Louis Pasteur is best known as the father of the germ theory of the disease, but he also played a key role in the development of vaccines and laid the foundation for the type of research now used to find a vaccine for COVID-19.
“Gentlemen, it is the microbes that will have the final word.” These words spoken by Louis Pasteur a century and a half ago are of disturbing significance today as we face the SARS CoV-2 virus that infects virtually every aspect of our lives Pasteur is perhaps best known for formulating the germ theory of the disease, but he is also one of the fathers of the science of immunology.
Everyone who wandered the landscape of Europe in the 1870s noticed fields of dead sheep. The animals had died of “anthrax”, the term derived from the Greek word for coal because of the characteristic black lesions associated with the disease. Anthrax has a long history, and some Bible scholars even suggest that it was responsible for the plague that struck the livestock in Egypt, as described in the story of the Exodus.
Pasteur was already aware that Aloys Pollender in Germany and Pierre Rayer and Casimir Davaine in France had established that some kind of bacterium was always present in sheep that died of anthrax. Antonie van Leeuwenhoek had already observed “Animalcules” through a microscope of his own design in 1676, but bacteria were not associated with disease until 1876, when Robert Koch in Germany inoculated mice with blood from the spleen of animals that had died of anthrax. The mice died, whereas mice inoculated with blood from the spleen of healthy animals did not. The difference was the presence of bacteria in the blood of the sick animals, which were eventually named Bacillus anthracis.
Transmission via blood was clearly possible, but this did not explain how sheep were infected. Pasteur began to ask questions that epidemiologists would ask today. How is it that sheep were more affected in some areas than in others? What was the difference? As it turned out, the disease was widespread where the dead sheep had been buried in fields where other animals were grazing. Why was that? How could bacteria from the buried animals infect others? Here we can refer to Pasteur’s other famous quote: “Chance favors the prepared mind.” The French chemist, yes, Pasteur was a chemist, noticed the soil was full of earthworms. Could these creatures be the infectious vectors? He succeeded in showing that this was indeed the case. The worms transported the bacteria to the surface and the bacteria spores then contaminated the grazing animals’ feed.
Now Pasteur’s attention turned to preventing anthrax. As early as 1879 he had shown that chicken cholera could be transmitted to healthy chickens by vaccinating them with a culture made from the blood of sick birds. As luck would have it, a holiday intervened and Pasteur left a culture dish sitting idly in the laboratory. When he then used this culture to infect healthy chickens, they did not get sick. When these birds were then inoculated with a fresh culture, they still did not develop the disease. Pasteur concluded that leaving the culture in the air had somehow weakened the microbes it contained, preventing them from causing disease, but enabling them to prevent subsequent infection. Could this also work for anthrax?
Following on from his chicken cholera experiments, Pasteur exposed anthrax cultures to oxygen, hoping that this would weaken the microbes and protect animals that were then exposed to a virulent form of the bacteria. In 1881 he conducted a historic demonstration in front of a crowd of observers. Twenty-four sheep, one goat and six cows were inoculated with his new “vaccine”, a term Pasteur had coined in honour of Edward Jenner, who had shown in 1798 that smallpox could be prevented by inoculation with pus from cowpox pustules.
A control group from the same mixture of animals remained unvaccinated. All animals were then inoculated with fresh anthrax bacilli. Two days later the masses gathered to see the results. Applause broke out when it became clear that all vaccinated animals were alive. In the control group, all sheep and goats were dead and the cows were sick.
Pasteur’s attention now turned to rabies, a disease that affects both humans and animals. It was clear that this was an infectious disease, but microscopic examination of blood and tissue was not conclusive. This is because rabies is not caused by a bacterium, but by a virus, a much smaller organism, which only became visible with the electron microscope in the 1930s. Nevertheless, Pasteur believed that anything that caused the disease could somehow be modified, just as he had done with chicken cholera and anthrax, and could be used to confer immunity. Finally, he discovered that infecting a rabbit with blood from a rabid animal did the job. Somehow the infectious agent that passed through the rabbit was attenuated so that it did not cause disease. The most important result was that a vaccine from the rabbit’s spinal cord successfully prevented infection. Pasteur demonstrated this protection in dogs and then, in a groundbreaking experiment, treated a boy bitten by a rabid dog with a series of injections that prevented the boy from developing rabies, making Pasteur an international hero.
Pasteur’s work stimulated vaccine research around the world, and today several attenuated live virus vaccines protect us from diseases such as measles, mumps and rubella. Inactivated bacteria and viruses or some fractions of them can also be used to induce immunity. Perhaps some brilliant scientists will find a way to protect us from COVID-19 and tone down Pasteur’s comment about microbes with the final word