Tag Archives: smallpox

What Benjamin Franklin’s battles with a deadly virus that swept Colonial America can teach us about our own struggles with anti-vaxxers

Benjamin Franklin. Creidt: Pixabay.

Exactly 300 years ago, in 1721, Benjamin Franklin and his fellow American colonists faced a deadly smallpox outbreak. Their varying responses constitute an eerily prescient object lesson for today’s world, similarly devastated by a virus and divided over vaccination three centuries later.

As a microbiologist and a Franklin scholar, we see some parallels between then and now that could help governments, journalists and the rest of us cope with the coronavirus pandemic and future threats.

Smallpox strikes Boston

Smallpox was nothing new in 1721. Known to have affected people for at least 3,000 years, it ran rampant in Boston, eventually striking more than half the city’s population. The virus killed about 1 in 13 residents – but the death toll was probably more, since the lack of sophisticated epidemiology made it impossible to identify the cause of all deaths.

What was new, at least to Boston, was a simple procedure that could protect people from the disease. It was known as “variolation” or “inoculation,” and involved deliberately exposing someone to the smallpox “matter” from a victim’s scabs or pus, injecting the material into the skin using a needle. This approach typically caused a mild disease and induced a state of “immunity” against smallpox.

Even today, the exact mechanism is poorly understood and not much research on variolation has been done. Inoculation through the skin seems to activate an immune response that leads to milder symptoms and less transmission, possibly because of the route of infection and the lower dose. Since it relies on activating the immune response with live smallpox variola virus, inoculation is different from the modern vaccination that eradicated smallpox using the much less harmful but related vaccinia virus.

The inoculation treatment, which originated in Asia and Africa, came to be known in Boston thanks to a man named Onesimus. By 1721, Onesimus was enslaved, owned by the most influential man in all of Boston, the Rev. Cotton Mather.

Cotton Mather heard about variolation from an enslaved West African man in his household named Onesimus. Credit: Wikimedia Commons.

Known primarily as a Congregational minister, Mather was also a scientist with a special interest in biology. He paid attention when Onesimus told him “he had undergone an operation, which had given him something of the smallpox and would forever preserve him from it; adding that it was often used” in West Africa, where he was from.

Inspired by this information from Onesimus, Mather teamed up with a Boston physician, Zabdiel Boylston, to conduct a scientific study of inoculation’s effectiveness worthy of 21st-century praise. They found that of the approximately 300 people Boylston had inoculated, 2% had died, compared with almost 15% of those who contracted smallpox from nature.

The findings seemed clear: Inoculation could help in the fight against smallpox. Science won out in this clergyman’s mind. But others were not convinced.

Stirring up controversy

A local newspaper editor named James Franklin had his own affliction – namely an insatiable hunger for controversy. Franklin, who was no fan of Mather, set about attacking inoculation in his newspaper, The New-England Courant.

frontpage of a 1721 newspaper
From its first edition, The New-England Courant covered inoculation. Wikimedia Commons

One article from August 1721 tried to guilt readers into resisting inoculation. If someone gets inoculated and then spreads the disease to someone else, who in turn dies of it, the article asked, “at whose hands shall their Blood be required?” The same article went on to say that “Epidemeal Distempers” such as smallpox come “as Judgments from an angry and displeased God.”

In contrast to Mather and Boylston’s research, the Courant’s articles were designed not to discover, but to sow doubt and distrust. The argument that inoculation might help to spread the disease posits something that was theoretically possible – at least if simple precautions were not taken – but it seems beside the point. If inoculation worked, wouldn’t it be worth this small risk, especially since widespread inoculations would dramatically decrease the likelihood that one person would infect another?

Franklin, the Courant’s editor, had a kid brother apprenticed to him at the time – a teenager by the name of Benjamin.

Historians don’t know which side the younger Franklin took in 1721 – or whether he took a side at all – but his subsequent approach to inoculation years later has lessons for the world’s current encounter with a deadly virus and a divided response to a vaccine.

Independent thought

You might expect that James’ little brother would have been inclined to oppose inoculation as well. After all, thinking like family members and others you identify with is a common human tendency.

That he was capable of overcoming this inclination shows Benjamin Franklin’s capacity for independent thought, an asset that would serve him well throughout his life as a writer, scientist and statesman. While sticking with social expectations confers certain advantages in certain settings, being able to shake off these norms when they are dangerous is also valuable. We believe the most successful people are the ones who, like Franklin, have the intellectual flexibility to choose between adherence and independence.

