Welcome to Stuff You Missed in History Class, a production of I Heart Radio. Hello, and welcome to the podcast. I'm Tracy V. Wilson. Now I'm Holly Fry. Foxes are one of many wild animals that share cities and other places with human beings, and in April, one of them made headlines after biting at least nine people around the US capital. When this story crossed my Twitter feed, I'm became incredibly invested in whether everybody who got bitten by this fox had gotten their rabies shots. Afterward, news articles were not telling me the answer to this information. Some of them were talking about a specific reporter or a specific congress person, but I was like, no, everybody, everybody needs to get the raby shots because foxes can carry rabies. Rabies is virtually always is fatal once people develop symptoms, once anyone developed symptoms, but today's rabies profile access is almost a dent effective at preventing that from happening. It is I think the most effective vaccine that we have in existence. So then when news broke that yes, this fox did have rabies, it was like just a big flashing, screaming side in my brain, like raby shots raby shots. Raby shots, Please tell me everyone got their rabies shots. Of course, then that made me want to do a podcast on rabies and the vaccine that prevents it, something that somehow I thought we already had stuff on. We don't, or if we do, I failed to find it. The vast majority of our listeners live in places where Raby's deaths in humans are extremely rare. Some parts of the world are rabies free, and here in the United States there were only five human deaths from rabies, and that was the highest number of annual rabies deaths in the United States in a decade. There are also places, though, where rabies is still endemic, and globally about fifty six thousand people die from it every year. That is not like that's a small number compared to something like the current pandemic, but they're fifty six thousand totally preventable deaths, Like we have what we need to prevent this, So I wanted to talk about that heads up though there's a lot of animal experimentation in this episode and deaths. Obviously, rabies is caused by rabies list of virus, which probably originated in Old World bats. This virus has existed on every continent except Antarctica and Australia for millennia, and although Australia is Rabi's free, it's home to a closely related virus called bat lists of virus. But in spite of the viruses connection to Bat's humanity's connection to rabies has mainly been through dogs. That connection show is up in the first written reference we have of rabies, that's in the Eshnuna code from roughly two thousand b c e. Shnano was a city and what's now Iraq, and some of its laws have survived on a pair of broken tablets that were found at an archaeological site near Baghdad. Here's one of the laws quote. If a dog is mad, and the authorities have brought the fact to the knowledge of its owner, if he does not keep it in, and it bites a man and causes his death, then the owner shall pay two thirds of amina of silver. If it bites a slave and causes his death, he shall pay fifteen shekels of silver. The first written reference to rabies in China is from the Zoo tradition, sometimes called the Zoo Commentary. This is a commentary on the spring and Autumn Annals, which chronicles a period of Chinese history stretching from seven twenty two to four eighty one b C. One passage in the Two Tradition describes people of the capital city of Sung chasing a rabid dog. The dog ran into the home of a minister named wat Chin, and the people chased after it. Wat Chin was afraid and fled the city, and about the fourth century BC, Aristotle wrote this and his History of Animals quote dogs suffer from three diseases, rabies, quincy, and sore feet. Rabies drives the animal mad, and any animal whatever, accepting man, will take the disease if bitten by a dog so afflicted, the disease is fatal to the dog itself and to any animal it may bite man accepted. So this translation makes it sound like Aristotle was saying that humans don't get rabies, but it's also been interpreted as meaning that people don't always develop rabies when bitten by a rabid dog, and that is true, or that people don't always die from the disease if they contract it, which is almost never true. People will have known that rabies was essentially always fatal for thousands of years, though Roman court physicians Scribonious Largest described rabies as incurable in the first century CE. In addition to being lethal, rabies progresses in a way that can be really terrifying. The exact symptoms can vary, but there are two broad categories, both of which end in coma and death. Paralytic rabies involves lethargy, weakness, and paralysis, and furious rabies involves agitation, aggression, and hyperactivity. The word rabies reflects this latter type that comes from the Latin for to rage, which may have roots in a Sanskrit word meaning to do violence. Lissa virus has a similar root. It comes from a Greek word meaning frenzy or madness, which was used to describe rabies as well as to describe irrational rage. Raby shows up a lot in popular cult sure, and that goes back thousands of years as well, including the use of rabies or rabid dogs as a metaphor for being mad or uncontrollable. For example, in the Iliad, which was written in about the eighth century b c. E. Homer describes Hector as a rabid dog. Rabies can also cause paralysis and spasms in the throat that make it impossible to swallow water. That's why it's also known as hydrophobia, and the second century CE Roman philosopher Celsus used the word hydrophobia in his description of the disease. Celsus also recognized that something was present in saliva that transmitted this illness, and he recommended a range of techniques to draw this substance out of wounds. Like the connection between rabies and aggressive rage, the connection between rabies and hydrophobia made its way into literature centuries ago. For example, in about the year five hundred, Klias A lean Is suggested that Homer's description of Tantalus in the Odyssey might have been inspired by rabies, since Tantalus is tormented by water that he cannot drink. It's also possible that rabies influenced ancient Greek depictions of Cerberus, the multi headed dog that guarded the underworld, and that those depictions of a mad beast with poison frothing from its jaws circled back to influence people's perceptions of rabies. So through these and other written references, we know that rabies had spread from wherever it originated, all through India, China, the Middle East, Greece, rome in Egypt by about fifteen hundred years ago, but we don't really know how widespread the disease was in any of these places, or how many deaths it caused among humans and other animals. That starts to change in the medieval period, when people started documenting large outbreaks of the disease within specific animals. These account it's primarily focused on outbreaks among dogs and other canids, including wolves and foxes. For example, an outbreak of wolf rabies struck Franconia in twelve seventy one. A massive outbreak among red foxes spread over parts of Europe between fifteen seventy one and fifteen eighty one, leading people to try to stop the disease by culling them. Sometimes these outbreaks could spread to other animals, including infecting people when they were bitten. At this point, we haven't mentioned rabies in the America's and that's because while rabies existed in the Americas through all this, rabid dogs probably did not. Based on genetic studies of the virus itself. Before European colonization, rabies and the America's primarily infected bats and skunks. There's some evidence that Indigenous peoples in ancient Central and South America regarded both bat bites and snake bites as potentially dangerous, treated bat bites with washing and cauterization with hot culls to try to prevent disease. Spanish colonists were reported being bitten by bats in the early fifteen hundreds, and in fifteen fourteen, Fernandez de Oviedo wrote about several soldiers dying after being bitten by vampire bats. Dog rabies is one of many diseases that Europeans introduced to the America's, and after that introduction, it spread to other animals and became far more likely to infect people, but that process did not happen nearly as quickly with rabies as it did with diseases like smallpox. Rabies typically has an incubation period of roughly three to eight weeks, although it can occasionally be much longer. Once symptoms appear, rabies is virtually always fatal within about ten days. When Europeans first started sailing to the America's, the voyage often took more than two months, so any dogs or other animals that had been infect did before setting sale usually developed symptoms and died or were killed while still at sea, so that meant introducing dog rabies to the America's required a voyage that was short enough for infected dogs to survive. It also required a large enough population of dogs and other mammals within a colony for the disease to keep circulating once it had been introduced. The first recorded outbreak of dog rabies in the Americas was reported in Mexico City in seventeen o nine, and by the end of the eighteenth century, dog rabies was widespread in most of the places in the Americas that Europeans had colonized. This in turn spread the disease to the continent's native animals, with some of those exposures leading to new strains of the virus that were adapted to specific species. We'll talk about how a vaccine was developed to prevent rabies after a sponsor break. By the eighteenth and nineteenth centuries, outbreaks of rabies were spread across a lot of the world and domesticated dogs and in wild animals. In North America, rabies became so widespread in skunks that they were nicknamed Phoebe cats like hydrophoby and phoebe tents were advertised as a way for cowboys to avoid being bitten by them in their sleep. In eighteen o three, and outbreak among wild foxes in France spread to dogs, pigs, and people. Bites from rabid wolves tended to be particularly lethal, in part because attacking wolves often bit people's faces or necks, meaning the virus was way closer to their brain, while rabid dogs usually bit people's