1 00:00:01,280 --> 00:00:04,000 Speaker 1: Welcome to Stuff You Missed in History Class, a production 2 00:00:04,120 --> 00:00:13,040 Speaker 1: of I Heart Radios How Stuff Works. Hello, and welcome 3 00:00:13,080 --> 00:00:16,640 Speaker 1: to the podcast. I'm Tracy V. Wilson and I'm Holly Fry. 4 00:00:17,040 --> 00:00:19,639 Speaker 1: We have gotten a lot of requests over the years 5 00:00:19,640 --> 00:00:26,320 Speaker 1: to talk about the drug the litamide, including from Ginger Cheyenne, Emily, Brittany, Randy, Rebecca, Hannah, Tricia, 6 00:00:26,400 --> 00:00:29,800 Speaker 1: Jackie and Terrell. And we've had some spikes in those 7 00:00:29,800 --> 00:00:32,239 Speaker 1: requestsed a couple of different points, including when this was 8 00:00:32,280 --> 00:00:35,400 Speaker 1: a plot line on the TV show called The Midwife. 9 00:00:35,560 --> 00:00:37,760 Speaker 1: We got some rite in a row over the last 10 00:00:37,800 --> 00:00:40,760 Speaker 1: couple of weeks. Uh. This has been described as the 11 00:00:40,800 --> 00:00:45,200 Speaker 1: biggest man made medical disaster of all time. From ninety 12 00:00:45,240 --> 00:00:48,479 Speaker 1: seven to nineteen sixty two, the litamide was marketed as 13 00:00:48,520 --> 00:00:51,199 Speaker 1: being completely safe and it was used as a treatment 14 00:00:51,240 --> 00:00:54,760 Speaker 1: for morning sickness, but it was not safe. At least 15 00:00:54,760 --> 00:00:58,160 Speaker 1: ten thousand people who were exposed to the litamide in 16 00:00:58,240 --> 00:01:00,840 Speaker 1: the womb were born with a ring as of disabilities 17 00:01:00,840 --> 00:01:03,560 Speaker 1: and medical conditions, and about forty percent of them didn't 18 00:01:03,560 --> 00:01:07,760 Speaker 1: survive infancy, and the drug also caused a really unknown 19 00:01:07,840 --> 00:01:12,039 Speaker 1: number of miscarriages and still births, possibly tens of thousands more. 20 00:01:12,800 --> 00:01:14,280 Speaker 1: A lot of the people who've asked us about this 21 00:01:14,319 --> 00:01:17,319 Speaker 1: episode have framed it in the context of babies, but 22 00:01:17,480 --> 00:01:20,720 Speaker 1: there are thousands of adults living today who were harmed 23 00:01:20,760 --> 00:01:23,600 Speaker 1: by this drug many parts of the world. They refer 24 00:01:23,680 --> 00:01:26,759 Speaker 1: to themselves as the Litta miters. As of when we're 25 00:01:26,760 --> 00:01:29,040 Speaker 1: recording this in twenty nineteen, most of these folks are 26 00:01:29,040 --> 00:01:31,399 Speaker 1: in their late fifties and early sixties, although as we 27 00:01:31,440 --> 00:01:34,080 Speaker 1: will discuss, there are also people who are a lot 28 00:01:34,120 --> 00:01:37,880 Speaker 1: younger than that. So people who weren't personally affected by 29 00:01:37,920 --> 00:01:40,399 Speaker 1: this might imagine this story as something that sort of 30 00:01:40,480 --> 00:01:43,399 Speaker 1: is confined back in the past, but it's really a 31 00:01:43,480 --> 00:01:46,720 Speaker 1: story that's ongoing until today, and it's also a long 32 00:01:46,840 --> 00:01:49,520 Speaker 1: enough story that we're covering it in two parts. So 33 00:01:49,560 --> 00:01:52,040 Speaker 1: today we're going to talk about what the litamide is, 34 00:01:52,560 --> 00:01:55,720 Speaker 1: the animal testing that let its manufacturer to market it 35 00:01:55,800 --> 00:01:59,320 Speaker 1: as safe and it's released onto the market. Next time 36 00:01:59,520 --> 00:02:02,440 Speaker 1: we will be talking more about its aftermath and how 37 00:02:02,440 --> 00:02:06,680 Speaker 1: it affected everything from drug regulations to abortion law. Um 38 00:02:06,720 --> 00:02:10,600 Speaker 1: there is some disability rights stuff along the way that 39 00:02:10,680 --> 00:02:14,000 Speaker 1: it's pretty appalling in terms of how people were treated, 40 00:02:14,400 --> 00:02:17,360 Speaker 1: and that's going to apply really to both episodes. Yeah, 41 00:02:17,360 --> 00:02:22,720 Speaker 1: obviously not a lighthearted rump today. Just heads up, as 42 00:02:22,720 --> 00:02:26,080 Speaker 1: if you had not gleaned to that already from Tracy's introme. So, 43 00:02:26,320 --> 00:02:29,520 Speaker 1: the letta mine is a taradogen, which means it's something 44 00:02:29,560 --> 00:02:33,840 Speaker 1: that disrupts development, and taradogens can affect any stage of development, 45 00:02:34,160 --> 00:02:36,520 Speaker 1: but the term is frequently used to describe things that 46 00:02:36,600 --> 00:02:40,280 Speaker 1: negatively affect the development of an embryo or fetus, including 47 00:02:40,320 --> 00:02:44,560 Speaker 1: causing miscarriage. And lots of things can act as taradogens, 48 00:02:44,639 --> 00:02:51,320 Speaker 1: including hyperthermia, infectious disease, environmental pollutants, and alcohol. Pharmaceuticals can 49 00:02:51,320 --> 00:02:55,040 Speaker 1: also have the potential to act as taradogens. Many countries 50 00:02:55,080 --> 00:02:58,160 Speaker 1: have some kind of a system now for categorizing the 51 00:02:58,320 --> 00:03:01,000 Speaker 1: level of risk and whether the dry is recommended for 52 00:03:01,120 --> 00:03:04,720 Speaker 1: use during pregnancy. So in the US, for example, these 53 00:03:04,760 --> 00:03:07,680 Speaker 1: categories range from A, in which the risk to a 54 00:03:07,760 --> 00:03:11,280 Speaker 1: fetus seems to be remote to category X, in which 55 00:03:11,320 --> 00:03:16,560 Speaker 1: the drugs risks during a pregnancy outweigh any possible benefits. Today, 56 00:03:16,760 --> 00:03:20,680 Speaker 1: drugs that fall into category X or otherwise have serious 57 00:03:20,760 --> 00:03:24,400 Speaker 1: teratgenic effects are typically only used with a range of 58 00:03:24,400 --> 00:03:28,440 Speaker 1: safety precautions in place. Patients who could become pregnant may 59 00:03:28,480 --> 00:03:31,560 Speaker 1: need to have a negative pregnancy test before they start treatment, 60 00:03:32,000 --> 00:03:34,720 Speaker 1: and they may also be required to use multiple forms 61 00:03:34,720 --> 00:03:37,800 Speaker 1: of birth control and be tested for pregnancy while they're 62 00:03:37,840 --> 00:03:42,120 Speaker 1: being treated. Since f d A, drug labeling rules in 63 00:03:42,160 --> 00:03:45,720 Speaker 1: the United States have required a section called quote Females 64 00:03:45,760 --> 00:03:50,000 Speaker 1: and Males of Reproductive Potential and that details these recommendations 65 00:03:50,080 --> 00:03:53,760 Speaker 1: along with whether the drug has been shown to cause infertility. Yeah, 66 00:03:53,760 --> 00:03:57,440 Speaker 1: the exact rules and laws obviously vary all over the world, 67 00:03:57,480 --> 00:04:00,840 Speaker 1: but even with these types of precautions, it's still possible 68 00:04:00,880 --> 00:04:03,080 Speaker 1: for a drug that's known to have these kinds of 69 00:04:03,120 --> 00:04:06,880 Speaker 1: effects to harm a developing fetus. A doctor might not 70 00:04:06,920 --> 00:04:09,920 Speaker 1: communicate the risks clearly enough for a patient might not 71 00:04:10,000 --> 00:04:13,840 Speaker 1: fully understand them, or contraceptives could fail for a variety 72 00:04:13,840 --> 00:04:17,800 Speaker 1: of reasons. Especially in places that don't have a robust 73 00:04:17,920 --> 00:04:21,520 Speaker 1: medical system, patients might share their medications with each other 74 00:04:21,600 --> 00:04:25,520 Speaker 1: without fully understanding the risks involved, and especially because these 75 00:04:25,520 --> 00:04:29,360 Speaker 1: same places don't often have the resources to really follow 76 00:04:29,440 --> 00:04:32,680 Speaker 1: up and monitor patients, it's possible that babies may be 77 00:04:32,800 --> 00:04:36,440 Speaker 1: born with disabilities or health effects that aren't ever reported 78 00:04:36,520 --> 00:04:39,800 Speaker 1: or connected back to the drug. Even in places that 79 00:04:39,880 --> 00:04:43,600 Speaker 1: do have really robust medical systems. The level of monitoring 80 00:04:43,680 --> 00:04:46,400 Speaker 1: and compliance involved with this can really be a lot. 81 00:04:46,920 --> 00:04:50,200 Speaker 1: Sometimes it is just not sustainable in real world conditions. 