WEBVTT - Tetanus 0:00:01.320 --> 0:00:04.240 Welcome to Stuff You Missed in History Class, a production 0:00:04.400 --> 0:00:14.680 of iHeartRadio. Hello, and welcome to the podcast. I'm Tracy V. 0:00:14.840 --> 0:00:19.439 Wilson and I'm Holly Frye. Hey. I'm thinking about vaccines 0:00:19.800 --> 0:00:26.440 a lot right now for reasons including rapidly growing measles 0:00:26.440 --> 0:00:28.960 outbreak that we have happening in the US right now. 0:00:29.000 --> 0:00:32.919 I originally had numbers of cases here in the outline, 0:00:33.520 --> 0:00:36.400 but that number increased by like two hundred just in 0:00:36.440 --> 0:00:38.599 the time that I was working on this. Yeah, it's 0:00:38.640 --> 0:00:40.960 impossible to track. By the time this comes out, those 0:00:41.040 --> 0:00:43.160 numbers would be woefully out. Sabe. Yeah, two more weeks 0:00:43.159 --> 0:00:45.800 are going to pass before this is out, so those 0:00:45.880 --> 0:00:50.040 numbers would be wrong anyway by then. Also, just a 0:00:50.080 --> 0:00:54.280 lot of upsetting and alarming developments happening in the US 0:00:54.360 --> 0:00:57.440 Department of Health and Human Services and the National Institute 0:00:57.480 --> 0:01:01.920 of Health. We have already done an episode on measles 0:01:02.200 --> 0:01:05.000 that came out on February twenty eighth of twenty twenty four, 0:01:05.080 --> 0:01:07.679 and that's a little bit more recent than we would 0:01:07.720 --> 0:01:10.880 typically rerun as a Saturday Classic. So I decided to 0:01:10.959 --> 0:01:14.920 take a look at another disease that's preventable today. Thanks 0:01:15.000 --> 0:01:18.920 to vaccines which do not cause autism. Not any vaccine, 0:01:18.920 --> 0:01:23.440 not for any disease. None of them cause autism. The disease, though, 0:01:23.480 --> 0:01:27.920 is tetanus. Since this is an episode about a medical development, 0:01:27.959 --> 0:01:31.240 of course there will be some medical experiment stuff in 0:01:31.280 --> 0:01:35.679 the episode, including some experiments involving animals. I really don't 0:01:35.680 --> 0:01:39.080 think any of that is particularly graphic, but just in case, 0:01:39.840 --> 0:01:44.600 Uh yeah, I can handle it based on my read through, 0:01:45.400 --> 0:01:48.960 which is a pretty low bar of getting upsetness. So 0:01:49.240 --> 0:01:53.480 I think we're safe. But if not, I'm sorry. Tetanus 0:01:53.520 --> 0:01:57.200 has probably been around for most of human history, possibly 0:01:57.240 --> 0:02:01.960 even longer. It's caused by the bacteria Clostridium tetani, which 0:02:02.000 --> 0:02:04.880 is present in the environment in a lot of the world. 0:02:05.320 --> 0:02:09.080 It's described with words like ubiquitous. In the words of 0:02:09.160 --> 0:02:12.160 John Sundwall in a lecture given under the auspices of 0:02:12.200 --> 0:02:16.639 the Kansas Academy of Science in nineteen seventeen, quote, this 0:02:16.760 --> 0:02:19.960 germ has a wide distribution, and its spores are found 0:02:20.080 --> 0:02:25.080 wherever there is dirt. Barnyards are veritable repositories for them. 0:02:25.720 --> 0:02:29.800 Rusty nails appear to be rendezvous. Even the dirt that 0:02:29.840 --> 0:02:34.000 besmears the healthy living child may contain millions of these 0:02:34.040 --> 0:02:38.079 spores of Tetanus basillai. The spores can only grow when 0:02:38.120 --> 0:02:41.040 they gain deep entrance into the body and are shut 0:02:41.080 --> 0:02:44.840 off from oxygen. One of the oldest known medical texts 0:02:44.880 --> 0:02:48.280 in the world is the Edwin Smith Surgical Papyrus, named 0:02:48.320 --> 0:02:50.959 for Edwin Smith, who bought it in eighteen sixty two. 0:02:51.880 --> 0:02:56.200 This Egyptian medical text dates back to about fifteen hundred BCE, 0:02:56.720 --> 0:02:59.320 and it includes a description of somebody with a head 0:02:59.440 --> 0:03:03.000 injury that penetrated all the way through the futures of 0:03:03.040 --> 0:03:08.480 the skull. Afterward, according to one translation, quote, the cord 0:03:08.600 --> 0:03:12.880 of his mandible is contracted. He discharges blood from both 0:03:12.919 --> 0:03:16.040 his nostrils and from both his ears, while he suffers 0:03:16.040 --> 0:03:21.440 with stiffness in his neck. As this patient's condition progresses quote, 0:03:21.480 --> 0:03:25.120 his mouth is bound, both his eyebrows are drawn, while 0:03:25.160 --> 0:03:29.959 his face is as if he wept. This earliest description 0:03:30.160 --> 0:03:34.639 is usually translated and interpreted as describing a case of tetanus, 0:03:35.000 --> 0:03:38.320 but it doesn't entirely convey what tetanus is like as 0:03:38.360 --> 0:03:42.520 an illness. Tetanus doesn't cause bleeding from the ears or nose. 0:03:42.880 --> 0:03:45.680 That was probably a product of the patient's head trauma, 0:03:46.320 --> 0:03:49.880 not the tetanus that followed it. Beyond that, without getting 0:03:49.920 --> 0:03:55.640 into a lengthy backgrounder on neurotransmitters, Claustritium tetani produces two toxins, 0:03:55.760 --> 0:04:00.360 and one of them, called tetanospasmen, interferes with neurotransmitter that 0:04:00.440 --> 0:04:05.880 control motor neuron activity. The nerves start firing uncontrollably, which 0:04:05.960 --> 0:04:11.400 causes intense muscle spasms. These can be excruciating and powerful 0:04:11.480 --> 0:04:14.720 enough to cause compression fractures or other breaks in a 0:04:14.760 --> 0:04:19.800 person's bones. Tetanus can also lead to suffocation and heart failure. 0:04:20.600 --> 0:04:24.120 Even with medical treatment, tetanus is fatal between ten and 0:04:24.240 --> 0:04:27.960 twenty percent of the time, and without treatment the fatality 0:04:28.040 --> 0:04:30.760 rate goes up to eighty five percent or even more. 0:04:32.120 --> 0:04:37.039 It sounds awful, yes it does. The muscles in the 0:04:37.080 --> 0:04:40.520 face and the jaw are often affected in tetanus, and 0:04:40.560 --> 0:04:43.400 that can cause a person to look like they are grinning. 0:04:44.160 --> 0:04:48.400 The spasms also cause tristmas, also known as lockjaw, and 0:04:48.440 --> 0:04:51.279 that can make it difficult or impossible for the persons 0:04:51.279 --> 0:04:55.200 who open their mouth. The Edwin Smith Papyrus offers a 0:04:55.400 --> 0:04:58.680 way to try to deal with this lock jaw that's 0:04:58.680 --> 0:05:02.080 by placing a wooden brace padded with linen in the 0:05:02.160 --> 0:05:05.240 patient's mouth to try to keep it open enough that 0:05:05.279 --> 0:05:08.839 they can be fed a liquid diet while being kept upright. 0:05:09.680 --> 0:05:13.840 Tetanus also appears in the Sashruda Samhita, which dates back 0:05:13.880 --> 0:05:16.719 to about the sixth century BCE and is one of 0:05:16.720 --> 0:05:21.080 the foundational texts of iervedic medicine. We did an episode 0:05:21.120 --> 0:05:25.120 on Sashruda in January of twenty nineteen. In a chapter 0:05:25.279 --> 0:05:29.040 on diseases of the nervous system, the Sashruda Samhita describes 0:05:29.080 --> 0:05:33.720 one caused by enraged or agitated value that's the air 0:05:33.800 --> 0:05:38.880 element in iervedic medicine. This disease quote rarely yields to 0:05:38.960 --> 0:05:42.760 medicine and is cured in rare instances only with the 0:05:42.800 --> 0:05:48.200 greatest difficulty. Its characteristic symptom being a paralysis of the jawbone, 0:05:48.520 --> 0:05:53.920 which makes deglutition extremely difficult. This disease in the text 0:05:53.960 --> 0:05:57.000 is described as bending the body like a bow and 0:05:57.120 --> 0:06:00.640 in its extreme form, fixing the eyes in their sockets, 0:06:01.040 --> 0:06:06.400 paralyzing the jaw and breaking the sides. The Chinese medical 0:06:06.480 --> 0:06:10.880 text known as the Yellow Emperor's Classic of Internal medicine 0:06:11.520 --> 0:06:15.000 is attributed to a semi mythical figure who's described as 0:06:15.040 --> 0:06:18.880 living around twenty six hundred BCE, but it was probably 0:06:18.920 --> 0:06:22.680 written more than two thousand years later than that. Traditional 0:06:22.720 --> 0:06:27.080 Chinese medicine incorporates the idea of energy channels or meridians 0:06:27.160 --> 0:06:30.800 in the body. The translation of the Yellow Emperor's Classic 0:06:30.839 --> 0:06:33.680 that I had access to for research didn't use the 0:06:33.680 --> 0:06:37.520 word tetanus anywhere, but it describes the collapse of the 0:06:37.640 --> 0:06:42.480 chi in the bladder and small intestine meridian as causing opisthoughtanus, 0:06:42.760 --> 0:06:48.040 stiffness in the back, convulsive spasms, paleness, and spontaneous sweating. 