ALL THE RAGE
IN FRENCH, rabies is called la rage, which is appropriate. Rabies draws on seemingly inexhaustible wells of fear and anger. The reasons for this go to a deep human anxiety about a dark wildness at the heart of nature. The wild beast is out there, just waiting for us, and the images of slavering dogs and their wild cousins, the wolves, are the face of that beast. Of the tens of thousands of people who succumb annually to this terrifying disease—sixty thousand reported in 2018—most are in the poor countries of the Southern Hemisphere, probably a quarter of them in India and China. In China, four epidemic waves, occurring at ten-year intervals from the mid-1950s on, killed at least 100,000 people. In the most severe of these, in the 1990s, more than 5 5,000 people are known to have died. After peaking at about 2,500 cases in 2004, the number of people who died from rabies in China dropped, reaching a low of 4 26 in 2018. In a ll countries, most human victims get the disease through dog bites.
The story of rabies is more complicated now than it was even fifty years ago. It used to be considered a disease of “mad dogs” that then bit people, and historically, that was mainly true. In much of the world, it still is. By the beginning of this millennium, other narratives about rabies had been constructed, based on a more complete scientific understanding.
After World War II, an epidemic of fox rabies swept out of the Soviet Union and westward across Europe. In the 1950s, fox rabies invaded southern Canada from the north, where it settled comfortably into the fox and skunk population.
Raccoon rabies was first recognized in Florida in the 1950s. From an initial small area, the disease spread north and west at about 25 miles per year. Then, in the 1970s, raccoon rabies was given a big boost; hunters from West Virginia decided they needed more raccoons to shoot and so brought several truckloads of them north. At least one raccoon in the bunch had rabies. By the 1980s and 1990s, raccoon rabies was speeding north through towns, cities, attics, and barns. By 1999, the rabid raccoons had reached the St. Lawrence River and were making their first crossings into Canada, just as Ontario had brought fox rabies under control through a wildlife vaccination program. There are two to three hundred raccoons per square mile in parts of southern Ontario: a disaster waiting to happen.
Rabies is kept alive by skunks in the Great Plains, coyotes in Texas, vampire bats in Latin America, and insectivorous bats just about everywhere. In the past decades, not only have scientists identified a much wider range of animals that harbor rabies than once was thought, but they have also identified different strains of virus. Some types of rabies virus are better adapted to raccoons, others to foxes, and still others to bats. In the mid-twentieth century, rabies was thought to be basically one disease, although a few oddball rabies-like viruses had been identified in Africa with names such as Oulou Fato (causing a non-fatal disease in dogs) and Duvenhage virus (which caused something that looked exactly like rabies but apparently wasn’t). Fifty years later, the scientific literature was carrying reports on “rabies-like” lyssaviruses discovered in bats in Australia, Southeast Asia, Europe, and a variety of other unexpected places. The closer one looks, the more complex the picture seems and the less stable and homogeneous the virus appears.
The word “rabies” itself comes from the Sanskrit rabhas, 3000 BC, and means “to do violence.” Chinese records from 555 BC use the same word for “mad dog” and the human disease hydrophobia. The Greek word lyssa is derived from a root meaning “violent”; according to Gerald Moss writing on mental disorder in antiquity (see Brothwell and Sandison, Diseases in Antiquity), lyssa originally seems to have meant “the rage that possesses the hero,” but, in the Iliad, lyssa is connected with “dog,” as in “mad dog.”
So the connection between mad dogs and clinical rabies, often referred to as hydrophobia, is very old. Descriptions of rabies, connecting mental derangement, fear of water (hydrophobia), and the association with mad dogs go back to the twenty-third century BC, in Babylon. Three hundred and fifty years before Louis Pasteur, Girolamo Fracastoro, an Italian scholar, described both the disease and the means of transmission.
“Lyssaviruses” is the name now given to the group of viruses to which rabies virus belongs. Lyssaviruses are members of rhabdoviruses, which are rod shaped, with one end flattened and the other rounded, like a bullet. This may be an appropriate shape, given the seriousness of the disease.
