Smallpox History : 500 Million Deaths, Jenner's Vaccine & Bioterrorism Risk

Just a few years ago, we witnessed the COVID-19 pandemic, which had a mortality rate of below 1 percent. Even that was enough to send the entire world into panic. Now imagine a pandemic with a 30 percent mortality rate. How terrifying would that be? The world has already faced such a devastating pandemic. Its name is smallpox.

From 1900 to 1977 — over those 77 years — 300 to 500 million people died from smallpox across the world. In comparison, the total death toll from COVID-19 was around 7 million. Smallpox has since been eradicated from the Earth — made possible through cows — and the search for a treatment for smallpox was what first brought the concept of vaccination into the world.

The History of Smallpox (Ancient Origins)

Although smallpox has been eliminated through the combined efforts of all nations, there are concerns that it could be used in the future as a bioterrorism agent, which could trigger a global health crisis.

The last smallpox patient in Asia was Rahima Banu. In 1975, she contracted smallpox at just one and a half years of age. Fortunately, she survived — though the marks of smallpox remained on her body.

Smallpox looks somewhat like chickenpox. Blisters appear on the body and gradually spread across the entire surface — a deeply uncomfortable sight. Smallpox is caused by the Variola virus. Typically, a person dies within 21 days of infection. Those who survive are left with scars, and in some cases, people go blind.

Throughout history, many civilizations were wiped out because of smallpox. The indigenous peoples of North America had no smallpox among them. But when Europeans traveled to North America, they brought smallpox with them. Since the indigenous people had little immunity against this new virus, the death rate among them was 60 to 90 percent. This allowed Spanish forces to seize indigenous territories with almost no resistance. In the Caribbean, the Taíno people were completely wiped out in the late 15th century due to smallpox spread by the Spanish. The entire population of the Caribbean fell by 80 to 90 percent. The same story played out with the Australian indigenous peoples. When Europeans arrived in Australia in the 1800s, smallpox spread there too. In 1789, many indigenous tribes around Sydney and its surroundings were wiped out in a smallpox epidemic.

Smallpox as a Weapon

Europeans even used smallpox as a weapon in some cases. For example, during the 1763 siege of Fort Pitt in Pennsylvania, British soldiers gave two smallpox-infected blankets to indigenous people — thinking they would die from the infection and direct warfare could be avoided. While there is no official documentation of exactly how many indigenous Americans died as a result, many were infected with smallpox. This is considered the world's first known use of a biological weapon.

Smallpox did not only affect indigenous peoples. Europeans themselves were severely devastated by it as well. For instance, from the 17th to the 18th century, smallpox epidemics broke out across Europe almost every year. It is estimated that in the 18th century alone, approximately 60 million Europeans died from smallpox.

The history of smallpox is ancient. The oldest evidence of smallpox comes from ancient times. In 1898, a mummy was found in Egypt — that of Pharaoh Ramesses V. The mummy showed marks on the face and body resembling smallpox, making it the oldest physical evidence of the disease. Ramesses V died around 1157 BC. Ancient texts from India and China also mention smallpox.

As for exactly when smallpox first appeared in the world, it cannot be said with certainty. However, it is believed that around 10,000 years ago, when humans began domesticating animals, smallpox began to spread among people — because Orthopox viruses similar to Variola are more commonly found in animals like cattle, goats, and pigs. Some also believe the virus may have jumped to humans from rats.

The First Attempt at a Solution

No matter how early smallpox began, there was no treatment for the disease until it was eradicated — though recently America has approved some antiviral medications. This raises the question: if there was no treatment for smallpox, how was it possible to eradicate it from the Earth entirely?

In 1717, an English woman named Lady Mary Wortley Montagu observed something in Turkey. There, the skin of healthy people was scratched and a small amount of smallpox material was applied to the wound. The idea was to expose the body to a tiny amount of the smallpox pathogen before a full infection could occur — so that immunity against smallpox would develop. The concept of building immunity through deliberate infection had existed for a long time, and was called inoculation. It was practiced in various ways in India, China, and Africa. 

For example, in medieval China, the Chinese would take blisters from a smallpox patient, dry them into a powder, place the powder in a pipe, and blow it into the nose of a healthy person. This method was not entirely safe — there was a 2 percent chance of dying from smallpox through inoculation. Even so, people went through with it, because it had been observed that those who had smallpox once never got it again. 