82 00:04:50,720 --> 00:04:53,200 Speaker 1: But none of these steps were in place when the 83 00:04:53,279 --> 00:04:56,279 Speaker 1: lita mine was developed, and no one knew about its 84 00:04:56,320 --> 00:04:58,839 Speaker 1: teratogenic effects when it was first put on the market. 85 00:04:59,440 --> 00:05:01,400 Speaker 1: So we're going to get into why that was in 86 00:05:01,400 --> 00:05:04,200 Speaker 1: a moment, but first we're going to have an overview 87 00:05:04,240 --> 00:05:07,760 Speaker 1: of the conditions and disabilities that the litamide causes in 88 00:05:07,800 --> 00:05:11,800 Speaker 1: a developing fetus. So the condition that's most associated with 89 00:05:11,880 --> 00:05:14,960 Speaker 1: the litamide is folk amelia, and that's when the bones 90 00:05:15,000 --> 00:05:18,880 Speaker 1: and a person's limbs are shortened or missing. This usually 91 00:05:18,920 --> 00:05:21,760 Speaker 1: affects the long bones and the arms and the legs, 92 00:05:21,800 --> 00:05:24,440 Speaker 1: so sometimes it results in the hands or the feet 93 00:05:24,480 --> 00:05:26,800 Speaker 1: being connected to the trunk of the body without a 94 00:05:26,880 --> 00:05:31,360 Speaker 1: limb in between. Most of the time these effects are symmetrical, 95 00:05:31,480 --> 00:05:35,440 Speaker 1: with both legs or both arms or all four limbs affected, 96 00:05:35,520 --> 00:05:39,000 Speaker 1: and the arms are affected the most often with the litamide. 97 00:05:39,320 --> 00:05:43,080 Speaker 1: The litamide can also cause a similar condition called amelia, 98 00:05:43,320 --> 00:05:46,440 Speaker 1: or the total absence of the limb. The litamide can 99 00:05:46,480 --> 00:05:50,120 Speaker 1: also affect a person's digits, including having extra or missing 100 00:05:50,120 --> 00:05:53,560 Speaker 1: fingers or toes. Sometimes the size and shape of the 101 00:05:53,600 --> 00:05:56,240 Speaker 1: bones can also cause the hands or feet to have 102 00:05:56,400 --> 00:05:59,359 Speaker 1: a different size or shape than a typical hand or foot. 103 00:05:59,800 --> 00:06:02,120 Speaker 1: The eyes and the ears can be affected as well. 104 00:06:02,400 --> 00:06:05,839 Speaker 1: They might be missing completely or missing parts of their structures, 105 00:06:05,880 --> 00:06:08,440 Speaker 1: and that can cause problems with a vision or hearing, 106 00:06:08,600 --> 00:06:12,000 Speaker 1: as well as blindness and deafness. These are the most 107 00:06:12,120 --> 00:06:16,120 Speaker 1: outwardly visible effects of the litamide exposure in utero, but 108 00:06:16,200 --> 00:06:20,279 Speaker 1: the drug can also cause internal organ damage, including heart, kidney, 109 00:06:20,600 --> 00:06:23,640 Speaker 1: nervous system, and g I problems, as well as damage 110 00:06:23,720 --> 00:06:27,120 Speaker 1: to the reproductive organs, and sometimes this is not immediately 111 00:06:27,160 --> 00:06:30,640 Speaker 1: apparent at birth, even after a medical examination, so these 112 00:06:30,680 --> 00:06:34,200 Speaker 1: conditions are then discovered later in life. People who are 113 00:06:34,240 --> 00:06:37,719 Speaker 1: exposed to the litamide before birth also have higher rates 114 00:06:37,720 --> 00:06:43,000 Speaker 1: of cognitive disabilities and epilepsy. Altogether, these and other effects 115 00:06:43,000 --> 00:06:45,400 Speaker 1: of the litamite exposure in the womb are known as 116 00:06:45,440 --> 00:06:49,680 Speaker 1: the litamide embryopathy or fetal the litamide syndrome. Most of 117 00:06:49,720 --> 00:06:53,359 Speaker 1: the research into the litamides effects was conducted on infants 118 00:06:53,400 --> 00:06:56,360 Speaker 1: in the nineteen sixties, and there hasn't been nearly as 119 00:06:56,440 --> 00:06:59,560 Speaker 1: much follow up from the medical community as people have 120 00:06:59,680 --> 00:07:02,840 Speaker 1: grown own and aged, so it's really possible that there 121 00:07:02,839 --> 00:07:06,160 Speaker 1: are other delayed effects that haven't been widely studied or 122 00:07:06,200 --> 00:07:09,600 Speaker 1: traced back to the litamide. One exception is whether the 123 00:07:09,640 --> 00:07:13,000 Speaker 1: litamides effects can be passed down to a person's children, 124 00:07:13,280 --> 00:07:17,360 Speaker 1: and the litamized effects don't appear to be inheritable. These 125 00:07:17,440 --> 00:07:20,040 Speaker 1: are a lot of different effects for one drug to cause, 126 00:07:20,200 --> 00:07:23,280 Speaker 1: and many people have several of them, and that's largely 127 00:07:23,320 --> 00:07:26,480 Speaker 1: tied to exactly when during the pregnancy that the litamite 128 00:07:26,520 --> 00:07:29,560 Speaker 1: exposure happened and what was developing within the embryo or 129 00:07:29,600 --> 00:07:33,080 Speaker 1: fetus at that time. The litamides effects tend to be 130 00:07:33,160 --> 00:07:36,640 Speaker 1: the most severe between twenty and thirty six days after conception. 131 00:07:37,440 --> 00:07:40,320 Speaker 1: At this point in pregnancy, things are moving very quickly, 132 00:07:40,400 --> 00:07:43,560 Speaker 1: with lots of growing and development happening in multiple body 133 00:07:43,600 --> 00:07:47,480 Speaker 1: systems all at once. Just one dose of the lidamide 134 00:07:47,520 --> 00:07:51,160 Speaker 1: can disrupt all of this, causing multiple negative health effects 135 00:07:51,280 --> 00:07:55,240 Speaker 1: or disabilities in at least fifty of pregnancies, and some 136 00:07:55,280 --> 00:07:58,080 Speaker 1: studies suggest at that rate is actually even higher than that, 137 00:07:58,400 --> 00:08:00,720 Speaker 1: and this is why the litamite it's use as a 138 00:08:00,840 --> 00:08:05,640 Speaker 1: morning sickness treatment affected so many people. So dramatically. Morning 139 00:08:05,680 --> 00:08:09,320 Speaker 1: sickness occurs in about sevent pregnancies, and it can happen 140 00:08:09,360 --> 00:08:11,360 Speaker 1: at any time of the day and at any point 141 00:08:11,440 --> 00:08:14,160 Speaker 1: during the pregnancy, but it's really the most common in 142 00:08:14,200 --> 00:08:17,920 Speaker 1: the first trimester. It's usually the worst from four to 143 00:08:18,080 --> 00:08:22,000 Speaker 1: seven weeks after conception, and that largely overlaps with the 144 00:08:22,040 --> 00:08:25,480 Speaker 1: window when the lidamides effects are also the most severe 145 00:08:25,920 --> 00:08:28,280 Speaker 1: and affect the most parts of the body. So we're 146 00:08:28,320 --> 00:08:30,560 Speaker 1: going to talk about how Solida Mine made it to 147 00:08:30,600 --> 00:08:34,120 Speaker 1: market without anyone discovering any of this after we first 148 00:08:34,160 --> 00:08:46,640 Speaker 1: pause for a sponsor break. Internationally, the pharmaceutical industry really 149 00:08:46,679 --> 00:08:50,000 Speaker 1: expanded dramatically after the end of World War two. People 150 00:08:50,040 --> 00:08:53,079 Speaker 1: needed treatments for illnesses and injuries that had resulted from 151 00:08:53,080 --> 00:08:57,520 Speaker 1: the war. Multiple countries had started establishing national health care 152 00:08:57,559 --> 00:08:59,720 Speaker 1: systems in the decades that we're leading up to the 153 00:08:59,760 --> 00:09:02,800 Speaker 1: war and then afterward, and that led to more demand 154 00:09:02,880 --> 00:09:07,080 Speaker 1: for medicines overall. There were also breakthroughs and various types 155 00:09:07,120 --> 00:09:11,760 Speaker 1: of medicines, including antibiotics and anti anxiety medications, and those 156 00:09:11,840 --> 00:09:15,360 Speaker 1: had also led pharmaceutical companies to develop new drugs very 157 00:09:15,440 --> 00:09:19,920 Speaker 1: aggressively to try to compete sedatives in particular, became incredibly 158 00:09:19,960 --> 00:09:23,960 Speaker 1: popular as a newly developed class of drugs. The sedative 159 00:09:24,000 --> 00:09:26,800 Speaker 1: known as Milltown was launched in nineteen fifty five, and 160 00:09:26,840 --> 00:09:30,520 Speaker 1: it quickly became the best selling drug in the United States. 