The Remedy

by Thomas Goetz

  By then, Pasteur had already had a spectacularly successful career. He had made breakthroughs in three fields (chemistry, biology, and industry), discoveries that brought him great acclaim and national honors, including a Grand Prize at the 1867 World’s Fair, membership in the Academy of Sciences, appointment as commander in the Legion of Honor, and an audience with Napoléon III. These laurels boosted the vanity in Pasteur, and in 1876 he tried to parlay his scientific esteem into political office. He presented himself as above partisanship, an emissary from the uncorrupted world of knowledge. “While politics with its senseless divisions saps our strength and fills our enemies with joy,” he said in a campaign speech, “steam, the telegraph, and countless other miracles are transforming the world.” The voters were less than convinced; in a three-way race for the local seat in the French Senate, Pasteur came in third, with just 62 votes.

  But politics was a diversion; his passion was the germ theory. He was the one who’d advanced it from mere theory; he was the one who had demonstrated the existence of germs in the first place. Yet now here came this Koch. Somehow Koch had propelled the germ theory toward acceptance in a way that Pasteur’s own discoveries never quite had. For all his work and all his acclaim, Pasteur had never established a chain of evidence so pristine and elegant, nor one so strong and convincing, as Koch had. This German doctor, he realized, might have something more than luck.

  Pasteur had come to the germ theory through practical, rather than theoretical circumstances. His original inquiry into fermentation, published in 1857, came at the request of a distillery in Lille, a city in northern France. Pasteur was a professor of chemistry at a nearby university when the distraught father of one of his students approached him. His distillery business, the man confessed, was failing for some mysterious reason. Rather than getting alcohol from his beet juice, the man told Pasteur, he was getting something like sour milk. Pasteur began an investigation and discovered that the juice was fermenting into lactic acid rather than alcohol. The cause, he discerned, was a bacterium that had polluted the brew, overpowering the yeast that would otherwise have done the work of making alcohol. This discovery essentially invented the field of microbiology.

  In 1861 he famously debunked the theory of spontaneous generation by proving, with a swan-neck flask, that germs were airborne. And in 1865 he showed that rapidly heating wine would preserve it from microbial spoilage, calling the process, eponymously, pasteurization.

  It was in that same year that Pasteur first approached the problem of disease—albeit disease in worms, not humans. A strange illness had afflicted the silkworms in the South of France, threatening the nation’s silk market, an essential component of the French economy. As the distiller had a few years before, the silk farmers appealed to Pasteur to investigate. The disease looked, at first, like a dusting of pepper on the worms (an attribute that gave it the name pébrine, a local term for “pepper”).

  Pasteur’s first theory was that the farmers simply needed to cull their stock of silkworm eggs and select a different batch. The silk farmers followed his advice, securing a new source of eggs at tremendous cost. But the next year, the spawn was a bust, as before. Horribly embarrassed, Pasteur kept at the problem until, finally, in 1869, he fixed on the right solution. The silkworms weren’t being inundated by one disease but by two, both of them bacterial. The solution, Pasteur realized, was to create a hygienic environment for them, one inhospitable for the bacteria: fresh air; dry, not damp, beds. The farmers grudgingly tried the new protocol and found that it worked. The next year’s crop was larger than ever. This was landmark research, perhaps the first time that a definitive cause of disease had been identified—it was six years before Koch’s work on anthrax—and it would be a model for future investigations.

  Beets and silkworms might seem far removed from medical science, but in fact both represented what are known today as model organisms—nonhuman species that are thoroughly studied so that their functions might shed light on how the human organism works. Pasteur’s work on fermentation, in fact, pioneered the idea of model organisms, to the extent that he was perhaps the first scientist to programmatically study yeast. Today, yeast is one of the most studied organisms on the planet and has contributed mightily to our understanding of DNA, cancer, and various biotechnologies. It was up to Pasteur, though, to suggest that what he’d learned about yeast might inform a larger understanding of other microbes and human health. As far back as 1859, he’d spotted this connection: “Everything indicates that infectious diseases owe their existence to similar causes” to fermentation.