And since it was believed that everyone would encounter smallpox at some point in their lives, being infected by a small amount before a full infection meant less risk of death and a guarantee of future immunity. So inoculation was the only available response to smallpox at the time — and people feared smallpox so deeply that inoculation seemed the comparatively safer choice.

In 1717, after witnessing inoculation in Turkey, Montagu attempted to bring it to England. At first her efforts met significant resistance. Later, inoculation was successfully applied to prisoners and orphans, which convinced England to adopt the method and name it variolation — after Variola, the name of the smallpox virus.

While being deliberately infected before contracting smallpox was certainly not a complete solution, it helped people develop a clearer understanding of smallpox. For instance, the 10 to 12 days after variolation were identified as the critical period during which smallpox symptoms would appear. During those days, the variolated person would be isolated — a separate or detached ship would be turned into a hospital. Even so, smallpox remained a source of terror, because once someone fell ill with it, there was nothing to do but leave it to fate. This drove the doctors of that era to search for something more effective.

Edward Jenner and the Birth of Vaccination

One such doctor was England's Edward Jenner. He noticed that in the village of Gloucestershire in England, those who kept cattle had a very low rate of smallpox infection. In particular, those who had been infected with cowpox never contracted smallpox. Cowpox is a disease of cattle that causes blisters on the udder similar to those of smallpox — but it is not fatal for cows and heals on its own after a few days. People who were in close contact with cattle and became infected with cowpox developed a few blisters that healed on their own — but as a bonus, they did not contract smallpox. In other words, they had developed immunity against smallpox.

After first noticing this in 1778, Jenner spent the next 18 years closely observing it and finally took steps to bring solid proof of it forward. In 1796, Jenner deliberately introduced cowpox material into the body of James Phipps, the eight-year-old son of his gardener. James developed a fever but recovered within a few days. Six weeks later, Jenner infected James with smallpox material. But no effect whatsoever was seen — James had developed immunity against smallpox. This meant that deliberately infecting oneself with cowpox was providing protection against the deadly smallpox.

Jenner published his findings and named his method vaccination — from the Latin word "vacca," meaning cow. Since his method was related to cows, he drew on the word "vacca" to name it vaccination. Today, of course, the word vaccination has a far broader meaning — it refers to receiving a vaccine against any disease.

The Resistance Vaccination Faced

After Jenner published his findings, instead of being praised, he was met with criticism. His discovery was mocked in various ways. However, as time passed, other doctors began applying Jenner's method and seeing results. Support for his approach gradually grew. But convincing ordinary people was not easy. Various religious groups opposed vaccination, claiming it was an act against the Creator's will and would anger God further. Those whose profession was variolation also opposed vaccination, fearing it would harm their livelihood. Since vaccination was associated with a cattle disease, many also found it disgusting. In Europe at the time, stories spread that vaccination would cause cow's body parts to grow on humans and that people would eventually turn into cows — and many paintings were made on this theme. It took considerable effort to establish vaccination as a normal practice.

In 1853, England became the first country to make vaccination compulsory. Over time, vaccination gradually became an accepted norm across Europe.

The Global Campaign to Eradicate Smallpox

Once the effectiveness of vaccination was understood, the next challenge was how to spread it everywhere. After the smallpox vaccine was developed in 1796, distributing it across the world was an eventful journey. Initially, a piece of cloth would be infected with the cowpox virus and transported by ship to distant places. 

There, a scratch would be made on a person's arm and the cloth tied over the wound — infecting that person with cowpox, who would then infect others. This method was used to bring vaccination as far as Canada. For greater distances, however, this method did not work. Beyond cloth, vaccination was also spread through liquid methods to various European countries. 

But the most effective method was the use of children — cowpox-infected children were sent by ship to distant countries, through whom cowpox then spread in those places. This continued until the end of World War II.

But even then, smallpox remained a name that struck terror. Because not being able to vaccinate every person in the world meant that if anyone contracted smallpox in one region, it would trigger an explosion of cases and spread to other regions as well.

After World War II, the World Health Organization (WHO) was established. In 1953, the WHO sought opinions on how to solve the global smallpox problem — because the smallpox vaccine did not provide lifelong protection, meaning that even after 100 percent vaccination in one country, smallpox could still be reintroduced from another country. 

