The History of Smallpox

Smallpox was a disease caused by the variola virus. About 7 to 19 days after infection, a fever would set in, followed by a bumpy rash breaking out across the face, arms, and legs. A person remained contagious until every last scab fell off. It spread mostly through prolonged face-to-face contact.

Even within the same disease, there were two distinct strains. If you caught the harsher one, variola major, as the U.S. Centers for Disease Control and Prevention puts it, 3 out of 10 people died. The milder variola minor was far less lethal. This difference will come up again later in the story of the very last patient.

The World Health Organization estimates that roughly 300 million people died from this disease in the 20th century alone. That figure is an estimate, not a census tally, and some sources place it even higher. Either way, it is a number larger than the casualties of any war in the 20th century.

Yet this disease also had several traits that worked in favor of eradication. First, the virus lived only in humans. That meant it had no animal reservoir, like cattle or mice, where it could hide and emerge again years later. Second, everyone who caught it developed a visible rash. Third, no one carried and spread the virus without showing symptoms. Once you found a patient, you could trace the entire chain of transmission.

It was a disease with nowhere to hide. This is why only two diseases in history have been declared eradicated from Earth, and only one of them is a human disease. The other is rinderpest, an illness that afflicted cattle—a livestock disease, not a human one. Polio and Guinea worm disease have entered the final stretch, but they are not finished yet.

These traits, of course, were merely necessary conditions. Having favorable conditions does not mean the work does itself. Even after people recognized those traits, it took a very long time before the disease was finally gone.

This disease has a very long history. There are reports that traces suspected to be smallpox were identified on the head of Egyptian Pharaoh Ramses V's mummy, and in written records, 4th-century Chinese accounts are among the earliest. In Europe, estimates suggest that in the 18th century alone, about 400,000 people died each year, and one-third of the survivors lost their eyesight.

Even before vaccines arrived, people did not just sit idly by. There was a method called variolation. It involved gently introducing pus or scabs from a smallpox patient into the skin of a healthy person. The person would usually suffer only a mild case and never catch it again. It is said to have been practiced long ago in Africa, India, China, and the Ottoman Empire. Exactly when and where it began remains unconfirmed in historical records even today.

In 1721 in London, Lady Mary Wortley Montagu had her four-year-old daughter inoculated this way. She had survived smallpox herself with facial scars and had lost her younger brother to the disease. That same year across the Atlantic, smallpox also struck Boston. The minister Cotton Mather had heard from Onesimus, an enslaved man in his household, that such inoculations were practiced in Africa, and recommended inoculation based on that. The physician Zabdiel Boylston put it into practice.

The results were recorded in numbers. Among those Boylston inoculated, 6 out of the 242 people died. For those who caught smallpox without inoculation, the death rate was about 14%. Looking only at the numbers, the answer seemed obvious, but it was not. The backlash was so fierce that Boylston's family was even threatened.

Those who opposed it had a point, too. Variolation was a method of putting actual smallpox into the body. Inoculated individuals sometimes died, and above all, while they were sick, they could transmit real smallpox to their neighbors. Protecting your own child meant putting the neighbor's child in danger. This was not a matter of superstition; it was a structural problem.

On May 14, 1796, English physician Edward Jenner extracted fluid from a blister on the hand of Sarah Nelmes. What Nelmes had was not smallpox, but cowpox caught from a cow. Jenner made two scratches on the arm of eight-year-old James Phipps and introduced the fluid. The boy became mildly ill and recovered. In July of that year, Jenner inoculated the same boy, this time with real smallpox pus. Nothing happened.

In 1798, Jenner published these results in a book. Alongside Phipps's case, he included the stories of thirteen people who had contracted cowpox. The word vacca in the Latin variolae vaccinae used in the book's title means 'cow.' This is how the word vaccine came from the cow.

The anecdote that Jenner got the idea from a countryside belief—that milkmaids never caught smallpox—is often cited. However, the story itself is not confirmed by historical records. All that is documented is that Nelmes, who was infected with cowpox, visited Jenner, and Jenner used that pus.

Safety was not the only reason this method replaced variolation. Cowpox does not transmit smallpox between humans. The dilemma from the previous chapter simply disappeared. Within 20 years of publication, the book was translated into Portuguese, French, Dutch, Italian, and Japanese. In 1807, Bavaria made vaccination mandatory for new military recruits.

