WEBVTT - Ep 59 Thalidomide: Justice Delayed, Justice Denied 0:00:01.560 --> 0:00:03.760 I was born in a body very different to my 0:00:03.800 --> 0:00:06.880 brother and sister. The only difference was that with me, 0:00:07.240 --> 0:00:10.080 my mum took one tablet in the early stages of pregnancy, 0:00:10.440 --> 0:00:13.680 and that one tablet sealed my fate in life. Can 0:00:13.720 --> 0:00:16.919 you just imagine the delivery room. Instead of the usual 0:00:17.079 --> 0:00:21.079 congratulations you have a beautiful, bouncing baby girl, there would 0:00:21.079 --> 0:00:24.720 have been absolute, hushed silence and gasps of horror as 0:00:24.760 --> 0:00:27.680 I was born. I was whisked away into a corner 0:00:27.760 --> 0:00:30.000 of the room and Mum never saw me for three 0:00:30.080 --> 0:00:32.959 days because the doctors decided that I was too grossly 0:00:33.040 --> 0:00:36.120 deformed for her to love me. These doctors didn't know 0:00:36.159 --> 0:00:39.200 my mum, who was the most wonderful woman in the world, 0:00:39.520 --> 0:00:42.280 and knowing what she went through with me breaks my heart. 0:00:42.760 --> 0:00:46.400 She lives with so much guilt for taking that one tablet. 0:00:47.040 --> 0:00:50.120 How did the drug affect me? For starters, I have 0:00:50.200 --> 0:00:53.040 no arms. I have three little fingers attached to a 0:00:53.080 --> 0:00:55.520 little hand that basically comes out of the side of 0:00:55.520 --> 0:00:58.960 my shoulders. There was also heaps of internal damage done 0:00:58.960 --> 0:01:01.480 to my heart and lungs, which has resulted in numerous 0:01:01.520 --> 0:01:05.240 open heart operations, and I still have more in the pipeline. 0:01:05.400 --> 0:01:08.840 My childhood was, of course, very different to any other child. 0:01:09.319 --> 0:01:11.800 I didn't walk until I was nearly seven, and then 0:01:11.800 --> 0:01:14.080 I had to be carried everywhere until I had major 0:01:14.120 --> 0:01:17.679 heart surgery when I was twelve. Although they repaired my heart, 0:01:17.720 --> 0:01:21.720 I still get extremely tired very quickly. I can't walk far, 0:01:21.880 --> 0:01:24.440 and I can't walk up hills as I get breathless, 0:01:24.800 --> 0:01:27.080 so I never knew the joy of running and skipping. 0:01:28.200 --> 0:01:30.640 The bullying has been horrid, to say the least, and 0:01:30.680 --> 0:01:33.120 that's not just by other kids who are bad enough, 0:01:33.440 --> 0:01:36.360 but by adults who are just as bad, if not worse. 0:01:36.959 --> 0:01:39.600 I have had doctors look down on me and say 0:01:39.640 --> 0:01:42.680 I am worthless and that I would never amount to anything. 0:01:43.240 --> 0:01:45.959 I have had doctors poking and probing my body like 0:01:46.000 --> 0:01:49.240 a lab rat because my body is so different, with 0:01:49.360 --> 0:01:52.320 no compassion as to how they were treating me. One 0:01:52.400 --> 0:01:55.560 doctor told me I would never have friends because who 0:01:55.560 --> 0:01:57.680 would want to be friends with someone with no arms. 0:01:58.560 --> 0:02:01.080 It also amazes me how people think they have the 0:02:01.160 --> 0:02:03.360 right to say the most horrid things to me when 0:02:03.360 --> 0:02:06.320 I'm out in public. It's no wonder that there are days, 0:02:06.400 --> 0:02:08.600 even weeks, where I do not leave the safety of 0:02:08.639 --> 0:02:12.360 my house. The pain in my body is horrendous and 0:02:12.440 --> 0:02:17.400 extremely debilitating. I need knee and hip replacements, but have 0:02:17.480 --> 0:02:20.360 been told that I can't have them as mechanical ones 0:02:20.400 --> 0:02:22.400 don't bend the way I need my body to bend, 0:02:23.000 --> 0:02:25.760 just so that I can eat and drink. Feet weren't 0:02:25.760 --> 0:02:28.000 meant to be hands, but that is exactly how I 0:02:28.120 --> 0:02:31.240 must do everything since I have no arms thanks to 0:02:31.320 --> 0:02:35.080 the litamide. Can you imagine getting dressed and eating or 0:02:35.120 --> 0:02:38.680 cleaning your teeth with your feet every day? It is 0:02:38.760 --> 0:03:23.080 no wonder my body is falling apart thanks to the litamide. 0:03:26.520 --> 0:03:29.680 Oh my god, Erin, Yeah I know. 0:03:32.200 --> 0:03:39.080 That was Trisha's story from the Solidamide Group Australia dot com. 0:03:39.160 --> 0:03:41.400 It was excerpts from her story, and I'll post the 0:03:41.440 --> 0:03:44.680 link to where you can read her full story, along 0:03:44.760 --> 0:03:52.320 with other people's stories who have been affected by thelamide. So, yeah, Hi, 0:03:52.600 --> 0:03:56.520 I'm Erin Welsh and I'm Erin almond Updake and this 0:03:56.640 --> 0:03:58.240 is this podcast will kill you. 0:03:59.080 --> 0:04:02.000 So you've probably figured out by now that today we're 0:04:02.000 --> 0:04:04.240 talking about solidimide. 0:04:04.640 --> 0:04:07.640 We are indeed a little a. 0:04:07.560 --> 0:04:11.440 Little different type of episode for us. It's not a disease, 0:04:11.560 --> 0:04:14.920 per se that we're talking about, but rather a drug. 0:04:15.440 --> 0:04:18.320 Yeah. I guess the only other one like this that 0:04:18.360 --> 0:04:22.120 we've done is aspirin. But this is going to be 0:04:22.160 --> 0:04:24.719 a very different story than aspirin. 0:04:25.360 --> 0:04:29.120 Wait a second, we did something else that was weird 0:04:29.240 --> 0:04:36.680 that wasn't a crossover lead lead that's the one. This 0:04:36.720 --> 0:04:37.159 is not that. 0:04:37.680 --> 0:04:43.039 This is not that. No, no, yeah, although this is heartbreaking, 0:04:43.200 --> 0:04:47.880 as you heard and as you will continue to hear. Yeah, yeah, 0:04:48.880 --> 0:04:52.159 all right, Well we have a piece of business to 0:04:52.240 --> 0:04:53.320 take care of, Aaron. 0:04:53.960 --> 0:04:55.839 It is quarantiney time. 0:04:56.240 --> 0:04:59.960 It is not what are we drinking this week? 0:05:00.440 --> 0:05:02.760 This week, we're drinking David and Goliath. 0:05:03.200 --> 0:05:07.120 Yes we are, and it is named David and Goliath, 0:05:07.279 --> 0:05:09.719 as you will find out later in the episode, because 0:05:09.839 --> 0:05:14.080 of all of the epic struggles to bring the dangers 0:05:14.120 --> 0:05:17.240 of the lidamide to light and how it's been basically 0:05:17.320 --> 0:05:21.320 like one fight after another and you know, with some 0:05:21.520 --> 0:05:22.479 triumphs in there. 0:05:22.520 --> 0:05:27.839 But yeah, yeah, and so Aaron, what's in David and Goliath? 0:05:28.360 --> 0:05:33.599 Yes, yes, it has lemon cello homemade. I would like 0:05:33.640 --> 0:05:39.640 to brag a gin and sometime simple. 0:05:39.360 --> 0:05:43.760 Syrup, fabulous, delicious, love it. 0:05:43.880 --> 0:05:46.800 And we will post the full recipe for the quarantine 0:05:46.960 --> 0:05:49.640 as well as the non alcoholic place Rita on all 0:05:49.680 --> 0:05:52.479 of our social media channels as well as our website. 0:05:52.480 --> 0:05:54.640 This podcast will Kill You dot com? 0:05:54.720 --> 0:05:59.159 Yes, well, any other business that we need to attend 0:05:59.200 --> 0:06:01.279 to Aaron the usual. 0:06:01.400 --> 0:06:03.960 You know, we have merch check it out This podcast 0:06:03.960 --> 0:06:07.520 will Kill You dot Com. We have a good Reads list. 0:06:07.640 --> 0:06:09.680 You can also find that on the books tab on 0:06:09.720 --> 0:06:13.120 our website, and we also have a Bookshop affiliate program, 0:06:13.160 --> 0:06:14.960 so you can find all the books that we talk 0:06:15.040 --> 0:06:17.520 about on the podcast through those links. 0:06:17.960 --> 0:06:21.400 Perfect. Well, shall we dive right in into what's going 0:06:21.480 --> 0:06:23.520 to be a very depressing episode? 0:06:23.800 --> 0:06:25.400 I think that we should. 0:06:27.120 --> 0:07:01.240 Let's take a quick break first. I think soamide, which 0:07:01.560 --> 0:07:06.320 is a synthetic derivative of glutamate or glutenic acid. So 0:07:06.520 --> 0:07:10.360 thilidamide is a drug. Aaron. You're going to talk about 0:07:10.440 --> 0:07:13.160 kind of what it used to be prescribed for and 0:07:13.680 --> 0:07:16.240 in the history, and I'm going to talk about what 0:07:16.280 --> 0:07:20.000 we use it for today. Spoiler alert, it's still out there. 0:07:21.000 --> 0:07:22.840 But what I want to focus on for the biology 0:07:22.840 --> 0:07:26.800 section is just what the effects are when it's used 0:07:27.120 --> 0:07:31.040 in pregnancy, since that's kind of the majority of the 0:07:31.120 --> 0:07:32.119 history of this drug. 0:07:32.200 --> 0:07:35.320 Am I right, Yeah, yeah, it's a huge part of it. 0:07:35.720 --> 0:07:39.960 Right. So Thlidamide is what's called a teratogen, which means 0:07:40.000 --> 0:07:42.720 it's a drug or a substance that when it's ingested 0:07:42.840 --> 0:07:47.160 or used during pregnancy, it results in congenital defects or 0:07:47.200 --> 0:07:53.120 malformations in the developing embryo or fetus. Okay, So to 0:07:53.240 --> 0:07:57.600 talk briefly about something that I love to talk about 0:07:57.640 --> 0:08:02.560 and think about, embryologic development in all animals, not just 0:08:02.640 --> 0:08:07.680 in humans. There's a very distinct pattern of embryologic development 0:08:08.320 --> 0:08:12.360 that has been extremely well studied. So we know all 0:08:12.400 --> 0:08:15.640 of the steps like from two cells to four cells 0:08:15.640 --> 0:08:19.640 to eight cells, et cetera. We know the steps of development, 0:08:20.080 --> 0:08:23.640 especially in humans, like down to the days okay, like 0:08:23.800 --> 0:08:25.920 what's going to develop in what order? 0:08:26.320 --> 0:08:29.960 Yeah, it's actually kind of incredible the amount of detailed 0:08:30.000 --> 0:08:31.400 information that we have on that. 0:08:31.600 --> 0:08:34.520 It's so cool. If you want like some real detail, 0:08:34.559 --> 0:08:38.160 I found a great website. It's called like embryology dot 0:08:38.200 --> 0:08:41.760 au or something. It's an Australian website and it has 0:08:41.960 --> 0:08:46.800 pictures of like every single stage. It's very cool. WHOA, Yeah, 0:08:46.880 --> 0:08:52.239 So in humans, the first eight weeks of development post fertilization, 0:08:52.559 --> 0:08:56.680 which in pregnancy we call ten weeks just stational age. 0:08:56.920 --> 0:09:01.679 That is the embryologic phase of development. At the end 0:09:01.720 --> 0:09:06.120 of this phase, so eight weeks post fertilization, ninety percent 0:09:06.400 --> 0:09:11.760 of the anatomical structures that an adult human has have formed. Wow, 0:09:12.200 --> 0:09:13.359 isn't that incredible? 0:09:13.640 --> 0:09:16.559 Yeah, that's oh wild, It's so cool. 0:09:16.960 --> 0:09:20.440 So any substances that have an effect on the developing 0:09:20.520 --> 0:09:24.440 embryo this early in the process can result in really 0:09:24.520 --> 0:09:29.000 significant effects downstream, right, versus drugs that might have an 0:09:29.000 --> 0:09:32.360 effect later in pregnancy, when most of the structures are 0:09:32.400 --> 0:09:36.800 already developed. Okay, all right, So that's sort of the 0:09:36.920 --> 0:09:44.080 brief overview. So the syndrome that tholidimide causes if ingested 0:09:44.120 --> 0:09:49.040 during pregnancy is called tholidamide embryopathy. That's like the Google 0:09:49.200 --> 0:09:51.280 term if you want to find it. It just means 0:09:51.360 --> 0:09:56.240 a pathogenesis in the embryo due to tholidimide. Okay. So 0:09:56.400 --> 0:10:00.960 there are a huge range of effects that thalinimide can have. 0:10:01.120 --> 0:10:04.040 Some of them I think are very characteristic. Like you 0:10:04.160 --> 0:10:07.000 might you might already have in your head an image 0:10:07.000 --> 0:10:09.000 I know you do erin because you've been researching this, 0:10:09.120 --> 0:10:11.760 but listeners, you might have an image in your mind 0:10:11.760 --> 0:10:15.800 when you hear the word solidimide M. But there's a 0:10:16.040 --> 0:10:22.359 massive range anywhere from very very severe to minimal effects, 0:10:23.200 --> 0:10:26.920 and this does make it really difficult to know if 0:10:27.000 --> 0:10:31.640 the syndrome that you're seeing is from tholitimide or from 0:10:31.679 --> 0:10:36.200 something else. Yep. Yeah, So we'll talk about kind of 0:10:36.200 --> 0:10:39.120 what the most common ones are and what the ones 0:10:39.160 --> 0:10:43.360 that are very much associated with solitimide and not really 0:10:43.400 --> 0:10:46.200 associated with other things, and kind of focus on those. 