Most Pandemic Viruses Jump to Humans Without Prior Adaptation, UC San Diego Study Finds

A latest University of California San Diego study published in Cell challenges the long-held assumption that animal viruses must first adapt before sparking human epidemics, and pandemics. Researchers found that most zoonotic viruses – those that spread from animals to humans, including SARS-CoV-2 – do not show evidence of special evolutionary adaptation before infecting people.

The study, led by Joel Wertheim, PhD, professor of medicine in the Division of Infectious Diseases and Global Public Health at UC San Diego School of Medicine, analyzed viral genomes from outbreaks caused by influenza A virus, Ebola virus, Marburg virus, mpox virus, SARS-CoV, and SARS-CoV-2. The team focused on the evolutionary period immediately before human outbreaks to identify any detectable imprint of pre-spillover adaptation.

No Evidence of ‘Pre-adaptation’ in Most Cases

Across these diverse viruses, investigators found a consistent pattern: selection pressures before zoonotic emergence were similar to those acting during routine circulation in animal reservoirs. This suggests that these viruses didn’t require rare, finely tuned adaptations in animals to infect humans. Instead, measurable changes in selection typically appeared only after sustained transmission began in people.

“From a broad epidemiological standpoint, our findings challenge the idea that pandemic viruses are evolutionarily special before they reach humans,” Wertheim said. “Rather than requiring rare, finely tuned adaptations in animals, many viruses may already possess the basic capacity to infect and transmit between humans. What matters most is human exposure to a diverse array of animal viruses.”

Sophisticated Analysis Validated with Known Viruses

The research team employed a sophisticated phylogenetic framework to measure changes in the intensity of natural selection across entire viral genomes. By comparing mutation rates, they determined whether natural selection was intensified, relaxed, or unchanged during key evolutionary transitions. The approach was validated using known examples of viruses propagated in cell culture or laboratory animals, which produced clear evolutionary signatures.

1977 H1N1 Flu: A Notable Exception

The study did identify one historical outlier: the reemergence of H1N1 influenza A virus in 1977. Unlike other zoonotic events analyzed, the 1977 H1N1 strain showed limited genetic divergence from 1950s viruses and a shift in selection consistent with viruses propagated in a laboratory.

“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 the 1977 H1N1 virus appeared almost unchanged after a 20-year absence, a pattern difficult to reconcile with natural evolution. The new findings add to this evidence, showing the virus also experienced selection similar to that seen in laboratory-adapted influenza strains.

Implications for Future Outbreak Investigations

The authors argue their work has important implications for interpreting 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 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.”

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.”

Key Takeaways

• Most zoonotic viruses do not show evidence of pre-adaptation before spilling over into humans.
• SARS-CoV-2 shows no genetic signal of lab adaptation, supporting a natural zoonotic origin.
• The 1977 H1N1 influenza pandemic likely originated from a laboratory strain.
• This research provides a framework for distinguishing natural spillovers from lab-related outbreaks.

Source: University of California – San Diego. Recent Pandemic Viruses Jumped to Humans Without Prior Adaptation, UC San Diego Study Finds. Published March 9, 2026.

Journal Reference: Havens, J. L., et al. (2026). Dynamics of natural selection preceding human viral epidemics and pandemics. Cell. DOI: 10.1016/j.cell.2026.02.006.