hands or arms. There was no cure for rabies and no way to tell whether a person would develop it after being bitten, and estimates of how many people developed rabies after a bite stretch all the way from five percent to Some of this is just because of imprecise record keeping, but it's also connected to how people responded to the disease. In many places, there was a widespread assumption that any animal that bit had rabies, and during outbreaks, people tended to hunt down and kill animals that they thought might be spreading disease. So a dog that bits someone in the midst of all of this might be rabid, or it might just be scared and cornered and trying to defend itself. Around the world, people tried various herbs and medical preparations to prevent or cure rabies, and because it was so lethal, many of these were also relied on the idea of divine intervention. For example, Hubertus, also called St. Hubert Is the patron saint of hunting, and one of his reported miracles involved curing somebody who had been bitten by a rabid dog. So inch of Europe people used a piece of iron called St. Hubert's key to cauterize bite wounds. As part of this treatment, a priest would also make a shallow cut over a person's forehead, place a black bandage over that, and the person wore that bandage for nine days. Some people even carried one of these keys around with them for protection. Long before the development of the germ theory of disease, people recognize that when someone was bitten by a rabid animal, something in the animals saliva was going into the wound and potentially causing rabies. So some of the other treatments for bites involved washing the wound, applying caustic chemicals to it, or cauterizing in whether it was with a Saint Hubertists key or with some other implement. If these treatments were done immediately, after a person was bitten. They may have helped reduce the chance of developing rabies by washing away the animals infected saliva. Thoroughly washing the wound is still step one in rabies prevention today, but none of this was enough to totally prevent the chance of developing the fatal disease. People also tried to prevent rabies by reducing the numbers of animals that could carry it and transmit it to humans and to other animals. For example, in eighteen sixty seven, the UK passed the Metropolitan Streets Act. Among other things, this act empowered police to collect and muzzle stray dogs, are dogs that were determined to be dangerous. This reportedly led to a drop in human cases of rabies in British cities. Also in the eighteenth and nineteen centuries, researchers were learning about rabies and working on ways to prevent it spread. During the earlier part of this time, researchers didn't yet know what a virus was. But trying to talk around that got really clunky. So we are still going to call it a virus in our discussion today. Yeah, it was a lot of incredibly stilted sentences before I was like, we're just it a virus, regardless of whether that individual research or knew what a virus was. So in seventeen sixty nine, Italian anatomist and pathologist John Morganni observed that rabies traveled via the nerves rather than traveling through the bloodstream. He made this connection because some patients reported a feeling of pins and needles or other neurological disturbances around the site of their original bite wounds. Morgan was correct. Once it enters the body, the rabies virus moves along the nerves until it gets to the brain and the rest of the central nervous system. After it gets to the brain, the rabies virus makes its way to the salivary glands, where it can cause excessive salivation, and although eighteen century researchers didn't quite have that part figured out, they did know that the disease was spread through saliva. In seventeen ninety three, Scottish surgeon John Hunter speculated that it would be possible to use a lancet to intentionally introduce an infected animals saliva into another animal, but it's not clear whether he tried this in practice. We also don't know whether German naturalist George Gottfried Zinca was familiar with Hunter's work, but in eighteen o four he brushed saliva from a rabid dog onto a cut he had made in the leg of a healthy dog. This previously healthy dog contracted rabies. He did the same thing with other healthy mammals, demonstrating that it was possible for the bite of an infected dog to infect animals of other species. In eighteen twenty one, French neurophysiologist Francois Magendie reported that he had infected a previously healthy dog with saliva from a person who had contracted rabies. Victor Gautier was a professor at the National Veterinary School in Lyon, France, and he started experimenting with rabies in eighteen seventy nine. He found that it was possible to transmit rabies from a dog to a rabbit, and then from that rabbit to another rabbit. Rabbits were smaller and easier to keep than dogs, and they were less dangerous research subjects than rabbid dogs were. Gaultier also found that the rabbits had a shorter incubation period of about eighteen days rather than a month or more that you might see in a dog. Gaultier did various experiments with infected animals saliva, attempting to see whether he could find some way of using this infectious material to prevent rabies. In eighteen eighty one, he injected rabies virus into the jugular veins of sheep and they didn't develop rabies, and then when he exposed one of them to saliva from a rabbit dog later on, it seemed like it was immune to the disease. French chemist and microbiologist Louis Pasteur started working on rabies at about this same time, and he was inspired by Gaultier success. Pastor already an extensive background in this kind of work. In the eighteen fifties, he had studied yeast and alcohol fermentation, as well as the ability for micro organisms to contaminate fermenting beverages. This had contributed to both the germ theory of disease and the development of pasteurization. In the eighteen sixties, he had identified a micro organism that was devastating the French silk industry, and in the eighteen seventies he studied animal diseases like anthrax and chicken colera, including developing an anthrax vaccine. While Pasteur had lots of experience in this kind of research, he had pretty much no experience in medicine or the clinical treatment of patients, so he relied on other people for this knowledge, including French physician and bacteriologist Emile Roux. A whole team of other scientists and doctors were involved in this work as well, including Charles Chamberlin, Emile Duclox, Louis Dulier, and Joseph grane A. This is definitely not a solo effort, and Pasteur was not always excited about crediting other people for their involvement in it. There are even some historians who have accused him of stealing other people's ideas. Much of Pastor's previous work had involved culturing bacteria and working from those cultures, and he started out trying to do the same thing with rabies. Since rabies is caused by a virus rather than a bacterium, Pastor's efforts to replicate his earlier process failed. He started working directly with the saliva of infected animals and then moved on to working with central nervous system matter. He found that if he exposed a healthy rabbit to rabies, it developed rabies. Then if he used that rabbit's central nervous system matter to expose another rabbit, that second rabbit also developed rabies, and the second rabbits infection seemed to be more virulent than the first. If he did this a third time, the third rabbit's infection was also more virulent than the seconds had been. He continued this serial passage of the virus from rabbits to rabbit until he had a strain of it that he described as fixed. It was consistent and how virulent it was, and it had an incubation period that was set at six or seven days. From there, Pastor air dried the spinal cords of rabbits that had died of that highly virulent fixed strain. The longer they dried, the weaker the virus became. That's a process called attenuation. When he exposed other animals to a small amount of this attenuated virus, they seemed to develop a resistance to rabies rather than becoming ill. From there, Pastor started to wonder whether it was possible to make an animal more resistant to rabies after it had already been bitten. Preventing it from developing the disease. Having successfully tested out this idea in dogs, he tried at it on two people, but he didn't publish on either of these attempts, so they were not known about until much later. One of these was a man who had been bitten by a dog, and while this man survived, it's also likely that he had not actually been exposed to rabies. The other was an eleven year old girl who had been bitten in the face by a puppy, and she had already started developing rabies symptoms. She died the day after she was given the treatment. On July four, nine year old Joseph Meister was repeatedly bitten by a dog in Alsace. The dog was believed to be rabid, and two days later the child was brought to Pestor for help. Emil Ru had been heavily involved in Pestor's research up to this point, and he refused to be involved in the boy's treatment because of ethical concerns. Pastor expressed some reluctance as well, but Joseph Granche and Alfred Vopien of the Academy to Medicine encouraged him to try with granch admit us during the treatment. Since Pastor was not a doctor, Joseph was given a series of inoculations over the span of ten days, starting with a very weak preparation and working up through ones that were less and less attenuated. Three months later, he had no sign of rabies. Another attempt was started with another patient shortly after Joseph Meister was declared to be in the clear. That was Jean Baptiste Jupel, a fourteen year old shepherd who had been mauled while saving a group of younger boys from a dog. Pastor reported his results to the French Academy of Science on October eighteen eighty five, while Dupeel's treatment was still ongoing. Told about his success with Joseph Meister and the fact that he had successfully inoculated fifty dogs against rabies before trying this process on a human. We're gonna talk more about what happened with all of this after we paused for a quick sponsor break. As a word of Pastor's