Truth, not victory

What happened next shows that Franklin, unlike his brother – and plenty of pundits and politicians in the 21st century – was more interested in discovering the truth than in proving he was right.

Perhaps the inoculation controversy of 1721 had helped him to understand an unfortunate phenomenon that continues to plague the U.S. in 2021: When people take sides, progress suffers. Tribes, whether long-standing or newly formed around an issue, can devote their energies to demonizing the other side and rallying their own. Instead of attacking the problem, they attack each other.

Franklin, in fact, became convinced that inoculation was a sound approach to preventing smallpox. Years later he intended to have his son Francis inoculated after recovering from a case of diarrhea. But before inoculation took place, the 4-year-old boy contracted smallpox and died in 1736. Citing a rumor that Francis had died because of inoculation and noting that such a rumor might deter parents from exposing their children to this procedure, Franklin made a point of setting the record straight, explaining that the child had “receiv’d the Distemper in the common Way of Infection.”

Writing his autobiography in 1771, Franklin reflected on the tragedy and used it to advocate for inoculation. He explained that he “regretted bitterly and still regret” not inoculating the boy, adding, “This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.”

A scientific perspective

Upper body of man with smallpox. Credit: National Museum of Health and Medicine.

A final lesson from 1721 has to do with the importance of a truly scientific perspective, one that embraces science, facts and objectivity.

Inoculation was a relatively new procedure for Bostonians in 1721, and this lifesaving method was not without deadly risks. To address this paradox, several physicians meticulously collected data and compared the number of those who died because of natural smallpox with deaths after smallpox inoculation. Boylston essentially carried out what today’s researchers would call a clinical study on the efficacy of inoculation. Knowing he needed to demonstrate the usefulness of inoculation in a diverse population, he reported in a short book how he inoculated nearly 300 individuals and carefully noted their symptoms and conditions over days and weeks.

The recent emergency-use authorization of mRNA-based and viral-vector vaccines for COVID-19 has produced a vast array of hoaxes, false claims and conspiracy theories, especially in various social media. Like 18th-century inoculations, these vaccines represent new scientific approaches to vaccination, but ones that are based on decades of scientific research and clinical studies.

We suspect that if he were alive today, Benjamin Franklin would want his example to guide modern scientists, politicians, journalists and everyone else making personal health decisions. Like Mather and Boylston, Franklin was a scientist with a respect for evidence and ultimately for truth.

When it comes to a deadly virus and a divided response to a preventive treatment, Franklin was clear what he would do. It doesn’t take a visionary like Franklin to accept the evidence of medical science today.

Mark Canada, Executive Vice Chancellor for Academic Affairs, Indiana University Kokomo and Christian Chauret, Dean of School of Sciences, Professor of Microbiology, Indiana University Kokomo

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Second smallpox drug approved by the FDA

The US Food and Drug Administration (FDA) has approved Tembexa (brincidofovir) to treat smallpox. This is the second approved smallpox drug; the first, TPOXX (tecovirimat), was approved in 2018.

TPOXX’s effectiveness against smallpox was established by studies conducted in animals infected with viruses that are closely related to the virus that causes smallpox, and was based on measuring survival at the end of the studies. More animals treated with TPOXX lived compared to the animals treated with placebo. TPOXX was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.

Smallpox, an acute contagious disease caused by the variola virus, was one of the most devastating diseases known to humanity and caused millions of deaths before it was eradicated. It is believed to have existed for at least 3,000 years.  

Credit: Science Museum.

The smallpox vaccine, created by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that a similar inoculation could be used to prevent smallpox in other people.

The World Health Organization (WHO) launched an intensified plan to eradicate smallpox in 1967. Widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. The WHO declared smallpox eradicated in 1980, but since then many nations have expressed concerns that the variola virus, which causes smallpox, could be used as a bioweapon.

Similar to TPOXX, the FDA also approved Tembexa under its Animal Rule. Human safety data on Tembexa was based on clinical trials involving primarily patients who were treated with the drug after they received hematopoietic stem cell transplants.

In the animal study for Tembexa (brincidofovir), the efficacy was defined by measuring the animals’ survival by the end of the studies. Results demonstrated that more animals with smallpox who were treated with brincidofovir survived compared with animals who were treated with the placebo.

