Louis Pasteur's Battle with Microbes and the Founding of Microbiology
Louis Pasteur's Battle with Microbes and the Founding of Microbiology
In 1800 the origins of infectious diseases were unknown and as mysterious as they had been in the Middle Ages. By 1900 the causes of many of these diseases that ravaged humans throughout history had been discovered, and methods such as vaccination and improved sanitation were being developed to deal with them. The main figure in this achievement was Louis Pasteur (1822-1895), a French scientist who first demonstrated the crucial role microbes (microscopic organisms) play in the life process. He established the germ theory of disease and was the first to show that vaccines against infectious diseases can be manufactured. Vaccinations against viral diseases, antibiotics, infection-free surgery, safe milk and food, effective sanitation systems: all these developments owe much to Pasteur, the founder of modern microbiology (the study of unicellular microorganisms and their activities).
In the early nineteenth century science and medicine seemed no farther advanced than they had been half a millennium earlier. Aristotle's concept that many plants and small animals were spontaneously generated from soil or decaying animal matter still influenced scientists. In medicine many still believed that human health was determined by internal "humors" that could be treated by drawing off the patient's blood. Blood-letting was so widespread that in 1833, 41 million leeches for this purpose were imported into France alone. Most importantly, although the existence of microbes had been known for two hundred years, very few scientists suspected, and no one had proven, their role in causing diseases.
As a result, infectious diseases such as tuberculosis, cholera, post-operative infection, typhoid, diphtheria, syphilis, puerperal (childbirth) fever, and malaria killed tens of thousands of people in Europe and America annually; millions more died worldwide from these and other infectious diseases such as yellow fever and plague. Cholera, for example, killed 145,000 people in France in 1854. Microbes also had a devastating economic impact by causing diseases that killed animals. Infectious diseases periodically struck the poultry, sheep, silkworm, and swine industries. In addition, problems caused by microbes in the vinegar, wine, and beer industries often spoiled production.
Although many nineteenth-century scientists struggled with these diseases, Pasteur is most often considered the founder of microbiology, in part for his remarkable success in dealing with many of these problems. Also, in science such credit often goes to the individual who convinces the world. Pasteur was very ambitious and vigorously sought recognition for his work, missing few opportunities to make it known to as wide an audience as possible. One of his assistants said Pasteur "neglected nothing . . . [in trying] to attract attention." It was these public relations activities that convinced the world of the importance of microbes.
Pasteur also benefited from the support of the vast hygiene movement that developed in Europe to combat diseases such as cholera and typhoid. Not knowing the causes of these diseases, the hygienists used scientifically worthless terminology such as "contagion," "miasma," and "morbid spontaneity." Since Pasteur's germ theory convincingly explained everything they could not, the hygienists threw the support of their powerful movement behind him, a major reason for Pasteur's deification in French and European public opinion.
In 1855 Pasteur was teaching chemistry in Lille, an industrial city in northern France. Microbiology got its start when he became interested in fermentation problems at a local distillery where sugar beets were fermented to alcohol through the addition of yeast. This led to his first encounter with microbes. Anton van Leeuwenhoek (1632-1723) had discovered microorganisms when, using microscopes, he found that uncountable billions of minute "animalcules" existed everywhere. But until Pasteur microorganisms had been studied only to establish their morphology (form and structure) and taxonomy (relationship to other microbes). Few nineteenth-century scientists suspected that microbes could cause disease; the idea that invisible organisms could kill humans and cattle seemed preposterous. Improved microscopes, Pasteur's skill in using them, and his intuitive genius would change that view. He would need these tools; microorganisms are extraordinarily diverse (some need air to live, others die in it; some thrive in cold environments, others succumb when deprived of heat). The fact that many microbes, particularly viruses, were too small to be seen with existing microscopes created further difficulties.
Pasteur's work on sugar beet ferment led to his announcement in 1857 that, contrary to the opinion of leading chemists, the yeast used in the process was a living microbe and necessary for successful fermentation. He found that the vats where the process failed contained no yeast, but instead had smaller microbes that killed the yeast. He concluded that microbes were living, and sometimes harmful, organisms. He also discovered the microbes that caused milk to turn sour and expanded his research into fermentation problems in the wine industry (and later into the brewing industry). He again discovered that microbes existed that could spoil the fermentation process. He found that if wine was heated for a brief period, the harmful microbes would be destroyed but the wine remained sound. Because of this, the heating of milk, wine, juices, and other liquids and food products to prevent the growth of harmful microorganisms is called "pasteurization."
Pasteur's work on fermentation brought him into a debate over spontaneous generation. While no scientist still believed that animals such as flies and mice spontaneously developed out of decaying matter, many assumed that microbes did spontaneously generate; in 1859 Félix Pouchet published a paper "proving" it. Pasteur disagreed. One of his talents was his ability to design clever experiments validating his contentions. In the controversy that followed, Pasteur's experimental genius led him to devise several methods to show that the microbes were carried in the air and did not arise spontaneously on nutrient-rich surfaces. In the most famous, he made flasks with long, narrow, horizontally curving "gooseneck" openings. Nutrient solutions were heated in the flasks to purify them: then Pasteur let unfiltered air enter through the gooseneck openings. Microbes settled in the curve of the goosenecks, but none appeared in the solutions, proving that air carried microbes but did not cause them to develop spontaneously.