success that preventing rabies started to spread, people started flocking to him for treatment. By the start of eighteen eighties six, he had treated at least three hundred and fifty people. They came from all over Europe and from the United States. In early December of eighteen eighty five, a dog bit at least seven other dogs and six children in Newark, New Jersey. Word of Pastor's work had made it to the US, and a local doctor published an appeal for funds to send the boys to Paris for treatment. Four of the boys were sent to Paris by steamer. The other two were determined to not have sufficient injuries to need treatment. American news coverage of these boys tripped to Paris and then they returned to the United States turned rabies vaccine into just a media station, and three of the boys were displayed at the Globe Museum in the Bowery in New York after they all got home. Not everyone agreed with what Pastor and his team were doing. Anti vivisectionists objected to the use of animals in this research. And as we've said, not everyone who is bitten by a rabid animal contracts rabies, and not every animal who bites someone is rabid. Since there was still not a test for rabies, determining whether an animal had it usually involved just waiting to see if it died. But that wasn't really possible if it had already been killed, or if it just couldn't be found. You could also expose a healthy animal to the brain or saliva of an animal who had bitten someone, but by the time the healthy animal showed any symptoms, it was just likely to be too late for the human patient. So critics made the point that Pasteur was potentially exposing people to rabies for no reason, and his inoculation caused somebody who had been bitten by a non rabid dog to then develop rabies because of their treatment. Critics also noted that some of pasteurs patients did die. By November of eighteen eighty six, seventeen hundred patients had received rabies injections, and ten of them had died. The uncertainty combined with the deaths to spark a huge amount of debate within the medical community about whether what Pasteur was doing was ethical or even medically necessary. The Academy Demnsen held a meeting on the subject on January eleventh, eighteen eighty seven. Although Pastor's critics were vocal, his supporters, led by Dr Joseph Granche, successfully defended his work. The Institute Pasteur was established on June fourth, eighteen eighty seven, and it opened on November fourteenth of that year. It focused on disease research and on providing rabies vaccine. By eight more than twenty thousand people had been treated at the Pastier Institute after a possible rabies exposure, and only nine six of them had died, or less than half of a percent of patients. To be clear, there was a lot about this early version of the vaccine that was inherently unsafe. It was basically made from animal brain or spinal corn tissue. There could for sure be complications, but this was still a dramatic improvement over an untreatable fatal disease. Discoveries about the rabies virus continued after this point. In three, Italian pathologist al Deci Negri discovered round and oval regions in the brains of animals that had died of rabies, which he called negribodies. At the time he thought they were some kind of parasite, but they actually arise as part of the reproductive cycle of the virus. This paved the way for the first rabies tests. While there are new methods for detecting rabies in brain matter, Today, negribodies are still sometimes used when those methods are not available. The most reliable tests do still involve examining an animal's brain, which is why living animals have to be euthanized to be tested for rabies. Refinements in the vaccine were also in the works. Pastor's methods didn't always produce a consistently potent vaccine, and if it was too potent, it could cause somebody to contract rabies. In the early twentieth century, researchers started using phenol to kill the virus rather than attenuating it through air drying. Viruses were cultured in tissues in NY six, which led to tissue cultured vaccines rather than using brain matter to make them. Today's rabies vaccines are mostly cultured in human cells or in chick embryos or some other cellular matter. Although some of Pastor's colleagues speculated about whether it would be possible to mass vaccinate dogs or other animals and lower the spread of rabies to people, serious efforts to do that didn't start until decades later, but efforts like that have led to the successful eradication of rabies in some parts of the world. There are too many rabies free countries today for us to try to name them all, but they include many islands, including many Caribbean islands, the Canary Islands, the Falkland Islands, the Galapagos Islands, the UK, Iceland, Japan, and New Zealand. Several nations in continental Europe are also considered rabies free, including much of Western Europe. We should note, though, that rabies free often means rabies free and terrestrial animals. There can still be rabies or other lists of viruses in bats, specifically, so even if you are somewhere that is considered rabies free, being bitten by a bat still warrants medical attention. Just in general, don't touch baths with your bare hands. You don't need to be afraid of bats. They're generally pretty shy and they're not gonna mess with you if you don't mess with that. But like, don't go grab one with your hands, which is so hard because they're so cute, not for me because I see one. Like if I see a bat somewhere that I don't expect to see a bat, I'm like that bat is definitely a problem. I'm not going anywhere near it. I will tell a bat story and are behind the scenes. As we said at the top of the show, rabies is still endemic in some parts of the world, including parts of Asia and Africa. About of human rabies deaths occur each year in India, with the vast majority of those exposures coming from dogs, and some serious outbreaks among wild animals started long after the raby's vaccine was developed. For example, rabies was identified in North American raccoons in nineteen thirty six, and there is an ongoing epidemic of rabies among rec coons all along the East Coast. There are efforts to get these and other outbreaks in wild animals under control, using things like oral rabies vaccine baits. Yeah, they're also mass vaccination campaigns. A lot of work on this. A lot of the deaths that occur around the world happen in children who just wanted to pet a dog and got bitten, so it is very sad. It's also possible for one animal to spark a huge exposure scenario even in places where rabies is relatively well controlled. For example, on October a family bought a kitten from a pet store in New Hampshire and then about three weeks later, this kitten developed seizures and died. After its death, it was determined to have had rabies. This kitten had been examined by a veterinarian and had a certificate of health before it was sold, but the pet store didn't have clear records of when animals had arrived there or been sold, so in the end, six hundred sixty five people received post exposure prophylaxis or PEP for rabies. These were people who had come into contact with that kitten, or who had bought other animals that had probably had contact with the kitten at the store, or people who had contact with those animals, people who worked at the store, people who visited the store and handled the animals. Really just on and on. The probable initial source for this whole thing was a raccoon that may have come into contact with three feral kittens that were then captured and sold at the store. As a side note, you may have heard that Raby's prophylaxis is a horrifying series of incredibly painful shots directly into the stomach with a gigantic and terrifying needle. It is not Older versions of Raby's PEP did involve a long series of fourteen to twenty one shots usually given in the abdomen. But that's just because the abdomen offered a lot more surface area to work with, not because the injections went into the stomach through a huge needle. Still, I mean to be clear, that is a lot of shots into a tender area, and the vaccine that was in use at the time could have a range of unpleasant side effects. Yeah, I would not want to get fourteen to twenty one shots all around my abdominat it. It was not a gigantically long needle going into people's actual stomachs. It's also not what is in use today. The current recommendation is that a person gets one dose of human rabies immune globulin and one dose of rabies vaccine shortly after the bite. The immune globulin is typically injected near the bite location, and then the vaccine typically goes into the deltoid region of the arm, where lots of other vaccines go. Then the person gets three more doses of vaccine that are spread out in the days that follow, again as injections into the shoulder area. Also using a vaccine that is like cultured and tissues and a lot safer than what was being used in the past. This process can be a little bit different for children or if a person is um you know, compromised, or if a person has been previously vaccinated for rabies. That's something that's typically only done based on a person's risk for being exposed to rabies. As another side note, we have been really really focused on bites here because the overwhelming majority of rabies exposures come from bites or possibly scratches. There are some other ways to contract the disease, but they're extraordinarily rare, like through the eyes or mucous membranes. If someone is exposed to aerosolized rabies virus in some way, or because rabies can closely resemble various types of encephalitis, it is sometimes missed as a diagnosis when doctors don't know that the person was bitten by an animal. This has led to an extremely small a number of rabies transmissions through organ transplants, although the risk of this is extremely remote. After their first report of it happening, many organ procurement organizations started including screening questions to try to rule out this possibility. Circling back around to rabies and pop culture, This was actually a plot line on the TV show Scrubs. Its sounds truly horrifying, but also like the disease process that rabies causes, like in the umbrella of encephalitis, And