SYMHC Classics: Rabies

This 2022 episode discusses how modern rabies prophylaxis is almost 100% effective at preventing human death from the bite of a rabid animal. How did people come to understand rabies, and then develop a vaccination for it? See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Holly Frey?

  This is an iHeart Podcast. Guaranteed Human. A rare disease diagnosis can change your life, but it doesn't have to define your future. In season seven of Untold Stories: Life with a Severe Autoimmune Condition, host Martine Hackett continues the conversation with people living with MG, CIDP, and the broader rare disease community, exploring what comes after diagnosis through stories of hope, progress, and connection. Produced by Ruby Studio in partnership with Argentix. Listen on the iHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

• 0:35Tracy V. Wilson?

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• 1:08Speaker 02

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• 1:37Speaker 03

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• 1:55Holly Frey?

  Happy Saturday. Our episode on the dick and metal had a brief mention of efforts to keep the UK free of rabies. And we also just got an email from listener Whitney on the subject of a mass rabies exposure in the news. And we have been working on plans for our trip to Morocco in November, which is a country considered to be a high risk for dog rabies. Basically, we're just thinking a lot about rabies right now.

• 2:20Tracy V. Wilson?

  So seemed like a good time to replay our May 9, 2022, episode on the history of rabies. Enjoy.

• 2:31Holly Frey?

  Welcome to Stuff You Missed in History Class, a production of iHeartRadio.

• 2:42Tracy V. Wilson?

  Hello and welcome to the podcast. I'm Tracy V. Wilson.

• 2:45Holly Frey?

  And I'm Holly Frey.

• 2:47Tracy V. Wilson?

  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 Capitol. When this story crossed my Twitter feed, I 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 congressperson. But I was like, no, everybody, everybody needs to get the rabies shots because foxes can carry rabies. Rabies is

• 3:29Tracy V. Wilson?

  virtually always fatal once people develop symptoms, once anyone develops symptoms. But today's rabies prophylaxis is almost 100% 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 sign in my brain going rabies shots, rabies shots, rabies 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.

• 4:10Tracy V. Wilson?

  The vast majority of our listeners live in places where rabies 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 in 2021. 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 56,000 people die from it every year. That is not, like, that's a small number compared to something like the current pandemic. But there are 56,000 totally preventable deaths. Like, we have what we need to prevent this. So I wanted to talk about that.

• 4:55Tracy V. Wilson?

  Heads up, though, there's a lot of animal experimentation in this episode. And deaths, obviously.

• 5:02Holly Frey?

  Rabies is caused by rabies lissavirus, which probably originated in old world bats. This virus has existed on every continent except Antarctica and Australia for millennia. And although Australia is rabies free, it's home to a closely related virus called bat lissavirus. But in spite of the virus's connection to bats, humanity's connection to rabies has mainly been through dogs.

• 5:29Tracy V. Wilson?

  That connection shows up in the first written reference we have of rabies. That's in the Isnunacode from roughly 2000 BCE. Isnuno was a city in 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 a mina of silver. If it bites a slave and causes his death, he shall pay 15 shekels of silver."

• 6:10Holly Frey?

  The first written reference to rabies in China is from the Zuo Tradition, sometimes called the Zuo Commentary. This is a commentary on the Spring and Autumn annals, which chronicles a period of Chinese history stretching from 722 to 481 B.C. One passage in the Zuo Tradition describes people of the capital city of Sung chasing a rabid dog. The dog ran into the home of a minister named Huacheng, and the people chased after it. Huacheng was afraid and fled the city.

• 6:43Tracy V. Wilson?

  In about the 4th century BCE, Aristotle wrote this in his History of Animals, quote, "Dogs suffer from three diseases: rabies, quincy, and sore feet. Rabies drives the animal mad, and any animal whatever, excepting 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 excepted."

• 7:11Holly Frey?

  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 have known that rabies was essentially always fatal for thousands of years, though. Roman court physician Scrabonius Largus described rabies as incurable in the 1st century C.E.