Pasteur, now living permanently in Paris, announced in 1862 that he was going to apply his germ theory of fermentation to the study of disease. The few other scientists who also believed infectious diseases were caused by microorganisms could not prove it with conclusive experimental evidence. Pasteur's first chance to do so came in 1865, when the government asked him to investigate why large numbers of silkworms were dying. After several years of experiments, he concluded that the silkworms were suffering from diseases caused by two different microbes. By 1866 he had developed a method allowing growers to isolate the healthy from the diseased worms, thus saving the industry.
Evidence was accumulating that Pasteur's germ theory was correct. A cholera epidemic (1854) in London let John Snow (1813-1858) demonstrate that proper sanitation was essential in fighting contagious diseases. In the 1860s Joseph Lister (1827-1912) developed antiseptic methods that killed bacteria during and after operations, greatly reducing deaths in surgery. In 1874 Lister credited Pasteur's germ theory with furnishing him with the "principle upon which alone the antiseptic system can be carried out." In Hungary Ignaz Semmelweis (1818-1865) announced in 1861 that he had greatly reduced deaths of women in labor through the use of antiseptics. Pasteur infuriated French physicians by constantly lecturing them that microbes on their unclean clothing, hands, and unsterile instruments were killing women in childbirth. By the 1880s the medical profession was won over to the importance of inhibiting the growth of microorganisms with antiseptics.
Meanwhile, a German doctor, Robert Koch (1843-1910), was also using the microscope as a weapon against disease. Staining his samples for better visibility and identification, Koch isolated the microbes that cause anthrax, cholera, and tuberculosis. While Koch was isolating and identifying various microbes of disease, Pasteur was heading in a more pragmatic direction. Edward Jenner (1749-1823) had used the fact that milkmaids who got cowpox (a mild disease) never contracted smallpox (a deadly disease) to develop the practice of vaccination. He injected small amounts of cowpox fluid into people, who were then protected against smallpox. No one knew what caused smallpox, but Jenner had shown that vaccination could prevent the disease. Pasteur wondered if he could develop vaccines for animal diseases in his laboratory. This had never been done before; Jenner's smallpox vaccine occurred naturally as cowpox.
The breakthrough came in 1880 when Pasteur was working on the microbe that causes fowl (chicken) cholera. He discovered that if he kept cultures of the microbe for long periods of time and then inoculated chickens with them, the fowls recovered from the disease. When he inoculated the same chickens with the most virulent pure culture, the animals were not affected—they were immune. He had invented a vaccine for fowl cholera. This discovery opened a whole new branch of microbiology, the study of immunity. Pasteur realized that weak microbes had stimulated the host (the chickens) to produce substances (antibodies) that protected them in the future. He now sought to apply this process of attenuation (weakening) to other microbe-caused diseases.
Fowl cholera was a rare disease. Anthrax, on the other hand, was a common and costly disease that killed thousands of animals annually. So in 1881, when Pasteur announced he had developed an anthrax vaccine on the same principle as his fowl cholera vaccine, he attracted international attention to a public test of it at Pouilly-le-Fort. Twenty-four sheep and a few cows were injected with Pasteur's vaccine; a similar number of sheep and cows were not. Two weeks later both groups were given lethal doses of anthrax culture. All the vaccinated animals lived, all the unvaccinated animals died, creating a milestone in the history of microbiology. Pasteur marketed the vaccine, and deaths caused by anthrax became rare. He also developed a vaccine against swine fever that was sold throughout Europe, further increasing his fame and spreading the concept of immunization.
Pasteur now decided to try to develop a vaccine for hydrophobia (rabies in humans). He could not identify the microbe causing rabies because it was a virus, too small to be seen by the microscopes of the period. Nor could he cultivate it in his laboratory, because viruses can only multiply in living cells. He injected the invisible microbe, which was known to be in the saliva of rabid animals, into rabbits. Since rabies attacks the nervous system, after the rabbits died he dried their spinal cords for several weeks. From these spinal cords he prepared a new solution that contained the microbe and injected it into a second series of rabbits. He repeated the procedure a dozen times, then vaccinated some dogs with the attenuated microbes. When they were bitten by rabid dogs, they were immune to the disease. But since all the dogs in France could not be vaccinated, Pasteur decided to try the vaccine on unvaccinated dogs after they had been bitten by rabid animals, but before the symptoms appeared. The procedure worked: the bitten dogs did not develop rabies.
The question was whether the same procedure would work on humans bitten by rabid animals. In 1885 Pasteur treated a boy badly bitten by a rabid dog with his vaccine; the boy survived, showing no symptoms of rabies. This was the first successful human vaccination with a manufactured vaccine. After successfully treating a second bite victim later that year, Pasteur became internationally famous. Within a few months victims of rabid animal attacks from as far away as Newark, New Jersey, and Smolensk, Russia, came to Paris for his vaccine. Contributions poured in, allowing him to build the Pasteur Institute; a building in which, because of failing health, he never worked. But he had made his contributions to science. He had convinced the world that microbes were alive, were connected to disease, and could be successfully battled by vaccination.
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