Rabid (18 page)

Louis Pasteur favored preventative strategies against infection, and he was a great admirer of Jenner and the principle of vaccination. By the time Pasteur began his own work on communicable diseases, Jenner’s legacy was firmly established, if still not well understood. The Académie Nationale de Médecine recommended general vaccination but was still struggling to differentiate the agent of the vaccine from that of smallpox itself. Pasteur’s interest extended well beyond smallpox. He was determined to figure out the general method for immunizing patients against all of the different pathogenic microbes being cultivated in his laboratory.

Chicken cholera was the first disease to yield its secrets to the Pasteur research team. This bacterial disease of fowl was rampant in France during the 1870s, bringing misfortune to poultry farmers across the countryside. According to one of Pasteur’s assistants, Émile Duclaux, the breakthrough was made after the culturing of microbes was interrupted for the summer holiday. When the new academic year commenced, it was noted that the bacteria that had been set aside no longer transmitted the disease.
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The formerly deadly germs produced no grave effect on experimentally infected healthy chickens. Intrigued, Pasteur took these same chickens and submitted them to a second experiment, alongside chickens that had never received inoculations. He infected both groups of animals with very fresh chicken cholera isolates, of determinately high virulence, and monitored them closely
for ill effect. Shortly, Pasteur was able to observe that the birds exposed originally to the aged bacteria resisted infection with the virulent strain, too, while the naive chickens succumbed.

The significance of this finding was not lost on Pasteur. Here was induced immunity from a mortal disease—not happened upon fortuitously in the cowshed like Jenner’s, but experimentally produced in the laboratory! If chicken lives could be spared through inoculation of laboratory-attenuated microbes, it did not require much imagination on Pasteur’s part for him to suppose his method may have potential for saving human lives as well. As a nod to Jenner, Pasteur referred to his method of chicken-cholera immunization as a “vaccine.”

Pasteur’s new vaccine soon attracted naysayers on several fronts: those who fought against all science based upon the germ theory; the anti-vaccinists (who had already honed their rhetoric against the Jennerian vaccine); and those scientific rivals who would have invented the chicken-cholera vaccine themselves if their own methodology had been more sound. Pasteur was in the midst of preparing his findings for the Académie Nationale de Médecine when his arguments with his rivals in that body became so heated that he received an invitation to duel from the aging surgeon Jules Guérin. (The sixty-year-old, hemiplegic Pasteur was delicately extricated from the challenge by friends in the Académie.)

To test the broader utility of his method, Pasteur turned his attention to a second veterinary disease, one with greater economic importance for French and European agriculture: anthrax. While capable, in rare instances, of dealing a farmer or veterinarian a grisly death, anthrax was most feared across rural Europe for its ability to depopulate a prosperous farm, leaving behind an indefinitely contaminated field. Spurred on by Robert Koch’s pioneering paper, Pasteur set out to attenuate the isolated anthrax bacillus in a similar manner as he had done with chicken cholera. He was soon successful: after achieving partial success with heat deactivation, the Pasteur team ultimately found that temperamental anthrax was best attenuated chemically, with carbolic
acid treatment.
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In the end, the pathogen proved no less amenable to laboratory domestication than chicken cholera had.

The furor among France’s scientists and medical men created by Pasteur’s announcement of the anthrax vaccine was so intense, so fevered, as to demand some public proof of his claims. The influential veterinarian Hippolyte Rossignol accused Pasteur of “microbiolatry” in an editorial in his
Veterinary Press.
He invited Pasteur to perform a public demonstration on Rossignol’s own Pouilly le Fort farm in the pastoral Brie region east of Paris. Pasteur accepted the challenge, eager for a means of advancing his doctrine of vaccination. He devised a simple experimental protocol: twenty-five sheep would be vaccinated against anthrax, fifty including these would be infected, an additional ten would serve as untreated controls. All sixty would be monitored for subsequent ill health. The demonstration, carried out during May 1881, was witnessed in its various stages by a large rabble of farmers, physicians, pharmacists, newspapermen, and, especially, veterinarians—many of whom remained as skeptical of Pasteur’s vaccine as they were of the germ theory that gave birth to it. Far away from the pasture where the vaccine trial took place, some of Europe’s most ardent germ theory supporters, Robert Koch and his assistants, suspicious that Pasteur’s strong public assertions regarding microbial attenuation rested on as-yet-unstable science, voiced their stern disbelief as well.
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Great excitement was focused on the final stage of the trial, when the vaccinated and unvaccinated groups would both be injected with virulent anthrax. At the last-minute insistence of one of the more passionately skeptical veterinary observers, a triple dose of live anthrax was administered to each of the experimental animals. Pasteur
himself vigorously shook the vial of anthrax prior to each inoculation, in order to prevent uneven distribution of the virulent principle. Other veterinary spectators demanded that the injections proceed with careful alternation between vaccinated and unvaccinated subjects. Pasteur assented indifferently to the various dictates of the veterinary crowd, never backing down from his assertion that “[t]he twenty-five unvaccinated sheep will perish; the twenty-five vaccinated ones will survive.”

