1 00:00:01,280 --> 00:00:04,320 Speaker 1: Welcome to Stuff you Missed in History Class, a production 2 00:00:04,400 --> 00:00:13,880 Speaker 1: of I Heart Radio. Hello, and welcome to the podcast. 3 00:00:13,920 --> 00:00:17,520 Speaker 1: I'm Tracy V. Wilson and I'm Holly Fry. Holly, when 4 00:00:17,560 --> 00:00:20,759 Speaker 1: you were a kid that you learned the story of penicillin, 5 00:00:23,200 --> 00:00:26,280 Speaker 1: I feel like I didn't get it until later. Okay, 6 00:00:26,480 --> 00:00:30,480 Speaker 1: do you remember what you learned? Um? You know, accidental 7 00:00:30,840 --> 00:00:33,360 Speaker 1: grew on mold because there was a rumor at our 8 00:00:33,400 --> 00:00:37,760 Speaker 1: school that you could make your own antibiotics in your bedroom. Well, 9 00:00:39,120 --> 00:00:42,760 Speaker 1: we'll talk about something similar to that, and you better 10 00:00:42,800 --> 00:00:46,040 Speaker 1: believe my crafty little brain was like, could I could 11 00:00:46,040 --> 00:00:51,360 Speaker 1: I start a little apothec area out of my classes? Uh? Maybe? 12 00:00:52,159 --> 00:00:55,280 Speaker 1: Um so, I, like a lot of people learned this 13 00:00:55,480 --> 00:00:59,240 Speaker 1: very basic story about Alexander Fleming leaving a Petri dish 14 00:00:59,240 --> 00:01:01,680 Speaker 1: out and a getting taminated with mold, and then it's 15 00:01:01,720 --> 00:01:05,160 Speaker 1: just sort of presented as voila penicillin. He did it 16 00:01:05,200 --> 00:01:13,319 Speaker 1: all by himself. That is not remotely accurate. Like the 17 00:01:13,400 --> 00:01:17,000 Speaker 1: Petri dish and mold part, that part kind of accurate, 18 00:01:17,040 --> 00:01:19,440 Speaker 1: at least we'll talk more about it. But like it 19 00:01:19,520 --> 00:01:25,920 Speaker 1: was not suddenly he had invented penicillin by himself at all. Uh, 20 00:01:26,040 --> 00:01:27,920 Speaker 1: so that's one of the things we're going to talk 21 00:01:27,959 --> 00:01:31,399 Speaker 1: about in today's episode. Also, though, this was just inspired 22 00:01:31,440 --> 00:01:34,920 Speaker 1: by an email from listener Abbey, which we actually read 23 00:01:35,040 --> 00:01:38,880 Speaker 1: on the show recently, and Abby mentioned that after World 24 00:01:38,880 --> 00:01:44,000 Speaker 1: War Two there was a penicillin recycling project and I 25 00:01:44,080 --> 00:01:49,000 Speaker 1: was like, I need to know more about this, uh, 26 00:01:49,040 --> 00:01:50,680 Speaker 1: And I didn't talk about it a lot in that 27 00:01:50,760 --> 00:01:54,920 Speaker 1: listener mail segment because it is gross. So just as 28 00:01:54,920 --> 00:01:58,080 Speaker 1: a heads up, there is a lot of mold in 29 00:01:58,160 --> 00:02:01,279 Speaker 1: this episode and if a Phray is like mold Broth 30 00:02:01,440 --> 00:02:06,040 Speaker 1: bothers you, maybe this is not the episode for you. 31 00:02:06,600 --> 00:02:10,600 Speaker 1: That's your punk band, mold Broth were also just there's 32 00:02:10,639 --> 00:02:14,120 Speaker 1: a lot of bodily fluids. There's also some animal testing, 33 00:02:14,440 --> 00:02:18,320 Speaker 1: just you know, I know people can be squeamish about 34 00:02:18,320 --> 00:02:23,040 Speaker 1: particular things. Just a heads up on all of that. So, 35 00:02:23,200 --> 00:02:27,000 Speaker 1: like we just said, the development of penicillin started but 36 00:02:27,120 --> 00:02:30,400 Speaker 1: definitely did not end, with the chance discovery of some 37 00:02:30,480 --> 00:02:33,280 Speaker 1: mold in a petri dish. We're going to get back 38 00:02:33,280 --> 00:02:36,760 Speaker 1: to that. But the discovery of a seemingly miraculous treatment 39 00:02:36,840 --> 00:02:40,480 Speaker 1: made from mold piqued the interest of medical historians who 40 00:02:40,520 --> 00:02:43,840 Speaker 1: started looking for earlier uses of mold as a treatment 41 00:02:43,880 --> 00:02:47,240 Speaker 1: for wounds or diseases, and it turned out there were 42 00:02:47,280 --> 00:02:49,800 Speaker 1: actually a lot of them. Yeah, the people who had 43 00:02:49,840 --> 00:02:53,440 Speaker 1: been using these obviously already knew about them, but there 44 00:02:53,440 --> 00:02:58,160 Speaker 1: had not really been a systemic historical look at it. Uh. 45 00:02:58,200 --> 00:03:02,440 Speaker 1: The vast majority of the treatments involved using mold to 46 00:03:02,520 --> 00:03:06,519 Speaker 1: make a topical preparation for wounds. So this included using 47 00:03:06,639 --> 00:03:10,680 Speaker 1: moldy soybeans and China, and moldy bread in Egypt, and 48 00:03:10,800 --> 00:03:13,760 Speaker 1: cheese mold in Greece, with all of those dating back 49 00:03:13,960 --> 00:03:19,080 Speaker 1: roughly three thousand years or more. Aboriginal and indigenous peoples 50 00:03:19,120 --> 00:03:22,520 Speaker 1: all around the world have used molds medicinally as well. 51 00:03:23,440 --> 00:03:27,359 Speaker 1: There's also some evidence that more than two thousand years ago, 52 00:03:27,520 --> 00:03:34,520 Speaker 1: people in northern Africa consumed something that contained enough tetracycline 53 00:03:34,520 --> 00:03:39,280 Speaker 1: to leave evidence of that on their bones. Tetracycline actually 54 00:03:39,360 --> 00:03:43,200 Speaker 1: comes from bacteria, not from mold, but the bacteria and 55 00:03:43,360 --> 00:03:46,960 Speaker 1: question form these branching filaments that look enough like a 56 00:03:47,000 --> 00:03:49,440 Speaker 1: fungus that it was classified as a fungus for a 57 00:03:49,480 --> 00:03:53,960 Speaker 1: really long time. In more recent times, herbalists and apothecaries 58 00:03:54,000 --> 00:03:58,040 Speaker 1: in Europe described medicinal mold preparations all through the seventeen 59 00:03:58,200 --> 00:04:02,440 Speaker 1: and eighteen centuries, and researchers looking into the historical use 60 00:04:02,480 --> 00:04:05,160 Speaker 1: of mold in the twentieth century found that a lot 61 00:04:05,240 --> 00:04:09,520 Speaker 1: of full remedies using mold were still around. One biochemist 62 00:04:09,640 --> 00:04:12,800 Speaker 1: described traveling through Europe and finding that each home had 63 00:04:12,800 --> 00:04:16,320 Speaker 1: a moldy loaf of bread stored in the kitchen rafters, 64 00:04:16,320 --> 00:04:19,120 Speaker 1: which would be used to prepare dressings for cuts or 65 00:04:19,160 --> 00:04:24,360 Speaker 1: other wounds. Other oral accounts described people intentionally growing mold 66 00:04:24,360 --> 00:04:28,200 Speaker 1: on oranges or other fruit or substances, or collecting it 67 00:04:28,240 --> 00:04:31,599 Speaker 1: from meat as it was being cured. We don't really 68 00:04:31,600 --> 00:04:34,839 Speaker 1: have a lot of detail about how effective these treatments 69 00:04:34,880 --> 00:04:38,120 Speaker 1: actually were. There weren't clinical studies or things like that 70 00:04:38,160 --> 00:04:42,719 Speaker 1: to reference. But there are so many different medicinal uses 71 00:04:42,839 --> 00:04:45,920 Speaker 1: for molds to treat infections in so many different parts 72 00:04:45,920 --> 00:04:49,240 Speaker 1: of the world that some medical historians have concluded that 73 00:04:49,320 --> 00:04:52,560 Speaker 1: at least some of them probably did have some real 74 00:04:52,680 --> 00:04:57,400 Speaker 1: antimicrobial efficacy. Some of the folks that were interviewed about 75 00:04:57,440 --> 00:05:01,120 Speaker 1: their folk remedies after penicillin was developed and they learned 76 00:05:01,160 --> 00:05:03,560 Speaker 1: that penicillin was made out of mold, they were kind 77 00:05:03,560 --> 00:05:07,520 Speaker 1: of like Oh yeah, we've been doing that forever, and 78 00:05:09,200 --> 00:05:12,760 Speaker 1: by the time Fleming spotted that contaminated culture plate, it 79 00:05:12,839 --> 00:05:17,479 Speaker 1: was already established that various bacteria, molds, and other organisms 80 00:05:17,480 --> 00:05:22,200 Speaker 1: could inhibit one another's growth. The term antibiosis was coined 81 00:05:22,200 --> 00:05:24,800 Speaker 1: by the end of the nineteenth century to describe this 82 00:05:24,880 --> 00:05:28,400 Speaker 1: antagonistic effect that micro organisms could have on one another, 83 00:05:29,360 --> 00:05:32,679 Speaker 1: and there may have even been some work with penicillium 84 00:05:32,880 --> 00:05:38,120 Speaker 1: mold specifically before Fleming made his discovery. Joseph Lister may 85 00:05:38,160 --> 00:05:41,599 Speaker 1: have successfully treated a patient with a filtrait made from 86 00:05:41,800 --> 00:05:46,159 Speaker 1: Penicillium glaucum as early as eighteen seventy seven. Around the 87 00:05:46,200 --> 00:05:50,200 Speaker 1: same time, there were other doctors and scientists experimenting with 88 00:05:50,200 --> 00:05:54,719 Speaker 1: whether penicillium mold killed other micro organisms in a lab. 89 00:05:56,040 --> 00:05:59,359 Speaker 1: None of this is totally certain, though, the taxonomy for 90 00:05:59,480 --> 00:06:02,960 Speaker 1: molds and other fungi was not very robust yet, and 91 00:06:03,000 --> 00:06:05,720 Speaker 1: the people who were doing this work were not experts 92 00:06:05,760 --> 00:06:09,719 Speaker 1: in mycology. It's possible that they were working with totally 93 00:06:09,880 --> 00:06:13,720 Speaker 1: different molds that they were just calling penicillium, and then 94 00:06:13,760 --> 00:06:16,920 Speaker 1: aside from that, none of them published a thorough description 95 00:06:17,120 --> 00:06:19,920 Speaker 1: of their work, So a lot of this conclusion is 96 00:06:19,960 --> 00:06:25,440 Speaker 1: based on notes which we're not necessarily complete. You cannot 97 00:06:25,560 --> 00:06:28,440 Speaker 1: replicate an experiment to test it if you don't really 98 00:06:28,480 --> 00:06:32,920 Speaker 1: know what went down right. The early twentieth century saw 99 00:06:32,960 --> 00:06:36,840 Speaker 1: the development of the first drugs that killed specific bacteria. 