Louis Pasteur and the History of Rabies Vaccination Development
Prologue
Today, I’m going to tell you a story about a superstar who was not a doctor but will always be remembered by his thousands of patients worldwide. He was a multi-talented genius who is sometimes also referred to as the “father of bacteriology.” Yes, I think many of you have anticipated his name. His name is engraved in golden letters in the history of medicine. He was none else than Louis Pasteur. Apart from many other discoveries, his greatest discovery was the rabies vaccine because even today, there is no specific treatment for rabies, and once the clinical diagnosis is established, death is 100% confirmed. Today’s story is about this great son of France!
What is rabies?
Rabies is the oldest fatal zoonotic disease (disease transmitted to humans by animals) known to man, with cases dating back 4000 years. It is caused by variants of Lyssavirus belonging to the Rhabdovirus family, which are found in several animal species across the world. It causes encephalitis (inflammation of the brain) and salivary gland infection in human beings and mammals. Human beings are mainly infected by dog bites or scratches or by the saliva of an infected dog, cat, or bat via the licking of an abrated area. In England, the main animal transmitting the infection is the fox.
Drawing in 1886 named ‘M. Pasteur's experiments in Paris for the cure of hydrophobia - the doctor and some of his patients,’ showcasing Russian peasants bitten by a mad wolf at Beloi, Smolensk (top right), Pasteur examining a young English girl, one of a family of four, bitten by a mad Newfoundland dog (bottom centre), English children from Bradford, Yorkshire - all bitten by the same mad dog (bottom right)
What are the 5 stages of rabies?
Stage 1: Incubation Period (4 to 8 weeks)
The period between the bite from a rabid animal and the appearance of the first clinical manifestation of the disease is known as the incubation period. In the case of rabies, it is 9 days to a few months, but for all practical purposes, this period has been found to be 4 to 8 weeks. It has been observed that if the bite is severe or closer to the brain, the incubation period is shorter. During the incubation period, the virus travels from the site of the bite to the Central Nervous System without symptoms.
Stage 2: Prodromal Stage (2 to 10 days)
The features of this stage are just like any other viral infection, e.g., fever, headache, severe weakness, fatigue, etc.
Stage 3: Acute Neurological Stage (2 to 7 days)
Features seen in this stage are anxiety, encephalitis, and hydrophobia. Hydrophobia means fear of water. Let me explain it to you. The patient feels thirsty. But the moment he tries to drink some fluid, there is a severe spasm of the diaphragm and most of the inspiratory muscles (muscles responsible for breathing in or inhalation). At this moment, if the patient forcibly tries to swallow the drink, he feels a severe compressive symptom in his throat muscles, which prevents the patient from drinking any fluid. This is the basic process of hydrophobia.
This third stage may be of 2 types, namely -
Furious rabies or hyperactive rabies (80% of the cases) - In this type, in addition to hydrophobia, the patient exhibits aerophobia (fear of air), muscle spasm, hyperactivity, aggressive behaviour, hallucination, salivation, altered voice, tachycardia (increased heart rate), anisocoria (unequal size of pupil of two eyes), high fever, etc. This type of rabies usually lasts for a week.
Paralytic rabies or dumb rabies (20% of the cases) - In this type, the patient gets paraesthesia (feeling of numbness, tingling, pricking, chilling, or burning), fever, headache, neck rigidity, and gradually advancing paralysis from the site of the bite towards the brain. Ultimately, the patient passes into a coma within a month.
Stage 4: Coma (0 to 14 days)
In this stage, there is severe brain dysfunction, paralysis, and respiratory failure. The patient becomes unresponsive and needs ventilator support.
Stage 5: Death
Most cases result in death due to respiratory failure. Survival is extremely rare, with very few cases of recovery (often with severe neurological damage).
Lithograph by F. Pirodon showcasing rabies vaccination in Pasteur's clinic in Paris
How to diagnose rabies?