Pasteur projected complete confidence but was privately anguished as he waited to learn the fate of the herd. As the hours ticked by and the only news from Rossignol’s farm was of a sick ewe from the vaccinated group, Pasteur’s resolve began to waver. But two days after the inoculation, all twenty-five of the unvaccinated sheep were dead, while all of the vaccinated sheep had survived. “As M. Pasteur foretold at two o’clock 23 sheep were dead,” the
Times
of London observed. “Two more died an hour later. The sheep which had been vaccinated frolicked and gave signs of perfect health. Farmers now know that a perfect prevention exists against anthrax.”

Pasteur was roundly congratulated, especially by France’s veterinarians, who had become his newest allies—allies who would prove extremely useful as his research progressed into the most fearsome disease known to that profession.

From anthrax, Pasteur turned his attention next to another veterinary disease, but one with widely understood consequences for people. Rabies, and its associated illness in humans, hydrophobia, did not claim so many French lives as others did. That said, it had a prominent place in the French imagination. For each one of the few hundred deaths from rabies registered each year in France, there were several bitten Frenchmen—or, more frequently, French children—who, along with their loved ones, spent many months in the agony of uncertainty: Would the wound lead to a grisly death from hydrophobia? In Pasteur’s youth, when his own village had been terrorized by the rabid wolf, the danger
was viscerally understood. But even as the scientist aged, the debate about whether rabies was a contagion or a spontaneous occurrence raged on among France’s prominent biologists, physicians, and veterinarians.

Pasteur’s collaborator Roux believed that Pasteur selected rabies as a subject for research as a calculated bit of stagecraft, so that his ideas about vaccination would attract maximum public interest. “This malady is one of those that cause the smallest number of victims among humans,” Roux later wrote. “If Pasteur chose it as an object of study, it was above all because the rabies virus has always been regarded as the most subtle and the most mysterious of all, and also because to everyone’s mind rabies is the most frightening and dreaded malady…. He thought that to solve the problem of rabies would be a blessing for humanity and a brilliant triumph for his doctrines.”

The Pasteur laboratory received its first mad dogs from M. J. Bourrel, the former army veterinarian whose 1874 survey had found the anti-contagionists ascendant. Bourrel had been studying rabies for some years without penetrating very deeply into its mysteries. He had, however, localized its contagious principle to the rabid animal’s saliva; given this fact, he recommended the precautionary measure of filing down the teeth of all dogs at large, so that should they become infected, they might not be able to penetrate skin and transmit the deadly agent. Bourrel could provide no better preventative than this, as his search for a rabies cure had led nowhere. He wrote in 1874 that his efforts in the laboratory had shown only that rabies is “impenetrable to science until now.” In the summer of 1880, while assisting him in the laboratory, Bourrel’s own nephew suffered the bite of a rabid dog and died following several days of torturous agony.

In December of that year, Bourrel provided the Pasteurians with two terrifying specimens of canine rabies for study. The first suffered from dumb, or paralytic, rabies. Its mute affliction was wretched to witness: a paralyzed, slack jaw, failing to support a limp, foam-covered tongue, and, above this, eyes full of “wistful anguish.” The second dog,
a victim of the more common furious form of the disease, terrorized the laboratory, menacing the scientists with its enraged, bloodshot gaze, its unpredictable lunges and fits, and its unforgettably mournful, hallucinatory howls.

