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Smallpox vaccination kits from the US civil war reveal historic virus

Traces of virus strains used to create smallpox vaccinations in the US civil war have been found

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Strains of viruses used for smallpox vaccines in the US during the civil war have been identified and their genomes reconstructed.

“The successful eradication of smallpox via vaccination shows the crucial importance that that practice has had within human history,” says Ana Duggan, who led a team of researchers to analyse smallpox vaccines while at McMaster University in Canada.

Smallpox, caused by the variola virus, killed approximately 30 per cent of the people it infected. It was officially eradicated in 1980 after concerted global vaccination efforts.


Early protective practices against smallpox involved infecting people with related viruses to induce a milder case of disease that would inoculate them against variola. This was usually done by applying some infected pus or scabs to a cut in the skin, a process known as variolation.

Duggan and her colleagues gathered genetic material from US civil war-era vaccination kits to identify the viruses used for smallpox vaccinations at the time. The team analysed five kits, part of a museum collection, that had been used by doctors in the greater Philadelphia area in the mid to late 19th century.

The kits contained lancets, tin boxes that held scab material and small glass plates for mixing fluid that had been collected from the blisters of infected people.

The team reconstructed the genomes of any viruses present by analysing the scabs and dried blister material from four kits. In one kit, which contained no direct evidence of biological material, the researchers soaked a tin box in a solution with enzymes that essentially hoover up the virus fragments without damaging the box.

All five of the viruses identified were strains of the vaccinia virus, which is only distantly related to variola, and is the cause of cowpox. None of the viral genetic material was intact, meaning that it wasn’t infectious. The team then pieced together the viral fragments like a jigsaw puzzle, with the aid of a computer algorithm as well as the genetic sequence of an intact vaccinia virus as a reference.

Previously identified variola strains from the 1940s to the 1970s were all remarkably similar, even though they were globally distributed, says Duggan. “That reduction in diversity in the 20th century was almost certainly in response to widespread vaccination,” she says.

The research illustrates the efforts that went into vaccination for almost 200 years before smallpox was eradicated, says Duggan.

Journal reference: Genome Biology, DOI: 10.1186/s13059-020-02079-z

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