  May we not believe by analogy that the day will come when easily applied preventive measures will stop the scourges whose sudden appearance devastates and terrifies entire populations, such as the yellow fever that has recently invaded Senegal and the Mississippi Valley or the plague that has raged on the banks of the Volga?

  Though Pasteur may have sensed the connection between human disease and the microbial world he was exploring, it would be years before he followed up the observation with real research.

  Perhaps he was gun-shy. After all, Pasteur’s first foray into human disease, back in 1865, hadn’t gone well. That year, a cholera epidemic broke out in Marseille and Paris, France’s two largest cities. Pasteur was recruited to lead the investigation. He searched for a germ he could identify, but in the wrong place: He examined the air in hospital wards rather than the blood in the victims’ cadavers. Maybe he was too willing to accept the miasma theory; maybe he wasn’t yet able to grasp the awesome implications of his own discoveries—that these germs he had discovered didn’t lurk just in beer and wine, but in human bodies, too. Whatever the reason, the cholera investigation was fruitless, and Pasteur soon retreated to his work on wine and silkworms.

  Eventually, though, medicine found him. In the 1860s, Joseph Lister was practicing surgery at the Glasgow Royal Infirmary. After reading Pasteur’s descriptions of fermenting cheeses and putrefied meat, Lister went to his hospital and caught a whiff of an infected wound alive with pus and the smell of putrefied flesh. The smell, he realized, was just as Pasteur had described it. Perhaps, Lister thought, this might be the smell of rotting flesh. (These days, that particular odor is foreign to our noses, but it wasn’t so uncommon in the time before refrigeration and pasteurization. Indeed, once it smacks your nasal passages, the odor is unforgettable.) Since Pasteur’s work had clearly argued that microbes caused this rot, Lister took the next step and proposed that, as with meat, so with wounds. Then he went a step further: If wounds did teem with microbes, then purging them with a bath of carbolic liquid or, later, a spray might eliminate infection from the start.

  Lister began to experiment with antiseptic methods in his operating room, publishing his remarkable results in The Lancet in 1867. Seven years later, in 1874, Lister finally mustered the courage to write Pasteur directly. Praising his “brilliant researches,” he told Pasteur that his discoveries had “furnished me with the principle upon which alone the antiseptic system can be carried out.” Writing back, Pasteur confessed that he was “rather uninformed” about Lister’s work—an astonishing admission given how decisive Lister’s prescriptions had been to the German success in the Franco-Prussian War and how they would seem to offer Pasteur some practical evidence for the germ theory. But Pasteur was savvy enough to politely return the favor, complimenting Lister on the “precision of your manipulations, and by your perfect understanding of the experimental method.”

  By 1878, Pasteur recognized that if medicine would not heed his advice and change from within, then he must muster the evidence and change it from without. The implications of the germ theory for medicine were too great, he realized, and the stakes (in human life) too grave, to ignore the opportunity any longer.

  Then came this curious news of Koch’s experiments in rural Germany, and Pasteur quickly decided upon a disease for his next investigation: anthrax. Though it hadn’t been a subject of his res
earch previously, anthrax made certain sense as a subject for him. After all, he was often guided by economic implications, and anthrax was of great cost and concern to agriculture, in France as in Germany. It was also clearly the work of microbes, as Koch had shown. What’s more, it was a disease that, unlike the silkworm parasites, sometimes crossed over into humans. Finally, it was a matter of pressing national interest; just months earlier, an outbreak of anthrax had run riot through the French department of Eure-et-Loir. So when Pasteur had another request, this time from the French minister of agriculture, asking him to investigate the disease, the answer was clear. How could a patriot refuse?

  He got to work right away. He began by culturing the bacteria, as Koch had; he took a sample of blood from an animal that had died of anthrax, diluted it in urine (used because of its sterility), then took a sample of the mixture and placed it in a second flask of urine. He repeated this process again and again, until, as his former assistant and first biographer Émile Duclaux described later, “the original drop of blood, the one that furnished the first seed, has been drowned in an ocean. . . . Only the bacterium has escaped dilution, for it multiplies in each one of the cultures.” Pasteur then injected a rabbit with a drop taken from the last flask. When the rabbit died, Pasteur had ably replicated Koch’s experiment and had proven to himself that the anthrax bacterium caused the disease.

