Infection and its control: the first vaccines

 Part 2

 Edward Jenner, a physician in Gloucestershire in the west of England, noted that milkmaids and blacksmiths got cowpox sores from cows and horses and these quickly healed.  Even before Jenner took an interest, the milkmaids knew that they could care for people ill with smallpox and not get the disease themselves. Jenner records this acquired immunity in a 1798 publication and confirmed it by experiment: he removed material from a milkmaid’s pustules, pricked the skin of a boy, who developed a sore, and then became immune to smallpox, which Jenner also inoculated into his arm.  The ethics and other aspects of the experiment deserve more detailed explanation, but Jenner’s results and their publication led to the first effective vaccine for a disease. It was used until smallpox was eliminated in the 1970s. What was missing in the years after Jenner’s discovery was a science of microbiology and what became the germ theory of infection and disease. 

 Beginning in 1857, Louis Pasteur showed that all fermentation was due to microorganisms. Wine, for example, is the product of a fermentation carried out by yeast. The wine of his native region, the Jura, was not very good. Wondering why, Pasteur looked at it under a microscope and discovered yeast and bacteria. Bacteria were ruining the wine. The vintners had to avoid bacterial contamination, which he told them how to do. In France, if you can save the wine industry of a region, you become a hero. Using the principles of microbiology, Pasteur improved French and British beer and rescued the silk industry in the south of France. He also realized that bacteria in a wound would grow at the expense of the patient and cause infection and disease. Reading these reports in about 1864 led Joseph Lister to develop antiseptic surgery.

 Pasteur infuriated the medical profession, which did not believe that anything as small as bacteria could kill a human being. Most physicians thought that the bacteria found in animals or patients were the result of disease and not its cause. They chastised Pasteur for being a chemist and not a physician. Pasteur, who was articulate and combative, almost a warrior, barely concealed his contempt. There were a few doctors who were exceptions — like Joseph Lister.  

 Pasteur came to vaccines late in his career. His laboratory was working on chicken cholera, which could kill all of the chickens or rabbits on a farm. His student, Charles Chamberland, had learned to grow the cholera bacteria in chicken broth and proved that these bacteria would quickly kill chickens. In the spring of 1879, Chamberland went fishing and left a flask of cholera bacteria on his lab bench for weeks. When he returned, he inoculated a batch of chickens with this stale culture, but the chickens did not become sick. He was about to start over with a fresh culture of bacteria and a new batch of chickens when Pasteur told him to inoculate lethal cholera bacteria into the chickens that had survived the stale culture. They survived, while the new batch of chickens all died. The cholera bacteria that had been left on the bench had become weakened, but could still cause immunity in chickens. 

 During the same period, the lab was working on anthrax, which killed many cattle and sheep in Europe. Pasteur sent Chamberland and Emile Roux, a physician who had joined the lab, to a farm near Chartres where they observed that anthrax was killing cattle and sheep, but not chickens. Pasteur reasoned that birds have a higher temperature (about 105F) than mammals (98.6F) and perhaps that was what protected the birds. It turned out to be true — anthrax bacteria could grow at 105F, but would not kill the animals. Here was a way to create another weakened bacteria for another vaccine, which Chamberland and Roux created and published. There was derision about the effectiveness of anthrax vaccination from veterinarians; after a dispute, a challenge was arranged at a village outside Paris called Pouilly-le-fort.  Under a strict protocol, 25 sheep were inoculated with the vaccine (there was one booster shot for them) and 25 left as unvaccinated controls. On May 31, 1881, all of the animals were infected with lethal anthrax. Two days later, the animals that had not been vaccinated were dead or dying. 

 Today there is a plaque on a stone barn in Pouilly-le-fort, but this very public trial, based on the ideas that microbes cause disease and that they can be weakened to make vaccines, introduced a new era to medicine. Soon hundreds of thousands of cattle and sheep across Europe were vaccinated for anthrax and losses dropped. 

 This short account leaves out a lot of detail, drama, doubt and even a little skullduggery, but it celebrates a milestone. Pasteur had not yet attacked a human disease, but the laboratory was working on rabies, a difficult and dangerous proposition. 

 Richard Kessin is professor of pathology and microbiology emeritus at Columbia University. He lives in Norfolk, Conn. This series of columns on Infection and its Control (and all previous columns) can be found at https://www.tricornernews.com/search/node/Richard%20Kessin/.