Smallpox and the COVID-19 Vaccine

Recently, there has been much debate about vaccines due to the global rollout of vaccines for COVID-19. What is lacking in most debates is historical context. So, in this article we will talk about the history of the smallpox vaccine, one of the first vaccines every produced and distributed widely to the masses.

The history of vaccines really starts with smallpox. Smallpox is a disease that most of us have never seen because it has been declared eradicated from the world since 1980. The last known case was in 1978, so this is essentially a disease that is now extinct from the world largely because of vaccinations.

The earliest written accounts of smallpox date back to about 1,000 BC in China where a deadly disease with all the known symptoms of smallpox is described.  There are also some ancient texts in India that also mention it. Some people believe that the pockmarks on the face of the mummy of Rameses V indicate a smallpox infection.  By around 500 AD, there are multiple written accounts from all over the world that clearly describe smallpox as we understand it in modern times.  By this time, the disease is endemic throughout Europe, Asia and Africa affecting millions of people.

When smallpox was introduced into the Americas by the Spanish and Portuguese conquistadors arriving in South America, it caused widespread death amongst the Aztecs and the Incas who had no previous exposure and no population level immunity to the disease.  Smallpox killed both the Incan and Aztec emperors and decimated the populations with over 40% of the population succumbing to the disease. By the 17^th century the native population of Mexico dropped from 25 million to 1.6 million largely due to smallpox.  This tremendous loss of life and sickness is one of the reasons that the Aztec and Incan Empires fell to the Spanish and Portuguese conquistadors even though the Europeans were outnumbered by more than 1000 to 1.

Even in the 20th century, people estimate between 300 and 500 million people worldwide died from smallpox. Smallpox is a disease that kills between 20 to 60 percent of people with a roughly 30% fatality rate.  This makes smallpox a disease with both high mortality and morbidity, with most of the survivors being left with disfiguring scars and many with very severe side effects like blindness.

Smallpox is caused by a virus called Variola, there’s Variola major and Variola minor. Variola major causes the more severe form with a high fatality rate while Variola minor has a less severe outcome with about a 1% fatality rate.

For thousands of years the virus ran unabated throughout the world.  Because it was so devastating, many civilizations thought of ways to try to prevent people from getting infected by smallpox.

Over time, people began to realize that those who had smallpox before and survived seemed to be protected from getting it again. So logically, smallpox survivors were called to care for people who had smallpox.  The next logical idea was to try to make people get smallpox but with the hope that they would only get a mild form of it.  This led to several different methods in various cultures around the world.

In China pustules from people with smallpox would be scraped off, dried, ground into powder and then blown through silver pipes into the noses of children to infect them (with hopefully a milder form of smallpox). In India, they would take some pustules and scratch them into the skin of the person they would try to infect. And then in Africa (Sudan in particular), when a child became ill with smallpox, the mothers of other children in the village would wrap pieces of cloth around the infected child and then later wrap the same cloth around their own child in the hopes of giving their children a mild disease which would protect them from severe disease. 

Eventually, the dominant method became the introduction of small amounts of pustule material into scratches in the skin.  This was called variolation and this practice was spread to North America from Europe. It became widely practiced and was effective when it worked but variolation had a 3% fatality rate.  While 3% fatality was thought by most people of that time to be acceptable to prevent a disease that is 30% fatal, some people wanted a better, safer method of prevention.

This leads to the story of Edward Jenner. Edward Jenner was a British physician who himself was variolated when he was a child.  He worked in the British countryside and was aware of the folklore that milkmaids who got cowpox were protected from smallpox.  Cowpox is a disease like smallpox that occurs in cows but is usually not severe and manifests as sores in their udders. And then when milkmaids and people that work for the cows touch them, they would get what they called cowpox in their hands which was usually a mild and benign sickness.  Edward Jenner decided to investigate this, and he wrote a book called An Inquiry Into the Causes and Effects of the Variolae Vaccinae which he self-published back in 1798.  The National Library of Medicine has digitized the actual book which anyone can read online now.  In the book he details various cases that he observed of people that got cowpox and then he tried to variolate them with smallpox, and they would not get any disease from the variolation. 

