1 00:00:01,280 --> 00:00:04,320 Speaker 1: Welcome to Stuff You Missed in History Class, a production 2 00:00:04,360 --> 00:00:13,640 Speaker 1: of I Heart Radio. Hello, and welcome to the podcast. 3 00:00:13,680 --> 00:00:17,000 Speaker 1: I'm Tracy B. Wilson and I'm Holly Frying if you 4 00:00:17,040 --> 00:00:19,520 Speaker 1: are just tuning in today. This is a two parter. 5 00:00:19,960 --> 00:00:23,160 Speaker 1: It is on the development of insulin. And last time 6 00:00:23,239 --> 00:00:26,599 Speaker 1: we talked about how diabetes has been described through history, 7 00:00:27,040 --> 00:00:30,120 Speaker 1: including how people were being treated with starvation diets in 8 00:00:30,160 --> 00:00:33,400 Speaker 1: the years just before the development of insulin, and today 9 00:00:33,440 --> 00:00:36,240 Speaker 1: we are going to tell the insulin part of the story, 10 00:00:36,800 --> 00:00:40,080 Speaker 1: which does build on research that we talked about last 11 00:00:40,120 --> 00:00:42,800 Speaker 1: time around. This will the easiest to understand if you 12 00:00:42,840 --> 00:00:45,519 Speaker 1: have heard part one. As was the case last time, 13 00:00:45,560 --> 00:00:49,120 Speaker 1: we're going to be talking about how experiments on animals 14 00:00:49,200 --> 00:00:52,040 Speaker 1: led to this discovery, as well as how the byproducts 15 00:00:52,120 --> 00:00:55,000 Speaker 1: of animals that were slaughtered for food we're used to 16 00:00:55,040 --> 00:00:58,520 Speaker 1: make insulin. It is not clear who coined the term insulin. 17 00:00:59,160 --> 00:01:02,120 Speaker 1: It comes from the word insula or island, as a 18 00:01:02,160 --> 00:01:04,720 Speaker 1: nod to the islets of langer Hans. As we talked 19 00:01:04,720 --> 00:01:07,080 Speaker 1: about in Part one. The islets of langer Hans are 20 00:01:07,120 --> 00:01:10,520 Speaker 1: cells in the pancreas that produce insulin and other hormones. 21 00:01:11,360 --> 00:01:14,480 Speaker 1: Jean de Meyer of Belgium used the word insuline with 22 00:01:14,560 --> 00:01:17,399 Speaker 1: an E on the end in nineteen o nine, and 23 00:01:17,440 --> 00:01:21,520 Speaker 1: apparently independently of that, Ernest Henry Starling, who coined the 24 00:01:21,520 --> 00:01:24,720 Speaker 1: word hormone, also used the word insulin with an E. 25 00:01:25,040 --> 00:01:29,479 Speaker 1: Four years later. In the early nineteenteen, Sir Edward Albert 26 00:01:29,640 --> 00:01:33,920 Speaker 1: Sharpie Schaffer also described a hypothetical substance secreted by the 27 00:01:33,920 --> 00:01:37,680 Speaker 1: islets of langer Hans, which controlled the body's glucose levels, 28 00:01:37,680 --> 00:01:40,600 Speaker 1: and he called that insulin. This time there was no 29 00:01:40,760 --> 00:01:43,840 Speaker 1: E on the end. None of these people are the 30 00:01:43,880 --> 00:01:48,240 Speaker 1: ones credited with the discovery of insulin, though that story 31 00:01:48,400 --> 00:01:51,800 Speaker 1: starts with Frederick Grant Banting. Banting was born on a 32 00:01:51,840 --> 00:01:55,200 Speaker 1: farm in Ontario, Canada, and initially he had planned to 33 00:01:55,240 --> 00:01:58,440 Speaker 1: go to divinity school, but after enrolling at the University 34 00:01:58,480 --> 00:02:02,080 Speaker 1: of Toronto, he's changed his major to medicine. When World 35 00:02:02,120 --> 00:02:05,320 Speaker 1: War One started, he joined the Canadian Army Medical Corps 36 00:02:05,360 --> 00:02:09,000 Speaker 1: and was placed on an accelerated medical study program. During 37 00:02:09,000 --> 00:02:11,360 Speaker 1: the war, he was wounded in action and awarded the 38 00:02:11,360 --> 00:02:15,959 Speaker 1: Military Cross in After the war was over, Banting completed 39 00:02:15,960 --> 00:02:18,720 Speaker 1: a surgical residency and tried to set up a private 40 00:02:18,720 --> 00:02:22,200 Speaker 1: surgical practice, it did not grow quickly enough for him 41 00:02:22,240 --> 00:02:24,359 Speaker 1: to make ends meet, so he also took a part 42 00:02:24,360 --> 00:02:28,119 Speaker 1: time teaching position at the University of Western Ontario that's 43 00:02:28,120 --> 00:02:31,680 Speaker 1: now known as Western University. The classes that he was 44 00:02:31,720 --> 00:02:35,280 Speaker 1: teaching included physiology, something that he had studied as part 45 00:02:35,280 --> 00:02:38,400 Speaker 1: of his own medical education, but also something that he 46 00:02:38,480 --> 00:02:41,120 Speaker 1: really needed to brush up on in order to teach. 47 00:02:41,800 --> 00:02:45,679 Speaker 1: On October thirty one, nineteen twenty, Banting was brushing up 48 00:02:45,720 --> 00:02:49,280 Speaker 1: on the pancreas he read a paper called the Relation 49 00:02:49,440 --> 00:02:52,399 Speaker 1: of the Islets of Longer Hauns to Diabetes with Special 50 00:02:52,480 --> 00:02:57,600 Speaker 1: Reference to Cases of Pancreatic Lithiasis by Moses Barron. This 51 00:02:57,760 --> 00:03:00,840 Speaker 1: paper discussed the autopsy of someone you turned out to 52 00:03:00,919 --> 00:03:04,119 Speaker 1: have a pancreatic stone that had totally blocked their main 53 00:03:04,160 --> 00:03:09,320 Speaker 1: pancreatic duct. The person's pancreas still had islets cells, but 54 00:03:09,400 --> 00:03:13,639 Speaker 1: the asiner cells had atrophied. This paper also noted earlier 55 00:03:13,720 --> 00:03:17,360 Speaker 1: experiments in which the main pancreatic ducts of various animals 56 00:03:17,360 --> 00:03:20,959 Speaker 1: had been partially or totally legated, which had caused similar results, 57 00:03:21,000 --> 00:03:23,480 Speaker 1: and that is research that we talked about some of 58 00:03:23,680 --> 00:03:27,919 Speaker 1: back in our previous episode. Banting was inspired by this idea. 59 00:03:28,320 --> 00:03:31,200 Speaker 1: He wrote a note in his journal which read, quote 60 00:03:31,600 --> 00:03:36,320 Speaker 1: diabetes legate pancreatic ducts of dog keep dogs alive till 61 00:03:36,360 --> 00:03:41,280 Speaker 1: assony degenerate, leaving islets. Try to isolate the internal secretion 62 00:03:41,640 --> 00:03:45,280 Speaker 1: of these to relieve glycosuria. So a few things to 63 00:03:45,440 --> 00:03:48,400 Speaker 1: note at this point. One of the Banting's note is 64 00:03:48,440 --> 00:03:52,600 Speaker 1: about glycosyria, or sugar in the urine, rather than blood sugar. 65 00:03:53,240 --> 00:03:56,040 Speaker 1: Banting also was not really aware of all those experiments 66 00:03:56,040 --> 00:03:58,800 Speaker 1: that we talked about in part one. He didn't really 67 00:03:58,880 --> 00:04:02,160 Speaker 1: realize that rees As had spent more than two decades 68 00:04:02,280 --> 00:04:06,000 Speaker 1: trying to do basically what he was describing without yielding 69 00:04:06,040 --> 00:04:08,840 Speaker 1: something that was safe enough to use in human patients. 70 00:04:09,320 --> 00:04:12,400 Speaker 1: It's also not clear how exactly that he thought he 71 00:04:12,480 --> 00:04:16,480 Speaker 1: might quote try to isolate the internal secretion of the 72 00:04:16,480 --> 00:04:19,520 Speaker 1: islets of langer huns, or whether he was thinking about 73 00:04:19,560 --> 00:04:22,960 Speaker 1: preparing a pancreatic extract or thinking he might try to 74 00:04:23,000 --> 00:04:26,680 Speaker 1: find the secretion itself. Later on, when he told people 75 00:04:26,760 --> 00:04:29,560 Speaker 1: from memory what he'd written down in his journal that night, 76 00:04:29,600 --> 00:04:33,080 Speaker 1: he said it was quote legate pancreatic ducts of dogs 77 00:04:33,320 --> 00:04:37,280 Speaker 1: weight six to eight weeks for degeneration, remove the residue, 78 00:04:37,320 --> 00:04:40,840 Speaker 1: and extract, and that is a lot more specific. Also, 79 00:04:41,320 --> 00:04:44,280 Speaker 1: part of Banting's basic idea here was a little bit off. 80 00:04:44,680 --> 00:04:48,039 Speaker 1: His rationale for causing the acid our cells to atrophy 81 00:04:48,279 --> 00:04:51,119 Speaker 1: was that they produced digestive enzymes, and he thought those 82 00:04:51,279 --> 00:04:55,120 Speaker 1: enzymes might destroy whatever vital substance was being produced in 83 00:04:55,160 --> 00:04:59,160 Speaker 1: the islets of langer Huns. But really these enzymes are 84 00:04:59,240 --> 00:05:02,839 Speaker 1: not active until they come into contact with other enzymes 85 00:05:02,839 --> 00:05:06,560 Speaker 1: in the small intestine. The relationships between those two different 86 00:05:06,600 --> 00:05:10,240 Speaker 1: sets of enzymes had been discovered back in nineteen o four. Also, 87 00:05:10,520 --> 00:05:14,760 Speaker 1: it's possible that there's some other explanation, but his misspellings 88 00:05:14,920 --> 00:05:19,320 Speaker 1: of both diabetes and glycosuria suggests that Banting wasn't all 89 00:05:19,360 --> 00:05:22,680 Speaker 1: that familiar with what he was writing about. So at 90 00:05:22,680 --> 00:05:24,840 Speaker 1: this point Banting went to his boss at the University 91 00:05:24,880 --> 00:05:28,760 Speaker 1: of Western Ontario about this idea. His boss referred him 92 00:05:28,800 --> 00:05:32,720 Speaker 1: to John James Rickard MacLeod at the University of Toronto. 