Winning scientific support for the germ theory of disease and thus revolutionizing the practice of truly effective medicine
LOUIS PASTEUR
(1822–1895)
Louis Pasteur came from an age of heroic science, created by the scientists Paul de Kruif profiled in his 1926 classic The Microbe Hunters—which included Pasteur among eleven others. They were explorers who dared confront the threats posed by an indifferent nature, an ignorant society, and, all too often, their own hidebound colleagues. Reading such a celebratory author like de Kruif today is to feel we are reading popular mythology rather than objective history. But the likes of Pasteur were in fact the knights of science, and the discoveries they made disrupted long-held beliefs, changed civilization, and struck a selfless blow for the value of fact-based enterprise and action in the service of saving and improving life. In the case of Louis Pasteur, by discovering that microorganisms cause both fermentation (vital to the wine industry, which was in turn vital to France) and disease (a threat to life), he advanced the science of vaccination in a world-changing way and closed the gap between the theorist and the experimentalist in science.
Louis Pasteur was born on December 27, 1822, in Dole, France, the middle child of five in a family of leather tanners. As a child, there was no hint of the scientist he would become. He was a passable student in elementary school, but his passion was not in his textbooks. He was an avid fisherman who also enjoyed drawing—a talent his neighbors and friends appreciated, since he gave away the many portraits he sketched. He earned a degree in philosophy and another in science and mathematics. The latter proved tough going for him, and he failed his first examination. Persevering, he went on to earn a degree in general science in 1842 and decided to venture the entrance exam for the École Normale Supérieure, the prestigious Parisian teachers’ college. Only through very hard work did he pass the entrance exam—and with a very high ranking. In 1845, Pasteur earned his master’s degree in science and, two years later, a doctorate, writing not one but two theses, in physics and in chemistry. He taught as a professor at the Dijon Lycée in 1848 and was subsequently appointed professor of chemistry at the University of Strasbourg. There he met, courted, and, in 1849, married Marie Laurent, daughter of the university rector. The marriage was fruitful, producing five children—but in an age in which bacterial disease was a poorly understood scourge, three of the Pasteur children would die of typhoid before reaching adulthood.
While waiting to find a full-time academic position, Pasteur had supported himself as a laboratory assistant at the École Normale. He used the laboratory there to pursue the research he had begun for his doctoral dissertation in chemistry, studying the property of “optical activity” exhibited by certain crystals or solutions, which rotate plane-polarized light clockwise or counterclockwise. Through exquisitely acute observation—perhaps his single greatest strength as a scientist—Pasteur showed that such optical activity was most often related to the shape of the crystals of a compound. From this, he concluded that it was the internal arrangement within the molecules themselves that twisted the light. This is a foundational hypothesis in the early development of structural chemistry, the study of molecules in three dimensions.
In 1852, Pasteur was promoted to chairman of the chemistry department at the University of Strasbourg and, two years later in 1854, accepted appointment as the first dean of the newly created faculty of sciences at Lille University. Here he began a long research project into the nature of fermentation, an important natural process, of course, but one of special concern to the French, whose lifestyle and economy were closely bound up with the making and consuming of wine.
The prevailing belief was that fermentation was a spontaneous process created by chemical reactions involving enzymes, which, at the time, were not yet directly associated with living organisms. Pasteur took the view of a small minority of scientists, that all fermentation is carried out by living microorganisms. By 1858, he was ready to publish his proofs, which were based on extremely precise observation and a well-informed idea of what to look for. “In the field of observation,” he told an audience at a ceremony marking his inauguration to the Faculty of Letters of Douai and the Faculty of Sciences of Lille, “chance favors only the prepared mind.”
Pasteur not only showed that fermentation was a biological process produced by the action of microorganisms, but that when the “wrong” microorganism contaminated wine, lactic acid, not just alcohol, was created, making the wine sour and spoiling it. Armed with this knowledge, Pasteur went on to create his “pasteurization” process in 1865. He found that when “raw” wine was heated to between 60°C and 100°C, the microorganisms that fermented the wine as lactic acid were killed, leaving only those that fermented it to alcohol. This process was a boon to the French wine industry. Pasteurization was later extended to many other spoilable substances and foodstuffs, most notably milk. Pasteur was not practicing “pure” theoretical science, but science in the service of life and livelihood.
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Pasteur was capable of intense focus, yet his vision was never monolithic. His studies of fermentation led him to believe that many diseases were, like fermentation, caused by microorganisms. This so-called germ theory was not Pasteur’s discovery: it had been adumbrated as early as the 1670s by Anton van Leeuwenhoek (1632–1723), the early pioneer of microscopy and microbiology. Between 1808 and 1813, the Italian entomologist Agostino Bassi (1773–1856) demonstrated that a microscopic “vegetable parasite” caused a costly disease of silkworms. Other scientists had their suspicions as well, but, even as late as the 1860s, the vast majority of physicians rejected the germ theory, arguing that the chief factor in any disease was some flaw, weakness, or imbalance within the body of the victim.