161 00:09:31,240 --> 00:09:34,000 Speaker 1: Drug manufacturers around the world we're trying to break into 162 00:09:34,040 --> 00:09:37,000 Speaker 1: this fast growing segment of the drug market, hoping for 163 00:09:37,040 --> 00:09:41,000 Speaker 1: a similar success of their own. West German pharmaceutical company 164 00:09:41,080 --> 00:09:45,080 Speaker 1: Shami grunenthalogy mbH was founded in nineteen forty six and 165 00:09:45,200 --> 00:09:48,160 Speaker 1: was one of the companies trying to rapidly develop new 166 00:09:48,240 --> 00:09:51,600 Speaker 1: drugs and bring them to market. In nineteen fifty four, 167 00:09:51,640 --> 00:09:53,880 Speaker 1: they synthesized the drug that would come to be known 168 00:09:53,920 --> 00:09:56,160 Speaker 1: as the litamided for the first time and they applied 169 00:09:56,200 --> 00:10:00,480 Speaker 1: for a patent. A paper describing the drugs pharmacological effects, 170 00:10:00,480 --> 00:10:03,839 Speaker 1: including its sedative effects, was published in nineteen fifty six, 171 00:10:04,360 --> 00:10:07,720 Speaker 1: and that paper, it was referred to as K seventeen, 172 00:10:08,360 --> 00:10:11,440 Speaker 1: was also when Grunenthal conducted some safety tests on this 173 00:10:11,480 --> 00:10:14,079 Speaker 1: new drug, and one of the tests that was conducted 174 00:10:14,240 --> 00:10:17,640 Speaker 1: is called the median lethal dose or LD fifty test, 175 00:10:18,080 --> 00:10:20,959 Speaker 1: and this test is conducted on lab animals and it's 176 00:10:21,040 --> 00:10:23,880 Speaker 1: used to determine how much of a substance it takes 177 00:10:23,880 --> 00:10:26,880 Speaker 1: for it to become deadly. The l D fifty is 178 00:10:26,880 --> 00:10:29,120 Speaker 1: the amount of the substance that it takes to kill 179 00:10:29,160 --> 00:10:32,840 Speaker 1: fifty of the test subjects. The LD fifty tests for 180 00:10:32,960 --> 00:10:36,160 Speaker 1: the litamide were conducted on mice and they suggested that 181 00:10:36,200 --> 00:10:39,280 Speaker 1: there was no dose, no matter how high, that would 182 00:10:39,280 --> 00:10:42,440 Speaker 1: be lethal and fifty percent of the subjects. Everyone thought 183 00:10:42,440 --> 00:10:44,960 Speaker 1: this was amazing in terms of the folks developing it. 184 00:10:44,960 --> 00:10:48,440 Speaker 1: It's set the litamide apart from other sedatives and sleep aids, 185 00:10:48,480 --> 00:10:51,599 Speaker 1: which could be lethal at high doses, like an overdose 186 00:10:51,679 --> 00:10:55,640 Speaker 1: could cause someone to die. Based on these results, Grudenthal 187 00:10:55,640 --> 00:10:59,200 Speaker 1: started marketing this drug as safe and non toxic. In 188 00:10:59,240 --> 00:11:02,840 Speaker 1: November of eighteen fifty six, Grunenthal began marketing a flu 189 00:11:02,960 --> 00:11:07,199 Speaker 1: remedy called grip X, which combines solidamined with other substances 190 00:11:07,240 --> 00:11:11,320 Speaker 1: like quinine and vitamin C. In ninety seven, it launched 191 00:11:11,360 --> 00:11:15,320 Speaker 1: several versions of a drug called coundragone, which was solidimized 192 00:11:15,400 --> 00:11:18,880 Speaker 1: for use as a daytime sedative or a nintime sleep aid. 193 00:11:19,600 --> 00:11:23,560 Speaker 1: Grip X and coundragone were available without a prescription. The 194 00:11:23,640 --> 00:11:25,520 Speaker 1: idea that you could just go to a pharmacy in 195 00:11:25,600 --> 00:11:28,920 Speaker 1: nineteen fifty seven and get a sedative over the counter 196 00:11:29,840 --> 00:11:34,040 Speaker 1: marketed as a sedative blows my mind just a little bit. Yeah, same, 197 00:11:34,679 --> 00:11:37,120 Speaker 1: I don't I don't know what to add to there. 198 00:11:37,480 --> 00:11:40,319 Speaker 1: There are plenty of drugs that have sleepiness or drowsiness 199 00:11:40,320 --> 00:11:42,800 Speaker 1: as a side effect, but like, if that's in the 200 00:11:42,920 --> 00:11:45,200 Speaker 1: US at least, you can't just walk up to a 201 00:11:45,280 --> 00:11:47,920 Speaker 1: counter and say I would like a sedative please and 202 00:11:47,960 --> 00:11:50,160 Speaker 1: get one. In many parts of the world, in the 203 00:11:50,240 --> 00:11:53,600 Speaker 1: nineteen fifties, it was common for doctors to prescribe or 204 00:11:53,600 --> 00:11:56,520 Speaker 1: recommend a variety of medicines of pregnant patients for the 205 00:11:56,520 --> 00:11:59,320 Speaker 1: sake of their physical comfort and mental health, and this 206 00:11:59,400 --> 00:12:04,400 Speaker 1: included sedatives and stimulants and other medications. The prevailing attitudes 207 00:12:04,440 --> 00:12:07,719 Speaker 1: about both prescription and over the counter medicines during pregnancy 208 00:12:07,800 --> 00:12:11,360 Speaker 1: was pretty cavalier compared to how it is today, and 209 00:12:11,440 --> 00:12:15,000 Speaker 1: soon after Contragone hit the market, patients and doctors started 210 00:12:15,040 --> 00:12:18,400 Speaker 1: reporting that it wasn't just providing RESTful sleep or a 211 00:12:18,480 --> 00:12:22,600 Speaker 1: calmer mood during pregnancy, it was also treating mourning sickness. 212 00:12:23,400 --> 00:12:27,000 Speaker 1: Soon doctors were recommending contragone for the off label use 213 00:12:27,080 --> 00:12:30,920 Speaker 1: of mourning sickness treatment and prevention. Patients who had taken 214 00:12:30,920 --> 00:12:33,640 Speaker 1: it were also recommending it to their pregnant friends and 215 00:12:33,760 --> 00:12:37,720 Speaker 1: family members. I mean, people who took this drug described 216 00:12:37,720 --> 00:12:41,200 Speaker 1: as being miraculous in terms of the difference that it 217 00:12:41,240 --> 00:12:44,240 Speaker 1: made in the morning sickness level. But none of the 218 00:12:44,280 --> 00:12:47,160 Speaker 1: tests that had been performed on solidamide before it was 219 00:12:47,200 --> 00:12:51,240 Speaker 1: released were conducted on pregnant animals, and even if they 220 00:12:51,280 --> 00:12:53,959 Speaker 1: had been, it turns out that mice and rats aren't 221 00:12:54,000 --> 00:12:57,240 Speaker 1: susceptible to solidamide in the same way that humans and 222 00:12:57,320 --> 00:13:00,320 Speaker 1: many other mammals are. Although there had been and some 223 00:13:00,360 --> 00:13:04,400 Speaker 1: clinical trials, no one in them had been pregnant. Also, 224 00:13:04,440 --> 00:13:08,520 Speaker 1: the clinical trials themselves were very small and not very thorough. 225 00:13:09,160 --> 00:13:12,080 Speaker 1: Testing on some other sedatives at this time had involved 226 00:13:12,080 --> 00:13:16,080 Speaker 1: things like examining the urine to analyze how the drug 227 00:13:16,120 --> 00:13:18,960 Speaker 1: had been broken down inside the body and how much 228 00:13:18,960 --> 00:13:21,760 Speaker 1: of the drug was being excreted without being broken down 229 00:13:21,800 --> 00:13:25,760 Speaker 1: at all. Nothing like this was performed for the litamide. 