As per WHO, to date, no single approved tests are available to diagnose human rabies infection ante-mortem (before death). Diagnosing rabies can be challenging, especially in the early stages, since at that point in time the virus has not spread widely throughout the nervous system, and once it has spread to the nervous system, diagnosis is pointless as then it is too late. Therefore, multiple laboratory tests are often performed. Three gold standard tests give the most accurate diagnosis. They are -
RT-PCR test (ante-mortem test, i.e., via sample from the live human patient) - A sample of fresh tissue from the brain, Cerebrospinal fluid (CSF), saliva, or nuchal skin biopsy is tested using reverse transcription polymerase chain reaction (RT-PCR) to detect the rabies virus RNA.
Direct fluorescent antibody test or DFA (postmortem test, i.e., via sample from the dead suspected rabid animal) - It is performed on the brain tissue of a suspected animal after death. It uses fluorescently labeled antibodies to detect rabies virus antigens in brain tissue under a fluorescence microscope.
Direct rapid immunohistochemistry test or DRIT (postmortem test, i.e., via sample from the dead suspected rabid animal) - This is also performed on the brain tissue of a suspected animal after death. It is an alternative to the Direct Fluorescent Antibody (DFA) test. It uses enzyme-linked antibodies instead of fluorescent ones, allowing detection with a standard light microscope. It is preferred in regions where fluorescence microscopy is unavailable.
How to prevent/manage rabies?
Rabies prevention/management depends on whether exposure has occurred (prevention) or symptoms have developed (clinical management).
Pre-Exposure Prophylaxis or PrEP (Preventing rabies before exposure)
High-risk individuals (e.g., veterinarians, lab workers, travelers to rabies-endemic areas) should be vaccinated against rabies irrespective of a specific rabies exposure.
Post-Exposure Prophylaxis or PEP (Preventing rabies after exposure)
For normal people, if rabies exposure is suspected (for instance, the person was bitten or scratched by a potentially rabid animal), he/she must be immediately tested for rabies, and in parallel, post-exposure prophylaxis (PEP), i.e., a series of rabies vaccines, should be administered as soon as possible, even before test results confirm the infection. Once symptoms appear (which means the virus has already reached the Central Nervous System), rabies is nearly always fatal.
Clinical Management of Symptomatic Rabies (Managing Rabies Once Symptoms Appear)
Once rabies symptoms develop, no specific treatment exists even today, and the disease is almost always fatal. Following supportive care is provided -
Sedation and pain relief via Benzodiazepines, opioids supplemented by chlorpromazine
Seizure control via anti-epileptic drugs
Hydration and nutrition via IV fluids and enteral feeding
Ventilation support for respiratory failure
Chromolothograph of Pasteur inoculating a man with the rabies virus
A journey through Louis Pasteur’s life
Before we arrive at how Pasteur discovered the rabies vaccine, we need to take a journey through Pasteur’s life to understand what events led to the discovery of the vaccine. Louis Pasteur (27th December 1822 to 28th September 1895) was born in a place called Dole in France to Jean-Joseph Pasteur and Jeanne Etiennette Roqui. They were poor tanners belonging to a Catholic family. The family moved to Marnoz initially in 1826 and then shifted to Arbois in 1827. Pasteur was admitted to primary school in 1831. According to the school report, he was found to be suffering from dyslexia and dysgraphia. Dyslexic children are found to have difficulties in understanding written words, and dysgraphic children are found to have difficulties in writing a paragraph. In his early school days he was found to be more interested in drawing and fishing rather than studying.
However, he managed to get admission to a secondary school at Besancon. This was a turning point in his academic career. From Besancon Royal College, he completed his Bachelor of Arts in 1840, then went on to complete his Bachelor of Science in 1842, followed by his Master of Science in 1845, and his PhD in 1847. After he got his Doctorate he got an offer for the post of Professor of Physics at Dijon lycee secondary school in 1848. Soon thereafter, he got a chance to teach his favourite subject, chemistry, as a professor at the University of Strasbourg.
This was the place where he met Marie Laurent (daughter of the Rector of University), who became the Secretary and writing assistant of Louis Pasteur. After a short courtship, they got married on 29th May 1849. They were blessed with five children. But unfortunately they lost three of them in their childhood due to typhoid fever. These heartbreaking losses deeply affected Pasteur and likely strengthened his determination to fight infectious diseases through science.