0:10:48.160 --> 0:10:53.840 So thlinimide often induces what's called focomelia, which was a 0:10:53.880 --> 0:10:54.680 new term for me. 0:10:54.880 --> 0:10:57.160 Actually, that was a new term for me too. 0:10:57.679 --> 0:11:02.760 Yeah, So focomelia is a shortening of the limbs that's 0:11:02.880 --> 0:11:06.959 usually most prominent in the proximal which means like your 0:11:07.040 --> 0:11:10.680 upper arm bones and upper leg bones compared to your 0:11:10.679 --> 0:11:14.880 distal like your forearms or your calfs or whatever. So 0:11:15.080 --> 0:11:17.920 you can end up with either very very short limbs, 0:11:18.400 --> 0:11:21.960 or you can have just like the hand bones and 0:11:22.000 --> 0:11:25.320 feet bones that are more directly attached to the shoulder 0:11:25.400 --> 0:11:29.800 or hip girdle, and that would be focomelia, or you 0:11:29.880 --> 0:11:32.680 can end up with complete loss of limbs, which is 0:11:32.720 --> 0:11:39.040 called amilia. But what's bizarre is that solidimide can also 0:11:39.160 --> 0:11:44.480 be associated with like polydactyle, which means having extra digits I. 0:11:44.480 --> 0:11:46.960 Have, Like, I can feel the questions coming up, and 0:11:47.000 --> 0:11:49.920 I'm just suppressing though, so I'm gonna just let you finish. 0:11:50.160 --> 0:11:52.000 Okay, great, because I don't know if I'm gonna have 0:11:52.040 --> 0:11:54.040 the answer to your question, darreon, but I'm gonna try 0:11:54.080 --> 0:11:59.400 really hard. Okay. One of the things though, that sets 0:11:59.520 --> 0:12:05.079 thlitim embryopathy apart from other genetic causes of shortened or 0:12:05.120 --> 0:12:09.319 missing limbs, and I think this is again very interesting, 0:12:09.480 --> 0:12:11.960 is that the shoulder. So if you look at the shoulder, 0:12:12.120 --> 0:12:15.560 it tends to be very pointed. And this is because 0:12:15.600 --> 0:12:19.160 the clavical tends to be a bit longer, and where 0:12:19.240 --> 0:12:22.760 the clavical attaches to your scapula, that's called the a 0:12:22.840 --> 0:12:27.559 chromioclavicular joint. So that joint tends to be very prominent 0:12:28.280 --> 0:12:34.240 in cases of theldamide embryopathy. Interesting, whereas some genetic causes 0:12:34.400 --> 0:12:38.000 of shortened or loss of limbs, that shoulder tends to 0:12:38.000 --> 0:12:39.959 be more sloped rather than pointed. 0:12:40.320 --> 0:12:44.760 Are you going to tell me why this happens? What's 0:12:44.800 --> 0:12:45.360 the function? 0:12:45.559 --> 0:12:48.240 Come on, I don't know that I'm going to quite honestly, 0:12:48.360 --> 0:12:55.960 really it's it's not really okay anyways, can moving on? Okay, now, 0:12:56.320 --> 0:13:02.600 those are the biggest characteristic typical Okay, focomelia, amelia, this 0:13:02.760 --> 0:13:07.120 prominent shoulder joint. When limbs are affected, it tends to 0:13:07.160 --> 0:13:11.640 be the what's called pre axial, which is your thumb 0:13:11.679 --> 0:13:14.880 side and your big toe side. Those sides of your 0:13:14.920 --> 0:13:19.080 hands and feet are affected before your post axial, So 0:13:19.120 --> 0:13:22.960 your pinky finger and little toe side of your limbs. 0:13:23.320 --> 0:13:27.760 Okay, So does that mean like you would be more 0:13:27.920 --> 0:13:30.760 likely to have your pinky finger and your ring finger 0:13:30.800 --> 0:13:33.480 intact and not have the first three fingers. 0:13:34.040 --> 0:13:36.720 Yeah, so it means that you wouldn't have your pinky 0:13:36.880 --> 0:13:40.920 and ring finger affected without also having your thumb affected. 0:13:41.000 --> 0:13:42.000 Gotcha, So, like. 0:13:41.960 --> 0:13:45.559 It affects that first in the case of thlamide embryopathy, 0:13:45.760 --> 0:13:49.679 which is different than some other causes of limb defects. 0:13:50.320 --> 0:13:53.560 The other thing about solamide embryopathy that sets it apart 0:13:53.559 --> 0:13:57.640 from some other causes is that it's almost always bilateral, 0:13:57.840 --> 0:14:02.720 if not perfectly bilateral, like absolutely equal shortening of limbs, 0:14:03.360 --> 0:14:06.520 at least mostly bilateral, so you're not going to have 0:14:06.640 --> 0:14:12.199 complete unilateral effects okay, and this, Erin, I know your 0:14:12.240 --> 0:14:16.520 question is always why this makes sense? Okay, because this 0:14:16.720 --> 0:14:21.080 is something that's affecting a developing embryo, and embryos develop symmetrically, 0:14:21.440 --> 0:14:24.760 and this is a toxic insult to that developing embryo. 0:14:25.160 --> 0:14:27.560 So it's not going to preferentially affect one side or 0:14:27.640 --> 0:14:33.040 the other. Gotcha ha, At least I had one, all right. 0:14:33.480 --> 0:14:35.880 And the other thing about philidamide is that the upper 0:14:35.920 --> 0:14:38.800 limbs are affected before the lower limbs, so the same 0:14:38.840 --> 0:14:41.880 way that the thumb is affected before the pinkies. You 0:14:41.960 --> 0:14:45.320 won't have loss of portions of your lower legs without 0:14:45.360 --> 0:14:47.840 also having loss of portions of your upper limbs. 0:14:48.160 --> 0:14:49.480 Ah, okay, okay. 0:14:49.200 --> 0:14:51.680 Do you ask me why? Erin? Ask me why? Why? 0:14:51.960 --> 0:14:52.560 Erin? Why? 0:14:52.760 --> 0:14:57.000 Okay? We don't fully know, but here's a hypothesis. Philidimide 0:14:57.040 --> 0:15:00.600 as it turns out, has a very narrow rain in 0:15:00.720 --> 0:15:06.520 which it has effects. Between twenty and thirty six days 0:15:06.640 --> 0:15:10.840 post fertilization is the window in which the lidamide exerts, 0:15:11.000 --> 0:15:15.800 especially its most severe effects, right, So that would be okay, 0:15:15.960 --> 0:15:18.880 that would be days thirty four to fifty after a 0:15:18.960 --> 0:15:22.960 last menstrual period. So gestational age five to seven. 0:15:22.640 --> 0:15:24.720 Weeks okay, which is very early. 0:15:25.280 --> 0:15:29.400 It's very early. It also happens to coincide with what 0:15:29.520 --> 0:15:31.920 is often the peak of morning sickness, which is like 0:15:31.960 --> 0:15:33.040 weeks four to twelve. 0:15:33.440 --> 0:15:36.640 All of these are very pertinent details to the history. 0:15:37.160 --> 0:15:42.560 I know it. And it also is when the limb 0:15:42.560 --> 0:15:49.600 buds are forming and the upper limb buds begin to 0:15:49.680 --> 0:15:54.640 form around day twenty six post fertilization, and the lower 0:15:54.680 --> 0:15:58.800 limb buds start to form one to two days later, okay, 0:15:59.200 --> 0:16:04.880 and grow from proximal so from like humorous to distal 0:16:05.080 --> 0:16:09.880 to your hands. So, depending on exactly what day you 0:16:09.920 --> 0:16:13.560 would have taken solidimide and how long your exposure is, 0:16:13.880 --> 0:16:16.720 your downstream effects are going to vary. A shorter or 0:16:16.760 --> 0:16:21.400 earlier exposure might only affect one small portion, like just 0:16:21.480 --> 0:16:27.120 your humorous bilaterally versus prolonged exposure, which could then go 0:16:27.160 --> 0:16:31.080 on to affect the distal arm and the leg and 0:16:31.120 --> 0:16:36.440 the distal leg gotcha. Okay. Now, limbs are not the 0:16:36.480 --> 0:16:40.200 only thing that can be affected in philidimide. Philimide can 0:16:40.240 --> 0:16:46.240 also cause eye damage and ear damage, including what's called microphthalmia, 0:16:46.280 --> 0:16:51.440 which means small eyes or complete loss of eyes and ophthalmos. 0:16:52.640 --> 0:16:55.440 It can cause absence or reduction of the ear, and 0:16:55.520 --> 0:16:58.560 again this is going to most often be bilateral, so 0:16:58.760 --> 0:17:02.920 on both ears. It can cause cleft lip or cleft palate. 0:17:03.520 --> 0:17:07.000 It can cause issues with the developing vertebrae. It can 0:17:07.040 --> 0:17:11.200 cause damage to nerves, which can cause things like eye palsies, 0:17:11.240 --> 0:17:14.479 so where you can't move your eyes properly because the 0:17:14.520 --> 0:17:18.200 nerves to your eyes have been damaged. And of course 0:17:18.400 --> 0:17:23.240 it can affect literally any of the developing internal organs 0:17:23.280 --> 0:17:26.320 as well, so your heart, your gi tract, your kidneys, 0:17:26.440 --> 0:17:31.320 you name it. Okay, right, So that's a lot of things, right, Yeah, 0:17:31.359 --> 0:17:34.320 which makes sense. I warned you, right, you're affecting an early, 0:17:34.760 --> 0:17:38.600 very very early stage of development. Okay, But of course, 0:17:38.640 --> 0:17:41.880 the biggest question that we try to answer is why 0:17:42.000 --> 0:17:45.000 or how like, how does this happen? Why did these 0:17:45.040 --> 0:17:49.879 specific things happen? Honestly, we don't know. 0:17:51.080 --> 0:17:53.920 Still, still, there were at least hypotheses. I read a 0:17:53.960 --> 0:17:54.440 few of them. 0:17:54.520 --> 0:17:57.520 There's always hypotheses erin, but that doesn't mean we know. 0:17:57.680 --> 0:17:59.760 Okay, I know, But are there good hypotheses? 0:18:00.040 --> 0:18:04.720 Yes, there are three, Okay, there are three good hypotheses 0:18:05.000 --> 0:18:09.840 that have the most support. Okay, one of them is 0:18:10.200 --> 0:18:14.159 the inhibition of angiogenesis, and this is something that we 0:18:14.320 --> 0:18:16.840 know that philidamide does because it's part of why we 0:18:16.960 --> 0:18:19.439 use it as a drug in other contexts today. So 0:18:19.480 --> 0:18:23.240 what does that mean? Angiogenesis is the process of blood 0:18:23.359 --> 0:18:28.480 vessel formation. So thlidamide is known to disrupt the formation 0:18:28.640 --> 0:18:34.399 of blood vessels, and it's not a far stretch to 0:18:34.480 --> 0:18:37.760 see how this disruption in the development of blood vessels 0:18:37.840 --> 0:18:41.000 to your arms would then cause a disruption in the 0:18:41.040 --> 0:18:44.600 growth of those arms in an embryo. But then that 0:18:44.720 --> 0:18:48.200 leads to a question, why does it affect the limbs 0:18:48.440 --> 0:18:53.560 so much more often than internal organs? Does it? Who knows? 0:18:53.640 --> 0:18:58.200 Because right it definitely has large effects on internal organs 0:18:58.240 --> 0:19:00.680 as well, and your limbs are a lot more or visible, 0:19:01.520 --> 0:19:04.680 so you see those effects more than you might see 0:19:04.720 --> 0:19:09.359 some effects on internal organs. But there's also some evidence 0:19:09.800 --> 0:19:14.560 that this is getting very nitty gritty detail, but the 0:19:15.200 --> 0:19:19.560 blood vessels developing in the limbs of an embryo lack 0:19:20.119 --> 0:19:24.840 smooth muscle at that particular stage and development when it 0:19:24.920 --> 0:19:29.000 is susceptible tooth so litamide, and that seems to be 0:19:29.359 --> 0:19:32.680 what allows the litamide to have an effect. So vessels 0:19:32.720 --> 0:19:35.840 that have smooth muscle are more resistant tooth soltamide. 