230 00:13:25,920 --> 00:13:28,839 Speaker 1: It also doesn't appear that these clinical trials were double 231 00:13:28,880 --> 00:13:32,199 Speaker 1: blind or involved any kind of comparison between the drug 232 00:13:32,240 --> 00:13:35,280 Speaker 1: anniple cebo. On top of that, the papers that were 233 00:13:35,280 --> 00:13:39,000 Speaker 1: published to support the litamide safety and efficacy read more 234 00:13:39,080 --> 00:13:42,480 Speaker 1: like doctors testimonials than research that was actually backed up 235 00:13:42,480 --> 00:13:46,120 Speaker 1: by data. Vitikin Lens, who was one of the doctors 236 00:13:46,120 --> 00:13:50,040 Speaker 1: who made the connection between the litamide and its teratogenic effects, 237 00:13:50,120 --> 00:13:53,400 Speaker 1: later said quote the papers published in nineteen fifty six 238 00:13:53,400 --> 00:13:56,520 Speaker 1: by Kun's at All on animal experiments and by Young 239 00:13:56,640 --> 00:14:01,040 Speaker 1: on clinical experiences with the linamide have so little scientific 240 00:14:01,120 --> 00:14:03,719 Speaker 1: value that, in my opinion, they should not have been 241 00:14:03,760 --> 00:14:07,040 Speaker 1: accepted for print. In other words, all this testing was 242 00:14:07,120 --> 00:14:11,920 Speaker 1: not very thorough or rigorous or well documented. Just one 243 00:14:12,040 --> 00:14:14,360 Speaker 1: example of how it all fell short is that it 244 00:14:14,440 --> 00:14:16,920 Speaker 1: later turned out that the reason that they could not 245 00:14:17,040 --> 00:14:21,000 Speaker 1: find a lethal dose of the litamide and mice wasn't 246 00:14:21,040 --> 00:14:24,880 Speaker 1: because the drug was inherently safe. It was because the 247 00:14:24,960 --> 00:14:29,640 Speaker 1: mice weren't actually absorbing most of it. Different preparations of 248 00:14:29,640 --> 00:14:32,120 Speaker 1: the drug that were tested later on and were more 249 00:14:32,160 --> 00:14:35,520 Speaker 1: easily absorbed turned out to be highly toxic. Based on 250 00:14:35,560 --> 00:14:39,040 Speaker 1: the litamide success in West Germany, Grunenthal began working on 251 00:14:39,120 --> 00:14:41,920 Speaker 1: distributing it to other parts of the world. It was 252 00:14:42,040 --> 00:14:46,080 Speaker 1: ultimately marketed and distributed through various other pharmaceutical companies in 253 00:14:46,200 --> 00:14:49,800 Speaker 1: forty six different countries under a range of brand names, 254 00:14:49,880 --> 00:14:53,240 Speaker 1: including dist of All in the UK and Australia and 255 00:14:53,320 --> 00:14:56,360 Speaker 1: soften On in parts of Europe. As all of that 256 00:14:56,480 --> 00:14:59,680 Speaker 1: was happening, doctors in places where the litamide was being 257 00:15:00,040 --> 00:15:02,960 Speaker 1: used to treat morning sickness, we're starting to encounter babies 258 00:15:03,000 --> 00:15:05,800 Speaker 1: who had a collection of health problems and disabilities that 259 00:15:05,800 --> 00:15:09,360 Speaker 1: they'd never really seen before. In nineteen fifty nine, a 260 00:15:09,360 --> 00:15:12,920 Speaker 1: gynecologist in Munich reported a baby born with folk amelia. 261 00:15:13,400 --> 00:15:16,280 Speaker 1: There wasn't a clear connection at that time, but later 262 00:15:16,360 --> 00:15:18,800 Speaker 1: on the doctor learned that the baby's mother had taken 263 00:15:18,840 --> 00:15:22,920 Speaker 1: gripp X while pregnant. This wasn't actually the earliest documented 264 00:15:23,000 --> 00:15:27,120 Speaker 1: case of solidamide having a teratogenic effect, That had happened 265 00:15:27,120 --> 00:15:29,720 Speaker 1: back in December of nineteen fifty six, before the drug 266 00:15:29,800 --> 00:15:32,600 Speaker 1: was even on the market. This case was a baby 267 00:15:32,680 --> 00:15:35,920 Speaker 1: born to a Grunenthal employee and his wife, and he 268 00:15:35,960 --> 00:15:38,800 Speaker 1: had been given free samples at work and their child 269 00:15:38,960 --> 00:15:42,720 Speaker 1: was born without ears. That connection was not uncovered until 270 00:15:42,800 --> 00:15:46,200 Speaker 1: much later. So at first doctors were reporting what they 271 00:15:46,200 --> 00:15:50,600 Speaker 1: described as this strange epidemic of folk amelia, but they 272 00:15:50,640 --> 00:15:54,600 Speaker 1: weren't really sure what was causing it, as that was happening, though, 273 00:15:54,720 --> 00:15:58,120 Speaker 1: doctors were noticing a different pattern and adults who were 274 00:15:58,120 --> 00:16:02,040 Speaker 1: taking the lidamide. As ly as April of nineteen fifty nine, 275 00:16:02,120 --> 00:16:06,080 Speaker 1: pharmacists were reporting that patients were experiencing things like tingling 276 00:16:06,200 --> 00:16:09,360 Speaker 1: hands and feet, or cold hands and feet, or a 277 00:16:09,400 --> 00:16:13,040 Speaker 1: sense of giddiness after taking the litamide. In October of 278 00:16:13,120 --> 00:16:17,000 Speaker 1: nineteen fifty nine, a doctor named Ralph Voss reported neuritis 279 00:16:17,280 --> 00:16:20,480 Speaker 1: or nerve inflammation and people who had taken contragne for 280 00:16:20,560 --> 00:16:25,000 Speaker 1: a year. Voss contacted Grunenthal, who told him quote, no 281 00:16:25,120 --> 00:16:28,680 Speaker 1: such side effects have come to our notice. Another doctor 282 00:16:28,760 --> 00:16:31,880 Speaker 1: named Horse Frankel was also working with patients that were 283 00:16:31,920 --> 00:16:36,080 Speaker 1: experiencing nearitis after taking the litamine. He wrote a paper 284 00:16:36,120 --> 00:16:40,080 Speaker 1: detailing twenty cases, but for unclear reasons, it wasn't printed 285 00:16:40,160 --> 00:16:45,040 Speaker 1: until nineteen sixty one. Meanwhile, Voss delivered a presentation on 286 00:16:45,080 --> 00:16:49,520 Speaker 1: the naritis issue on April nineteen sixty In December of 287 00:16:49,560 --> 00:16:52,680 Speaker 1: that year, a letter titled is the litamide to blame 288 00:16:52,840 --> 00:16:56,040 Speaker 1: was printed in the British Medical Journal. It was written 289 00:16:56,080 --> 00:17:00,400 Speaker 1: by A Leslie Florence of Aberdeenshire, and it described four 290 00:17:00,440 --> 00:17:05,320 Speaker 1: cases of tingling, cold extremities, leg cramps, and other side effects, 291 00:17:05,320 --> 00:17:09,399 Speaker 1: and adult patients taking the lidamide, these improved, but they 292 00:17:09,400 --> 00:17:13,080 Speaker 1: didn't really go away when the patients stopped taking the drug. 293 00:17:13,520 --> 00:17:16,320 Speaker 1: The letter included the line quote it would appear that 294 00:17:16,400 --> 00:17:20,280 Speaker 1: these symptoms could possibly be a toxic effect of the lidamide. 