0:06:48.839 --> 0:06:54.360 Once that sweating stops, the patient dies. Apisthoughtanus is the extreme, 0:06:54.680 --> 0:06:59.400 very arching spasms that are associated with tetanus. The first 0:06:59.400 --> 0:07:02.520 thing we'd think of as a really clear clinical description 0:07:02.640 --> 0:07:06.039 of tetanus from a more Western medical perspective is from 0:07:06.080 --> 0:07:11.280 Greek physician Hippocrates, written around the fifth century BCE. In 0:07:11.320 --> 0:07:17.760 a treatise on Internal afflictions, Hippocrates describes three types of tetanus. First, 0:07:17.800 --> 0:07:21.320 when it follows a wound, Hippocrates says, the patient's quote 0:07:21.640 --> 0:07:25.240 jaws are fixed and he is unable to open his mouth, 0:07:25.800 --> 0:07:30.360 his eyes shed tears and look awry. His back becomes rigid. 0:07:30.680 --> 0:07:34.600 He cannot bend his legs, nor his arms and spine. 0:07:34.680 --> 0:07:38.760 Hippocrates describes this disease as severe and requiring a media 0:07:38.800 --> 0:07:44.320 attention and in many cases fatal. For treatment, Hippocrates advises 0:07:44.400 --> 0:07:49.200 anointing the patient with warm oil infused with wormwood, bay leaves, 0:07:49.360 --> 0:07:53.360 or hen made seed with frankincense soaked in white wine. 0:07:54.160 --> 0:07:58.320 According to Hippocrates, the second type of tetanus is similar, 0:07:58.440 --> 0:08:02.920 but it starts with angina also pronounced angina that's chest pain, 0:08:03.400 --> 0:08:06.880 or with a saff infection or separation of the tonsils, 0:08:07.360 --> 0:08:10.679 and occasionally it can also start with a wound. Quote 0:08:10.800 --> 0:08:14.760 this patient is drawn backwards and cries aloud from the 0:08:14.800 --> 0:08:18.040 pain in his back and chest. He is drawn so 0:08:18.440 --> 0:08:22.320 forcefully that the attendants can hardly prevent him from falling 0:08:22.440 --> 0:08:26.560 out of bed. Then the third form is less lethal, 0:08:26.880 --> 0:08:30.280 arising from some of the same possible causes or from 0:08:30.400 --> 0:08:36.240 having fallen backward. Another work by Hippocrates called on Epidemics, 0:08:36.360 --> 0:08:41.400 also includes several examples of tennis cases, One developed after 0:08:41.440 --> 0:08:46.000 a surgery, another after a javelin wound after a person's 0:08:46.040 --> 0:08:49.600 finger was crushed by an anchor after an ankle injury 0:08:49.640 --> 0:08:54.040 whose treatment involved irritating the wound, after being injured by 0:08:54.080 --> 0:08:57.239 a piece of wood from a missile thrown by a catapult. 0:08:58.400 --> 0:09:02.080 In the words of Roman author Alice Cornelius Celsus in 0:09:02.160 --> 0:09:05.760 the first century CE, quote, there is no disease more 0:09:05.880 --> 0:09:09.720 distressing and more acute than that which, by a sort 0:09:09.760 --> 0:09:13.319 of rigor of the sinews, now draws down the head 0:09:13.400 --> 0:09:16.280 to the shoulder blades, now the chin to the chest, 0:09:16.800 --> 0:09:20.800 now stretches out the next straight and immobile. The Greeks 0:09:20.880 --> 0:09:25.960 call the first aposthotanus, the next amprosthotanus, and the last tetanus, 0:09:26.360 --> 0:09:31.560 although some with less exactitude use these terms indiscriminately. For 0:09:31.800 --> 0:09:36.120 centuries after this, European medical writing on tetanus tended to 0:09:36.160 --> 0:09:40.760 be really similar. Many physicians base their work on Hippocrates. 0:09:41.600 --> 0:09:45.800 Even if Hippocrates wasn't cited, they still usually described tetanus 0:09:45.840 --> 0:09:49.840 as following a wound. Most commented on how often the 0:09:49.880 --> 0:09:53.600 condition was fatal, and many of the recommended treatments related 0:09:53.600 --> 0:09:56.680 to things that one might hope would relieve the spasms, 0:09:57.160 --> 0:10:00.360 like being rubbed with oils or wines or liniments or 0:10:00.400 --> 0:10:04.600 wrapped in warm dressings or given warm baths. In the 0:10:04.640 --> 0:10:09.840 sixteenth century, past podcast subject Amboise Parre developed an instrument 0:10:09.920 --> 0:10:13.000 to open a tetanus patient's mouth so that they could 0:10:13.000 --> 0:10:16.839 be fed. Overall, the focus was on trying to get 0:10:16.840 --> 0:10:20.040 the muscles to relax and supporting the patient with the 0:10:20.120 --> 0:10:24.160 hope that they would recover, but often a certainty that 0:10:24.240 --> 0:10:28.520 they would not. Knowledge of the cause of tetanus and 0:10:28.600 --> 0:10:31.480 how to treat and prevent it didn't really start to 