1 00:00:01,240 --> 00:00:04,000 Speaker 1: Welcome to Stuff You Missed in History Class, a production 2 00:00:04,120 --> 00:00:12,639 Speaker 1: of I Heart Radios How Stuff Works. Hello, and welcome 3 00:00:12,680 --> 00:00:18,079 Speaker 1: to the podcast. I'm Holly Fry and I'm Tracy Wilson. UH. 4 00:00:18,120 --> 00:00:21,480 Speaker 1: For all of recorded history, Tracy, and certainly before history 5 00:00:21,560 --> 00:00:24,680 Speaker 1: is being recorded, humans have been experiencing pain of one 6 00:00:24,720 --> 00:00:28,720 Speaker 1: form or another. That might seem like we're leading into 7 00:00:28,800 --> 00:00:31,880 Speaker 1: a very dark place, but really we're talking about ways 8 00:00:31,960 --> 00:00:35,280 Speaker 1: that we've managed an alleviated pain, and today, of course, 9 00:00:35,360 --> 00:00:39,440 Speaker 1: we're also talking about fairly minor ones in this case. Um, 10 00:00:39,680 --> 00:00:41,920 Speaker 1: it's just as simple as like running to your local 11 00:00:41,960 --> 00:00:44,519 Speaker 1: drug store or supermarket or even big box store to 12 00:00:44,560 --> 00:00:47,879 Speaker 1: pick up non prescription pain relief easy peas. And we're 13 00:00:47,880 --> 00:00:50,720 Speaker 1: going to talk today about specifically one of the possible 14 00:00:50,720 --> 00:00:53,240 Speaker 1: pain relievers that you might reach for in such a circumstance, 15 00:00:53,240 --> 00:00:57,480 Speaker 1: which is aspirin, from its natural based substance salison to 16 00:00:57,560 --> 00:01:00,680 Speaker 1: the invention of its synthetic derivative form that still use. 17 00:01:01,160 --> 00:01:04,640 Speaker 1: The story of aspirin is longer than people might expect, 18 00:01:04,720 --> 00:01:08,600 Speaker 1: and it also has its own controversy and conflict. For example, 19 00:01:08,640 --> 00:01:10,880 Speaker 1: there is one man whose name always comes up and 20 00:01:11,000 --> 00:01:13,399 Speaker 1: is credited with inventing aspirin, and we're going to get 21 00:01:13,400 --> 00:01:16,200 Speaker 1: to him and whether he should get credit because there 22 00:01:16,240 --> 00:01:18,920 Speaker 1: have been some challenges to that. But first we need 23 00:01:18,959 --> 00:01:22,520 Speaker 1: to talk about the ancient history of the medicinal base 24 00:01:22,520 --> 00:01:24,200 Speaker 1: of this, as well as some of the other people 25 00:01:24,240 --> 00:01:27,120 Speaker 1: who figure into the development of our knowledge about the 26 00:01:27,120 --> 00:01:31,520 Speaker 1: workings of salicylic acid and its medicinal possibilities. Yeah, and 27 00:01:31,600 --> 00:01:34,640 Speaker 1: just to be super clear, we're not suggesting that like 28 00:01:34,800 --> 00:01:37,679 Speaker 1: every pain that a person could have can be solved 29 00:01:37,680 --> 00:01:39,800 Speaker 1: with a quickly little trip to the store to pick 30 00:01:40,959 --> 00:01:43,080 Speaker 1: but I got a headache, I'm going to run across 31 00:01:43,120 --> 00:01:48,160 Speaker 1: the street and get some Yes. Yeah, the general day 32 00:01:48,160 --> 00:01:52,120 Speaker 1: to day minor pains, the minor aches and pains, not 33 00:01:52,240 --> 00:01:55,760 Speaker 1: the more serious stuff. So salison is found in the 34 00:01:55,800 --> 00:01:58,920 Speaker 1: bark of the white willow tree and in winter green leaves, 35 00:01:59,000 --> 00:02:01,320 Speaker 1: as well as a number of other plant life in 36 00:02:01,440 --> 00:02:04,840 Speaker 1: various concentrations, and it can be converted pretty easily in 37 00:02:04,880 --> 00:02:08,400 Speaker 1: a lab or in the human body into salacelic acid. 38 00:02:08,639 --> 00:02:10,760 Speaker 1: And then this can get a little bit confusing because 39 00:02:10,800 --> 00:02:15,400 Speaker 1: sometimes the two seem to be used almost interchangeably. Yeah. 40 00:02:15,680 --> 00:02:19,080 Speaker 1: Even in in my research, there were moments where people 41 00:02:19,080 --> 00:02:21,400 Speaker 1: were talking about the history of this and they were 42 00:02:21,960 --> 00:02:26,600 Speaker 1: pretty casually tossing them back and forth. But that's not 43 00:02:26,840 --> 00:02:30,480 Speaker 1: exactly correct. Uh, And we'll talk about how even in 44 00:02:30,520 --> 00:02:32,880 Speaker 1: the medical community that's been a problem at various points 45 00:02:32,880 --> 00:02:37,160 Speaker 1: in time. UH. Salacelic acid is what's called beta hydroxy acid, 46 00:02:37,240 --> 00:02:39,720 Speaker 1: and you have probably heard of it before because it 47 00:02:39,800 --> 00:02:42,160 Speaker 1: is used to tout various skin cares all the time. 48 00:02:42,600 --> 00:02:46,120 Speaker 1: And that's because beta hydroxy acids are excellent exfoliance, and 49 00:02:46,320 --> 00:02:49,639 Speaker 1: unlike alpha hydroxy acids, which are also very good exfoliance, 50 00:02:50,120 --> 00:02:53,360 Speaker 1: beta hydroxy acids are also really good at reducing wrinkles 51 00:02:53,360 --> 00:02:56,560 Speaker 1: and improving overall skin texture, and they don't have the 52 00:02:56,600 --> 00:03:00,160 Speaker 1: same tendency to cause irritation that their alpha hydroxy counterparts do. 53 00:03:01,000 --> 00:03:04,040 Speaker 1: It is also anti fungal, anti infective, and it can 54 00:03:04,080 --> 00:03:07,120 Speaker 1: be used to remove and heal epidermal problems like calluses 55 00:03:07,160 --> 00:03:11,160 Speaker 1: and wartz. In addition to all of that, salaslic acid 56 00:03:11,200 --> 00:03:13,840 Speaker 1: can also help with pain, and that's something that humans 57 00:03:13,840 --> 00:03:16,080 Speaker 1: have known about for a very long time, although they 58 00:03:16,080 --> 00:03:18,600 Speaker 1: didn't have that name for it and didn't understand how 59 00:03:18,639 --> 00:03:22,600 Speaker 1: this pain relief was relating to salison. The first record 60 00:03:22,680 --> 00:03:25,200 Speaker 1: that we have of willow bark being used as a 61 00:03:25,240 --> 00:03:29,280 Speaker 1: pain remedy comes from Samaria four thousand years ago, and 62 00:03:29,360 --> 00:03:32,120 Speaker 1: in addition to relieving pain, it was also used to 63 00:03:32,160 --> 00:03:35,720 Speaker 1: treat inflammation and fever. And this knowledge of the extract 64 00:03:35,760 --> 00:03:38,160 Speaker 1: of willow bark as a medicinal compound did not stay 65 00:03:38,160 --> 00:03:41,800 Speaker 1: in Mesopotamia traveled the globe. In China, going back at 66 00:03:41,840 --> 00:03:44,320 Speaker 1: least two thousand years, willow was being used to treat 67 00:03:44,400 --> 00:03:49,760 Speaker 1: everything from the common