The Fermentation Theory (1857)
Pasteur’s discovery journey started in the 1950s with the ‘Fermentation Theory.’ Pasteur studied how sugar turned into alcohol in wine and beer production and found out that microscopic living organisms called yeasts converted sugar into alcohol through biological activity, breaking the earlier belief that it was purely a chemical process.
But preserving this alcohol produced by the yeast was also a challenge. During the 1850s, French winemakers and brewers struggled with wine and beer turning sour. Some scientists thought spontaneous generation (the idea that life arises from non-living matter) was the cause. Pasteur suspected that some other microorganism (like yeast) was responsible for the spoilage. When he researched, he realized that wine and beer turned sour instead of fermenting properly due to the formation of lactic acid produced by a bacteria named lactobacillus. This discovery led him to propose that different microorganisms produce different fermentation products -
Good fermentation, i.e., alcohol fermentation (Ethanol) - caused by yeast
Bad fermentation, i.e., lactic acid fermentation (Spoilage) - caused by bacteria
This led to the ‘Fermentation Theory,’ which stated that fermentation was caused by living microorganisms, specifically yeasts and bacteria. This meant fermentation was a biological process rather than a chemical process, which was the earlier belief.
The Germ Theory of Disease (1861)
The above discovery led him to wonder if microbes could also cause diseases. This later led to the ‘Germ Theory of Disease’ where he stated that microorganisms (germs) are the cause of many diseases. This was a groundbreaking idea because, at the time, people believed diseases were caused by “miasma” (bad air) or “spontaneous generation” (life arising from non-living matter).
To prove Germ Theory and disprove the theory of ‘Spontaneous Generation,’ Pasteur designed his famous swan-neck flask experiment. He placed yeast water in a swan-necked flask that only allowed air to enter but trapped microbes. The broth remained sterile. Only when the flask was open to dust and micro-organisms did fermentation occur, proving that microbes came from the environment, not spontaneously. This experiment disproved spontaneous generation and supported the idea that microbes cause infections.
Glass flask used by Louis Pasteur
Pasteurization (1865)
In order to preserve liquor and prevent spoilage without altering the beverage's quality, Pasteur developed a mild heat treatment process. He found that heating wine to about 55°C (131°F) for a short time killed bacteria but preserved flavor. He later proposed that a similar process can also be applied to milk, fruit juices, and other beverages. The name of his method came to be known as the Pasteurization, which is a food preservation technique that focuses on partial sterilization by mild heating to eliminate germs and extend shelf life.
Pasteurization involves controlled heating of a liquid or food product to a specific temperature for a set time to kill harmful microorganisms, followed by rapid cooling to prevent recontamination and preserve quality.
Steps in the Pasteurization process
Heating Phase - The liquid (e.g., milk, juice, beer) is heated to a specific temperature.
Holding Phase - It is maintained at this temperature for a required time to kill bacteria.
Cooling Phase - The liquid is rapidly cooled to prevent the regrowth of bacteria, maintain taste, texture, and nutritional value, and extend shelf life.
Types of Pasteurization Techniques
| Method | Temperature | Time | Cooling | Application |
|---|---|---|---|---|
| Batch Pasteurization - Low-Temperature, Long-Time (LTLT) | 63°C (145°F) | 30 minutes | Slow cooling | Small-scale dairy processing (milk, cheese) |
| Flash Pasteurization - High-Temperature, Short-Time (HTST) | 72°C (161°F) | 15 seconds | Rapid cooling to 4°C (39°F) | Most commercial milk and juices |
| Sterilization - Ultra-High Temperature (UHT) | 135–150°C (275–302°F) | 2–5 seconds | Cooled to room temp | Long-shelf-life milk, boxed juices |
| Ultra-Pasteurization (UP) | 125°C (257°F) | 2–5 seconds | Rapid cooling | Extended-shelf-life dairy products |
Louis Pasteur working on Pasteurization techniques
Prevention of Silkworm Disease (1865 - 1869) and first major stroke (1868)
In the 1860s, France’s silk industry was struggling because of a mysterious disease that was killing silkworms. The disease had spread across Europe and Asia, causing massive economic losses. The condition was becoming worse, and all silk industries were likely to be closed by 1865. In 1865, Pasteur was asked by the French government to investigate and find a solution.