295 00:17:20,680 --> 00:17:24,080 Speaker 1: By May of nineteen sixty one, Grudenthal had received reports 296 00:17:24,119 --> 00:17:27,080 Speaker 1: of more than one thousand cases of neuritis that were 297 00:17:27,119 --> 00:17:30,600 Speaker 1: connected to thelidamide. The company was forced to make the 298 00:17:30,640 --> 00:17:34,760 Speaker 1: drug available only by prescription. Before that point, it had 299 00:17:34,760 --> 00:17:37,960 Speaker 1: been responsible for more than half of the company's gross revenues, 300 00:17:38,080 --> 00:17:41,720 Speaker 1: and it was West Germany's most popular over the counter sedative, 301 00:17:42,000 --> 00:17:46,280 Speaker 1: with more than twenty million tablets sold each month. Even 302 00:17:46,359 --> 00:17:49,480 Speaker 1: after these reports of neurological side effects and after it 303 00:17:49,520 --> 00:17:54,240 Speaker 1: became available only by prescription, Grunenthal continued to market solidamide 304 00:17:54,280 --> 00:17:58,639 Speaker 1: as completely safe, even during pregnancy. So we should note 305 00:17:58,640 --> 00:18:01,679 Speaker 1: that even today, it is very common for a drug's 306 00:18:01,680 --> 00:18:04,960 Speaker 1: side effects, including some very serious side effects, to be 307 00:18:05,000 --> 00:18:08,040 Speaker 1: discovered after the drug is approved and out on the market, 308 00:18:08,720 --> 00:18:12,600 Speaker 1: even when they're meticulously controlled and carefully planned out. Clinical 309 00:18:12,640 --> 00:18:16,479 Speaker 1: trials are very small compared to the general population, and 310 00:18:16,520 --> 00:18:18,720 Speaker 1: the real world has a lot of factors that might 311 00:18:18,760 --> 00:18:22,080 Speaker 1: not be present in the context of a controlled study. 312 00:18:22,119 --> 00:18:25,880 Speaker 1: But it's clear that Grunenthal's original testing on the litamide 313 00:18:25,920 --> 00:18:28,959 Speaker 1: was not very thorough, and the company does not appear 314 00:18:29,000 --> 00:18:31,480 Speaker 1: to have looked into whether all these reports of near 315 00:18:31,560 --> 00:18:34,600 Speaker 1: rytis pointed to a greater problem with the drug. And 316 00:18:34,680 --> 00:18:38,159 Speaker 1: in nineteen sixty one doctors started making connections between the 317 00:18:38,200 --> 00:18:42,119 Speaker 1: litamide as used for morning sickness and the drugs teratogenic effects. 318 00:18:42,600 --> 00:18:45,880 Speaker 1: One was the German doctor vitikin Lens who we mentioned earlier, 319 00:18:46,119 --> 00:18:49,240 Speaker 1: and he had noticed the unusual increase in phok melia 320 00:18:49,359 --> 00:18:51,480 Speaker 1: and other conditions that we now know as part of 321 00:18:51,480 --> 00:18:55,320 Speaker 1: fetal the litamide syndrome. He went back through medical records 322 00:18:55,359 --> 00:18:57,920 Speaker 1: and he found that this pattern had started very suddenly. 323 00:18:58,520 --> 00:19:01,119 Speaker 1: He didn't initially know what the exact cause was, but 324 00:19:01,200 --> 00:19:03,480 Speaker 1: he was confident that there was one, and that it 325 00:19:03,560 --> 00:19:06,639 Speaker 1: might be some kind of chemical exposure, like an undisclosed 326 00:19:06,680 --> 00:19:10,520 Speaker 1: chemical spill, or perhaps a new household product. Thousands of 327 00:19:10,560 --> 00:19:14,080 Speaker 1: miles away. Dr William McBride was working at a hospital 328 00:19:14,119 --> 00:19:17,480 Speaker 1: in Australia and on May fourth, nineteen sixty one, a 329 00:19:17,600 --> 00:19:21,119 Speaker 1: baby was born there with both folk Amelia and bowel atresia, 330 00:19:21,200 --> 00:19:23,560 Speaker 1: which is a condition in which part of the bowel 331 00:19:23,680 --> 00:19:27,600 Speaker 1: is blocked are absent. Thousands of babies were born every 332 00:19:27,640 --> 00:19:29,920 Speaker 1: year at the hospital, but this was the first time 333 00:19:29,960 --> 00:19:32,280 Speaker 1: in its history that a baby had been born with 334 00:19:32,320 --> 00:19:36,400 Speaker 1: that combination of conditions. Two more babies with folk amelia 335 00:19:36,520 --> 00:19:39,960 Speaker 1: and bowel atricia were born between May fourth and June eight. 336 00:19:40,640 --> 00:19:44,159 Speaker 1: McBride realized all three had been exposed to the lidamide, 337 00:19:44,320 --> 00:19:46,679 Speaker 1: which had been on the market in Australia since June 338 00:19:46,680 --> 00:19:50,679 Speaker 1: of nineteen sixty. On June he convinced the hospital to 339 00:19:50,760 --> 00:19:54,920 Speaker 1: withdraw the litamide from use and informed the drug company Distillers, 340 00:19:55,160 --> 00:19:58,439 Speaker 1: which was distributing the litamide in Australia. This was the 341 00:19:58,480 --> 00:20:01,800 Speaker 1: first published letter specif typically linking the litamide to its 342 00:20:01,880 --> 00:20:05,720 Speaker 1: teratogenic effects. McBride later told The New York Times that 343 00:20:05,760 --> 00:20:08,960 Speaker 1: he also wrote to the company headquarters in London, but 344 00:20:09,080 --> 00:20:12,119 Speaker 1: quote the reply from the medical director of the London 345 00:20:12,160 --> 00:20:15,919 Speaker 1: office implied that I was utterly wrong. His high handed 346 00:20:16,040 --> 00:20:18,919 Speaker 1: letter implying that I was just a colonial annoyed me. 347 00:20:19,359 --> 00:20:22,640 Speaker 1: I was determined to prove I was right. The following month, 348 00:20:22,760 --> 00:20:26,720 Speaker 1: Dr Hans Vicker documented twenty babies with folk amelia, five 349 00:20:26,760 --> 00:20:28,800 Speaker 1: of which were known to have been exposed to the 350 00:20:28,880 --> 00:20:32,040 Speaker 1: lidamide in the womb. But Viker had been told in 351 00:20:32,280 --> 00:20:34,919 Speaker 1: error that the litamide was being used very widely in 352 00:20:34,920 --> 00:20:38,119 Speaker 1: the US, but that the US was not experiencing the 353 00:20:38,119 --> 00:20:41,960 Speaker 1: folk amelia epidemic that other countries were. He learned from 354 00:20:42,000 --> 00:20:44,320 Speaker 1: Dr Lens that this was not true, and when he 355 00:20:44,359 --> 00:20:48,080 Speaker 1: went back through his records specifically looking for the litamide, 356 00:20:48,200 --> 00:20:51,840 Speaker 1: he confirmed its use in even more cases. After his 357 00:20:51,920 --> 00:20:56,119 Speaker 1: communication with Viker, Lens called Grunenthal and was told to 358 00:20:56,160 --> 00:20:59,040 Speaker 1: expect a visit from somebody in a few days. He 359 00:20:59,200 --> 00:21:02,159 Speaker 1: told them that the needed attention immediately, that in a 360 00:21:02,200 --> 00:21:05,000 Speaker 1: few days hundreds more people could be taking this drug 361 00:21:05,040 --> 00:21:08,640 Speaker 1: for the first time. Lens also sent a registered letter 362 00:21:08,720 --> 00:21:12,040 Speaker 1: to the company on November sixteenth, nineteen sixty one, detailing 363 00:21:12,080 --> 00:21:16,919 Speaker 1: his concerns. Meanwhile, in Australia, drug company distillers removed the 364 00:21:16,960 --> 00:21:20,080 Speaker 1: litamide from the market on November twenty one. It was 365 00:21:20,160 --> 00:21:23,520 Speaker 1: only after all this that Grudenthal finally took action, pulling 366 00:21:23,560 --> 00:21:27,800 Speaker 1: the litamide off the German market on November nineteen sixty one. 367 00:21:28,160 --> 00:21:30,639 Speaker 1: As words spread, it was taken off the market in 368 00:21:30,680 --> 00:21:35,359 Speaker 1: the UK on December two. On December sixteenth, Solidamide and 369 00:21:35,400 --> 00:21:39,639 Speaker 1: Congenital Abnormalities was published in The Lancet. The lidamide was 370 00:21:39,680 --> 00:21:41,879 Speaker 1: taken off the market in more countries in the weeks 371 00:21:41,880 --> 00:21:45,680 Speaker 1: that followed. It was banned worldwide in nineteen sixty two, 372 00:21:45,720 --> 00:21:49,040 Speaker 1: although in some places it was not formally made illegal 373 00:21:49,119 --> 00:21:52,280 Speaker 1: until much later. It was only after all of this 374 00:21:52,440 --> 00:21:54,679 Speaker 1: that there was any kind of formal study of the 375 00:21:54,720 --> 00:21:58,600 Speaker 1: litamide and pregnant animals. Dr McBride had actually tried to 376 00:21:58,600 --> 00:22:00,920 Speaker 1: do this in Australia, but he didn't really have any 377 00:22:00,960 --> 00:22:03,439 Speaker 1: experience in how to perform this kind of trial or 378 00:22:03,640 --> 00:22:05,960 Speaker 1: access to the lab animals that he would need to 379 00:22:06,080 --> 00:22:08,919 Speaker 1: do it. The results of this study were published in 380 00:22:08,920 --> 00:22:12,359 Speaker 1: a letter to The Lancet on April nineteen sixty two, 381 00:22:12,400 --> 00:22:15,800 Speaker 1: showing that the litamide had similar to ratogenic effects and 382 00:22:15,880 --> 00:22:18,640 Speaker 1: rabbits as it was now clear to be having in humans. 