100 00:06:36,960 --> 00:06:40,400 Speaker 1: In the eighteen seventies, German physician Paul Erlick had noticed 101 00:06:40,400 --> 00:06:43,919 Speaker 1: that chemical dies changed the color of some bacteria and 102 00:06:44,040 --> 00:06:47,839 Speaker 1: not others. This was a precursor to the Graham staining 103 00:06:47,880 --> 00:06:51,560 Speaker 1: method that is still used today to broadly classify bacteria 104 00:06:51,720 --> 00:06:55,360 Speaker 1: as gram positive and gram negative based on how they 105 00:06:55,400 --> 00:06:59,080 Speaker 1: respond to the stain. Erlick started to wonder if it 106 00:06:59,120 --> 00:07:02,320 Speaker 1: was also possible well to discover a substance that killed 107 00:07:02,400 --> 00:07:07,320 Speaker 1: some bacteria but not others. In nine researchers in Erlick's 108 00:07:07,400 --> 00:07:12,240 Speaker 1: lab discovered that the arsenic compound arsphenamine killed the bacteria 109 00:07:12,280 --> 00:07:16,640 Speaker 1: that caused syphilis. This drug was marketed as salver sand, 110 00:07:16,800 --> 00:07:19,119 Speaker 1: and it was also known as six oh six because 111 00:07:19,120 --> 00:07:22,800 Speaker 1: it was the six hundred and sixth preparation that had 112 00:07:22,840 --> 00:07:25,120 Speaker 1: been tested in Erle's lab. As part of this project. 113 00:07:25,800 --> 00:07:28,840 Speaker 1: Salver sand was found to be effective against other infectious 114 00:07:28,880 --> 00:07:32,720 Speaker 1: diseases as well. This was really the first effective treatment 115 00:07:32,720 --> 00:07:38,680 Speaker 1: for syphilis and the first modern antimicrobial compound. Erlick described 116 00:07:38,760 --> 00:07:41,280 Speaker 1: this use of a chemical to kill cells in the 117 00:07:41,320 --> 00:07:44,960 Speaker 1: body using the word chemotherapy, and he coined the term 118 00:07:45,080 --> 00:07:49,400 Speaker 1: magic bullet to describe the drug's ability to target pathogens. 119 00:07:50,240 --> 00:07:54,360 Speaker 1: Erly's lab had been systematically testing one arsenic compound after 120 00:07:54,400 --> 00:07:58,520 Speaker 1: another when it developed salversen. On the other hand, Alexander 121 00:07:58,560 --> 00:08:01,000 Speaker 1: Fleming's discovery of pennas sill in a little less than 122 00:08:01,040 --> 00:08:04,920 Speaker 1: twenty years later, was an accident. He was interested in 123 00:08:04,960 --> 00:08:09,240 Speaker 1: the anti microbial properties of the body's own fluids and secretions. 124 00:08:09,880 --> 00:08:13,080 Speaker 1: He coined the term licensign to describe a substance in 125 00:08:13,160 --> 00:08:16,760 Speaker 1: things like mucus, tears, and saliva that seemed to inhibit 126 00:08:16,800 --> 00:08:21,040 Speaker 1: bacterial growth. He reportedly made this discovery when he had 127 00:08:21,040 --> 00:08:23,920 Speaker 1: a cold. He cultured his own mucus in a petri 128 00:08:24,040 --> 00:08:26,960 Speaker 1: dish and then later discovered that the area around the 129 00:08:27,040 --> 00:08:31,480 Speaker 1: mucus wasn't growing bacteria. In some versions of this story, 130 00:08:31,600 --> 00:08:35,640 Speaker 1: his office was perpetually untidy, and this petrie dish had 131 00:08:35,840 --> 00:08:38,200 Speaker 1: sat there forgotten in some clutter for a couple of 132 00:08:38,240 --> 00:08:43,040 Speaker 1: weeks before he made the discovery. His discovery of penicillin 133 00:08:43,280 --> 00:08:48,160 Speaker 1: had some similarities. This time, he was studying staff bacteria, 134 00:08:48,360 --> 00:08:50,920 Speaker 1: and all of his petri dishes were supposed to be 135 00:08:51,000 --> 00:08:53,800 Speaker 1: in an incubator when he left for a two week 136 00:08:53,920 --> 00:08:58,239 Speaker 1: vacation in nineteen eight. One of them, though, was apparently 137 00:08:58,360 --> 00:09:01,760 Speaker 1: left on a lab bench by accident. When he got 138 00:09:01,760 --> 00:09:04,880 Speaker 1: back to the office on September three, he noticed the 139 00:09:05,040 --> 00:09:08,680 Speaker 1: misplaced Petrie dish that had been contaminated with mold, and 140 00:09:08,720 --> 00:09:12,560 Speaker 1: the area around the mold, he saw colonies of staff 141 00:09:12,640 --> 00:09:17,000 Speaker 1: bacteria that we're dying. We don't know exactly where the 142 00:09:17,040 --> 00:09:21,600 Speaker 1: mold contamination came from. One possibility is an open window, 143 00:09:21,840 --> 00:09:24,360 Speaker 1: and another is a mycology lab that was in the 144 00:09:24,440 --> 00:09:28,600 Speaker 1: same building. And this discovery was only possible because the 145 00:09:28,640 --> 00:09:31,440 Speaker 1: petrie dish was left out on a bench. If it 146 00:09:31,480 --> 00:09:33,920 Speaker 1: had gone into the incubator like it was supposed to, 147 00:09:34,400 --> 00:09:37,520 Speaker 1: the staff bacteria would have flourished, but the temperature would 148 00:09:37,520 --> 00:09:40,400 Speaker 1: have been wrong for the mold to grow. Beyond this, 149 00:09:40,679 --> 00:09:44,439 Speaker 1: other details are really hazy. Fleming did not take careful 150 00:09:44,520 --> 00:09:47,520 Speaker 1: notes about exactly what he was looking at when either 151 00:09:47,679 --> 00:09:51,720 Speaker 1: he or one of his assistants spotted this petrie dish. 152 00:09:51,920 --> 00:09:55,160 Speaker 1: His later descriptions about exactly how the mold and the 153 00:09:55,200 --> 00:09:59,280 Speaker 1: bacteria were interacting with one another could be contradictory. When 154 00:09:59,280 --> 00:10:02,800 Speaker 1: he published his discovery and the British Journal of Experimental 155 00:10:02,840 --> 00:10:06,880 Speaker 1: Pathology in June of nine, he made it sound as 156 00:10:06,880 --> 00:10:10,280 Speaker 1: though he routinely left his staff culture on plates on 157 00:10:10,320 --> 00:10:14,280 Speaker 1: the bench for extended periods, rather than that often repeated 158 00:10:14,360 --> 00:10:16,960 Speaker 1: story that this was one that was forgotten while he 159 00:10:17,000 --> 00:10:21,480 Speaker 1: was on vacation. He also described the mold as most 160 00:10:21,600 --> 00:10:27,319 Speaker 1: resembling Penicillium rubrum, and other researchers later corrected that identification 161 00:10:27,360 --> 00:10:34,199 Speaker 1: to penicillium notatam. That June paper describes various experiments Fleming 162 00:10:34,520 --> 00:10:37,120 Speaker 1: and his colleagues did with a filtrate made from the 163 00:10:37,160 --> 00:10:40,520 Speaker 1: broth the mold was growing in. He coined the term 164 00:10:40,520 --> 00:10:44,320 Speaker 1: penicillin to describe this fil trait because writing quote mold 165 00:10:44,400 --> 00:10:48,600 Speaker 1: broth filtrate over and over was apparently cumbersome. He did 166 00:10:48,640 --> 00:10:52,240 Speaker 1: some basic toxicity tests and small mammals by injecting them 167 00:10:52,280 --> 00:10:54,640 Speaker 1: with this fil trait, and it did not seem to 168 00:10:54,679 --> 00:10:58,079 Speaker 1: be toxic. But he doesn't seem to have tried injecting 169 00:10:58,160 --> 00:11:01,160 Speaker 1: animals with one of the bacteria that he knew penicillin 170 00:11:01,240 --> 00:11:03,800 Speaker 1: killed in a petri dish to see if that worked 171 00:11:03,800 --> 00:11:08,160 Speaker 1: in a living body as well. He did test penicillin's 172 00:11:08,160 --> 00:11:14,320 Speaker 1: activity against