cold to hemorrhages. Hippocrates documented the 68 00:03:49,800 --> 00:03:52,800 Speaker 1: idea of a team made from willow bark to tame 69 00:03:52,920 --> 00:03:56,160 Speaker 1: pain during childbirth right around the transition from the fifth 70 00:03:56,160 --> 00:03:59,880 Speaker 1: to the fourth century BC. Several hundred years later, and 71 00:04:00,040 --> 00:04:04,080 Speaker 1: other Greek physician Diascorites routinely took advantage of the anti 72 00:04:04,120 --> 00:04:08,320 Speaker 1: inflammatory properties of willow bark when treating his patients. Plenty 73 00:04:08,320 --> 00:04:11,120 Speaker 1: of the Elder and Galen also wrote about their uses 74 00:04:11,120 --> 00:04:13,560 Speaker 1: of the extract of willow bark, and then in the 75 00:04:13,600 --> 00:04:17,080 Speaker 1: seventeen sixties, Reverend Edmund Stone, who was a member of 76 00:04:17,080 --> 00:04:20,440 Speaker 1: the Royal Society in addition to being an Oxford Shure vicar, 77 00:04:20,839 --> 00:04:24,120 Speaker 1: conducted his own study of the potential medicinal properties of 78 00:04:24,160 --> 00:04:27,520 Speaker 1: willow bark based entirely on a hunch. As an asside, 79 00:04:27,520 --> 00:04:31,640 Speaker 1: you will also see him mentioned as Reverend Edward Stone. 80 00:04:32,520 --> 00:04:35,760 Speaker 1: Both show up. Don't be confused. In his own writing, 81 00:04:35,760 --> 00:04:39,279 Speaker 1: though he uses Edmund. But he wrote out his findings 82 00:04:39,320 --> 00:04:42,280 Speaker 1: in a letter to the Royal Society titled an Account 83 00:04:42,320 --> 00:04:44,159 Speaker 1: of the success of the Bark of the Willow in 84 00:04:44,200 --> 00:04:46,599 Speaker 1: the Cure of eg Use, which he wrote to the 85 00:04:46,680 --> 00:04:50,080 Speaker 1: Right Honorable George, Earl of Macclesfield, who was the Society's 86 00:04:50,120 --> 00:04:53,440 Speaker 1: president at the time. So in this account Stone made 87 00:04:53,440 --> 00:04:56,800 Speaker 1: it clear that he believed he had identified something really important, 88 00:04:56,920 --> 00:04:59,200 Speaker 1: and he wrote in the opening quote, among the many 89 00:04:59,279 --> 00:05:02,400 Speaker 1: useful discuss breaths which this age hath made, there are 90 00:05:02,560 --> 00:05:05,080 Speaker 1: very few which better deserve the attention of the public 91 00:05:05,120 --> 00:05:07,640 Speaker 1: than what I am going to lay before your lordship. 92 00:05:08,000 --> 00:05:11,039 Speaker 1: And Stone goes on to describe in this letter how 93 00:05:11,080 --> 00:05:14,080 Speaker 1: he accidentally tasted the willow bark of a tree and 94 00:05:14,080 --> 00:05:16,320 Speaker 1: he was kind of blown over by how bitter it was, 95 00:05:16,839 --> 00:05:19,520 Speaker 1: and he noticed that willows grew in the same places 96 00:05:19,520 --> 00:05:22,480 Speaker 1: that egg used. Were common ailments so a us or 97 00:05:22,520 --> 00:05:26,080 Speaker 1: intense episodes of fever or shivering. They've often been associated 98 00:05:26,080 --> 00:05:30,799 Speaker 1: with malaria, and Stone believed that quote, many natural maladies 99 00:05:30,920 --> 00:05:34,279 Speaker 1: carry their cures along with them, or that their remedies 100 00:05:34,360 --> 00:05:37,440 Speaker 1: lie not far from their cures. So he knew of 101 00:05:37,560 --> 00:05:41,120 Speaker 1: other bitter plants that had healing properties, including the Peruvian 102 00:05:41,200 --> 00:05:45,400 Speaker 1: chinchona tree, which also contains salison in its bark. So 103 00:05:45,560 --> 00:05:48,440 Speaker 1: he thought the bitter willow, growing so near to where 104 00:05:48,480 --> 00:05:51,880 Speaker 1: eggus were common might similarly offer a solution to the 105 00:05:51,920 --> 00:05:55,719 Speaker 1: fevers that he saw in his community. So Stone said 106 00:05:55,839 --> 00:05:58,719 Speaker 1: that he looked for information on the willow being used before. 107 00:05:59,360 --> 00:06:01,680 Speaker 1: He did not have access to the various accounts and 108 00:06:01,720 --> 00:06:04,520 Speaker 1: records that we mentioned, because all he could find was 109 00:06:04,520 --> 00:06:07,160 Speaker 1: the name of the tree and botany books that he consulted. 110 00:06:07,920 --> 00:06:11,520 Speaker 1: He found nothing about its pharmaceutical possibilities. This is a 111 00:06:11,560 --> 00:06:16,240 Speaker 1: way where we are very spoiled by the Internet and 112 00:06:16,400 --> 00:06:21,239 Speaker 1: search engines. Yes, I often think when we're talking about 113 00:06:22,080 --> 00:06:28,160 Speaker 1: historical scientists, mathematicians, philosophers, etcetera, like what would they do 114 00:06:28,320 --> 00:06:31,160 Speaker 1: at the command of information that we have at our 115 00:06:31,200 --> 00:06:35,720 Speaker 1: fingertips in our pockets. But so, Stone, not finding anything 116 00:06:35,800 --> 00:06:38,560 Speaker 1: himself on willow ever being used in this way, set 117 00:06:38,560 --> 00:06:41,839 Speaker 1: out to do some experimenting, and the Reverend Stone gathered 118 00:06:41,880 --> 00:06:44,280 Speaker 1: a pound of willow bark over the course of a summer, 119 00:06:44,279 --> 00:06:46,160 Speaker 1: and then he put it in a bag and he 120 00:06:46,240 --> 00:06:49,479 Speaker 1: hung this bag outside of a baker's oven for three months, 121 00:06:49,600 --> 00:06:51,880 Speaker 1: and while it sat there, it was exposed not to 122 00:06:52,040 --> 00:06:54,440 Speaker 1: direct heat but from the indirect heat of the stove 123 00:06:54,960 --> 00:06:57,720 Speaker 1: for this prolonged period of time, and over that time 124 00:06:57,760 --> 00:07:00,640 Speaker 1: the contents of the bag dried out and just crumbled 125 00:07:00,640 --> 00:07:03,799 Speaker 1: the powder. Once he had this powder, Stone started giving 126 00:07:03,800 --> 00:07:06,240 Speaker 1: it to people in very tiny amounts, at first just 127 00:07:06,320 --> 00:07:09,160 Speaker 1: twenty grains of the powder as a dose. So if 128 00:07:09,160 --> 00:07:12,520 Speaker 1: there was anything toxic in this substance, the negative impact 129 00:07:12,560 --> 00:07:15,920 Speaker 1: to his patients would hopefully be pretty minimal. As the 130 00:07:15,920 --> 00:07:18,880 Speaker 1: people he was treating for ague appeared to tolerate this 131 00:07:19,080 --> 00:07:22,560 Speaker 1: little dried powder, he started giving them additional doses, still 132 00:07:22,600 --> 00:07:26,120 Speaker 1: pretty small, every four hours, and then he carefully observed 133 00:07:26,160 --> 00:07:29,200 Speaker 1: the results, and his patients had