AAs the world anxiously wakes up its hopes that vaccines will stop the coronavirus pandemic, scientists are still learning from the first global scourge to be eradicated by vaccination.
Ancient DNA detectives analyzing Civil War era artifacts with 21st century sequencing techniques have recreated five viral vaccine genomes assembled to combat smallpox in the 1860s, finding that they were quite different from those used a century then to finally eliminate the disease.
Surprisingly, the scientists were able to retrieve viral molecules from scabs, blisters, pus, and other biological traces that remained in knife-shaped lancets, tin boxes, and glass slides hidden in leather vaccination kits discovered at a medical history museum in Philadelphia Doctors brought these personalized cases to inoculate smallpox soldiers and citizens, while North and South fought on nearby battlefields more than 150 years ago. The vaccines were not manufactured in laboratories or factories at the time, but were grown in a human chain of people exposed to mild but related cousins of smallpox.
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Their work reveals how the smallpox viruses used in those early vaccines slowly evolved within the largest family of orthopoxviruses, with a surprising variety of strains classified to fight a deadly virus. Although hesitant to link their findings to current vaccine efforts, the researchers said their work is a reminder that distantly related viruses may play a role in protection, depending on how fast the target pathogen evolves.
“One of the reasons you have lifelong immunity is because the virus changes so little over the course of its history,” said Hendrik Poinar, director of the McMaster University Ancient DNA Center and co-author of the article published Sunday in Genome Biology. “This work points out the importance of observing the diversity of these vaccine strains. We don’t know how many could provide cross protection against a wide range of viruses, such as the flu or coronavirus. “
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Knowing the genomic sequence of ancient smallpox vaccines can shed light on viruses used in the past to immunize against the disease, said Clarissa Damaso, associate professor of virology and molecular biology at the Federal University of Rio de Janeiro in Brazil. She was not involved in the investigation. “These samples are now the oldest smallpox vaccine samples ever sequenced. I think we need to dig deeper into this, trying to find samples of older vaccines and closer to the path taken by Edward Jenner until the 20th century. “
It is a discovery that almost did not happen. While visiting a new employee, Robert Hicks, then director of the Mütter Museum in Philadelphia, saw the Civil War vaccination kits in a drawer intended to hold phlebotomy instruments. Immediately recognizing them for what they were, he had the museum staff send the kits, which had been donated by doctors who used them in the 1860s, to the Centers for Disease Control and Prevention in case they carried smallpox.
Nine samples were analyzed to detect the presence of variola, which is the smallpox virus; vaccinia, the virus used in vaccination; and other viruses of the orthopoxvirus family. The vaccine, but not variola, was detected in scabs and returned to the museum. No results were obtained from the lancets or glass swabs, but Anna Dhody, acting co-director and curator at the Mütter Museum, suggested that kits be sent to McMaster for genomic sequencing designed to detect “old” DNA, a genetic material that is more than a Centennial Co-author of the current article, she had previously worked with Poinar at McMaster on pandemic cholera strains from 1849
Dhody, who has a background in forensic science, hoped that Poinar would find something in the kits, based on his knowledge of how medicine was practiced in the 19th century.
“The doctors did not wash anything before the discovery of the germ theory, “he said.” And I am sure they did not wash them before they donated them to us. “
To understand the source of the vaccines, McMaster scientists reconstructed and analyzed five different genomes. All were slightly different vaccine strains, and all were only distantly related to the virus that causes smallpox. Their slow evolution probably meant that they maintained enough similarity with variola to prevent smallpox. Decades later, “vaccine farms” produced animal vaccines, and production became an industrial process in the 1900s, but scientists did not believe that the smallpox or smallpox vaccine was present in the vaccines of 1800. Nor did they appear in the first smallpox vaccines, other investigation has shown.
The new document’s most important finding is that smallpox vaccines used in the US during the 19th century were significantly different from those used in the 20th century to finally eradicate smallpox in 1980, said José Esparza, a former virologist. affiliated with the World Health Organization and the Bill and Melinda Gates Foundation that studies and collects smallpox vaccine artifacts, including a 1902 vial. “The mystery of the origin and evolution of the smallpox vaccine remains to be solved.”
In the 1860s, when the Civil War was convulsing the United States, vaccination had changed little since a discovery by Edward Jenner in 1796. The British physician then observed that milkmaids rarely contracted smallpox, a virus so deadly that 30% of the patients died; the survivors were disfigured and sometimes blinded by the disease. He suspected that infection with cowpox, a milder disease in the same orthopoxvirus family than the variola that causes smallpox, protected milkmaids. To prove his theory, Jenner scratched milkmaid sores on the skin of an 8-year-old boy. years later, safely exposing him to smallpox and ushering in the era of vaccination.
If we shudder when experimenting with a child, we could also go back on the way vaccines were made and distributed the first time: Life-saving molecules were incubated in one person to pass on to the next by transferring scabs or pus from one person to another. the striped arms of the next. This “passage” often took advantage of enslaved women or Africans, sometimes on ocean voyages bringing vaccines between the New World and the Old. Three of the five genomes reconstructed from the Mütter kits come from women.
In the decade before Jenner tested her hypothesis on dairy and smallpox in England, the College of Physicians was founded in Philadelphia. In 1863, the university created the Mütter Museum, where those leather vaccine kits were later deposited. Philadelphia was also home to the second largest hospital in the Civil War, after Washington, DC
These tools from pioneering public health workers are among other meticulously preserved medical treasures at the museum. The slides and lancets showed no signs of biological residue, but the successful sampling left them intact, raising hopes of discovering more secrets in the ancient DNA of other historical artifacts.
“From the perspective of ancient DNA and from the perspective of medical history, nondestructive sampling of museum artifacts will be really important,” said Ana Duggan, a genomics researcher at the Public Health Agency of Canada, a research associate at the McMaster Old DNA Center and co-author of the new article. Today, “vaccination history is important to public health practice.”
How 23 initiatives global race to clinical trials of Covid-19 vaccine candidates, butwe long for a solution. Poinar is concerned that the public will wait for a vaccine sooner than it can safely be ready.
“There are still so many unknowns about SARS-Cov-2 that it will take longer than most people think or want to expect,” he said. “I think we expect science to advance rapidly, but part of the benefit we have in hindsight is that it takes a long time to get all the answers. If you want something effective and safe, you have to wait. “
Other people may not want the vaccine at all, as long as one is available, Poinar said. One of the lessons from the smallpox study is that the most successful and celebrated vaccination campaign in history fought against a fierce and visible enemy.
“One of the big differences is that when you have something like smallpox that devastates 30% of the population, it kills many young children, and it’s terribly disfiguring, you can imagine that the compliance rate is very high,” he said. “People wanted that [vaccine]. It was fear of smallpox, which I don’t think we’ll see now. [with Covid-19] because it is invisible. “