various microbes in a petri dish, including Staphylococcus, streptococcus, 173 00:11:14,360 --> 00:11:17,640 Speaker 1: and new Macoccus, as well as what was described at 174 00:11:17,640 --> 00:11:22,520 Speaker 1: the time as Basillus influenza and Basillus diph theory a 175 00:11:22,520 --> 00:11:27,880 Speaker 1: penicillin was particularly effective against all the pyogenic cocai, so 176 00:11:28,080 --> 00:11:31,000 Speaker 1: the ones that ended with caucus in that list, but 177 00:11:31,120 --> 00:11:34,440 Speaker 1: it wasn't as effective against the bassilla. So if he 178 00:11:34,559 --> 00:11:38,040 Speaker 1: had a petri dish that was growing both staff bacteria 179 00:11:38,240 --> 00:11:42,560 Speaker 1: and Bacillus influenza, he could use penicillin to kill only 180 00:11:42,640 --> 00:11:47,319 Speaker 1: the staff, leaving that Basillus culture in place. Side note. 181 00:11:47,400 --> 00:11:52,360 Speaker 1: Today Basillus influenza is known as Hemophilis influenze. It got 182 00:11:52,440 --> 00:11:56,600 Speaker 1: the influenze moniker when people thought that it caused influenza, 183 00:11:56,640 --> 00:12:00,520 Speaker 1: which it does not. Influenza is caused by a riss. 184 00:12:01,120 --> 00:12:04,760 Speaker 1: Just to keep things a little confusing for everybody. That 185 00:12:04,880 --> 00:12:06,679 Speaker 1: was one of the things about reading this paper was 186 00:12:06,720 --> 00:12:08,480 Speaker 1: then needing to go and look like, what did they 187 00:12:08,520 --> 00:12:10,640 Speaker 1: call that? Now? I don't think that's what they call 188 00:12:10,720 --> 00:12:15,320 Speaker 1: that now. Fleming didn't really have the skills or expertise 189 00:12:15,400 --> 00:12:18,920 Speaker 1: to try to extract this fil trait into a usable medicine. 190 00:12:19,480 --> 00:12:23,200 Speaker 1: His research students Stuart Craddock and Frederick Ridley both worked 191 00:12:23,200 --> 00:12:25,400 Speaker 1: on this, and both of them were credited at the 192 00:12:25,480 --> 00:12:29,040 Speaker 1: end of the published paper. Fleming also sent samples of 193 00:12:29,080 --> 00:12:32,040 Speaker 1: the mold to anyone who asked for it, but he 194 00:12:32,120 --> 00:12:36,120 Speaker 1: didn't really make any headway into turning penicillin into a medicine, 195 00:12:36,200 --> 00:12:40,240 Speaker 1: and he stopped working with it in ninety one. We'll 196 00:12:40,280 --> 00:12:43,000 Speaker 1: talk about how it did become a medicine after a 197 00:12:43,040 --> 00:12:55,960 Speaker 1: sponsor break. When Alexander Fleming was working with penicillin at 198 00:12:56,000 --> 00:12:59,040 Speaker 1: the end of the nineteen twenties, he was mostly approaching 199 00:12:59,040 --> 00:13:02,720 Speaker 1: it as something would have uses in a laboratory, such 200 00:13:02,720 --> 00:13:06,320 Speaker 1: as using it to isolate different cultures from one another 201 00:13:06,440 --> 00:13:09,960 Speaker 1: depending on whether they were sensitive to penicillin. One of 202 00:13:10,000 --> 00:13:14,319 Speaker 1: his students, Cecil George Payne, does seem to have successfully 203 00:13:14,400 --> 00:13:19,840 Speaker 1: used penicillin to cure eye infections in newborns in nineteen thirty, 204 00:13:20,000 --> 00:13:22,040 Speaker 1: as well as to treat a minor who had an 205 00:13:22,080 --> 00:13:26,600 Speaker 1: infected scratch on his cornea, but Pain did not publish 206 00:13:26,679 --> 00:13:30,120 Speaker 1: anything about this success, and he also does not seem 207 00:13:30,160 --> 00:13:33,559 Speaker 1: to have realized until much later that he had been 208 00:13:33,600 --> 00:13:37,920 Speaker 1: looking at something that could have revolutionized medicine. Meanwhile, in 209 00:13:38,040 --> 00:13:42,560 Speaker 1: nineteen thirty two, German bacteriologist Gerhard Domac was studying a 210 00:13:42,640 --> 00:13:46,199 Speaker 1: red dye that hadn't been in effective antibacterial in a 211 00:13:46,240 --> 00:13:49,679 Speaker 1: petri dish, but turned out to treat strip infections in 212 00:13:49,760 --> 00:13:54,280 Speaker 1: mice and staff infections in rabbits. This die was developed 213 00:13:54,320 --> 00:13:57,480 Speaker 1: into the drug Protonsal, the first sulfa drug and the 214 00:13:57,520 --> 00:14:00,240 Speaker 1: first drug used to treat and prevent a ray inache 215 00:14:00,240 --> 00:14:05,000 Speaker 1: of bacterial infections in humans. Unlike Salversen, which was primarily 216 00:14:05,080 --> 00:14:08,360 Speaker 1: used to treat civilist Protonsal could treat a variety of 217 00:14:08,400 --> 00:14:13,480 Speaker 1: grand positive bacteria. Do Mac was awarded the Nobel Prize 218 00:14:13,480 --> 00:14:17,199 Speaker 1: and Physiology or Medicine for this work in nineteen thirty nine, 219 00:14:17,400 --> 00:14:21,160 Speaker 1: but the Nazi Party had forbidden Germans to accept the 220 00:14:21,200 --> 00:14:25,240 Speaker 1: Nobel Prize. This was because the Nobel Peace Prize had 221 00:14:25,320 --> 00:14:29,920 Speaker 1: previously been awarded to German pacifist Carl von Ostiski in 222 00:14:30,040 --> 00:14:35,640 Speaker 1: nineteen thirty five. Do Mac accepted the prize anyway. Afterward, 223 00:14:35,720 --> 00:14:38,920 Speaker 1: he was arrested by the Gestapo and forced to write 224 00:14:38,960 --> 00:14:42,560 Speaker 1: to the Nobel Committee rejecting the prize. He wasn't able 225 00:14:42,600 --> 00:14:45,480 Speaker 1: to get his medal for having won the Nobel Prize 226 00:14:45,520 --> 00:14:47,360 Speaker 1: until after the end of World War Two, and he 227 00:14:47,400 --> 00:14:51,040 Speaker 1: never actually got the monetary award. As a side note, 228 00:14:51,200 --> 00:14:54,960 Speaker 1: we mentioned Paul Erlick earlier in the episode. The street 229 00:14:55,040 --> 00:14:58,440 Speaker 1: in Frankfurt where his institute was located was named after him, 230 00:14:58,800 --> 00:15:01,320 Speaker 1: but it was renamed to the Nazis came to power 231 00:15:01,440 --> 00:15:04,880 Speaker 1: because he was Jewish. Erlake was no longer living at 232 00:15:04,880 --> 00:15:08,040 Speaker 1: this point. He had died after a stroke in nineteen fifteen. 233 00:15:08,840 --> 00:15:11,520 Speaker 1: So the same year that Domac was awarded the Nobel 234 00:15:11,600 --> 00:15:15,480 Speaker 1: Prize for developing the first sulfa drug, researchers at the 235 00:15:15,520 --> 00:15:19,680 Speaker 1: Sir William Dunn School of Pathology at Oxford University started 236 00:15:19,800 --> 00:15:24,920 Speaker 1: studying penicillin. There had been a Department of Pathology at 237 00:15:24,960 --> 00:15:29,040 Speaker 1: Oxford for decades, but this school was almost brand new. 238 00:15:29,120 --> 00:15:32,119 Speaker 1: It had opened in nineteen thirty five after the university 239 00:15:32,200 --> 00:15:35,520 Speaker 1: received funds from the estate of the late Sir William Dunn, 240 00:15:35,960 --> 00:15:40,160 Speaker 1: which is what funded the new school. Australian pathologist Howard 241 00:15:40,160 --> 00:15:44,320 Speaker 1: Walter Florey had been appointed Professor of Pathology and the 242 00:15:44,440 --> 00:15:48,120 Speaker 1: research team he recruited included Ernst Chaine, who was a 243 00:15:48,200 --> 00:15:51,600 Speaker 1: Jewish biochemist who had fled to the UK from Germany 244 00:15:51,640 --> 00:15:55,640 Speaker 1: after the Nazi Party came to power. Floory, Chain and 245 00:15:55,680 --> 00:15:58,880 Speaker 1: others at Oxford had been inspired by Domac's success with 246 00:15:58,960 --> 00:16:03,720 Speaker 1: sulfa drugs, and in eight they started studying the enzyme lyssyme, 247 00:16:03,800 --> 00:16:08,440 Speaker 1: which Alexander Fleming had discovered. Chain also found Fleming's earlier 248 00:16:08,480 --> 00:16:12,200 Speaker 1: paper on the anti microbial effects of penicillium mold, and 249 00:16:12,320 --> 00:16:15,560 Speaker 1: Oxford already had a sample of Fleming's mold on hand. 250 00:16:16,240 --> 00:16:20,480 Speaker 1: The team started working with it in nine. Fleming and 251 00:16:20,560 --> 00:16:23,600 Speaker 1: his team at St Mary's had been mostly working with 252 00:16:23,680 --> 00:16:27,240 Speaker 1: small amounts of mold and a petri dish. Florian Chain, 253 00:16:27,360 --> 00:16:30,040 Speaker 1: on the other hand, we're trying to extract enough of 254 00:16:30,080 --> 00:16:33,080 Speaker 1: the active substance to test whether it could be used 255 00:16:33,200 --> 00:16:36,400 Speaker 1: as a medicine. Even though they were going to start 256 00:16:36,440 --> 00:16:40,920 Speaker 1: with mice, which are very small, this required a lot 257 00:16:41,200 --> 00:16:44,600 Speaker 1: of mold, so much more mold