383 00:22:18,960 --> 00:22:21,119 Speaker 1: We're going to talk about the aftermath of all of this, 384 00:22:21,359 --> 00:22:23,600 Speaker 1: and about why the US isn't one of the countries 385 00:22:23,600 --> 00:22:26,280 Speaker 1: that we have talked about so far. After we first 386 00:22:26,280 --> 00:22:37,200 Speaker 1: paused for another sponsor break between nineteen fifty seven and 387 00:22:37,320 --> 00:22:40,399 Speaker 1: nineteen sixty two, The litamide was sold in forty six 388 00:22:40,440 --> 00:22:43,640 Speaker 1: different countries around the world, but it was never officially 389 00:22:43,640 --> 00:22:48,240 Speaker 1: introduced in the United States. Richardson Meryl, the drug company, 390 00:22:48,280 --> 00:22:51,280 Speaker 1: had planned to distribute the litamide in the US under 391 00:22:51,320 --> 00:22:54,960 Speaker 1: the trade named Kevi Don Meryl submitted an application to 392 00:22:55,000 --> 00:22:57,840 Speaker 1: the Food and Drug Administration. At that time, the US 393 00:22:57,880 --> 00:23:01,320 Speaker 1: did have some laws that we're governing the drug approval process. 394 00:23:01,680 --> 00:23:05,399 Speaker 1: That application was given to Dr Francis Oldham Kelsey to review. 395 00:23:05,920 --> 00:23:09,360 Speaker 1: Kelsey was born on Vancouver Island in British Columbia, Canada, 396 00:23:09,760 --> 00:23:12,840 Speaker 1: and she had first started studying unsafe pharmaceuticals while she 397 00:23:12,920 --> 00:23:16,040 Speaker 1: was a graduate student at the University of Chicago, and 398 00:23:16,080 --> 00:23:19,120 Speaker 1: there she earned both her PhD and her medical degree. 399 00:23:19,440 --> 00:23:22,240 Speaker 1: At the university, Dr Eugene Galing was trying to figure 400 00:23:22,240 --> 00:23:24,359 Speaker 1: out what had caused the deaths of more than one 401 00:23:24,560 --> 00:23:27,040 Speaker 1: d people who had taken a drug called Elixir of 402 00:23:27,040 --> 00:23:30,160 Speaker 1: Sulfonilla mine, and Kelsey was one of the graduate students 403 00:23:30,200 --> 00:23:33,120 Speaker 1: who helped pinpoint the cause as a solvent that had 404 00:23:33,160 --> 00:23:36,119 Speaker 1: been used to add a raspberry flavor to make the 405 00:23:36,200 --> 00:23:39,240 Speaker 1: drug less bitter. Kelsey was really new to the job 406 00:23:39,280 --> 00:23:41,639 Speaker 1: as a drug application reviewer at the f d A. 407 00:23:42,200 --> 00:23:45,040 Speaker 1: The kevin On application was only the second one that 408 00:23:45,119 --> 00:23:47,240 Speaker 1: she had been given, and in her account, it was 409 00:23:47,280 --> 00:23:49,040 Speaker 1: given to her because she was new and it was 410 00:23:49,080 --> 00:23:52,359 Speaker 1: supposed to be an easy one. The littamide was already 411 00:23:52,400 --> 00:23:54,760 Speaker 1: being used in countries all over the world. It was 412 00:23:54,800 --> 00:23:58,080 Speaker 1: regarded as completely safe, so really this process seemed like 413 00:23:58,080 --> 00:24:02,760 Speaker 1: a formality. But when Kelsey started reviewing the application, sheep 414 00:24:02,840 --> 00:24:06,359 Speaker 1: had some concerns about the litamne safety testing, a lot 415 00:24:06,440 --> 00:24:09,359 Speaker 1: of those same problems that we talked about before, and 416 00:24:09,400 --> 00:24:12,040 Speaker 1: after some back and forth with Meryl, she rejected the 417 00:24:12,080 --> 00:24:17,280 Speaker 1: application on November tenth, nineteen sixty. Meryl reapplied in December. 418 00:24:17,359 --> 00:24:19,840 Speaker 1: Kelsey read the letter in the British Medical Journal about 419 00:24:19,960 --> 00:24:22,480 Speaker 1: neuropathy and people that had taken the lidomide, which he 420 00:24:22,520 --> 00:24:25,840 Speaker 1: talked about before the break. She pushed back on Meryl, 421 00:24:25,960 --> 00:24:29,440 Speaker 1: noting that a simple sleep age shouldn't be causing neuropathy 422 00:24:29,480 --> 00:24:31,840 Speaker 1: and that a drug that was causing neuropathy could not 423 00:24:31,960 --> 00:24:35,240 Speaker 1: be as safe and non toxic as the company was claiming. 424 00:24:35,720 --> 00:24:38,639 Speaker 1: This went back and forth for weeks. At one point 425 00:24:38,720 --> 00:24:42,679 Speaker 1: Kelsey met with executives from the company and, in her words, quote, 426 00:24:42,960 --> 00:24:45,080 Speaker 1: I had the feeling throughout the day that they were 427 00:24:45,160 --> 00:24:48,520 Speaker 1: at no time being wholly frank with me. As Kelsey 428 00:24:48,560 --> 00:24:52,399 Speaker 1: continued to refuse to approve the kevidan application, more and 429 00:24:52,520 --> 00:24:55,320 Speaker 1: more information was coming out about the effects that the 430 00:24:55,400 --> 00:24:58,280 Speaker 1: litamide was having on the nervous systems of adults and 431 00:24:58,320 --> 00:25:02,960 Speaker 1: on prenatal development. Merrill finally withdrew its application in April 432 00:25:03,000 --> 00:25:06,240 Speaker 1: of nineteen sixty two, as countries were banning the litamide. 433 00:25:06,680 --> 00:25:10,359 Speaker 1: President John F. Kennedy later awarded Dr Kelsey the President's 434 00:25:10,400 --> 00:25:14,200 Speaker 1: Award for Distinguished Federal Civilian Service, and she was awarded 435 00:25:14,280 --> 00:25:17,360 Speaker 1: numerous other honors for her work in drug safety. During 436 00:25:17,440 --> 00:25:22,040 Speaker 1: her lifetime. She died, and I think so that was 437 00:25:22,080 --> 00:25:25,480 Speaker 1: pretty recently. For her part, Kelsey insisted that this was 438 00:25:25,520 --> 00:25:28,919 Speaker 1: a team effort and that her colleagues and supervisors should 439 00:25:28,920 --> 00:25:32,320 Speaker 1: also get the credit. Even though thelidamide did not receive 440 00:25:32,400 --> 00:25:36,080 Speaker 1: FDA approval for distribution in the US, the US did 441 00:25:36,160 --> 00:25:40,960 Speaker 1: have cases of fetal palidamide syndrome. Richardson. Merrill had distributed 442 00:25:41,000 --> 00:25:43,840 Speaker 1: more than two million doses of the drug two doctors 443 00:25:43,920 --> 00:25:46,800 Speaker 1: as samples, and those have been given to patients either 444 00:25:46,840 --> 00:25:51,359 Speaker 1: as sedatives or to treat mourning sickness. At least seventeen 445 00:25:51,400 --> 00:25:54,760 Speaker 1: people in the United States were born with fetal palidamide syndrome. 