0:10:31.559 --> 0:10:34.880 advance until the nineteenth century, which we will get to 0:10:35.080 --> 0:10:47.600 after a sponsor break. As we said, before the break, 0:10:47.800 --> 0:10:51.840 people figured out that tetanus was connected to wounds thousands 0:10:51.880 --> 0:10:55.480 of years ago, but it wasn't until the nineteenth century 0:10:55.520 --> 0:10:57.520 that we started to get a sense of exactly what 0:10:57.720 --> 0:11:01.440 was happening inside those wounds and elsewhere in the body. 0:11:02.440 --> 0:11:06.040 In eighteen thirty eight, Luigi Carlo Ferini gave an address 0:11:06.120 --> 0:11:09.880 before the Medical Turgical Society of Bologna in which he 0:11:10.120 --> 0:11:14.000 described the use of electricity in the treatment of tetanus. 0:11:14.800 --> 0:11:17.760 He had based this on the work of Carlo Mettiucci, 0:11:17.960 --> 0:11:22.920 who was experimenting with electricity and frogs. Farini found that 0:11:23.000 --> 0:11:25.920 the application of direct current to the body of a 0:11:26.000 --> 0:11:29.880 patient who had developed tetanus after a gunshot wound seemed 0:11:29.920 --> 0:11:35.160 to interrupt the spasms. Unfortunately, this effect was temporary. It 0:11:35.240 --> 0:11:39.240 lasted only about thirty minutes. This didn't really provide a 0:11:39.280 --> 0:11:43.000 breakthrough in the understanding of tetanus, but it was connected 0:11:43.040 --> 0:11:46.640 to the electrical activity of the neurons that is part 0:11:46.679 --> 0:11:51.280 of the disease. Several discoveries were made. In eighteen eighty four, 0:11:52.080 --> 0:11:56.800 Italian scientists Antonio Carle and Giorgio Rotone had both studied 0:11:56.800 --> 0:12:00.920 medicine in Turin. They exposed a rat but to fluid 0:12:00.960 --> 0:12:03.599 from a sore from someone who had died of tetanus, 0:12:04.000 --> 0:12:08.440 and that rabbit also developed tetanus. This showed some kind 0:12:08.520 --> 0:12:11.920 of contagion was causing the disease. But to be clear, 0:12:12.200 --> 0:12:16.600 tetanus is not transmitted from person to person. You would 0:12:16.640 --> 0:12:20.760 have to really do something on purpose like this. Also 0:12:20.760 --> 0:12:24.000 in eighteen eighty four, Arthur Nicolier, who was a twenty 0:12:24.040 --> 0:12:28.160 two year old medical student in Germany, identified a bacillus 0:12:28.280 --> 0:12:31.600 in the soil. If you look at this basillis under 0:12:31.640 --> 0:12:34.880 a microscope, it looks kind of like a tiny straight pin. 0:12:35.240 --> 0:12:38.880 There's this rod like basillis with a knob on the end. 0:12:39.720 --> 0:12:43.240 That knob is the spore. Today, we know that these 0:12:43.280 --> 0:12:48.320 spores are incredibly hearty, they are resistant to most disinfectants, 0:12:48.679 --> 0:12:52.120 and they can survive freezing and being autoclaved at a 0:12:52.120 --> 0:12:54.920 temperature of one hundred and twenty one degrees celsius or 0:12:54.920 --> 0:12:57.920 two forty nine point eight fahrenheit for ten or fifteen minutes. 0:12:58.880 --> 0:13:02.880 Nicolier induce tetanus in mice by injecting them with soil 0:13:02.960 --> 0:13:07.640 that was contaminated with this spore forming basillis. He concluded 0:13:07.640 --> 0:13:11.560 that the basillis produced a poison that acted similarly to strychnine. 0:13:12.320 --> 0:13:15.840 Within a few years, multiple researchers all concluded that this 0:13:15.920 --> 0:13:20.679 basillis could produce a toxin. While Nicolier was able to 0:13:20.920 --> 0:13:24.400 find the tetanus basillis in the soil, he was not 0:13:24.720 --> 0:13:28.520 able to isolate it in a lab. Credit for that 0:13:28.760 --> 0:13:33.680 goes to Japanese physician and bacteriologist Kitasato Shiva Siburo in 0:13:33.800 --> 0:13:37.839 eighteen eighty nine. Kitasato was born in Japan and had 0:13:37.880 --> 0:13:41.240 earned his medical degree from the University of Tokyo Medical 0:13:41.320 --> 0:13:45.559 School in eighteen eighty three. Two years later, the Japanese 0:13:45.679 --> 0:13:48.800 government had sent him to the Institute of Hygiene in 0:13:48.920 --> 0:13:54.719 Berlin to study bacteriology and infectious diseases with groundbreaking microbiologist 0:13:54.840 --> 0:13:59.800 Robert Koch. It was while in Berlin that Quitasato isolated 0:13:59.840 --> 0:14:05.680 the tetanus bacillis Clestridium tetanani is an anaerobic microorganism, so 0:14:05.840 --> 