Pasteur analyzed the silkworms under a microscope and discovered that there were two separate diseases killing silkworms:
Pébrine – caused by a microscopic parasite (Nosema bombycis).
Flacherie – a bacterial infection worsened by poor hygiene.
Pasteur advised silkworm farmers to only breed healthy silkworm eggs by carefully inspecting them under a microscope. He also introduced hygiene measures, like keeping silkworm farms clean and isolating sick worms. By following his method, the silk industry gradually recovered. His findings also strengthened the ‘Germ Theory.’
The silkworm recovered, but Pasteur, due to the hard work during this period, had a major stroke in 1868, which limited his physical functions. He got paralysis of the muscles of his left side. In medical terminology, it is called left-sided hemiplegia. Despite physical restrictions, Pasteur did not stop his work, and now he concentrated on the development of vaccines.
String of silkworm cocoons, used by Pasteur in research on silkworm disease
Accidental Discovery of Chicken Cholera Vaccine (1879)
In the late 1870s, Pasteur was studying chicken cholera, a deadly disease in poultry. He cultured the causative bacteria (Pasteurella multocida) and infected chickens to study how the disease spread. One day, Pasteur’s assistant accidentally left a bacterial culture exposed to air while Pasteur was away. The bacteria, when left unused for weeks, became weakened (attenuated). When Pasteur returned, he used the old bacterial culture to infect chickens. Instead of dying, the chickens only developed mild symptoms and recovered. Curious, Pasteur then infected the same chickens with a fresh, virulent culture of P. multocida. To his surprise, the previously infected chickens survived, while newly infected ones died. Pasteur realized that weakened (attenuated) bacteria had stimulated the immune system without causing severe disease. This was the first artificially induced immunity against a bacterial infection and was a major breakthrough, as it led to the principle of vaccination and paved the way for vaccines against bacterial and viral diseases.
Chamberland filter used by Pasteur and Chamberland in work on chicken cholera and anthrax
Discovery of Anthrax Vaccine (1881)
In the 1870s, Robert Koch had already identified Bacillus anthracis as the cause of anthrax, a deadly disease affecting sheep, cattle, and humans. Pasteur wanted to find a way to prevent anthrax infections in animals.
Pasteur had already developed weakened cholera bacteria for a chicken cholera vaccine. He believed that exposing animals to a weakened form of B. anthracis could protect them from severe anthrax. Pasteur’s team, including Émile Roux, exposed B. anthracis bacteria to oxygen and heat, weakening them. This process inactivated the bacteria, preventing them from causing full disease while still triggering an immune response.
To prove his vaccine worked, Pasteur conducted a high-profile public test at Pouilly-le-Fort, France. 25 sheep were vaccinated (2 doses, 12 days apart). 25 sheep were left unvaccinated as a control group. After vaccination, all 50 sheep were exposed to live B. anthracis. All vaccinated sheep survived. All unvaccinated sheep died within a few days. The experiment was a major success, proving that vaccination could prevent anthrax.
Louis Pasteur in his laboratory researching on anthrax vaccine
Discovery of Rabies Vaccine (1885)
Inspired by the discovery of the Anthrax vaccine, Pasteur, wth the help of two doctors, started collecting the saliva and brain tissue of rabid dogs and rabbits. Pasteur needed to weaken the virus so it wouldn’t cause disease but could still stimulate immunity. He injected the virus into rabbits and monkeys. After the rabbits were dead, he used to take out the spinal cord and dry them for 5–15 days. Older, dried samples became less virulent, creating a weakened virus. Pasteur injected this weakened rabies virus into dogs and rabbits. The vaccinated animals survived even when later exposed to fully virulent rabies.
