Since the COVID-19 pandemic began, we have been waiting for a vaccine: a hero in a syringe to end the pandemic and give us our normal lives back. Unfortunately, however, the process of modern vaccine production is time-consuming and far from easy. After the right molecules have been discovered, the vaccine has to pass through a series of preclinical and clinical trials in which it is tested on animals and humans.

Then, a company has to apply for approval by the competent public health agency in the country or region of production, such as the FDA in the US or the EMA in Europe. If a vaccine does receive approval, it then has to be mass-produced and distributed, possibly worldwide.

In centuries gone by, however, producing a vaccination was not such a tedious task. Even clinical trials were easy back then: One could just try it on a servant and hope for the best. The concept of vaccination is pretty simple. It is based on the response of our immune system. Whenever our immune system encounters a disease-causing foreign body in the form of a virus or bacterium, it produces antibodies against part or parts of it. Upon a second encounter, the antibodies catch the pathogen and prevent it from causing illness.

But some diseases are deadly or cause severe symptoms, so it is better to avoid them once and for all by being vaccinated, if possible. A vaccine contains inactive or weak viruses or bacteria that the body can use as a template to produce antibodies without getting ill. Although some vaccines cause symptoms such as mild fever or fatigue, these are usually not nearly as bad as those caused by the actual illnesses.

In 1796, the English physician and scientist Edward Jenner attempted the first vaccination procedure against smallpox using material from a lesion caused by cowpox, a disease contracted from a similar virus. Jenner is now widely known as the “father of immunology.” Interestingly enough, however, Jenner did not discover vaccination: He just popularised a common concept called “variolation.” The word variolation is derived from “variola,” the name given to the virus causing smallpox. At the time, variolation meant using dried scabs from a smallpox patient to give another person immunity. A person who has been variolated will develop a milder course of the illness.

Smallpox is one of the deadliest diseases known to humankind. Thirty out of 100 people infected by smallpox used to die of the disease. Variolation used dried scabs from smallpox that harboured the virus. Several methods were followed. Some physicians rubbed the dried scabs against the skin of the person who was to be made immune. The Chinese ground dried scabs into powder, exposed it to hot steam, which damaged viral particles and reduced the amount of infection that could be transmitted, then blew the powder up a person’s nose.

The most popular variolation method in Europe was inoculation: The smallpox material obtained from a patient or a victim was injected subcutaneously into a person using a needle. It now sounds somewhat barbaric to insert a needle harbouring a dangerous virus into someone, especially given the fact that there was no guarantee of surviving the procedure. But smallpox was such a serious matter that the risk seemed worth taking for many.

Variolation can traced back to China, India and the Arabian Peninsula; the origin not quite clear. The practice then reached Constantinople, today’s Istanbul, brought there by people from North Africa or the Arabs. Variolation is not risk-free; in fact, variolated individuals could spread the virus and even die themselves. However, the death rate was significantly lower — 1 to 100 — when a person acquired the virus through variolation as opposed to becoming infected naturally.

In 1959, the World Health Organization initiated a global smallpox eradication campaign. After many challenges were overcome, the WHO announced in 1980 that the disease had been eradicated. The vaccine has not only prevented many deaths, but saved millions of children from having to endure scarring or deformities for the rest of their lives.