0:14:09.959 doing this required Kitasato to develop new methods for growing 0:14:10.040 --> 0:14:15.720 bacteria while also keeping them isolated from the air. Kitasato 0:14:15.840 --> 0:14:19.280 started working with physiologist Emil von Behring, who is from 0:14:19.320 --> 0:14:24.240 West Prussia in what's now Germany. While Kitasato was studying tetanus, 0:14:24.320 --> 0:14:28.520 von Behring was studying diphtheria. We have talked about diphtheria 0:14:28.560 --> 0:14:31.320 in our episode on the Nome Serum run that ran 0:14:31.360 --> 0:14:35.480 as a Saturday Classic on January twenty second, twenty twenty two. 0:14:36.000 --> 0:14:40.560 These diseases have some similarities. They're both caused by bacteria 0:14:40.680 --> 0:14:45.440 producing toxins rather than by those bacteria reproducing and proliferating 0:14:45.480 --> 0:14:49.360 within the body. This is one reason why still today 0:14:49.640 --> 0:14:53.760 there's no definitive lab test for tetanus. Once a person 0:14:53.800 --> 0:14:57.680 has developed symptoms, tetanus bacteria are found in their wound 0:14:58.120 --> 0:15:00.920 only about thirty percent of the time time, and the 0:15:00.960 --> 0:15:03.760 bacteria can also be present in the wounds of people 0:15:03.800 --> 0:15:08.400 who have no symptoms and never develop the disease. In 0:15:08.560 --> 0:15:13.040 eighteen ninety, Kitasato and von Behring published a paper titled 0:15:13.160 --> 0:15:17.800 the Mechanism of Immunity and Animals to Diphtheria and Tetanus. 0:15:18.640 --> 0:15:22.080 This paper described a method they had found to prevent 0:15:22.200 --> 0:15:26.920 tetanus and healthy animals. From an English translation of the paper, 0:15:27.160 --> 0:15:30.160 they summed it up in a sentence quote, the immunity 0:15:30.200 --> 0:15:33.920 of rabbits and mice which have been immunized against tetanus 0:15:34.280 --> 0:15:37.840 depends on the ability of the cell free blood fluid 0:15:38.200 --> 0:15:43.240 to render harmless the toxic substance which the Tetanus bacillis produces. 0:15:44.080 --> 0:15:47.680 In their experiments, these two men exposed animals to a 0:15:47.720 --> 0:15:51.880 weakened version of the toxin, gradually building up their immunity. 0:15:52.800 --> 0:15:55.280 Then they did a series of experiments to show that 0:15:55.320 --> 0:15:58.880 the blood serum of these animals could neutralize the toxins 0:15:59.320 --> 0:16:04.400 in other aias animals. In other words, the serum contained antitoxins, 0:16:04.720 --> 0:16:10.120 also called antibodies. Kittasato and von Bearing injected rabbits with 0:16:10.280 --> 0:16:14.080 serum that contained these antibodies, and then they exposed the 0:16:14.200 --> 0:16:18.200 rabbits to an amount of tetanus bacteria that had previously 0:16:18.280 --> 0:16:23.360 been proven to be fatal. Every rabbit remained healthy. And 0:16:23.400 --> 0:16:26.040 then the same was true if the treated rabbits were 0:16:26.080 --> 0:16:29.760 injected with tetanus toxin instead of with the bacteria that 0:16:29.840 --> 0:16:34.000 produce it. These rabbits could withstand a dose of toxin 0:16:34.080 --> 0:16:37.080 that was twenty times higher than what it would take 0:16:37.120 --> 0:16:41.800 to kill an untreated rabbit. Kittasato and von Bearing also 0:16:41.960 --> 0:16:46.040 said that the serum from these immune animals could be 0:16:46.160 --> 0:16:49.800 used as a therapeutic treatment on animals that had already 0:16:49.840 --> 0:16:54.520 developed tetanus. A week after this paper was published, Von 0:16:54.560 --> 0:16:58.080 Bearing published another paper on his own, which was focused 0:16:58.080 --> 0:17:01.920 only on diphtheria, and the work he started eventually led 0:17:01.920 --> 0:17:05.880 to a reliable treatment for that disease. He was awarded 0:17:05.880 --> 0:17:08.920 the Nobel Prize in Physiology or Medicine for this work 0:17:08.960 --> 0:17:12.119 in nineteen oh one, the first time that prize was 0:17:12.160 --> 0:17:16.080 ever awarded. Since the Nobel Prize committee was focused on 0:17:16.119 --> 0:17:20.320 diphtheria and not tetanus, Kitasato was not included in the 0:17:20.359 --> 0:17:25.520 award or mentioned in the speech. Side note. Kitasato left 0:17:25.640 --> 0:17:29.960 Germany in eighteen ninety one, returning to Japan and establishing 0:17:30.000 --> 0:17:34.600 his own laboratory that was later subsidized by the Japanese government. Then, 0:17:34.600 --> 0:17:37.399 in eighteen ninety four, he was sent to Hong Kong 0:17:37.560 --> 0:17:42.239 during an epidemic of bubonic plague. There he isolated and 0:17:42.359 --> 0:17:46.200 identified the Bacillis that was causing that disease, a couple 0:17:46.200 --> 0:17:51.160 of days before Swiss researcher Alexandra Yersen made the same discovery. 