if a doctor doesn't know that a person was bitten by an animal or picked up a bat or whatever, like it's most doctors have never seen a case of rabies in their career, and it's not the thing that first comes to mind. In two thousand four, fifteen year old Gina Geezy and her medical team made headlines after she became the first person known to survive rabies after starting to develop symptoms. She had picked up and been bitten by a bat, and although her wound was cleaned with hydrogen per beside, she wasn't taken in for further treatment. She started developing symptoms about a month later, and then about six days into her illness reported having been bitten by the bat. Doctors placed ge Zy in a medically induced coma and gave her anti viral drugs and other treatments. These treatments continued until tess suggested that her body was fighting off the virus, and at that point she was brought out of the coma. She survived this experience, and news outlets have continued to report on her life into the year one. At the time, this seemed like a hopeful sign that what came to be known as the Milwaukee Protocol would make it possible to cure people after they started showing symptoms of rabies, but efforts to replicate that success have been largely unsuccessful. One paper in the Journal of the Brazilian Society of Tropical Medicine traced thirty eight published uses of the Milwaukee Protocol, including one use of a similar protocol called the Recipe proto Call. Only eleven of those patients survived, with all but five of them having moderate to severe complications afterward. This is certainly an improvement over a disease with an essentially fatality rate, but these numbers may be deceptively optimistic. Three of the people who were described as having survived did make it through the most critical part of the illness, but they still died. At least one of the patients may not have actually had rabies, and there's been no coordinated method for tracking when this protocol has or hasn't been attempted. It's likely that anyone who tried it and succeeded would publish their results. But it's also possible that people who tried it and failed have not yet. There are some papers like Opinion Commentary written by teams of doctors that are like this does not work and we need to stop focusing our effort on it, and others that are a little bit more like this may need some other refining before it could work. Aside from all that, though, all the patients described in these publications spent at least a month in the hospital with extensive care throughout their stay, so it's extremely unlikely that this protocol could really be put into use in the places where human deaths from rabies are the most prevalent. These places tend to be rural and poor without a lot of health care infrastructure. Places where people don't have access to Raby's profile axis are likely to also be places where people don't have access to a hospital that could support this kind of treatment. Also, it's extremely clear at this point that coordinated programs of public education and dog vaccinations and sometimes vaccinations in particular wild animals, can lower the number of human Raby's deaths enormously, and places that don't have the resources to support those kinds of programs and initiatives are really likely not to have the resources to support hundreds or thousands of people with long term hospital stays and medically induced comas. It's like, even if this worked, it would really be working for the wealthiest countries in the world and not the places where treatment is most needed. So all of that said, the global cost of rabies is roughly eight point six billion dollars per year, and more than fifteen million people per year received rabies PEP. This protocol can be really expensive. In the United States, it can cost between twelve hundred and sixty hundred dollars. Yeah, that's like one estimate that I can saw that I saw. I saw something that were even higher than that. September twenty eight every year is World Raby's Day. That's also the anniversary of the death of Louis Pasteur. Well, that's a basic history of rabies. Rabies. My my hope is that in the future will at least get to the point where the places in the world that have lots of free roaming dogs also have those dogs vaccinated, because that's really where like so much feeding back into the greater environment and so much feeding into humans cases of rabies, Like it's all interconnected with the dogs. Yeah. I think we mentioned it at the top of our episode on the history of veterinary medicine that one of the vets at my practice participates in a program where she goes to countries where the dog population is not well vaccinated and tries to just do as many vaccinations as they can in a short period of time. Yeah, they had gone some mallowe I think. And Malawi's target is like se of the dog population vaccinated, which would do a lot to reduce the number of human deaths, but still would like there would still be a reservoir of circulating rabies among dog populations. There are a lot of sad parts to that, but one of the saddest parts is like a lot of the a lot of the people who die of rabies are like just a kid that wanted to pet a dog. So anyway, uh, I haven't a listener mail it's about animals, um, it's not about rabies. It's from Kaylee, And it followed our episodes on Shackleton. Kaylee rode in and said, Hi, Holly and Tracy, I'm a huge fan of yours. I've been listening to your podcast for years. I finally have something to write to you about. I just listened to the Endurance episodes. I can't wait for your behind the scenes episodes about it. I'm a children's librarian in Maine, and it's my job to try to read as many books in our children's collection in order to give recommendations. Well, a twenty nineteen book called Fearless Felines thirty True Tales of Courageous Cats came across my desk a few months back, and as an avid cat lover, I opened up the book and immediately started reading. The first story I happened to see was about Mrs Chippy, the explorer cat aboard the Endurance. According to this children's book and other research, I found, Mrs Chippy would climb in the rigging and walker along the narrow ship rails, even in bad weather. There was one episode where Mrs Chippy jumped through the porthole and the crew had to rescue him after he spent ten minutes in the water. When I read the part about the ship getting stuck in shackleton, making tough decisions and this meant no more Mrs Chippy, I absolutely lost it and hit in the library basement, bawling my eyes out. As a highly sensitive person, sometimes I wonder if I can make it as a children's librarian from all the books I've read that have caused tears. Fast forward to more recent weeks than I was driving to work and listening to NPR and the story of the Endurance wreckage being discovered came on. A descendant of Shackleton was talking about how their great grandfather was a hero and brave and all I could do was hell but he killed Mrs Chippy at the radio, listening to your episodes about Shackleton and the Endurance gave me another perspective. Though Shackleton clearly cared about his crew, from their health to the morale. Their situation was dire, and I'm glad Mrs Chippy, along with the puppies and dogs, didn't starve to death. You probably found this in your research. But mc nish, the carpenter on the Endurance, held a grudge against Shackleton after the whole Mrs Shippy Ordeal McNish died penniless and was buried in an unmarked grave. In nineteen thirty. The New Zealand Antarctic Society gave him a headstone in nineteen fifty nine, and then in two thousand four, a life size bronze statue of Mrs Chippy was built on his grave. Visiting his grave and the Mrs Chippy memorial is now on my bucket list and if I make it, I'll be sure to send a picture. But in the meantime, here's a picture of my cat family I rescued last summer. Past regards from a librarian considering joining Peter Cayley, thank you so much for this email. You are not the only person who commented in some way about being angry at Shackleton about Mrs Chippy. Like when we put the episode on our on our social media, there were various comments that said things like he killed Mrs Chippy, he's a monster of and it uh, it reminded me a little bit um. Some years ago, we were having a conversation about potential future episode topics and suggestions on our Facebook page or somewhere, and there were a lot of people who were asking for LM. Montgomery, who wrote Ann of Green Gables, who was definitely on my to do list for an episode. And there was one particular person who had been apparently traumatized by a scene in one of the later books that involves a cat being killed, and then was like commenting in reply to every single person who suggested that topic with like how horrible the cat death was, And I was like you, clearly, this is something that really upset you as a child. But attitudes about animals were very different at the time, and like what people thought of as the humane way to treat animals not the same as we think of now when we think of pets as family members. A very different situation, and I understand how upsetting it can be. But like Kaylee, I'm glad that the animals who were with Shackleton, although we could have a whole argument about whether they should have been there in the first place, glad that they did not face some of the dire situations of of hunger and cold and all of that that the that the men faced. Um, so thank you for this email and the picture. And the story is about Mrs Chippy. I didn't put a lot about Mrs Chippy in the episode itself because I didn't want to make the end of Mrs Chippy even sadder than it already was. Like part of me didn't even want to put the name Mrs Chippy in there, but some how that made it harder. Um, so thank you for giving me the chance to share some Mrs Chippy stories. You would like to write to us about this or any other podcasts for a history podcast at iHeart radio dot com. And we're all over social media at MS in history That's Real Fight or Facebook, Twitter, Pinterest, and Instagram. And you can subscribe to our show on the iHeart Radio app or wherever you like to get your podcasts. Stuff you Missed in History Class is a production of I heart Radio. For more podcasts from I heart Radio, visit the iHeart Radio app, Apple Podcasts, or wherever you listen to your favorite shows.