To Pasteur, this was a non-answer. In the 1860s, he took up where Bassi had left off, looking for the precise cause of pébrine, a silkworm disease wreaking havoc on the French silk industry. He isolated the microorganism associated with the disease (Nosema bombycis—the name supplied by another researcher in 1870) and created a method by which silkworm eggs could be screened for infection, and the infected eggs discarded and destroyed. As he had done for wine, so Pasteur did for silk: he saved an industry.
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In 1868, while he was engaged in his silkworm studies, Pasteur suffered a stroke, which left him partially paralyzed on the left side. Two years later, France was defeated in the Franco-Prussian War (1870–1871). In the aftermath of the war, Emperor Louis-Napoléon, with whom Pasteur had entered into negotiations for a new state-of-the-art laboratory, was overthrown. Such was Pasteur’s hard-won prestige, however, that the new republican government did not hesitate to agree to fund a new laboratory and to award Pasteur a salary sufficient to free him from his academic and administrative duties so that he could devote himself exclusively to the study of disease.
His first target was anthrax, a costly scourge of livestock. In the course of studying this disease, however, one of those happy accidents that bring a breakthrough to the “prepared mind” drew Pasteur to make a detour into the study of fowl (or chicken) cholera. From an eminent veterinarian, he received cultures of fowl cholera, which he cultivated using chicken broth. Some of the culture was spoiled, however, and failed to infect Pasteur’s experimental chickens. Not wanting to waste the still-healthy birds, he attempted to infect them with a fresh culture—only to discover that they would not get sick. His conclusion was that the bacteria in the spoiled culture were not dead, just weakened, or attenuated. Infecting the chickens with attenuated bacteria produced no disease or very mild disease—but it did leave the chickens immune to the disease.
Using a weak strain of a disease to immunize against its virulent form was not new. It had been used against smallpox in the eighteenth century. What Pasteur discovered was that one could artificially attenuate disease organisms by treating them with heat or chemicals or a combination of the two. He applied what he had accidentally discovered with fowl cholera to anthrax, producing vaccines from weakened anthrax bacteria. He proved the effectiveness of his vaccines in public demonstrations at Pouilly-le-Fort in 1881.
Pasteur also discovered the truth behind what farmers believed were “cursed fields”—plots of pasturage that seemed to infect all the animals who grazed them. When Pasteur learned that farmers buried in these fields animals that had died of anthrax, he theorized that earthworms brought the bacteria from the decaying carcasses to the surface of the soil. To prove this, he examined earthworm excrement microscopically and discovered the anthrax bacillus in the material. Prevention of such infection was simple, he declared: do not bury dead animals in the grazing fields.
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Pasteur decided that it was time to move his work into the prevention of human disease, but he was faced with ethical problems in how to conduct his experiments and also with a more specific problem: he was a chemist, not a physician. He decided to research a disease that afflicted both animals and human beings, so that he could focus at least his initial investigation on the animals. The most obvious and urgent among such diseases was rabies, which infects animals and can be transmitted to human beings via a bite. In fact, human beings rarely contracted the disease; but, when they did, the symptoms were horrific and almost invariably fatal. For this reason, rabies created disproportionate terror. The treatment commonly used after a person had been bitten by a rabid animal—cauterization of the bite with a red-hot iron—was not only brutal but ineffective.
Pasteur faced other problems in researching the disease, especially with regard to finding a vaccine. The microorganism that caused rabies had so far defied identification, and all efforts to culture it in vitro—in a culture dish—had failed. Pasteur discovered that rabies could, however, be injected into other species and attenuated. He used rabies attenuated in monkeys and, later, in rabbits to inoculate dogs. This protected healthy dogs as well as animals already bitten by another rabid animal. He was, however, reluctant to make any kind of trial on a human being—until July 6, 1885, when a nine-year-old boy named Joseph Meister was brought to him. The sick child had been bitten by a rabid dog and was almost certainly doomed to a terrible death. Believing he had nothing to lose, Pasteur inoculated Joseph with attenuated rabies, even though he could not identify the microorganism. (In the days before the scanning electron microscope, no one could have. The disease was caused not by a bacterial organism, but by a virus, not large enough to be visible to nineteenth-century optical technology.)
The result was historically momentous. Meister recovered, showing that a cure for rabies had been found, along with a preventative vaccine for animals. Vaccination, which had been limited mainly to smallpox, now became a widely accepted form of prophylaxis as well as a treatment for active disease. Medical scientists became interested in developing attenuated vaccines for a wide variety of diseases. Before Pasteur’s work with the rabies vaccination, physicians could do little for patients afflicted with major infectious diseases, except to give palliative and supportive care. Pasteur’s work began a movement, at long last, to arm physicians with effective medicines.
People from all over the world made cash contributions to the Institut Pasteur, which Louis Pasteur founded on June 4, 1887 to study biology, microorganisms, diseases, and vaccines. Officially opened in Paris in 1888, the Institut is now a global network with some thirty branches and is a living monument to the scientist, who died on September 28, 1895.