The viruses, once insinuated through the skin into the muscle, multiply, find a nerve, and then float up the axon toward the brain, periodically pausing at junctions of nerve cells to reproduce. This trip to the brain may take anywhere from a few weeks to more than a year. Once in the brain, the viruses multiply again and then travel out the nerves to all the body’s organs, including the salivary glands. With its brain commandeered and damaged by the viruses, the animal behaves in strange ways.
There are two main forms of the disease: furious rabies, in which the animal attacks unsuspecting victims; and dumb rabies, in which the animal mopes around and sinks into depression. An interesting study using game theory calculated that the best strategy for viruses to perpetuate themselves in animal populations would be to have variable incubation periods, variable symptoms, and variable social behaviors. It is pretty hard to learn which animals to avoid if they exhibit no consistent patterns. Natural selection seems to have provided for just such a wild-card combination.
Although descriptions of the disease, and its connection with badly behaving dogs, have been around for a long time, describing this devilish disease clinically did nothing to make it go away or even to tame it. Historically, some people killed themselves when they were bitten by what they thought was a rabid dog, more terrified of the disease than of any possible consequences in an afterlife. Other treatments have included holding people under water until they got better or drowned, a case of trying to treat the symptoms (fear of water) without getting at the cause, or feeding them various parts of chickens or dogs. No treatments, including the best technologies at our disposal today, are effective once the clinical signs set in.
Since the prehistoric human emigration from the gardens of our African and Middle Eastern Edens, dogs have been our most constant and faithful friends and companions. When we were hungry hunters, they guided us to prey. They have guided and guarded our sheep and cattle, sometimes paying for it with their lives. When we settled into agriculturally based settlements, they guarded our properties, barking at the approach of strangers. Our collective lives seem to have been a long march to the ultimate control of nature, and dogs have been a happy part of that march.
Control of nature has brought us many benefits. We grow genetically improved maize and coffee in neat, fertilized fields, accompanied by our tail-wagging canine friends, whom we have taught obedience. But nature has dark secrets. Just when we think we have control, it slips away. Volcanoes that seem to be asleep erupt in a grand, destructive passion. The microbial populations carried by the chickens destined for “every pot” rebelled. The dogs were more direct; they turned on us, snarling and biting and bringing death and madness; it is as if our own children were attacking us. Thus, when Louis Pasteur, in the last great scientific effort of his life, tackled rabies, he was facing the demons that always haunt us: the ones that say, what if all the things we think are normal and good suddenly turn on us?
Pasteur didn’t need to stare down one of the most fearsome zoonotic diseases in history. He had figured out why beer, wine, and milk spoiled and how to prevent it: pasteurization. He had saved the French silk industry from death by a disease that ravaged the silkworms. He had, quite spectacularly, discovered and publicly demonstrated how to prevent anthrax.
In May 1882, at the farm town of Pouilly le Fort just south of Paris, before the watchful eyes of a skeptical media, Pasteur injected fifty sheep with virulent (disease-causing) anthrax bacteria. Half the sheep had been vaccinated with an attenuated form of the bacteria he had grown in the laboratory; the other half had been left alone. The twenty-five that were vaccinated lived. Those who were not vaccinated died. Some estimates are that the vaccination of sheep and cattle that followed saved the French enough money to cover their war reparations to Prussia for having lost the 1870 Franco-Prussian War.
Having a vaccine is great, but it is not a panacea. When a disease occurs sporadically, or if people are very poor, vaccination isn’t practiced, which gives the disease a chance to make periodic comebacks. Anthrax is still with us, partly as a bio-terrorist threat, but more importantly as a zoonosis. The spores last in the soil for a very long time. Outbreaks still occur in animals in parts of Canada and the United States (often associated with bison or cattle on the range), southern Europe, and parts of Africa and Asia. Human cases continue to occur in India, Turkey, and several other countries. In the United States in 2006, a man who carried dried goat hides back from Côte d’Ivoire came down with anthrax.