Welcome to Stuff You Missed in History Class, a production of I Heart Radio. Hello, and welcome to the podcast. I'm Tracy V. Wilson. Now I'm Holly Fry. Foxes are one of many wild animals that share cities and other places with human beings, and in April, one of them made headlines after biting at least nine people around the US capital. When this story crossed my Twitter feed, I'm became incredibly invested in whether everybody who got bitten by this fox had gotten their rabies shots. Afterward, news articles were not telling me the answer to this information. Some of them were talking about a specific reporter or a specific congress person, but I was like, no, everybody, everybody needs to get the raby shots because foxes can carry rabies. Rabies is virtually always is fatal once people develop symptoms, once anyone developed symptoms, but today's rabies profile access is almost a dent effective at preventing that from happening. It is I think the most effective vaccine that we have in existence. So then when news broke that yes, this fox did have rabies, it was like just a big flashing, screaming side in my brain, like raby shots raby shots. Raby shots, Please tell me everyone got their rabies shots. Of course, then that made me want to do a podcast on rabies and the vaccine that prevents it, something that somehow I thought we already had stuff on. We don't, or if we do, I failed to find it. The vast majority of our listeners live in places where Raby's deaths in humans are extremely rare. Some parts of the world are rabies free, and here in the United States there were only five human deaths from rabies, and that was the highest number of annual rabies deaths in the United States in a decade. There are also places, though, where rabies is still endemic, and globally about fifty six thousand people die from it every year. That is not like that's a small number compared to something like the current pandemic, but they're fifty six thousand totally preventable deaths, Like we have what we need to prevent this, So I wanted to talk about that heads up though there's a lot of animal experimentation in this episode and deaths. Obviously, rabies is caused by rabies list of virus, which probably originated in Old World bats. This virus has existed on every continent except Antarctica and Australia for millennia, and although Australia is Rabi's free, it's home to a closely related virus called bat lists of virus. But in spite of the viruses connection to Bat's humanity's connection to rabies has mainly been through dogs. That connection show is up in the first written reference we have of rabies, that's in the Eshnuna code from roughly two thousand b c e. Shnano was a city and what's now Iraq, and some of its laws have survived on a pair of broken tablets that were found at an archaeological site near Baghdad. Here's one of the laws quote. If a dog is mad, and the authorities have brought the fact to the knowledge of its owner, if he does not keep it in, and it bites a man and causes his death, then the owner shall pay two thirds of amina of silver. If it bites a slave and causes his death, he shall pay fifteen shekels of silver. The first written reference to rabies in China is from the Zoo tradition, sometimes called the Zoo Commentary. This is a commentary on the spring and Autumn Annals, which chronicles a period of Chinese history stretching from seven twenty two to four eighty one b C. One passage in the Two Tradition describes people of the capital city of Sung chasing a rabid dog. The dog ran into the home of a minister named wat Chin, and the people chased after it. Wat Chin was afraid and fled the city, and about the fourth century BC, Aristotle wrote this and his History of Animals quote dogs suffer from three diseases, rabies, quincy, and sore feet. Rabies drives the animal mad, and any animal whatever, accepting man, will take the disease if bitten by a dog so afflicted, the disease is fatal to the dog itself and to any animal it may bite man accepted. So this translation makes it sound like Aristotle was saying that humans don't get rabies, but it's also been interpreted as meaning that people don't always develop rabies when bitten by a rabid dog, and that is true, or that people don't always die from the disease if they contract it, which is almost never true. People will have known that rabies was essentially always fatal for thousands of years, though Roman court physicians Scribonious Largest described rabies as incurable in the first century CE. In addition to being lethal, rabies progresses in a way that can be really terrifying. The exact symptoms can vary, but there are two broad categories, both of which end in coma and death. Paralytic rabies involves lethargy, weakness, and paralysis, and furious rabies involves agitation, aggression, and hyperactivity. The word rabies reflects this latter type that comes from the Latin for to rage, which may have roots in a Sanskrit word meaning to do violence. Lissa virus has a similar root. It comes from a Greek word meaning frenzy or madness, which was used to describe rabies as well as to describe irrational rage. Raby shows up a lot in popular cult sure, and that goes back thousands of years as well, including the use of rabies or rabid dogs as a metaphor for being mad or uncontrollable. For example, in the Iliad, which was written in about the eighth century b c. E. Homer describes Hector as a rabid dog. Rabies can also cause paralysis and spasms in the throat that make it impossible to swallow water. That's why it's also known as hydrophobia, and the second century CE Roman philosopher Celsus used the word hydrophobia in his description of the disease. Celsus also recognized that something was present in saliva that transmitted this illness, and he recommended a range of techniques to draw this substance out of wounds. Like the connection between rabies and aggressive rage, the connection between rabies and hydrophobia made its way into literature centuries ago. For example, in about the year five hundred, Klias A lean Is suggested that Homer's description of Tantalus in the Odyssey might have been inspired by rabies, since Tantalus is tormented by water that he cannot drink. It's also possible that rabies influenced ancient Greek depictions of Cerberus, the multi headed dog that guarded the underworld, and that those depictions of a mad beast with poison frothing from its jaws circled back to influence people's perceptions of rabies. So through these and other written references, we know that rabies had spread from wherever it originated, all through India, China, the Middle East, Greece, rome in Egypt by about fifteen hundred years ago, but we don't really know how widespread the disease was in any of these places, or how many deaths it caused among humans and other animals. That starts to change in the medieval period, when people started documenting large outbreaks of the disease within specific animals. These account it's primarily focused on outbreaks among dogs and other canids, including wolves and foxes. For example, an outbreak of wolf rabies struck Franconia in twelve seventy one. A massive outbreak among red foxes spread over parts of Europe between fifteen seventy one and fifteen eighty one, leading people to try to stop the disease by culling them. Sometimes these outbreaks could spread to other animals, including infecting people when they were bitten. At this point, we haven't mentioned rabies in the America's and that's because while rabies existed in the Americas through all this, rabid dogs probably did not. Based on genetic studies of the virus itself. Before European colonization, rabies and the America's primarily infected bats and skunks. There's some evidence that Indigenous peoples in ancient Central and South America regarded both bat bites and snake bites as potentially dangerous, treated bat bites with washing and cauterization with hot culls to try to prevent disease. Spanish colonists were reported being bitten by bats in the early fifteen hundreds, and in fifteen fourteen, Fernandez de Oviedo wrote about several soldiers dying after being bitten by vampire bats. Dog rabies is one of many diseases that Europeans introduced to the America's, and after that introduction, it spread to other animals and became far more likely to infect people, but that process did not happen nearly as quickly with rabies as it did with diseases like smallpox. Rabies typically has an incubation period of roughly three to eight weeks, although it can occasionally be much longer. Once symptoms appear, rabies is virtually always fatal within about ten days. When Europeans first started sailing to the America's, the voyage often took more than two months, so any dogs or other animals that had been infect did before setting sale usually developed symptoms and died or were killed while still at sea, so that meant introducing dog rabies to the America's required a voyage that was short enough for infected dogs to survive. It also required a large enough population of dogs and other mammals within a colony for the disease to keep circulating once it had been introduced. The first recorded outbreak of dog rabies in the Americas was reported in Mexico City in seventeen o nine, and by the end of the eighteenth century, dog rabies was widespread in most of the places in the Americas that Europeans had colonized. This in turn spread the disease to the continent's native animals, with some of those exposures leading to new strains of the virus that were adapted to specific species. We'll talk about how a vaccine was developed to prevent rabies after a sponsor break. By the eighteenth and nineteenth centuries, outbreaks of rabies were spread across a lot of the world and domesticated dogs and in wild animals. In North America, rabies became so widespread in skunks that they were nicknamed Phoebe cats like hydrophoby and phoebe tents were advertised as a way for cowboys to avoid being bitten by them in their sleep. In eighteen o three, and outbreak among wild foxes in France spread to dogs, pigs, and people. Bites from rabid wolves tended to be particularly lethal, in part because attacking wolves