than Fleming had been 258 00:16:44,640 --> 00:16:48,880 Speaker 1: working with. Hospital bed pants turned out to be just 259 00:16:49,000 --> 00:16:52,400 Speaker 1: about the right size and shape to grow this mold in, 260 00:16:53,200 --> 00:16:55,520 Speaker 1: but most of the ones on hand were needed by 261 00:16:55,680 --> 00:16:59,760 Speaker 1: hospital patients, so the team at Oxford started repurposing what 262 00:17:00,080 --> 00:17:04,560 Speaker 1: her vessels they could scrounge up, jars and food tens, 263 00:17:05,080 --> 00:17:10,560 Speaker 1: milk churns, fuel cans, all kinds of things. I love 264 00:17:10,600 --> 00:17:14,760 Speaker 1: that it's a little hodgepodgy. It's very hodgepodgy. It was 265 00:17:14,840 --> 00:17:18,360 Speaker 1: also really a team effort. Over the course of the project, 266 00:17:18,440 --> 00:17:21,439 Speaker 1: six women were paid two pounds a week to tend 267 00:17:21,640 --> 00:17:25,600 Speaker 1: to the fermenting mold. They were Ruth Callo, Claire Eniot, 268 00:17:25,640 --> 00:17:30,520 Speaker 1: Betty Cook, Peggy Gardner, Megan Lancaster and Patricia mckegney, and 269 00:17:30,520 --> 00:17:35,080 Speaker 1: they were nicknamed the Penicillin Girls. Norman Heatley developed a 270 00:17:35,119 --> 00:17:38,359 Speaker 1: method to extract penicillin from the mold broth into amyl 271 00:17:38,440 --> 00:17:43,520 Speaker 1: acetate and then back into water. Edward Abraham developed techniques 272 00:17:43,560 --> 00:17:49,720 Speaker 1: to purify it, and on May nine, almost exactly ten 273 00:17:49,960 --> 00:17:54,280 Speaker 1: years after the British Journal of Experimental Pathology received Fleming's 274 00:17:54,320 --> 00:17:59,040 Speaker 1: paper on penicillin, they conducted an experiment involving eight mice. 275 00:18:00,080 --> 00:18:03,880 Speaker 1: All eight of the mice were injected with Streptococcus bacteria. 276 00:18:03,960 --> 00:18:06,840 Speaker 1: Then four of the mice were injected with penicillin and 277 00:18:06,880 --> 00:18:11,160 Speaker 1: the other four were left untreated. The four untreated mice 278 00:18:11,359 --> 00:18:15,320 Speaker 1: died but the other four who got penicillin all survived. 279 00:18:16,040 --> 00:18:20,400 Speaker 1: Other tests on animals followed, including studies on rats and cats. 280 00:18:21,080 --> 00:18:25,800 Speaker 1: They tested penicillin's efficacy against multiple bacteria. In addition to 281 00:18:25,960 --> 00:18:29,520 Speaker 1: strep and staff, there was Claustridium septicum, which can cause 282 00:18:29,560 --> 00:18:34,200 Speaker 1: gas gang green, and penicillin was dramatically effective against all 283 00:18:34,240 --> 00:18:37,960 Speaker 1: of them with little to no toxicity to their test subjects. 284 00:18:38,720 --> 00:18:42,840 Speaker 1: In August of nineteen forty, Chain, Floury, Heatley, and others 285 00:18:42,880 --> 00:18:47,479 Speaker 1: published Penicillin as a Chemotherapeutic Agent in the journal The Lancet, 286 00:18:48,080 --> 00:18:52,639 Speaker 1: detailing the basic findings of their research. It was clear 287 00:18:52,840 --> 00:18:56,520 Speaker 1: from this work that penicillin could potentially be a life 288 00:18:56,560 --> 00:19:00,800 Speaker 1: saving drug for human beings, and at this point, aside 289 00:19:00,800 --> 00:19:03,240 Speaker 1: from the medicines we have talked about in this episode, 290 00:19:03,240 --> 00:19:07,560 Speaker 1: there just weren't many effective options to treat bacterial infections. 291 00:19:08,160 --> 00:19:11,480 Speaker 1: That meant that minor illnesses like strep throat could lead 292 00:19:11,520 --> 00:19:16,240 Speaker 1: to much more serious problems like rheumatic fever. Life threatening 293 00:19:16,240 --> 00:19:20,160 Speaker 1: infections could develop an injuries that had seemed really superficial. 294 00:19:21,160 --> 00:19:25,120 Speaker 1: People like Ignace cell Vice and Joseph Lister had advocated 295 00:19:25,119 --> 00:19:29,000 Speaker 1: for things like hand washing and sterile surgical techniques to 296 00:19:29,040 --> 00:19:31,600 Speaker 1: cut down on the likelihood that a person would contract 297 00:19:31,720 --> 00:19:36,520 Speaker 1: an infection during childbirth or surgery, but infections could still happen, 298 00:19:36,880 --> 00:19:39,159 Speaker 1: and often there just was not much that could be 299 00:19:39,240 --> 00:19:43,240 Speaker 1: done about it SELFA drugs had been a huge step 300 00:19:43,359 --> 00:19:47,840 Speaker 1: forward in providing broadly effective treatments for bacterial infections, but 301 00:19:47,920 --> 00:19:50,880 Speaker 1: a lot of people were allergic to them, and most 302 00:19:50,880 --> 00:19:54,200 Speaker 1: of them could also cause a range of unpleasant side effects. 303 00:19:54,760 --> 00:19:57,879 Speaker 1: So figuring out whether penicillin could be a usable drug 304 00:19:57,960 --> 00:20:01,680 Speaker 1: in people and not just small mammals was a huge priority. 305 00:20:01,840 --> 00:20:05,600 Speaker 1: And since people are significantly bigger than mice, that meant 306 00:20:05,720 --> 00:20:08,360 Speaker 1: that the team needed to grow a lot more mold. 307 00:20:09,040 --> 00:20:12,280 Speaker 1: But at this point the UK was a war Germany 308 00:20:12,320 --> 00:20:16,320 Speaker 1: had invaded Poland on September one, nine and both the 309 00:20:16,480 --> 00:20:19,840 Speaker 1: UK and France had declared war on Germany two days later. 310 00:20:20,720 --> 00:20:23,239 Speaker 1: That meant that a lot of equipment and materials were 311 00:20:23,280 --> 00:20:26,399 Speaker 1: now dedicated to the war effort. For the sake of 312 00:20:26,480 --> 00:20:30,760 Speaker 1: time and expense, Norman Heatley designed a flat, rectangular pottery 313 00:20:30,840 --> 00:20:34,119 Speaker 1: vessel with a spout that was stackable and glazed on 314 00:20:34,160 --> 00:20:38,080 Speaker 1: the inside to make it watertight. The team eventually used 315 00:20:38,200 --> 00:20:41,399 Speaker 1: seven hundred of these vessels to produce about five hundred 316 00:20:41,520 --> 00:20:45,199 Speaker 1: liters of mold broth every week, but this was a 317 00:20:45,320 --> 00:20:50,640 Speaker 1: slow and cumbersome, kind of fiddly process. Even with all 318 00:20:50,920 --> 00:20:54,720 Speaker 1: seven hundred vessels in use, it took about four weeks 319 00:20:54,760 --> 00:20:59,080 Speaker 1: to make enough penicillin to treat one human patient, and 320 00:20:59,160 --> 00:21:02,720 Speaker 1: it took once for all seven hundred of those vessels 321 00:21:02,760 --> 00:21:05,720 Speaker 1: to be ready. At the end of nineteen forty, only 322 00:21:05,800 --> 00:21:08,440 Speaker 1: about ninety of them were all set and had been 323 00:21:08,480 --> 00:21:12,280 Speaker 1: seated with mold spores. The first attempt to treat a 324 00:21:12,320 --> 00:21:15,840 Speaker 1: person with penicillin made from all of this mold started 325 00:21:15,840 --> 00:21:20,760 Speaker 1: on February twelve, ninety one. That patient was Albert Alexander, 326 00:21:20,880 --> 00:21:25,720 Speaker 1: and there are multiple conflicting descriptions of how he became injured. 327 00:21:26,520 --> 00:21:30,280 Speaker 1: In some accounts, he cut himself shaving, In others, he 328 00:21:30,359 --> 00:21:34,560 Speaker 1: scratched himself while pruning roses, and still others he was 329 00:21:34,640 --> 00:21:38,320 Speaker 1: injured in a bombing during the Blitz. But regardless of 330 00:21:38,359 --> 00:21:41,560 Speaker 1: the cause, it is documented that he had a very 331 00:21:41,600 --> 00:21:45,200 Speaker 1: serious infection that was certain to be fatal if left untreated. 332 00:21:46,280 --> 00:21:50,760 Speaker 1: Alexander showed promising signs of recovery within twenty four hours 333 00:21:50,760 --> 00:21:55,400 Speaker 1: of being treated with penicillin, but because so little penicillin 334 00:21:55,520 --> 00:21:58,040 Speaker 1: had been made at this point, they had to collect 335 00:21:58,119 --> 00:22:00,919 Speaker 1: his urine and extract the pen sillin out of it 336 00:22:01,119 --> 00:22:06,359 Speaker 1: and then reuse it. So the body excretes penicillin really rapidly, 337 00:22:06,840 --> 00:22:09,520 Speaker 1: and roughly seventy percent of it comes out in the 338 00:22:09,680 --> 00:22:12,760 Speaker 1: urine unchanged, it could be more or less than that. 339 00:22:12,880 --> 00:22:15,359 Speaker 1: I saw numbers that were literally from one percent to 340 00:22:17,280 --> 00:22:21,440 Speaker 1: It's possible to recover half or more of that excreted 341 00:22:21,520 --> 00:22:24,600 Speaker 1: penicillin using the same basic method that was used to 342 00:22:24,640 --> 00:22:27,560 Speaker 1: extract it from the mold broth in the first place. 