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The Story Of Vaccination And The Defeat Of An Old Enemy

This article forms part of the IFLScience exciting editorial calendar for 2023.

Russell is a Science Writer with IFLScience and has a PhD in the History of Science, Medicine and Technology

Dr. Russell Moul

Russell is a Science Writer with IFLScience and has a PhD in the History of Science, Medicine and Technology.

Science Writer

A group of 18th century people stand opposite three modern scientists in white lab coats. There are large smallpox viruses floating above their heads.

Smallpox was a scourge to the human race for centuries, but in the 18th century, the first effective vaccines were developed to combat it. Over the next few centuries, these methods of prophylaxis were improved, leading to smallpox being eradicated in the late 20th century. Image Credit: Shutterstock/ superoke/ CharacterFamily70/ Macrovector/ IFLScience Creative Team

In recent years we have learned a lot about various efforts to limit the spread of diseases, such as COVID-19, through global vaccination efforts, but did you know immunization has a long and fascinating history? 

Far from being a modern technique, the principle of vaccination has been utilized for several centuries, and there is evidence that the principles underpinning it are even older than that. So, what is a vaccine and where did the idea come from?


What are vaccines and how do they work?

When your body is invaded by harmful microorganisms, such as bacteria or viruses, your immune system mounts a defense against the infection as a response. It does this by producing three types of white blood cells – Macrophages, B-lymphocytes, and T-lymphocytes

Macrophages engulf and digest invasive germs, as well as any dead or dying cells, leaving behind parts of the organisms, called antigens. The body sees these antigens as a threat, so B-lymphocytes produce antibodies to fight them. Meanwhile, T-lymphocytes learn to recognize specific germs so that antibodies can be produced to fight them again in the future. 

A vaccine can help your immune system with its defense efforts against disease by mimicking the infection. Although there are various types of vaccine, they all operate on this same principle by using antigens (a foreign substance that causes the immune system to produce antibodies against it) to generate acquired immunity to certain infectious diseases. 

Essentially, the antigens mimic a particular disease, causing the body to respond as it would against the actual infection. This arms the immune system with the right cells needed to fight the infection in the future. So, although the vaccine does not contain the original disease, only a weakened or inactive version in the form of the antigens, the body is nevertheless taught to recognize the real causative organism.


In some cases, a vaccine may need multiple doses over a period of time to enable it to perform properly. This is because the body may need time to make long-lived antibodies and to develop the T-lymphocytes for the specific organism. 

Unfortunately, no vaccine is perfect and they do not guarantee that someone will not contract a disease. But they have proven time and time again to be a robust, safe, and effective means of protecting people.

“The speckled monster”: smallpox  

The history of vaccination is deeply connected to that of an old enemy – smallpox. This infectious disease plagued many of our ancestors, killing indiscriminately and in vast numbers for centuries. 

Although we do not know where it came from, evidence of smallpox rashes on Egyptian mummies suggest it is at least 3,000 years old. Over the years, the disease traveled along the various communication channels that opened across the world to enable trade, war, and migration. In short, wherever people went, smallpox followed. But while it is often assumed that vaccinations, or at least the principle, were first developed in early 18th century Britain (where it was referred to as inoculation), the practice is actually far older. 


There is evidence of vaccinations being widely used in Asia and parts of Africa to protect people from smallpox as early as 200 BCE. Here, small amounts of smallpox pus would be transferred to a healthy person to give them a mild form of the disease, which was meant to be less lethal than a natural infection. 

The first known written accounts for inoculation date to around mid-16th century China. Although the documented evidence is limited, it seems one of the more common methods of inoculation involved blowing powdered smallpox scabs into a child’s nostrils (a technique known as insufflation). In other techniques, the scab may be extracted in water, or, in another, a pus-coated cotton plug was inserted up the nose. 

India is also known to have experimented with inoculation before it was practiced in the West. According to 18th century accounts from English settlers, it was performed by piercing smallpox pustules with a needle and then pricking a healthy person in the arm several times. It is possible that techniques like this had been in use for several centuries prior to the English presence in the country. 

Inoculation did not appear in Europe until the early 18th century when Lady Mary Wortley Montagu noticed how Turkish peasants would hold smallpox parties for inoculation (or engrafting as she referred to it) purposes. Once back in Britain, she had her two children inoculated using similar techniques. The idea became extremely influential within British medical circles and soon spread across Europe. 