often bit people's faces or necks, meaning the virus was way closer to their brain, while rabid dogs usually bit people's hands or arms. There was no cure for rabies and no way to tell whether a person would develop it after being bitten, and estimates of how many people developed rabies after a bite stretch all the way from five percent to Some of this is just because of imprecise record keeping, but it's also connected to how people responded to the disease. In many places, there was a widespread assumption that any animal that bit had rabies, and during outbreaks, people tended to hunt down and kill animals that they thought might be spreading disease. So a dog that bits someone in the midst of all of this might be rabid, or it might just be scared and cornered and trying to defend itself. Around the world, people tried various herbs and medical preparations to prevent or cure rabies, and because it was so lethal, many of these were also relied on the idea of divine intervention. For example, Hubertus, also called St. Hubert Is the patron saint of hunting, and one of his reported miracles involved curing somebody who had been bitten by a rabid dog. So inch of Europe people used a piece of iron called St. Hubert's key to cauterize bite wounds. As part of this treatment, a priest would also make a shallow cut over a person's forehead, place a black bandage over that, and the person wore that bandage for nine days. Some people even carried one of these keys around with them for protection. Long before the development of the germ theory of disease, people recognize that when someone was bitten by a rabid animal, something in the animals saliva was going into the wound and potentially causing rabies. So some of the other treatments for bites involved washing the wound, applying caustic chemicals to it, or cauterizing in whether it was with a Saint Hubertists key or with some other implement. If these treatments were done immediately, after a person was bitten. They may have helped reduce the chance of developing rabies by washing away the animals infected saliva. Thoroughly washing the wound is still step one in rabies prevention today, but none of this was enough to totally prevent the chance of developing the fatal disease. People also tried to prevent rabies by reducing the numbers of animals that could carry it and transmit it to humans and to other animals. For example, in eighteen sixty seven, the UK passed the Metropolitan Streets Act. Among other things, this act empowered police to collect and muzzle stray dogs, are dogs that were determined to be dangerous. This reportedly led to a drop in human cases of rabies in British cities. Also in the eighteenth and nineteen centuries, researchers were learning about rabies and working on ways to prevent it spread. During the earlier part of this time, researchers didn't yet know what a virus was. But trying to talk around that got really clunky. So we are still going to call it a virus in our discussion today. Yeah, it was a lot of incredibly stilted sentences before I was like, we're just it a virus, regardless of whether that individual research or knew what a virus was. So in seventeen sixty nine, Italian anatomist and pathologist John Morganni observed that rabies traveled via the nerves rather than traveling through the bloodstream. He made this connection because some patients reported a feeling of pins and needles or other neurological disturbances around the site of their original bite wounds. Morgan was correct. Once it enters the body, the rabies virus moves along the nerves until it gets to the brain and the rest of the central nervous system. After it gets to the brain, the rabies virus makes its way to the salivary glands, where it can cause excessive salivation, and although eighteen century researchers didn't quite have that part figured out, they did know that the disease was spread through saliva. In seventeen ninety three, Scottish surgeon John Hunter speculated that it would be possible to use a lancet to intentionally introduce an infected animals saliva into another animal, but it's not clear whether he tried this in practice. We also don't know whether German naturalist George Gottfried Zinca was familiar with Hunter's work, but in eighteen o four he brushed saliva from a rabid dog onto a cut he had made in the leg of a healthy dog. This previously healthy dog contracted rabies. He did the same thing with other healthy mammals, demonstrating that it was possible for the bite of an infected dog to infect animals of other species. In eighteen twenty one, French neurophysiologist Francois Magendie reported that he had infected a previously healthy dog with saliva from a person who had contracted rabies. Victor Gautier was a professor at the National Veterinary School in Lyon, France, and he started experimenting with rabies in eighteen seventy nine. He found that it was possible to transmit rabies from a dog to a rabbit, and then from that rabbit to another rabbit. Rabbits were smaller and easier to keep than dogs, and they were less dangerous research subjects than rabbid dogs were. Gaultier also found that the rabbits had a shorter incubation period of about eighteen days rather than a month or more that you might see in a dog. Gaultier did various experiments with infected animals saliva, attempting to see whether he could find some way of using this infectious material to prevent rabies. In eighteen eighty one, he injected rabies virus into the jugular veins of sheep and they didn't develop rabies, and then when he exposed one of them to saliva from a rabbit dog later on, it seemed like it was immune to the disease. French chemist and microbiologist Louis Pasteur started working on rabies at about this same time, and he was inspired by Gaultier success. Pastor already an extensive background in this kind of work. In the eighteen fifties, he had studied yeast and alcohol fermentation, as well as the ability for micro organisms to contaminate fermenting beverages. This had contributed to both the germ theory of disease and the development of pasteurization. In the eighteen sixties, he had identified a micro organism that was devastating the French silk industry, and in the eighteen seventies he studied animal diseases like anthrax and chicken colera, including developing an anthrax vaccine. While Pasteur had lots of experience in this kind of research, he had pretty much no experience in medicine or the clinical treatment of patients, so he relied on other people for this knowledge, including French physician and bacteriologist Emile Roux. A whole team of other scientists and doctors were involved in this work as well, including Charles Chamberlin, Emile Duclox, Louis Dulier, and Joseph grane A. This is definitely not a solo effort, and Pasteur was not always excited about crediting other people for their involvement in it. There are even some historians who have accused him of stealing other people's ideas. Much of Pastor's previous work had involved culturing bacteria and working from those cultures, and he started out trying to do the same thing with rabies. Since rabies is caused by a virus rather than a bacterium, Pastor's efforts to replicate his earlier process failed. He started working directly with the saliva of infected animals and then moved on to working with central nervous system matter. He found that if he exposed a healthy rabbit to rabies, it developed rabies. Then if he used that rabbit's central nervous system matter to expose another rabbit, that second rabbit also developed rabies, and the second rabbits infection seemed to be more virulent than the first. If he did this a third time, the third rabbit's infection was also more virulent than the seconds had been. He continued this serial passage of the virus from rabbits to rabbit until he had a strain of it that he described as fixed. It was consistent and how virulent it was, and it had an incubation period that was set at six or seven days. From there, Pastor air dried the spinal cords of rabbits that had died of that highly virulent fixed strain. The longer they dried, the weaker the virus became. That's a process called attenuation. When he exposed other animals to a small amount of this attenuated virus, they seemed to develop a resistance to rabies rather than becoming ill. From there, Pastor started to wonder whether it was possible to make an animal more resistant to rabies after it had already been bitten. Preventing it from developing the disease. Having successfully tested out this idea in dogs, he tried at it on two people, but he didn't publish on either of these attempts, so they were not known about until much later. One of these was a man who had been bitten by a dog, and while this man survived, it's also likely that he had not actually been exposed to rabies. The other was an eleven year old girl who had been bitten in the face by a puppy, and she had already started developing rabies symptoms. She died the day after she was given the treatment. On July four, nine year old Joseph Meister was repeatedly bitten by a dog in Alsace. The dog was believed to be rabid, and two days later the child was brought to Pestor for help. Emil Ru had been heavily involved in Pestor's research up to this point, and he refused to be involved in the boy's treatment because of ethical concerns. Pastor expressed some reluctance as well, but Joseph Granche and Alfred Vopien of the Academy to Medicine encouraged him to try with granch admit us during the treatment. Since Pastor was not a doctor, Joseph was given a series of inoculations over the span of ten days, starting with a very weak preparation and working up through ones that were less and less attenuated. Three months later, he had no sign of rabies. Another attempt was started with another patient shortly after Joseph Meister was declared to be in the clear. That was Jean Baptiste Jupel, a fourteen year old shepherd who had been mauled while saving a group of younger boys from a dog. Pastor reported his results to the French Academy of Science on October eighteen eighty five, while Dupeel's treatment was still ongoing. Told about his success with Joseph Meister and the fact that he had successfully inoculated fifty dogs against rabies before trying this process on a human. We're