0:17:52.000 --> 0:17:56.760 Although Kitasato published his work on this first, Yarson's was 0:17:56.920 --> 0:18:01.359 seen as more conclusively linking the disease to the basillis, 0:18:01.400 --> 0:18:06.040 and that bacillus today is known as Rcinia pestis after him. 0:18:06.800 --> 0:18:11.359 Quitasato and von Bhring had made definitive connections between tetanus bacteria, 0:18:11.720 --> 0:18:15.119 the toxin it produced, and the protective value of blood 0:18:15.200 --> 0:18:18.960 serum from animals that had developed an immunity to that toxin, 0:18:19.800 --> 0:18:23.439 but their work was just small animals like rabbits, guinea pigs, 0:18:23.480 --> 0:18:27.520 and mice. It didn't immediately lead to workable treatments for 0:18:27.680 --> 0:18:32.520 humans or for other large animals. That started to change 0:18:32.520 --> 0:18:37.040 in eighteen ninety five, when Edmund Nocard reported success with 0:18:37.280 --> 0:18:43.040 horses tetanus bacteria really thrive in horse manures, so tetanus 0:18:43.080 --> 0:18:47.800 could be a serious problem for cavalry units, farmers, basically 0:18:47.880 --> 0:18:51.440 anywhere that there were lots of horses. No Card was 0:18:51.480 --> 0:18:55.440 a veterinarian, a veterinary professor, and a biologist who had 0:18:55.440 --> 0:18:59.880 worked with Louis Pasteur. After his initial success, no Card 0:19:00.000 --> 0:19:04.480 produced about seven thousand files of anti tetanus serum and 0:19:04.560 --> 0:19:09.440 he distributed it among his veterinary colleagues. The first anti 0:19:09.480 --> 0:19:15.600 tetanus serums used in humans followed not long afterward. Throughout history, 0:19:15.920 --> 0:19:18.760 one of the groups most at risk for tetanus infection 0:19:19.000 --> 0:19:22.879 has been newborn babies, but among medical researchers in the 0:19:22.960 --> 0:19:26.479 late nineteenth century, tetanus was more often thought of as 0:19:26.520 --> 0:19:30.040 a hazard on the battlefield. There had been five hundred 0:19:30.160 --> 0:19:33.600 five reported cases during the US Civil War with a 0:19:33.640 --> 0:19:37.520 mortality rate of eighty nine percent, and three hundred and 0:19:37.520 --> 0:19:40.840 fifty reported cases during the Franco Prussian War with a 0:19:40.880 --> 0:19:45.560 mortality rate of ninety percent. Tetanus became a bigger threat 0:19:45.640 --> 0:19:48.800 during World War One, which started about twenty years after 0:19:48.840 --> 0:19:52.240 not cards discoveries, and we'll get into that after a 0:19:52.280 --> 0:20:05.159 sponsor break earlier In the episode, we read from a 0:20:05.240 --> 0:20:09.600 lecture given by John Sundwall in nineteen seventeen. Here is 0:20:09.680 --> 0:20:13.080 something else that lecture had to say about tetanus quote. 0:20:13.160 --> 0:20:16.359 It is known as the fourth of July bacillis. It 0:20:16.560 --> 0:20:20.760 was once a customed to exhibit our copious and excessive 0:20:20.920 --> 0:20:28.240 patriotism with every form of pyrotechnic art. Frequently premature explosions 0:20:28.280 --> 0:20:32.639 of the firecrackers, et cetera drove the accumulated dirt on 0:20:32.720 --> 0:20:36.879 the hand with its numerous spores, deep into the skin, 0:20:37.480 --> 0:20:40.639 and as a rule, the obituary column of the local 0:20:40.720 --> 0:20:44.320 press within a few days would announce the subsequent fate 0:20:44.480 --> 0:20:49.080 of many of our little patriots. This basic idea also 0:20:49.200 --> 0:20:53.199 applied to the battlefield during World War One. Advances in 0:20:53.280 --> 0:20:57.000 munitions and explosive meant that more soldiers were being struck 0:20:57.040 --> 0:21:01.440 with shrapnel and debris that could drive tetanusors deep into 0:21:01.440 --> 0:21:05.520 their bodies a lot more often. The proliferation of trench 0:21:05.600 --> 0:21:09.240 warfare also meant that more soldiers were developing conditions like 0:21:09.600 --> 0:21:12.840 trench foot and frostbite, both of which could lead to 0:21:12.880 --> 0:21:15.680 breaks in the skin that could