Ancient Smallpox DNA Uncovers the Atlantic Journey of a Deadly Virus

It sounds like something out of a detective novel, but a group of scientists at Trinity College Dublin has actually pulled tiny fragments of a virus out of centuries‑old bones. The DNA they recovered belongs to variola virus – the pathogen that caused smallpox – and it comes from two individuals buried in northern Chile sometime between the late 1400s and early 1600s.

Until now, historians and epidemiologists have had to rely on written accounts and population estimates to piece together how smallpox swept across the Americas after Europeans set foot on the continent. Those records were useful, but they never gave a direct, genetic link between the Old‑World strains that devastated Indigenous peoples and the virus that eventually disappeared from the globe. This new study finally provides that missing connection.

“We’ve essentially found the molecular fingerprint of a European smallpox virus in the New World,” explains Dr. Shigeki Nakagome of Trinity’s School of Medicine. “It’s the first time we can say with confidence that the disease travelled across the Atlantic during the colonial era, and not just by inference.”

The recovered genomes belong to a branch of variola that no longer exists today. Phylogenetic analysis shows this extinct lineage sitting somewhere between medieval European variants and the later strains that plagued the world in the 18th and 19th centuries. In other words, the virus was caught in a kind of evolutionary pause as it rode the wave of colonisation.

Dr. Lara Cassidy, a geneticist on the project, adds, “We observed a long period of change up until the 16th century, then the rate of evolution slowed dramatically during the height of the epidemics in the 17th and 18th centuries.” This lull makes sense when you consider that the virus suddenly found an almost entirely naïve host population – millions of people with no immunity at all. The pathogen didn’t need to tweak itself much to spread.

But the story doesn’t end there. The researchers also noticed that once vaccination started to take hold in the 19th century, the virus’s evolutionary tempo picked up again. “It appears that the introduction of widespread immunity forced the virus to adapt once more,” says PhD student Bruno Romero González. “That’s a striking reminder of how our public‑health actions can reshape pathogen evolution.”

Beyond confirming the colonial origin of the disease, the work highlights a broader principle: when a pathogen lands in a massive, susceptible population, natural selection may favour preserving a successful genotype rather than driving further change. Conversely, when immunity rises – whether through infection or vaccination – the evolutionary pressure can shift, prompting new adaptations.

These findings echo today’s battles with influenza, COVID‑19, and monkeypox, where human movement, immunity gaps, and vaccination campaigns all play into how viruses mutate and spread. By digging into ancient DNA, scientists are gaining a clearer picture of the past, which in turn helps us anticipate future epidemiological twists.

Smallpox itself is a unique case in the annals of infectious disease. After killing an estimated 300–500 million people over centuries, a global eradication effort led by the World Health Organization succeeded in wiping it out, with the last natural case recorded in Somalia in 1977 and the disease officially declared eradicated in 1980. It remains the only human disease ever eliminated worldwide.

The Trinity study not only cements smallpox’s role in the tragic collapse of Indigenous populations after European contact, but also showcases the power of ancient pathogen genomics. As researchers continue to extract genetic clues from old remains, we can expect more surprises about how our history and microbes have been intertwined.