343 00:22:28,560 --> 00:22:32,040 Speaker 1: Even with the penicillin that had been reclaimed from his urine, 344 00:22:32,320 --> 00:22:37,439 Speaker 1: there wasn't enough to totally cure Alexander's infection. Eventually, the 345 00:22:37,480 --> 00:22:40,720 Speaker 1: team had given him all of the penicillin they had, 346 00:22:41,080 --> 00:22:44,199 Speaker 1: and after they ran out, his infection returned and he 347 00:22:44,320 --> 00:22:49,720 Speaker 1: died on March fift So it's clear that making enough 348 00:22:49,840 --> 00:22:52,680 Speaker 1: penicillin to do a clinical trial it was going to 349 00:22:52,760 --> 00:22:55,920 Speaker 1: be a huge challenge. With all this effort, they had 350 00:22:55,960 --> 00:22:59,679 Speaker 1: not made enough to successfully treat even one patient, Although 351 00:22:59,680 --> 00:23:02,880 Speaker 1: folk sing on treating children would have allowed the team 352 00:23:02,920 --> 00:23:06,040 Speaker 1: to use smaller doses. At this point, the priority was 353 00:23:06,160 --> 00:23:09,960 Speaker 1: really confirming the penicillin worked in adults, and then if 354 00:23:09,960 --> 00:23:14,920 Speaker 1: it did, supplying Allied troops with it. Infections were a 355 00:23:15,000 --> 00:23:18,800 Speaker 1: major major cause of death for wounded soldiers, and effective 356 00:23:18,800 --> 00:23:22,879 Speaker 1: treatments for bacterial illnesses could also allow six soldiers to 357 00:23:22,960 --> 00:23:26,760 Speaker 1: return to duty faster, but the prospects for doing that 358 00:23:26,840 --> 00:23:30,640 Speaker 1: in the UK were grim. Although there were British companies 359 00:23:30,640 --> 00:23:34,280 Speaker 1: that were interested in working with penicillin, most were dedicated 360 00:23:34,320 --> 00:23:37,840 Speaker 1: to critical wartime work involving drugs and other chemicals that 361 00:23:37,920 --> 00:23:42,160 Speaker 1: were already known to have a use. Plus British factories 362 00:23:42,200 --> 00:23:46,160 Speaker 1: were at risk of being bombed or otherwise attacked. Floor 363 00:23:46,400 --> 00:23:50,320 Speaker 1: and his team also understood that if Britain were invaded, 364 00:23:50,680 --> 00:23:53,639 Speaker 1: they might need to destroy their research work to prevent 365 00:23:53,720 --> 00:23:57,200 Speaker 1: it from being captured by the Germans. But they were 366 00:23:57,240 --> 00:24:02,320 Speaker 1: also really unwilling to risk loseing their penicillium mold entirely. 367 00:24:03,160 --> 00:24:08,120 Speaker 1: Norman Heatley suggested that several of them intentionally rub mold 368 00:24:08,359 --> 00:24:11,080 Speaker 1: into their coats so that if they had to flee, 369 00:24:11,359 --> 00:24:16,800 Speaker 1: they could just wear their samples with them undetected. Why 370 00:24:16,800 --> 00:24:22,360 Speaker 1: does everybody a miss on this transport? Smell weird? Smells well, 371 00:24:22,480 --> 00:24:26,800 Speaker 1: Musty in one, Floor and Heatley went to the United 372 00:24:26,840 --> 00:24:30,000 Speaker 1: States to try to find pharmaceutical companies that could help. 373 00:24:30,760 --> 00:24:33,400 Speaker 1: Work in the UK didn't stop at this point or 374 00:24:33,440 --> 00:24:37,040 Speaker 1: in other countries that had started experimenting with penicillium, but 375 00:24:37,119 --> 00:24:40,639 Speaker 1: the focus on mass producing penicillin shifted to the US, 376 00:24:41,119 --> 00:24:51,879 Speaker 1: and we'll talk more about that. After a sponsor break 377 00:24:53,160 --> 00:24:56,840 Speaker 1: in June of one, Howard Florey and Norman Heatley took 378 00:24:56,880 --> 00:25:00,720 Speaker 1: a series of flights to get from the UK to US. 379 00:25:00,760 --> 00:25:04,320 Speaker 1: These flights were paid for by the Rockefeller Foundation, which 380 00:25:04,359 --> 00:25:07,600 Speaker 1: had also done some of the funding for their research. 381 00:25:08,520 --> 00:25:12,119 Speaker 1: When they left, they had treated a total of six 382 00:25:12,480 --> 00:25:17,280 Speaker 1: patients with penicillin. In addition to Albert Alexander. One other 383 00:25:17,320 --> 00:25:22,640 Speaker 1: patient had died, but that patient died of a ruptured aneurysm, 384 00:25:22,680 --> 00:25:26,560 Speaker 1: not of the infection that the penicillin was treating. There 385 00:25:26,640 --> 00:25:30,760 Speaker 1: was just not enough penicillin to treat more people than that. 386 00:25:31,640 --> 00:25:35,399 Speaker 1: As Floor and Heatley were preparing to go, the Oxford 387 00:25:35,400 --> 00:25:38,800 Speaker 1: team was preparing and freeze drying as much penicillin as 388 00:25:38,840 --> 00:25:42,160 Speaker 1: possible for them to take with them. Floor was also 389 00:25:42,240 --> 00:25:46,880 Speaker 1: finishing a second paper titled Further Observations on Penicillin, which 390 00:25:46,880 --> 00:25:50,280 Speaker 1: went on to be published that August. There had been 391 00:25:50,320 --> 00:25:53,200 Speaker 1: a lot of debate about whether to publish this paper. 392 00:25:53,880 --> 00:25:56,320 Speaker 1: On the one hand, it contained a lot of information 393 00:25:56,359 --> 00:25:59,200 Speaker 1: that could save people's lives, but on the other hand, 394 00:25:59,480 --> 00:26:03,480 Speaker 1: there were scerns about Germany or its allies producing penicillin, 395 00:26:03,800 --> 00:26:06,119 Speaker 1: which could provide them with an advantage in the war, 396 00:26:06,440 --> 00:26:09,359 Speaker 1: and that paper would give them a lot more information 397 00:26:09,400 --> 00:26:12,840 Speaker 1: to do it. There were similar debates among the Oxford 398 00:26:12,880 --> 00:26:17,040 Speaker 1: team about whether to patent penicillin. A lot of them 399 00:26:17,080 --> 00:26:21,600 Speaker 1: found the idea of patenting any medicine to be just appalling, 400 00:26:22,080 --> 00:26:26,040 Speaker 1: while Ernst Shane argued that penicillin was their work and 401 00:26:26,119 --> 00:26:29,960 Speaker 1: it deserves to be protected. Chane also thought that their 402 00:26:30,080 --> 00:26:33,640 Speaker 1: ongoing struggles to get enough funding for their work would 403 00:26:33,640 --> 00:26:36,679 Speaker 1: be totally resolved if it could just be paid for 404 00:26:36,960 --> 00:26:41,679 Speaker 1: through licensing fees from a patent. Chane was also deeply 405 00:26:41,760 --> 00:26:44,359 Speaker 1: disappointed by not being part of this trip to the 406 00:26:44,400 --> 00:26:46,679 Speaker 1: United States, and this is something that seems to have 407 00:26:46,760 --> 00:26:51,159 Speaker 1: caused a huge rift between him and Floor since the 408 00:26:51,160 --> 00:26:53,080 Speaker 1: whole purpose of this trip was to try to get 409 00:26:53,119 --> 00:26:56,080 Speaker 1: manufacturing started, and Heatley was the person who had been 410 00:26:56,080 --> 00:26:59,120 Speaker 1: focused on manufacturing like it makes sense that Heatley would 411 00:26:59,119 --> 00:27:03,159 Speaker 1: be the person ago. They also wanted to minimize the 412 00:27:03,200 --> 00:27:06,240 Speaker 1: number of people going for the sake of secrecy. This 413 00:27:06,320 --> 00:27:08,800 Speaker 1: decision made sense, but Chain seems to have been incredibly 414 00:27:08,880 --> 00:27:12,280 Speaker 1: upset by it. The US had passed the Lend Lease 415 00:27:12,320 --> 00:27:16,320 Speaker 1: Act in March of ninety one, which established a framework 416 00:27:16,359 --> 00:27:19,040 Speaker 1: for the United States to provide the allies with things 417 00:27:19,080 --> 00:27:24,560 Speaker 1: like weapons, vehicles, materials, machinery, and facilities that would promote 418 00:27:24,560 --> 00:27:28,720 Speaker 1: the defense of the United States. The manufacturer of penicillin 419 00:27:29,119 --> 00:27:33,040 Speaker 1: seemed to fall under that definition, but Floury and Heatley 420 00:27:33,080 --> 00:27:35,919 Speaker 1: still had to find a pharmaceutical company that had the 421 00:27:36,000 --> 00:27:39,159 Speaker 1: interest and the ability to try to produce penicillin on 422 00:27:39,160 --> 00:27:42,560 Speaker 1: a commercial scale. They had a series of meetings and 423 00:27:42,640 --> 00:27:45,720 Speaker 1: disappointments and kind of stops and starts, and then Floury 424 00:27:45,840 --> 00:27:49,920 Speaker 1: and Heatley wound up at the Department of Agriculture's Northern 425 00:27:50,040 --> 00:27:55,240 Speaker 1: Regional Research Laboratory or n r r L and Peoria, Illinois, 426 00:27:55,680 --> 00:27:58,800 Speaker 1: which already had a fermentation division, which was very handy 427 00:27:59,160 --> 00:28:04,560 Speaker 1: since they grew penicillin by fromenting. Researchers there started working 428 00:28:04,600 --> 00:28:08,480 Speaker 1: on finding ways to grow penicillium mold. A lot faster 429 00:28:08,560 --> 00:28:10,920 Speaker 1: than it had been. They started on that work in July. 430 00:28:13,080 --> 00:28:17,440 Speaker 1: This was a multi step process. At Oxford, researchers had 431 00:28:17,440 --> 00:28:20,720 Speaker 1: been growing the mold in a broth in flat, rectangular 432 00:28:20,800 --> 00:28:25,119 Speaker 1: pottery vessels. In Illinois, researchers figured out that growing it 433 00:28:25,240 --> 00:28:29,840 Speaker 1: in corn steep liquor yielded about ten times more penicillin. 