0:19:36.240 --> 0:19:40.760 And how how does that very among internal organs at 0:19:40.760 --> 0:19:43.480 that stage? Like are there some that have more smooth 0:19:43.560 --> 0:19:44.280 muscle or less? 0:19:44.560 --> 0:19:48.320 Yeah, most of the internal organs have smooth muscle on 0:19:48.400 --> 0:19:52.440 their vessels as embryos like during that stage of development, 0:19:52.440 --> 0:19:54.760 whereas the limbs are what don't right? 0:19:54.840 --> 0:19:57.720 But is there any variation within those or within the 0:19:57.760 --> 0:19:58.560 internal organs? 0:19:58.600 --> 0:20:01.399 Great question? Probably I don't know the answer to that. 0:20:02.320 --> 0:20:07.320 Okay, here's another question, and gosh, here maybe it's jumping 0:20:07.359 --> 0:20:12.360 the gun. But okay, how long does the litamide stay 0:20:12.880 --> 0:20:16.959 in your body? And like why that that window is 0:20:17.040 --> 0:20:17.760 so narrow? 0:20:17.880 --> 0:20:18.120 Still? 0:20:18.560 --> 0:20:20.320 But yeah, I don't get it. 0:20:20.320 --> 0:20:22.159 It's a very good question. So the half life of 0:20:22.200 --> 0:20:24.560 the litamite is actually very short. It's like five to 0:20:24.640 --> 0:20:28.640 seven hours, okay, So that means that it's pretty rapidly 0:20:28.680 --> 0:20:33.440 excreted from your body, all right, And the question as 0:20:33.480 --> 0:20:35.840 to why is it only that particular window is a 0:20:35.840 --> 0:20:39.720 really good one. A lot of studies have shown in rats, 0:20:39.920 --> 0:20:42.240 which I'm sure you'll talk about are not a great model, 0:20:42.840 --> 0:20:47.840 and also in humans earlier exposure. So before twenty days 0:20:47.840 --> 0:20:51.720 often results in spontaneous pregnancy loss. Okay, so then the 0:20:51.800 --> 0:20:55.760 effects necessarily exactly the effects have been so dramatic that 0:20:55.520 --> 0:20:59.400 the that embryo is no longer viable, whereas after that 0:20:59.480 --> 0:21:05.080 period of thirty six days post fertilization, it's not clear 0:21:05.119 --> 0:21:09.960 what the effects are in humans. In rats, later exposure 0:21:10.040 --> 0:21:13.879 can induce brain damage in the fetal rat, okay, but 0:21:14.119 --> 0:21:17.560 whether that happens with solidamide, it it's not at least 0:21:17.560 --> 0:21:22.879 clear from what we know about humans. That makes sense, okay, 0:21:22.920 --> 0:21:26.720 but that is all just angiogenesis. So that's just one hypothesis. 0:21:27.080 --> 0:21:29.400 We have a couple more, but luckily they're shorter because 0:21:29.400 --> 0:21:32.280 they're not as interesting or they're not as easy to 0:21:32.400 --> 0:21:38.400 explain at least. So another hypothesis is that philidamide induces 0:21:38.480 --> 0:21:42.719 the creation of free radicals. We've talked a lot about 0:21:43.400 --> 0:21:49.359 radical reactive oxygen species. Yeah, so philidamide does that, and 0:21:49.400 --> 0:21:53.760 so it's thought that that production can then cause damage 0:21:53.800 --> 0:21:57.000 that results in what we see. Not a ton more 0:21:57.000 --> 0:22:00.439 detail I can give you beyond that. And then the 0:22:00.480 --> 0:22:02.680 third one I'm going to give you even less detail 0:22:02.720 --> 0:22:06.800 on because it's beyond my scope of being able to explain. 0:22:07.040 --> 0:22:11.439 But we know a few of the molecular targets that 0:22:11.520 --> 0:22:16.800 philidimide interacts with. So the specific genes that pholidimide seems 0:22:16.800 --> 0:22:23.920 to have an interaction with these are seriblonde and SALL four. 0:22:24.400 --> 0:22:27.600 What's very interesting is that there is a genetic disorder 0:22:28.119 --> 0:22:33.360 associated with mutations in the gene sa L four that 0:22:33.440 --> 0:22:38.600 result in really similar phenotypes, so really similar limb defects 0:22:38.640 --> 0:22:42.120 that we see in soholidimide. But this is a genetic disorder, 0:22:42.160 --> 0:22:47.480 like a hereditary disorder. So it's like, that's kind of 0:22:47.520 --> 0:22:50.600 an appealing hypothesis in that way that maybe pholidimide is 0:22:50.640 --> 0:22:54.560 interacting with this gene somehow which is turning something on, 0:22:54.760 --> 0:22:59.159 turning something off that's causing these limb defects. 0:22:59.640 --> 0:23:04.080 Does that gene have an impact on angiogenesis? 0:23:04.440 --> 0:23:08.680 Good question, not that we know of. Okay, yeah, so 0:23:09.320 --> 0:23:12.480 that's a really good question because we know that theladamide 0:23:12.520 --> 0:23:16.440 has all these effects downstream, right. It has effects on nerves, 0:23:16.480 --> 0:23:20.440 it has effects on cartilage, it has effects on all 0:23:20.480 --> 0:23:22.960 these different things. But the real question is like what's 0:23:23.000 --> 0:23:26.600 the first like what is the first disruption that results 0:23:26.640 --> 0:23:29.040 in all these downstream effects? And that is what we 0:23:29.160 --> 0:23:30.880 don't fully understand yet. 0:23:31.200 --> 0:23:34.119 M hmm, Yeah, a lot to take in. 0:23:35.280 --> 0:23:41.159 Yeah, this is a lot, right, and it's depressing. That's 0:23:41.200 --> 0:23:43.080 what I have for you. I'm not going to talk 0:23:43.119 --> 0:23:45.600 about what we use the litamide for today until the 0:23:45.640 --> 0:23:46.520 current events section. 0:23:47.000 --> 0:23:48.800 Okay, good, I'll talk a little bit about it, but 0:23:50.119 --> 0:23:50.800 I bet you will. 0:23:51.280 --> 0:23:55.800 So, Aaron, where did we come up with this drug? 0:23:56.640 --> 0:23:59.720 What the heck we've already kind of elluded it's it 0:23:59.760 --> 0:24:02.479 was you in pregnancy. Tell me, why tell me all 0:24:02.520 --> 0:24:04.600 about it? I want to know everything. 0:24:05.119 --> 0:24:08.399 Oh man, let's take a short break first. 0:24:08.800 --> 0:24:38.040 Okay. 0:24:38.720 --> 0:24:42.640 I think most people have heard of thelidamie before and 0:24:42.680 --> 0:24:46.280 its association with congenital defects. And the story that I 0:24:46.320 --> 0:24:50.720 remember learning in college was brief, like, in the nineteen sixties, 0:24:50.840 --> 0:24:53.560 a drug was developed that ended up causing these really 0:24:53.600 --> 0:24:58.320 severe congenital abnormalities, and when that link was discovered, it 0:24:58.359 --> 0:24:59.040 was pulled from. 0:24:58.920 --> 0:25:01.480 The market, Right, That's the story we heard. 0:25:02.119 --> 0:25:04.240 Yeah, and it was used I think as like a 0:25:04.320 --> 0:25:08.040 teaching moment of how a medication can have enormous unforeseen 0:25:08.080 --> 0:25:11.359 side effects and to represent just how far we've come 0:25:11.480 --> 0:25:15.160 in terms of our policies for drug regulation. And safety, 0:25:15.600 --> 0:25:18.480 almost like a cautionary tale about the price of progress. 0:25:18.800 --> 0:25:22.080 Yeah, and animal studies. I remember learning it in the 0:25:22.080 --> 0:25:23.920 context of animal studies. Mm hmm. 0:25:24.080 --> 0:25:25.480 That's a huge component to this. 0:25:25.760 --> 0:25:26.400 Yeah. 0:25:26.560 --> 0:25:29.480 But as it turns out, the story of the Litamyde 0:25:29.560 --> 0:25:33.200 is much much deeper than that. It always is, Erin, 0:25:34.720 --> 0:25:37.919 and I just have to say that. You know, like, 0:25:38.040 --> 0:25:41.560 we've been doing this podcast for three years now, we're 0:25:41.600 --> 0:25:44.560 going on our fourth year. Yeah, and you'd think that 0:25:44.680 --> 0:25:48.480 after reading about all of the various accounts of horrible 0:25:48.680 --> 0:25:52.080 unethical things that people do, I would cease to be 0:25:52.119 --> 0:25:53.720 shocked at some point. 0:25:54.000 --> 0:25:56.160 Oh no, Erin, but no. 0:25:58.359 --> 0:26:01.719 So with that to set the tone, let's get started. 0:26:04.240 --> 0:26:07.080 I'm sorry, okay, all right, deep, all right. 0:26:08.320 --> 0:26:13.000 Let's begin with an origin story, that of Kemi Grunenthal, 0:26:13.200 --> 0:26:17.520 the company that created the Linnamide Grunental. I'm just shortening 0:26:17.560 --> 0:26:20.119 it to that from this point on, I was created 0:26:20.160 --> 0:26:23.680 in West Germany in nineteen forty six, the year after 0:26:23.720 --> 0:26:27.560 World War two ended. And who better to staff a 0:26:27.560 --> 0:26:31.879 pharmaceutical company than a bunch of convicted mass murderers and 0:26:31.920 --> 0:26:32.720 war criminals. 0:26:32.920 --> 0:26:35.919 Oh oh, like the uh Nuremberg. 0:26:36.600 --> 0:26:41.760 Yeah, Basically it was like Nuremberg was like a a hiring, 0:26:41.880 --> 0:26:43.320 Yeah hiring. 0:26:42.600 --> 0:26:47.680 It turns out yeah cool, great, awesome. 0:26:49.359 --> 0:26:54.240 So convicted of mass murder, slavery, and crimes against humanity 0:26:54.280 --> 0:26:59.359 at the Nuremberg trials, Nazee Otto Ambrose actually ended up 0:26:59.359 --> 0:27:03.199 as the chair of Grunenthal's supervisory board and oversaw the 0:27:03.200 --> 0:27:04.440 production of the LDAMIDE. 0:27:04.680 --> 0:27:06.280 I already hate this story erin. 0:27:06.880 --> 0:27:10.040 I know it's really it's all downhill from here. Great 0:27:10.720 --> 0:27:13.800 m hm, but it's important to know. I feel like 0:27:13.800 --> 0:27:15.800 this is this is such an important story and it's 0:27:15.840 --> 0:27:19.639 been so underreported throughout its history. We've shortened it to 0:27:19.680 --> 0:27:23.320 this very tight little narrative, and I was shocked to 0:27:23.320 --> 0:27:25.719 read about all of the stuff that's like beneath the surface. 0:27:26.200 --> 0:27:31.480 So with that, so, before Otto Ambrose landed this position 0:27:31.520 --> 0:27:35.360 at Greenenthal, he had worked on chemical weapons and nerve agents. 0:27:35.920 --> 0:27:39.240 He had used slave labor from those imprisoned at Auschwitz, 0:27:39.720 --> 0:27:43.240 and was also involved in having another concentration camp built 0:27:43.320 --> 0:27:48.960 that was closer for convenience for his work. After serving 0:27:49.040 --> 0:27:51.959 three years of his eight year sentence, he was granted 0:27:52.000 --> 0:27:56.560 clemency by the US. He promptly landed that position at Grenental. 0:27:56.960 --> 0:28:00.520 Great another war criminal and murderer that found a job 0:28:00.560 --> 0:28:04.439 at Grunental was Heinz Baumbcotter, an SS doctor at a 0:28:04.440 --> 0:28:08.400 concentration camp outside Berlin where he would oversee executions, pick 0:28:08.480 --> 0:28:11.879 up people for gas chamber, and dabble heavily in medicalized 0:28:11.880 --> 0:28:16.880 torture using injections, explosives and chemicals. He too was convicted 0:28:16.920 --> 0:28:20.040 of these crimes and was actually sentenced to life, but 0:28:20.400 --> 0:28:22.840 was led out in eight years and immediately found a 0:28:22.920 --> 0:28:27.199 job at Grunenthal as a salesperson. And those weren't the 0:28:27.200 --> 0:28:32.600 only ones. There was also Ernst gunther Schenck, another SS doctor, 0:28:32.800 --> 0:28:35.960 and Martin Stemler, a Nazi who wrote copious amounts on 0:28:35.960 --> 0:28:39.680 how German people were racially superior, and he actually ended 0:28:39.760 --> 0:28:43.680 up head of Grunenthal's pathology department. And in general, it 0:28:43.680 --> 0:28:45.840 should be said that Grunenthal was no special case of 0:28:45.920 --> 0:28:49.640 hiring Nazi war criminals. In general, they actually found work 0:28:49.640 --> 0:28:53.200 pretty easily after their conviction, including in the US for instance, 0:28:53.280 --> 0:28:57.280 on research projects. But the question is what role did 0:28:57.480 --> 0:29:00.880 these Nazis play in the development and motion of the 0:29:00.920 --> 0:29:04.320 lidamide And for the names that I've already listed, it 0:29:04.360 --> 0:29:07.240 actually doesn't seem like they played much of a very 0:29:07.280 --> 0:29:10.680 active role, perhaps in sales or the general overseeing of 0:29:10.720 --> 0:29:14.400 the development. But there's one more name that I haven't 0:29:14.480 --> 0:29:20.040 yet mentioned, okay, and that's Heinrich Muchter. Also, I'm sorry 0:29:20.080 --> 0:29:24.720 if I'm horribly mispronouncing all of these names, all of them. 0:29:25.000 --> 0:29:26.280 You mean you don't speak German? 