  News of Pasteur’s research soon made its way to Koch in Wöllstein. Koch agonized over the idea that the French giant was tackling the same terrain he had. Just months ago, nobody in the world seemed to care about anthrax, but now here was the most famous scientist in Europe, the man who had forced the germ theory from the impossible to the probable, working on the same microbe. But, if Koch felt threatened, there was little he could do about it. In a letter to Cohn back in Breslau, Koch mentioned that he’d read a translation of Pasteur’s experiment and found it “very interesting,” he granted. “If I only could study Pasteur’s work in the original French.”

  His anxiety was surely made worse by the fact that Pasteur seemed entirely ignorant, perhaps willfully so, of Koch’s work. Indeed, it was as if Koch had never existed to Pasteur. In these first publications on anthrax, Pasteur referred to the anthrax bacteria as bacteridia, using the term coined by his countryman Davaine in 1863, rather than Koch’s term, Bacillus anthracis. (In a footnote, Pasteur did make a passing reference to Koch’s work by referring to the “Bacillus anthracis of the Germans.”)

  In his next experiments, though, Pasteur demonstrated how his pragmatic approach might be more profoundly useful than Koch’s laboratory work. In particular, he wondered about the mystery of anthrax’s “champs maudits,” or “cursed fields.” Upon these fields, entire flocks of livestock might die of the disease in one season. Then the disease would disappear for years, only to return and unleash its terror once again. If bacteria caused the disease, Pasteur wondered, what happened to them in those intervening years? Where did they go—and why did they later come back?

  To solve the mystery, Pasteur began searching for anthrax’s hiding place, somewhere in the natural environment. He found it almost in plain sight: in the soil itself. When the animals died en masse, farmers would routinely bury them in a pit, dug in the same fields where they dropped. Some carcasses, inevitably, would be less than a meter below the surface. That was deep enough to keep the bacteria away for several years. But over time, the lowly earthworm would make its way through the carcasses and slowly nudge the microbes and their spores back up toward the surface, where they would at last attach to the next season’s grass. Then a sheep or cow eating thistle or sharp grass might get a little dirt in its mouth. The thistle or grass would inflict tiny cuts in the animal’s mouth, and the spores would opportunistically enter the body.

  It was a brilliant bit of sleuthing on Pasteur’s part, as rationally thorough as Koch’s research in the anthrax life cycle had been. Pasteur’s work gave vision to a different life cycle of the disease, on a human, rather than bacteriological, scale. His finding had significant implications for farmers. He laid down the law for them: “You must prevent your animals from grazing in pastures where dead bodies have been buried. Fields where crops are grown must not be used as cemeteries. Grazing or raising forage must not take place on land where dead bodies are buried.”

  Pasteur wasn’t satisfied, though, with trodding on the familiar ground of causality. By this time he thought he understood how anthrax worked—how it lived and how it killed. This gave him an advantage, he thought; perhaps he could turn the microbe against itself. Maybe he could create a way to stop it.

  In 1879 he began a side project on chicken cholera, a persistent bane of the French poultry farmer. He had successfully isolated the bacterium and was tinkering with various cultures of it. One day, by chance, he noticed that some cultures, though clearly identifiable as the chicken cholera microbe, didn’t actually produce disease in birds. The microbes seemed to have lost their potency. This might have been merely frustrating, if Pasteur hadn’t recalled the work of Edward Jenner, nearly a century before, on smallpox.

  In 1796, Jenner, a well-respected doctor in southern England, observed that milkmaids often came down with cowpox, a debilitating but usually mild illness, apparently as a result of their work. He subsequently observed that those maids who’d had cowpox rarely contracted smallpox, a far more serious but similar disease. At the time, it was already known that people could be immunized against smallpox with an injection of a bit of tissue from somebody with the disease, a process known as variolation. But this was a dangerous practice, as a not-insignificant number of people so immunized actually came down with the disease and died, and thus variolation was far from widespread.