93 00:05:33,240 --> 00:05:36,000 Speaker 1: McLeod was born in Scotland and had studied medicine at 94 00:05:36,000 --> 00:05:39,320 Speaker 1: the University of Aberdeen. He had also taught at several 95 00:05:39,400 --> 00:05:43,719 Speaker 1: universities and institutes in Europe and North America before becoming 96 00:05:43,760 --> 00:05:47,440 Speaker 1: professor of physiology at the University of Toronto and also 97 00:05:47,600 --> 00:05:52,159 Speaker 1: director of its physiological Laboratory. McLeod was a leading expert 98 00:05:52,200 --> 00:05:56,039 Speaker 1: in carbohydrate metabolism at the time, and in nineteen he 99 00:05:56,040 --> 00:06:00,560 Speaker 1: had published Diabetes, Its Pathology and Physiology. He had been 100 00:06:00,560 --> 00:06:03,719 Speaker 1: trying to identify which part of the nervous system controlled 101 00:06:03,720 --> 00:06:08,200 Speaker 1: the liver's glycogen storage functions. Unlike Banting, McLeod knew all 102 00:06:08,240 --> 00:06:11,200 Speaker 1: about those earlier attempts to make a pancreatic extract that 103 00:06:11,240 --> 00:06:14,360 Speaker 1: could treat diabetes, and he thought there was some kind 104 00:06:14,400 --> 00:06:16,680 Speaker 1: of pancreatic secretion that could be the key to an 105 00:06:16,720 --> 00:06:19,880 Speaker 1: effective treatment, but he had his doubts about it's ever 106 00:06:19,960 --> 00:06:23,920 Speaker 1: being isolated and used. And it wasn't just that McLeod 107 00:06:24,000 --> 00:06:26,680 Speaker 1: had doubts about whether it was possible at all to 108 00:06:26,800 --> 00:06:31,479 Speaker 1: make a usable pancreatic extract. Those earlier researchers also all 109 00:06:31,560 --> 00:06:35,279 Speaker 1: had training and skills and experience that Banting just didn't have. 110 00:06:36,120 --> 00:06:38,960 Speaker 1: Mcloud's impression of Banting was that he had a very basic, 111 00:06:39,120 --> 00:06:43,000 Speaker 1: textbook level understanding of the pancreas and its role in diabetes, 112 00:06:43,080 --> 00:06:47,000 Speaker 1: and really this was pretty accurate. So McLeod was reluctant 113 00:06:47,040 --> 00:06:51,400 Speaker 1: to offer Banting the lab space, assistance, materials and animals 114 00:06:51,440 --> 00:06:54,160 Speaker 1: that he was going to need to research his idea. 115 00:06:54,320 --> 00:06:57,400 Speaker 1: The two men had multiple meetings to talk through the situation, 116 00:06:58,080 --> 00:07:00,719 Speaker 1: and then when McLeod finally agreed to let Banting do 117 00:07:00,920 --> 00:07:04,320 Speaker 1: some experiments over the summer, Banting actually got a little 118 00:07:04,360 --> 00:07:07,920 Speaker 1: nervous about it. Banding still thought that his idea might 119 00:07:08,000 --> 00:07:10,720 Speaker 1: lead to a breakthrough, but he also understood that if 120 00:07:10,760 --> 00:07:13,600 Speaker 1: he left his practice and his job to pursue an 121 00:07:13,640 --> 00:07:16,120 Speaker 1: idea that didn't work out, he would basically have to 122 00:07:16,120 --> 00:07:19,600 Speaker 1: start his career over while also trying to pay off 123 00:07:19,640 --> 00:07:24,360 Speaker 1: debts from a failed project. On March eighth, one, Banting 124 00:07:24,400 --> 00:07:27,560 Speaker 1: and McLeod finally agreed on the terms of the project. 125 00:07:27,920 --> 00:07:30,040 Speaker 1: The work would take place over the summer of nine 126 00:07:30,880 --> 00:07:34,680 Speaker 1: starting in mid May. Two students, Charles Best and Edward 127 00:07:34,680 --> 00:07:38,080 Speaker 1: Clark Noble, would assist Banting. They would divide the summer 128 00:07:38,120 --> 00:07:41,120 Speaker 1: between the two of them. These two young men flipped 129 00:07:41,120 --> 00:07:43,520 Speaker 1: a coin to see who would take the first shift 130 00:07:43,600 --> 00:07:46,280 Speaker 1: with Banting, with Best planning to take the first half 131 00:07:46,280 --> 00:07:48,880 Speaker 1: of the project and Noble planning to take the second half. 132 00:07:49,520 --> 00:07:52,280 Speaker 1: Best at that point had finished his bachelor's degree in 133 00:07:52,280 --> 00:07:56,120 Speaker 1: physiology and biochemistry and was preparing to start medical school. 134 00:07:56,480 --> 00:07:59,920 Speaker 1: For about a month, Banting, Best in McLeod all were 135 00:08:00,080 --> 00:08:03,360 Speaker 1: together in the lab, with McLeod fine tuning their plan 136 00:08:03,520 --> 00:08:07,200 Speaker 1: and process and surgical techniques and instructing them on how 137 00:08:07,200 --> 00:08:11,040 Speaker 1: to best prepare an extract. Then in mid June he 138 00:08:11,160 --> 00:08:14,720 Speaker 1: left for a vacation in Scotland that he had previously arranged. 139 00:08:15,400 --> 00:08:18,520 Speaker 1: We will talk about how Bantings and bests work proceeded 140 00:08:18,600 --> 00:08:21,120 Speaker 1: over the summer, which will have more about their animal 141 00:08:21,160 --> 00:08:31,960 Speaker 1: experiments after a quick sponsor break. When Frederick Banting and 142 00:08:32,040 --> 00:08:35,160 Speaker 1: Charles Best started their experiments on dogs to try to 143 00:08:35,200 --> 00:08:38,120 Speaker 1: find a treatment for diabetes, things did not go well. 144 00:08:38,920 --> 00:08:41,720 Speaker 1: Their plan was to legate the pancreatic ducts of some 145 00:08:41,800 --> 00:08:44,000 Speaker 1: of the dogs, which would cause the assent our cells 146 00:08:44,000 --> 00:08:47,280 Speaker 1: to atrophy, but theoretically at least leave the islets of 147 00:08:47,320 --> 00:08:51,040 Speaker 1: longer hunts mostly unaffected. By that point, Banting would have 148 00:08:51,200 --> 00:08:54,600 Speaker 1: learned that the digestive enzymes were inactive while they were 149 00:08:54,600 --> 00:08:58,160 Speaker 1: actually in the pancreas. But this atrophy of the assenter 150 00:08:58,200 --> 00:09:00,920 Speaker 1: cells would at least in theory, deuced the amount of 151 00:09:00,960 --> 00:09:03,800 Speaker 1: material that needed to be removed from the extract before 152 00:09:03,800 --> 00:09:07,319 Speaker 1: it could be safely used. Once enough time had passed 153 00:09:07,400 --> 00:09:11,800 Speaker 1: after this legation procedure to allow the asdenter cells to atrophy, 154 00:09:11,840 --> 00:09:15,240 Speaker 1: they would euthanize the dog and remove its pancreas, using 155 00:09:15,280 --> 00:09:19,120 Speaker 1: it to prepare an extract. Then they'd inject that extract 156 00:09:19,200 --> 00:09:23,280 Speaker 1: into another dog whose pancreas had been removed entirely. However, 157 00:09:23,559 --> 00:09:27,360 Speaker 1: these surgical procedures could be difficult. It was also summer, 158 00:09:27,480 --> 00:09:30,600 Speaker 1: so the facilities where they were working were hot and uncomfortable. 159 00:09:31,040 --> 00:09:33,319 Speaker 1: Several of the dogs that they were working with died 160 00:09:33,400 --> 00:09:37,199 Speaker 1: of infections or other complications, and they started buying stray 161 00:09:37,320 --> 00:09:41,280 Speaker 1: dogs as replacements. It was mid July before they had 162 00:09:41,320 --> 00:09:45,760 Speaker 1: a deep pancreatized dog and one with an atrophied pancreas 163 00:09:45,800 --> 00:09:48,400 Speaker 1: ready to work at the same time. The process of 164 00:09:48,440 --> 00:09:52,880 Speaker 1: preparing a pancreatic extract was also long and complex. It 165 00:09:52,920 --> 00:09:57,679 Speaker 1: included chopping the pancreas, chilling it, grinding it up, filtering it, 166 00:09:57,800 --> 00:10:01,040 Speaker 1: and warming it back up to body temperature. On July, 167 00:10:02,600 --> 00:10:06,680 Speaker 1: they tried injecting their extract for the first time. Although 168 00:10:06,720 --> 00:10:09,719 Speaker 1: the sugar levels in the dog's urine did drop, they 169 00:10:09,840 --> 00:10:13,280 Speaker 1: rose again pretty quickly. The dog died the next day, 170 00:10:13,400 --> 00:10:17,240 Speaker 1: most likely from an infection. Banting and Best kept trying, though. 