How Sheep’s Blood Helped Disprove This Wacky Nineteenth-Century Theory of Illness

Scientists didn’t understand that bacteria caused disease, but then enter Louis Pasteur

Kat Eschner

sheep.jpg

Long before it was put into letters to major news outlets , anthrax was a major problem for livestock farmers.

Whole herds died in so-called "cursed fields," and human lives as well as the food supply were threatened. But until people started to understand bacteria and how it spread, the future wasn't looking good.

Back in the 19th century, before it was definitively known that bacteria and viruses caused illness by being spread from host to host, many people subscribed to the theory of "spontaneous generation"—that living organisms could be generated from non-living matter. By the late 19th century, writes Encyclopedia Britannica , scientists had ceased to believe that, for instance, cheese could spontaneously generate mice, but spontaneous generation at the microbial level was still accepted.

That meant that when scientists studied diseases like anthrax and even found anthrax bacteria in an infected animal’s bloodstream, they didn’t understand that the bacteria had anything to do with the disease, and assumed that it was either a symptom or an unrelated phenomenon. Meanwhile, bacterial diseases spread unchecked. 

Enter French scientist Louis Pasteur, already famous for his work with preserving milk and other foodstuffs through pasteurization. His work on developing an anthrax vaccine helped scientists understand how people (and animals) got sick. On this day in 1877,  Pasteur went to a slaughterhouse at Chartres, France, to get blood samples from the corpses of animals who died of anthrax. It was the beginning of an interest in the disease that would lead to the first vaccine for anthrax and more proof of the germ theory of disease.

Animals that eat plants are more susceptible to anthrax than humans or other species, writes the World Health Organization, although humans can and do get anthrax by coming into contact with infected animals or eating their meat. The herbivores frequently get the infection by eating grass or other plants that have been contaminated with Bacillus anthracis , a bacterium which can live for decades without a host. 

Animal doctors and scientists couldn’t agree on the cause of anthrax, just like they couldn’t reach scientific consensus on the cause of any other infection. They could see a bacterium in the blood of beasts that died of anthrax—but scientists who supported spontaneous generation maintained that the bacteria was unrelated to the disease.

Pasteur was working on a hunch: not long before he started his work, a microbiologist named Robert Koch had isolated a bacteria that he theorized caused anthrax. Koch built on work Pasteur had previously done, and in turn Pasteur (who was famously competitive) built on Koch's work with anthrax. They both believed bacteria caused disease, but that theory was controversial at the time, and anthrax was at the fore of the controversy. “Scientists all over Europe raced to prove or disprove its tenets using different diseases, most notably anthrax,” write molecular biologists Erika R. Sams, Marvin Whiteley and Keith H. Turner.

Chartres, a French city, had suffered a number of anthrax outbreaks in animals, writes medical historian Steven Lehrer. Pasteur started there. “At a local slaughterhouse, [Pasteur] obtained anthrax-infested blood from the carcasses of a horse, a sheep and a cow,” Lehrer writes. That blood formed part of the basis of a paper he published in a French science journal about a month later—the beginning of research into anthrax that would be important to developing the first vaccine for anthrax and debunking the spontaneous generation theory of disease once and for all.

But despite his advances, Pasteur never fully understood germs, and nor did many of his contemporaries. He instead believed that germs caused diseases by essentially sucking out nutrients. However, Pasteur's incomplete knowledge of germ theory still allowed him to develop vaccines for anthrax and rabies, saving many lives in the process.

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Kat Eschner | | READ MORE

Kat Eschner is a freelance science and culture journalist based in Toronto.

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  • Scientific Biographies

Louis Pasteur

During the mid- to late 19th century, Pasteur demonstrated that microorganisms cause disease and discovered how to make vaccines from weakened, or attenuated, microbes. He developed the earliest vaccines against fowl cholera, anthrax, and rabies.

louis pasteur sheep experiment

Louis Pasteur (1822–1895) is revered by his successors in the life sciences as well as by the general public. In fact, his name provided the basis for a household word— pasteurized .

His research, which showed that microorganisms cause both fermentation and disease, supported the germ theory of disease at a time when its validity was still being questioned. In his ongoing quest for disease treatments he created the first vaccines for fowl cholera; anthrax, a major livestock disease that in recent times has been used against humans in germ warfare; and the dreaded rabies.

