Civil War-Era Vaccination Kits Yield New Clues About History of Smallpox Vaccine

Researchers were able to sequence the genomes of five smallpox vaccines used by doctors in the 1860s

A small leather vaccination kit, with small lancets and glass slides used for inoculating soldiers against smallpox during the Civil War
A vaccination kit from the American Civil War. Image courtesy of McMaster University

Robert Hicks, then the director of the Mütter Museum in Philadelphia, was giving a tour to a new employee when he peeked in a drawer and spotted them: five Civil War-era vaccination kits, complete with small knife-like lancets, glass slides and scabs from infected humans.

As Elizabeth Cooney reports for Stat News, Hicks immediately realized he had stumbled onto a historical medical treasure, and sent the kits away for further research. This month, a team of researchers at McMaster University in Canada published a completed study of the kits in Genome Biology, revealing new clues about the murky history of the only infectious disease to be successfully eradicated by humans: smallpox.

Smallpox, caused by the variola virus and one of the deadliest diseases in human history, plagued the world since as far back as the third century B.C., as Katherine J. Wu reported for Smithsonian magazine in 2018. The disease killed nearly a third of the people it infected and often left survivors with severe scarring and hearing or sight loss, according to a McMaster statement.

Over the course of the Civil War, both Confederate and Union troops died in the thousands from a number of diseases, including smallpox. At the time, doctors’ only line of defense against the brutal disease was inoculation, as Kat Eschner reported for Smithsonian magazine in 2017. Using kits like the ones Hicks found, doctors would use pus or other infected materials from people with diseases similar to smallpox and apply them to wounds to build up a person’s immunity to the virus.

As Francesca Giuliani-Hoffman reports for CNN, the McMaster scientists did not find any variola virus in the kits. Remarkably, however, they were able to carefully collect fragments of viral vaccine DNA that had been preserved in the scab materials, tools, tins and leather cases of the vaccination kits for more than 150 years, by soaking the items in chemical solutions. Led by researcher Ana Duggan, the team then reassembled the molecules “like a jigsaw puzzle” and sequenced the DNA of five separate viral vaccination strains, reports Donna Lu for New Scientist.

Most notably, the McMaster team discovered that the five vaccine strains used in the Civil War kits were very different from the vaccines used in the 1970s and ‘80s to eradicate the disease, reports Cooney.

“Our Civil War-era vaccines and the vaccines of the 20th century were all vaccinia virus, however (ours) are not identical to any of those later commercial vaccines,” Duggan tells CNN.

“…Medicine and vaccine development are very different today than they were in the 19th century—but it’s evidence that exploring multiple vaccine sources and strategies all have potential,” she continues.

“An overriding concern about vaccine design is how from an evolutionary standpoint—the vaccine strain must be to the one causing disease in order to prevent illness,” McMaster University explains in the statement. This study shows that Civil War-era doctors were using distantly related viruses to provide smallpox protection.

“This work points to the importance of looking at the diversity of these vaccine strains found out in the wild,” Hendrik Poinar, the director of the McMaster Ancient DNA Centre, adds in the statement. “We don’t know how many could provide cross protection from a wide range of viruses, such as flus or coronaviruses.”

The history of the smallpox vaccine can be traced back to English physician Edward Jenner, as Wu reports. In 1796, Jenner performed highly unethical experiments on an eight-year-old boy, James Phipps, after realizing that milkmaids who had suffered from cowpox, a milder relative of smallpox, were seemingly immune to smallpox.

For much of the following century, inoculation became common practice as a way to fend off the disease. Milder viruses related to smallpox were “grown” and then harvested from chains of infected humans, which often involved using women and enslaved Africans as human incubators for disease, according to Stat.

However, much about early smallpox vaccinations remain a mystery, as Wu reported in 2018. For instance, researchers are still uncertain if the modern smallpox vaccine, known as the vaccinia virus, descended from horses or cows.

Jose Esparza, a virologist specializing in historic smallpox vaccines who was not affiliated with the study, tells STAT that this study, while exciting, leaves many questions about the history of the smallpox vaccine still unanswered. “The mystery of the origin and evolution of the smallpox vaccine remains to be solved,” he says.

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