171 00:10:17,520 --> 00:10:19,920 Speaker 1: When Edward Noble came back to the lab to take 172 00:10:19,960 --> 00:10:22,400 Speaker 1: over his shift as assistant, he found that the two 173 00:10:22,440 --> 00:10:24,880 Speaker 1: of them had worked out this whole rhythm and flow 174 00:10:24,960 --> 00:10:27,600 Speaker 1: to their work. At that point, Noble thought that if 175 00:10:27,600 --> 00:10:30,680 Speaker 1: he tried to take Best's place, as was previously planned, 176 00:10:30,720 --> 00:10:33,240 Speaker 1: he would just become a hindrance to the project. He 177 00:10:33,280 --> 00:10:36,280 Speaker 1: would have to learn everything that Best was doing pretty 178 00:10:36,360 --> 00:10:39,200 Speaker 1: routinely at that point, so he left Best to it, 179 00:10:39,400 --> 00:10:41,480 Speaker 1: although he did come back to the project later on, 180 00:10:41,559 --> 00:10:45,080 Speaker 1: which we will get to. In August, Banting and Best 181 00:10:45,360 --> 00:10:49,000 Speaker 1: ran out of legated dogs, so they switched to using 182 00:10:49,000 --> 00:10:52,360 Speaker 1: the whole pancreas something that, as it turned out, worked 183 00:10:52,400 --> 00:10:56,200 Speaker 1: just as well. They kept refining their work and taking notes, 184 00:10:56,240 --> 00:10:59,360 Speaker 1: and when McLeod returned to the lab on September one, 185 00:10:59,520 --> 00:11:03,280 Speaker 1: they had results. This seemed promising. They were still seeing 186 00:11:03,320 --> 00:11:06,600 Speaker 1: some complications, but their extract did seem to be lowering 187 00:11:06,600 --> 00:11:11,240 Speaker 1: the glucose levels of deep pancreatized dogs. McLeod, as we 188 00:11:11,320 --> 00:11:15,280 Speaker 1: said earlier, was very skeptical about this whole project from 189 00:11:15,320 --> 00:11:18,080 Speaker 1: the very beginning, and he was surprised enough at these 190 00:11:18,120 --> 00:11:22,320 Speaker 1: results that he questioned whether they were accurate. Banting was 191 00:11:22,480 --> 00:11:25,920 Speaker 1: highly insulted by the suggestion, and the two men butted 192 00:11:25,920 --> 00:11:30,280 Speaker 1: heads over it. Ultimately, McLeod told them to repeat their experiment. 193 00:11:30,840 --> 00:11:34,280 Speaker 1: Apart from taking offense at being questioned about the accuracy 194 00:11:34,320 --> 00:11:38,440 Speaker 1: of his work, Banting was also worried about his finances. 195 00:11:38,480 --> 00:11:40,880 Speaker 1: He had planned to take the summer to do this research, 196 00:11:41,280 --> 00:11:43,920 Speaker 1: but he had not planned for it to continue into 197 00:11:43,920 --> 00:11:47,560 Speaker 1: the next academic year. He also thought the facilities where 198 00:11:47,559 --> 00:11:50,800 Speaker 1: he'd spent the summer working left a lot to be desired. 199 00:11:51,320 --> 00:11:53,880 Speaker 1: For example, he said that they couldn't scrub the floors 200 00:11:53,880 --> 00:11:57,120 Speaker 1: thoroughly because if they did, water leaked through the ceiling 201 00:11:57,160 --> 00:11:59,959 Speaker 1: of the room below. He thought that was to blame 202 00:12:00,000 --> 00:12:02,160 Speaker 1: for some of the infections and the deaths of their 203 00:12:02,200 --> 00:12:06,760 Speaker 1: research animals. So Banting asked for a salary and one 204 00:12:06,840 --> 00:12:09,040 Speaker 1: for best as well as repairs to the floor of 205 00:12:09,040 --> 00:12:11,880 Speaker 1: the lab and an assistant to take care of the animals. 206 00:12:12,360 --> 00:12:15,280 Speaker 1: Banting also asked for a biochemist to be added to 207 00:12:15,280 --> 00:12:18,320 Speaker 1: the team to help them better refine their pancreatic extract. 208 00:12:19,040 --> 00:12:22,240 Speaker 1: McLeod didn't think they were ready for that last step yet, 209 00:12:22,280 --> 00:12:26,160 Speaker 1: but he did give Banting and Best retroactive salaries. He 210 00:12:26,280 --> 00:12:28,800 Speaker 1: also hired somebody to take care of the dogs and 211 00:12:29,040 --> 00:12:33,000 Speaker 1: arranged to have the laboratory floor waterproofed with tar, which 212 00:12:33,080 --> 00:12:36,079 Speaker 1: was like the least expensive way to deal with this 213 00:12:36,160 --> 00:12:40,640 Speaker 1: water seepage problem. Eventually, Banting and Best tried another source 214 00:12:40,679 --> 00:12:44,760 Speaker 1: for their pancreas tissue. After learning that fetal and newborn 215 00:12:44,840 --> 00:12:48,520 Speaker 1: calves had proportionally more islet cells than older animals do. 216 00:12:49,000 --> 00:12:53,439 Speaker 1: They started buying fetal pancreas from slaughterhouses. They still had 217 00:12:53,440 --> 00:12:56,120 Speaker 1: trouble getting enough pancreas for their work, though, so they 218 00:12:56,200 --> 00:13:00,600 Speaker 1: ultimately started using the whole pancreas of adult animals, also 219 00:13:00,720 --> 00:13:05,560 Speaker 1: purchased from slaughterhouses. In November of one, Banting and Best 220 00:13:05,640 --> 00:13:10,120 Speaker 1: published a paper, the Internal Secretion of the Pancreas. Banting 221 00:13:10,240 --> 00:13:14,440 Speaker 1: also presented the paper publicly that December in New Haven, Connecticut. 222 00:13:14,920 --> 00:13:19,359 Speaker 1: This presentation once again caused tension between Banting and McLeod. 223 00:13:19,920 --> 00:13:22,720 Speaker 1: Banting was just not a very good public speaker, and 224 00:13:22,800 --> 00:13:24,760 Speaker 1: some of the people who were in the audience on 225 00:13:24,840 --> 00:13:27,280 Speaker 1: that day were literally at the top of their field. 226 00:13:27,760 --> 00:13:30,760 Speaker 1: He just didn't have the breadth of knowledge to answer 227 00:13:30,840 --> 00:13:33,920 Speaker 1: some of the very probing questions that they asked him. 228 00:13:33,920 --> 00:13:38,679 Speaker 1: When Banting had trouble fielding questions, McLeod stepped in. He 229 00:13:38,800 --> 00:13:41,200 Speaker 1: did have that breadth of knowledge, and he was also 230 00:13:41,320 --> 00:13:45,200 Speaker 1: polished and well spoken in his presentation. He also used 231 00:13:45,200 --> 00:13:48,640 Speaker 1: the word we a lot, something that wasn't necessarily unusual 232 00:13:48,800 --> 00:13:51,920 Speaker 1: considering that the work was happening in his lab ultimately 233 00:13:52,000 --> 00:13:56,680 Speaker 1: under his supervision. But Banting felt like McLeod was taking 234 00:13:56,720 --> 00:13:59,720 Speaker 1: credit for work that he had not actually done. And 235 00:13:59,800 --> 00:14:02,959 Speaker 1: the audience that day was the research director for Eli 236 00:14:03,040 --> 00:14:06,160 Speaker 1: Lily Pharmaceuticals, who asked if the company could be involved 237 00:14:06,160 --> 00:14:09,640 Speaker 1: in this project, and in McLeod's opinion, once again, they 238 00:14:09,640 --> 00:14:13,200 Speaker 1: were not there yet. By the end of though, McLeod 239 00:14:13,240 --> 00:14:16,440 Speaker 1: thought the project was promising enough that he finally did 240 00:14:16,480 --> 00:14:20,200 Speaker 1: bring on a biochemist, James Bertram Collop, who took a 241 00:14:20,200 --> 00:14:23,600 Speaker 1: sabbatical from the University of Alberta at Edmonton to work 242 00:14:23,640 --> 00:14:27,400 Speaker 1: on it. McLeod also dedicated the whole lab to the project, 243 00:14:27,600 --> 00:14:30,200 Speaker 1: thinking that they were on the verge of a life 244 00:14:30,200 --> 00:14:35,080 Speaker 1: saving breakthrough. The extraction method that Collip developed was a 245 00:14:35,120 --> 00:14:40,280 Speaker 1: lot more effective but also still very involved. I initially 246 00:14:40,360 --> 00:14:43,560 Speaker 1: had like all of the steps written into this outline, 247 00:14:43,560 --> 00:14:47,720 Speaker 1: and it went on for paragraphs. He realized that different 248 00:14:47,760 --> 00:14:51,840 Speaker 1: pancreatic materials could be extracted at different strengths of alcohol, 249 00:14:51,920 --> 00:14:56,000 Speaker 1: and so he developed this method that included multiple extraction steps, 250 