Then came the special moment when a mother brought her 9-year-old son to Pasteur. She said that her name is Marie Angelique and she comes from Alsace. She further told that her son Joseph Meister was attacked by a rabid dog and the dog has bitten her son for at last 12 to 14 times. The local people of the area told that there was no chance of survival for Joseph, and they also told the name of Pasteur, who was trying to save people who were bitten by rabid dogs. Dr. Pasteur highlighted the risk to the mother that if the experiment became unsuccessful, she could lose her son. Before Pasteur completed his sentence, the mother replied she was ready to accept any fate. Dr. Pasteur told the mother to wait because before they could go for the first human experiment, they would have to decide the matter in a meeting. Because Pasteur was not a doctor, he would have to depend on the suggestions of his medical board.
In the meeting, almost all were against human experiments at such an early stage. Only one doctor who was very close to Pasteur said if no one was ready to help, he alone would complete the experiment if Dr. Pasteur allowed him. His name was Dr. Grancher. Since Pasteur couldn’t legally treat patients, Dr. Grancher took responsibility for administering the first rabies vaccine to Joseph Meister. After some days, it was seen that all those people who were bitten by the rabid dog, along with Joseph, died except Joseph. The whole world was wonderstruck by this news and hailed him as a hero!
Dr. Grancher inoculating Joseph Meister in presence of Louis Pasteur
Foundation of the Pasteur Institute (1887)
In the meantime, Dr. Pasteur declared that he wished he had an institute called the Pasteur Institute. Well wishers of Dr. Pasteur immediately raised funds for the construction of such institute. Dr. Grancher was a tuberculosis specialist. So, after his job on rabid dog was over at the Pasteur institute, he wanted to go back to his original research work on tuberculosis. But Dr. Pasteur requested him to stay some time more with him. Dr. Grancher engaged himself to find out the suitable place for the erection of the new Pasteur Institute at Paris. Ultimately, the Pasteur Institute was built on June 4th, 1887, and the inauguration ceremony was held on 14th November, 1888. The inaugural address was given by Dr. Grancher as per the request of Pasteur. In the meantime Dr. Grancher became so popular that he was elevated to Grand Officer of the legion of honor by French President Sadi Carnot.
Statue of Louis Pasteur in La Sorbonne at Paris
Awards and Honors
Louis Pasteur (1822–1895) received numerous awards and honors for his groundbreaking work in microbiology, vaccination, and pasteurization e.g., Rumford medal (1856), Copley medal (1874), Grand Cross of the Legion of Honor (1881) which is the highest civilian and military honor in France, Albert medal (1882), Leeuwenhoek Medal (1895), etc. Pasteur was elected as a member of the French Academy of Sciences (1862), one of the highest scientific honors in France, and as a member of the French Academy of Medicine (1873) despite not being a doctor. He was also regarded as one of the greatest scientists of the 19th century.
Bronze statue of Louis Pasteur by Riccardo Galli, Italian artist
Death
Pasteur suffered from multiple strokes throughout his later life. His first major stroke occurred in 1868, which left him partially paralyzed on his left side. Despite his health issues, he continued working on vaccines and infectious diseases for over 25 years. Over time, his condition worsened, leading to a final stroke that ultimately caused his death. Pasteur spent his last days at his estate in Marnes-la-Coquette, surrounded by his family and close colleagues.
Epilogue
To conclude this story, I would like to reflect on the last words of Louis Pasteur. In the final days of his life, Pasteur was severely affected by multiple strokes, leaving him physically weakened and unable to speak much. However, his mind remained sharp and focused. Before he left for his heavenly abode, lying on his death bead, he murmured for one last time, "I cannot, but I must." These simple yet profound words reflected his lifelong dedication to science, even in the face of such physical adversity. I hope the next generation reads about Louis Pasteur's legacy and takes inspiration from his unbreakable spirit and unwavering commitment to the pursuit of knowledge!
This article is authored by my father Dr. Kamal Kumar Sengupta. He is a retired doctor with a five-decade-long career as an eye surgeon, a patented inventor of ophthalmic surgical instruments, and an author of ocular pharmacology textbooks. Post-retirement, he decided to invest his time in writing motivational stories from across the globe that will inspire future generations to experience the world, explore ideas, and follow their dreams. I hope you liked this article and if you did, don’t forget to let us know in the comments below!
All images in the article are royalty-free images from jstor.org used for visualization purposes only. We hold no copyright on the images.
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