Eventually, he got to case number 16 who was a dairymaid named Sarah Nelms who got cowpox on her hands.  Jenner scraped one of the pustules and he purposely infected a healthy 8-year-old boy named James Phillips who was the son of his gardener. James developed cowpox and was sick for a few days and then recovered.  A few months later, he variolated the boy with smallpox and the boy never developed any symptoms of smallpox.  Edward Jenner then repeated this procedure on several other children with the same result. He named this method “vaccination” to differentiate it from “variolation” and he originated the word from the word Vacca, which is Latin for cow.  

After confirmation that cowpox was protective against smallpox, Jenner wrote and published the booklet and told the medical community of that time.  They were skeptical as medical officials should be, but eventually, it was accepted that this worked. England made mandatory vaccinations for smallpox a requirement.

This set up an uproar at that time from a small segment of the population. People believed all kinds of things about vaccination. They believed that people who were vaccinated would turn into cows or at least give them bovine characteristics by giving them cowpox. There are pictures of little cows growing out of people. They believed that it was not God’s intention to use a lesser animal and to inject parts of it into people (although they were not actually using cow parts, they were using a virus that was first found in a cow).

Many years later when Canada made vaccination mandatory for smallpox, there were many of the same types of complaints about the smallpox vaccine that we see today with the COVID vaccine. “People who get the vaccine are just mindless sheep. Vaccination is an infringement of our civil liberties.  Do not be alarmed by smallpox. It is not dangerous; the real danger is the vaccine. Vaccination does not prevent smallpox. Vaccination actually causes loathsome and often fatal diseases. Many children are killed outright, and thousands have had their health ruined by it. The vaccine does not lessen the severity of the fatality of smallpox. The proportion of vaccinations who have had smallpox has steadily increased. Most of the people who get smallpox are people who have been vaccinated.”

There was also the tactic of quoting from medical professionals who were against the vaccine as we see today as well.  Resistance to compulsory vaccination programs continued into the 1920s when armed citizens would evict medical workers with vaccines from their towns. 

However, mandatory vaccine programs continued and were highly successful and by the 1950s, smallpox was eradicated in the United States.  In 1959, the World Health Organization (WHO) started a mass vaccination plan to rid the world of smallpox. It was difficult because they had to vaccinate people through wars and conflicts, and reach remote, almost inaccessible places. Eventually, they got it done and the world was declared free of smallpox on May 8th, 1980. This disease, that had killed over a billion people throughout history and 300 million in just the 20th century with a 30% fatality rate, was finally eradicated.

Today, children are no longer vaccinated against smallpox because there’s no need to. However, there are two locations in the world that officially store and handle the virus that causes smallpox. They are the Centers for Disease Control in Atlanta, Georgia and the State Research Center of Biology and Biotechnology in Koltsovo, Russia.

Because no one has been vaccinated since 1980 and there is little to no immunity in the population, it is one of the viruses that could be a significant weapon for bioterrorism or as a bioweapon. Because of that fact, the United States keeps a strategic store of smallpox vaccine with enough stores to vaccinate every person in the United States.

So, as we see the roll-out of the COVID-19 vaccine in all its various forms and hear/read all the debates about it, it’s worth remembering the history of the first ever vaccine ever developed.

A few interesting little-known facts about the smallpox vaccine: 

While many medical texts and history books credit Edward Jenner with first vaccinations and he indeed is the person who did the work to make it a viable medical practice, the first vaccination was actually done by a farmer named Benjamin Jesty who purposely infected his family and workers with cowpox during a smallpox outbreak in his area almost 20 years before Edward Jenner vaccinated James Philips. 

Also, the modern virus used as a smallpox vaccine is called Vaccinia but vaccinia is not the virus that causes cowpox.  Over time, during laboratory production of the vaccine, somehow the virus changed so that the virus in the vaccine, when it was finally identified, turned out to be Vaccinia rather than the cowpox virus.

Smallpox is so far the only disease to be completely eradicated from the natural world.  There are currently efforts to do the same with polio which has been eradicated in all parts of the world except for Afghanistan and Pakistan.

Steve Lee, MD, PhD

Dr. Lee is a surgical oncologist and associate professor at Loma Linda University School of Medicine and currently serves as Vice Chairman of the Head and Neck Surgery Department and co-director of the Center for Skull Base Surgery. He lives in Redlands, CA with his wife and two daughters and enjoys dragging them out into the great outdoors every chance he gets.