00:14:56,400 --> 00:14:59,920 Speaker 1: with the results of those extractions being concentrated in centrifu, 251 00:15:00,040 --> 00:15:04,160 Speaker 1: huged and precipitated. It went on. He also discovered that 252 00:15:04,240 --> 00:15:07,920 Speaker 1: the extracts lowered the blood sugar of rabbits, so they 253 00:15:07,960 --> 00:15:11,960 Speaker 1: no longer needed to work with deep pancreatized dogs. Edward 254 00:15:12,040 --> 00:15:15,160 Speaker 1: Clark Noble rejoined the project at this point to help 255 00:15:15,160 --> 00:15:18,360 Speaker 1: with the studies on rabbits. Running parallel to this work 256 00:15:18,400 --> 00:15:21,920 Speaker 1: at the University of Toronto were developments in blood sugar testing, 257 00:15:22,240 --> 00:15:25,120 Speaker 1: which made it easier to test their extracts effects on 258 00:15:25,160 --> 00:15:28,600 Speaker 1: blood sugar directly, rather than relying on how it affected 259 00:15:28,600 --> 00:15:32,720 Speaker 1: glucose levels in the urine. More efficient and effective blood 260 00:15:32,720 --> 00:15:35,840 Speaker 1: sugar testing was a huge part of the ongoing development 261 00:15:35,880 --> 00:15:40,280 Speaker 1: of insulin. In late December of Banting tried one of 262 00:15:40,320 --> 00:15:44,480 Speaker 1: their extracts on a human subject. Dr Joseph Gilchrist had 263 00:15:44,480 --> 00:15:47,920 Speaker 1: been one of Banting's classmates and had developed diabetes not 264 00:15:48,000 --> 00:15:51,840 Speaker 1: long after they graduated from medical school. This extract did 265 00:15:51,880 --> 00:15:53,920 Speaker 1: not work at all, though, and it wasn't because the 266 00:15:53,960 --> 00:15:57,280 Speaker 1: extract itself was bad. Even if they had made completely 267 00:15:57,360 --> 00:16:01,400 Speaker 1: pure insulin, if taken orally, that would have been digested 268 00:16:01,440 --> 00:16:04,080 Speaker 1: in the stomach way before it could have been absorbed 269 00:16:04,080 --> 00:16:08,320 Speaker 1: into the bloodstream. In January of the team was ready 270 00:16:08,400 --> 00:16:11,640 Speaker 1: for their first attempt at injecting their extract into a 271 00:16:11,760 --> 00:16:15,920 Speaker 1: human patient. The patient was Leonard Thompson, who was fourteen 272 00:16:16,000 --> 00:16:19,600 Speaker 1: years old and critically ill. He weighed only sixty five 273 00:16:19,640 --> 00:16:23,000 Speaker 1: pounds that's about thirty ms when he was admitted to 274 00:16:23,000 --> 00:16:27,160 Speaker 1: Toronto General Hospital. He had been on a starvation diet 275 00:16:27,280 --> 00:16:29,920 Speaker 1: like we talked about in Part one, which had taken 276 00:16:30,000 --> 00:16:33,360 Speaker 1: him down to about four hundred fifty calories per day. 277 00:16:33,760 --> 00:16:37,360 Speaker 1: His daily yearine output was about four leaders that's more 278 00:16:37,360 --> 00:16:40,560 Speaker 1: than a gallon. A typical amount is more like eight 279 00:16:40,600 --> 00:16:43,720 Speaker 1: hundred to two thousand million leaders. And he was also 280 00:16:43,800 --> 00:16:47,240 Speaker 1: showing signs of diabetic keto acidosis, which is when the 281 00:16:47,280 --> 00:16:50,600 Speaker 1: body starts burning fat instead of sugar for fuel and 282 00:16:50,640 --> 00:16:52,920 Speaker 1: as a result, acids start to build up in the 283 00:16:52,920 --> 00:16:57,160 Speaker 1: blood stream. So this whole time Banting had felt like 284 00:16:57,240 --> 00:17:01,080 Speaker 1: McLeod had been stealing credit for his work, second guessing him, 285 00:17:01,160 --> 00:17:04,639 Speaker 1: and undermining him every step of the way. Added to 286 00:17:04,680 --> 00:17:07,520 Speaker 1: all of that, Banting could not really control this first 287 00:17:07,600 --> 00:17:10,359 Speaker 1: human trial at all. He did not have the background 288 00:17:10,440 --> 00:17:12,840 Speaker 1: or the experience that was needed to run a trial 289 00:17:12,880 --> 00:17:16,040 Speaker 1: on human subjects. He also did not have the authority 290 00:17:16,080 --> 00:17:19,800 Speaker 1: to work with patients at Toronto General Hospital, So when 291 00:17:19,840 --> 00:17:23,439 Speaker 1: it came to their first human trial, Banting really insisted 292 00:17:23,480 --> 00:17:26,720 Speaker 1: that they use an extract that he and Best had prepared. 293 00:17:27,080 --> 00:17:31,960 Speaker 1: They did this on January eleventh. Of This preparation did 294 00:17:32,040 --> 00:17:35,879 Speaker 1: lower Leonards blood sugar somewhat, but it did not alleviate 295 00:17:35,920 --> 00:17:39,480 Speaker 1: any of his outward symptoms of diabetes. The boy also 296 00:17:39,520 --> 00:17:43,160 Speaker 1: developed an abscess at one of the injection sites. Colip, 297 00:17:43,160 --> 00:17:46,120 Speaker 1: who was still refining his methods for extraction, really went 298 00:17:46,160 --> 00:17:49,399 Speaker 1: into overdrive at this point, finally producing an extract he 299 00:17:49,440 --> 00:17:52,520 Speaker 1: thought was pure enough to use. Several days later. They 300 00:17:52,560 --> 00:17:55,720 Speaker 1: tried again with this extract on January twenty three of 301 00:17:55,840 --> 00:17:59,480 Speaker 1: nineteen twenty two, and this time the results were immediately 302 00:17:59,600 --> 00:18:04,360 Speaker 1: and dramatically affected. Leonard's blood sugar dropped significantly, as did 303 00:18:04,400 --> 00:18:06,959 Speaker 1: the glucose in his urine, and he also was just 304 00:18:07,240 --> 00:18:10,199 Speaker 1: visibly improved. It was obvious to other people that he 305 00:18:10,240 --> 00:18:14,280 Speaker 1: was doing better. In the words of Charles Best's notes quote, 306 00:18:14,680 --> 00:18:18,199 Speaker 1: daily injections of the extract were made from January to 307 00:18:18,240 --> 00:18:24,280 Speaker 1: February fourth, accepting January and February fourth. This resulted in 308 00:18:24,320 --> 00:18:28,840 Speaker 1: an immediate improvement. The excretion of sugar became much less, 309 00:18:29,320 --> 00:18:33,600 Speaker 1: the acetone bodies disappeared from the urine. The boy became brighter, 310 00:18:33,880 --> 00:18:38,639 Speaker 1: more active, looked better, and said he felt stronger. Leonard, 311 00:18:38,640 --> 00:18:41,399 Speaker 1: whose condition had been critical when he was admitted, lived 312 00:18:41,440 --> 00:18:46,120 Speaker 1: another ten years. After the success, though, the ongoing backbiting 313 00:18:46,119 --> 00:18:49,200 Speaker 1: and hostility in the lab became even more dramatic, and 314 00:18:49,240 --> 00:18:59,239 Speaker 1: we will get to that. After another sponsor break at 315 00:18:59,359 --> 00:19:02,199 Speaker 1: Leonard Tom Sin was getting his first injections of a 316 00:19:02,320 --> 00:19:07,720 Speaker 1: working pancreatic extract. The already contentious relationships among the team 317 00:19:07,800 --> 00:19:12,160 Speaker 1: from the University of Toronto got even worse. James Callip, 318 00:19:12,200 --> 00:19:15,200 Speaker 1: who had not shared the details of his extraction method 319 00:19:15,200 --> 00:19:18,679 Speaker 1: with anyone else, threatened to quit the project and patent 320 00:19:18,760 --> 00:19:21,800 Speaker 1: it himself. The details here are a little bit sketchy, 321 00:19:22,000 --> 00:19:25,480 Speaker 1: but Banting was outraged and he and Collip had a 322 00:19:25,520 --> 00:19:29,359 Speaker 1: physical altercation in the lab, with Banting grabbing Collip by 323 00:19:29,359 --> 00:19:31,960 Speaker 1: the color of his coat and slamming him into a chair, 324 00:19:32,480 --> 00:19:35,159 Speaker 1: and Best writing that he had to restrain Banting with 325 00:19:35,320 --> 00:19:40,800 Speaker 1: all of his force. After this, on January two, Banting, Best, 326 00:19:40,840 --> 00:19:43,119 Speaker 1: and call Up all signed a memo that none of 327 00:19:43,160 --> 00:19:46,119 Speaker 1: them would be seeking a patent for insulin. This was 328 00:19:46,160 --> 00:19:49,879 Speaker 1: part of a manufacturing agreement with Connu Laboratories, which is 329 00:19:49,880 --> 00:19:53,040 Speaker 1: a public pharmaceutical company that had been established in Canada 330 00:19:53,119 --> 00:19:57,160 Speaker 1: during World War One to make diphtheria anti toxin. After 331 00:19:57,240 --> 00:20:01,160 Speaker 1: that first successful treatment of Leonard Thompson, six more patients 332 00:20:01,160 --> 00:20:05,200 Speaker 1: were treated in February of nineteen two. From there, they 333 00:20:05,200 --> 00:20:08,600 Speaker 1: moved quickly into a clinical trial, and at that point 334 00:20:08,680 --> 00:20:12,160 Speaker 1: the project largely moved out of Bantings and Best's hands. 