It is thus no stretch to say that by 1885 Pasteur had given the world strong teeth, Happy Hours, French silk pajamas, and a vaccine for anthrax. What better legacy could a man leave the world?
So, he didn’t need to turn his mind to rabies. But he did it. No one at the time knew about viruses. Scientists such as Robert Koch had barely started sorting out the relationships between the much larger bacteria and disease. But Pasteur had figured out that the brain and spinal cord were the tissues most affected in rabid animals and most able to cause disease if injected into new animals.
Taking spinal cord tissue from rabid dogs, he injected it into rabbits, which also became rabid. He then took spinal cord from the rabid rabbits and allowed it to dry. The longer it dried, the less potent was the tissue in producing rabies. Starting with the “weakest” tissue he had, he injected dogs with more and more potent disease-causing tissues until the dogs were completely resistant. But would the procedure work in people? Pasteur wasn’t sure he was ready to try.
On July 6, 1885, a mother from Alsace brought her nine-year-old son to Pasteur. On July 4, the boy had been badly mauled by a rabid dog. He could hardly walk. The mother pleaded. Could Pasteur use his miracle cure? With some trepidation, he began the treatment with rabbit spinal cord that had been air-dried for fifteen days. Over the next ten days, the boy was injected (under the skin) with increasingly potent mixtures. The boy, Joseph Meister, lived. Then a shepherd came for treatment. Then hundreds more people, until, by the time I came along (much, much later!) everyone knew about the dreaded—and very effective—Pasteur treatment. Traveling by truck, bus, train and on foot through Turkey, Iran, Afghanistan, India, and Nepal in the 1960s, I knew to stay away from strangely acting dogs. But I also knew about the fourteen painful shots in the stomach, which could save my life.
All of this seems very far away from many of us today. By the 1970s, when I went through veterinary college, a pre-exposure vaccine had been grown in duck eggs, which, I would think, was good for rabbit lovers but something of a conundrum for duck lovers. One of my classmates fainted while being vaccinated—perhaps, as an animal lover, pondering this conundrum. Now effective pre-exposure vaccines are grown in human tissue culture (another ethical dilemma). There are also effective post-exposure vaccinations, which are designed to block the virus from entering the nerves from the bite wound. These new post-exposure treatments are considerably less traumatic than the Pasteur treatment; they are called post-exposure prophylaxis (PEP), which sounds almost cheerful, with sexual overtones.
It seems that we have faced one of our darkest fears and won. We have tamed nature. For most of the world, however, this is a mirage.
For many people in North America and Europe, it is hard to imagine the situations in Guatemala, China, and India, where mad dogs and hydrophobia are not just figures of speech. Yet Guatemala, where beauty meets grief, and happy Mayans meet war and rabies, is only a holiday flight away. The beautiful old Quiche Mayan city of Quetzaltenango (“Xela”), Guatemala’s second-largest city, set in a high mountain valley, does not immediately inspire terror. In October and November of 2000, rabies reared its ugly head, and four people died horrible deaths, all bitten by dogs. The Ministry of Health initiated a program to destroy stray dogs, but it ran out of strychnine and ran into protests from animal rights organizations.
The other animal carrying rabies in Latin America is the so-called “common” vampire bat, Desmodus rotundus. The very mention of this animal raises hackles. Vampire bats and people shared the same New World tropical ecosystems for some ten thousand years, and stories of these blood-feeding bats and the disease they carried have been part of some of the most ancient cultures in tropical America. However uneasy this relationship must have been, it was thrown way off kilter when the Europeans arrived with their cattle—blood for everyone! In the twentieth century, the main argument against vampire bats was not so much that they attacked people (which they occasionally did) but that they caused economic losses to cattle, both through causing paralytic rabies and from the effects of drinking blood.