provide an entry point 0:21:15.720 --> 0:21:19.639 for tetanus bacteria. Over the course of the war, doctors 0:21:19.680 --> 0:21:24.520 also concluded that infections with aerobic bacteria could facilitate tetanus 0:21:24.520 --> 0:21:28.720 infections by consuming the oxygen in a wound, leaving an 0:21:28.840 --> 0:21:33.959 environment that was hospitable to the anaerobic Tetanus bacillis. In 0:21:34.000 --> 0:21:38.399 the years before the war, researchers had started producing tetanus 0:21:38.440 --> 0:21:42.760 antitoxin for use in humans by building up the immunity 0:21:42.840 --> 0:21:47.240 of horses and then harvesting their serum. By the time 0:21:47.440 --> 0:21:51.840 the war started, the Institute Pasteur was preparing about eighty 0:21:52.000 --> 0:21:56.840 thousand vials of tetanus anti toxin for humans using about 0:21:56.880 --> 0:22:02.560 three hundred horses. By nineteen the institute had nearly fifteen 0:22:02.840 --> 0:22:07.040 hundred horses, producing more than six hundred thousand vials of 0:22:07.119 --> 0:22:11.159 anti toxin per month. The Institute Pastor was not the 0:22:11.200 --> 0:22:14.399 only place that was doing this. That's just what I 0:22:14.440 --> 0:22:18.560 had the numbers for. Over the course of the war, essentially, 0:22:18.600 --> 0:22:22.840 through trial and error, civilian and military doctors and surgeons 0:22:22.880 --> 0:22:27.399 worked out treatment and prevention protocols for tetanus in injured soldiers, 0:22:27.640 --> 0:22:31.159 and that was through use of these serums. Ultimately, the 0:22:31.200 --> 0:22:35.440 treatment started with treating the wound itself, excizing all wounds 0:22:35.440 --> 0:22:39.640 and removing all the damage tissue, ideally within twelve hours 0:22:39.640 --> 0:22:43.000 of the injury. This is because doctors found a clear 0:22:43.080 --> 0:22:46.520 connection between the presence of tetanus bacteria and the wounds 0:22:46.520 --> 0:22:50.760 of soldiers whose injuries were surgically treated and those who weren't. 0:22:51.480 --> 0:22:54.560 Like we said earlier, it's often not possible to find 0:22:54.600 --> 0:22:57.760 bacteria in the wounds of people who developed tetanus, but 0:22:57.840 --> 0:23:02.160 there was still a clear correlation there. Tetanus rates were 0:23:02.200 --> 0:23:05.960 lower in soldiers whose wounds had been exized, even if 0:23:06.040 --> 0:23:09.760 that first excision didn't lead to satisfactory wound healing and 0:23:09.800 --> 0:23:13.679 it had to be redone and then after their wounds 0:23:13.680 --> 0:23:18.000 were excised, the soldiers were treated with tetanus antibody serum, 0:23:18.359 --> 0:23:21.760 both as a prophylactic measure if there was enough available, 0:23:22.000 --> 0:23:25.560 and as a treatment if they started developing signs of tetanus. 0:23:26.320 --> 0:23:29.919 One bulletin from the UK War Office Committee for the 0:23:29.960 --> 0:23:34.720 Study of Tetanus advised nurses to be alert for symptoms quote. 0:23:34.880 --> 0:23:39.320 All nursing sisters engaged in dressing wounds should be warned 0:23:39.400 --> 0:23:42.560 to give the alarm if the muscles round the wound 0:23:43.040 --> 0:23:45.840 are found to be harder or more rigid than the 0:23:45.920 --> 0:23:50.240 muscles of the uninjured limb or side. Over the course 0:23:50.280 --> 0:23:55.040 of the war, doctors also developed standard doses of tetanus antitoxin. 0:23:55.800 --> 0:23:59.560 By nineteen nineteen, the prophylactic dose was five hundred units 0:23:59.600 --> 0:24:03.440 contained in three cubic centimeters or less of horse serum. 0:24:04.080 --> 0:24:07.240 A unit was quote ten times the least quantity of 0:24:07.359 --> 0:24:10.800 anti technic serum necessary to save the life of a 0:24:10.840 --> 0:24:14.280 three hundred and fifty gram guinea pig for ninety six hours, 0:24:14.359 --> 0:24:18.080 against the official test dose of a standard toxin furnished 0:24:18.280 --> 0:24:21.320 by the Hygienic Laboratory of the Public Health and Marine 0:24:21.320 --> 0:24:27.400 Hospital Service, a super easy unit of measures. I'm assuming 0:24:27.560 --> 0:24:31.439 that the Germans had a different standard, probably at this point, 0:24:31.560 --> 0:24:37.760 maybe not. Under ideal circumstances, an injured soldier was given 0:24:37.800 --> 0:24:41.840 the first prophylactic dose by injection as soon as he 0:24:41.880 --> 0:24:46.200 had been removed