335 00:20:12,920 --> 00:20:15,119 Speaker 1: As we said earlier, Banting just did not have the 336 00:20:15,160 --> 00:20:19,120 Speaker 1: training or experience to run a clinical trial on human subjects, 337 00:20:19,520 --> 00:20:22,200 Speaker 1: and he was deeply frustrated by his exclusion, and he 338 00:20:22,320 --> 00:20:26,560 Speaker 1: tried to cope, unfortunately by drinking to excess. On March 339 00:20:26,600 --> 00:20:29,960 Speaker 1: two of nineteen twenty two, a paper was published in 340 00:20:30,000 --> 00:20:34,439 Speaker 1: the Canadian Medical Association journal called Pancreatic Extracts in the 341 00:20:34,480 --> 00:20:44,080 Speaker 1: Treatment of Diabetes melitists. It's authors were F. G. Banting, C. H. Best, J. B. Collip, W. R. Campbell, A. A. Fletcher, J. 342 00:20:44,320 --> 00:20:47,760 Speaker 1: J R. McLeod, and E. C. Noble. The two names 343 00:20:47,800 --> 00:20:50,400 Speaker 1: from that long list of authors that we haven't mentioned 344 00:20:50,400 --> 00:20:53,840 Speaker 1: specifically before this point our Campbell and Fletcher, and those 345 00:20:53,920 --> 00:20:57,679 Speaker 1: were the doctors who administered the actual injections to the 346 00:20:57,720 --> 00:21:02,399 Speaker 1: diabetes patients. On May third, nine two, McLeod presented a 347 00:21:02,480 --> 00:21:06,960 Speaker 1: paper called the Effects Produced on Diabetes by Extracts of Pancreas. 348 00:21:07,800 --> 00:21:11,119 Speaker 1: It described that extract as insulin, once again from the 349 00:21:11,240 --> 00:21:14,520 Speaker 1: Latin route for islands and apparently not related to the 350 00:21:14,600 --> 00:21:17,719 Speaker 1: earlier uses of the same term from the same source. 351 00:21:18,400 --> 00:21:22,199 Speaker 1: Both Banting and Best refused to go to this presentation. 352 00:21:22,760 --> 00:21:26,440 Speaker 1: Between roughly these two papers, between March and May, the 353 00:21:26,520 --> 00:21:29,760 Speaker 1: clinical trials of insulin had run into a huge stumbling 354 00:21:29,800 --> 00:21:34,880 Speaker 1: block When Connaught laboratories tried to replicate Collips extraction methods. 355 00:21:34,960 --> 00:21:39,359 Speaker 1: It just didn't work. Multiple sources described this as Collip 356 00:21:39,520 --> 00:21:43,200 Speaker 1: losing the knack for making insulin, or as problems with 357 00:21:43,400 --> 00:21:47,879 Speaker 1: translating Collips small scale batches from the laboratory into a 358 00:21:48,080 --> 00:21:52,080 Speaker 1: large scale production. They finally did resolve the issues and 359 00:21:52,160 --> 00:21:56,640 Speaker 1: started production in mid May of ninety two. For Banting's part, 360 00:21:56,800 --> 00:21:59,160 Speaker 1: he believed that Collip had wanted to keep his method 361 00:21:59,280 --> 00:22:02,520 Speaker 1: secret for his own benefit, and that consequently he had 362 00:22:02,600 --> 00:22:05,439 Speaker 1: not kept good enough records, and that that's why they 363 00:22:05,480 --> 00:22:09,679 Speaker 1: were having so much trouble. One patient died during this shortage, 364 00:22:09,760 --> 00:22:13,760 Speaker 1: and Banting and call Up had another massive altercation. As 365 00:22:13,800 --> 00:22:17,240 Speaker 1: words started to spread about insulin, families started trying to 366 00:22:17,320 --> 00:22:20,560 Speaker 1: get their children included in the clinical trials. The most 367 00:22:20,680 --> 00:22:23,960 Speaker 1: famous of these patients was Elizabeth Hughes, who was daughter 368 00:22:24,080 --> 00:22:27,920 Speaker 1: of former New York Governor Charles Hughes. Her father, Charles 369 00:22:28,040 --> 00:22:30,840 Speaker 1: later became Secretary of State in nineteen twenty one and 370 00:22:31,000 --> 00:22:34,280 Speaker 1: Chief Justice of the U. S. Supreme Court. Elizabeth had 371 00:22:34,320 --> 00:22:37,280 Speaker 1: been born in nineteen oh seven and had developed diabetes 372 00:22:37,359 --> 00:22:41,080 Speaker 1: in nineteen nineteen. Elizabeth had been one of doctor Frederick 373 00:22:41,160 --> 00:22:44,680 Speaker 1: Allen's patients and had been on a starvation diet before 374 00:22:44,760 --> 00:22:48,560 Speaker 1: starting insulin therapy. Alan saw her at a conference later 375 00:22:48,640 --> 00:22:51,760 Speaker 1: in nine two, and she was so improved that he 376 00:22:51,920 --> 00:22:55,840 Speaker 1: literally did not recognize her. She later wrote. Quote Dr 377 00:22:55,920 --> 00:22:59,480 Speaker 1: Allen said, with his mouth wide open. Oh, and that's 378 00:22:59,480 --> 00:23:03,400 Speaker 1: all he did, and after starting insulin therapy, Elizabeth lived 379 00:23:03,440 --> 00:23:06,840 Speaker 1: until the age of seventy three. Soon there was so 380 00:23:07,200 --> 00:23:10,560 Speaker 1: much demand for insulin that cannot labs could not produce 381 00:23:10,720 --> 00:23:13,040 Speaker 1: enough on their own, and that is when Eli Lilly 382 00:23:13,119 --> 00:23:16,720 Speaker 1: and Company was brought on to increase the output. This 383 00:23:17,000 --> 00:23:20,840 Speaker 1: led to yet another challenge, which was trying to standardize 384 00:23:21,040 --> 00:23:24,800 Speaker 1: this treatment across two different drug makers who were operating 385 00:23:24,880 --> 00:23:28,719 Speaker 1: in two different countries. It wasn't yet possible to measure 386 00:23:28,760 --> 00:23:32,240 Speaker 1: the strength of insulin itself. You had to administer a 387 00:23:32,359 --> 00:23:35,000 Speaker 1: sample of it to rabbits and then measure the rabbits 388 00:23:35,080 --> 00:23:38,960 Speaker 1: blood glucose levels to figure it out. One issue in 389 00:23:39,040 --> 00:23:41,440 Speaker 1: this whole process turned out to be because the two 390 00:23:41,800 --> 00:23:45,960 Speaker 1: drug makers were using different sized rabbits, with one of 391 00:23:46,080 --> 00:23:48,720 Speaker 1: them using rabbits that had been fasted and the other 392 00:23:48,920 --> 00:23:51,879 Speaker 1: using rabbits that had been fed normally. He seemed like 393 00:23:52,000 --> 00:23:56,520 Speaker 1: such small but important details, very very important details. Uh. 394 00:23:56,680 --> 00:24:00,359 Speaker 1: This standardization process ultimately led to the first deaf nition 395 00:24:00,520 --> 00:24:03,240 Speaker 1: of a unit of insulin, which was the amount that 396 00:24:03,280 --> 00:24:05,359 Speaker 1: it took to lower the blood sugar of a rabbit 397 00:24:05,440 --> 00:24:10,920 Speaker 1: weighing two kilograms from zero point one to zero point 398 00:24:11,040 --> 00:24:15,040 Speaker 1: zero four five, with that drop happening over five hours 399 00:24:15,240 --> 00:24:18,240 Speaker 1: and the rabbit having been fasted for twenty four hours. 400 00:24:19,200 --> 00:24:22,199 Speaker 1: Insulin is still measured in units today, but we can 401 00:24:22,240 --> 00:24:26,040 Speaker 1: also measure insulin itself now, so today one unit is 402 00:24:26,080 --> 00:24:30,040 Speaker 1: equivalent to thirty four point seven micrograms of crystalline insulin. 403 00:24:30,440 --> 00:24:37,160 Speaker 1: Throughout the nineteen twenties, Connaught Laboratories, ELI Lily, and numerous doctors, clinicians, researchers, 404 00:24:37,240 --> 00:24:40,680 Speaker 1: and others were working on standardizing insulin, with one of 405 00:24:40,720 --> 00:24:44,639 Speaker 1: the major contributors being Sir Henry Dale. Sometimes he's described 406 00:24:44,640 --> 00:24:46,679 Speaker 1: as being the person who did it, but like there 407 00:24:46,720 --> 00:24:50,920 Speaker 1: were a lot of people and entities involved. Another big project, 408 00:24:51,040 --> 00:24:54,720 Speaker 1: including most of these same basic entities, was refining the 409 00:24:54,880 --> 00:24:59,320 Speaker 1: extraction process and improving the yield of that process over 410 00:24:59,440 --> 00:25:01,920 Speaker 1: a few year or as drug manufacturers went from being 411 00:25:01,920 --> 00:25:05,600 Speaker 1: able to extract fifteen units of insulin from a kilogram 412 00:25:05,680 --> 00:25:10,160 Speaker 1: of pancreas to extracting almost four hundred units per kilogram. 