Bats go back at least 50 million years. They are among the earliest mammals, and were here well before humanity stumbled on to the scene. They probably (mostly) came out of Laurasia, one of the two giant continents (the other being Gondwana) into which Pangaea, the original mother of all continents, split about 250 million years ago. Laurasia later fragmented into North America, Asia, and Europe.
Globally, there are about eleven hundred species of bats—20 to 25 percent of all mammals. In Latin America, there are nearly 250 species of bats; more than half of all mammals there are bats. Of the Latin American bats, about 70 percent eat insects, some of them up to five hundred insects an hour, which would be reason enough to protect them. But they may be just as important for flowering and fruiting plants, for pollination and seed dispersal. The list of plants that rely on bat pollination and spread in the wild includes everything from bananas and avocados to dates, figs, peaches, mangoes, tequila, and durian, although the last of these is, in my books, a somewhat dubious distinction.
Some bat pollinators can be considered “keystone” species: if they are eliminated, a cascade of extinctions could devastate the ecosystems in which they live. Fewer than one in a thousand, from three species, are vampires. When people first responded to vampire bat rabies, however, they did not know these things. They did not want to know. Whatever the motivation, the responses reflected the old, deep fear and rage and ranged from dynamiting, burning, poisoning, and gassing caves to leaving out poisoned bananas. Bananas for blood feeders? Clearly, the bats killed were not all vampires.
In the 1970s and 1980s, more targeted campaigns were mounted to vaccinate cattle or smear anticoagulants on them for the bats to pick up and then share with each other during grooming. In the 1990s, new patterns emerged. In some rural areas, when pigs and cattle rapidly disappeared (as many farms disappeared and livestock rearing was consolidated to respond to free trade “imperatives”), the bats looked for new sources of food and found people. In other cases, when people moved into wilderness areas—as in mining camps in the Amazon—and the bats’ usual wildlife sources of food disappeared, they again looked to the delicate-skinned gourmet food—people.
Thanks largely to the works of scientific humanists like Pasteur, this dark, uncontrollable wildness at the heart of nature seems far away for many people in North America and Europe. In these places (with the exception of the Russian Federation), almost all the rabies reported is from wildlife (foxes, skunks, raccoons, mongooses, bats) and only in a few cases from domestic animals such as cats, dogs, or cattle. Human cases are rare in the United States and Canada, and for an increasing number of them, either we don’t know how people got it, or the route of exposure was unusual.
Most years, no one gets rabies in Canada, the United States, or Europe. For the United States, 2004 was an exceptional year: four people died after receiving organ transplants from an infected donor. Two others were bitten by rabid dogs while outside the United States, and one person was infected from a bat but (unusually and perhaps miraculously) survived without having received vaccination ahead of time. When people do succumb, often weeks to months after exposure, it is indeed a terrible way to die. In Canada, there were only four cases of human rabies between 2000 and 2012; two were from exposures outside the country, and two were from domestic bats. In the U.S., there are one to three cases annually, most from exposure to bats, but also from raccoons, dogs, and still, very occasionally, from organ transplants. No matter the source of the virus, or route of exposure, the disease ends with hydrophobia, convulsions, salivation, asphyxia, and death.
One can understand why WHO leads a “United Against Rabies” program, the aim of which is “Zero human rabies deaths by 2030.” I can even almost understand why, in Alberta in the early 1950s, the government started an all-out war that left in its wake the bodies of about 50,000 red foxes, 35,000 coyotes, 4,200 wolves, 7,500 lynx, 1,850 bears, 500 skunks, and 164 cougars. If it was not an act of science, its ferocity betrayed a passion that deserves, I think, respect.
In the late 1980s, Ontario started one of the biggest public health programs directed at rabies in the world. Many physicians and public health workers will be surprised to hear this information, because they have the mistaken notion that public health has something to do with the delivery of medical care. This supposition is only rarely true. When I began working as a veterinarian in Ontario, in the 1980s, there were fifteen hundred to three thousand cases of rabies per year in the province. This was one of the highest reported rates of any jurisdiction in the Western Hemisphere. I hasten to add that, unlike the situation in China, these were non-human animal cases.