Early Life and Education

Pasteur was born in Dole, France, the middle child of five in a family that had for generations been leather tanners. Young Pasteur’s gifts seemed to be more artistic than academic until near the end of his years in secondary school. Spurred by his mentors’ encouragement, he undertook rigorous studies to compensate for his academic shortcomings in order to prepare for the École Normale Supérieure, the famous teachers’ college in Paris. He earned his master’s degree there in 1845 and his doctorate in 1847.

Study of Optical Activity

While waiting for an appropriate appointment, Pasteur continued to work as a laboratory assistant at the École Normale. There he made further progress on the research he had begun for his doctoral dissertation—investigating the ability of certain crystals or solutions to rotate plane-polarized light clockwise or counterclockwise, that is, to exhibit “optical activity.” He was able to show that in many cases this activity related to the shape of the crystals of a compound.

He also reasoned that there was some special internal arrangement to the molecules of such a compound that twisted the light—an “asymmetric” arrangement. This hypothesis holds an important place in the early history of structural chemistry—the field of chemistry that studies the three-dimensional characteristics of molecules.

Fermentation and Pasteurization

Louis Pasteur in his laboratory, holding a jar containing the spinal cord of a rabbit infected with rabies, which he used to develop a vaccine against the disease.

Pasteur secured his academic credentials with scientific papers on this and related research and was then appointed in 1848 to the faculty of sciences in Strasbourg and in 1854 to the faculty in Lille. There he launched his studies on fermentation. Pasteur sided with the minority view among his contemporaries that each type of fermentation is carried out by a living microorganism.

At the time the majority believed that fermentation was spontaneously generated by a series of chemical reactions in which enzymes—themselves not yet securely identified with life—played a critical role.

In 1857 Pasteur returned to the École Normale as director of scientific studies. In the modest laboratory that he was permitted to establish there, he continued his study of fermentation and fought long, hard battles against the theory of spontaneous generation. Figuring prominently in early rounds of these debates were various applications of his pasteurization process, which he originally invented and patented (in 1865) to fight the “diseases” of wine.

He realized that these were caused by unwanted microorganisms that could be destroyed by heating wine to a temperature between 60° and 100°C. The process was later extended to all sorts of other spoilable substances, such as milk.

Germ Theory

At the same time Pasteur began his fermentation studies, he adopted a related view on the cause of diseases. He and a minority of other scientists believed that diseases arose from the activities of microorganisms—germ theory. Opponents believed that diseases, particularly major killer diseases, arose in the first instance from a weakness or imbalance in the internal state and quality of the afflicted individual.

In an early foray into the causes of particular diseases, in the 1860s, Pasteur was able to determine the cause of the devastating blight that had befallen the silkworms that were the basis for France’s then-important silk industry. Surprisingly, he found that the guilty parties were two microorganisms rather than one.

A New Laboratory

Pasteur did not, however, fully engage in studies of disease until the late 1870s, after several cataclysmic changes had rocked his life and that of the French nation. In 1868, in the middle of his silkworm studies, he suffered a stroke that partially paralyzed his left side. Soon thereafter, in 1870, France suffered a humiliating defeat at the hands of the Prussians, and Emperor Louis-Napoléon was overthrown. Nevertheless, Pasteur successfully concluded with the new government negotiations he had begun with the emperor.

The government agreed to build a new laboratory for him, to relieve him of administrative and teaching duties, and to grant him a pension and a special recompense in order to free his energies for studies of diseases.

Attenuating Microbes for Vaccines: Fowl Cholera and Anthrax

In his research campaign against disease Pasteur first worked on expanding what was known about anthrax, but his attention was quickly drawn to fowl cholera. This investigation led to his discovery of how to make vaccines by attenuating, or weakening, the microbe involved. Pasteur usually “refreshed” the laboratory cultures he was studying—in this case, fowl cholera—every few days; that is, he returned them to virulence by reintroducing them into laboratory chickens with the resulting onslaught of disease and the birds’ death.

Glassware of the same type Louis Pasteur would have used to culture microorganisms.

Months into the experiments, Pasteur let cultures of fowl cholera stand idle while he went on vacation. When he returned and the same procedure was attempted, the chickens did not become diseased as before. Pasteur could easily have deduced that the culture was dead and could not be revived, but instead he was inspired to inoculate the experimental chickens with a virulent culture. Amazingly, the chickens survived and did not become diseased; they were protected by a microbe attenuated over time.

Realizing he had discovered a technique that could be extended to other diseases, Pasteur returned to his study of anthrax. Pasteur produced vaccines from weakened anthrax bacilli that could indeed protect sheep and other animals. In public demonstrations at Pouilly-le-Fort before crowds of observers, twenty-four sheep, one goat, and six cows were subjected to a two-part course of inoculations with the new vaccine, on May 5, 1881, and again on May 17. Meanwhile a control group of twenty-four sheep, one goat, and four cows remained unvaccinated.