some improvement, but none 134 00:07:29,240 --> 00:07:32,000 Speaker 1: of them were cured of their problems. But as they 135 00:07:32,000 --> 00:07:35,600 Speaker 1: still seem to have no negative reactions to this experimental treatment, 136 00:07:35,960 --> 00:07:39,880 Speaker 1: Stone increased the dose, noting quote I grew bolder with it, 137 00:07:40,000 --> 00:07:43,280 Speaker 1: and in a few days increase the dose to two scruples, 138 00:07:43,320 --> 00:07:46,640 Speaker 1: and the eggu was soon removed. So a scruple is 139 00:07:46,640 --> 00:07:49,960 Speaker 1: that initial dose. It's twenty grains, so Stone was basically 140 00:07:50,000 --> 00:07:53,280 Speaker 1: doubling the dosage. Stone continued on with his study for 141 00:07:53,440 --> 00:07:56,960 Speaker 1: five years, noting that over and over in fifty cases 142 00:07:57,000 --> 00:07:59,920 Speaker 1: his patients eggus were either cured or in a few 143 00:08:00,120 --> 00:08:03,360 Speaker 1: very severe cases, they were made much better. Stone's letter 144 00:08:03,400 --> 00:08:05,640 Speaker 1: goes on to talk about the trees themselves and how 145 00:08:05,680 --> 00:08:08,280 Speaker 1: abundant they are and how easy to access, and he 146 00:08:08,320 --> 00:08:11,280 Speaker 1: concluded with quote, I have no other motives for publishing 147 00:08:11,320 --> 00:08:14,680 Speaker 1: this valuable specific then that it may have a fair 148 00:08:14,720 --> 00:08:18,800 Speaker 1: and full trial in all its variety of circumstances and situations, 149 00:08:19,040 --> 00:08:22,320 Speaker 1: and that the world may reap the benefits accruing from it. 150 00:08:22,680 --> 00:08:24,560 Speaker 1: So coming up, we're going to talk about some of 151 00:08:24,560 --> 00:08:27,840 Speaker 1: the advances in chemistry that enabled scientists who more fully 152 00:08:27,920 --> 00:08:31,520 Speaker 1: understand why willow bark helped with pain and fever. But 153 00:08:31,600 --> 00:08:33,320 Speaker 1: first we are going to pause and have a little 154 00:08:33,360 --> 00:08:44,360 Speaker 1: sponsor break. So while Reverend Stone's work and his success 155 00:08:44,360 --> 00:08:47,640 Speaker 1: with patients came from using willow bark, he didn't really 156 00:08:47,720 --> 00:08:50,480 Speaker 1: understand the chemistry involved. He knew that it was the 157 00:08:50,520 --> 00:08:53,120 Speaker 1: bark or something in it, but that was it, and 158 00:08:53,160 --> 00:08:56,439 Speaker 1: it wasn't until the eighteen hundreds that significant strides were 159 00:08:56,480 --> 00:09:00,320 Speaker 1: made in isolating and identifying the naturally occurring agent that 160 00:09:00,440 --> 00:09:04,360 Speaker 1: had these beneficial properties. In the eighteen twenties and thirties, 161 00:09:04,400 --> 00:09:07,560 Speaker 1: there were a number of advancements in the scientific communities 162 00:09:07,640 --> 00:09:10,720 Speaker 1: understanding of what it was about willow tree bark and 163 00:09:10,760 --> 00:09:14,760 Speaker 1: other plants that offered pain relief and anti inflammatory properties 164 00:09:14,800 --> 00:09:17,520 Speaker 1: to patients, and every step was building on the work 165 00:09:17,559 --> 00:09:20,280 Speaker 1: of one that came before it. In eighteen twenty eight, 166 00:09:20,320 --> 00:09:23,880 Speaker 1: a professor of pharmacology and Munich named Johann Buchner made 167 00:09:23,880 --> 00:09:27,400 Speaker 1: a big breakthrough. He was able to extract and purify 168 00:09:27,480 --> 00:09:29,800 Speaker 1: the compound that was doing all of that good, and 169 00:09:29,840 --> 00:09:32,880 Speaker 1: he named it salison, that is based on the Latin 170 00:09:32,920 --> 00:09:37,040 Speaker 1: word for willow salax. In the following year, French pharmacist 171 00:09:37,160 --> 00:09:40,760 Speaker 1: Are LaRue built on Buchner's work. He was able to 172 00:09:40,800 --> 00:09:44,960 Speaker 1: isolate a pure crystalline form of salison in eighteen twenty nine. 173 00:09:45,320 --> 00:09:48,520 Speaker 1: In eighteen thirty eight, Raphael Peria, who was a chemist 174 00:09:48,559 --> 00:09:52,280 Speaker 1: from Italy, was able to produce salasilic acid in a lab. 175 00:09:52,800 --> 00:09:56,000 Speaker 1: He did this by resolving the chemical structure of salison 176 00:09:56,160 --> 00:10:00,240 Speaker 1: into a sugar and salasil alcohol and then oxidiz the 177 00:10:00,280 --> 00:10:05,000 Speaker 1: salsill alcohol to produce salasilic acid. The precise chemical structure 178 00:10:05,160 --> 00:10:09,040 Speaker 1: of salasil alcohol was identified by two German chemists at 179 00:10:09,120 --> 00:10:13,839 Speaker 1: Markburg University, ERMANN. Cloba and E. Lautman at the end 180 00:10:13,880 --> 00:10:16,720 Speaker 1: of the eighteen fifties, and over the next fifteen years 181 00:10:16,760 --> 00:10:19,640 Speaker 1: that teams were continued until they were able to develop 182 00:10:19,679 --> 00:10:24,360 Speaker 1: a process for industrial production of salasillic acid. The Hayden 183 00:10:24,480 --> 00:10:28,240 Speaker 1: Chemical Company in Germany started producing synthetic salacillic acid for 184 00:10:28,320 --> 00:10:31,440 Speaker 1: pain and fever in eighteen seventy four, making them the 185 00:10:31,480 --> 00:10:35,720 Speaker 1: first commercial producer. In the eighteen seventies, Thomas mclegan, the 186 00:10:35,840 --> 00:10:40,160 Speaker 1: medical superintendent at Dundee Royal Infirmary in Scotland, had a 187 00:10:40,160 --> 00:10:43,319 Speaker 1: lot of patients with rheumatism, and he noticed that there 188 00:10:43,320 --> 00:10:47,240 Speaker 1: were similarities between the symptoms of those patients and patients 189 00:10:47,280 --> 00:10:51,160 Speaker 1: with fevers that weren't related to rheumatism. The patients with 190 00:10:51,320 --> 00:10:55,720 Speaker 1: general fevers had often been successfully treated with Chinchona bark, which, 191 00:10:55,760 --> 00:10:58,800 Speaker 1: as we mentioned in the section on Reverend edmund Stone, 192 00:10:59,000 --> 00:11:02,800 Speaker 1: contains sal wison, and so mclegan decided to test the 193 00:11:02,840 --> 00:11:06,600 Speaker 1: bark extract salison out for himself, just as Stone had, 194 00:11:06,640 --> 00:11:08,840 Speaker 1: although obviously there was a little more knowledge about it 195 00:11:08,880 --> 00:11:11,400 Speaker 1: at this point. And in this case, the doctor first 196 00:11:11,480 --> 00:11:15,000 Speaker 1: tested the substance on himself, and he approached this as 197 00:11:15,040 --> 00:11:18,240 Speaker 1: a progressive test. So first he took five grains and 198 00:11:18,320 --> 00:11:21,040 Speaker 1: had no negative reaction, and then he took ten grains 199 00:11:21,360 --> 00:11:24,319 Speaker 1: which was similarly benign, and then he took thirty with 200 00:11:24,400 --> 00:11:28,160 Speaker 1: no quote inconvenience or discomfort, and at that point he 201 00:11:28,200 --> 00:11:31,000 Speaker 1: was convinced that salison was safe, so he next used 202 00:11:31,040 --> 00:11:34,319 Speaker 1: it to address a rheumatic patient with a fever, high 203 00:11:34,320 --> 00:11:38,000 Speaker 1: heart rate, and swollen and achy joints. This patient was 204 00:11:38,080 --> 00:11:41,560 Speaker 1: given twelve grains of salison at a time, repeating the 205 00:11:41,559 --> 00:11:45,200 Speaker 1: dose every three hours. After seven doses over the course 206 00:11:45,240 --> 00:11:48,480 Speaker 1: of a twenty four hour period, the patient's condition had improved. 