gonna talk more about what happened with all of this after we paused for a quick sponsor break. As a word of Pastor's success that preventing rabies started to spread, people started flocking to him for treatment. By the start of eighteen eighties six, he had treated at least three hundred and fifty people. They came from all over Europe and from the United States. In early December of eighteen eighty five, a dog bit at least seven other dogs and six children in Newark, New Jersey. Word of Pastor's work had made it to the US, and a local doctor published an appeal for funds to send the boys to Paris for treatment. Four of the boys were sent to Paris by steamer. The other two were determined to not have sufficient injuries to need treatment. American news coverage of these boys tripped to Paris and then they returned to the United States turned rabies vaccine into just a media station, and three of the boys were displayed at the Globe Museum in the Bowery in New York after they all got home. Not everyone agreed with what Pastor and his team were doing. Anti vivisectionists objected to the use of animals in this research. And as we've said, not everyone who is bitten by a rabid animal contracts rabies, and not every animal who bites someone is rabid. Since there was still not a test for rabies, determining whether an animal had it usually involved just waiting to see if it died. But that wasn't really possible if it had already been killed, or if it just couldn't be found. You could also expose a healthy animal to the brain or saliva of an animal who had bitten someone, but by the time the healthy animal showed any symptoms, it was just likely to be too late for the human patient. So critics made the point that Pasteur was potentially exposing people to rabies for no reason, and his inoculation caused somebody who had been bitten by a non rabid dog to then develop rabies because of their treatment. Critics also noted that some of pasteurs patients did die. By November of eighteen eighty six, seventeen hundred patients had received rabies injections, and ten of them had died. The uncertainty combined with the deaths to spark a huge amount of debate within the medical community about whether what Pasteur was doing was ethical or even medically necessary. The Academy Demnsen held a meeting on the subject on January eleventh, eighteen eighty seven. Although Pastor's critics were vocal, his supporters, led by Dr Joseph Granche, successfully defended his work. The Institute Pasteur was established on June fourth, eighteen eighty seven, and it opened on November fourteenth of that year. It focused on disease research and on providing rabies vaccine. By eight more than twenty thousand people had been treated at the Pastier Institute after a possible rabies exposure, and only nine six of them had died, or less than half of a percent of patients. To be clear, there was a lot about this early version of the vaccine that was inherently unsafe. It was basically made from animal brain or spinal corn tissue. There could for sure be complications, but this was still a dramatic improvement over an untreatable fatal disease. Discoveries about the rabies virus continued after this point. In three, Italian pathologist al Deci Negri discovered round and oval regions in the brains of animals that had died of rabies, which he called negribodies. At the time he thought they were some kind of parasite, but they actually arise as part of the reproductive cycle of the virus. This paved the way for the first rabies tests. While there are new methods for detecting rabies in brain matter, Today, negribodies are still sometimes used when those methods are not available. The most reliable tests do still involve examining an animal's brain, which is why living animals have to be euthanized to be tested for rabies. Refinements in the vaccine were also in the works. Pastor's methods didn't always produce a consistently potent vaccine, and if it was too potent, it could cause somebody to contract rabies. In the early twentieth century, researchers started using phenol to kill the virus rather than attenuating it through air drying. Viruses were cultured in tissues in NY six, which led to tissue cultured vaccines rather than using brain matter to make them. Today's rabies vaccines are mostly cultured in human cells or in chick embryos or some other cellular matter. Although some of Pastor's colleagues speculated about whether it would be possible to mass vaccinate dogs or other animals and lower the spread of rabies to people, serious efforts to do that didn't start until decades later, but efforts like that have led to the successful eradication of rabies in some parts of the world. There are too many rabies free countries today for us to try to name them all, but they include many islands, including many Caribbean islands, the Canary Islands, the Falkland Islands, the Galapagos Islands, the UK, Iceland, Japan, and New Zealand. Several nations in continental Europe are also considered rabies free, including much of Western Europe. We should note, though, that rabies free often means rabies free and terrestrial animals. There can still be rabies or other lists of viruses in bats, specifically, so even if you are somewhere that is considered rabies free, being bitten by a bat still warrants medical attention. Just in general, don't touch baths with your bare hands. You don't need to be afraid of bats. They're generally pretty shy and they're not gonna mess with you if you don't mess with that. But like, don't go grab one with your hands, which is so hard because they're so cute, not for me because I see one. Like if I see a bat somewhere that I don't expect to see a bat, I'm like that bat is definitely a problem. I'm not going anywhere near it. I will tell a bat story and are behind the scenes. As we said at the top of the show, rabies is still endemic in some parts of the world, including parts of Asia and Africa. About of human rabies deaths occur each year in India, with the vast majority of those exposures coming from dogs, and some serious outbreaks among wild animals started long after the raby's vaccine was developed. For example, rabies was identified in North American raccoons in nineteen thirty six, and there is an ongoing epidemic of rabies among rec coons all along the East Coast. There are efforts to get these and other outbreaks in wild animals under control, using things like oral rabies vaccine baits. Yeah, they're also mass vaccination campaigns. A lot of work on this. A lot of the deaths that occur around the world happen in children who just wanted to pet a dog and got bitten, so it is very sad. It's also possible for one animal to spark a huge exposure scenario even in places where rabies is relatively well controlled. For example, on October a family bought a kitten from a pet store in New Hampshire and then about three weeks later, this kitten developed seizures and died. After its death, it was determined to have had rabies. This kitten had been examined by a veterinarian and had a certificate of health before it was sold, but the pet store didn't have clear records of when animals had arrived there or been sold, so in the end, six hundred sixty five people received post exposure prophylaxis or PEP for rabies. These were people who had come into contact with that kitten, or who had bought other animals that had probably had contact with the kitten at the store, or people who had contact with those animals, people who worked at the store, people who visited the store and handled the animals. Really just on and on. The probable initial source for this whole thing was a raccoon that may have come into contact with three feral kittens that were then captured and sold at the store. As a side note, you may have heard that Raby's prophylaxis is a horrifying series of incredibly painful shots directly into the stomach with a gigantic and terrifying needle. It is not Older versions of Raby's PEP did involve a long series of fourteen to twenty one shots usually given in the abdomen. But that's just because the abdomen offered a lot more surface area to work with, not because the injections went into the stomach through a huge needle. Still, I mean to be clear, that is a lot of shots into a tender area, and the vaccine that was in use at the time could have a range of unpleasant side effects. Yeah, I would not want to get fourteen to twenty one shots all around my abdominat it. It was not a gigantically long needle going into people's actual stomachs. It's also not what is in use today. The current recommendation is that a person gets one dose of human rabies immune globulin and one dose of rabies vaccine shortly after the bite. The immune globulin is typically injected near the bite location, and then the vaccine typically goes into the deltoid region of the arm, where lots of other vaccines go. Then the person gets three more doses of vaccine that are spread out in the days that follow, again as injections into the shoulder area. Also using a vaccine that is like cultured and tissues and a lot safer than what was being used in the past. This process can be a little bit different for children or if a person is um you know, compromised, or if a person has been previously vaccinated for rabies. That's something that's typically only done based on a person's risk for being exposed to rabies. As another side note, we have been really really focused on bites here because the overwhelming majority of rabies exposures come from bites or possibly scratches. There are some other ways to contract the disease, but they're extraordinarily rare, like through the eyes or mucous membranes. If someone is exposed to aerosolized rabies virus in some way, or because rabies can closely resemble various types of encephalitis, it is sometimes missed as a diagnosis when doctors don't know that the person was bitten by an animal. This has led to an extremely small a number of rabies transmissions through organ transplants, although the risk of this is extremely remote. After their first report of it happening, many organ procurement organizations started including screening questions to try to rule out this possibility. Circling back around to rabies and pop culture, This was actually a plot line on the TV show Scrubs. Its