A child mummy from 17th century Lithuania bears the first evidence of variola, the virus that causes smallpox. Credit: Kiril Cachovski/Lithuanian Mummy Project.

Mummified child found in 17th century Lithuanian crypt might crack the mystery of smallpox virus

A child mummy from 17th century Lithuania bears the first evidence of variola, the virus that causes smallpox. Credit: Kiril Cachovski/Lithuanian Mummy Project.

A child mummy from 17th century Lithuania bears the first evidence of variola, the virus that causes smallpox. Credit: Kiril Cachovski/Lithuanian Mummy Project.

The earliest infected person with smallpox we know of is a child who lived in Lithuania around 1665. The mummified remains were discovered in a crypt under a church and inside the tissue, researchers found smallpox DNA which they sequenced. The findings suggest that smallpox originated far earlier than previously believed.

A sneaky virus

Thanks to global vaccination efforts, smallpox was completely eradicated in the 1970s. Before the advent of vaccines, however, the virus killed millions of people. When European settlers first arrived in North and South America, they simply plowed through the native populations aided by the new disease they brought with them.

Today, the virus can only be found in safely stored containers in labs around the world. Yet, despite the fact that smallpox has been eradicated, we still don’t know the whole picture, like where it came from.

Most viral infections originate in animals. For instance, HIV/AIDS originated from chimps and other primates and is thought to have first infected humans at least a century ago. The origin of Ebola and Zika can also be traced to primates and monkeys. Malaria comes from mosquitoes while swine-flu is self-explanatory. Smallpox, however, seems to be a ‘human thing’. It infects no other animal and if it did appear first in an animal (other types of pox do, like camelpox) we don’t know who that animal is.

“Scientists don’t yet fully comprehend where smallpox came from and when it jumped into humans,” says evolutionary geneticist Hendrik Poinar, senior author of the study, director of the McMaster Ancient DNA Centre and a researcher with Michael G. DeGroote Institute of Infectious Disease Research. “This research raises some interesting possibilities about our perception and age of the disease.”

Poinar and colleagues were on the lookout for ancient pathogens that lurk across the millions of Medieval tombs. They weren’t specifically looking for smallpox, but were very happy they found it in such old remains. It’s the earliest evidence of smallpox anyone has found.

After they sequenced the virus’ DNA and determined its age, they compared the genome to those of more recent strains collected in the 1940s to 1970s. The phylogenetic analysis can trace evolutionary mutations back in time to the earliest common ancestor, essentially offering an estimate of when the virus first surfaced.

This photograph of a smallpox victim appeared in the Baltimore Health News in 1939 as a warning to people who had not been vaccinated. Credit: Chapin Library of Rare Books, Williams College.

This photograph of a smallpox victim appeared in the Baltimore Health News in 1939 as a warning to people who had not been vaccinated. Credit: Chapin Library of Rare Books, Williams College.

Previously, scientists used to believe smallpox first appeared thousands of years ago. Some have pointed to other mummies from ancient Egypt which bear pockmark scars. It wasn’t ever very clear because those marks could have been made by measles or chicken pox.

The new study establishes a much finer timeline of the virus’ origin. The analysis suggests the common ancestor to all strains of smallpox first appeared sometime between 1588 and 1645, as reported in Current Biology. It doesn’t seem like a coincidence that this period was marked by many smallpox outbreaks around Europe.

“This study sets the clock of smallpox evolution to a much more recent time-scale” said evolutionary biologist Eddie Holmes, a professor at the University of Sydney, Australia. “Although it is still unclear what animal is the true reservoir of smallpox virus and when the virus first jumped into humans.”

It’s likely that other strains of the smallpox-causing virus were live and kicking earlier than the one that infected the 17th-century child. To wind the clock even further back, scientists need to investigate more tombs — the older the better.

This is no mere scientific inquiry. Though smallpox is officially eradicated, it’s possible it can resurface. If it does, we need to be prepared to throw everything we have at it. Knowing how the virus, and others like it, first appeared will be extremely important.

“While smallpox was eradicated in human populations, we can’t become lazy or apathetic about its evolution — and possible reemergence — until we fully understand its origins,” says Ana Duggan, a post doctoral fellow in the McMaster Ancient DNA Centre.”