It took much longer for this method to reach Korea. While Jeong Yak-yong, Yi Gyu-gyeong, and Choe Han-gi had earlier introduced it in writing, actual procedures began in 1879. Ji Seok-yeong studied vaccination for two months at Jesaeng Clinic in Busan. In December of that year, on his way to Deoksan-myeon in Chungju, where his in-laws lived, he vaccinated around 40 people, starting with his two-year-old brother-in-law. The following year, he accompanied the Susinsa diplomatic mission to Japan, learned how to produce vaccine lymph, and returned with 50 bottles of it to open a vaccination clinic in Seoul. In 1900, the number of people vaccinated that year was recorded at 46,027.

Even well over a century and a half after Jenner's book was published, smallpox remained scattered across the world. While it had virtually disappeared from Europe and North America, people were still dying from it every year in Africa, South Asia, and Brazil. It was not because humanity didn't know how to stop it. The vaccine was already there.

In May 1958, at the World Health Assembly held in Minneapolis in the United States, Soviet Deputy Minister of Health Viktor Zhdanov presented a lengthy report. It was a proposal to wipe the disease off the face of the Earth entirely. The Soviet Union pledged 25 million doses of freeze-dried vaccine. His logic was fascinating: as long as even a single country harbors the disease, even disease-free countries must keep vaccinating and keep quarantining. That ongoing cost, he argued, was far greater than the cost of eradication.

This calculus still holds true today. Vaccination doesn't just protect the person who receives it; it also lowers the odds that those around them will get sick. The benefits spill over to others, while the cost falls on the individual getting the shot. The exact same dynamic plays out between nations. If your own country is free of the disease, your incentive to pay for prevention in other countries weakens. When everyone thinks that way, the last endemic pockets remain. And as long as those pockets remain, everyone has to keep spending money.

In 1959, the Assembly passed a unanimous resolution. The assessment was that smallpox could be eradicated if 80% of the population in endemic areas was vaccinated within 4 to 5 years. Yet the resolution included no reporting system, no protocol for containing outbreaks, and no target deadline. The World Health Organization's resources were heavily tilted toward malaria, and the smallpox budget remained negligible for years.

The game changed in May 1966. A proposal by France to start smaller and a compromise plan from the United States were voted down one after the other, and the full budget of $2,415,000 for smallpox was put to a vote. The result was passage by just 2 votes. It remains the narrowest budget vote in the history of the World Health Organization. That sum was meant to run programs across 41 countries, amounting to less than $60,000 a year per country. Even so, it accounted for 4.7% of the organization's total budget, roughly ten times the previous year's allocation.

The opposition wasn't simply being stingy. Everyone had been watching the malaria eradication campaign struggle for years. At the time, worrying that launching yet another massive initiative and failing could undermine the organization's credibility was an entirely reasonable concern.

The Intensified Eradication Programme began in January 1967. At the time, smallpox was endemic across 33 countries, home to a combined population of 1.2 billion. In that year alone, an estimated 10 million to 15 million people contracted the disease, and roughly 2 million died.

The starting conditions were grim. That year, only 31% of vaccine batches met the standards tested by the World Health Organization. It was estimated that no more than 15% of the vaccines actually used in endemic countries met quality standards. The campaign essentially started with most of its weapons failing to perform as needed.

What made the program work was not a brand-new discovery, but using three existing tools properly. The first was a heat-stable vaccine. Liquid vaccines quickly lose their potency in hot climates. Between the late 1940s and early 1950s, Leslie Collier at the Lister Institute refined a technique of adding peptone to the vaccine and freeze-drying it. The resulting powdered vaccine held up against the heat. Suddenly, vaccines could be transported without refrigeration. Without it, running campaigns in tropical regions would have been far more difficult.

The second was the needle. In 1965, Benjamin Rubin ground down the eye of a sewing machine needle to create a two-pronged, fork-like tip. A single drop of vaccine was held naturally between the prongs, eliminating the need to measure doses, and all a worker had to do was press it against the skin several times. It took just one day to learn. This meant that even non-medical personnel could become vaccinators.

The third was the biggest turning point. Around 1966, William Foege, working in Nigeria, ran into a severe vaccine shortage. He simply lacked the supplies to follow the official guideline of vaccinating 80% of the population. So he flipped the order of operations. He first identified where cases were emerging, and vaccinated only those who had likely come into contact with the patients. Instead of trying to douse the whole area, he soaked the perimeter where the flames were about to spread.