434 00:28:30,800 --> 00:28:34,240 Speaker 1: This was convenient because corn steep liquor is a byproduct 435 00:28:34,280 --> 00:28:37,280 Speaker 1: of the wet milling process and people were already trying 436 00:28:37,320 --> 00:28:40,600 Speaker 1: to find a practical use for it. Those vessels and 437 00:28:40,680 --> 00:28:43,880 Speaker 1: Oxford were also rectangular and flat, because the mold was 438 00:28:43,960 --> 00:28:47,640 Speaker 1: essentially growing as a flat surface layer, and researchers in 439 00:28:47,720 --> 00:28:50,920 Speaker 1: Peoria thought it would be more efficient to grow the 440 00:28:51,000 --> 00:28:55,880 Speaker 1: mold in a submerged medium, but this also required they're 441 00:28:56,000 --> 00:28:59,840 Speaker 1: finding a different strain of penicillium mold that would grow 442 00:29:00,080 --> 00:29:05,800 Speaker 1: really well while submerged and also produced the antimicrobial substance 443 00:29:05,800 --> 00:29:08,880 Speaker 1: that they need, because not all of the penicillium strains 444 00:29:08,880 --> 00:29:13,400 Speaker 1: really did that very well. This involved gathering mold from 445 00:29:13,440 --> 00:29:15,680 Speaker 1: all over the world, which they did with the help 446 00:29:15,720 --> 00:29:18,760 Speaker 1: of the Army Transportation Corps, and they tested all these 447 00:29:18,760 --> 00:29:22,960 Speaker 1: samples in the lab. They Eventually, though, found a sample 448 00:29:23,120 --> 00:29:27,840 Speaker 1: growing on a moldy cantelope that worked really well. This 449 00:29:28,080 --> 00:29:31,520 Speaker 1: find is usually credited to lab assistant Mary kay Hunt, 450 00:29:31,520 --> 00:29:36,040 Speaker 1: who was nicknamed Moldy Mary. She had found this cantelope 451 00:29:36,120 --> 00:29:38,640 Speaker 1: not in some far reaching place brought back by the 452 00:29:38,720 --> 00:29:41,920 Speaker 1: Army Transportation Corp, but at a local Peoria fruit market. 453 00:29:42,720 --> 00:29:46,680 Speaker 1: The strain of the mold, Penicillium chrysogenum, was about a 454 00:29:46,880 --> 00:29:50,760 Speaker 1: hundred times more productive than the other strains they tried. 455 00:29:51,600 --> 00:29:54,720 Speaker 1: Even as the research lab figured out ways to increase 456 00:29:54,800 --> 00:29:58,920 Speaker 1: the yield of penicillium mold, they still needed pharmaceutical or 457 00:29:59,000 --> 00:30:03,040 Speaker 1: chemical manufact ers to actually get a penicillin drug into production. 458 00:30:03,960 --> 00:30:07,120 Speaker 1: A group of pharmaceutical companies and the federal government met 459 00:30:07,200 --> 00:30:11,840 Speaker 1: in October of to coordinate both the production process and 460 00:30:12,040 --> 00:30:17,080 Speaker 1: information sharing. The goal was to first produce enough penicillin 461 00:30:17,120 --> 00:30:20,480 Speaker 1: for clinical trials, and then, if those were successful, to 462 00:30:20,640 --> 00:30:23,600 Speaker 1: scale up production to make as much as could be 463 00:30:23,680 --> 00:30:27,280 Speaker 1: needed for Allied troops. This was a huge and really 464 00:30:27,360 --> 00:30:32,160 Speaker 1: unprecedented level of cooperation that was also gonna be really tricky. 465 00:30:32,400 --> 00:30:36,160 Speaker 1: John L. Smith from Fieser had this to say about it, quote, 466 00:30:36,240 --> 00:30:40,280 Speaker 1: the mold is as temperamental as an opera singer. The 467 00:30:40,440 --> 00:30:45,120 Speaker 1: yields are low, the isolation is difficult, the extraction is murder, 468 00:30:45,400 --> 00:30:51,280 Speaker 1: the purification invites disaster, and the essay is unsatisfactory. So 469 00:30:51,360 --> 00:30:55,600 Speaker 1: the Office of Science, Research and Development helped coordinate information 470 00:30:55,680 --> 00:30:59,800 Speaker 1: sharing about methods and techniques to do this successfully. Along 471 00:30:59,840 --> 00:31:04,840 Speaker 1: with managing fifty seven different research contracts related to it, 472 00:31:05,600 --> 00:31:09,720 Speaker 1: The War Production Board also worked with twenty five different 473 00:31:09,760 --> 00:31:13,960 Speaker 1: companies to scale up production of penicillin. They narrowed it 474 00:31:13,960 --> 00:31:16,960 Speaker 1: down to those twenty five after investigating more than a 475 00:31:17,080 --> 00:31:20,360 Speaker 1: hundred seventy five different companies to determine whether they were 476 00:31:20,400 --> 00:31:23,640 Speaker 1: suitable or not. The first patient in the US to 477 00:31:23,680 --> 00:31:26,920 Speaker 1: be treated with penicillin was thirty three year old and Miller, 478 00:31:27,320 --> 00:31:31,800 Speaker 1: who had developed septicemia after a pregnancy loss. Her treatment 479 00:31:31,880 --> 00:31:35,720 Speaker 1: started on March fourteenth, ninety two, and it required half 480 00:31:35,800 --> 00:31:39,680 Speaker 1: the penicillin that was in existence in the US at 481 00:31:39,680 --> 00:31:43,440 Speaker 1: that point. Also in nineteen forty two, back in the UK, 482 00:31:43,800 --> 00:31:47,720 Speaker 1: Alexander Fleming got some penicillin from the Oxford Group, which 483 00:31:47,920 --> 00:31:50,480 Speaker 1: was still at work, used that to treat one of 484 00:31:50,520 --> 00:31:53,480 Speaker 1: his patients, and when that treatment was successful, he got 485 00:31:53,520 --> 00:31:57,040 Speaker 1: a huge right up about it in the times. This 486 00:31:57,200 --> 00:32:00,480 Speaker 1: article didn't actually mention Floory or any of the other 487 00:32:00,520 --> 00:32:04,479 Speaker 1: researchers at the Oxford team, though, and this really started 488 00:32:04,520 --> 00:32:09,080 Speaker 1: to build the perception that penicillin was solely Fleming's work. 489 00:32:10,000 --> 00:32:13,640 Speaker 1: Fleming also seemed willing to take that credit, and Flory 490 00:32:13,800 --> 00:32:16,160 Speaker 1: didn't want to talk to the press and also didn't 491 00:32:16,200 --> 00:32:18,920 Speaker 1: want the rest of the Oxford team to talk to 492 00:32:19,040 --> 00:32:22,800 Speaker 1: the press, just really starting the ball rolling on this 493 00:32:22,920 --> 00:32:28,120 Speaker 1: being just Alexander Fleming's own work and nobody else's. The 494 00:32:28,240 --> 00:32:31,040 Speaker 1: fact that all of this was happening during World War 495 00:32:31,120 --> 00:32:35,000 Speaker 1: Two came along with a number of ethical dilemmas. One 496 00:32:35,160 --> 00:32:38,280 Speaker 1: that we referenced earlier was how careful researchers should be 497 00:32:38,360 --> 00:32:43,640 Speaker 1: about making sure information about penicillin and penicillin production wasn't 498 00:32:43,760 --> 00:32:48,920 Speaker 1: available to Germany or its allies. Doctors and medical ethicists 499 00:32:48,960 --> 00:32:51,960 Speaker 1: generally agreed that if a patient needed penicillin and the 500 00:32:51,960 --> 00:32:55,719 Speaker 1: penicillin was available, they could have it, regardless of their 501 00:32:55,800 --> 00:33:00,560 Speaker 1: nationality or what army they fought for. But since access 502 00:33:00,600 --> 00:33:04,520 Speaker 1: to penicillin could also create a military advantage, people also 503 00:33:04,600 --> 00:33:08,240 Speaker 1: believe that information about how to make it or samples 504 00:33:08,280 --> 00:33:12,120 Speaker 1: of the mold itself should not be shared, not with Germany, 505 00:33:12,160 --> 00:33:16,000 Speaker 1: and not with any countries likely to cooperate with Germany. 