Rabid (21 page)

Emile Roux, Pasteur’s closest collaborator during the creation of vaccines against fowl cholera and anthrax, and who had been so instrumental in devising an attenuation method for the rabies virus, would go on to develop serum therapy against diphtheria toxin. Élie Metchnikoff, a Russian biologist who had trained in Germany with
Koch, would help, during his time at the Institut Pasteur, to lay the scientific foundations of immunology by describing the mechanisms of cellular immunity. Albert Calmette, after establishing a Pasteur Institute in Saigon, would build on the antitoxin research of Roux and develop antivenom serum therapy for snakebites. Later, at a Pasteur Institute he had founded in Lille, Calmette would join Jules Guérin, another Pasteur disciple, in his work on tuberculosis; together they would identify the famous BCG (Bacillus Calmette-Guérin), a strain of bovine TB that functioned as a human vaccine. Alexandre Yersin, a Swiss physician who was working under Roux when the Institut Pasteur was inaugurated, went on to spend his most productive years in Indochina. When a plague outbreak threatened Hong Kong in 1894, Yersin quickly established a field laboratory in the afflicted city and within days had discovered the plague bacillus. He furthermore determined that the dead rats littering Hong Kong were the origin of the deadly epidemic and quickly developed and began production of a lifesaving serum therapy against plague. Charles Nicolle, who met Pasteur only once, worked under Roux and Metchnikoff, then later at the Pasteur Institute in Tunis. He determined that typhus was spread by the human louse and that leishmaniasis was transmitted from dogs to humans by the bite of the sand fly. Jules Bordet, who worked in Metchnikoff’s laboratory from 1894 to 1901, made great progress in the field of immunology, particularly concerning humoral immunity, and he discovered the bacillus responsible for whooping cough after creating a Pasteur Institute in Belgium. Together, these early Pasteurians would further the laboratory-based approach to medical problems favored by their master and would carry his doctrines linking science, medicine, and public health to all the corners of the earth.

Pasteur’s remains were interred not in the Panthéon but instead, according to his family’s wishes, in a specially appointed crypt beneath the Institut Pasteur. There, fifteen years later, his wife, Marie, would be laid to rest also. Mosaics depicting Pasteur’s research triumphs watched over the tombs—and so did Joseph Meister, who, years after
being the first to be vaccinated successfully against the horror of rabies, became the concierge of the institute. When the Nazis, on occupying Paris, attempted to visit the Pasteur crypt in 1940, Meister bravely refused to unlock the gate for them. Soon after this discouraging event, he took his own life.

Then, as now, Pasteurian science remained very much alive. Soldiers at the front in that war, on both sides of the battle, were protected from disease with Pasteurian vaccines, treated for illness with Pasteurian sero-therapies, and benefited from hygienic first aid and surgical techniques based on Pasteurian asepsis. As remains the case today, there were then still scientists ready to argue against Pasteurian principles—but history would take little note. Indeed, though many miraculous cures lay in the future, no figure in medicine since has ever enjoyed the heroic status conferred upon Louis Pasteur, conqueror of rabies.

*
Duclaux’s account was supported by the biography written by Pasteur’s son-in-law, René Vallery-Radot, but some modern scholars dispute it. In 1985, based on a thorough study of Pasteur’s notebooks, the French historian Antonio Cadeddu asserted an alternate history: Pasteur’s collaborator Roux determined the method for attenuation of chicken cholera through prolonged, deliberate laboratory experiment—without the knowledge of Pasteur.

*
The superior technique of carbolic acid attenuation was devised by the veterinary researcher Henri Toussaint and perfected by Pasteur’s assistants, Roux and Charles Chamberland, after Pasteur had already announced the creation of attenuated anthrax using temperature manipulation.

†
The Koch group, which relied on different culture methods than did the Pasteur laboratory, doubted the particulars of Pasteur’s thermal method of attenuation.

Cover of a pulp horror novel, 1977.

I
t is impossible to overstate how utterly Louis Pasteur, during just two decades of work in the late nineteenth century, remade mankind’s understanding of rabies. His great discovery did not just radically reduce the number of humans dying from hydrophobia in the West each year. Through his invention of a preventative rabies vaccine for dogs, he also significantly reduced the incidence of the disease in the animal most responsible for spreading it. Moreover, during the course of the twentieth century, Pasteur’s treatment for humans was improved and refined. Growing the vaccine in duck embryos (and later in cell cultures), rather than in rabbits, simplified the process and standardized the product. Researchers eventually discovered that supplementing the postexposure vaccine with rabies immunoglobulin, derived from the blood plasma of already-vaccinated humans, would markedly improve the success rate. As death from rabies declined in the West, the disease came to exist in the public consciousness largely as an archaic holdover from an earlier age: seldom seen, nearly mythical. Not only did rabies cease to be a meaningful cause of death in industrialized countries; it became largely absent from the streets and
lanes. No longer did rabies threaten to invade the home, to colonize the trusted creature sleeping at the hearth.

At the same time, though, even as the oldest animal infection receded as a public menace, the pioneering work of microbiologists was establishing that a whole host of other diseases were, in fact, linked to similar diseases in beasts. This includes, of course, the titan of them all, the bubonic plague. (The flea-borne pathogen that Alexandre Yersin isolated in 1894 was later renamed in his honor—
Yersinia pestis
—and in 2010, using skeletons from plague pits, it was proved beyond doubt that this pathogen had been the cause of the Black Death.) All of human history prior to the twentieth century had been haunted by rabies as an unforestallable and invariably fatal infection from animals. In the twentieth century, as rabies receded, it was replaced by a rapid succession of equally horrific and, in many cases, far more dangerous zoonoses.