Shortly after I arrived in Ontario, I visited a dairy farm to check on a cow that was “off her feed.” She was a normal-looking black-and-white Holstein. She just wouldn’t eat, and she was a little wobbly in the hind end. In most places in the world, one might think of some physical injury or indigestion or perhaps a toxin. Then I had to remind myself that this was not just anywhere in the world. This was Ontario in the 1980s. If an animal acts strangely, think rabies. That is indeed what she had. It was also in this rabid context that, in August 1986, a woman delivered four cute puppies to a humane shelter in a Canadian city. What she did not tell the people at the shelter was that the pups, along with their mother, had been in contact with a fox on the farm where they lived. Nor did she tell them what her veterinarian had told her five days before, that all the dogs should be destroyed or quarantined.
The day they arrived at the shelter, two of the pups were taken to a nursing home as part of a visitation program. Over the next twenty-four hours, all four pups were adopted.
Over the next week, one of the puppies had diarrhea and vomiting and then died. A second also got sick and died. Although neither puppy was afflicted with a great rush of biting madness, both, it turned out, had rabies. A total of 139 people were required to have PEP. This disproportion between the event (exposure to one animal) and the post-exposure vaccination numbers is fairly common; 665 people needed PEP a fter exposure to a rabid kitten in New Hampshire in 1994, and 400 people were treated after a goat at a county fair in New York came down with rabies in 1996.
No one at the nursing home or shelter actually got rabies, whether because of luck or good management or PEP we can never be sure. The mother dog remained healthy through all these events. One of the local physicians, drawing on the deep fear I alluded to earlier, pontificated that this story showed why animals should not be allowed in nursing homes. But that is a simplistic focus on disease and ignores health completely. The appropriate lesson is that all relationships carry benefits and risks and that understanding can reduce but not remove risks. Andrea Ellis of Health Canada and I developed a little booklet, Good for Your Animals, Good for You, which sets out rules for people who want to use animals in schools and nursing homes. The rules relevant to rabies are simple; wild animals that are friendly to people should be assumed to be sick until proved otherwise, and animals of unknown origin should never be put into contact with people until they (the animals!) have been properly vaccinated and observed for a couple of weeks.
But risk reduction for disease is ultimately not just a personal act. It is also a function of social programs. If the amount of rabies in the populations that surround us can be reduced, then the probability that people will come into contact with it will also be reduced, regardless of their behavior. If that can be done, we don’t need to fear a descent into a hell of madness every time someone gets bitten.
Although most of the cases in Ontario in the 1980s were in wildlife, public health officials and physicians had to investigate 1 5,000 to 2 5,000 a nimal-human encounters every year, simply because the level of suspicion remained high. Because rabies was so common in animals, every animal bite could bring the deadly disease. Some farsighted biologists decided that the problem should be addressed at its source. Most of those wildlife cases, they discovered, could be traced back to the way the virus circulated in foxes. If the scientists could control fox rabies, they might be able to get a handle on the whole situation. Killing the animals, they realized, could well cause an even bigger epidemic as new, young (and sometimes rabid) foxes moved from the surrounding areas into the vacated territories and fought with each other.
The vaccination program was based on previous experience with vaccinating foxes in Europe, a series of astute field observations of fox behavior in Ontario, very clever mathematical models, and the hard work of some long-suffering wildlife biologists. They calculated that vaccinating about 70 percent of the foxes would bring the epidemic under control. The vaccine was delivered from airplanes, and by hand, in the form of edible baits. The baits are labeled “Do Not Eat,” on the sometimes questionable assumption that people are more likely to read and obey such a warning than foxes. This taming of nature has been (if I may say so) wildly successful. The number of cases had dropped to fewer than one hundred per year by the new millennium.