207 00:11:48,840 --> 00:11:52,080 Speaker 1: The fever and heart rate were both reduced significantly, although 208 00:11:52,120 --> 00:11:55,200 Speaker 1: they were still slightly above normal. Two more days of 209 00:11:55,240 --> 00:11:59,040 Speaker 1: treatment reduced swelling and alleviated the patient's pain. After two 210 00:11:59,080 --> 00:12:02,160 Speaker 1: more years of trial with his patients, mclegan published his 211 00:12:02,240 --> 00:12:05,560 Speaker 1: results in The Lancet, and this article features eight case 212 00:12:05,559 --> 00:12:09,600 Speaker 1: studies of patients with varying degrees of rheumatism, and he wrote, quote, 213 00:12:09,679 --> 00:12:13,000 Speaker 1: the sudden arrest of the painful symptoms and the coincident 214 00:12:13,200 --> 00:12:16,640 Speaker 1: rapid fall of pulse and temperature followed so immediately on 215 00:12:16,679 --> 00:12:19,760 Speaker 1: the administration of the salason that it is impossible not 216 00:12:19,840 --> 00:12:23,760 Speaker 1: to attribute them to its use. Cases of acute rheumatism 217 00:12:23,800 --> 00:12:27,120 Speaker 1: do sometimes improve in the most unexpected manner, but I 218 00:12:27,200 --> 00:12:30,160 Speaker 1: never saw a case get well so quickly as those 219 00:12:30,200 --> 00:12:33,520 Speaker 1: of which I have given details above. Maclegan went on 220 00:12:33,559 --> 00:12:37,160 Speaker 1: to say that salison was the most effective treatment for rheumatism, 221 00:12:37,360 --> 00:12:40,080 Speaker 1: and also that its use, dosage, and effects should be 222 00:12:40,160 --> 00:12:44,800 Speaker 1: carefully documented. Interestingly, he believed that salasilic acid, which had 223 00:12:44,800 --> 00:12:48,440 Speaker 1: been isolated and was favored by some medical practitioners, was 224 00:12:48,679 --> 00:12:52,800 Speaker 1: not as effective or palatable a treatment as salison. Even 225 00:12:52,880 --> 00:12:55,520 Speaker 1: during this time, there was some confusion about whether the 226 00:12:55,600 --> 00:12:59,920 Speaker 1: terms salasin and salasilic acid were two separate things among 227 00:13:00,080 --> 00:13:02,640 Speaker 1: some members of the medical community. Yeah, I did see 228 00:13:02,960 --> 00:13:06,400 Speaker 1: a note in one article about mclegan that, uh, there 229 00:13:06,480 --> 00:13:09,160 Speaker 1: was a doctor that wrote him an apology note because 230 00:13:09,160 --> 00:13:11,439 Speaker 1: he got really mad that this guy kept confusing the 231 00:13:11,520 --> 00:13:14,720 Speaker 1: two terms. But this is what brings us to a 232 00:13:14,760 --> 00:13:20,080 Speaker 1: familiar name bear the firm Farban Fabric and Barm Friedrich 233 00:13:20,160 --> 00:13:23,520 Speaker 1: Bear and Company started as a die company, but in 234 00:13:23,559 --> 00:13:26,040 Speaker 1: the eight nineties the decision was made that the company 235 00:13:26,080 --> 00:13:29,720 Speaker 1: would turn its efforts to pharmaceuticals. And this might seem 236 00:13:29,760 --> 00:13:32,920 Speaker 1: like a weird gearshift to go from pigments to pharmaceuticals, 237 00:13:32,960 --> 00:13:35,880 Speaker 1: but both involved chemistry and this was a new and 238 00:13:35,920 --> 00:13:39,160 Speaker 1: growing field. And additionally, the company had a really good 239 00:13:39,240 --> 00:13:42,320 Speaker 1: name among consumers, and so it was able to leverage 240 00:13:42,360 --> 00:13:45,800 Speaker 1: that brand trust into these new ventures. So we've been 241 00:13:45,840 --> 00:13:49,400 Speaker 1: talking about how practitioners like the Reverend Stone were very 242 00:13:49,440 --> 00:13:52,720 Speaker 1: careful in dosage of salison and how in Stone's cases 243 00:13:52,720 --> 00:13:55,720 Speaker 1: in particular, he recorded no negative side effects, but that 244 00:13:55,880 --> 00:13:58,960 Speaker 1: is really not an accurate picture of the use of 245 00:13:59,080 --> 00:14:02,600 Speaker 1: oral salas like acid treatment. Over time, it can cause 246 00:14:02,679 --> 00:14:08,640 Speaker 1: significant issues with digestive health, including nausea, ulcers, vomiting. These 247 00:14:08,720 --> 00:14:11,720 Speaker 1: are all things that can come from using salsolic acid 248 00:14:11,840 --> 00:14:16,120 Speaker 1: as a medicine over time. Yeah, salason is more easily tolerated. 249 00:14:16,120 --> 00:14:18,160 Speaker 1: We're going to get into why in a minute. But 250 00:14:18,400 --> 00:14:22,000 Speaker 1: salasilic acid, once it's isolated, is a lot rougher on 251 00:14:22,200 --> 00:14:25,520 Speaker 1: the gastro intestinal tract, and this is what leads us 252 00:14:25,880 --> 00:14:29,320 Speaker 1: to the name that is most commonly associated with aspirin's origins, 253 00:14:29,360 --> 00:14:32,880 Speaker 1: and that is Felix Hoffman. And Hoffman, who was born 254 00:14:32,960 --> 00:14:35,880 Speaker 1: in eighteen sixty eight, initially pursued a career as a 255 00:14:35,880 --> 00:14:39,600 Speaker 1: pharmacist when he finished his education, but soon he realized 256 00:14:39,680 --> 00:14:41,760 Speaker 1: that he actually wanted to do some more in depth 257 00:14:41,800 --> 00:14:43,880 Speaker 1: science and become a chemist, and so he went back 258 00:14:43,920 --> 00:14:48,120 Speaker 1: to school In he finished his graduate work with honors, 259 00:14:48,200 --> 00:14:50,680 Speaker 1: and he joined Bear as a chemist in their newly 260 00:14:50,800 --> 00:14:56,840 Speaker 1: established pharmaceuticals division. In Hoffman added the acetal group H 261 00:14:56,960 --> 00:15:00,320 Speaker 1: three c O to salsilic acid. The result was a 262 00:15:00,360 --> 00:15:03,600 Speaker 1: setle salasilic acid, which