446 00:25:55,440 --> 00:25:58,480 Speaker 1: Richardson Merrill was also the company that marketed the lidamite 447 00:25:58,480 --> 00:26:01,719 Speaker 1: in Canada, where it stayed down the market until March second, 448 00:26:01,840 --> 00:26:04,920 Speaker 1: nineteen sixty two. It's possible that there were a lot 449 00:26:04,960 --> 00:26:08,520 Speaker 1: more than seventeen people, because only about half of those 450 00:26:08,560 --> 00:26:11,280 Speaker 1: folks parents had gotten the litamite in the US. The 451 00:26:11,320 --> 00:26:14,760 Speaker 1: rest of them had gotten it while traveling, So it's 452 00:26:14,800 --> 00:26:16,840 Speaker 1: totally possible that there are a lot more people that 453 00:26:16,920 --> 00:26:22,080 Speaker 1: just aren't recorded in that that official list. Babies continued 454 00:26:22,119 --> 00:26:24,480 Speaker 1: to be born with feetle with the litamite syndrome after 455 00:26:24,520 --> 00:26:27,679 Speaker 1: the drug was banned around the world, including babies that 456 00:26:27,720 --> 00:26:31,560 Speaker 1: were conceived after the bands. People who had bought or 457 00:26:31,640 --> 00:26:34,520 Speaker 1: been given the medicine before it was pulled from the 458 00:26:34,600 --> 00:26:38,440 Speaker 1: shelves still had it in their medicine cabinets. People who 459 00:26:38,520 --> 00:26:41,520 Speaker 1: had not heard about the drug's effects continued to take 460 00:26:41,560 --> 00:26:44,200 Speaker 1: it or to share it with other people. Some people 461 00:26:44,200 --> 00:26:46,520 Speaker 1: had also just been given a sample of a few 462 00:26:46,520 --> 00:26:50,280 Speaker 1: pills in an envelope that was maybe labeled with dosage instructions, 463 00:26:50,280 --> 00:26:52,199 Speaker 1: but not with the name of the drugs, so they 464 00:26:52,280 --> 00:26:54,639 Speaker 1: might not have even known that it was the litamide 465 00:26:54,680 --> 00:26:58,119 Speaker 1: that they were taking. In some countries, governments and medical 466 00:26:58,160 --> 00:27:01,320 Speaker 1: associations tried to warn the public lick about the dangers 467 00:27:01,359 --> 00:27:03,520 Speaker 1: of the litamide and urged them to go through their 468 00:27:03,520 --> 00:27:06,280 Speaker 1: medicine cabinets to make sure they did not have the 469 00:27:06,359 --> 00:27:10,320 Speaker 1: litamide or any unlabeled pills. One person who was a 470 00:27:10,320 --> 00:27:13,680 Speaker 1: big part of this outreach was Dr Helen Brook Tausig, 471 00:27:13,680 --> 00:27:17,480 Speaker 1: along with surgical technician Vivian Thomas and surgeon Alfred Blaylock. 472 00:27:17,880 --> 00:27:20,400 Speaker 1: Tausig was one of the people who developed a surgical 473 00:27:20,440 --> 00:27:23,760 Speaker 1: treatment for the tetrology of fellow, which caused what was 474 00:27:23,800 --> 00:27:26,359 Speaker 1: then known as blue Baby syndrome. That is on the 475 00:27:26,400 --> 00:27:30,639 Speaker 1: list for another episode, especially Dr Tausig and Vivian Thomas 476 00:27:30,960 --> 00:27:35,399 Speaker 1: um in particular. In January of nineteen sixty two, Tausig 477 00:27:35,480 --> 00:27:38,040 Speaker 1: learned about what was happening in Europe, and she flew 478 00:27:38,119 --> 00:27:41,680 Speaker 1: overseas to examine babies who had been harmed by the litamide. 479 00:27:41,920 --> 00:27:44,080 Speaker 1: When she got back to the US, she undertook an 480 00:27:44,080 --> 00:27:48,240 Speaker 1: extensive campaign to try to raise awareness about the drug's effects, 481 00:27:48,280 --> 00:27:52,119 Speaker 1: including speaking before the American College of physicians and writing 482 00:27:52,200 --> 00:27:55,199 Speaker 1: numerous articles meant for a general audience to try to 483 00:27:55,280 --> 00:27:59,000 Speaker 1: warn people about the drug, but this didn't happen everywhere. 484 00:27:59,560 --> 00:28:02,400 Speaker 1: In austra Alia, for example, distillers pulled the drug off 485 00:28:02,400 --> 00:28:05,119 Speaker 1: the market in nineteen sixty one and warned the Australian 486 00:28:05,160 --> 00:28:08,480 Speaker 1: government of the drugs teratogenic effects, but there was not 487 00:28:08,720 --> 00:28:13,240 Speaker 1: a wide scale effort to notify pharmacies, hospitals, doctors offices, 488 00:28:13,680 --> 00:28:16,760 Speaker 1: or the public about what was happening. As many as 489 00:28:16,800 --> 00:28:20,000 Speaker 1: a quarter of the thelidamide survivors born in Australia were 490 00:28:20,040 --> 00:28:24,600 Speaker 1: conceived after December nineteen sixty one. In Spain, it took 491 00:28:24,760 --> 00:28:27,879 Speaker 1: years for the government to formally outlost solidamide or to 492 00:28:27,960 --> 00:28:31,440 Speaker 1: remove it from the official Register of Drugs, and sometimes 493 00:28:31,480 --> 00:28:34,399 Speaker 1: warnings used the term the liidamide while the drug was 494 00:28:34,440 --> 00:28:38,000 Speaker 1: being sold under other brand names. There were seven different 495 00:28:38,000 --> 00:28:41,600 Speaker 1: brands of the litamide sold in Japan alone. Even in 496 00:28:41,640 --> 00:28:44,440 Speaker 1: places with more coordinated efforts to warn people about the 497 00:28:44,520 --> 00:28:47,440 Speaker 1: dangers of the drug, the first generation of the litamide 498 00:28:47,440 --> 00:28:50,880 Speaker 1: survivors included people born as late as nineteen sixty four 499 00:28:51,200 --> 00:28:55,120 Speaker 1: and possibly even later. Because all of this traced back 500 00:28:55,160 --> 00:28:58,440 Speaker 1: to a drug that they had believed was safe. This 501 00:28:58,600 --> 00:29:02,360 Speaker 1: whole crisis led to just an incredible and crushing sense 502 00:29:02,400 --> 00:29:07,320 Speaker 1: of shame, grief, depression, and anger for everyone involved, whether 503 00:29:07,320 --> 00:29:10,160 Speaker 1: they had prescribed the drug or taken it or given 504 00:29:10,200 --> 00:29:13,240 Speaker 1: it to a friend or family member. Many babies born 505 00:29:13,280 --> 00:29:16,720 Speaker 1: with solidamide embryopathy died in their first year of life. 506 00:29:17,440 --> 00:29:20,960 Speaker 1: Those who survived usually had multiple disabilities that have seriously 507 00:29:21,040 --> 00:29:23,959 Speaker 1: affected the rest of their lives, which means that this 508 00:29:24,000 --> 00:29:27,760 Speaker 1: whole crisis was exacerbated by attitudes about disability and the 509 00:29:27,800 --> 00:29:31,840 Speaker 1: state of disability rights. The various countries where solidamide was 510 00:29:31,920 --> 00:29:35,920 Speaker 1: sold all had their own nuances, but in general, disability 511 00:29:36,000 --> 00:29:38,840 Speaker 1: was more heavily stigmatized than it is now, and doctors 512 00:29:38,880 --> 00:29:42,920 Speaker 1: approached the subject very differently than they do today. So 513 00:29:43,000 --> 00:29:46,160 Speaker 1: if you read articles written about this crisis as it 514 00:29:46,200 --> 00:29:48,840 Speaker 1: was unfolding, a lot of them don't even sound like 515 00:29:48,880 --> 00:29:53,520 Speaker 1: they're describing human beings worthy of life. The default response, 516 00:29:53,680 --> 00:29:57,640 Speaker 1: even among medical professionals, was often to see these newborns 517 00:29:57,720 --> 00:30:00,760 Speaker 1: as a hopeless and even monstrous track agedy, rather than 518 00:30:00,800 --> 00:30:03,520 Speaker 1: as a person who could live and thrive with the 519 00:30:03,600 --> 00:30:07,719 Speaker 1: right care and accessibility. There were even cases and suspected 520 00:30:07,720 --> 00:30:11,760 Speaker 1: cases of infanticide. In one documented example, a Belgian woman 521 00:30:11,840 --> 00:30:15,360 Speaker 1: named Suzanne Vanderputt admitted to killing her daughter with barbiturous 522 00:30:15,360 --> 00:30:18,800 Speaker 1: dissolved in milk. She was acquitted in nineteen sixty two, 523 00:30:19,080 --> 00:30:23,000 Speaker 1: and many countries, doctors recommended that babies with folk amelia 524 00:30:23,160 --> 00:30:26,720 Speaker 1: or other disabilities be placed in institutions rather than being 525 00:30:26,760 --> 00:30:29,959 Speaker 1: sent home with their families, regardless of the level of 526 00:30:30,040 --> 00:30:33,640 Speaker 1: care that the baby actually needed. My mom worked in 527 00:30:33,760 --> 00:30:37,560 Speaker 1: long term care for kids with multiple disabilities for years 528 00:30:37,560 --> 00:30:40,440 Speaker 1: and years, and she definitely worked with kids who needed 529 00:30:40,520 --> 00:30:44,160 Speaker 1: some kind of twenty four hour medical