0:29:26.480 --> 0:29:29.600 I do not, and I probably should consult someone who 0:29:29.680 --> 0:29:33.760 speaks German to talk about these names. But well, here 0:29:33.800 --> 0:29:39.160 we are. During World War Two, Muchter worked in Poland 0:29:39.600 --> 0:29:42.320 as the deputy head of the Institute for Virus and 0:29:42.360 --> 0:29:46.440 Typhus Research, where he was involved in countless instances of 0:29:46.520 --> 0:29:50.560 medicalized torture. After the war, he fled Poland and the 0:29:50.600 --> 0:29:54.080 criminal charges that he faced there, and immediately was given 0:29:54.120 --> 0:29:57.480 a job at Grunenthal, and not just any job, but 0:29:57.560 --> 0:30:01.920 the director of research and development. He was also promised 0:30:01.960 --> 0:30:05.640 a percentage of sales in addition to his salary. Sales 0:30:05.640 --> 0:30:10.480 which would later include the Litamide. The Litamide would make 0:30:10.600 --> 0:30:16.160 Muchter incredibly wealthy. In nineteen sixty one, which spoiler was 0:30:16.200 --> 0:30:19.840 the last year that it was sold, Mucter's bonus was 0:30:20.080 --> 0:30:26.880 twenty two times his actual salary. What mm hmm, okay, 0:30:27.520 --> 0:30:30.360 So why did I spend so much time just now 0:30:30.440 --> 0:30:34.080 on the Nazi backgrounds of the people working or running 0:30:34.080 --> 0:30:39.080 the show at Grunenthal. Why it's because later on I 0:30:39.120 --> 0:30:44.120 know that you'll be asking, whether literally or rhetorically, just 0:30:44.160 --> 0:30:47.240 like I did, how could this happen? How could a 0:30:47.280 --> 0:30:52.600 company be so without morals? And when a company is 0:30:52.680 --> 0:30:56.719 comprised of people who are accustomed to a complete disregard 0:30:56.800 --> 0:31:00.240 for humanity and human life, as well as a culture 0:31:00.320 --> 0:31:04.160 of extreme respect for authority, you basically have a recipe 0:31:04.160 --> 0:31:08.360 for criminal negligence. Not I should note that it takes 0:31:08.480 --> 0:31:12.000 Nazis to be greedy or a moral or to put 0:31:12.040 --> 0:31:14.720 the bottom line above human lives, But in this case, 0:31:14.760 --> 0:31:16.800 I do think it's an important part of the background. 0:31:17.840 --> 0:31:21.040 So now let's get to the medical context in which 0:31:21.080 --> 0:31:25.480 the litamide was developed and introduced. So throughout the first 0:31:25.520 --> 0:31:29.440 half of the twentieth century, the use of barbiturates had 0:31:29.520 --> 0:31:34.719 steadily risen, especially in Europe, North America and Australia, and 0:31:34.760 --> 0:31:38.200 with this rise also came recognition of the dangers that 0:31:38.240 --> 0:31:43.400 barbiturates carry, such as addiction, overdose, and respiratory system suppression, 0:31:44.360 --> 0:31:47.360 and the growing awareness of this meant that the market 0:31:47.440 --> 0:31:50.880 was ripe for a safer alternative, especially when it came 0:31:50.960 --> 0:31:55.480 to sleep aids. So when grunental doctors on the hunt 0:31:55.480 --> 0:31:59.520 for a new antibiotic stumbled upon the litamide, who structure 0:31:59.640 --> 0:32:03.160 closely resembled that of barbiturates, they were hopeful it might 0:32:03.200 --> 0:32:07.040 act as a sedative and hypnotic. The next step was 0:32:07.080 --> 0:32:10.760 simply to test it out. Rats were supposedly given doses 0:32:10.800 --> 0:32:13.800 of the drug and observed for sleepiness as compared to 0:32:13.880 --> 0:32:17.520 non drugged rats, and the scientists came to the conclusion that, yes, 0:32:17.680 --> 0:32:21.720 this drug did have a sedative effect, which is interesting 0:32:21.880 --> 0:32:26.320 considering that no sleep was actually observed in the animals 0:32:26.840 --> 0:32:29.280 and no one was able to replicate the experiments. 0:32:30.480 --> 0:32:31.280 That's what. 0:32:32.080 --> 0:32:34.520 So it has something to do with something called a 0:32:34.640 --> 0:32:37.400 jiggle cage, and I'm not going to go into it, 0:32:37.400 --> 0:32:40.480 but basically it measures like the amount of like jiggle 0:32:40.520 --> 0:32:43.200 that the rats are, like movement that the rats would make, 0:32:43.840 --> 0:32:47.880 and the less movement they think they they figured translated 0:32:47.920 --> 0:32:49.360 into a more sedative effect. 0:32:49.560 --> 0:32:51.959 Right, So the rets just weren't moving around, but they 0:32:51.960 --> 0:32:53.160 weren't necessarily sleeping. 0:32:53.640 --> 0:32:57.320 Yeah, and it doesn't really hold up. No one could 0:32:57.320 --> 0:33:00.239 ever replicate it, so there's no telling what really wanted on. 0:33:01.280 --> 0:33:05.239 Additional experiments continued testing the safety of the drug, and 0:33:05.360 --> 0:33:08.880 the company gave it an A plus plus. Apparently there 0:33:09.000 --> 0:33:11.480 was no amount of drug that they could give the 0:33:11.600 --> 0:33:12.720 rats that would kill them. 0:33:12.960 --> 0:33:15.800 Okay, that we just know is false, because you can 0:33:15.880 --> 0:33:17.360 kill a rat with water. 0:33:17.680 --> 0:33:21.719 Okay, uh huh, I know, I know. But just because 0:33:21.760 --> 0:33:24.440 you don't instantly die from the drug doesn't mean that 0:33:24.480 --> 0:33:27.480 there won't be short or long term side effects. Right 0:33:27.800 --> 0:33:31.120 and crucially, no studies were conducted on the safety of 0:33:31.160 --> 0:33:38.000 the drug in pregnant animals, remember that, So rather than 0:33:38.280 --> 0:33:42.320 test animals pregnant or not for side effects, best to 0:33:42.400 --> 0:33:46.440 move on right to humans right naturally, And since we 0:33:46.560 --> 0:33:48.680 know that the company makeup at the time was at 0:33:48.760 --> 0:33:51.840 least in part Nazi, why not resort to what's familiar 0:33:52.040 --> 0:33:56.960 e g. Medicalized torture. So, for example, forty developmentally disabled 0:33:57.000 --> 0:34:01.280 children were given doses of the lidamide to twenty times 0:34:01.320 --> 0:34:04.960 that of the recommended dose for an adult, all without 0:34:04.960 --> 0:34:08.760 the parents' knowledge. Of course, two of the children died 0:34:09.360 --> 0:34:13.680 and one lost their sight. The doctor in charge of this, 0:34:13.880 --> 0:34:16.600 doctor Lange, said there's no way that the deaths were 0:34:16.640 --> 0:34:19.000 attributable to thlidamide. 0:34:18.520 --> 0:34:19.480 O my. 0:34:21.239 --> 0:34:24.440 Uh huh. And hidden among all of these glowing reports 0:34:24.480 --> 0:34:27.720 of the super safe and effective new sedative, some warning 0:34:27.760 --> 0:34:31.040 bells were going off. One doctor who had been given 0:34:31.080 --> 0:34:34.200 samples of the drug discontinued use because there appeared to 0:34:34.239 --> 0:34:38.480 be nerve damage after extended use, and another because it 0:34:38.640 --> 0:34:42.440 caused slight constipation in his patience, which I really appreciate. 0:34:42.640 --> 0:34:47.919 He's just like some people can't poop you well, backed up, well, 0:34:47.920 --> 0:34:50.759 and a lot of And his justification for this was that, like, 0:34:50.800 --> 0:34:53.400 you know what, this is not a life saving drug, 0:34:53.480 --> 0:34:56.319 This is not an essential drug. This is simply like 0:34:56.640 --> 0:34:59.520 an above and beyond and if it's causing discomfort, then 0:34:59.520 --> 0:35:00.719 there's no to give it. 0:35:01.360 --> 0:35:03.400 Can I ask you again what year this was? That? 0:35:03.480 --> 0:35:06.560 Like the already doctors had access to this drug. 0:35:07.040 --> 0:35:10.120 So in nineteen fifty four is when the littamide was 0:35:10.200 --> 0:35:13.799 discovered or developed. In a nineteen fifty seven it was 0:35:13.880 --> 0:35:18.160 released for public consumption. Okay, wow, so with three years, yeah, yeah, 0:35:18.239 --> 0:35:21.480 which is very fast in today's standards. 0:35:21.680 --> 0:35:21.879 Right. 0:35:22.600 --> 0:35:25.400 And so at this point the scientists at Grunenthal still 0:35:25.440 --> 0:35:28.880 weren't sure how the drug actually worked on a molecular level, 0:35:28.960 --> 0:35:31.040 which seems like we still don't truly know, but. 0:35:31.080 --> 0:35:33.800 Still aren't so can't fault him for that one single 0:35:33.840 --> 0:35:34.359 tiny thing. 0:35:35.800 --> 0:35:38.720 Nor did they know how long it stayed in the body. 0:35:39.560 --> 0:35:42.200 But none of this slowed the enthusiasm for the drug, 0:35:42.680 --> 0:35:46.239 and the litamide was launched in Germany in October of 0:35:46.360 --> 0:35:50.960 nineteen fifty seven under the name Kontragen, with hundreds of 0:35:51.000 --> 0:35:55.320 thousands of ads and letters directed towards doctors and pharmacists. 0:35:55.840 --> 0:35:56.360 Wow. 0:35:56.440 --> 0:36:01.319 Its biggest selling point was its absolute safety a toxicity, 0:36:02.520 --> 0:36:06.440 and this hype machine worked far outside the German borders 0:36:06.480 --> 0:36:10.120 as well. The pharmaceutical companies all over the world fought 0:36:10.120 --> 0:36:12.720 to license this wonder drug for sale in their country. 0:36:13.280 --> 0:36:16.560 So one of these companies was Distiller's Biochemical, which was 0:36:16.600 --> 0:36:19.719 an offshoot of Distillers, which sold some of the most 0:36:19.719 --> 0:36:23.160 recognizable liquor brands around the world. It was based in 0:36:23.200 --> 0:36:26.360 the UK, and Distillers won the bid to sell the 0:36:26.400 --> 0:36:28.960 linamide under the brand name dist of All in the 0:36:29.080 --> 0:36:32.440 UK and then also in Australia the year later in 0:36:32.520 --> 0:36:36.279 nineteen fifty nine, opting to have Grenenthal continue producing the 0:36:36.360 --> 0:36:38.800 drug while they would just package it and sell it 0:36:38.880 --> 0:36:42.799 under their name. Advertising for the litamide under any of 0:36:42.800 --> 0:36:46.759 its brand names almost solely consisted of assurances of its 0:36:46.800 --> 0:36:48.160 absolute safety. 0:36:48.600 --> 0:36:52.719 And sorry, at this point, it's marketed just as a 0:36:52.920 --> 0:36:55.880 sedative that is safer than barbituates. 0:36:56.120 --> 0:36:59.520 Yes, so it began just to be so that was 0:36:59.560 --> 0:37:02.399 how it was promoted to doctors, and then doctors sort 0:37:02.440 --> 0:37:05.200 of prescribed it for any manner of like sleep aid, 0:37:05.800 --> 0:37:09.120 sedative for people of varying age, like it just became 0:37:09.200 --> 0:37:12.600 sort of this like cure all type of drugging. And 0:37:12.680 --> 0:37:15.760 it also was not prescription. It was over the counter. 