would eventually come to be known 263 00:15:03,680 --> 00:15:07,280 Speaker 1: as aspirin. And this sounds like a really insightful experiment, 264 00:15:07,520 --> 00:15:09,680 Speaker 1: and you could say that it is, but really Hoffman 265 00:15:09,800 --> 00:15:12,960 Speaker 1: was a setulating a lot of different molecules to potentially 266 00:15:12,960 --> 00:15:18,600 Speaker 1: create patentable medicines. Bears early medicines uh fantacetin and tanning 267 00:15:18,960 --> 00:15:21,920 Speaker 1: were also developed using this same process in projects that 268 00:15:21,920 --> 00:15:25,800 Speaker 1: were run by other chemists. The origin for Hoffman's experiment 269 00:15:25,880 --> 00:15:28,960 Speaker 1: has a number of different stories to it. One version 270 00:15:29,040 --> 00:15:32,360 Speaker 1: is that his boss at Bear, Arthur Irun, had tested 271 00:15:32,440 --> 00:15:35,240 Speaker 1: him with figuring out a way to make salacilic acid 272 00:15:35,320 --> 00:15:39,160 Speaker 1: more tolerable. The other was that his father took salasilic 273 00:15:39,200 --> 00:15:42,240 Speaker 1: acid for his rheumatism and was experiencing the negative side 274 00:15:42,240 --> 00:15:44,800 Speaker 1: effects that come along with using it for a prolonged period. 275 00:15:44,880 --> 00:15:47,800 Speaker 1: So Hoffman was driven by a desire to help him. 276 00:15:48,000 --> 00:15:50,920 Speaker 1: There's another man involved in this named Einrich Dresser, and 277 00:15:50,920 --> 00:15:53,200 Speaker 1: he ran the pharmaceutical lab at Bear and it was 278 00:15:53,280 --> 00:15:57,240 Speaker 1: his responsibility to test Hoffman's new substance. And Dresser was 279 00:15:57,320 --> 00:16:00,520 Speaker 1: slow to work with a setle salasilic acid. He openly 280 00:16:00,560 --> 00:16:03,040 Speaker 1: said that he thought it had no value and moreover, 281 00:16:03,120 --> 00:16:05,400 Speaker 1: that it could be damaging to the heart. There was 282 00:16:05,440 --> 00:16:09,320 Speaker 1: another acetylated compound created by Hoffman around the same time, 283 00:16:09,400 --> 00:16:12,080 Speaker 1: which Dresser thought would be a lot more lucrative, and 284 00:16:12,120 --> 00:16:16,520 Speaker 1: that was heroin. Hoffman had created it when he ascetilated morphine, 285 00:16:16,760 --> 00:16:20,080 Speaker 1: but that was not patentable because it had been discovered 286 00:16:20,120 --> 00:16:24,040 Speaker 1: by another scientist twenty five years earlier. Bear sold heroin 287 00:16:24,240 --> 00:16:27,040 Speaker 1: as a pain reliever and a cough suppressant for years. 288 00:16:27,680 --> 00:16:29,960 Speaker 1: Many other companies did too. We don't don't want to 289 00:16:30,000 --> 00:16:32,840 Speaker 1: put that all on Bear. You have probably seen as a. 290 00:16:33,320 --> 00:16:35,960 Speaker 1: I'm presuming if you're a listener that you're a history fan, 291 00:16:36,240 --> 00:16:40,160 Speaker 1: you've probably seen like the old timey adverts for heroin 292 00:16:40,440 --> 00:16:43,040 Speaker 1: as like a magical cure. All. But after more than 293 00:16:43,080 --> 00:16:47,280 Speaker 1: a year of this aspirin compound being developed, Dresser, after 294 00:16:47,320 --> 00:16:50,760 Speaker 1: getting pressure from Arthur Eiken Groun, who also uh kind 295 00:16:50,800 --> 00:16:54,000 Speaker 1: of got some other people at Bear involved in the 296 00:16:54,040 --> 00:16:56,120 Speaker 1: cause to kind of push for this thing to get tested, 297 00:16:56,680 --> 00:17:00,600 Speaker 1: got back to Hoffman's aceetal salicilic acid and Reser first 298 00:17:00,640 --> 00:17:03,320 Speaker 1: tested it on himself and then he ran an animal study, 299 00:17:03,800 --> 00:17:07,480 Speaker 1: and next Bear ran tests in hospitals. Ike and Groon 300 00:17:07,600 --> 00:17:10,800 Speaker 1: started this more widespread trial of the new compound, offering 301 00:17:10,800 --> 00:17:13,480 Speaker 1: it to doctors to use with their patients, and the 302 00:17:13,600 --> 00:17:17,560 Speaker 1: results were as hoped, This new medication successfully treated patients, 303 00:17:17,840 --> 00:17:21,600 Speaker 1: particularly as a pain reliever. The full clinical trials were 304 00:17:21,600 --> 00:17:26,480 Speaker 1: published in early Bayer was quick to recognize the financial 305 00:17:26,480 --> 00:17:29,320 Speaker 1: potential of aspirin, and we will talk about its entry 306 00:17:29,400 --> 00:17:32,240 Speaker 1: into the market after we pause for another word from 307 00:17:32,240 --> 00:17:42,280 Speaker 1: a sponsor. The German patent application that Bear filed was 308 00:17:42,320 --> 00:17:45,879 Speaker 1: actually rejected to other chemists in Europe had created the 309 00:17:45,920 --> 00:17:50,280 Speaker 1: acetyl salicylic acid before Hoffman. Although those were in lab scenarios, 310 00:17:50,320 --> 00:17:53,800 Speaker 1: and even though they submitted patents, neither of those parties 311 00:17:53,800 --> 00:17:55,880 Speaker 1: had been able to create a stable version that could 312 00:17:55,880 --> 00:17:58,680 Speaker 1: go to market. But Bayer went ahead and fouled a 313 00:17:58,720 --> 00:18:02,360 Speaker 1: patent application in the US and that was accepted. It 314 00:18:02,440 --> 00:18:05,080 Speaker 1: was written by Felix Hoffman, and it begins quote, be 315 00:18:05,119 --> 00:18:08,720 Speaker 1: it known that I, Felix Hoffman, doctor of Philosophy, chemist, 316 00:18:08,840 --> 00:18:11,840 Speaker 1: as signer to the Farman Forbeacon of elber Field Company 317 00:18:11,840 --> 00:18:15,520 Speaker 1: of New York, residing at elber Field, Germany, have invented 318 00:18:15,560 --> 00:18:18,640 Speaker 1: a new and useful improvement in the manufacture or production 319 00:18:18,680 --> 00:18:22,320 Speaker 1: of aceetal salacilic acid. And Hoffman described his process in 320 00:18:22,400 --> 00:18:25,879 Speaker 1: detail in that patent paper, writing quote, in producing my 321 00:18:25,920 --> 00:18:29,199 Speaker 1: new compound, I can proceed as follows, without limiting myself 322 00:18:29,240 --> 00:18:32,960 Speaker 1: to the particulars. Given a mixture prepared from fifty parts 323 00:18:32,960 --> 00:18:36,679 Speaker 1: of salacillic acid and seventy five parts acetic anhydride is 324 00:18:36,720 --> 00:18:39,800 Speaker 1: heated for about two hours at about one fifty degrees 325 00:18:39,840 --> 00:18:43,960 Speaker 1: centigrade in a vessel provided with a reflux condenser. Thus 326 00:18:44,000 --> 00:18:46,639 Speaker 1: a clear liquid is obtained from which, on cooling, a 327 00:18:46,680 --> 00:18:50,159 Speaker 1: crystalline mass is separated, which is the acetal salacilic acid. 328 00:18:50,880 --> 00:18:53,760 Speaker 1: It is freed from the acetic and hydride by pressing 329 00:18:53,840 --> 00:18:57,720 Speaker 1: and then recrystallized from dry chloroform. The acid is thus 330 00:18:57,720 --> 00:19:01,120 Speaker 1: obtained in the shape of glittering white and needles melting 331 00:19:01,200 --> 00:19:04,760 Speaker 1: at about one thirty five degrees centigrade, which are easily 332 00:19:04,800 --> 00:19:09,840 Speaker 1: soluble in benzene alcohol, glacial acetic acid, and chloroform, but 333 00:19:10,000 --> 00:19:14,760 Speaker 1: difficultly soluble in cold water. On March six nine, aspirin 334 00:19:14,880 --> 00:19:17,879 Speaker 1: was registered as a trademark, named by the Beer Company. 