On May 31 all the animals were inoculated with virulent anthrax bacilli, and two days later, on June 2, the crowd reassembled. Pasteur and his collaborators arrived to great applause. The effects of the vaccine were undeniable: the vaccinated animals were all alive. Of the control animals all the sheep were dead except three wobbly individuals who died by the end of the day, and the four unprotected cows were swollen and feverish. The single goat had expired too.

Rabies and the Beginnings of the Institut Pasteur

Pasteur then wanted to move into the more difficult area of human disease, in which ethical concerns weighed more heavily. He looked for a disease that afflicts both animals and humans so that most of his experiments could be done on animals, although here too he had strong reservations. Rabies, the disease he chose, had long terrified the populace, even though it was in fact quite rare in humans. Up to the time of Pasteur’s vaccine, a common treatment for a bite by a rabid animal had been cauterization with a red-hot iron in hopes of destroying the unknown cause of the disease, which almost always developed anyway after a typically long incubation period.

Rabies presented new obstacles to the development of a successful vaccine, primarily because the microorganism causing the disease could not be specifically identified; nor could it be cultured in vitro (in the laboratory and not in an animal). As with other infectious diseases, rabies could be injected into other species and attenuated. Attenuation of rabies was first achieved in monkeys and later in rabbits.

Meeting with success in protecting dogs, even those already bitten by a rabid animal, on July 6, 1885, Pasteur agreed with some reluctance to treat his first human patient, Joseph Meister, a nine-year-old who was otherwise doomed to a near-certain death. Success in this case and thousands of others convinced a grateful public throughout the world to make contributions to the Institut Pasteur.

Historian Bert Hansen discusses his book,  Picturing Medical Progress from Pasteur to Polio.

It was officially opened in 1888 and continues as one of the premier institutions of biomedical research in the world. Its tradition of discovering and producing vaccines is carried on today by the pharmaceutical company Sanofi Pasteur.

A Great Experimenter and Innovative Theorist

Pasteur’s career shows him to have been a great experimenter, far less concerned with the theory of disease and immune response than with dealing directly with diseases by creating new vaccines. Still it is possible to discern his notions on the more abstract topics. Early on he linked the immune response to the biological, especially nutritional, requirements of the microorganisms involved; that is, the microbe or the attenuated microbe in the vaccine depleted its food source during its first invasion, making the next onslaught difficult for the microbe.

Later he speculated that microbes could produce chemical substances toxic to themselves that circulated throughout the body, thus pointing to the use of toxins and antitoxins in vaccines. He lent support to another view by welcoming to the Institut Pasteur Élie Metchnikoff and his theory that “phagocytes” in the blood—white corpuscles—clear the body of foreign matter and are the prime agents of immunity.

Featured image: Portrait of Louis Pasteur , photograph of Louis Pasteur taken in 1886, reproduced in the 1911 biography   The Life of Louis Pasteur . Science History Institute

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How solving this medical mystery saved lives

In this episode, we’ll tell the tale of how a 19th-century duel led to a medical breakthrough. Chemist Louis Pasteur was challenged to prove that invisible agents (germs) caused diseases, and he did so by using sheep. With the world’s media at attention and 50 sheep at the ready, the science community waited with bated breath for the reveal that would revolutionize medical science and save countless lives.

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How Solving This Medical Mystery Saved Lives

In this episode, we’ll tell the tale of how a 19th-century duel led to a medical breakthrough. Chemist Louis Pasteur was challenged to prove that invisible agents (germs) caused diseases, and he did so by using sheep. With the world’s media at attention and 50 sheep at the ready, the science community waited with bated breath for the reveal that would revolutionize medical science and save countless lives.

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Experimentation du virus charbonneux: “Le Pelerin,” 1922. Homage a Louis Pasteur. Dessin de Damblans.

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Figure

Experimentation du virus charbonneux: “Le Pelerin,” 1922. Homage a Louis Pasteur. Dessin de Damblans

In 1881, Louis Pasteur announced his theory that vaccinating livestock, in effect giving animals a disease, would protect them from that disease. Many contemporaries of Pasteur were skeptical about this radical idea as they were skeptical about the germ theory of disease. One of these contemporaries, the famous veterinarian Monsieur H. Rossignol, challenged Pasteur to test his theory in public by vaccinating animals on his farm at Pouilly-Le-Fort, a small village outside Paris.