0:37:16.400 --> 0:37:22.000 Uh oh mm hm, oh, okay, I didn't know that, okay, 0:37:22.239 --> 0:37:23.439 m hmm. Yeah. 0:37:24.200 --> 0:37:28.279 So one ad that is very unsettling in light of 0:37:28.320 --> 0:37:30.840 all that would happen and all we know now showed 0:37:30.880 --> 0:37:34.320 a small child on a stool rummaging through the medicine cabinet. 0:37:34.320 --> 0:37:37.200 It's a picture of him and this kid has in 0:37:37.280 --> 0:37:40.680 his hands an unlabeled bottle, with the implication that there's 0:37:40.719 --> 0:37:44.319 about to be a horrible overdose of some drug. But 0:37:44.360 --> 0:37:46.680 then the ad makes it clear that it's actually dist 0:37:46.680 --> 0:37:50.360 of all, with the quote this child's life may depend 0:37:50.480 --> 0:37:52.000 on the safety of dist of all. 0:37:52.880 --> 0:37:56.440 Oh that's bad, is that not? 0:37:57.080 --> 0:38:02.080 That's bad, horrible, but because it was at least superficially 0:38:02.120 --> 0:38:05.880 safer than barbiturates, a point that sales rep were urged 0:38:05.920 --> 0:38:09.160 to hammer on over and over again, it really grew 0:38:09.160 --> 0:38:13.359 in popularity. In some places, sales of the litamide were 0:38:13.440 --> 0:38:16.000 second only to aspirin. 0:38:16.200 --> 0:38:19.960 Wow, which, like our hitty, We've talked about the problems there. 0:38:20.080 --> 0:38:23.120 We've talked about how popular aspirin was and some of 0:38:23.120 --> 0:38:24.360 the problems with aspirin. 0:38:25.719 --> 0:38:26.040 Wow. 0:38:26.320 --> 0:38:28.960 Though, Wow second to aspirin. 0:38:28.719 --> 0:38:32.160 And by nineteen sixty it was the best selling sleeping 0:38:32.200 --> 0:38:33.080 pill in Germany. 0:38:34.360 --> 0:38:34.960 Wow. 0:38:35.360 --> 0:38:39.600 A liquid form was advertised as being a great sedative 0:38:39.640 --> 0:38:42.360 for children. 0:38:42.640 --> 0:38:45.799 Why are you sedating your children? Oh? Stop it? 0:38:45.880 --> 0:38:50.160 And it gets worse because it had the nickname cinema 0:38:50.239 --> 0:38:53.560 juice or the baby sit because parents could just drug 0:38:53.600 --> 0:38:55.480 their kids with the littamide and go off to the 0:38:55.520 --> 0:38:57.200 movies and not have to worry about them. 0:38:57.520 --> 0:39:05.040 Mike, do not drug your child to sleep. Cinema juice. 0:39:06.200 --> 0:39:11.800 Yeah. So, despite being hailed as this incredibly safe drug, 0:39:12.200 --> 0:39:14.920 reports of some side effects of the lidamine started to 0:39:15.040 --> 0:39:20.440 trickle in, not of congenital defects or still births or miscarriages, 0:39:20.480 --> 0:39:24.799 but rather peripheral nerve damage. Doctors began to bring these 0:39:24.840 --> 0:39:29.120 reports to Grunental, and in response, Grunenthal did not pull 0:39:29.160 --> 0:39:32.080 the drug from the market, nor did they further investigate 0:39:32.120 --> 0:39:35.040 these claims or run any additional experiments to see what 0:39:35.120 --> 0:39:39.200 might be going on. Rather, they lied, they denied, and 0:39:39.280 --> 0:39:44.840 they spied. Ooh. Grunenthal hired a PI to follow around 0:39:44.920 --> 0:39:49.160 the doctors that made these complaints because they were convinced 0:39:49.160 --> 0:39:52.440 that a rival pharmaceutical company such as Bayer was behind 0:39:52.480 --> 0:39:56.399 it all. Wow, there's absolutely no truth to this. By 0:39:56.400 --> 0:40:00.000 the way, the little mind does cause nerve damage. 0:40:00.400 --> 0:40:03.560 Yeah, that's like the number one side effect that causes 0:40:03.600 --> 0:40:05.600 it to be discontinued in use today. 0:40:05.840 --> 0:40:10.360 Mm hmm. And this PI even followed the victims of 0:40:10.520 --> 0:40:14.799 nerve damage to see whether they would seek compensation, and 0:40:15.560 --> 0:40:19.560 he gathered dirt on both patients and doctors involved in 0:40:19.600 --> 0:40:20.280 these reports. 0:40:21.000 --> 0:40:21.680 Wow. 0:40:21.840 --> 0:40:26.160 Uh huh. When one Grunental rep went to sell more 0:40:26.280 --> 0:40:29.560 thalidamide to a psychiatric wing and a hospital, he heard 0:40:29.600 --> 0:40:32.560 no reports of nerve damage, and he attributed this to 0:40:32.719 --> 0:40:35.560 a lack of reporting, writing in a letter to his 0:40:35.640 --> 0:40:39.600 boss's quote, maybe the idiots are happy when there's tingling. 0:40:42.320 --> 0:40:46.240 Uh huh, and another employee one uped this despicable remark 0:40:46.320 --> 0:40:50.400 by suggesting that the lidamide be combined with other ingredients 0:40:50.440 --> 0:40:52.760 so that the nerve damage could be blamed on those 0:40:52.800 --> 0:40:58.360 compounds instead. What uh huh, this is real, This really happened. 0:40:58.560 --> 0:41:02.640 So then they're like, yes, sure, whatever, it causes nerve damage, 0:41:02.680 --> 0:41:06.839 but like that doesn't Oh my god, erin, I know. 0:41:07.120 --> 0:41:09.600 I know. Just breathe. You have to just practice, like 0:41:09.640 --> 0:41:11.040 focus on your breathing during this. 0:41:11.360 --> 0:41:12.799 I don't know if I can do that. You're just 0:41:12.800 --> 0:41:17.040 gonna hear like a for the background of this whole episode. 0:41:17.080 --> 0:41:18.120 No one's gonna want to listen. 0:41:22.040 --> 0:41:28.160 Yes. So, so, while while internally Grunental began to more 0:41:28.200 --> 0:41:31.480 closely watch the drug, they at no point made any 0:41:31.480 --> 0:41:35.080 public announcement regarding it, fighting any pressure to put a 0:41:35.120 --> 0:41:38.360 warning on the bottle or make it prescription only. And 0:41:38.440 --> 0:41:41.800 Grunenthal wasn't the only one to be receiving these reports either. 0:41:42.480 --> 0:41:46.240 Distillers the licensee in the UK and Australia had learned 0:41:46.239 --> 0:41:49.360 of potential nerve damage and immediately slapped a warning label 0:41:49.680 --> 0:41:54.080 on its packaging. They asked Grunental about the nerve damage, 0:41:54.160 --> 0:41:56.839 and they were assured that it was only in very 0:41:56.920 --> 0:42:00.759 rare cases and they cleared up quickly. Also not true. 0:42:01.040 --> 0:42:04.360 Some nerve damage was permanent, if not like the majority 0:42:04.400 --> 0:42:08.040 of it. But then another concern came to light. Distillers 0:42:08.080 --> 0:42:11.280 had been developing a liquid version of the lidamide, similar 0:42:11.320 --> 0:42:15.319 to the cinema juice that Grunenthal had made, and they 0:42:15.320 --> 0:42:18.600 were in the process of running some preliminary tests using 0:42:18.640 --> 0:42:22.240 animals rats I think in particular, when some disturbing results 0:42:22.280 --> 0:42:26.160 came to light. The animals were dying at like not 0:42:26.440 --> 0:42:30.200 very high doses, and apparently the liquid was much more 0:42:30.239 --> 0:42:33.279 toxic than the pill form, and so these claims of 0:42:33.360 --> 0:42:35.440 extreme safety were unfounded. 0:42:35.840 --> 0:42:38.360 And that's the one you're giving to babies so you 0:42:38.400 --> 0:42:40.000 could go watch a movie. 0:42:40.360 --> 0:42:44.600 And the company brought their concerns and these results to Grunentol, 0:42:45.160 --> 0:42:47.600 who assured them that they had run similar tests but 0:42:47.719 --> 0:42:51.879 no animals had died, suggesting that it might be due 0:42:51.920 --> 0:42:56.440 to a difference insensitivities between German and English mice. 0:42:56.880 --> 0:43:02.600 That what come on, I know. 0:43:03.080 --> 0:43:08.840 I know. So this logic, if you can even call it, that, 0:43:09.200 --> 0:43:13.560 we cannot shaky to begin with. It completely falls apart 0:43:13.640 --> 0:43:16.840 with the first published report of nerve damage in connection 0:43:16.920 --> 0:43:21.400 with the litamide, titled is the Litamide to Blame? And 0:43:21.440 --> 0:43:25.000 written by Scottish doctor Leslie Florence, published in the British 0:43:25.000 --> 0:43:30.480 Medical Journal in December of nineteen sixty. Immediately following this publication, 0:43:30.960 --> 0:43:33.480 tons of doctors wrote to Florence saying that they had 0:43:33.480 --> 0:43:37.080 seen the same thing in their patients, and his letter 0:43:37.320 --> 0:43:41.920 was a pivotal moment in the history of the litamide 0:43:41.960 --> 0:43:44.960 because it not only created the momentum that would increase 0:43:45.000 --> 0:43:48.240 scrutiny of the super safe drug, but it also played 0:43:48.280 --> 0:43:51.600 a huge role in one of the biggest triumphs of 0:43:51.719 --> 0:43:56.239 drug regulation or oversight. At this time early nineteen sixty one, 0:43:56.760 --> 0:43:59.560 the litamide was a big hit in the countries where 0:43:59.560 --> 0:44:03.200 it's pretty was licensed, but there was still one big 0:44:03.360 --> 0:44:08.160 untapped market, the United States. Grunenthal had been working with 0:44:08.239 --> 0:44:11.160 its US licensee for over a year to try to 0:44:11.160 --> 0:44:14.080 get the drug on the market in the US. In 0:44:14.239 --> 0:44:18.960 anticipation of the eventual approval, they had stockpilot the litamide 0:44:19.560 --> 0:44:22.600 and they were basically all ready to go except for 0:44:22.719 --> 0:44:29.799 one thing FDA approval. FDA Medical Officer and mdphd I 0:44:29.880 --> 0:44:38.480 believe Francis Oldham Kelsey had raised a list of questions 0:44:38.560 --> 0:44:42.240 and concerns about the drug, and none of the answers 0:44:42.280 --> 0:44:45.000 that she was ever given made her any more assured 0:44:45.200 --> 0:44:49.600 in the safety of the litamide, and the hopeful licensee company, 0:44:49.680 --> 0:44:53.000 Richardson Merrill, was not used to not getting their way, 0:44:53.640 --> 0:44:57.839 and so they essentially harassed her. They complained to her 0:44:57.920 --> 0:45:00.000 boss to try to get someone else on the case, 0:45:00.600 --> 0:45:05.000 and they made like over fifty contacts to her, which 0:45:05.040 --> 0:45:07.880 was like, highly against regulation. There wasn't supposed to be 0:45:07.960 --> 0:45:11.160 any contact between like the medical officer and the drug company. 0:45:11.400 --> 0:45:14.200 They weren't even supposed to know who she was, like, oh, 0:45:14.520 --> 0:45:18.680 her name, but her boss gave them not only her 0:45:18.760 --> 0:45:22.040 name but her phone number, which is, oh my god, bizarre. 0:45:22.800 --> 0:45:28.080 So anyway, so Kelsey was already feeling super suspicious of 0:45:28.120 --> 0:45:31.840 the company's demands when in early nineteen sixty one, she 0:45:31.920 --> 0:45:36.000 stumbled across Leslie Florence's article about the lidamite and nerve damage, 0:45:36.480 --> 0:45:39.880 something that the US licensee rep had failed to mention. 0:45:40.440 --> 0:45:44.200 So she called a meeting to basically call them out. 0:45:44.560 --> 0:45:46.680 She was like, all right, let's have a meeting. So 0:45:47.400 --> 0:45:50.080 is there something you're not telling me? They're like, no, no, 0:45:50.160 --> 0:45:52.680 everything's great, Like this drug is the best thing that's 0:45:52.680 --> 0:45:55.720 ever been invented. And she's like, what about this paper 0:45:56.400 --> 0:45:59.040 And they're like, oh no, it's it's nothing like that. 0:45:59.480 --> 0:46:04.000 That's just whatever, you know, And she was like, Okay, 0:46:04.280 --> 0:46:08.680 here's a list of questions that I need thorough answers 0:46:08.719 --> 0:46:13.719 for scientifically supported. Among these questions were what were the 0:46:13.760 --> 0:46:17.720 long term side effects, how and when did nerve damage occur? 0:46:18.680 --> 0:46:22.719 What levels led to overdose? And the new one, which 0:46:22.840 --> 0:46:27.480 hadn't really been asked that much before, was was the 0:46:27.520 --> 0:46:29.320 litamide safe during pregnancy? 