335 00:19:18,040 --> 00:19:20,760 Speaker 1: The name takes the A from a seatle s p 336 00:19:20,960 --> 00:19:23,720 Speaker 1: I R from the genus of plants that are alternative 337 00:19:23,760 --> 00:19:27,800 Speaker 1: sources of salasin, which is spuria. The end suffix was 338 00:19:27,840 --> 00:19:30,880 Speaker 1: a popular one at the time in drug names, heroin 339 00:19:31,000 --> 00:19:33,800 Speaker 1: being another example. Yeah, they're at number if you look 340 00:19:33,800 --> 00:19:35,520 Speaker 1: at drugs being developed at the time. The end in 341 00:19:35,640 --> 00:19:39,600 Speaker 1: i am. The first aspirin that appeared in tablet form 342 00:19:39,720 --> 00:19:42,480 Speaker 1: rather than a powder was in nineteen hundred, although powder 343 00:19:42,520 --> 00:19:46,400 Speaker 1: aspirin continued to be offered, and these various options made 344 00:19:46,400 --> 00:19:49,520 Speaker 1: it incredibly easy for doctors to prescribe, and aspirin can 345 00:19:49,560 --> 00:19:53,040 Speaker 1: actually still only be acquired with a prescription. Up until 346 00:19:53,160 --> 00:19:56,080 Speaker 1: nineteen fifteen, even in dosages that we today would easily 347 00:19:56,080 --> 00:19:58,840 Speaker 1: be able to buy without one. In nine nineteen, Bayer 348 00:19:58,960 --> 00:20:02,040 Speaker 1: lost its exclusive civility right to use the name aspirin 349 00:20:02,240 --> 00:20:06,040 Speaker 1: through its US patent. As part of the reparations for 350 00:20:06,119 --> 00:20:09,360 Speaker 1: World War One, the company had to sell its US factories. 351 00:20:09,680 --> 00:20:12,960 Speaker 1: Sterling Incorporated bought the rights to olive Bear's US drug 352 00:20:12,960 --> 00:20:16,919 Speaker 1: properties for three million dollars. The name didn't stay trademarked 353 00:20:16,960 --> 00:20:19,880 Speaker 1: under Sterling, though, and it's been considered a generic term 354 00:20:19,880 --> 00:20:22,840 Speaker 1: in the US for decades and dozens of other countries. 355 00:20:22,880 --> 00:20:26,040 Speaker 1: Though it's still a trademarked name, Bear was able to 356 00:20:26,080 --> 00:20:28,560 Speaker 1: get the international trademark on the name back when it 357 00:20:28,600 --> 00:20:32,320 Speaker 1: bought it from Smith Climb Beacham for one billion dollars. 358 00:20:32,359 --> 00:20:34,600 Speaker 1: That large price tag was not only for the trademark 359 00:20:34,640 --> 00:20:37,000 Speaker 1: on the name Aspirin. That acquisition was rolled into a 360 00:20:37,080 --> 00:20:40,280 Speaker 1: larger deal that included other points and other drugs as well. 361 00:20:40,920 --> 00:20:44,240 Speaker 1: Smith Climb Beecham had bought out Sterling's worldwide rights, so 362 00:20:44,359 --> 00:20:47,399 Speaker 1: in countries where the trademark is still held, Aspirin was 363 00:20:47,440 --> 00:20:50,720 Speaker 1: once again under the Bear umbrella. Funny detail on all 364 00:20:50,720 --> 00:20:53,840 Speaker 1: of this was that exactly how Hoffman's work with salasilic 365 00:20:53,920 --> 00:20:57,320 Speaker 1: acid actually made the substance more tolerable to people, djusting 366 00:20:57,320 --> 00:21:01,119 Speaker 1: it was still a little fuzzy a Essentially, he transformed 367 00:21:01,160 --> 00:21:04,480 Speaker 1: it into a new molecule that one doesn't trigger issues 368 00:21:04,520 --> 00:21:07,320 Speaker 1: in the g I tract, and two is converted back 369 00:21:07,359 --> 00:21:10,200 Speaker 1: to salasilic acid by the body, so that the pain 370 00:21:10,280 --> 00:21:13,280 Speaker 1: and fever relief characteristics of it still apply. But that 371 00:21:13,359 --> 00:21:16,520 Speaker 1: whole process was not really understood until the nineteen seventies. 372 00:21:16,840 --> 00:21:18,960 Speaker 1: It was only after work in the second half of 373 00:21:19,000 --> 00:21:22,719 Speaker 1: the twentieth century that the potential benefits of aspirin related 374 00:21:22,760 --> 00:21:25,440 Speaker 1: to heart disease and stroke came to be known. Now, 375 00:21:25,600 --> 00:21:28,280 Speaker 1: how things actually played out at Bear related to the 376 00:21:28,280 --> 00:21:31,920 Speaker 1: discovery of aspirin have continued to be debated. We mentioned 377 00:21:31,920 --> 00:21:35,200 Speaker 1: when we first introduced that segment the two different stories 378 00:21:35,240 --> 00:21:37,600 Speaker 1: about how the experiments that led to the development of 379 00:21:37,640 --> 00:21:40,679 Speaker 1: aspirin actually began, but that is not the end of it. 380 00:21:41,000 --> 00:21:45,200 Speaker 1: In forty seven years after Hoffman's development of aspirin and 381 00:21:45,240 --> 00:21:49,640 Speaker 1: the Bear Lab, Arthur Eikenrin, while being held at theresians 382 00:21:49,680 --> 00:21:53,320 Speaker 1: Dot concentration camp because he was Jewish, wrote his version 383 00:21:53,359 --> 00:21:56,399 Speaker 1: of this story in this letter, which is in the 384 00:21:56,440 --> 00:21:59,160 Speaker 1: Bear Archives. He said that he was the one who 385 00:21:59,160 --> 00:22:01,639 Speaker 1: wanted to come up with a version of salasilic acid 386 00:22:01,680 --> 00:22:05,840 Speaker 1: that would diminish these negative gastro intestinal side effects. According 387 00:22:05,880 --> 00:22:08,679 Speaker 1: to his account, he wrote down all the instructions and 388 00:22:08,760 --> 00:22:12,280 Speaker 1: Hoffman carried them out without really understanding any of it. 389 00:22:12,840 --> 00:22:15,960 Speaker 1: Ike and Grun also published this account in nineteen forty nine, 390 00:22:16,160 --> 00:22:18,879 Speaker 1: three years after Hoffman's death, he published that in the 391 00:22:18,880 --> 00:22:23,400 Speaker 1: German periodical Pharmacy. In the nineteen nineties, Walter