• 7:42Tracy V. Wilson?

  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.

• 8:05Tracy V. Wilson?

  The word rabies reflects this latter type. It comes from the Latin for "to rage," which may have roots in a Sanskrit word meaning "to do violence." Lysavirus 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.

• 8:27Holly Frey?

  Rabies shows up a lot in popular culture, 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 8th century BCE, Homer describes Hector as a rabid dog.

• 8:47Tracy V. Wilson?

  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. In the 2nd century CE, Roman philosopher Selsis used the word hydrophobia in his description of the disease. Selsis 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.

• 9:18Holly Frey?

  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 500, Caleus Aurelianus 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.

• 9:57Tracy V. Wilson?

  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, and Egypt by about 1,500 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.

• 10:29Holly Frey?

  These accounts primarily focused on outbreaks among dogs and other canids, including wolves and foxes. For example, an outbreak of wolf rabies struck Franconia in 1271. A massive outbreak among red foxes spread over parts of Europe between 1571 and 1581, 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.

• 10:58Tracy V. Wilson?

  At this point, we haven't mentioned rabies in the Americas. 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 in the Americas 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, and treated bat bites with washing and cauterization with hot coals to try to prevent disease. Spanish colonists were reported being bitten by bats in the early 1500s.

• 11:42Tracy V. Wilson?

  And in 1514, Fernandez de Oviedo wrote about several soldiers dying after being bitten by vampire bats.

• 11:51Holly Frey?

  Dog rabies is one of many diseases that Europeans introduced to the Americas. 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 10 days. When Europeans first started sailing to the Americas, the voyage often took more than two months. So any dogs or other animals that had been infected before setting sail usually developed symptoms and died or were killed while still at sea.

• 12:36Tracy V. Wilson?

  So that meant introducing dog rabies to the Americas 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 1709. And by the end of the 18th 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

• 13:19Tracy V. Wilson?

  that were adapted to specific species.

• 13:22Holly Frey?

  We'll talk about how a vaccine was developed to prevent rabies after a sponsor break.

• 13:30Speaker 04

  First thought is like, wow, how are we going to do all this?

• 13:33Tracy V. Wilson?

  Hey, everybody, it's Tracy from Stuff You Missed in History Class. That's Alan Goya, a planning engineer at AT&T. He's talking about Intuit Dome, home of the Los Angeles Clippers, where every seat, screen, phone, and transaction is connected with AT&T fiber and 5G, defining the fan's experience. And Alan's master plan made it all possible.

• 13:53Speaker 04

  It was going to rival anything that was already built. And that takes quite a bit of people and different teams to all be on the same page.

• 14:01Tracy V. Wilson?

  That includes field services manager Drexel Jones. His team made sure it all came together and held up on game day.

• 14:08Speaker 05

  Through what Alan's whole crew designed, we connected the event visitors to the world.

• 14:13Tracy V. Wilson?

  And after years of hard work and collaboration, it was opening night.

• 14:17Speaker 05

  To actually see the whole stadium light up and data is flowing is a beautiful thing.

• 14:21Speaker 04

  What the fans experienced is incredible. It gave me a lot of pride.

• 14:25Tracy V. Wilson?

  AT&T, connecting fans to what they love. Connecting changes everything. AT&T.

• 14:31Tracy V. Wilson?

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• 15:13Tracy V. Wilson?

  Blue, you can DIY trusted ADT home security in a snap. Head to ADT.com/BLU to build your system today. And to hear more about home protection and other grown-up topics, check out new episodes of Grown-Up Stuff on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

• 15:37Tracy V. Wilson?