0:46:29.840 --> 0:46:30.880 Yeah. 0:46:31.280 --> 0:46:35.080 For more than six months, the company continued to fight 0:46:35.239 --> 0:46:39.160 for the license in the US, but still Kelsey held 0:46:39.160 --> 0:46:43.360 her ground. She felt that their answers were not satisfactory. 0:46:43.640 --> 0:46:46.240 The drug would remain off the shelves in the US, 0:46:46.960 --> 0:46:49.520 and when it was finally revealed that the littamide greatly 0:46:49.520 --> 0:46:53.799 harmed the fetus if taken during pregnancy, Francis Kelsey's role 0:46:53.840 --> 0:46:56.600 in preventing its licensing in the US earned her a 0:46:56.600 --> 0:47:00.279 great fame. However, there is a dark side to the 0:47:00.360 --> 0:47:05.080 story in the US. Even though thlidomide was never officially 0:47:05.200 --> 0:47:09.160 for sale here, millions of samples were sent out across 0:47:09.200 --> 0:47:13.759 the US by the hopeful licensee Richardson Merril. To do this, 0:47:13.920 --> 0:47:16.960 they exploited some loopholes to get the drug into the 0:47:17.040 --> 0:47:20.800 hands of doctors all over the US in promotional events 0:47:20.840 --> 0:47:25.840 masquerading as clinical trials. Over two point five million pills 0:47:25.920 --> 0:47:29.279 were handed out to more than twelve hundred doctors, which 0:47:29.400 --> 0:47:31.920 gave them to around twenty thousand people. 0:47:32.480 --> 0:47:32.920 Wow. 0:47:33.200 --> 0:47:37.640 Richardson Merrill rep. Doctor Pogue. I think that's how you 0:47:37.640 --> 0:47:40.640 say it. Ghost wrote an article under the name of 0:47:40.680 --> 0:47:44.520 a Cincinnati GP and submitted it to the American Journal 0:47:44.560 --> 0:47:48.760 of Obstetrics and Gynecology stating how wonderfully the drug worked 0:47:48.800 --> 0:47:51.160 and how safe it was for the fetus or newborn, 0:47:51.800 --> 0:47:55.160 but no studies had actually been done, but it got 0:47:55.160 --> 0:48:01.360 published anyway. This GP, by the way, was no stranger 0:48:01.440 --> 0:48:04.120 to this practice of like putting his name on an 0:48:04.239 --> 0:48:07.959 article that he didn't write, and he continually denied any 0:48:08.040 --> 0:48:09.200 wrongdoing in this. 0:48:09.840 --> 0:48:10.400 Wow. 0:48:11.600 --> 0:48:15.120 Four months passed after the news of the link between 0:48:15.160 --> 0:48:20.040 the lidamide and congenital defects before Richardson Merrill finally told 0:48:20.200 --> 0:48:23.240 the doctors involved in these quote unquote studies to stop 0:48:23.280 --> 0:48:26.960 their research and return all the remaining samples, four months 0:48:26.960 --> 0:48:29.240 after it had been pulled from German markets. 0:48:29.719 --> 0:48:32.800 Four months after it had been pulled from German markets. 0:48:34.719 --> 0:48:39.960 When the extent of their deceit and for shady behavior, 0:48:40.239 --> 0:48:44.800 I mean that's like not inadequate, it's not adjective, but yeah, 0:48:44.840 --> 0:48:47.840 when it was discovered, the FDA pushed for Richardson Merrill 0:48:47.880 --> 0:48:52.560 to face criminal charges, which of course they didn't. Okay, 0:48:52.600 --> 0:48:54.479 So I wanted to tell that part about the US 0:48:54.560 --> 0:48:57.120 and one big chunk, so I skipped ahead a little bit. 0:48:57.719 --> 0:49:00.400 So now it's backtracked to before the link between the 0:49:00.440 --> 0:49:03.000 littamide and congenital abnormalities was uncovered. 0:49:03.280 --> 0:49:05.240 Yeah, like more detail please? 0:49:05.520 --> 0:49:08.640 Yeah? So okay. So, alongside its success as an extremely 0:49:08.680 --> 0:49:12.160 popular sleeping aid, the littamide was also freely handed out 0:49:12.160 --> 0:49:15.880 as a treatment for morning sickness, uncontrolled vomiting, and pregnancy 0:49:16.400 --> 0:49:18.959 and just general anxiety for pregnant. 0:49:18.640 --> 0:49:22.480 People because you know those hysterical pregnanty. 0:49:21.920 --> 0:49:26.640 The hysterical pregnant people. In some instances it was specifically 0:49:26.680 --> 0:49:31.560 advertised for those uses. In one distiller's brochure, they claimed 0:49:31.600 --> 0:49:35.200 that quote, it is with absolute safety that dist of 0:49:35.200 --> 0:49:38.400 all can be administered to pregnant or breastfeeding women without 0:49:38.680 --> 0:49:42.759 any adverse effects on the mother or the child. The 0:49:42.840 --> 0:49:45.759 reports of nerve damage associated with the drug led to 0:49:45.800 --> 0:49:49.319 its starting to require a prescription in some countries, and 0:49:49.400 --> 0:49:52.640 it also prompted additional questions about the safety of the drug, 0:49:52.760 --> 0:49:56.480 especially as it related to pregnancy. Grunenthal, of course, was 0:49:56.600 --> 0:50:00.960 quick to dismiss and mislead any and all inquiries. For instance, 0:50:01.000 --> 0:50:03.920 when one pharmacist wrote to the company in November nineteen 0:50:04.000 --> 0:50:06.600 sixty on the suspicion that the drug had caused birth 0:50:06.640 --> 0:50:10.439 defects in one of his patients, they replied immediately, dear 0:50:10.520 --> 0:50:14.600 mister pharmacist, based on all observations and findings on hand 0:50:14.600 --> 0:50:18.120 to date, in particular from gynecological departments, we can negate 0:50:18.239 --> 0:50:22.960 any causal connection. To date, not a single indication exists 0:50:23.040 --> 0:50:26.840 at all to suggest that a human or animal, irrespective 0:50:26.880 --> 0:50:30.600 of age, could suffer any form of liver damage through kontragen. 0:50:31.200 --> 0:50:34.200 We therefore feel safe in assuming that the liver damage 0:50:34.239 --> 0:50:36.920 diagnosed shortly after the birth of the baby you are 0:50:36.960 --> 0:50:39.680 referring to is not to be connected with the mother's 0:50:39.719 --> 0:50:44.040 contragen use. They didn't ask questions about the mother. They 0:50:44.040 --> 0:50:47.919 didn't investigate these claims further or ask a hospital about 0:50:47.960 --> 0:50:55.320 any increase in congenital malformations. They just denied. They asked 0:50:55.360 --> 0:50:58.800 an ob to use the drug and report on its findings. 0:50:59.480 --> 0:51:03.920 This doc gave the little Mine exclusively to breastfeeding mothers. 0:51:04.120 --> 0:51:07.200 He refused to give it to pregnant people, and reported 0:51:07.200 --> 0:51:11.960 that it appeared safe to both mother and baby. Bits 0:51:11.960 --> 0:51:15.239 and pieces of his report were misleadingly used in an 0:51:15.280 --> 0:51:20.560 advertising letter that Grunenthal sent to German doctors. Quote, dear doctor, 0:51:20.880 --> 0:51:24.560 during pregnancy and lactation, the female organism is subject to 0:51:24.600 --> 0:51:28.920 particular stresses. The female organism, female. 0:51:28.600 --> 0:51:33.239 Organism ross is disgusting. 0:51:36.280 --> 0:51:44.759 Okay, I'll continue. Sleeplessness, inner unrest, and tiredness are recurring complaints. 0:51:45.040 --> 0:51:50.040 Inner unrest does that mean? Like? What what does that mean? 0:51:50.440 --> 0:51:50.680 Oh? 0:51:51.040 --> 0:51:52.120 I'm gonna lose it. 0:51:52.440 --> 0:51:54.879 I know this is this is definitely the most rage 0:51:54.920 --> 0:51:58.200 inducing episode like we've had in a very long time. 0:51:59.440 --> 0:52:02.640 It is there for often necessary to prescribe a sedative 0:52:02.680 --> 0:52:06.560 and hypnotic, which is harmless to mother and baby. When 0:52:06.560 --> 0:52:11.040 the Obie docs saw this letter, he was appalled by 0:52:11.040 --> 0:52:13.480 how they had misconstrued his words to indicate that the 0:52:13.520 --> 0:52:16.560 drug had also been tested to be safe and pregnant people. 0:52:17.400 --> 0:52:19.480 I don't know if he took issue with the female 0:52:19.560 --> 0:52:21.200 organism or inner unrest part. 0:52:21.640 --> 0:52:25.920 He probably didn't, quite honestly, he was an OBI in 0:52:26.040 --> 0:52:32.360 the fifties. I don't know. Maybe he did. I shouldn't assume, 0:52:32.520 --> 0:52:33.319 but we'll never know. 0:52:33.760 --> 0:52:38.919 I think that's the bottom line. In February nineteen sixty one, 0:52:39.320 --> 0:52:42.720 a pharmaceutical firm reached out to Grunenthal to ask whether 0:52:42.760 --> 0:52:44.879 there were any data on the safety of the drug 0:52:44.920 --> 0:52:47.759 for fetuses, because they wanted to develop it as a 0:52:47.760 --> 0:52:50.040 potential way to prevent miscarriages. 0:52:51.960 --> 0:52:53.880 I know, oh horrifying. 0:52:54.600 --> 0:52:57.680 Grunental responded that they had never done any experiments, but 0:52:58.120 --> 0:53:00.640 they could prove useful even though they're there's been nothing 0:53:00.680 --> 0:53:03.920 so far to make them doubt it's absolute safety. They 0:53:04.000 --> 0:53:06.560 never took it upon themselves to run the experiments and 0:53:06.640 --> 0:53:10.440 to look directly at the link. Ever, when a finished 0:53:10.520 --> 0:53:16.560 doctor asked them three straightforward direct questions. One does the 0:53:16.640 --> 0:53:21.920 lidamide cross the placenta? Answer not known? Two? Can't the 0:53:21.960 --> 0:53:27.280 litamide have a damaging effect on the fetus? Answer improbable? Three? 0:53:27.960 --> 0:53:30.400 In what part of the body is the litamide broken 0:53:30.440 --> 0:53:36.440 down answer, probably by the liver. What yeah, this. 0:53:36.640 --> 0:53:39.520 Wasn't made things up, and then didn't even answer like, 0:53:40.400 --> 0:53:42.319 it's also it's not even the liver. 0:53:44.040 --> 0:53:46.480 This was in July of nineteen sixty one, so the 0:53:46.560 --> 0:53:49.520 drug had been out for four years at this point 0:53:49.600 --> 0:53:54.200 and had been developed seven years earlier. They had ample 0:53:54.200 --> 0:53:58.080 opportunity to do all kinds of studies, and not to 0:53:58.160 --> 0:54:01.240 mention that they had received reports a possible link between 0:54:01.320 --> 0:54:05.280 the lidamide and congenital defects as early as August nineteen 0:54:05.360 --> 0:54:05.879 fifty eight. 0:54:07.520 --> 0:54:09.640 That's like a year after it was out. 0:54:09.840 --> 0:54:14.000 Right, which, yeah, just as with the peripheral nerve damage. 0:54:14.000 --> 0:54:18.799 Though while their outward position was deny internally, Grunenthal began 0:54:18.880 --> 0:54:22.480 looking into the matter. Fears and alerts continued to pile 0:54:22.560 --> 0:54:26.520 up during nineteen sixty one. By the summer, Grunental employees 0:54:26.880 --> 0:54:29.760 refuse to take the drug because of the side effects, 0:54:30.560 --> 0:54:33.960 and Mucht himself said he would not prescribe it if 0:54:34.000 --> 0:54:37.040 he were a doctor. He was like, I would not 0:54:37.120 --> 0:54:39.960 prescribe the drug. It's not safe, but we're going to 0:54:40.040 --> 0:54:45.280 keep selling it. The company's own lawyers were like, wow, 0:54:45.480 --> 0:54:48.400 you didn't do any experiments. There's no way that the 0:54:48.440 --> 0:54:51.320 insurance company is going to cover you. Don't go to trial, 0:54:51.560 --> 0:54:55.399 just settle your screwed. What would it take for there 0:54:55.440 --> 0:55:01.080 to be some oversight, some looking into these claims. Well, 0:55:01.280 --> 0:55:03.200 one thing's for sure, it wasn't going to be done 0:55:03.200 --> 0:55:07.319 by Grunenthal. The two main people involved in uncovering the 0:55:07.360 --> 0:55:11.400 link between the litamide and congenital defects were an Australian 0:55:11.400 --> 0:55:16.319 ob named William McBride and a German doctor named vidukind 0:55:17.080 --> 0:55:22.440 I hope that's right. Lens McBride is typically credited as 0:55:22.480 --> 0:55:24.960 the first person to recognize that the litamide was at 0:55:25.000 --> 0:55:28.960 the root of an epidemic of congenital abnormalities, although later 0:55:29.000 --> 0:55:31.200 he would face his own controversy when it was real 0:55:31.239 --> 0:55:34.120 that he had fabricated some of his research results and 0:55:34.280 --> 0:55:36.480 he would be stripped of his medical license. 