Sneader, pharmaceutical 392 00:22:23,480 --> 00:22:27,000 Speaker 1: historian and deputy head of the Department of Pharmaceutical Sciences 393 00:22:27,080 --> 00:22:30,520 Speaker 1: at the University of Strathclyde, Glasgow, took up the cause 394 00:22:30,600 --> 00:22:32,720 Speaker 1: of Ike and Grun's credit, and one of the key 395 00:22:32,760 --> 00:22:36,000 Speaker 1: pieces of Sneader's argument hinges on what he believed might 396 00:22:36,000 --> 00:22:39,520 Speaker 1: have been a mistranslation of one of Hoffman's eight seven notes, 397 00:22:39,960 --> 00:22:43,120 Speaker 1: which may have confused verb tense a little bit. While 398 00:22:43,160 --> 00:22:46,520 Speaker 1: most translations indicate that Hoffman was saying the compound was 399 00:22:46,560 --> 00:22:49,520 Speaker 1: about to be tested, Sneeeder put forth the idea that 400 00:22:49,600 --> 00:22:52,600 Speaker 1: actually should be translated to indicate that it already was 401 00:22:52,680 --> 00:22:55,840 Speaker 1: being tested, i e. The work that Hoffman was doing 402 00:22:55,920 --> 00:23:00,480 Speaker 1: was corroborative of an existing process rather than developmental. In 403 00:23:01,720 --> 00:23:05,160 Speaker 1: the year anniversary of the patent and Felix Hoffman's name, 404 00:23:05,720 --> 00:23:09,639 Speaker 1: Bear issued a press release addressing this ongoing debate about 405 00:23:09,640 --> 00:23:14,119 Speaker 1: Hoffman and Arthur eikenrun. The release states, quote the claim 406 00:23:14,160 --> 00:23:17,560 Speaker 1: that not Hoffman but his colleague, doctor Arthur ken Green 407 00:23:17,680 --> 00:23:21,679 Speaker 1: is responsible for the development cannot be proven. The statement 408 00:23:21,720 --> 00:23:24,520 Speaker 1: goes on to mention Walter Sneeeder and his assertion that 409 00:23:24,520 --> 00:23:27,159 Speaker 1: Hoffman was working off notes by iken Groen and that 410 00:23:27,480 --> 00:23:30,199 Speaker 1: I can Green should be giving credit. But Bear's stance 411 00:23:30,280 --> 00:23:33,159 Speaker 1: was that Iken Groun was never Hoffman superior, that they 412 00:23:33,160 --> 00:23:35,679 Speaker 1: were equals, and so it would be weird for him 413 00:23:35,720 --> 00:23:38,720 Speaker 1: to have assigned him a task, and that Sneider's claims 414 00:23:38,760 --> 00:23:43,840 Speaker 1: contradicted established documentation. Some of the confusion, the company claims, 415 00:23:43,960 --> 00:23:46,439 Speaker 1: comes from the fact that Iken gron did have a 416 00:23:46,480 --> 00:23:50,720 Speaker 1: subordinate named Hoffman, but that was Fritz Hoffman, not Felix. 417 00:23:51,080 --> 00:23:54,040 Speaker 1: The Bear account points out that Arthur Iiken Grew never 418 00:23:54,160 --> 00:23:57,040 Speaker 1: claimed credit for aspirin until he was in his eighties, 419 00:23:57,240 --> 00:24:00,800 Speaker 1: after instances over five decades when he attributed the work 420 00:24:00,800 --> 00:24:03,520 Speaker 1: to Felix Hoffman. Of course, there's a case to be 421 00:24:03,560 --> 00:24:05,919 Speaker 1: made that because he was Jewish, he might never have 422 00:24:06,000 --> 00:24:08,320 Speaker 1: felt that he had the agency in Germany to be 423 00:24:08,359 --> 00:24:10,360 Speaker 1: able to do that. And one of the places, though 424 00:24:10,400 --> 00:24:13,359 Speaker 1: where Sneader's case for Ike and Groon kind of falls apart, 425 00:24:13,880 --> 00:24:16,439 Speaker 1: is also noted in that press release. So in his 426 00:24:16,480 --> 00:24:19,760 Speaker 1: paper on the subject, Sneader mentions that Hoffman was never 427 00:24:19,800 --> 00:24:23,280 Speaker 1: publicly credited with the invention of aspirin until nineteen thirty four. 428 00:24:23,920 --> 00:24:26,000 Speaker 1: The assertion there is that this was an attempt to 429 00:24:26,040 --> 00:24:28,879 Speaker 1: write the Jewish ken Groun out of the record during 430 00:24:28,880 --> 00:24:32,520 Speaker 1: a period of intense anti semitism in Germany. But the 431 00:24:32,520 --> 00:24:35,680 Speaker 1: problem there is that Hoffman was credited on the patent 432 00:24:35,720 --> 00:24:38,680 Speaker 1: application all the way back in eight nine, as well 433 00:24:38,720 --> 00:24:41,119 Speaker 1: as another paperwork that dated back to when he was 434 00:24:41,200 --> 00:24:45,040 Speaker 1: doing the experiments in eighteen ninety seven. Beyer's statement concludes 435 00:24:45,080 --> 00:24:47,880 Speaker 1: by noting that both ken Grud and Hoffman were researchers 436 00:24:47,960 --> 00:24:51,239 Speaker 1: working for Beyer in eighteen nine seven, basically saying they 437 00:24:51,240 --> 00:24:54,200 Speaker 1: were in a work for higher a situation. The statement 438 00:24:54,240 --> 00:24:56,840 Speaker 1: finished with quote, it would have made no difference to 439 00:24:56,920 --> 00:24:59,440 Speaker 1: either the company or the success of the aspirin brand, 440 00:24:59,520 --> 00:25:02,320 Speaker 1: whether one or the other is considered the first to 441 00:25:02,440 --> 00:25:05,480 Speaker 1: succeed in the acetylation of salas so like acid for 442 00:25:05,480 --> 00:25:09,560 Speaker 1: the first time in a chemically pure and stable form. Yeah, 443 00:25:09,640 --> 00:25:11,800 Speaker 1: it's easy for a big company to go. It doesn't 444 00:25:11,840 --> 00:25:14,000 Speaker 1: matter who got credit, neither of them was really getting 445 00:25:14,000 --> 00:25:16,119 Speaker 1: anything out of it. But of course the different people 446 00:25:16,280 --> 00:25:19,359 Speaker 1: involved in this effort it matters a great deal. We 447 00:25:19,400 --> 00:25:22,159 Speaker 1: have talked of many times and several times lately about 448 00:25:22,160 --> 00:25:26,520 Speaker 1: how scientific discovery and credit is an issue of great 449 00:25:26,560 --> 00:25:30,840 Speaker 1: debate and great passion. So um, but which of the 450 00:25:30,880 --> 00:25:36,040 Speaker 1: bear scientists truly invented aspirin will likely never be conclusively settled. 