506 00:33:16,280 --> 00:33:19,640 Speaker 1: There are a lot of articles discussing whether, in fact 507 00:33:19,720 --> 00:33:22,640 Speaker 1: somebody in Germany did or did not receive one of 508 00:33:22,720 --> 00:33:26,600 Speaker 1: Fleming's samples way earlier in this whole story, before the 509 00:33:26,640 --> 00:33:32,520 Speaker 1: hostilities started. Within the US, another ethical issue was access 510 00:33:32,560 --> 00:33:37,000 Speaker 1: to penicillin, because once clinical trials were complete, the penicillian 511 00:33:37,240 --> 00:33:41,080 Speaker 1: being produced was going to be reserved almost exclusively for 512 00:33:41,240 --> 00:33:45,800 Speaker 1: military use. At the same time, they were definitely going 513 00:33:45,840 --> 00:33:49,400 Speaker 1: to be civilians whose lives would be lost without it. 514 00:33:49,800 --> 00:33:54,760 Speaker 1: Dr Chester Kiefer was responsible for rationing penicillin to civilians 515 00:33:54,840 --> 00:33:59,400 Speaker 1: and was absolutely inundated with requests for it. This led 516 00:33:59,640 --> 00:34:03,480 Speaker 1: some people to figure out ways to make their own penicillin. 517 00:34:04,360 --> 00:34:08,239 Speaker 1: For example, on November tenth three, Julius A. Vogel, who 518 00:34:08,320 --> 00:34:11,720 Speaker 1: was the plants physician at a steel plant in Pennsylvania, 519 00:34:12,400 --> 00:34:16,360 Speaker 1: figured out how to make penicillin in his kitchen see 520 00:34:16,480 --> 00:34:22,560 Speaker 1: my plan as a kid was not completely because I 521 00:34:22,640 --> 00:34:26,840 Speaker 1: had the knowledge of a plant position. Vogel based his 522 00:34:26,880 --> 00:34:30,320 Speaker 1: work on an earlier discovery by George Robinson and James 523 00:34:30,320 --> 00:34:35,880 Speaker 1: Wallace at Singer Laboratory at Allegheny General Hospital in Pittsburgh, Pennsylvania. 524 00:34:36,080 --> 00:34:39,880 Speaker 1: On October eighth, n they reported that they had found 525 00:34:39,880 --> 00:34:42,239 Speaker 1: a way to make a topical treatment by soaking a 526 00:34:42,280 --> 00:34:45,760 Speaker 1: gauze pad and penicillium mold and then letting it grow 527 00:34:45,840 --> 00:34:49,800 Speaker 1: in a petri dish for four or five days. Vogel, 528 00:34:49,880 --> 00:34:52,840 Speaker 1: who had been disabled following a serious infection in his 529 00:34:52,960 --> 00:34:55,920 Speaker 1: knee as a child, built on this to turn his 530 00:34:56,000 --> 00:34:59,719 Speaker 1: kitchen into a miniature factory for treating similarly mold and 531 00:34:59,800 --> 00:35:03,719 Speaker 1: few used gauze. Vogel's wife, Unice, was a big part 532 00:35:03,719 --> 00:35:06,600 Speaker 1: of this process, making the auger for the petri dishes 533 00:35:06,920 --> 00:35:11,480 Speaker 1: and sterilizing the equipment between batches. As you can imagine, 534 00:35:11,520 --> 00:35:14,000 Speaker 1: all of this required a lot of careful planning to 535 00:35:14,080 --> 00:35:16,799 Speaker 1: keep a steady supply of mold that was the right 536 00:35:16,920 --> 00:35:21,720 Speaker 1: age to produce penicillin. Yeah, Vogel talked a lot about 537 00:35:21,760 --> 00:35:25,240 Speaker 1: how if penicillin had existed when he was a child, 538 00:35:26,400 --> 00:35:30,440 Speaker 1: he probably would not have almost died and then had 539 00:35:30,480 --> 00:35:32,960 Speaker 1: like a disability that affected him for the rest of 540 00:35:33,000 --> 00:35:37,360 Speaker 1: his life. Vogel presented his development at the Department of 541 00:35:37,400 --> 00:35:42,400 Speaker 1: Industrial Research on November eleven, and he got a lot 542 00:35:42,480 --> 00:35:45,880 Speaker 1: of criticism from the research community and from the companies 543 00:35:45,880 --> 00:35:50,399 Speaker 1: that were working on mass producing penicillin. There were some 544 00:35:50,640 --> 00:35:55,040 Speaker 1: understandable concerns about the potential for penicillin made at home 545 00:35:55,120 --> 00:35:59,839 Speaker 1: to be contaminated in some way, but Vogel reportedly used 546 00:35:59,880 --> 00:36:03,840 Speaker 1: these gauze pads that steel mills all over the area, 547 00:36:04,000 --> 00:36:07,760 Speaker 1: treating workers who had on the job accidents and otherwise 548 00:36:07,800 --> 00:36:10,560 Speaker 1: would have just not had access to any antibiotics at all. 549 00:36:11,600 --> 00:36:16,000 Speaker 1: Yet another ethical conundrum arose after Floory and Chain traveled 550 00:36:16,000 --> 00:36:19,960 Speaker 1: to Northern Africa in ninety three to test penicillin on 551 00:36:20,040 --> 00:36:25,120 Speaker 1: wounded soldiers and realized that it was also effective against gonaihea. 552 00:36:26,000 --> 00:36:29,080 Speaker 1: Before this point, penicillin had been envisioned as something that 553 00:36:29,120 --> 00:36:31,760 Speaker 1: would save the lives of soldiers who had been seriously 554 00:36:31,880 --> 00:36:35,360 Speaker 1: entered in battle or had contracted a serious illness like 555 00:36:35,480 --> 00:36:40,719 Speaker 1: bacterial pneumonia, but gonahea, especially in its early stages, is 556 00:36:40,760 --> 00:36:45,000 Speaker 1: more of a nuisance. Winston Churchill reportedly said that penicillin 557 00:36:45,080 --> 00:36:49,200 Speaker 1: should be used for the quote best military advantage, which 558 00:36:49,239 --> 00:36:52,680 Speaker 1: meant when supplies were limited, getting soldiers who had gonaha 559 00:36:52,800 --> 00:36:57,280 Speaker 1: back into peak condition, rather than treating seriously injured soldiers 560 00:36:57,320 --> 00:37:00,880 Speaker 1: who were going to be sent back home. I supplies 561 00:37:00,920 --> 00:37:04,960 Speaker 1: were not limited for that much longer, though. Fiser's first 562 00:37:05,080 --> 00:37:08,640 Speaker 1: plant for the commercial production of penicillin opened in Brooklyn, 563 00:37:08,680 --> 00:37:13,240 Speaker 1: New York, on March first, nineteen. By that point, clinical 564 00:37:13,280 --> 00:37:17,719 Speaker 1: trials had showed that penicillin was clearly beneficial against a 565 00:37:17,920 --> 00:37:22,799 Speaker 1: range of pathogenic bacteria. Refinements to the production process and 566 00:37:23,160 --> 00:37:26,040 Speaker 1: to the mold itself using things like X rays and 567 00:37:26,200 --> 00:37:31,920 Speaker 1: UV light continued to increase the yield. Meanwhile, Alexander Fleming, 568 00:37:32,400 --> 00:37:34,560 Speaker 1: who wasn't involved with any of this, was on the 569 00:37:34,640 --> 00:37:39,600 Speaker 1: cover of Time magazine on May fifteenth. By this point, 570 00:37:39,800 --> 00:37:42,640 Speaker 1: pharmaceutical companies in the U s we're trying to produce 571 00:37:42,840 --> 00:37:46,160 Speaker 1: enough penicillin to meet the needs of the D Day invasion. 572 00:37:47,000 --> 00:37:50,680 Speaker 1: Propaganda posters were hung on the walls of penicillin factories 573 00:37:50,760 --> 00:37:53,640 Speaker 1: reminding workers that they were doing it for the troops, 574 00:37:54,360 --> 00:37:59,080 Speaker 1: and production of penicillin in the US expanded rapidly. Twenty 575 00:37:59,120 --> 00:38:01,680 Speaker 1: one billion units of the drug had been made in 576 00:38:01,800 --> 00:38:05,520 Speaker 1: nineteen forty three, and in nineteen forty five it had 577 00:38:05,600 --> 00:38:09,800 Speaker 1: jumped to six point eight trillion. In March of nineteen 578 00:38:09,880 --> 00:38:13,200 Speaker 1: forty five, the US was able to lift rationing restrictions 579 00:38:13,239 --> 00:38:16,600 Speaker 1: on penicillin and make it commercially available to the public. 580 00:38:17,320 --> 00:38:21,000 Speaker 1: After the liberation of Paris in nineteen forty four, American 581 00:38:21,040 --> 00:38:25,800 Speaker 1: military hospitals throughout France started trying to extend the supply 582 00:38:25,960 --> 00:38:30,920 Speaker 1: of penicillin in the country, which is what inspired this episode. 583 00:38:31,840 --> 00:38:35,759 Speaker 1: The French military Penicillin Team was established, and starting in 584 00:38:35,880 --> 00:38:40,080 Speaker 1: January of nineteen forty five, the team collected urine from 585 00:38:40,120 --> 00:38:43,840 Speaker 1: patients to reclaim the penicillin in it. So if a 586 00:38:43,920 --> 00:38:47,160 Speaker 1: patient was being treated with penicillin, their bed was barked 587 00:38:47,160 --> 00:38:50,160 Speaker 1: with a placard to note that their urine should be collected. 588 00:38:50,880 --> 00:38:52,840 Speaker 1: Patients who are well enough to get up and go 589 00:38:52,920 --> 00:38:56,640 Speaker 1: to the bathroom themselves were instructed to urinate in flasks 590 00:38:56,760 --> 00:38:59,400 Speaker 1: that were just left around the wards for that purpose. 