0:55:36.920 --> 0:55:40.800 Why are all these humans? 0:55:41.800 --> 0:55:42.080 I know? 0:55:42.640 --> 0:55:43.719 I know? 0:55:46.000 --> 0:55:46.080 So? 0:55:46.200 --> 0:55:48.920 He had also been giving his patients the lidamide at 0:55:48.920 --> 0:55:53.120 the request of distillers, and when he delivered three babies 0:55:53.200 --> 0:55:56.799 in short succession that all had severe congenital defects, some 0:55:56.960 --> 0:56:00.800 very similar to one another, he immediately suspected that's something 0:56:00.920 --> 0:56:05.480 specific was causing these and eventually, though not as soon 0:56:05.520 --> 0:56:08.239 as you might think. He landed on the linamide, and 0:56:08.400 --> 0:56:11.240 he brought his suspicions to the sales rep who passed 0:56:11.280 --> 0:56:14.680 on his concerns, which were dismissed as having no basis. 0:56:14.680 --> 0:56:20.360 In fact, this was in June nineteen sixty one. McBride 0:56:20.400 --> 0:56:22.720 took it upon himself to see if he could induce 0:56:22.760 --> 0:56:26.400 some of these congenital abnormalities in an animal experiment involving 0:56:26.400 --> 0:56:29.400 guinea pigs and mice. But he didn't use a control 0:56:29.480 --> 0:56:34.000 group and didn't compare doses. He simply looked for malformations 0:56:34.040 --> 0:56:36.600 similar to the ones that he had observed in humans, 0:56:36.800 --> 0:56:39.719 and he didn't find any, and so a seed of 0:56:39.800 --> 0:56:40.680 doubt was planted. 0:56:41.040 --> 0:56:42.879 This is what happens if you don't have a lot 0:56:42.920 --> 0:56:45.240 of training and research study design. 0:56:46.800 --> 0:56:52.160 Yeah, very true. And still though for months he continued 0:56:52.160 --> 0:56:55.319 to run these experiments and to ask distillers to look 0:56:55.360 --> 0:56:58.360 into the matter and even to pull the drug until 0:56:58.360 --> 0:56:59.840 additional testing was done. 0:57:00.320 --> 0:57:02.600 That's a very reasonable request. 0:57:02.440 --> 0:57:05.919 It is, But they didn't listen. They didn't they didn't 0:57:05.920 --> 0:57:09.480 take him up on that. And over in Germany, around 0:57:09.480 --> 0:57:12.560 the same time that McBride was developing his own suspicions 0:57:12.600 --> 0:57:17.120 about the lidamide lens vidukin Lens was beginning to notice 0:57:17.160 --> 0:57:21.320 an unusual increase in congenital defects when a man whose 0:57:21.440 --> 0:57:24.880 wife and sister both gave birth to babies with very 0:57:24.920 --> 0:57:27.840 similar congenital abnormalities. 0:57:27.400 --> 0:57:31.280 And that's weird your wife and your sister. No, maybe 0:57:31.280 --> 0:57:31.919 it's not that weird. 0:57:32.160 --> 0:57:34.360 Well, so at first she was like, is it genetic? 0:57:34.440 --> 0:57:36.720 Is it something with that? But then as the head 0:57:36.840 --> 0:57:40.640 of a children's clinic at Hamburg University, he recognized that 0:57:40.680 --> 0:57:43.760 these were not only like probably not linked to genetics, 0:57:43.800 --> 0:57:48.200 but that they were incredibly rare. Right, these were ones 0:57:48.240 --> 0:57:50.240 that you would see every like, I don't know how 0:57:50.280 --> 0:57:55.080 many years, two in short succession. Was like red flag, 0:57:55.160 --> 0:57:58.840 something's going on. Yeah, yeah, And so he was like, okay, 0:57:59.000 --> 0:58:02.080 I'm I want to see whether there's a common factor 0:58:02.200 --> 0:58:06.840 between this, and in his research he learned that there 0:58:06.880 --> 0:58:09.280 were several more children that had been born with the 0:58:09.280 --> 0:58:13.240 same deformities like in his area. And then he was like, okay, 0:58:13.320 --> 0:58:16.080 now it's time for like full on detective work. So 0:58:16.120 --> 0:58:20.160 he launched this investigation, calling doctors around the country and 0:58:20.240 --> 0:58:25.360 digging through medical reports and newspapers. By his estimate, in 0:58:25.400 --> 0:58:29.520 the last couple of years there were two hundred times 0:58:29.840 --> 0:58:37.200 more congenital defects than usual. Whoa can you imagine tallying 0:58:37.240 --> 0:58:44.720 those numbers with like the dawning horror? Oh my, Yeah. 0:58:45.400 --> 0:58:48.400 He was convinced that there was a single element that 0:58:48.560 --> 0:58:49.280 was causing this. 0:58:49.600 --> 0:58:50.120 Uh huh. 0:58:50.280 --> 0:58:54.320 He thought maybe detergent, maybe something else, nuclear falloup, maybe 0:58:54.320 --> 0:58:56.920 some sort of other like face lotion was one of 0:58:56.920 --> 0:59:00.600 the things, I think, But eventually he land on the 0:59:00.680 --> 0:59:04.560 lidamide after asking detailed drug histories of the mothers that 0:59:04.600 --> 0:59:08.760 he interviewed. He brought this evidence to Grunenthal and asked 0:59:08.760 --> 0:59:11.880 that the littam I'd be withdrawn from sale. The company 0:59:11.960 --> 0:59:13.800 was like, all right, yeah, yeah, sure, we can talk 0:59:13.800 --> 0:59:18.560 about it, and he was like, that's not good enough. 0:59:19.120 --> 0:59:21.800 So he sent an express letter that declared that he 0:59:21.880 --> 0:59:25.480 thought it was irresponsible to quote wait for the strict 0:59:25.640 --> 0:59:29.040 scientific proof. I consider it necessary to withdraw the drug 0:59:29.120 --> 0:59:33.080 immediately from the market until its innocuousness as a tarratogenic 0:59:33.160 --> 0:59:40.600 agent in man is proved with certainty reasonable a reasonable, like. 0:59:40.480 --> 0:59:42.600 The most basic of reasonable. 0:59:43.760 --> 0:59:46.880 And so he like, you know, he forced them to 0:59:46.920 --> 0:59:49.680 have a meeting with him and in the meeting, they 0:59:49.680 --> 0:59:53.880 simply tried to discredit his research and then later threatened 0:59:53.960 --> 0:59:59.560 him with legal action. Irony of all ironies. Grunenthal then 0:59:59.680 --> 1:00:02.920 appear to try to start a smear campaign against Lens 1:00:02.960 --> 1:00:06.640 by saying, isn't this the son of the Nazi eugenicist 1:00:06.680 --> 1:00:12.760 Fritz Lens? What? Just like my what? 1:00:12.760 --> 1:00:12.960 What? 1:00:14.280 --> 1:00:17.600 But Lens wouldn't let it drop. Even when faced with 1:00:17.760 --> 1:00:21.440 Lens's detective work and reports from distillers of six babies 1:00:21.440 --> 1:00:24.440 who died from complications after their mother took the litamide, 1:00:24.480 --> 1:00:28.960 they refused to stop sales. They said, We'll let the 1:00:29.000 --> 1:00:31.920 doctors know what Lens thinks of the litamide, but that's it. 1:00:32.880 --> 1:00:37.080 But then a newspaper article appeared that shared Lens' findings 1:00:37.080 --> 1:00:40.280 and said that a popular sleeping pill not naming the 1:00:40.360 --> 1:00:46.000 litamide outright or Kuntergen, was responsible for a huge increase 1:00:46.080 --> 1:00:49.760 in birth defects. And that was the final straw for 1:00:49.840 --> 1:00:52.080 Grunental and the litamide. 1:00:52.200 --> 1:00:55.720 So it took a newspaper article like it took public opinion, 1:00:55.840 --> 1:00:57.400 Essentiallykelly Yes. 1:00:58.000 --> 1:01:01.760 It would finally be withdrawn from the market on November 1:01:01.800 --> 1:01:06.080 twenty sixth, nineteen sixty one, which was eleven days after 1:01:06.240 --> 1:01:11.520 Lenz first brought his findings to the company. But they 1:01:11.560 --> 1:01:13.840 had known about it before then, Let's not make that mistake, 1:01:14.040 --> 1:01:16.520 of course, not to mention the nerve damage. 1:01:16.760 --> 1:01:17.040 Yeah. 1:01:18.960 --> 1:01:23.320 Despite these enormous revelations, the media was a bit slow 1:01:23.400 --> 1:01:26.480 to pick up the story outside of Germany, in part 1:01:26.520 --> 1:01:32.120 because the involved companies discouraged local coverage, and distillers had 1:01:32.200 --> 1:01:35.280 to approach to Grunenthal to be like, hey, this guy 1:01:35.400 --> 1:01:39.000 McBride is saying that the littamide might be causing congenital defects. 1:01:39.360 --> 1:01:43.840 Do you know anything about this? And Grunental replying, oh, yeah, yeah, 1:01:43.880 --> 1:01:49.280 we're pulling the drug from the market. What so should 1:01:49.320 --> 1:01:51.480 we do that too, Like, yeah, you should do that. 1:01:53.080 --> 1:01:56.000 And I should note that although the littamide was pulled 1:01:56.040 --> 1:01:58.960 from the shelves in Germany in November nineteen sixty one, 1:01:59.160 --> 1:02:03.000 in many other countries it remained on the shelves for 1:02:03.240 --> 1:02:05.919 months after this connection had been made. 1:02:06.440 --> 1:02:06.760 Jeez. 1:02:07.240 --> 1:02:09.960 Some companies said, oh, you know, we'll sell what we've 1:02:09.960 --> 1:02:12.360 got and then we'll pretend like we ran out of stock. 1:02:15.000 --> 1:02:18.600 Literally it continued in some places, I think Japan, it 1:02:18.680 --> 1:02:22.360 was sold for months and months and months after like 1:02:22.720 --> 1:02:25.480 just absolutely. I can't wrap my brain around this. 1:02:25.880 --> 1:02:29.960 I can't either, I literally. I mean it's because the 1:02:29.960 --> 1:02:33.240 bottom line is money, right, right, mm hmm, that's it. 1:02:34.640 --> 1:02:37.360 Okay, Yeah, this is a very disheartening episode. 1:02:37.400 --> 1:02:40.320 I'm sorry, it really is so. 1:02:40.440 --> 1:02:42.880 But you know, even when the dangers of the drug 1:02:42.920 --> 1:02:47.480 began to come to light, Grinental didn't acknowledge their wrongdoing. Instead, 1:02:47.520 --> 1:02:51.120 they promised to fight for the lidamide quote to the last, 1:02:51.320 --> 1:02:55.680 with all measures. Within a few days of pulling the 1:02:55.760 --> 1:02:58.480 drug from the market, they started working on their legal 1:02:58.520 --> 1:03:01.959 defense strategy, no knowing that many legal battles lay ahead 1:03:01.960 --> 1:03:06.240 of them. In nineteen sixty seven, nine Grunental executives faced 1:03:06.320 --> 1:03:11.800 criminal charges, including negligent homicide in Germany. And if you 1:03:11.920 --> 1:03:15.240 thought you couldn't be any more disgusted by this company, 1:03:16.000 --> 1:03:20.640 I'm sorry to say that you were wrong. God, Aaron, 1:03:21.000 --> 1:03:23.800 I know because I'm about to tell you some of 1:03:23.840 --> 1:03:28.280 their defense strategies. Number One, they insisted that there was 1:03:28.400 --> 1:03:32.720 no evidence that the litamide cause nerve damage or fetal malformations, 1:03:33.000 --> 1:03:37.880 finding doctors who would actually support that claim. Number Two, 1:03:38.320 --> 1:03:41.560 that even if the litamide caused these supposed defects, a 1:03:41.680 --> 1:03:44.400 fetus has no legal rights in Germany, so it wasn't 1:03:44.440 --> 1:03:46.600 against the law to damage a fetus. 1:03:48.360 --> 1:03:51.520 I'm sorry. Oh okay, uh huh. 1:03:51.600 --> 1:03:54.880 Number three, there were many other compounds that were far 1:03:54.960 --> 1:04:00.080 more likely to be responsible, including detergents, nuclear fallout, and television. 