Rossignol’s challenge came early in Pasteur’s efforts to prove the germ theory of disease and develop vaccines. No vaccine had been tested yet outside the laboratory. The risk of having something go wrong with the experiment was very high. Pasteur, however, took the challenge, confident that what had worked with 14 sheep in the laboratory would work with 50 in the field.

In early May, 25 animals at Rossignol’s farm were inoculated for “charbon,” a disease now known as anthrax. Another 25 received no vaccine. On May 31, all 50 animals were injected with a culture of very virulent anthrax. Within 2 days, a group of farmers, veterinarians, pharmacists, and agriculture officials gathered at Rossignol’s farm to observe the results of the experiment. The results were as Pasteur had anticipated: all 25 sheep that had not been inoculated had died; all 25 inoculated sheep were in perfect health.Those gathered at Pouilly-Le-Fort that day witnessed the first successful vaccine and the introduction of effective protection against anthrax.

Anthrax, an ancient disease reported by Homer and Hippocrates as extremely deadly, killed thousands of animals each year. Pasteur’s vaccine provided not only protection against anthrax but also proof for the germ theory of disease. Protection against anthrax opened the door for vaccines against smallpox and other diseases. From Pasteur’s work emerged the disciplines of immunology and bacteriology, which eventually led to vaccination of millions of people and prevention of many diseases.

Abstracted from Hero for Our Time by Paul Trachtman, Smithsonian, January 2002.
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  2. PASTEUR, Louis (1822-1895) French chemist and bacteriologist

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  4. LOUIS PASTEUR (1822-1895). /nFrench chemist and microbiologist. Pasteur

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COMMENTS

  1. How Sheep’s Blood Helped Disprove This Wacky Nineteenth ...

    His work on developing an anthrax vaccine helped scientists understand how people (and animals) got sick. On this day in 1877, Pasteur went to a slaughterhouse at Chartres, France, to get blood...

  2. Anthrax vaccine - Wikipedia

    In May 1881, Pasteur performed a famous public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat and several cows. The animals of one group were twice injected, with an interval of 15 days, with an anthrax vaccine prepared by Pasteur; a control group was left unvaccinated.

  3. Louis Pasteur - Science History Institute

    Pasteur produced vaccines from weakened anthrax bacilli that could indeed protect sheep and other animals. In public demonstrations at Pouilly-le-Fort before crowds of observers, twenty-four sheep, one goat, and six cows were subjected to a two-part course of inoculations with the new vaccine, on May 5, 1881, and again on May 17.

  4. The first live attenuated vaccines - Nature

    Awareness of Edward Jenner’s pioneering studies of smallpox vaccination (Milestone 2) led Louis Pasteur (1822–1895) to propose that vaccines could be found for all virulent diseases.

  5. How solving this medical mystery saved lives

    What do milk, sheep, and vaccines have in common? Louis Pasteur. Learn how he helped prove to the world that germs cause disease and usher in an unprecedented era of medical breakthroughs.

  6. How Solving This Medical Mystery Saved Lives - Education

    In this episode, we’ll tell the tale of how a 19th-century duel led to a medical breakthrough. Chemist Louis Pasteur was challenged to prove that invisible agents (germs) caused diseases, and he did so by using sheep.

  7. Pasteur's life and pioneering work - The Lancet

    In a controlled experiment in front of witnesses, Pasteur exposed two groups of 25 sheep to virulent anthrax; the entire unvaccinated control group died, whereas those vaccinated with five drops of attenuated anthrax bacilli survived.

  8. MILESTONE 3 The first live attenuated vaccines - Nature

    The first live attenuated vaccines. Awareness of Edward Jenner’s pioneering studies of smallpox vaccination (MILESTONE 2) led Louis Pasteur (1822–1895) to propose that vaccines could be found...

  9. Pasteur, Louis (1822-1895) -- from Eric Weisstein's World of ...

    When 50 sheep were then injected with anthrax, all 25 control sheep died while all inoculate sheep survived. Therefore, Pasteur demonstrated that the weakened anthrax lost its virulence but still could confer immunity.

  10. Experimentation du virus charbonneux: “Le Pelerin,” 1922 ...

    Experimentation du virus charbonneux: “Le Pelerin,” 1922. Homage a Louis Pasteur. Dessin de Damblans. In 1881, Louis Pasteur announced his theory that vaccinating livestock, in effect giving animals a disease, would protect them from that disease.