Civil War era smallpox vaccines were genetically similar, recent study finds


The researchers analyzed the genomes of virus fragments found in smallpox vaccination kits used during the Civil War.  The kits are located in the Mütter Museum of the College of Physicians of Philadelphia.
Enlarge / / The researchers analyzed the genomes of virus fragments found in smallpox vaccination kits used during the Civil War. The kits are located in the Mütter Museum of the College of Physicians of Philadelphia.

JD Howell / McMaster University

Scientists around the world are currently working feverishly to develop an effective vaccine against COVID-19 to curb the global pandemic that has claimed nearly 600,000 human lives worldwide (and counting). Meanwhile, a collaboration between scientists at McMaster University, the University of Sydney and historians at the Mütter Museum in Philadelphia, is looking for possible clues in the past. They have analyzed the genome of smallpox virus fragments used in vaccines during the Civil War, according to a new article published in the journal Genome Biology.

“Understanding the history, evolution, and the ways these viruses can function as vaccines is of great importance in contemporary times,” said evolutionary geneticist Hendrik Poinar, director of the McMaster Ancient DNA Center, on the fundamentals of the research. “This work points to the importance of looking at the diversity of these vaccine strains discovered in nature. We do not know how many could provide cross protection against a wide range of viruses, such as influenza or coronaviruses.”

The World Health Organization declared that smallpox was a disease eradicated in 1979, and many people do not remember how devastating it could be. It started with a high fever and severe vomiting, followed by a skin rash. The victim would then develop sores, which eventually fell off and fell, scarring the skin. About three out of ten of those infected died, and survivors generally had scars for life, sometimes even blinded or permanently disabled.

The Chinese had been inoculating people against smallpox since the 1500s. European physicians in the early 18th century relied on variolation (the use of smallpox to induce immunity) to control the spread of smallpox, in which scrapings Smallpox pustules were scratched on a person’s arm or inhaled through the nose. Although those who received the treatment developed common smallpox symptoms such as fever and rash, the number of deaths was significantly lower.

This undated E. Board painting shows British physician Edward Jenner administering his first vaccine against eight-year-old James Phipps on May 14, 1796.
Enlarge / / This undated E. Board painting shows British physician Edward Jenner administering his first vaccine against eight-year-old James Phipps on May 14, 1796.

Bettmann / Getty Images

In the late 1700s, a handful of doctors in England and Germany noted that people infected with the mildest smallpox appeared to be immune to smallpox, and there were a couple of tests of early vaccination in humans. For example, in 1774, a farmer in Dorset, England, named Benjamin Jesty, successfully vaccinated his wife and children with smallpox. But it was the English physician Edward Jenner who is credited with introducing the smallpox vaccine into conventional medical practice.

Jenner had also realized that smallpox-infected milkmaids were largely immune to smallpox. Then, on May 14, 1796, he scraped the pus from the smallpox blisters from the hands of a milkmaid named Sarah Nelmes. (The skin of the cow, Blossom, given to her by the Nelmes smallpox is displayed in the library of the St. George’s School of Medicine.) She then inoculated a boy named James Phipps (her gardener’s son) with the scrapings, which resulted in a mild fever, but no full-blown illness. Subsequently, she exposed the boy to the variola virus several times, however, the young Phipps never developed smallpox. Jenner tested his method on 23 additional subjects (including his one-year-old son Robert), before publishing his findings. By 1840, the British government had banned variolation and supplied free smallpox vaccines to the general population.

During the United States Civil War (1861-1865), smallpox turned out to be a scourge that devastated both Union and Confederate troops. Along with quarantines and the burning of infected clothing and blankets, soldiers on both sides of the conflict had to be vaccinated against smallpox to control the spread of the disease. In reality, the requirement was often ignored in the rush to recruit new soldiers, although it still helped curb the deadly outbreaks and led to widespread smallpox vaccination of American civilians after the war ended. The scabs were typically harvested from smallpox scabs from infected children, soldiers, even the cows themselves, and shipped to army surgeons. (In one notable case, a scab was collected from a young, ill-reputed woman also infected with syphilis, thereby spreading the STD to soldiers vaccinated with that material.)

According to the authors of this latest study, Philadelphia was the second largest hospital city serving the influx of sick and wounded soldiers. The Mütter Museum, a true mecca for the curious morbid, was founded in 1863 to house the various medical devices and specimens for research and teaching, including smallpox vaccination kits and related instruments. The latter included folding lancets, small glass plates used to mix fluids, and tin boxes to hold crust material. The museum supplied five vaccination kits dating from the mid to late 19th century for the study. Four kits were of the leather roll-up variety; the fifth contained a tool known as an “automatic vaccinator”.

Co-author Ana Duggan, a former postdoc in McMaster's Department of Anthropology, analyzes a viral sample in the laboratory.
Enlarge / / Co-author Ana Duggan, a former postdoc in McMaster’s Department of Anthropology, analyzes a viral sample in the laboratory.

JD Howell, McMaster University

The scientists collected nine samples of virus fragments from the five kits and then reconstructed and analyzed their genomes. (They were even able to recover viral fragments by taking nondestructive samples from the artifacts that showed no obvious signs of biological residue.) The objective was to describe the evolutionary relationships of smallpox viruses used in Civil War era vaccines within the smallpox virus class. like an everything.

The results showed that a particular strain of the virus (VACV) was circulating before the 20th century and was closely related to a commercially produced vaccination strain manufactured in Philadelphia in 1902. In other words, there was very little diversity among the strains commonly used by Doctors in the area during the Civil War, despite the fact that there was no standardization of vaccines for more than a century.

Furthermore, the vaccinia strains used for vaccination were then distantly related to the virus that causes smallpox. The authors state that their slow mutation rate is the reason they offer protection against smallpox. That provides a useful clue as to how closely a vaccine, evolutionarily speaking, must be close to the virus that causes disease in order to be effective in preventing disease.

The researchers also noted similarities between the construction of the kits, which were custom-made (bespoke) and not available in catalogs at the time, and their contents. “There was a common wisdom about how vaccination was practiced in this particular era,” they concluded. “In fact, the similarity in the virus strains, not only of these five Civil War era kits, but of the 1902 strain … suggests that there may be a common source of material in the Philadelphia area.” .

The authors believe that their work points the way to a new non-destructive approach to studying medical history. “Vaccination is a wonderful process with a rich medical history that we must celebrate,” said co-author Ana Duggan, now at the Canadian Public Health Agency. “Medical museums are incredible repositories of our past and our collective history. The new tools we develop in this work allow us to begin investigating how medical sources, procedures, and techniques have changed over time.”

DOI: Genome Biology, 2020. 10.1186 / s13059-020-02079-z (About DOIs).