In 1958, the Soviet health minister advised the WHO to launch a worldwide smallpox campaign, and that year the program was launched. At that point, there were five major areas in the world where smallpox was epidemic-level. With cooperation from various countries, a massive effort began. Massive production of the smallpox vaccine was started. Thousands of health workers went into the field in Brazil, Africa, and South Asia — showing people photographs of what could happen to someone infected with smallpox to convince them. In many places, health workers faced various challenges but remained committed to their goal.

India's Last Battle Against Smallpox

The world's last major smallpox epidemic occurred in India in 1974. At that time, 110,000 people in Uttar Pradesh and Bihar were infected with smallpox, and 20,000 died. After that, the Indian government launched its vaccination program with the utmost sincerity. Approximately 135,000 health workers visited 120 million homes across 600,000 villages searching for smallpox patients and conducting vaccination campaigns. 

Vaccinating a population as vast as India's was extraordinarily challenging — if even a few people in a village were missed, the risk of an epidemic remained. This was precisely why, despite the WHO's worldwide vaccination program launched in 1958, an epidemic still occurred in India in 1974. As a result of the Indian government's sincere and determined effort, India's last smallpox patient was seen in May 1975.

The world's last smallpox patient was found in 1977 in Somalia. And the last person to die of smallpox was an English woman who was unfortunately infected by the smallpox virus in a laboratory and died in 1978.

On May 8, 1980, the World Health Organization officially declared that smallpox had been completely eradicated from the Earth. From that point, the global smallpox vaccination program was gradually discontinued. After 1980, no one was vaccinated against smallpox anymore.

Edward Jenner's Legacy

Dr. Jenner's small discovery saved the lives of 5 million people every year. He is today considered the Father of Immunology. The smallpox virus has been eradicated from its natural sources in the world — however, two countries still keep it in storage: the United States and Russia.

After the world was declared free of smallpox, the WHO asked all countries to transfer their laboratory stocks of the smallpox virus to either the United States or Russia, or to destroy them. While officially only two countries claim to have the virus, many believe some countries may not have destroyed their stocks. 

Even if we accept that only the US and Russia have the virus, there is still reason for concern — both countries were supposed to destroy the virus, but mutual distrust prevented either from doing so. The US claims Russia may be planning to use smallpox for bioterrorism in the future; Russia makes the same claim about the US.

The Threat of Bioterrorism Today

Consider this: since 1980, smallpox vaccination has been discontinued. As a result, everyone born after 1980 has no immunity against smallpox. This means that today, it would be alarmingly easy to trigger a smallpox epidemic. Biological weapons are currently a massive threat. On top of smallpox, various countries are working on genetically modified viruses — the sole purpose of which could be to use them as weapons in the future. It took 18 months to develop a vaccine against a relatively less deadly virus like COVID-19. Imagine how catastrophic it would be if a genetically modified, more powerful virus were deliberately released.

The way Dr. Jenner conducted vaccine trials on an eight-year-old child would certainly not be acceptable by today's human rights standards — anyone doing the same today would face imprisonment, fines, and possibly even the death penalty. But Jenner's era was different. The concept of human rights was different then. In fact, human rights evolve over time. There was once a time when people were forcibly enslaved and sold like goods. Today, all medical experiments are first conducted on guinea pigs or other animals before being applied to humans.

Though smallpox is no longer heard of, chickenpox and monkeypox still exist. These are not as dangerous as smallpox. The US Food and Drug Administration (FDA) has approved two antiviral drugs — Tecovirimat and Brincidofovir — one in 2018 and the other in 2021. These are effective against Orthopox viruses like smallpox. 

Tecovirimat blocks a protein called VP37 of the Variola virus, preventing the virus from spreading effectively within cells. Brincidofovir (Tembexa) blocks the virus's DNA synthesis, preventing it from replicating. Although smallpox no longer exists, these drugs are effective against other Orthopox viruses like monkeypox. They have also been developed as treatments in case of a future bioterrorist attack using the Variola virus, and many countries are already stockpiling them.

As life has become easier with the passage of time, new and complex challenges have also emerged. Dealing with them requires technological advancement — that is the only way. Falling behind technologically leaves no option but to look toward others or depend on other nations.