The most fatal of these struck like a tsunami between 1917 and 1920, when some 50 to 100 million people worldwide—roughly 3 percent of the global population—died of a particularly nasty strain of influenza, the so-called Spanish flu. At the time, medicine believed influenza to be a uniquely human malady. But throughout 1918, during the height of the epidemic, reports trickled in about uncommon animal ailments that seemed to mirror the symptoms of flu. At a veterinary hospital of the French army, a shocking number of horses had been laid low with such a syndrome. In South Africa and Madagascar, it was primates, baboons, and monkeys felled by the hundreds; in northern Ontario it was moose, dead in the brush. But most ravaged of all was the Iowan pig. First noted at the Cedar Rapids Swine Show in the fall of 1918, flu-like symptoms spread over the succeeding months to literally millions of hogs. The veterinarian J. S. Koen, who tracked the disease while in the employ of the federal Bureau of Animal Industry, reported its toll in stark terms. “Sudden and severe onslaught. Patient very sick and distressed…. Muscular soreness, nervous and excitable. Congestion of eyes. Watery discharge from
eyes and nostrils…. Temperatures usually high, many instances up to 108°F. Rapid loss of flesh, may lose as much as five pounds per day. Extreme physical weakness. Very rapid progress through herd. Lasts four or five days and patient begins to recover about the time death is expected.” But recovery never arrived for the thousands of pigs, or roughly 1 to 2 percent of cases, that perished from the infection.

Just calling this pig malady a “flu” was enough to invite skepticism from scientists and hand-wringing from the pork industry, which worried that reports of a deadly human flu in pigs could turn the public stomach against its products. But Koen stood his ground. “I believe I have as much to support this diagnosis in pigs as the physicians have to support a similar diagnosis in man,” he wrote, and went on:

It was, as the historian Alfred W. Crosby later wrote, “a peroration…worthy of Luther standing before the Emperor at Worms.”

Over the course of the next twenty years, four scientists working on both sides of the Atlantic—Richard Shope, based in Princeton, New Jersey, at the laboratories of the Rockefeller Institute for Medical Research, and a team of three in the United Kingdom (Wilson Smith, Christopher Andrewes, and Patrick Laidlaw)—endeavored to prove Koen’s intemperate assertion correct. In 1928, Shope was back in his home state of Iowa investigating so-called hog cholera (in fact, unrelated to the human virus of that name) when he started looking into Koen’s theory. The following fall, when the swine infection hit the
herds again in full force, Shope returned to collect tissue samples and mucus secretions, and by 1931 he and his mentor, Paul Lewis, had isolated what would later be confirmed as the swine flu virus.

Meanwhile, the three English scientists, also at work on the problem of flu, employed a domesticated animal that until then had stayed on the sidelines of the quandary: namely, the ferret. In the mid-1920s, Laidlaw had coauthored some pathbreaking research on distemper, a nasty respiratory illness in dogs that he and his collaborator demonstrated could easily be spread to ferrets. Now he and his collaborators on flu were attempting to pass the human strain of the disease to ferrets. In 1933 they succeeded, isolating a virus from diseased humans that created a comparable illness in twenty-six ferrets. Perhaps more important, they also demonstrated that Pfeiffer’s bacillus, a bacterium that for decades had been suspected as the cause of influenza, had no effect at all.

That same year Shope, with whom the three were now working in excited collaboration, used his swine virus to produce flu in ferrets. And this was not just any flu; it was a horrific, Spanish-style flu, characterized by the same bloody pneumonia that had swept away millions in the global pandemic. By May 1935, in a lecture at St. John’s College, Laidlaw was able to state confidently his opinion—one borne out by all subsequent discoveries—that “the virus of swine influenza is really the virus of the great pandemic of 1918 adapted to the pig and persisting in that species ever since.”

This retrospective understanding of the 1918 pandemic was just the first such awakening in a century replete with terrifying zoonoses. U.S. soldiers returned from the Korean War with a sinister strain of hantavirus, a nasty hemorrhagic fever acquired from rats. In the late 1960s, Africans were falling ill from Lassa fever, also the handiwork of rats. The 1980s saw the emergence not just of AIDS but of the terrifying Ebola, also a disease from monkeys that, at its most acute, can induce terrible death involving bleeding from all bodily orifices. More recently, two strains of animal influenza—the onset of the avian flu
and the robust return of the swine flu—killed thousands of people and prompted thousands more to hide for months behind surgical masks. Despite the slow ebb of rabies as a killer of men, the preceding century nevertheless supplied humans with countless reasons to eye their animal neighbors warily.

By the 1930s, rabies in America had largely subsided in humans, though their dogs were a different matter. This was especially the case in the South; a report from late in that decade put the infection rate among the dogs of Birmingham, Alabama, at 1 percent—a shocking number for a virus that kills all of its canine hosts. Though the canine vaccine was by then widely available, whites in the region vaccinated just 40 percent of their dogs, and African Americans only one in ten. The human death rate had been brought low but remained real: more than 250 deaths were logged in the American South during the 1930s, a per capita rate not dissimilar to the pre-Pasteur hysterias in eighteenth-century England.