But the deadliest blow came from something entirely different: smallpox and other infectious diseases that decimated Indigenous populations. “Smallpox was one of the deadliest infectious diseases in human history,” said Trinity College geneticist and study co-author Shigeki Nakagome. In the Americas, smallpox and other viral diseases are believed to have killed 90 percent of Indigenous people. This suggests the virus had reached an evolutionary optimum and could spread without needing to adapt further, since those populations had no immunity. Three years later, the World Health Organization declared smallpox the first, and so far only, infectious disease ever eradicated worldwide.