413 00:25:10,680 --> 00:25:14,160 Speaker 1: In late nineteen twenty two, George Wilden at ELI Lily 414 00:25:14,240 --> 00:25:18,600 Speaker 1: developed a method for isoelectric precipitation of insulin, but the 415 00:25:18,720 --> 00:25:23,040 Speaker 1: relationships among banting best McLeod and call up, we're not 416 00:25:23,160 --> 00:25:27,159 Speaker 1: nearly as productive. In September of nine two, hoping to 417 00:25:27,280 --> 00:25:30,440 Speaker 1: create a definitive account of the discovery of insulin and 418 00:25:30,520 --> 00:25:34,160 Speaker 1: put all of the arguing to rest, Colonel Albert Gooderham 419 00:25:34,280 --> 00:25:37,040 Speaker 1: asked Banting, Best in mcleoud to each right up their 420 00:25:37,080 --> 00:25:40,679 Speaker 1: account of what happened. By that point, coleb had returned 421 00:25:40,720 --> 00:25:44,200 Speaker 1: to the University of Alberta at Edmonton, but McLeod wrote 422 00:25:44,280 --> 00:25:47,280 Speaker 1: him and asked for his thoughts. This whole process did 423 00:25:47,359 --> 00:25:52,440 Speaker 1: not really resolve anything, though. Banting characterized McLeod as constantly 424 00:25:52,600 --> 00:25:56,160 Speaker 1: undermining and criticizing him and taking credit for his work, 425 00:25:56,240 --> 00:25:58,440 Speaker 1: and he ended his write up with an appendix of 426 00:25:58,600 --> 00:26:02,120 Speaker 1: six additional is that he said showed quote a lack 427 00:26:02,240 --> 00:26:06,760 Speaker 1: of trust and cooperation on mcloud's part. McLeod characterized his 428 00:26:06,920 --> 00:26:11,040 Speaker 1: caution as very reasonable, giving bantings and experience, and he 429 00:26:11,160 --> 00:26:13,639 Speaker 1: pointed out that he had frequently taken a lot of 430 00:26:13,760 --> 00:26:16,920 Speaker 1: care to give credit to Banting and Best whenever that 431 00:26:17,040 --> 00:26:21,919 Speaker 1: credit was due. Best's account was relatively brief and fairly 432 00:26:22,000 --> 00:26:25,760 Speaker 1: neutral between the two of them, although Banting, Best, and 433 00:26:25,880 --> 00:26:29,400 Speaker 1: McLeod had all agreed not to personally apply for patents 434 00:26:29,480 --> 00:26:33,000 Speaker 1: on insulin as part of their agreement with Connent Laboratories. 435 00:26:33,600 --> 00:26:37,520 Speaker 1: Patents were needed to ensure quality and safety. This was 436 00:26:37,600 --> 00:26:39,959 Speaker 1: a brand new drug that could be life threatening if 437 00:26:40,040 --> 00:26:43,199 Speaker 1: made incorrectly, not just because of all the side effects 438 00:26:43,200 --> 00:26:46,320 Speaker 1: that we talked about earlier from poorly made extract, but 439 00:26:46,440 --> 00:26:49,000 Speaker 1: because of formulation that was too weak or too strong 440 00:26:49,400 --> 00:26:52,840 Speaker 1: could be life threatening for patients. At the same time, 441 00:26:53,200 --> 00:26:56,719 Speaker 1: the goal was to make insulin widely available as quickly 442 00:26:56,800 --> 00:26:59,760 Speaker 1: as possible and for it to be affordable. An in 443 00:27:00,000 --> 00:27:03,080 Speaker 1: Culin Committee had been established in early nineteen twenty two 444 00:27:03,160 --> 00:27:07,919 Speaker 1: to help coordinate patenting and licensing issues. Numerous patents were 445 00:27:08,000 --> 00:27:10,760 Speaker 1: issued on insulin and the process for making it in 446 00:27:10,800 --> 00:27:14,520 Speaker 1: the early nineteen twenties. By nineteen twenty six, insulin was 447 00:27:14,600 --> 00:27:17,240 Speaker 1: patented in twenty six different countries, and it had become 448 00:27:17,280 --> 00:27:20,680 Speaker 1: the standard of care in managing type one diabetes, especially 449 00:27:20,960 --> 00:27:24,679 Speaker 1: around the world. The relationship among those men who had 450 00:27:24,760 --> 00:27:28,879 Speaker 1: created it was never smooth, though in many ways. Banting 451 00:27:29,000 --> 00:27:33,200 Speaker 1: became the face of the discovery. On August nineteen twenty three, 452 00:27:33,280 --> 00:27:36,280 Speaker 1: he was on the cover of Time magazine. He received 453 00:27:36,359 --> 00:27:39,960 Speaker 1: numerous awards and honors, and he met King George the fifth. 454 00:27:40,760 --> 00:27:44,000 Speaker 1: The Banting and Best Chair of Medical Research was established 455 00:27:44,040 --> 00:27:47,120 Speaker 1: at the University of Toronto, and Banting was the first 456 00:27:47,200 --> 00:27:51,080 Speaker 1: person appointed to it. However, none of that seemed to 457 00:27:51,280 --> 00:27:55,159 Speaker 1: outweigh Banting's feelings about another award, which was the nineteen 458 00:27:55,600 --> 00:27:59,280 Speaker 1: three Nobel Prize and Physiology or Medicine, which was awarded 459 00:27:59,359 --> 00:28:04,199 Speaker 1: to both him and McLeod. Banting was so outraged at 460 00:28:04,280 --> 00:28:07,800 Speaker 1: McLeod's inclusion and getting the Nobel Prize that he threatened 461 00:28:07,880 --> 00:28:11,320 Speaker 1: to decline the award until somebody pointed out to him 462 00:28:11,359 --> 00:28:14,679 Speaker 1: how unfortunate it would be for the very first Canadian 463 00:28:14,760 --> 00:28:19,359 Speaker 1: Nobel laureate to refuse the honor. Banting ultimately decided to 464 00:28:19,440 --> 00:28:22,400 Speaker 1: give best half of his prize money, and McLeod gave 465 00:28:22,480 --> 00:28:25,160 Speaker 1: half of his prize money to call it. The team 466 00:28:25,280 --> 00:28:28,200 Speaker 1: also faced criticism from a number of directions in the 467 00:28:28,240 --> 00:28:33,520 Speaker 1: early nineteen twenties. Anti vivisectionists objected to the research in general, 468 00:28:34,080 --> 00:28:36,879 Speaker 1: and to Banting's admission that they had been buying stray 469 00:28:36,920 --> 00:28:40,280 Speaker 1: dogs off the streets when they ran out of research animals, 470 00:28:40,760 --> 00:28:44,200 Speaker 1: some of which may have actually been people's pets. Within 471 00:28:44,280 --> 00:28:47,000 Speaker 1: the medical community, there were people who criticized the whole 472 00:28:47,080 --> 00:28:50,240 Speaker 1: project because even though it had a good outcome, it 473 00:28:50,360 --> 00:28:54,920 Speaker 1: had started with Bantings fundamentally incorrect ideas. And then there 474 00:28:55,040 --> 00:28:57,960 Speaker 1: was Nicolay Paul Askew, who he talked about briefly in 475 00:28:58,080 --> 00:29:01,840 Speaker 1: Part one. He claimed aimed that Banting and McLeod had 476 00:29:02,000 --> 00:29:04,800 Speaker 1: stolen his work and that they had only become known 477 00:29:04,880 --> 00:29:07,320 Speaker 1: as the people to discover insulin because they had just 478 00:29:07,520 --> 00:29:11,880 Speaker 1: made the first commercially viable extract. Poliscue had sent Banting 479 00:29:12,000 --> 00:29:14,720 Speaker 1: his papers in ninety one and had asked him to 480 00:29:14,840 --> 00:29:17,440 Speaker 1: keep up a correspondence with him, but Banting had never 481 00:29:17,560 --> 00:29:22,280 Speaker 1: answered him. Banting and Best had also mischaracterized some of 482 00:29:22,360 --> 00:29:25,960 Speaker 1: Poliscue's earlier work in their own writing, something that really 483 00:29:26,000 --> 00:29:28,800 Speaker 1: seems to have been because of a mistranslation of a 484 00:29:28,920 --> 00:29:32,720 Speaker 1: document that was in French, rather than a deliberate misstatement 485 00:29:32,840 --> 00:29:35,360 Speaker 1: on their parts, like trying to cover something up. And 486 00:29:35,440 --> 00:29:37,840 Speaker 1: we should also know that there are still people who 487 00:29:38,040 --> 00:29:40,760 Speaker 1: make the argument that Polisque should be credited as the 488 00:29:40,800 --> 00:29:44,560 Speaker 1: discoverer of insulin, while others point out that he also 489 00:29:44,680 --> 00:29:48,040 Speaker 1: published multiple anti Semitic documents and that he helped found 490 00:29:48,320 --> 00:29:52,280 Speaker 1: anti Semitic parties that later formed the fascist organization known 491 00:29:52,320 --> 00:29:55,800 Speaker 1: as the Iron Guard in Romania. In a strange turn 492 00:29:55,920 --> 00:29:59,440 Speaker 1: of events, the one collaborator that Banting was actually on 493 00:29:59,560 --> 00:30:01,320 Speaker 1: good turn arms with at the end of his life 494 00:30:01,400 --> 00:30:04,520 Speaker 1: was James Collop, who he had shoved into a chair 495 00:30:04,640 --> 00:30:07,720 Speaker 1: earlier in this story. By the