At the same time, similar ideas were starting to take root in the American colonies. Here, enslaved West Africans had long been practicing a technique that they had brought with them when they were violently dispersed across the Americas. Unfortunately, a lack of documented evidence means we are unable to fully understand the extent to which enslaved or free people of African descent practiced this type of prophylaxis. But there is still enough surviving evidence to suggest that it was often practiced away from the European physicians who had no knowledge of it. 

In a famous case, Cotton Mather, the preacher who was indirectly involved in the Salem Witch Trials, publicized this lineage when he wrote that, before hearing of inoculation “anywhere in Europe” he had heard “from a servant of my own an account of its being practised in Africa.” Mather was no stranger to the sorrow infectious disease brought with it, having lost one of his wives and two of his 15 children to a measles outbreak in 1713. So, when he was told about the marvels of inoculation by his slave, Onesimus, in 1716, he took note. He not only sent an enthusiastic letter about the practice to the Royal Society in London, but he also later advocated for the practice when smallpox broke out in Massachusetts in 1721.

The dawn of vaccinations

So far, the inoculation practices were effective, however, there was always the risk that someone would develop full-blown smallpox and not only die but also spread the disease further. It wasn’t until 1796 that the world saw the first effective vaccine that was far safer. 


Edward Jenner was an English country doctor who performed the traditional form of inoculation. He learned that, among the local countryfolk living in Gloucestershire, England, a cattle disease known as cowpox would sometimes transfer to humans, especially milkmaids. And, more miraculously, people who caught cowpox seemed to be immune to smallpox. 

Never one to miss the opportunity for an experiment, Jenner took pustule matter from a milkmaid called Sarah Nelmes and used it to inoculate an 8-year-old boy called James Phipps, in May 1796. Phipps developed a slight fever but quickly recovered. Then, several weeks later, Jenner repeated the process with smallpox pus and found that the process did not take – Phipps, it seems, was immune and the first person to be vaccinated. 

Edward Jenner vaccinating various people with cowpox 'matter' which causes small cows to emerge from their bodies.
Edward Jenner developed the first effective vaccine using cowpox "matter" to give people resistance to smallpox. This technique paved the way for modern vaccination methods that eventually eradicated smallpox in the late 20th century. Image credit: Library of Congress, Prints & Photographs Division, Public Domain via Wikimedia Commons

As with today, not everyone agreed with the process. Some people spread rumors that the vaccination would turn them into cows, while religious authorities argued that it was immoral to stop a disease that was an expression of God’s will. But despite these and other voices of opposition, the procedure was deemed safe and effective through repeated testing by 1801.

The power of smallpox vaccinations soon spread across the world and became mandatory in Britain and parts of America, and other places, in the 1840s and 1850s. This led to the introduction of smallpox vaccination certificates to prove individuals were safe to travel. Despite this success, the disease continued to ravage some parts of the world, with over 2 million people dying from it every year. 

The road to eradication 

Throughout the 19th and early 20th centuries, research and experimentation in vaccination procedures not only sought to improve their delivery but to extend the number of diseases they could prevent. In 1872, Louis Pasteur, the famous French chemist, created the first lab-produced vaccine for fowl cholera, which not only introduced the name “vaccine” to common language but also helped prove the Germ Theory of Disease. Pasteur and his proteges would go on to develop vaccines for other diseases, such as anthrax and rabies. 

By the 1950s, advanced techniques for preservation meant that heat-stable, freeze-dried smallpox vaccines could be stored without refrigeration. Soon, vaccination had led to the elimination of smallpox in Western Europe, North America, and Japan. But the disease remained a threat as long as the effort was not coordinated. 

Then, in 1959, the World Health Assembly called for a global approach to finally beat the ancient enemy. In the same year, the World Health Organization (WHO) launched its Smallpox Eradication Programme, which made brave steps towards this overall aim. Over the next two decades, scientists from across the world, including the US and the Soviet Union who were at odds during the height of the Cold War, shared resources and expertise to deliver vaccinations. Thanks to this combined effort, the WHO was able to declare that, across the world, smallpox had finally been eradicated in 1980. 

This was the first time in history that a known disease, a raging killer, had been stopped by human intervention. There has not been a single case of smallpox occurring naturally ever since.


All “explainer” articles are confirmed by fact checkers to be correct at time of publishing. Text, images, and links may be edited, removed, or added to at a later date to keep information current.


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