  Guess who's back in the house? The old gays return for season two of Silver Linings, their hit podcast from iHeart's Ruby Studio in partnership with ViiV Healthcare. Just wait until you hear what hosts Robert McMillan and Jess A. have in store this time around. They strut back down memory lane navigating life, love, loss, and everything that shaped them along the way. And as usual, someone just might break into song. From leather bars to bathhouses, dance floors to drag brunch, nothing stays off limits. These are the kinds of insights that can only come from experience. So listen to your elders, honey, and discover the silver linings you can take with you. All sass, zero filter,

• 16:19Tracy V. Wilson?

  and decades of perspective from four friends proving that queer joy only gets better with age on the podcast that never gets old. Listen to Silver Linings, available on the iHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

• 16:37Tracy V. Wilson?

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• 17:21Tracy V. Wilson?

  find people who can help drive results. Spend less time searching and more time actually interviewing candidates who check all your boxes. Less stress, less time, more results. Get your $75 Sponsored Job credit today at indeed.com/podcast. Terms and conditions apply. Hiring now, then this is a job for Indeed Sponsored Jobs. By the 18th and 19th centuries, outbreaks of rabies were spread across a lot of the world in domesticated dogs and in wild animals.

• 18:02Tracy V. Wilson?

  In North America, rabies became so widespread in skunks that they were nicknamed phoebicats, like hydrophobia. And phoebi tents were advertised as a way for cowboys to avoid being bitten by them in their sleep. In 1803, an 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.

• 18:33Tracy V. Wilson?

  Meaning the virus was way closer to their brain, while rabid dogs usually bit people's hands or arms.

• 18:40Holly Frey?

  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 5% to 50%. 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 bit someone in the midst of all of this might be rabid, or it might just be scared and cornered and trying to defend itself.

• 19:21Tracy V. Wilson?

  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 Saint 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 in much of Europe, people used a piece of iron called Saint 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.

• 20:05Tracy V. Wilson?

  Some people even carried one of these keys around with them for protection.

• 20:09Holly Frey?

  Long before the development of the germ theory of disease, people recognized that when someone was bitten by a rabid animal, something in the animal's 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 it, whether it was with a Saint Hubertus's 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 animal's infected saliva.

• 20:45Holly Frey?

  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.

• 20:55Tracy V. Wilson?

  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 1867, the UK passed the Metropolitan Streets Act. Among other things, this act empowered police to collect and muzzle stray dogs or dogs that were determined to be dangerous. This reportedly led to a drop in human cases of rabies in British cities.

• 21:23Holly Frey?

  Also, in the 18th and 19th centuries, researchers were learning about rabies and working on ways to prevent its 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.

• 21:42Tracy V. Wilson?

  Yeah, it was a lot of incredibly stilted sentences before I was like, we're just calling it a virus, regardless of whether that individual researcher knew what a virus was. So in 1769, Italian anatomist and pathologist John Morgagni 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. Morgagni 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.

• 22:25Holly Frey?

  After it gets to the brain, the rabies virus makes its way to the salivary glands, where it can cause excessive salivation. And although 18th century researchers didn't quite have that part figured out, they did know that the disease was spread through saliva. In 1793, Scottish surgeon John Hunter speculated that it would be possible to use a lancet to intentionally introduce an infected animal's saliva into another animal, but it's not clear whether he tried this in practice.

• 22:55Tracy V. Wilson?

  We also don't know whether German naturalist George Gottfried Zinko was familiar with Hunter's work, but in 1804, 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 1821, French neurophysiologist François Magendy reported that he had infected a previously healthy dog with saliva from a person who had contracted rabies.

• 23:37Holly Frey?

  Victor Gaultier was a professor at the National Veterinary School in Lyon, France, and he started experimenting with rabies in 1879. 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 rabid dogs were. Gaultier also found that the rabbits had a shorter incubation period of about 18 days, rather than a month or more that you might see in a dog.

• 24:10Tracy V. Wilson?

  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 1881, 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 rabid dog later on, it seemed like it was immune to the disease.

• 24:36Holly Frey?

  French chemist and microbiologist Louis Pasteur started working on rabies at about this same time, and he was inspired by Gaultier's success. Pasteur already had an extensive background in this kind of work. In the 1850s, he had studied yeast and alcohol fermentation, as well as the ability for microorganisms to contaminate fermenting beverages. This had contributed to both the germ theory of disease and the development of pasteurization. In the 1860s, he had identified a microorganism that was devastating the French silk industry. And in the 1870s, he studied animal diseases like anthrax and chicken cholera, including developing an anthrax vaccine.

