Most Pandemic Viruses Didn’t Evolve to Infect Us—We Just Made It Easy For Them

The world remains on alert as the Nipah virus, a zoonotic pathogen, draws increasing scrutiny from global health officials. A new study published in Cell challenges long-held assumptions about how viruses jump from animals to humans, suggesting the risk of spillover events may be significantly higher than previously understood.

Researchers at the University of California, San Diego, examined the genomes of influenza A, Ebola, Marburg, mpox, SARS-CoV, and SARS-CoV-2, analyzing viral evolution immediately before and during outbreaks. Contrary to the prevailing theory that viruses require specific adaptive mutations to infect humans, the study found no evidence of such pre-adaptation in the viruses examined. Instead, the research indicates that many viruses may already possess the capacity to infect humans, and spillover occurs primarily through increased human exposure to animal reservoirs.

“From an evolutionary perspective, we find no evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence,” said Joel Wertheim, professor of medicine at UC San Diego and senior author of the study. This finding bolsters the argument for a natural zoonotic origin for the virus that caused the COVID-19 pandemic, countering theories suggesting laboratory manipulation.

The researchers employed a phylogenetic framework to measure selection pressure on viral genomes at three stages: within animal hosts, immediately before spillover, and during the initial stages of human outbreaks. They found that natural selection intensity remained normal before the viruses jumped to humans, with significant changes emerging only after human-to-human transmission began. This suggests that the viruses weren’t “preparing” for the leap, but rather adapting *after* encountering human populations.

The study also included an analysis of viruses propagated in laboratory settings, allowing researchers to differentiate between evolutionary signals associated with natural transmission and those resulting from lab adaptation. While most recent pandemics appear to stem from natural spillover events, the team identified one notable exception: the reappearance of the H1N1 influenza A virus in 1977 after a 20-year absence.

The 1977 H1N1 outbreak has long been suspected of originating from a laboratory strain, potentially linked to a failed vaccine trial. Wertheim’s team found molecular evidence supporting this theory, noting that the virus exhibited selection pressures consistent with lab-adapted flu strains and live-attenuated vaccines. “Our results provide new molecular evidence supporting the long-suspected idea that the H1N1 pandemic was sparked by a laboratory strain,” Wertheim stated.

The findings underscore the critical role of habitat loss and human encroachment on wildlife areas in driving zoonotic spillover events. According to the World Wildlife Fund, zoonotic diseases are often the result of conditions created by human activity, including proximity to livestock, habitat degradation, and the trade of captive wildlife. A recent report by NPR highlighted a U.N. Prediction of a rise in zoonotic diseases due to increasing habitat loss. Time Magazine also reported on the importance of protecting wildlife habitats to prevent future pandemics.

The National Wildlife Federation’s recent report, “In Harm’s Way,” further emphasizes the vulnerability of both wildlife and humans to emerging infectious diseases. The researchers emphasize that understanding the origins of pandemics is crucial for future preparedness. While laboratory accidents represent a potential risk, the study suggests prioritizing efforts to reduce human exposure to animal viruses through surveillance, prevention, and habitat conservation.

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