time Banting died in 496 00:30:07,880 --> 00:30:10,360 Speaker 1: nineteen forty, he had fallen out with Best, who he 497 00:30:10,440 --> 00:30:14,800 Speaker 1: had previously been close to. That year, being nineteen forty, 498 00:30:15,040 --> 00:30:17,680 Speaker 1: Best was scheduled to travel to Europe to act as 499 00:30:17,720 --> 00:30:21,320 Speaker 1: a medical liaison during World War Two. He canceled that 500 00:30:21,480 --> 00:30:25,040 Speaker 1: trip and Banting took his place, reportedly telling a friend 501 00:30:25,200 --> 00:30:28,440 Speaker 1: just before leaving, quote, if they ever give that chair 502 00:30:28,560 --> 00:30:31,840 Speaker 1: of mine to that expletive deleted Best, I'll roll over 503 00:30:32,000 --> 00:30:35,920 Speaker 1: in my grave. Having made that statement, Banting's flight on 504 00:30:36,040 --> 00:30:40,240 Speaker 1: this trip crashed after taking off from Gander Bay, Newfoundland, 505 00:30:40,360 --> 00:30:44,880 Speaker 1: on February nineteen forty. Banting survived the actual crash, but 506 00:30:45,040 --> 00:30:47,680 Speaker 1: died of his injuries before he could be rescued. In 507 00:30:47,880 --> 00:30:50,880 Speaker 1: terms of the other three of those first four contributors, 508 00:30:51,280 --> 00:30:54,560 Speaker 1: Charles Best did succeed Banting as the chair of the 509 00:30:54,640 --> 00:30:58,320 Speaker 1: Banting and Best Department of Medical Research. He continued to 510 00:30:58,360 --> 00:31:00,800 Speaker 1: do groundbreaking work on insta land and he was part 511 00:31:00,840 --> 00:31:03,880 Speaker 1: of the development of the drug heperin. He died on 512 00:31:04,000 --> 00:31:07,840 Speaker 1: March thirty first, nineteen seventy eight. John McLeod left the 513 00:31:07,960 --> 00:31:11,680 Speaker 1: University of Toronto for the University of Aberdeen in ninety eight, 514 00:31:11,880 --> 00:31:14,120 Speaker 1: and he died in nineteen thirty five at the age 515 00:31:14,160 --> 00:31:18,000 Speaker 1: of fifty nine. James Collup ultimately became the Dean of 516 00:31:18,080 --> 00:31:21,640 Speaker 1: Medicine at the University of Western Ontario. He died on 517 00:31:21,760 --> 00:31:26,080 Speaker 1: June nineteenth, nineteen sixty five. There have been a lot 518 00:31:26,320 --> 00:31:29,880 Speaker 1: of developments in the worlds of endo chronology, diabetes and 519 00:31:29,960 --> 00:31:33,800 Speaker 1: insulin since the nineteen twenties. That first preparation made in 520 00:31:33,920 --> 00:31:36,960 Speaker 1: nineteen twenty two only lasted for about six hours and 521 00:31:37,080 --> 00:31:40,040 Speaker 1: people could have really dramatic spikes and blood sugar as 522 00:31:40,120 --> 00:31:42,000 Speaker 1: it wore off. He had to be really careful with it, 523 00:31:42,680 --> 00:31:46,080 Speaker 1: so researchers started trying to develop versions of insulin that 524 00:31:46,120 --> 00:31:50,320 Speaker 1: would be absorbed more gradually and predictably and would last longer. 525 00:31:50,960 --> 00:31:55,200 Speaker 1: Researchers also worked on isolating insulin itself and figuring out 526 00:31:55,240 --> 00:31:59,840 Speaker 1: its exact chemical structure. John j Abel crystallized insulin and 527 00:32:00,040 --> 00:32:03,840 Speaker 1: nineteen twenty six ten years later, insulin was combined with 528 00:32:03,920 --> 00:32:06,680 Speaker 1: the hormone protomine to make a version that was absorbed 529 00:32:06,760 --> 00:32:10,600 Speaker 1: more slowly and consistently. In nineteen thirty nine, a version 530 00:32:10,680 --> 00:32:13,520 Speaker 1: that combined protomine and zinc was introduced that could last 531 00:32:13,600 --> 00:32:17,959 Speaker 1: for up to forty eight hours. Slow acting, buffered lente 532 00:32:18,080 --> 00:32:23,120 Speaker 1: insulin's were developed in the early nineteen fifties. Beyond McLeod 533 00:32:23,200 --> 00:32:26,760 Speaker 1: and Best, multiple other researchers have been awarded Nobel Prizes 534 00:32:26,880 --> 00:32:30,520 Speaker 1: for work that was related to insulin. In nineteen fifty five, 535 00:32:30,640 --> 00:32:33,760 Speaker 1: Frederick Sanger was awarded the Nobel Prize in Chemistry for 536 00:32:33,920 --> 00:32:37,000 Speaker 1: his work in identifying the amino acids that make up 537 00:32:37,000 --> 00:32:40,880 Speaker 1: a molecule of insulin. In nineteen sixty four, Dorothy Mary 538 00:32:41,000 --> 00:32:44,680 Speaker 1: Crowfitt Hodgkin was awarded the Nobel Prize and Chemistry quote 539 00:32:44,720 --> 00:32:48,080 Speaker 1: for her determinations by X ray techniques of the structures 540 00:32:48,120 --> 00:32:53,000 Speaker 1: of important biochemical substances. One of those important biochemical substances 541 00:32:53,120 --> 00:32:57,000 Speaker 1: was insulin. Then, in nineteen seventy seven, rosalind Yellow was 542 00:32:57,080 --> 00:32:59,960 Speaker 1: one of the recipients of the Nobel Prize in Physiology 543 00:33:00,000 --> 00:33:04,520 Speaker 1: Your Medicine Quote for the development of radio immuno assays 544 00:33:04,600 --> 00:33:08,200 Speaker 1: of peptid hormones. This was tied to a discovery that 545 00:33:08,320 --> 00:33:12,280 Speaker 1: people who got injections of hormones, including insulin, could develop 546 00:33:12,320 --> 00:33:16,080 Speaker 1: antibodies to that hormone. Those two decades saw a lot 547 00:33:16,280 --> 00:33:20,000 Speaker 1: of other advances in addition to those Nobel prizes. You're 548 00:33:20,080 --> 00:33:23,760 Speaker 1: in glucose self test strips were introduced in the nineteen sixties. 549 00:33:24,360 --> 00:33:27,160 Speaker 1: In nineteen sixty three and nineteen sixty five, two different 550 00:33:27,240 --> 00:33:31,280 Speaker 1: teams each synthesized insulin for the first time. The first 551 00:33:31,360 --> 00:33:34,920 Speaker 1: insulin pump was also developed in nineteen sixty three, although 552 00:33:34,960 --> 00:33:37,040 Speaker 1: at the time it required a pump the size of 553 00:33:37,080 --> 00:33:42,080 Speaker 1: a backpack. Amy's Diagnostics introduced the first blood glucometer in 554 00:33:42,200 --> 00:33:46,960 Speaker 1: nineteen sixty nine. The first fully synthetic insulin was introduced 555 00:33:47,000 --> 00:33:51,440 Speaker 1: in nineteen seventy five, was made using recombinant DNA rather 556 00:33:51,560 --> 00:33:55,760 Speaker 1: than by extracting insulin from animal pancreas. Before this point, 557 00:33:55,840 --> 00:33:59,360 Speaker 1: it took an estimated twenty steers or eighty hogs to 558 00:33:59,400 --> 00:34:02,400 Speaker 1: get enough insulin for a patient for one year, and 559 00:34:02,720 --> 00:34:07,280 Speaker 1: although most people are using synthetic insulince now, animal sourced 560 00:34:07,360 --> 00:34:09,879 Speaker 1: insulin is still made today and there are still people 561 00:34:09,880 --> 00:34:12,880 Speaker 1: who are using it to manage their diabetes. The ability 562 00:34:12,920 --> 00:34:16,680 Speaker 1: to synthesize insulin made it possible for researchers to create 563 00:34:16,760 --> 00:34:20,680 Speaker 1: insulin analogs in the nineteen eighties and nineties. These have 564 00:34:20,840 --> 00:34:24,640 Speaker 1: slightly different amino acid chains from human insulin, so they 565 00:34:24,719 --> 00:34:27,000 Speaker 1: lower blood sugar the way that insulin does, but they 566 00:34:27,080 --> 00:34:30,120 Speaker 1: also behave a little bit differently in the body. In 567 00:34:30,239 --> 00:34:32,960 Speaker 1: most cases, they're made to be absorbed more quickly or 568 00:34:33,080 --> 00:34:37,160 Speaker 1: more slowly than human insulin. Is this research into ways 569 00:34:37,239 --> 00:34:40,920 Speaker 1: to improve insulin is ongoing, including attempts to make insulin 570 00:34:41,200 --> 00:34:44,560 Speaker 1: that can be administered orally. In the United States, there 571 00:34:44,600 --> 00:34:48,160 Speaker 1: have been a lot of headlines about how expensive insulin 572 00:34:48,239 --> 00:34:50,920 Speaker 1: has become, and a big reason for that is that 573 00:34:51,000 --> 00:34:54,879 Speaker 1: all these refinements and synthetic analogs and other developments, they're 574 00:34:54,880 --> 00:34:58,360 Speaker 1: all patented and so drugmakers can set their own price, 575 00:34:58,840 --> 00:35:01,840 Speaker 1: and especially with these newer versions, there's just not a 576 00:35:01,960 --> 00:35:06,520 Speaker 1: generic alternative available. In