The First Vaccines

While Europe was experiencing a smallpox epidemic, Jenner had observed that many women who worked as milkmaids contracted a form of cowpox, a disease that affected cattle. These women developed only mild symptoms. In contrast, smallpox was severe and often fatal among the general population. Jenner hypothesized that exposure to cowpox might be protecting these women from contracting human smallpox.

The English physician Edward Jenner was the first to create an experimental vaccine for a disease, smallpox. The 8-year-old boy James Phipps was the first to receive it in May 1796.

Although his experiment would not be permitted today due to ethical concerns, at the time, Jenner was able to directly test his theory on healthy individuals. In 1776, he decided to infect a child by exposing him to a woman suffering from cowpox. As expected, the child developed a mild illness, with only a slight fever, and recovered within a few days. Jenner then exposed the boy to human smallpox, and as predicted, the child did not fall ill. This first experience led to Jenner being recognized as the inventor of vaccination.

Building on that foundation and with the experience he gained from studying cholera, Pasteur took another step forward in the 1880s, during an anthrax epidemic (also known as splenic fever) that was ravaging France, affecting both sheep and humans.

A few years earlier, the German physician Robert Koch (1843-1910) — the same one later credited with identifying the tuberculosis bacillus — had already isolated the bacteria responsible for anthrax, Bacillus anthracis, so Pasteur decided to test whether a weakened variant of the same microorganism could provide protection against infection. If successful, his method would not require using a sick animal, making it safer for humans as well.

The first step was to cultivate the bacillus in his laboratory to obtain a weaker version. Cultivating a microorganism in a lab involves placing a sample from an infected tissue into a glass container, adding a nutrient-rich substance to feed the organisms, and then waiting for them to grow.

After completing this task and obtaining weakened bacilli, he conducted a test on sheep, whose success convinced even the most skeptical of the time.

The experiment took place on a farm south of Paris, called Pouilly-le-Fort, and involved vaccinating 50 sheep. At 12-day intervals, half of those sheep were given two doses of vaccines with different levels of virulence, while the other group received none. Twelve days later, all 50 sheep were exposed to a highly virulent strain of natural anthrax. Pasteur predicted that only the vaccinated sheep would survive, while the others would die.

It was 1881, and the test was carried out under the watchful eyes of physicians and scientists who were doubtful of the possibility. The results were conclusive: only the unvaccinated sheep died. The event became known as the Pouilly-le-Fort Experiment, and its impact was so significant that, in 1882, Pasteur was elected a member of the French Academy of Sciences. The anthrax vaccine was applied on a large scale across Europe, dramatically reducing sheep mortality.

Pouilly-le-Fort, France, the site of the first clinical trial of a vaccine.

Additionally, as part of his research, Pasteur identified how the disease was transmitted by observing that the bacillus could be carried by maggots infesting the carcasses of dead sheep. When these maggots came into contact with healthy animals, they spread the infection. This discovery also helped reduce the spread of anthrax.

Pasteur continued to astonish the scientific community of his time. His achievements emerged from studies in both the wine industry and veterinary science, contributing revolutionary insights into the nature and functions of microbes and germs. It was no surprise, then, that the success in treating animal diseases led Pasteur to shift his focus toward human medicine.

During these years, the scientist had suffered a stroke, which left him with paralysis in one arm. However, this did not stop his work, and later, rabies became his focus of study.

Although not very common in humans, rabies was a deadly disease that affected the nervous system of both children and adults.

However, the initial stages of his research were quite frustrating. On one hand, the microscopes of the time were not powerful enough to visualize the virus. In fact, it was only in 1962, with the invention and development of the first electron microscopes, that the rabies virus was observed for the first time.

Furthermore, the first tests Pasteur conducted on dogs, together with his collaborator Émile Roux (1853-1933) — who would later become the director of the Pasteur Institute in Paris for 29 years — were unsuccessful.

Positive results finally began to emerge when they conducted studies on infected rabbits. From samples of these animals' spinal cords, they managed to produce a vaccine containing live viruses, but with reduced virulence. Pasteur then injected sections of spinal cord from these rabbits into infected dogs, later administering preparations with more virulent strains of the virus. These dogs did not develop the disease; they were protected by the vaccination.

But that path was not easy. Pasteur and his collaborators, Roux and Charles Chamberland (1851-1908), had to work with rabid dogs and rabbits, handling infected tissue, conducting trials, and witnessing many failures. It was only in 1884 that Pasteur, Roux, and Chamberland were able to announce their achievement to the Academy of Sciences of France, which appointed a study committee to evaluate the effectiveness of the method. However, despite the satisfactory results with dogs, Pasteur and the experts of the time were not entirely confident about trying it on humans.

A year later, a woman came to his laboratory seeking help to save her young son, who had been bitten 14 times by a rabid dog. The boy, Joseph Meister, was certain to die, so they ultimately decided to test the vaccine on him. Thus, the physician Jacques-Joseph Grancher —since Pasteur was not a doctor—, he injected the weakened virus into the boy over several weeks.

Portrait of Louis Pasteur with Joseph Meister (left). Illustration published in Harper's Weekly in December 1885 showing a child with rabies symptoms receiving the new vaccine developed by Pasteur (right).

The anxiety for a positive outcome from the treatment proposed for Joseph Meister was such that Pasteur took a brief vacation in Burgundy. At all times, he awaited a telegram informing him of the worst outcome. But that message never arrived. Upon his return to Paris, the chemist found out the news that the boy had completely recovered. 

The press, Pasteur, and the rabies vaccine: portrayed as a saint in "Le Courrier Français" on April 4, 1886 (left); as an angel in "Le Don Quichotte" on March 13, 1886 (center); and as an icon in "Le Petit Journal" on October 13, 1895, after his death. (© Institut Pasteur, Musée Pasteur).

However, the vaccine was only used for the second time a year later, in 1885, when a 15-year-old teenager, Jean-Baptiste Jupille, arrived after being bitten while defending other children from a rabid dog.

It was then that the treatment spread and attracted thousands of people seeking the same remedy. Out of a total of 2,500 vaccinated within a few months, only ten did not survive.

Thus, the first effective vaccine in humans emerged, which not only led to the development of others against different diseases but also planted in Pasteur's mind his next scientific legacy.