  The milkmaids’ immunity, though, suggested an experiment. Jenner took some pus from a blister on the hands of a maid named Sarah Nelmes and injected it into the arms of eight-year-old James Phipps, the son of Jenner’s gardener. The boy came down with a fever but quickly recovered. Then came another experiment, one that was purely the logical next step but that was also so dangerous that no medical board would have tolerated it today: Jenner took live smallpox and injected the boy (just eight years old!) with it. Nothing happened. He tried again, and still young Phipps was fine. It was a remarkable discovery: a safe way to protect people from a disease.

  Jenner’s new process (later known as vaccination, from the Latin root vaca, for “cow”) would soon become widespread. In time, many European countries adopted it into law, and it ultimately has saved millions of lives worldwide. For eighty years, Jenner’s feat would be unequaled. (Smallpox would be eliminated from the face of the earth in 1973, the first and, as of now, still the only disease to be entirely eradicated from the human population.)

  Pasteur had Jenner’s breakthrough in mind when he noticed his weakened bacteria. With an inkling of what might happen next, he injected the weakened microbe into several birds, waited a few days, and then injected the birds again with a fresh, pure sample of active chicken cholera. The birds survived, just as Pasteur had hoped they might. They had been vaccinated, protected against disease.

  This was terrific news for chicken farmers, and a few years earlier, it might have satisfied Pasteur as well. But this time Pasteur decided to repeat the experiment on animals with anthrax. For a few months, he worked in his laboratory on the rue d’Ulm in Paris. In March 1881 he announced that he had devised a technique; they might attenuate the anthrax bacterium. But it needed a practical test, not in the laboratory but in the dust and fields of a farmyard. So, in April 1881, Pasteur accepted an invitation to conduct a public test of his vaccine.

  The experiment took place on May 5, 1881, on a farm in the town of Pouilly-le-Fort, a village just forty-odd kilometers outside Paris. The farm was typically, beautifully French: The barn and stable were fortified with thick stone walls, and the fields and pastures rolled out amiably toward the horizon. Pasteur, who had a natural flair for spectacle, had eagerly
allowed the experiment to be publicized. As a result, the farm was crowded with hundreds of spectators: farmers, politicians, veterinarians, and, most significantly, journalists. In a large pen, sixty animals (cows, sheep, and goats) were crowded together. The local Society of French Farmers had provided the animals for the experiment.

  The atmosphere was noisy and festive. Amid the animals’ bleating and baaing and mooing, Pasteur began his experiment. First he examined the animals, rejecting two sheep and one cow as suspiciously weak. Then he began the vaccinations, injecting a syringe of anthrax culture into twenty-four sheep, six cows, and one goat; the bacteria was living but attenuated, meaning it had been bred into a less virulent strain. He also included a control group of about the same number of animals; these were not inoculated. Thus ended the first day of the demonstration. The crowd dispersed, and Pasteur and his assistants returned to Paris.

  Less than two weeks later, on May 17, the experiment resumed. Before just as large a crowd, Pasteur gave the experimental group a second injection of the vaccine. Then, on May 31, he returned and gave all the animals, including the control group, a dose of fresh, strong anthrax culture, enough to kill. The parties then agreed to meet again in forty-eight hours to observe the results.

  Among the unvaccinated control animals, the disease quickly did its work. Over the next two days, animals started breathing heavily and stopped eating. Their legs buckled, and they began falling over dead. Soon bodies littered the pens, and ailing animals stepped around the carcasses of their brethren until they, too, dropped dead. By June 2 all the unvaccinated sheep and the goat were dead, and most of the unvaccinated cows were on their way there. Even to farmers, used to dead animals, it was a horrific sight.

  But the vaccinated animals were just fine. There they were, grazing in the next pasture, just as they had been for the past month. These animals were healthy—thriving, even—and entirely oblivious to the carnage just a few meters away.