from the line of fire. Subsequent injections 0:24:46.240 --> 0:24:50.119 were shown to significantly reduce the risk of developing tetanus, 0:24:50.119 --> 0:24:54.359 but whether soldiers actually got those additional doses just really 0:24:54.400 --> 0:24:58.560 depended on whether there was enough serum available and whether 0:24:58.680 --> 0:25:02.720 the medical staff had the capacity to do it. If 0:25:02.760 --> 0:25:06.720 they were just really overwhelmed. It might not happen even 0:25:06.760 --> 0:25:10.159 when soldiers only got one injection, though they tended to 0:25:10.200 --> 0:25:14.040 have milder or more localized cases of tetanus if they 0:25:14.080 --> 0:25:18.720 still developed it. Doses of anti toxin for treatment rather 0:25:18.760 --> 0:25:23.040 than prophylaxis, could be much higher, ranging from fifty thousand 0:25:23.160 --> 0:25:26.120 to one hundred thousand units in the early days of treatment, 0:25:26.520 --> 0:25:29.719 depending on whether the patient's body seemed to be responding 0:25:29.800 --> 0:25:32.840 to it. One of the reasons for working out the 0:25:32.920 --> 0:25:37.200 lowest effective dose of antitoxin was, of course, to conserve 0:25:37.280 --> 0:25:40.960 a limited supply, but another was the risk of severe 0:25:41.000 --> 0:25:43.960 allergic reactions to the horse serum, which was known as 0:25:44.040 --> 0:25:48.560 serum sickness. This risk seemed to be higher at higher doses. 0:25:49.160 --> 0:25:52.600 For example, a nineteen nineteen report by the UK War 0:25:52.640 --> 0:25:55.840 Office Committee for the Study of Tetanus reported that two 0:25:55.880 --> 0:26:00.000 million prophylactic doses of anti tetanic serum had been administered 0:26:00.200 --> 0:26:03.240 to soldiers being treated in England, and there had been 0:26:03.440 --> 0:26:07.840 eleven cases of shock related to the serum. All of 0:26:07.880 --> 0:26:11.919 those patients did recover, but in the fourteen hundred cases 0:26:11.920 --> 0:26:15.040 of tetanus they were treated with therapeutic doses in England, 0:26:15.320 --> 0:26:18.720 there were forty nine cases of shock, or three point 0:26:18.840 --> 0:26:23.240 five percent of the patients. Among those patients, twelve died 0:26:23.440 --> 0:26:27.240 or zero point eight percent of those fourteen hundred cases, 0:26:27.800 --> 0:26:30.600 but some of those deaths likely were not related to 0:26:30.640 --> 0:26:34.280 the anti toxins, so this was rare, but it could happen. 0:26:35.040 --> 0:26:40.600 The development of tetanus anti taxin almost completely eliminated tetanus 0:26:40.640 --> 0:26:44.280 among injured soldiers by the end of the war. For example, 0:26:44.400 --> 0:26:47.240 in France, at the start of the war, about one 0:26:47.280 --> 0:26:50.120 and a quarter percent of the soldiers who were admitted 0:26:50.160 --> 0:26:54.600 to the hospital developed tetanus, and all of those patients died. 0:26:55.560 --> 0:26:59.120 After the tetanus anti toxin serum was introduced to that 0:26:59.240 --> 0:27:03.840 number of tetans cases dropped to zero. Results were pretty 0:27:03.840 --> 0:27:07.760 similar across other armies involved on both sides of the war. 0:27:08.800 --> 0:27:12.879 While tetanus anti toxin could be administered to soldiers prophylactically 0:27:13.040 --> 0:27:16.520 after they were injured, it wasn't a vaccine that could 0:27:16.520 --> 0:27:20.320 offer more long term resistance to the disease. But in 0:27:20.400 --> 0:27:25.439 nineteen twenty four, another French veterinarian and bacteriologists, Gaston Ramon, 0:27:26.000 --> 0:27:30.800 developed the first tetanus vaccine. Ramon had previously developed a 0:27:30.840 --> 0:27:36.320 similar vaccine for diphtheria. This vaccine is known as tetanus toxoid. 0:27:37.040 --> 0:27:40.720 Toxoid is a toxin that's been inactivated so that it's 0:27:40.800 --> 0:27:44.800 no longer dangerous, so the immune system learns to produce 0:27:44.880 --> 0:27:48.400 antibodies to the toxin before it encounters the real thing. 0:27:49.200 --> 0:27:52.560 This vaccine can also help prevent tetanus from developing if 0:27:52.560 --> 0:27:56.600 it's administered to an otherwise unvaccinated person after they have 0:27:56.720 --> 0:28:01.159 sustained an injury. During World War Two, so tetanus toxoid 0:28:01.240 --> 0:28:05.040 became a routine vaccine administered to soldiers, and then it 0:28:05.080 --> 0:28:08.520