591 00:39:00,120 --> 00:39:03,920 Speaker 1: Officials were understandably a little concerned that these flasks that 592 00:39:03,960 --> 00:39:07,600 Speaker 1: people were peeing into could themselves become a source of infection, 593 00:39:08,160 --> 00:39:11,600 Speaker 1: so the penicillin team collected them all twice a day. 594 00:39:12,520 --> 00:39:15,960 Speaker 1: After the war, manufacturing methods for penicillin that had been 595 00:39:15,960 --> 00:39:19,399 Speaker 1: developed in the US were introduced in the UK, which 596 00:39:19,400 --> 00:39:22,279 Speaker 1: meant that the same researchers who had originally developed the 597 00:39:22,360 --> 00:39:26,280 Speaker 1: drug had to pay licensing fees to access American methods 598 00:39:26,320 --> 00:39:30,680 Speaker 1: to produce it. Although penicillin itself had not been patented, 599 00:39:31,080 --> 00:39:35,640 Speaker 1: some of the manufacturing methods had been new. Penicillin factories 600 00:39:35,680 --> 00:39:38,799 Speaker 1: were also established around the world as nations started making 601 00:39:38,800 --> 00:39:42,759 Speaker 1: their own supply or expanded production from research that they 602 00:39:42,760 --> 00:39:46,680 Speaker 1: had been doing is the war was going on. Alexander Fleming, 603 00:39:46,800 --> 00:39:50,920 Speaker 1: Earnsports Chain, and Howard Walter Floory were jointly awarded the 604 00:39:50,960 --> 00:39:56,759 Speaker 1: Nobel Prize in Physiology or Medicine in that same year. 605 00:39:56,960 --> 00:40:01,920 Speaker 1: The chemical structure of penicillin was confirmed by Dorothy Crowfort Hodgkin, 606 00:40:02,360 --> 00:40:05,680 Speaker 1: and that paved the way for synthetic forms of penicillin. 607 00:40:06,280 --> 00:40:11,480 Speaker 1: Penicillin's effect on medicine was massive, and many other antibiotics followed. 608 00:40:12,080 --> 00:40:14,640 Speaker 1: Stripped a mic in, which was the first truly effective 609 00:40:14,680 --> 00:40:18,799 Speaker 1: treatment for tuberculosis, was developed in nineteen three. We have 610 00:40:18,920 --> 00:40:21,760 Speaker 1: covered that and the controversy around who should be credited 611 00:40:21,800 --> 00:40:26,239 Speaker 1: with discovering it on the podcast in This is an 612 00:40:26,320 --> 00:40:30,879 Speaker 1: enormous advance in medicine, but by the nineteen fifties, some 613 00:40:30,960 --> 00:40:36,720 Speaker 1: bacteria were already becoming resistant to penicillin, including some strains 614 00:40:36,760 --> 00:40:41,200 Speaker 1: of staff bacteria and This was something that Fleming had foreseen, 615 00:40:41,480 --> 00:40:44,800 Speaker 1: and he warned about it in his Nobel Prize address, quote, 616 00:40:45,480 --> 00:40:49,160 Speaker 1: it is not difficult to make microbes resistant to penicillin 617 00:40:49,200 --> 00:40:53,200 Speaker 1: in the laboratory by exposing them to concentrations not sufficient 618 00:40:53,239 --> 00:40:56,480 Speaker 1: to kill them, and the same thing has occasionally happened 619 00:40:56,480 --> 00:41:00,120 Speaker 1: in the body. The time may come when penicilla and 620 00:41:00,239 --> 00:41:03,319 Speaker 1: can be bought by anyone in the shops. Then there 621 00:41:03,400 --> 00:41:06,960 Speaker 1: is the danger that the ignorant man may easily underdose 622 00:41:07,080 --> 00:41:11,200 Speaker 1: himself and by exposing his microbes to non lethal quantities 623 00:41:11,239 --> 00:41:16,240 Speaker 1: of the drug, make them resistant. This is obviously still 624 00:41:16,280 --> 00:41:19,040 Speaker 1: a problem. You have probably heard about it in your 625 00:41:19,120 --> 00:41:21,920 Speaker 1: day to day life at some point, and it's compounded 626 00:41:21,960 --> 00:41:24,600 Speaker 1: by the fact that most antibiotics in use today were 627 00:41:24,640 --> 00:41:28,560 Speaker 1: developed between the nineteen forties and the nineteen sixties, along 628 00:41:28,560 --> 00:41:33,279 Speaker 1: with the widespread use of antibiotics in agriculture. In the 629 00:41:33,280 --> 00:41:36,160 Speaker 1: World Health Organization warned that the world is nearing the 630 00:41:36,200 --> 00:41:41,000 Speaker 1: point of a post antibiotic era and currently describes antibiotic 631 00:41:41,080 --> 00:41:44,480 Speaker 1: resistance as one of the biggest threats to global health, 632 00:41:44,840 --> 00:41:49,880 Speaker 1: food security, and development. Yeah the use of penicillin after 633 00:41:50,040 --> 00:41:53,080 Speaker 1: and other antibiotics after the discovery and sort of the 634 00:41:53,080 --> 00:41:56,440 Speaker 1: Golden Age of antibiotics could be a whole other episode. 635 00:41:57,400 --> 00:42:01,799 Speaker 1: We're living through it. You have listener mail for us 636 00:42:02,560 --> 00:42:06,560 Speaker 1: I do. I have listener mail from Susan, and Susan says, hello, 637 00:42:06,719 --> 00:42:09,799 Speaker 1: I just finished listening to your episode on hypertension. I 638 00:42:09,880 --> 00:42:12,040 Speaker 1: enjoy your podcasts, and I wanted to say thank you 639 00:42:12,080 --> 00:42:14,560 Speaker 1: for that episode. Like Tracy, I have to monitor my 640 00:42:14,600 --> 00:42:18,040 Speaker 1: BP at home and so appreciated a detailed history of 641 00:42:18,080 --> 00:42:21,920 Speaker 1: the condition. I did not realize that dogs could be 642 00:42:21,960 --> 00:42:25,640 Speaker 1: affected by hypertension until one of my dogs was diagnosed 643 00:42:25,640 --> 00:42:28,040 Speaker 1: with a heart murmur. When he went in for his 644 00:42:28,160 --> 00:42:31,680 Speaker 1: e k G, his BP was to ten. The vet 645 00:42:31,760 --> 00:42:35,000 Speaker 1: said their readings should be like ours, when twenty is normal. 646 00:42:35,480 --> 00:42:38,120 Speaker 1: My sweet Baron has been on medication since then and 647 00:42:38,160 --> 00:42:41,879 Speaker 1: it has worked wonders. My other dog, Ramona, recently had 648 00:42:41,920 --> 00:42:45,000 Speaker 1: to have hers checked. Hers was one fourteen, so she's good. 649 00:42:45,520 --> 00:42:48,520 Speaker 1: I've always appreciated the work that vets and vet texts do, 650 00:42:48,640 --> 00:42:50,720 Speaker 1: but I can't imagine what it takes to read blood 651 00:42:50,719 --> 00:42:54,280 Speaker 1: pressure on a dog. I've attached pictures of the baby's 652 00:42:54,400 --> 00:42:57,400 Speaker 1: Ramona is pictured with cuttles the resident boss Lady. I 653 00:42:57,480 --> 00:43:00,320 Speaker 1: was fortunate enough to travel to Europe the summer. Having 654 00:43:00,400 --> 00:43:04,080 Speaker 1: listened to your episode on Margaret Cavendish, I made sure 655 00:43:04,120 --> 00:43:07,600 Speaker 1: to see your tomb at Westminster Abbey picture attached. My 656 00:43:07,680 --> 00:43:10,080 Speaker 1: day job is middle school science teacher, but I'm a 657 00:43:10,120 --> 00:43:12,520 Speaker 1: history buff and very much enjoy listening to your podcast. 658 00:43:12,560 --> 00:43:14,120 Speaker 1: Thank you for all you do season. Thank you so 659 00:43:14,200 --> 00:43:17,000 Speaker 1: much for this email. Season. One of the things that 660 00:43:17,080 --> 00:43:19,960 Speaker 1: crossed my mind in the many, many, many minutes that 661 00:43:20,000 --> 00:43:22,919 Speaker 1: I have spent taking my own blood pressure at home 662 00:43:23,320 --> 00:43:26,759 Speaker 1: is could my cats have high blood pressure? How would 663 00:43:26,760 --> 00:43:32,719 Speaker 1: we even find that out? I'm just gonna say probably 664 00:43:32,760 --> 00:43:35,680 Speaker 1: the answer is yes, if it can also occur in dogs. 665 00:43:36,520 --> 00:43:38,439 Speaker 1: Thank you so much for the email and the dog 666 00:43:38,520 --> 00:43:43,640 Speaker 1: pictures and the picture of Margaret Cavendish's tomb. I don't 667 00:43:43,680 --> 00:43:46,839 Speaker 1: remember if I looked up pictures of that when I 668 00:43:46,880 --> 00:43:49,160 Speaker 1: was researching that episode, but it was more ornate than 669 00:43:49,200 --> 00:43:52,719 Speaker 1: I had it in my head. So thank you for 670 00:43:52,760 --> 00:43:55,400 Speaker 1: all of that. If you would like to send us 671 00:43:55,400 --> 00:43:58,600 Speaker 1: a note about the sereny other podcast or history podcast 672 00:43:58,680 --> 00:44:01,160 Speaker 1: that I heart radio dot com. IM in all over 673 00:44:01,280 --> 00:44:03,640 Speaker 1: social media and missed in history. That's where you'll find 674 00:44:03,640 --> 00:44:07,160 Speaker 1: our Facebook, Twitter, Pinterest, and Instagram and you can subscribe 675 00:44:07,160 --> 00:44:10,120 Speaker 1: to our show, um I heart Radio app, or wherever 676 00:44:10,160 --> 00:44:17,959 Speaker 1: else you'd like to get your podcasts. Stuff you Missed 677 00:44:17,960 --> 00:44:20,400 Speaker 1: in History Class is a production of I heart Radio. 678 00:44:20,719 --> 00:44:23,560 Speaker 1: For more podcasts from I heart Radio, visit the iHeart 679 00:44:23,640 --> 00:44:26,719 Speaker 1: Radio app, Apple Podcasts, or wherever you listen to your 680 00:44:26,760 --> 00:44:27,480 Speaker 1: favorite shows.