L. Kosakovsky Pond and Jordan D. Zehr acknowledge support from NIH (AI183870, GM151683, GM144468) and the NSF (grant DBI/2419522). Jonathan E. Pekar acknowledges support from NIH-NIAID (T15LM011271) and the UC San Diego Merkin Fellowship. Michael Worobey acknowledges support from NIH-NIAID (contract no. 75N93021C00015). Edyth Parker and Kristian G. Andersen acknowledge support from the NIH (grant U01AI151812). Kristian G. Andersen also acknowledges support from the NIH (grant U19AI135995). Joel O. Wertheim acknowledges support from NIH-NIAID (R01AI135992).

Jonathan E. Pekar, Michael Worobey, Kristian G. Anderson, and Joel O. Wertheim have received consulting fees and/or provided compensated expert testimony on SARS-CoV-2 and the COVID-19 pandemic.