• 25:19Tracy V. Wilson?

  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 Emil Roux.

• 25:36Tracy V. Wilson?

  A whole team of other scientists and doctors were involved in this work as well, including Charles Chamberlain, Emile Duclos, Louis Thullier, and Joseph Granchet. This was 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.

• 26:01Holly Frey?

  Much of Pasteur'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, Pasteur'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.

• 26:26Tracy V. Wilson?

  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 rabbit's 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 second's had been. He continued this serial passage of the virus from rabbit to rabbit until he had a strain of it that he described as fixed. It was consistent in how virulent it was, and it had an incubation period that was set at six or seven days.

• 27:09Holly Frey?

  From there, Pasteur 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, Pasteur 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.

• 27:43Tracy V. Wilson?

  Having successfully tested out this idea in dogs, he tried 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 11-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.

• 28:15Holly Frey?

  On July 4th, 1885, 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 Pasteur for help. Emile Roux had been heavily involved in Pasteur's research up to this point, and he refused to be involved in the boy's treatment because of ethical concerns. Pasteur expressed some reluctance as well, but Joseph Granchet and Alfred Vauquien of the Académie de Médecin encouraged him to try, with Granchet administering the treatment since Pasteur was not a doctor.

• 28:51Tracy V. Wilson?

  Joseph was given a series of inoculations over the span of 10 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 14-year-old shepherd who had been mauled while saving a group of younger boys from a dog. Pasteur reported his results to the French Academy of Science on October 26th, 1885, while Jupel's treatment was still ongoing, told about his success with Joseph Meister and the fact that he had successfully inoculated 50 dogs against

• 29:36Tracy V. Wilson?

  rabies before trying this process on a human.

• 29:39Holly Frey?

  We're going to talk more about what happened with all of this after we pause for a quick sponsor break.

• 29:48Tracy V. Wilson?

  Guess who's back in the house? The old gays return for season two of Silver Linings, their hit podcast from iHeart's Ruby Studio in partnership with Vive Healthcare. Just wait until you hear what hosts Robert McMillan and Jesay have in store this time around. They strut back down memory lane navigating life, love, loss, and everything that shaped them along the way. And as usual, someone just might break into song. From leather bars to bathhouses, dance floors to drag brunch, nothing stays off limits. These are the kinds of insights that can only come from experience. So, listen to your elders, honey, and discover the silver linings you can take with you. All sass, zero filter, and decades of perspective from four friends proving that queer joy

• 30:33Tracy V. Wilson?

  only gets better with age on the podcast that never gets old. Listen to Silver Linings, available on the iHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

• 30:48Tracy V. Wilson?

  For any small business owner, there's a moment when you realize the next hire could be the difference between staying busy and actually growing. The challenge is finding the right person without wasting time sorting through candidates who aren't the right fit. That's where Indeed Sponsored Jobs comes in. When workplace chaos hits and you need someone who can step in and make a difference, this is a job for sponsored jobs. It helps put your job in front of candidates who match the criteria that matter most to you, whether that's skills, experience, certifications, or location. And you're certainly not alone in using Indeed. Join the 3.3 million employers worldwide that use Indeed to connect with quality talent that fits their needs. That's millions of businesses turning to Indeed to help solve hiring challenges

• 31:32Tracy V. Wilson?

  and find people who can help drive results. Spend less time searching and more time actually interviewing candidates who check all your boxes. Less stress, less time, more results. Get your $75 sponsored job credit today at indeed.com/podcast. Terms and conditions apply. Hiring now, then this is a job for Indeed Sponsored Jobs.

• 31:58Holly Frey?