During the same month, a doctor named Odilon Lannelongue contacted Pasteur about a five-year-old patient, bitten on the face one month prior to hospitalization, now racked by all the classic symptoms of rabies: restlessness, convulsions, aggression, hydrophobia. The child suffered mightily for fewer than twenty-four hours in the hospital and then died, his mouth full of the viscous mucus he had been unable to swallow. Within four hours after the child’s death, Pasteur collected a sample of the mucus. Upon his return to the laboratory, he inoculated some of the diluted mucus into a group of rabbits—a procedure, published more than a decade earlier by the veterinarian Pierre Victor Galtier, proven to determine whether rabies was present in the saliva of suspect dogs. But the rabbits inoculated with the child’s mucus surprised Pasteur, and contradicted precedent, by dying too quickly: they died in only thirty-six hours, when it should have taken weeks. Rabbits inoculated with saliva from those dead rabbits died nearly as rapidly. Moreover, the rabbits died of apparent respiratory failure, not neurological disease as would be typical of rabies. Dr. Lannelongue and his colleague Dr. Maurice Raynaud, after repeating the experiment themselves, eagerly announced proof that the child had died of rabies. If they were correct, this also would represent the first documented case of human-to-animal transmission of the disease.

Pasteur did not commit himself. He cultured a figure-eight-shaped microbe from the blood of the dead rabbits in veal broth and tested its virulence in more rabbits and also in dogs. Again, it swiftly dispatched its recipients. With further investigation, Pasteur and his assistants found that they could isolate and culture this organism from patients who were hospitalized with illnesses completely different from rabies—even from healthy adults. Pasteur named the microbe pneumococcus
and declared that he was “absolutely ignorant of any connection that there may be between this new disease and hydrophobia.”

Critics seized on this as evidence of the slipperiness of germ theory. Pasteur claims to be working on one disease, they sneered, but instead is working on another. To this notion Pasteur responded indignantly, “This is indeed a new disease produced by a new microbe; neither the microbe nor the disease has been described before. This tenacity in research, Monsieur, is the honor of our work, and it was because we, my collaborators and myself, pursued these experimental combinations that we were able to demonstrate that the new disease existed in the buccal mucus of children who had died of the same disease as well as in the saliva of perfectly healthy persons. It was then, and only then, that I had the right to assert that the new disease had no relation with rabies.”

If rabies was not pneumococcus, then what was it, exactly? Despite a thorough investigation using all the tools of the Pasteur laboratory, no combination of methods and media available to Pasteur and his assistants would yield a microbial cause for rabies. Even as Pasteur’s team discovered that the infectious principle for rabies resided in the central nervous system as well as in the salivary glands, they failed to culture a pathogen from either location. Thanks largely to the work of Pasteur himself, it was by this time a basic tenet of medical science that infectious diseases are caused by specific demonstrable microorganisms. Robert Koch’s famous “postulates,” first articulated in 1880, had made clear the relationship between microorganisms and disease, defining a disease-causing microbe as one that appears exclusively in diseased individuals; that can be isolated and cultured from a diseased host; that will cause disease when next introduced into a susceptible host; and that can be subsequently recovered from the experimental host and shown to be identical in culture to the microbe originally isolated. For rabies, not a single one of these conditions
had been met. Koch’s precepts have often been summed up with the phrase “one disease, one microbe,” and Pasteur concurred with this view, but his vision saw a third term in this equation: one vaccine. He believed that every disease-causing microbe, once isolated, could be attenuated so as to safely confer immunity on a potential host. But it was hard to see how this equation could hold true unless a pathogen could be isolated, identified, trapped under glass, and then tamed.

Pasteur referred to the unseen—and apparently unseeable—agent of rabies as a virus. As his biographer Patrice Debré observed a century later, the word “virus” had until that point been associated with a darkly mysterious etiology: with miasmas, with poisons, with plagues. Rabies behaved as though it were a microbic contagion, and so Pasteur maintained absolute faith that it was one, even though he could neither culture it in broth nor observe it under the light microscope. The word “virus” conveyed his uncertainty of rabies’ specific form and characteristics. It was not until 1898 that a “virus” was scientifically defined as a microbe that is invisible under the light microscope and can pass through a filter designed to trap bacteria; it was not until 1903 that it was experimentally demonstrated that the agent of rabies fit squarely within this category.