This method came to be called surveillance-containment, or ring vaccination. The results were remarkable. Transmission was broken with far fewer vaccinations. Diseases do not spread randomly; they travel along lines of human contact. Once you block the pathways along those lines, there is no need to cover everyone. Foege himself modestly declined the credit, insisting he was not the one who came up with it. Records from the World Health Organization also note that an older method used in the UK followed the same basic structure.

For surveillance and containment to work, you first have to know where the patients are. But as a disease recedes, finding those patients gets much harder. The rarer the remaining cases become, the greater the effort required to track down a single person.

India faced this challenge head-on. In 1974, it reported 188,003 cases—the country's largest epidemic of the 20th century. While a massive outbreak was indeed underway, stepped-up surveillance also meant that previously hidden hotspots were finally brought to light. That sudden spike in numbers was the beginning of the end. Starting late that year, search teams went door-to-door across India's 100 million households for six days every month. A force of 33,000 health workers and more than 100,000 field workers scoured 575,721 villages and 2,641 cities and towns.

Finding cases also came with cash rewards. Bounties were offered to anyone who reported a patient, as well as to the health workers who confirmed the case. The reward started small, but steadily rose to as much as $1,000 by 1978. Whenever search teams entered a village, they would ask the locals if they knew how much the bounty was. Their answers were a clever way to gauge just how recently news of the campaign had reached that community.

In October 1975, three-year-old Rahima Banu was discovered in the village of Kuralia on Bhola Island, Bangladesh. She was the last person in the world to contract naturally occurring variola major. An eight-year-old girl named Bilkisunnessa reported her case and reportedly received a reward of 250 taka.

The very last naturally occurring case came two years later. In October 1977, Ali Maow Maalin, a hospital cook in Merca, Somalia, contracted the virus. He had caught variola minor, the milder form of smallpox, and he recovered. Even though he had crossed paths with many contacts, not a single person caught it from him. He later served as a local coordinator in the campaign to eradicate polio.

What came next was the truly difficult part. Proving the presence of a disease takes just one patient, but proving its absence is an entirely different story. That is why countries continued rigorous surveillance for more than two years after their last recorded patient, followed by visits from international commissions to verify the results. Inspectors checked whether reporting systems actually worked, whether locals could recognize the disease, and what turned up when suspected chickenpox specimens were tested. They even surveyed populations for facial pockmarks. Yet scar surveys had one major blind spot: scars only remain on those who survive. A scar survey could prove the disease had once been there, but it could never reveal how many had died. In the end, 21 commissions traveled across 61 countries.

The last naturally occurring case was reported in 1977. Yet the final person to die of smallpox came the following year. Not from nature, but from a laboratory.

Three laboratory-associated infections have been recorded in the United Kingdom. In 1949, a new staff member handled infected equipment on the very day of being vaccinated, effectively inoculating themselves. There were no secondary infections. The second case, in 1973, took a different turn. A technician visiting a smallpox laboratory became infected and showed only very mild symptoms, but due to a delayed diagnosis, stayed in a general hospital ward. During that time, two visitors coming to see the patient in the adjacent bed contracted the virus, and both died.

The third incident occurred in 1978 at the University of Birmingham Medical School. Medical photographer Janet Parker worked on the floor right above the smallpox laboratory. How she became infected was never definitively determined. The Global Commission's final report simply recorded it as an 'unknown route.' Parker died on September 11 of that year. She transmitted the virus to only one person, who experienced very mild symptoms. Henry Bedson, the microbiologist who directed the laboratory, took his own life before Parker passed away.

These three incidents tell us something crucial: that a single office one floor above could threaten the achievement of the entire world. No matter how confined a virus may be, as long as that confined space is connected to the outside world, danger remains. Following the tragedy, the United Kingdom overhauled its regulations for handling dangerous pathogens.

That same year, the World Health Organization set up the 'Smallpox Rumour Register' in Geneva. Whenever rumors of smallpox surfaced anywhere, this desk registered every single one and investigated it in person. It was the painstaking work of checking again and again, even while knowing that nothing would be found.

In December 1979, the Global Commission for the Certification of Smallpox Eradication held its final meeting in Geneva and reached its conclusion: eradication had been achieved worldwide, and there was no evidence that smallpox would return as an epidemic. Then, on May 8, 1980, the 33rd World Health Assembly officially proclaimed this by resolution: "The world and all its peoples have won freedom from smallpox."