  We've all done it, tumble down an internet rabbit hole trying to self diagnose. And sometimes doing our own research can leave us more anxious than informed. Your feed is packed with wellness trends telling you to cold plunge, protein max, detox, track your sleep. But what's actually real? What's exaggerated? What's just wrong? That's exactly what Health vs. Hype from the American Medical Association and iHeartMedia's Ruby Studio is here to find out. Each episode, Emmy nominated science communicator Trace Dominguez, who's racked up billions of views across PBS, Discovery Channel, and YouTube, talks to doctors, influencers, and real people trying these trends.

• 32:41Holly Frey?

  Not to cancel them, not to hype them more, but to actually understand them. Because when it comes to your health, who you listen to matters. Start asking better questions and listen to Health vs. Hype on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

• 33:01Speaker 06

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• 33:43Speaker 06

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• 34:02Tracy V. Wilson?

  As word of Pasteur's success at preventing rabies started to spread, people started flocking to him for treatment. By the start of 1886, he had treated at least 350 people. They came from all over Europe and from the United States. In early December of 1885, a dog bit at least seven other dogs and six children in Newark, New Jersey. Word of Pasteur'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.

• 34:47Tracy V. Wilson?

  American news coverage of these boys' trip to Paris and then their return to the United States turned rabies vaccine into just a media sensation. And three of the boys were displayed at the Globe Museum in the Bowery in New York after they all got home.

• 35:04Holly Frey?

  Not everyone agreed with what Pasteur 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.

• 35:46Tracy V. Wilson?

  So critics made the point that Pasteur was potentially exposing people to rabies for no reason. And that his inoculation might cause somebody who had been bitten by a non-rabid dog to then develop rabies because of their treatment. Critics also noted that some of Pasteur's patients did die. By November of 1886, 1,700 patients had received rabies injections and 10 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.

• 36:28Holly Frey?

  The Academy de Médecin held a meeting on the subject on January 11th, 1887. Although Pasteur's critics were vocal, his supporters, led by Dr. Joseph Granchet, successfully defended his work.

• 36:42Tracy V. Wilson?

  The Institute Pasteur was established on June 4th, 1887, and it opened on November 14th of that year. It focused on disease research and on providing rabies vaccine. By 1898, more than 20,000 people had been treated at the Pasteur Institute after a possible rabies exposure and only 96 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 cord tissue. There could for sure be complications, but this was still a dramatic improvement over

• 37:25Tracy V. Wilson?

  an untreatable fatal disease.

• 37:29Holly Frey?

  Discoveries about the rabies virus continued after this point. In 1903, Italian pathologist Aldeki Negri discovered round and oval regions in the brains of animals that had died of rabies, which he called Negri bodies. 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 newer methods for detecting rabies in brain matter today, Negri bodies 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.

• 38:14Tracy V. Wilson?

  Refinements in the vaccine were also in the works. Pasteur'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 20th century, researchers started using phenol to kill the virus rather than attenuating it through air drying. Viruses were cultured in tissues in 1936, 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.

• 38:54Holly Frey?

  Although some of Pasteur'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.

• 39:37Tracy V. Wilson?

  We should note, though, that rabies-free often means rabies-free in terrestrial animals. There can still be rabies or other lissaviruses 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 bats with your bare hands. You don't need to be afraid of bats. They're generally pretty shy and they're not going to mess with you if you don't mess with them, but like, don't go grab one with your hand.

• 40:09Holly Frey?

  Which is so hard because they're so cute.

• 40:12Tracy V. Wilson?

  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 am not going anywhere near it.

• 40:22Holly Frey?

  I will tell a backstory and our behind the scenes.

• 40:25Tracy V. Wilson?

  Okay.

• 40:26Holly Frey?

  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 40% 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 rabies vaccine was developed. For example, rabies was identified in North American raccoons in 1936, and there is an ongoing epidemic of rabies among raccoons 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.

• 41:06Tracy V. Wilson?