assistance. This was 530 00:30:44,240 --> 00:30:46,480 Speaker 1: not the case with a lot of children who were 531 00:30:46,520 --> 00:30:51,080 Speaker 1: born after being exposed to the linamide. Sometimes medical staff 532 00:30:51,240 --> 00:30:54,840 Speaker 1: took newborns away from the delivery room before their parents 533 00:30:54,880 --> 00:30:57,880 Speaker 1: had held them or even seen them, and a lot 534 00:30:57,920 --> 00:31:01,080 Speaker 1: of places, parents who took their baby home did so 535 00:31:01,240 --> 00:31:06,040 Speaker 1: against medical advice and after being strongly discouraged from doing 536 00:31:06,080 --> 00:31:09,360 Speaker 1: so by their doctors. And whether a child was growing 537 00:31:09,440 --> 00:31:12,600 Speaker 1: up in an institution or at home, most communities were 538 00:31:12,720 --> 00:31:15,600 Speaker 1: far less accessible than they are today, and today there 539 00:31:15,680 --> 00:31:17,560 Speaker 1: is still a long way to go. In most of 540 00:31:17,600 --> 00:31:21,200 Speaker 1: the world, schools and other public buildings were not accessible 541 00:31:21,240 --> 00:31:25,000 Speaker 1: for wheelchairs. Parents, teachers, and administrators had little to no 542 00:31:25,280 --> 00:31:27,840 Speaker 1: education or experience in how to make a home or 543 00:31:27,880 --> 00:31:31,400 Speaker 1: a school accessible to children with these types of disabilities. 544 00:31:32,080 --> 00:31:36,440 Speaker 1: Prosthetics and adaptive devices had not really been developed for children. So, 545 00:31:36,520 --> 00:31:40,160 Speaker 1: in other words, there were barriers everywhere, physical barriers to 546 00:31:40,200 --> 00:31:43,840 Speaker 1: being able to access facilities, and societal barriers due to 547 00:31:44,000 --> 00:31:48,800 Speaker 1: prevailing attitudes about disability. US includes the litamied survivors who 548 00:31:48,800 --> 00:31:52,600 Speaker 1: have described being bullied and harassed by peers and by 549 00:31:52,680 --> 00:31:55,920 Speaker 1: adults because of their disabilities. The ones who grew up 550 00:31:55,920 --> 00:31:58,960 Speaker 1: in care have often described feeling like strangers every time 551 00:31:59,000 --> 00:32:01,680 Speaker 1: they visited their family, least once they got older. But 552 00:32:01,800 --> 00:32:06,320 Speaker 1: really this is us as full of information and heartbreaking 553 00:32:06,320 --> 00:32:09,320 Speaker 1: as this is simply the beginning of the story. The 554 00:32:09,400 --> 00:32:13,040 Speaker 1: Solido mine crisis led to totally revised drug standards around 555 00:32:13,080 --> 00:32:17,280 Speaker 1: the world, a criminal investigation, and decades of lawsuits and 556 00:32:17,520 --> 00:32:21,440 Speaker 1: ongoing efforts to get access to necessary support and services. 557 00:32:21,800 --> 00:32:24,360 Speaker 1: And we're going to talk about all of that next time. 558 00:32:25,120 --> 00:32:28,240 Speaker 1: I also have a little bit of listener mail to 559 00:32:28,520 --> 00:32:33,160 Speaker 1: close us out, all right, This is from Rachel. Rachel says, Hello, ladies, 560 00:32:33,200 --> 00:32:35,560 Speaker 1: I listened to your episode on the women of the 561 00:32:35,600 --> 00:32:39,520 Speaker 1: Civil War and loved it, especially learning about Elizabeth Thorne. 562 00:32:39,560 --> 00:32:42,040 Speaker 1: So fantastic, but it made me think about how other 563 00:32:42,120 --> 00:32:45,240 Speaker 1: women have played a part in military service. I've listened 564 00:32:45,240 --> 00:32:47,720 Speaker 1: to your episodes on the Night Witches and the six 565 00:32:47,760 --> 00:32:51,200 Speaker 1: Triple eight, Central Postal Directory Battalion and others, but I 566 00:32:51,240 --> 00:32:54,440 Speaker 1: really wanted to look into more Canadian history, seeing as 567 00:32:54,480 --> 00:32:57,120 Speaker 1: that's where I am from, and I stumbled across the 568 00:32:57,240 --> 00:33:01,560 Speaker 1: Nursing Sisters. The Nursing Sisters started out as volunteers during 569 00:33:01,600 --> 00:33:05,680 Speaker 1: the South African War, but eventually gained a relative rank 570 00:33:05,760 --> 00:33:08,760 Speaker 1: as lieutenants and then officers. By World War One, they 571 00:33:08,760 --> 00:33:11,360 Speaker 1: were nicknamed the Bluebirds because of their blue dresses and 572 00:33:11,400 --> 00:33:14,480 Speaker 1: white veils, which I just love, and by the end 573 00:33:14,520 --> 00:33:16,680 Speaker 1: of World War Two they had been renamed as the 574 00:33:16,800 --> 00:33:20,960 Speaker 1: Royal Canadian Army Medical Corps. Another interesting fact, two of 575 00:33:21,000 --> 00:33:24,280 Speaker 1: the Nursing Sisters, Meta Hodge and Eleanor Thompson, in World 576 00:33:24,320 --> 00:33:26,840 Speaker 1: War One, became the first women to be awarded a 577 00:33:26,920 --> 00:33:30,480 Speaker 1: wartime Medal of Valor in Canada. There's a great heritage 578 00:33:30,480 --> 00:33:33,560 Speaker 1: minute on this story which I'll link below, and then 579 00:33:34,560 --> 00:33:37,880 Speaker 1: moving on to a more personal note. Also, I'm not 580 00:33:37,920 --> 00:33:40,960 Speaker 1: sure if you remember Momo the historian hound, but that's 581 00:33:41,000 --> 00:33:43,080 Speaker 1: my dog, and I wanted to thank you again for 582 00:33:43,160 --> 00:33:45,880 Speaker 1: getting us through so many awful bats. I don't know 583 00:33:45,920 --> 00:33:47,520 Speaker 1: if I could do it without you, guys, so I've 584 00:33:47,520 --> 00:33:50,120 Speaker 1: added pictures of her into Thanks again, and have a 585 00:33:50,160 --> 00:33:53,440 Speaker 1: great day, ladies. I was from Rachel. Thank you so much. Rachel. 586 00:33:53,640 --> 00:33:57,040 Speaker 1: Of course we even remember Momo this story and hound 587 00:33:57,240 --> 00:34:00,960 Speaker 1: Mo Mo such a good dog. Thank you so much 588 00:34:01,040 --> 00:34:04,480 Speaker 1: for this um this email and for sharing this information 589 00:34:04,520 --> 00:34:06,680 Speaker 1: about the nursing sisters. I don't know if they will 590 00:34:06,720 --> 00:34:09,239 Speaker 1: make it into a full episode at some point, but 591 00:34:09,360 --> 00:34:11,479 Speaker 1: in case they do not, there's a little tidbit about 592 00:34:11,560 --> 00:34:14,239 Speaker 1: it about them for our listeners. If you would like 593 00:34:14,320 --> 00:34:16,280 Speaker 1: to write to us about this or any other podcast, 594 00:34:16,360 --> 00:34:18,719 Speaker 1: where at History podcast at how stuff Works dot com. 595 00:34:18,760 --> 00:34:21,080 Speaker 1: And then we're all over social media at miss in History, 596 00:34:21,120 --> 00:34:24,960 Speaker 1: and that's where you'll find our Facebook, Twitter, Pinterest, and Instagram. 597 00:34:25,080 --> 00:34:27,040 Speaker 1: You can come to our website, which is missed in 598 00:34:27,080 --> 00:34:29,040 Speaker 1: History dot com, and you'll find show notes for all 599 00:34:29,080 --> 00:34:31,080 Speaker 1: the episodes Holly and I have never done together in 600 00:34:31,080 --> 00:34:34,279 Speaker 1: a searchable archive of every episode ever. And you can 601 00:34:34,320 --> 00:34:37,319 Speaker 1: subscribe to the show on Apple podcast. I heart Radio app, 602 00:34:37,400 --> 00:34:44,160 Speaker 1: and wherever else to get your podcasts. Stuff you Missed 603 00:34:44,160 --> 00:34:46,520 Speaker 1: in History Class is a production of I heart Radio's 604 00:34:46,520 --> 00:34:49,440 Speaker 1: How Stuff Works. For more podcasts for my heart Radio, 605 00:34:49,600 --> 00:34:52,759 Speaker 1: visit the iHeart radio app, Apple Podcasts, or wherever you 606 00:34:52,840 --> 00:34:54,040 Speaker 1: listen to your favorite shows.