Now, in North America, attention has focused on rabid raccoons, which have spread all through the eastern seaboard and are eyeing the land of better health care across the river at Niagara Falls, Canada, and on bats, since it is from them—or increasingly, from “unknown” exposures, which may or may not be bats or aerosolized bat excretions—that people are getting the disease. Still, globally, dog-related rabies accounts for 9 0 percent of a ll cases in people, and dogs kill lots more people than bats even when the pooches don’t have rabies.
There are some effective responses to this global situation. Dog-population-control programs and vaccines, for instance, could bring rabies under control throughout the world pretty quickly. Louis Pasteur and his intellectual descendants would say, with very good reason, that we can experiment and think our way out of our fears. Pasteur urged his fellow citizens to worship in the sacred temples of scientific laboratories. He was convinced that in so doing, humanity would learn not just to conquer disease but also to turn away from fanaticism and barbarism and to find wealth, well-being, and harmony with nature.
Given Pasteur’s lofty ideals, the death of one of his most celebrated patients was thus doubly tragic. In 1940, Joseph Meister, the man whose life Pasteur had saved with his vaccine, was serving as gatekeeper to the Pasteur Institute in Paris, when the German invaders—who, like their Soviet partners, pursued an ideologically driven, supposedly dispassionate science—demanded that he open Pasteur’s crypt. Rather than opening the crypt to the barbarians and thus desecrating the grave of the man who had saved, and given pleasure to, so many lives, Meister committed suicide.
Pasteur was a consummate scientist of his time. He brought the world into his laboratory, and then took the results back out to the world. He did not do his work in some secretive corporate or government laboratory, trying to make money, save face, or make a name for himself. He worked in the open and thus open to challenge. The network of scientific institutes he founded, beginning with the second Pasteur Institute in Saigon (now Ho Chi Minh City) in 1891, spans the globe.
But not all of humanity works in the laboratory; many are kept out by language and money and a scientific culture of disciplinary obfuscation and exclusion. Vaccines are useless unless they are distributed and administered. As WHO reports: “Treating a rabies exposure, where the average cost of rabies post-exposure prophylaxis (PEP) is US$40 in Africa, and US$49 in Asia, can be a catastrophic financial burden on affected families whose average daily income is around US$1–2 per person.”
In 2008, my wife, Kathy, and I were in Malawi, East Africa, to help lead a workshop, sponsored by Veterinarians without Borders/Vétérinaires sans Frontières–Canada, on rabies control. The day we arrived there were reports in the papers of five people who had been attacked by rabid hyenas at a local college campus. Two were killed and chewed up immediately. One died a day later in hospital. At the time the workshop started, one person was still in hospital; his face had been partly eaten away and the doctors had grafted tissue from his buttocks on to his face. Understandably the workshop participants had a heightened awareness of the importance of rabies.
Partway through the first day, participants were assigned to small groups and asked to share personal stories about rabies. The recent hyena attacks were on many people’s minds. One person said her children had discovered one of the people who had been badly chewed up. In another group, a wildlife officer lowered his trousers and showed the scar where he had been attacked by one of the rabid hyenas. He and a police officer had been out hunting the animals when one of them attacked, which is unusual behavior for hyenas. The men fired their guns at the beast and it kept coming, dropped, got up and charged again, dropped after being fired upon, and got up again. It finally dropped a third time just in front of the wildlife officer. He poked it with his gun and the hyena leaped up and clamped on to his thigh in its death throes. The men were out of bullets, so they had to beat the animal with their gun butts and pry the mouth off the wildlife officer’s leg. He was able to get wound treatment and rabies vaccine, which takes a couple of days to work. In Western countries, victims are usually given antibodies to rabies (immune globulin) but there is a worldwide shortage and it is very expensive, and the Malawian medical staff didn’t have any available.
This is, I underline, a preventable disease. A globally successful rabies control program, or even, for all practical purposes, its near-eradication as a human disease, is possible. All that is required is something approaching a sense of human solidarity and international justice.