451 00:25:36,280 --> 00:25:39,600 Speaker 1: It's interesting reading modern more modern accounts of the whole 452 00:25:39,640 --> 00:25:42,000 Speaker 1: thing that they do kind of mention that this this 453 00:25:42,080 --> 00:25:44,679 Speaker 1: debate goes on, although some completely just go with the 454 00:25:44,680 --> 00:25:48,439 Speaker 1: Felix Hoffman version. Kind of fascinating, but that is the 455 00:25:48,480 --> 00:25:51,480 Speaker 1: invention of aspirin. Do you have some listener mail also 456 00:25:51,920 --> 00:25:55,919 Speaker 1: I do. This is from our listeners Summer, and she 457 00:25:56,080 --> 00:25:59,920 Speaker 1: is writing to us about our recent episode The crampuson 458 00:26:00,000 --> 00:26:03,480 Speaker 1: Friend's Holiday Special four and specifically the Seven Lucky Gods. 459 00:26:03,520 --> 00:26:05,359 Speaker 1: And she writes, my name is Summer, and I've been 460 00:26:05,359 --> 00:26:08,040 Speaker 1: listening to your podcast for probably four years now. I 461 00:26:08,080 --> 00:26:10,560 Speaker 1: started when I needed something to do while sewing costumes 462 00:26:10,560 --> 00:26:13,200 Speaker 1: for the high school drama club I run. My family 463 00:26:13,200 --> 00:26:14,879 Speaker 1: and I have lived in Japan for nine and a 464 00:26:14,960 --> 00:26:17,399 Speaker 1: half years now. My husband teaches at a high school 465 00:26:17,400 --> 00:26:19,919 Speaker 1: on an American military base. I had to write in 466 00:26:19,960 --> 00:26:22,359 Speaker 1: after listening to the seven Lucky Gods segment because I 467 00:26:22,359 --> 00:26:25,199 Speaker 1: have a crazy story about them. My friend Amanda and 468 00:26:25,240 --> 00:26:27,640 Speaker 1: I decided to do a seven Lucky Gods tour last 469 00:26:27,720 --> 00:26:31,400 Speaker 1: January in Yokahoma. Many cities or areas have their own 470 00:26:31,400 --> 00:26:33,840 Speaker 1: tours that can either be walked or driven in one day. 471 00:26:34,400 --> 00:26:36,679 Speaker 1: I've been driving in Japan for many years now, so 472 00:26:36,720 --> 00:26:39,840 Speaker 1: I felt confident and comfortable getting around, but there are 473 00:26:39,880 --> 00:26:43,040 Speaker 1: always surprises here. There are many roads that are technically 474 00:26:43,040 --> 00:26:45,400 Speaker 1: two lane, but in reality only one car can fit 475 00:26:45,440 --> 00:26:49,040 Speaker 1: down them. Also, something Google Maps struggles with is knowing 476 00:26:49,080 --> 00:26:52,040 Speaker 1: where the real entrance to a place is. These two 477 00:26:52,080 --> 00:26:54,560 Speaker 1: things conspired against us on our quest to get all 478 00:26:54,600 --> 00:26:57,000 Speaker 1: seven of our Lucky Gods. On our way to the 479 00:26:57,040 --> 00:27:00,080 Speaker 1: fifth stop, we were following our Google Maps instructions that 480 00:27:00,160 --> 00:27:02,880 Speaker 1: led us into a residential neighborhood with those two lane 481 00:27:02,960 --> 00:27:05,960 Speaker 1: roads that only fit my minivan. We went up a 482 00:27:06,040 --> 00:27:08,280 Speaker 1: hill and Google instructed us to turn at the top, 483 00:27:08,280 --> 00:27:10,879 Speaker 1: which made sense because directly in front of us was 484 00:27:10,920 --> 00:27:13,040 Speaker 1: a set of stairs, though I started to spect this 485 00:27:13,160 --> 00:27:15,080 Speaker 1: was not going to work, as the road that I 486 00:27:15,119 --> 00:27:17,879 Speaker 1: turned onto was now gravel bordered on the left by 487 00:27:17,880 --> 00:27:19,960 Speaker 1: a wall and on the right by a steep twenty 488 00:27:19,960 --> 00:27:23,560 Speaker 1: ft drop off with no guardrail. We drove very slowly 489 00:27:23,560 --> 00:27:26,639 Speaker 1: on this road for about twenty and turned again, only 490 00:27:26,720 --> 00:27:29,159 Speaker 1: to discover that we were now definitely on something that 491 00:27:29,240 --> 00:27:32,440 Speaker 1: was more akin to a sidewalk. It ended about twenty 492 00:27:32,800 --> 00:27:35,640 Speaker 1: in front of us in stairs, which we obviously were 493 00:27:35,680 --> 00:27:38,680 Speaker 1: not going to drive down. I now had the unenviable 494 00:27:38,720 --> 00:27:41,359 Speaker 1: task of backing up around two corners on a not 495 00:27:41,600 --> 00:27:45,080 Speaker 1: road about seven ft wide in a minivan. Also did 496 00:27:45,160 --> 00:27:47,359 Speaker 1: I mention the cliff drop off on one side and 497 00:27:47,440 --> 00:27:49,959 Speaker 1: my three year old in the back seat. Thank Heavens 498 00:27:49,960 --> 00:27:52,320 Speaker 1: for backup cameras and my friend Amanda, who got out 499 00:27:52,359 --> 00:27:55,040 Speaker 1: and helped guide me around the corners and the telephone pools. 500 00:27:55,280 --> 00:27:57,000 Speaker 1: When we finally got back on a real road, we 501 00:27:57,080 --> 00:27:59,159 Speaker 1: parked the car and laughed from the sheer terror of 502 00:27:59,200 --> 00:28:01,399 Speaker 1: it all. We assume the stairs in front of us 503 00:28:01,400 --> 00:28:03,760 Speaker 1: were a back entrance to the shrine and we wandered 504 00:28:03,760 --> 00:28:06,000 Speaker 1: on him. Sure enough it was and we were able 505 00:28:06,040 --> 00:28:08,920 Speaker 1: to get our very lucky God and continue on, though 506 00:28:08,960 --> 00:28:11,760 Speaker 1: this time with a little less reliance on Google. I 507 00:28:11,800 --> 00:28:15,120 Speaker 1: look forward to doing another tour in Kamakura in although 508 00:28:15,160 --> 00:28:17,359 Speaker 1: I will probably do it on foot. Thank you for 509 00:28:17,400 --> 00:28:20,200 Speaker 1: creating such a fun and informative podcast. I always recommend 510 00:28:20,240 --> 00:28:23,399 Speaker 1: your episode on Staco and the One Thousand Cranes to 511 00:28:23,440 --> 00:28:26,160 Speaker 1: any friends that visit Hiroshima. That story is very close 512 00:28:26,200 --> 00:28:28,200 Speaker 1: to my heart after directing a show on it, and 513 00:28:28,240 --> 00:28:30,280 Speaker 1: I wept like a child at the mention of the 514 00:28:30,320 --> 00:28:33,440 Speaker 1: Hiroshima Peace Park. I we I get weepy just thinking 515 00:28:33,480 --> 00:28:36,000 Speaker 1: about it. See um, thank you for being my company 516 00:28:36,080 --> 00:28:38,440 Speaker 1: while I saw hundreds of costumes and drive around on 517 00:28:38,560 --> 00:28:41,280 Speaker 1: Adventures in Japan um summer. This is such a fun, 518 00:28:41,400 --> 00:28:44,959 Speaker 1: slightly terrifying story. I agree. The backup camera is magic. 519 00:28:46,520 --> 00:28:48,920 Speaker 1: I'm glad you're safe. That drop off sounds very scary 520 00:28:48,960 --> 00:28:53,120 Speaker 1: to me, and I uh. I hope that your visit 521 00:28:53,160 --> 00:28:55,240 Speaker 1: to all the Lucky Gods granted you luck for the 522 00:28:55,240 --> 00:28:57,280 Speaker 1: rest of the year, that you never found yourself in 523 00:28:57,360 --> 00:29:00,160 Speaker 1: such a precarious position. Again. Uh. If you had to 524 00:29:00,200 --> 00:29:02,600 Speaker 1: write to us, you can do so at History podcast 525 00:29:02,680 --> 00:29:05,320 Speaker 1: at I heart radio dot com. 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