Written by Ishaabhya Tripathi
The distressing and devastating impact of rabies has been chronicled since the second millennium B.C., with ancient Babylonian texts describing a slack jaw and sudden, frenzied rage in dogs. Even the term ‘rabies’ descends from the Latin rabere, meaning ‘to rave’, which is in turn the root of the modern English word ‘rage’. Its clinical name lyssavirus can be traced back to Lyssa, the Ancient Greek goddess of rage and fury, who was said to make dogs go mad and kill their owner. Despite rabies’ infamy affecting the language that we used and continue using today—as well as its essentially 100% mortality rate—immediate news of its vaccine was received without much ceremony internationally.
The rabies vaccine is just one of Louis Pasteur’s numerous and invaluable contributions to immunology. However, this wasn’t Pasteur’s area of interest at first; his road to immunology was nearly two decades in the making. Broadly, this ‘road’ consists of four key steps: his research on microbes, his work on immunisation, isolating pathogens, then finally, the successful deployment of the rabies vaccine.
Pasteur’s theories were received warily at first because he wasn’t a medical specialist. Rather, he was a chemist, and his extensive research in this field led to him being appointed professor of Chemistry at the University of Lille; this in turn led to his research on fermentation after being consulted about a contamination issue affecting a distillery in his region. After proving that microbes were the root cause of wine contamination, Pasteur heated the wine to around 60 degrees Celsius to kill the microbes—a process known today as ‘pasteurisation’. Pasteur saw the success that pasteurisation had with regards to sterilising milk and was inspired to apply his knowledge of bacteriology to yet another contamination crisis. This time, it was about silkworms—France’s domestic production of silk was endangered by an unknown disease that affected silkworms. Five years of investigation led Pasteur to the realisation that seemingly healthy silkworm eggs were actually contaminated by bacteria that was present in silkworms’ red blood cells. In an academic presentation, Pasteur likened the blood infection to mould spores, with the presence of dead silkworms and silkworm waste explaining the contamination that led to disease throughout France’s silkworm nurseries. Pasteur’s observation of how disease was harboured and spread served as an introduction to wider research concerning infectious diseases.
In terms of immunology, his first breakthrough was the vaccine he developed for cholera in chickens. After performing bacterial culture tests on the chicken cholera bacteria, Pasteur found that the cultures stopped being infectious, but still kept their pathogenic traits. Pasteur injected healthy chickens with the weakened form of the disease (as produced by the cultures) and found that they were immune to the infectious variant of chicken cholera. This served as a stepping stone towards his work on other infectious diseases. Before his work on rabies, Pasteur gained experience with another deadly zoonotic disease: anthrax.
Pasteur’s work went in tandem with that of a German scientist, Robert Koch, who isolated the bacteria that causes anthrax. Pasteur confirmed Koch’s conclusion; they both independently proved that the bacteria was responsible for anthrax infections. In much the same way as chicken cholera, Pasteur used bacteria cultures to develop the anthrax vaccine. Anthrax was epidemic amongst livestock at the time, so there was a lot of pressure placed on Pasteur and his vaccine. A very highly publicised experiment, in which fifty sheep were injected with the anthrax bacteria, with half of these vaccinated, proved the efficacy of Pasteur’s discovery: the vaccinated sheep lived, whilst the unvaccinated ones died.
At first, Pasteur attempted to approach the rabies vaccine in a similar way to chicken cholera and anthrax. However, this didn’t work because—unlike cholera and anthrax, whose bacilli are visible through a microscope, the rabies virus was too small to see. Additionally, since rabies is a virus, the bacteria culture tests that formed the basis of the anthrax and cholera vaccines would not work in this case. Pasteur used the saliva of rabid animals to infect rabbits. The infected rabbits died, but Pasteur noticed something important: the virus had a very long and varied incubation period. His experiments were not the most reliable because of the variable incubation period, but he amended this by using infected brain matter instead of saliva. This induced rabies in rabbits far more quickly and gave Pasteur a chance to research how to weaken the virus, just like he’d done with his vaccines for anthrax and cholera.
Pasteur had to find the appropriate strength of the virus with which he infected the test animals. By increasing the virulence of the disease, he found a constant, in that he found the exact potency needed for the rabbits to show symptoms of rabies. He called this constant the virus fixe. He used this to infect a rabbit, which later died of the virus. Pasteur suspected that the prolonged incubation period related to the time that the virus needed to multiply and infect the entire central nervous system. He kept pieces of the infected spinal cord in aseptic conditions, away from light, and at the same temperature throughout. He observed that the cord of the infected rabbit became steadily less effective at inducing infection. Twelve days later, the cord did not induce rabies at all. Pasteur’s method of drawing cultures weakened diseases, but in this case, he neutralised the rabies virus instead of weakening it. He tested the vaccine on fifty dogs who, after inoculation, did not contract rabies after being bitten by rabid dogs or being infected with the virus fixe. The virus’s long incubation period suggested that the vaccine would be suitable for prophylactic use even after exposure to rabies; Pasteur later proved this by having two dogs contract rabies and showing how the vaccinated dog survived whilst the unvaccinated one succumbed to the disease. Post-exposure prophylaxis was crucial to the survival of Joseph Meister—a nine-year-old boy who was brought to Pasteur for treatment after being attacked by a dog, but before showing symptoms of rabies. Pasteur was not fully confident in administering his rabies treatment to humans, but was compelled to apply it anyway because of the severity of the boy’s injuries (the dog bit him fourteen times) and because the dog that bit him had to be put down after showing symptoms of rabies. In July 1885, Joseph Meister received thirteen doses of the rabies vaccine, with the final inoculation containing a virulent form of rabies. He survived.
This was a medical breakthrough that would save millions of lives from the terrible impact of rabies. The day on which Pasteur died in 1895—September 28th—is commemorated as World Rabies Day in order to honour his discovery and legacy.
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Featured Image Credit: author, Unknown. English: Louis Pasteur Performing an Experiment. September 26, 2013. Britannica Kids. https://commons.wikimedia.org/wiki/File:Louis_Pasteur_experiment.jpg.
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