There is another, less-noticed passage in the commission's report. Noting 45 cases of monkeypox identified up to that point in West and Central Africa, it recommended continuing surveillance of the disease. At the time, the commission judged that the virus had little potential to spread as an epidemic. Based on the data available then, it was a reasonable conclusion.

Just because eradication was declared does not mean the virus completely vanished from the Earth. Research stocks were kept. Today, they remain in two places: the US Centers for Disease Control and Prevention and Russia's VECTOR Institute. The World Health Organization inspects both facilities every 2 years.

A decision to destroy them was already made once. In 1996, the World Health Assembly set a deadline for destruction. However, a 1999 resolution authorized retaining the stocks, citing the need for further research on antiviral drugs, improved vaccines, and the virus's genetic structure. The deadline was extended again in 2002, and once more in 2007. The 2024 Assembly decided to keep the stocks in place and continue inspections. No new destruction deadline was set.

Both sides have valid reasons. Those in favor of retention argue that live virus samples are necessary to validate diagnostic tools and treatments. Those advocating destruction argue that as long as the samples exist, the risk of accidents and leaks persists. The three laboratory accidents discussed in the previous chapter serve as the basis for that concern.

Yet the landscape of the debate itself has fundamentally shifted. In 2023, a World Health Organization advisory committee pointed out that technology capable of synthesizing the virus from scratch using only its genetic sequence has become an actual reality. Destroying test tubes is entirely different from erasing information. Pointing to waning population immunity and a growing immunocompromised population, the same committee noted that preparedness against smallpox is currently insufficient.

This is why vaccines are still maintained today. The World Health Organization directly stores 2.7 million doses in Switzerland and periodically checks their potency. In addition, France, Germany, Japan, and the United States have separately pledged about 28 million doses.

Those preparations were actually put to use. Starting in May 2022, mpox broke out across multiple countries. The World Health Organization declared a Public Health Emergency of International Concern on July 23 of that year and lifted it on May 10 of the following year. Over 92,000 confirmed cases were reported across 116 countries. The monkeypox virus belongs to the same genus as the smallpox virus. As a result, vaccines and therapeutics prepared for smallpox were deployed during this outbreak, and the World Health Organization even reissued guidance on how to administer vaccines using a bifurcated needle.

One detail must be interpreted with caution. It is difficult to conclude flatly that mpox spread simply because smallpox vaccination stopped. Waning immunity due to the cessation of vaccination is only one of the factors cited in the records; the advisory committee also highlights the rise of immunosuppressive conditions, mutations in the virus itself, and limited access to diagnostics and vaccines. Just because two trends are observed alongside each other does not mean one can be asserted as the cause of the other.

There is no need to try to predict the future. Instead, guided by the rules this story has revealed, let’s look at where we should watch to spot the shifting ground first.

First is the disposal of the remaining virus. Deadlines were set and postponed three times, and now there is no deadline at all. You just need to watch whether the debate shifts back toward setting another deadline, or moves toward rules governing genetic data. Destroying a test tube and destroying a blueprint are two entirely different things.

Second is the final stretch. Polio and Guinea worm disease are in that stretch right now. What smallpox proved was that as cases drop, the cost of finding a single patient actually rises. Rather than looking at the number of remaining patients, it is more accurate to track how much is being spent to find the very last one.

Third is the budget when nothing happens. The most vulnerable point in this story was not technology, but money. The budget to keep the program running barely passed by 2 votes, and even now, long after the disease has vanished, maintaining vaccine stockpiles, inspections, and rumor registries costs money. The longer the quiet years drag on, the harder it becomes to defend these expenses. Successful disease prevention makes it look as if nothing ever happened.

Fourth is the footprint left on other diseases. Vaccines and treatments developed for smallpox were deployed during the mpox outbreak, and instructions on using bifurcated needles were issued once again. When you look at how assets built for one disease are repurposed for the next, you can also see where investments are accumulating right now.

Finally, just one more thing. There are many sides in this story that were pushed aside. Those who opposed variolation were not blinded by superstition; they saw the real risk of spreading the disease to neighbors. The countries in 1966 that urged starting on a smaller scale were not being cheap; they were watching earlier programs struggle. The judgment that monkeypox had zero chance of sparking an epidemic was also reasonable given the data available at the time.

It is easy to say they were wrong. We already know the outcome. When the next disease is wiped out, no one yet knows which side we will be standing on.