general, the lower cost alternatives that 577 00:35:06,680 --> 00:35:10,839 Speaker 1: are available we're developed decades ago, so they haven't had 578 00:35:10,880 --> 00:35:13,719 Speaker 1: all those tweaks and things like absorption rates that we 579 00:35:13,880 --> 00:35:18,000 Speaker 1: just talked about. Using insulin to manage diabetes is a lifelong, 580 00:35:18,560 --> 00:35:21,920 Speaker 1: daily process and researchers are still trying to find a 581 00:35:21,960 --> 00:35:25,360 Speaker 1: way to treat diabetes directly, rather than using insulin to 582 00:35:25,480 --> 00:35:30,040 Speaker 1: manage its effects. This can include pancreatic graphs or transplants, 583 00:35:30,200 --> 00:35:32,600 Speaker 1: or finding a way to prevent the body's immune system 584 00:35:32,960 --> 00:35:36,800 Speaker 1: from damaging the pancreas in the first place. The introduction 585 00:35:36,840 --> 00:35:39,719 Speaker 1: of insulin also made it possible for people with diabetes 586 00:35:39,800 --> 00:35:43,600 Speaker 1: to live much longer, so research is ongoing into ways 587 00:35:43,680 --> 00:35:47,040 Speaker 1: to treat and prevent the complications that can arise later 588 00:35:47,160 --> 00:35:52,120 Speaker 1: in life, including retinopathy, neuropathy, and foot problems. So that 589 00:35:52,800 --> 00:35:57,279 Speaker 1: in two parts is insulin? Yeah? Uh, you did some 590 00:35:57,520 --> 00:35:59,440 Speaker 1: listener mail on part one? Do you have some more 591 00:35:59,520 --> 00:36:03,720 Speaker 1: for part do I do? It is from Ian. Ian 592 00:36:04,120 --> 00:36:07,760 Speaker 1: sends a note about Woolworth's lunch counters, and Ian says, Hi, ladies, 593 00:36:07,800 --> 00:36:10,080 Speaker 1: thank you for your episode on the lunch counter sit ins. 594 00:36:10,440 --> 00:36:12,560 Speaker 1: Although it does feel funny to say thank you for 595 00:36:12,640 --> 00:36:16,040 Speaker 1: an episode which essentially involved people being nasty to each 596 00:36:16,040 --> 00:36:18,200 Speaker 1: other for something they did not choose, like the color 597 00:36:18,320 --> 00:36:21,040 Speaker 1: of their skin. If you want to have lunch at 598 00:36:21,080 --> 00:36:24,120 Speaker 1: a Woolworths lunch counter, you can still do so. If 599 00:36:24,160 --> 00:36:27,720 Speaker 1: you visit Sydney, Australia. The Woolworths at town Hall Station 600 00:36:27,880 --> 00:36:29,960 Speaker 1: still has a lunch counter on the top floor of 601 00:36:30,040 --> 00:36:33,799 Speaker 1: its store. It's not quite the same Woolworths though. Many 602 00:36:33,880 --> 00:36:36,480 Speaker 1: years ago I got a new workmate who had just 603 00:36:36,760 --> 00:36:39,480 Speaker 1: moved from South Africa to Australia. He told me his 604 00:36:39,600 --> 00:36:42,560 Speaker 1: wife had worked as a store manager for Woolworths in 605 00:36:42,640 --> 00:36:45,640 Speaker 1: South Africa, but that it wasn't the same store as 606 00:36:45,680 --> 00:36:47,560 Speaker 1: the one we had in Australia, so I looked it 607 00:36:47,640 --> 00:36:51,120 Speaker 1: up out of curiosity. The original woolworth was founded in 608 00:36:51,200 --> 00:36:55,480 Speaker 1: eighteen seventy nine and Utica, New York by Frank Winfield Woolworth. 609 00:36:56,000 --> 00:36:58,880 Speaker 1: The store name was either Woolworth without an S on 610 00:36:58,960 --> 00:37:01,360 Speaker 1: the end, or with and an apostrophe and an S 611 00:37:01,440 --> 00:37:04,360 Speaker 1: on the end. It was originally a discount five and 612 00:37:04,440 --> 00:37:07,479 Speaker 1: dime store, specializing in selling items five to ten cents, 613 00:37:07,560 --> 00:37:10,360 Speaker 1: and grew to become at one time the largest department 614 00:37:10,400 --> 00:37:13,799 Speaker 1: store chain in the world. The podcast Useless Information did 615 00:37:13,840 --> 00:37:16,120 Speaker 1: a Christmas special last year that talked about how it 616 00:37:16,200 --> 00:37:20,600 Speaker 1: popularized Christmas tree decorations in the US. Sadly, changing times 617 00:37:20,640 --> 00:37:23,000 Speaker 1: in competition from new stores like Walmart led to its 618 00:37:23,080 --> 00:37:27,840 Speaker 1: decline in the original Woolworths department stores were closed and 619 00:37:27,920 --> 00:37:30,800 Speaker 1: the parent company focused on its foot locker brand instead. 620 00:37:31,560 --> 00:37:38,800 Speaker 1: Woolworths did, however, set up several overseas subsidiaries in Mexico, Germany, Austria, Cyprus, Britain, etcetera. 621 00:37:39,360 --> 00:37:42,440 Speaker 1: The German and Mexican subsidiaries still survived, but the British 622 00:37:42,520 --> 00:37:44,640 Speaker 1: chain went out of business in two thousand nine. This 623 00:37:44,800 --> 00:37:47,640 Speaker 1: was kind of sad, as Woolworths was a British institution. 624 00:37:47,800 --> 00:37:49,840 Speaker 1: My mom even worked in one when she was in 625 00:37:49,920 --> 00:37:53,120 Speaker 1: high school in England in the nineteen sixties. Meanwhile, back 626 00:37:53,200 --> 00:37:57,399 Speaker 1: in some Australian businessmen want to set up their own 627 00:37:57,480 --> 00:38:00,480 Speaker 1: woolworth style store. They had one or two ideas for 628 00:38:00,520 --> 00:38:02,719 Speaker 1: the name, but they found the name Woolworths had not 629 00:38:02,880 --> 00:38:07,160 Speaker 1: been registered in Australia, so they copied the name. Note 630 00:38:07,239 --> 00:38:10,319 Speaker 1: this spelling has an S on the end and no apostrophe. 631 00:38:10,880 --> 00:38:13,839 Speaker 1: Wolworths Australia started as a department store, but after World 632 00:38:13,880 --> 00:38:18,040 Speaker 1: War Two started selling groceries and developed its own supermarket chain. Eventually, 633 00:38:18,040 --> 00:38:21,239 Speaker 1: the department stores were rebranded as Big w for Big 634 00:38:21,280 --> 00:38:24,720 Speaker 1: Woolworths and continue today, competing with the discount department stores 635 00:38:24,760 --> 00:38:28,520 Speaker 1: like Target and Kymart. Woolworth's and its arch rival Coals 636 00:38:28,560 --> 00:38:31,799 Speaker 1: are two big supermarket chains in Australia and control something 637 00:38:31,880 --> 00:38:36,200 Speaker 1: like eighty percent of the market. It continues on from there, 638 00:38:36,320 --> 00:38:38,879 Speaker 1: but the part about the Australian Woolworths was the part 639 00:38:38,960 --> 00:38:40,960 Speaker 1: that I really wanted to read because I found that 640 00:38:41,000 --> 00:38:44,239 Speaker 1: all very interesting. Thank you so much to Ian for 641 00:38:44,360 --> 00:38:46,800 Speaker 1: writing in about that. Something that we didn't really mention 642 00:38:47,040 --> 00:38:48,880 Speaker 1: in the episode or in any of the listener mail 643 00:38:48,880 --> 00:38:50,400 Speaker 1: at this point is that a lot of the former 644 00:38:50,520 --> 00:38:54,400 Speaker 1: Woolworth's buildings have been converted into something like the building 645 00:38:54,480 --> 00:38:58,360 Speaker 1: is still standing with the original historic Woolworths facade on 646 00:38:58,440 --> 00:39:01,279 Speaker 1: there um. And one that I have been to is 647 00:39:01,400 --> 00:39:04,920 Speaker 1: now the Woolworth Walk in Asheville, North Carolina, which is 648 00:39:05,000 --> 00:39:08,600 Speaker 1: like an art and studio space that also has a 649 00:39:08,719 --> 00:39:12,560 Speaker 1: fifties style lunch counter in there. So if you'd like 650 00:39:12,600 --> 00:39:14,640 Speaker 1: to write to us about this or anither podcast or 651 00:39:14,640 --> 00:39:17,440 Speaker 1: a history podcast at iHeart radio dot com and then 652 00:39:17,480 --> 00:39:19,520 Speaker 1: we're all over social media at missed in History. That's 653 00:39:19,520 --> 00:39:23,279 Speaker 1: where you'll find our Facebook, Twitter, Pinterest, and Instagram, and 654 00:39:23,640 --> 00:39:26,239 Speaker 1: you can subscribe to our show on Apple podcast The 655 00:39:26,320 --> 00:39:28,840 Speaker 1: iHeart Radio app, and anywhere else to get your podcasts. 656 00:39:34,040 --> 00:39:36,200 Speaker 1: Stuff you Missed in History Class is a production of 657 00:39:36,280 --> 00:39:39,439 Speaker 1: I heart Radio. For more podcasts from i heart Radio, 658 00:39:39,680 --> 00:39:42,800 Speaker 1: visit the iHeart radio app, Apple Podcasts, or wherever you 659 00:39:42,960 --> 00:39:44,240 Speaker 1: listen to your favorite shows.