sounds truly horrifying, but also like the disease process that rabies causes, like in the umbrella of encephalitis, And if a doctor doesn't know that a person was bitten by an animal or picked up a bat or whatever, like it's most doctors have never seen a case of rabies in their career, and it's not the thing that first comes to mind. In two thousand four, fifteen year old Gina Geezy and her medical team made headlines after she became the first person known to survive rabies after starting to develop symptoms. She had picked up and been bitten by a bat, and although her wound was cleaned with hydrogen per beside, she wasn't taken in for further treatment. She started developing symptoms about a month later, and then about six days into her illness reported having been bitten by the bat. Doctors placed ge Zy in a medically induced coma and gave her anti viral drugs and other treatments. These treatments continued until tess suggested that her body was fighting off the virus, and at that point she was brought out of the coma. She survived this experience, and news outlets have continued to report on her life into the year one. At the time, this seemed like a hopeful sign that what came to be known as the Milwaukee Protocol would make it possible to cure people after they started showing symptoms of rabies, but efforts to replicate that success have been largely unsuccessful. One paper in the Journal of the Brazilian Society of Tropical Medicine traced thirty eight published uses of the Milwaukee Protocol, including one use of a similar protocol called the Recipe proto Call. Only eleven of those patients survived, with all but five of them having moderate to severe complications afterward. This is certainly an improvement over a disease with an essentially fatality rate, but these numbers may be deceptively optimistic. Three of the people who were described as having survived did make it through the most critical part of the illness, but they still died. At least one of the patients may not have actually had rabies, and there's been no coordinated method for tracking when this protocol has or hasn't been attempted. It's likely that anyone who tried it and succeeded would publish their results. But it's also possible that people who tried it and failed have not yet. There are some papers like Opinion Commentary written by teams of doctors that are like this does not work and we need to stop focusing our effort on it, and others that are a little bit more like this may need some other refining before it could work. Aside from all that, though, all the patients described in these publications spent at least a month in the hospital with extensive care throughout their stay, so it's extremely unlikely that this protocol could really be put into use in the places where human deaths from rabies are the most prevalent. These places tend to be rural and poor without a lot of health care infrastructure. Places where people don't have access to Raby's profile axis are likely to also be places where people don't have access to a hospital that could support this kind of treatment. Also, it's extremely clear at this point that coordinated programs of public education and dog vaccinations and sometimes vaccinations in particular wild animals, can lower the number of human Raby's deaths enormously, and places that don't have the resources to support those kinds of programs and initiatives are really likely not to have the resources to support hundreds or thousands of people with long term hospital stays and medically induced comas. It's like, even if this worked, it would really be working for the wealthiest countries in the world and not the places where treatment is most needed. So all of that said, the global cost of rabies is roughly eight point six billion dollars per year, and more than fifteen million people per year received rabies PEP. This protocol can be really expensive. In the United States, it can cost between twelve hundred and sixty hundred dollars. Yeah, that's like one estimate that I can saw that I saw. I saw something that were even higher than that. September twenty eight every year is World Raby's Day. That's also the anniversary of the death of Louis Pasteur. Well, that's a basic history of rabies. Rabies. My my hope is that in the future will at least get to the point where the places in the world that have lots of free roaming dogs also have those dogs vaccinated, because that's really where like so much feeding back into the greater environment and so much feeding into humans cases of rabies, Like it's all interconnected with the dogs. Yeah. I think we mentioned it at the top of our episode on the history of veterinary medicine that one of the vets at my practice participates in a program where she goes to countries where the dog population is not well vaccinated and tries to just do as many vaccinations as they can in a short period of time. Yeah, they had gone some mallowe I think. And Malawi's target is like se of the dog population vaccinated, which would do a lot to reduce the number of human deaths, but still would like there would still be a reservoir of circulating rabies among dog populations. There are a lot of sad parts to that, but one of the saddest parts is like a lot of the a lot of the people who die of rabies are like just a kid that wanted to pet a dog. So anyway, uh, I haven't a listener mail it's about animals, um, it's not about rabies. It's from Kaylee, And it followed our episodes on Shackleton. Kaylee rode in and said, Hi, Holly and Tracy, I'm a huge fan of yours. I've been listening to your podcast for years. I finally have something to write to you about. I just listened to the Endurance episodes. I can't wait for your behind the scenes episodes about it. I'm a children's librarian in Maine, and it's my job to try to read as many books in our children's collection in order to give recommendations. Well, a twenty nineteen book called Fearless Felines thirty True Tales of Courageous Cats came across my desk a few months back, and as an avid cat lover, I opened up the book and immediately started reading. The first story I happened to see was about Mrs Chippy, the explorer cat aboard the Endurance. According to this children's book and other research, I found, Mrs Chippy would climb in the rigging and walker along the narrow ship rails, even in bad weather. There was one episode where Mrs Chippy jumped through the porthole and the crew had to rescue him after he spent ten minutes in the water. When I read the part about the ship getting stuck in shackleton, making tough decisions and this meant no more Mrs Chippy, I absolutely lost it and hit in the library basement, bawling my eyes out. As a highly sensitive person, sometimes I wonder if I can make it as a children's librarian from all the books I've read that have caused tears. Fast forward to more recent weeks than I was driving to work and listening to NPR and the story of the Endurance wreckage being discovered came on. A descendant of Shackleton was talking about how their great grandfather was a hero and brave and all I could do was hell but he killed Mrs Chippy at the radio, listening to your episodes about Shackleton and the Endurance gave me another perspective. Though Shackleton clearly cared about his crew, from their health to the morale. Their situation was dire, and I'm glad Mrs Chippy, along with the puppies and dogs, didn't starve to death. You probably found this in your research. But mc nish, the carpenter on the Endurance, held a grudge against Shackleton after the whole Mrs Shippy Ordeal McNish died penniless and was buried in an unmarked grave. In nineteen thirty. The New Zealand Antarctic Society gave him a headstone in nineteen fifty nine, and then in two thousand four, a life size bronze statue of Mrs Chippy was built on his grave. Visiting his grave and the Mrs Chippy memorial is now on my bucket list and if I make it, I'll be sure to send a picture. But in the meantime, here's a picture of my cat family I rescued last summer. Past regards from a librarian considering joining Peter Cayley, thank you so much for this email. You are not the only person who commented in some way about being angry at Shackleton about Mrs Chippy. Like when we put the episode on our on our social media, there were various comments that said things like he killed Mrs Chippy, he's a monster of and it uh, it reminded me a little bit um. Some years ago, we were having a conversation about potential future episode topics and suggestions on our Facebook page or somewhere, and there were a lot of people who were asking for LM. Montgomery, who wrote Ann of Green Gables, who was definitely on my to do list for an episode. And there was one particular person who had been apparently traumatized by a scene in one of the later books that involves a cat being killed, and then was like commenting in reply to every single person who suggested that topic with like how horrible the cat death was, And I was like you, clearly, this is something that really upset you as a child. But attitudes about animals were very different at the time, and like what people thought of as the humane way to treat animals not the same as we think of now when we think of pets as family members. A very different situation, and I understand how upsetting it can be. But like Kaylee, I'm glad that the animals who were with Shackleton, although we could have a whole argument about whether they should have been there in the first place, glad that they did not face some of the dire situations of of hunger and cold and all of that that the that the men faced. Um, so thank you for this email and the picture. And the story is about Mrs Chippy. I didn't put a lot about Mrs Chippy in the episode itself because I didn't want to make the end of Mrs Chippy even sadder than it already was. Like part of me didn't even want to put the name Mrs Chippy in there, but some how that made it harder. Um, so thank you for giving me the chance to share some Mrs Chippy stories. You would like to write to us about this or any other podcasts for a history podcast at iHeart radio dot com. And we're all over social media at MS in history That's Real Fight or Facebook, Twitter, Pinterest, and Instagram. 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