  Yeah, there are also mass vaccination campaigns, a lot of work on this. A lot of the deaths that occur around the world happen in children who like 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 5th, 1994, 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

• 41:48Tracy V. Wilson?

  was sold, but the pet store didn't have clear records of when animals had arrived there or been sold. So in the end, 665 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

• 42:29Tracy V. Wilson?

  that may have come into contact with three feral kittens that were then captured and sold at the store.

• 42:35Holly Frey?

  As a side note, you may have heard that rabies 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 rabies PEP did involve a long series of 14 to 21 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.

• 43:13Tracy V. Wilson?

  Yeah, I would not want to get 14 to 21 shots all around my abdominal tissues.

• 43:19Holly Frey?

  Oh, no, thank you.

• 43:21Tracy V. Wilson?

  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 in tissues and a lot safer than what was being used in the past.

• 44:06Tracy V. Wilson?

  This process can be a little bit different for children, or if a person is immunocompromised, 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.

• 44:21Holly Frey?

  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 number of rabies transmissions through organ transplants. Although the risk of this is extremely remote, after their first report of it happening,

• 45:05Holly Frey?

  many organ procurement organizations started including screening questions to try to rule out this possibility. Circling back around to rabies in pop culture, this was actually a plotline on the TV show Scrubs.

• 45:17Tracy V. Wilson?

  It's, 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 2004, 15-year-old Gina Giese 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 peroxide, she wasn't taken in for further treatment. She started developing symptoms about a month later, and then about six days into

• 46:02Tracy V. Wilson?

  her illness, reported having been bitten by the bat.

• 46:06Holly Frey?

  Doctors placed Giese in a medically induced coma and gave her antiviral drugs and other treatments. These treatments continued until tests 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 2021.

• 46:27Tracy V. Wilson?

  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 38 published uses of the Milwaukee Protocol, including one use of a similar protocol called the Resife Protocol. Only 11 of those patients survived, with all but five of them having moderate to severe complications afterward.

• 47:05Holly Frey?

  This is certainly an improvement over a disease with an essentially 100% 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.

• 47:40Tracy V. Wilson?

  Yeah, 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 healthcare infrastructure.

• 48:21Tracy V. Wilson?

  Places where people don't have access to rabies prophylaxis are likely to also be places where people don't have access to a hospital that could support this kind of treatment.

• 48:33Tracy V. Wilson?

  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 rabies 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.

• 49:14Holly Frey?

  So, all of that said, the global cost of rabies is roughly $8.6 billion per year, and more than 15 million people per year receive rabies PEP. This protocol can be really expensive. In the United States, it can cost between $1,200 and $6,500.

• 49:33Tracy V. Wilson?

  Yeah, that's like one estimate that I can saw, that I saw, I saw some that were even higher than that. September 28th of every year is World Rabies Day. That's also the anniversary of the death of Louis Pasteur. Well, that's a basic history of rabies.

• 49:48Holly Frey?

  Rabies.

• 49:50Tracy V. Wilson?

  My, my hope is that in the future, we'll 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.

• 50:18Holly Frey?

  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, the dog population is not well vaccinated.

• 50:32Tracy V. Wilson?

  Yeah.

• 50:32Holly Frey?

  And tries to just do as many vaccinations as they can in a short period of time.

• 50:38Tracy V. Wilson?

  Yeah, they, uh, they had gone to Malawi, I think, and Malawi's target is like 70% 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.

• 51:02Holly Frey?

  Yeah.

• 51:08Tracy V. Wilson?

  Thanks so much for joining us on this Saturday. If you'd like to send us a note, our email address is [email protected]. And you can subscribe to the show on the iHeartRadio app, Apple Podcasts, or wherever you listen to your favorite shows.

• 51:30Holly Frey?

  A rare disease diagnosis can change your life, but it doesn't have to define your future. In season seven of Untold Stories: Life with a Severe Autoimmune Condition, host Martine Hackett continues the conversation with people living with MG, CIDP, and the broader rare disease community, exploring what comes after diagnosis through stories of hope, progress, and connection. Produced by Ruby Studio in partnership with Argenx, listen on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

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