1:03:59.600 --> 1:04:01.680 Rays yep, those television rays. 1:04:03.040 --> 1:04:07.240 Number four, that the tholidamide actually helped save those babies 1:04:07.280 --> 1:04:09.400 who would otherwise have not survived. 1:04:10.200 --> 1:04:12.680 Okay, that just literally doesn't make any sense. 1:04:12.880 --> 1:04:15.160 M They were like, oh, well, they would have. They 1:04:15.160 --> 1:04:17.240 would have like either died or been still born or 1:04:17.280 --> 1:04:21.240 miscarried or whatever. But the the litamide actually allowed them 1:04:21.240 --> 1:04:24.439 to survive. With those with those fetal malformations. 1:04:24.640 --> 1:04:27.520 That okay, mm hmm. 1:04:28.360 --> 1:04:32.880 And number five the most appalling, that the congenital defects 1:04:32.880 --> 1:04:39.320 were actually caused by the mothers themselves in botched abortion attempts. Yeah, 1:04:40.040 --> 1:04:44.320 this was one of their defense strategies. I wrote down 1:04:44.360 --> 1:04:49.160 a few adjectives and then I ran out like deplorable, disgusting, despicable, 1:04:49.320 --> 1:04:51.960 Like I don't know what else. There's there aren't words. 1:04:52.160 --> 1:04:56.000 I don't have any word. There aren't words. What. 1:04:57.200 --> 1:05:00.800 There's no way that this company would not held accountable 1:05:00.840 --> 1:05:07.160 for their actions. Right, ugh, wrong, wrong, the trial dragged 1:05:07.200 --> 1:05:10.960 on and on and on, and after three years of 1:05:11.080 --> 1:05:14.880 tedious proceedings, the trial ended with basically a slap on 1:05:14.920 --> 1:05:18.760 the wrist for Grunental and German law forbade them from 1:05:18.800 --> 1:05:23.680 being further prosecuted. For decades, they admitted no wrongdoing, even 1:05:23.760 --> 1:05:28.280 at times playing the victim. How this unforseeable tragedy has 1:05:28.400 --> 1:05:31.520 haunted the Wertz family, who still owns Grunental, which is 1:05:31.600 --> 1:05:36.560 still an operating company by the way, for years, Aaron, 1:05:37.120 --> 1:05:40.400 I know this is a tough one. 1:05:40.640 --> 1:05:41.560 Yeah, it really is. 1:05:42.280 --> 1:05:47.920 According to CBC, an estimated twenty four thousand babies worldwide 1:05:48.000 --> 1:05:52.120 were born with the lidamide induced malformations, with an additional 1:05:52.160 --> 1:05:57.600 one hundred and twenty three thousand still births and miscarriages. Wow, 1:05:57.640 --> 1:05:59.480 and those are conservative estimates. 1:05:59.640 --> 1:06:01.280 Yeah. 1:06:01.320 --> 1:06:05.080 The story of the legal battles for compensation for those 1:06:05.120 --> 1:06:09.000 babies now adults affected by the litamide is an entire 1:06:09.080 --> 1:06:12.880 podcast in and of itself, not just an episode, And 1:06:13.000 --> 1:06:15.640 while I won't go into a ton of detail, I 1:06:15.680 --> 1:06:19.400 will of course recommend further reading. The long and short 1:06:19.400 --> 1:06:23.040 of it is that any sort of justice has either 1:06:23.120 --> 1:06:28.439 been long delayed or denied entirely. It has been an 1:06:28.560 --> 1:06:33.840 upward battle every step of the way, with incredible obstacles. 1:06:34.560 --> 1:06:38.320 For example, in England there was a press gag for years, 1:06:38.800 --> 1:06:42.120 so the story of distillers and the litamide could not 1:06:42.200 --> 1:06:45.800 be written about for years and years and years. Yeah, 1:06:45.840 --> 1:06:47.640 it's really interesting. 1:06:48.000 --> 1:06:49.400 How can you even do that? 1:06:51.000 --> 1:06:53.680 So there's a whole documentary that I'll recommend that goes 1:06:53.680 --> 1:06:56.080 into it in great detail. It's called Attacking the Devil. 1:06:56.600 --> 1:06:56.920 What. 1:06:57.440 --> 1:07:00.840 Yeah, it has to do with not biasing a court 1:07:00.880 --> 1:07:03.760 case essentially by public opinion or whatever. 1:07:03.840 --> 1:07:06.200 Because it was still in a court case was. 1:07:06.160 --> 1:07:10.320 Still but like once that court case starts, then it's 1:07:10.360 --> 1:07:15.080 a press gag until it's over. But that gag, that 1:07:15.160 --> 1:07:18.400 press gag prevented the public support that may have led 1:07:18.440 --> 1:07:24.240 to more accountability and actually adequate compensation rather than like 1:07:24.360 --> 1:07:29.200 the extremely i mean shockingly paltry pensions that they received. 1:07:30.040 --> 1:07:32.520 And since then there's been a lot more like struggle 1:07:32.560 --> 1:07:34.680 and fight. I mean, just like the story is ongoing. 1:07:34.760 --> 1:07:38.080 I think this is another big aspect of it. But 1:07:38.240 --> 1:07:42.080 also you know, in this of course, just like the 1:07:42.160 --> 1:07:44.440 name of our quarantine suggests, there are a lot of 1:07:44.480 --> 1:07:49.680 incredible people that have stood up against these pharmaceutical companies 1:07:49.800 --> 1:07:51.800 and saying, you know what, no, like you will be 1:07:51.840 --> 1:07:54.840 held accountable. You're going to like help us at the 1:07:54.960 --> 1:07:58.240 very least we can't we can't get the lives that 1:07:58.240 --> 1:08:01.720 we could have had back. You were going to help us, 1:08:01.880 --> 1:08:04.520 like live as comfortably as possible. You know that's and 1:08:04.560 --> 1:08:10.200 I think that's yeah. So there are still people continuing 1:08:10.200 --> 1:08:15.760 this fight today. In August twenty twelve, Grunenthal's chief executive, 1:08:15.920 --> 1:08:21.040 Harold Stock, gave the first and only public apology, if 1:08:21.080 --> 1:08:23.519 it can be called that, on behalf of the company, 1:08:23.600 --> 1:08:26.840 at the unveiling of a statue of a victim of 1:08:26.880 --> 1:08:31.040 the lidamide quote. We ask that you regard our long 1:08:31.160 --> 1:08:34.160 silence as a sign of the silent shock that your 1:08:34.200 --> 1:08:35.599 fate has caused us. 1:08:36.120 --> 1:08:40.479 What m h are you that's not even close to 1:08:40.520 --> 1:08:41.280 an apology. 1:08:41.600 --> 1:08:46.880 No, no, Before I wrap up with the story of 1:08:46.880 --> 1:08:49.400 the little Mites comeback, I want to address one line 1:08:49.439 --> 1:08:52.680 of defense that was used by both Grunenthal and Distillers 1:08:52.680 --> 1:08:54.200 to absolve them of any guilt. 1:08:54.439 --> 1:08:56.800 Why it's just going to make me angrier. 1:08:56.720 --> 1:09:00.160 I know, I know. And this line of defense well, well, 1:09:00.320 --> 1:09:02.800 so it's important because this line of defense has been 1:09:02.880 --> 1:09:06.200 misused in the narrative of the lidamide that is often told. 1:09:06.960 --> 1:09:10.439 So the story of the litamide often places the drug 1:09:10.560 --> 1:09:14.400 at the center of drug testing reform, particularly in ensuring 1:09:14.439 --> 1:09:18.400 a drug safety during pregnancy. Yes, and to be fair, 1:09:18.560 --> 1:09:21.839 the enormous media attention given to that the litamide tragedy 1:09:22.640 --> 1:09:27.120 did bring increased scrutiny to drug testing and awareness and 1:09:27.200 --> 1:09:31.599 regulation and about how what might be safe for a 1:09:31.640 --> 1:09:35.240 pregnant person might not be safe for a fetus. But 1:09:35.600 --> 1:09:39.200 the whole oh, we didn't test the drug in pregnant 1:09:39.280 --> 1:09:42.120 animals because it just wasn't done at the time. And 1:09:42.280 --> 1:09:44.000 you know, at the time, no one knew that a 1:09:44.080 --> 1:09:47.400 drug could affect the fetus and not the mother. Like 1:09:47.479 --> 1:09:52.360 that doesn't fly one little bit. So let's not pretend 1:09:52.400 --> 1:09:56.640 like that's what's going on. Because when the litamide was developed, 1:09:57.000 --> 1:09:59.800 there were plenty of drug companies that were testing their 1:10:00.080 --> 1:10:03.919 rugs on pregnant animals to ensure its safety in the fetus, 1:10:04.360 --> 1:10:08.320 because people had long observed that some drugs may be 1:10:08.520 --> 1:10:12.599 toxic to a fetus but not the person carrying the fetus. 1:10:12.840 --> 1:10:16.160 Okay, and here's another thing, Arin, because I feel like 1:10:16.280 --> 1:10:22.240 when I learned this story it was this story. It 1:10:22.520 --> 1:10:27.519 was what I remember was that it was like, oh, 1:10:27.640 --> 1:10:31.439 we even tested it in some animal models, but in 1:10:31.600 --> 1:10:36.000 a lot of mammalian animals that we often use for 1:10:36.720 --> 1:10:40.840 testing drug testing, it doesn't cause those effects in the fetus. 1:10:41.120 --> 1:10:43.439 So they're like, we just didn't know, and so it's 1:10:43.479 --> 1:10:46.479 like the importance of using the correct animal model. That's 1:10:46.479 --> 1:10:49.600 the context that I remember learning the filidamide story is 1:10:49.640 --> 1:10:52.720 like choosing the quote correct animal model for doing these 1:10:52.760 --> 1:10:56.040 studies in but like, this is so far, so far 1:10:56.120 --> 1:10:56.720 beyond that. 1:10:57.240 --> 1:10:59.840 Oh, it's so far beyond that. And also like, I 1:10:59.840 --> 1:11:01.599 do you think that is part of it? Like that 1:11:01.800 --> 1:11:04.280 was sort of something that brought to light the fact 1:11:04.320 --> 1:11:08.559 that you know, it further illustrated differences between some mammal 1:11:08.600 --> 1:11:11.960 species and humans and how you can't necessarily make a 1:11:12.040 --> 1:11:18.479 connection between those. But the lidamide still does affect rats 1:11:18.960 --> 1:11:21.320 during pregnancy, and so it. 1:11:21.240 --> 1:11:24.920 Doesn't cause the same defects that we see. There isn't 1:11:24.960 --> 1:11:28.160 a good mammalian model for the limb defects that we 1:11:28.240 --> 1:11:30.920 see in mammals. 1:11:31.240 --> 1:11:34.560 So I think there actually were some pregnant rats included 1:11:34.560 --> 1:11:37.320 in some of the studies, and there was note taken 1:11:37.400 --> 1:11:40.120 of the fact that there was an overall reduced litter size, 1:11:40.160 --> 1:11:43.320 which should be a red flag for all. And secondly, 1:11:44.080 --> 1:11:48.120 the rats were found to have resorption scars on their uterus, 1:11:48.400 --> 1:11:52.040 which happens when a fetus develops and then dies or 1:11:52.080 --> 1:11:55.080 like doesn't make it to like birth right. 1:11:55.080 --> 1:11:57.160 So there were red flags even if there weren't the 1:11:57.240 --> 1:12:01.479 exact like congenital abnormality these that were seen in humans. 1:12:03.200 --> 1:12:06.680 But then after the link between congenital defects and the 1:12:06.720 --> 1:12:10.200 littamide came to light, a researcher at Distillers was like, okay, 1:12:10.560 --> 1:12:12.400 we need to do some studies to see whether this 1:12:12.560 --> 1:12:15.880 is like happening in animal models, you know, realizing like, oh, 1:12:15.920 --> 1:12:18.479 we should have done this a long time ago. And 1:12:19.320 --> 1:12:22.960 he tested the drug on rabbits and voila, like it 1:12:23.080 --> 1:12:25.799 was very similar to what they were seeing in humans. 1:12:25.840 --> 1:12:28.360 Like there were congenital defects. It was some New Zealand 1:12:28.360 --> 1:12:32.360 white rabbit or something like that species. Weird, okay, So anyway, 1:12:32.439 --> 1:12:35.759 that defense, like all of their defenses, does not hold 1:12:35.800 --> 1:12:43.920 any water. All right, the final section come back. So 1:12:44.320 --> 1:12:46.960 when the littamide was pulled off the market in nineteen 1:12:47.000 --> 1:12:51.240 sixty one, its mechanism of action was still unknown, and 1:12:51.280 --> 1:12:54.040 I wrote that not knowing that we still don't know it. 1:12:54.120 --> 1:12:55.479 I mean we know a lot more. 1:12:55.600 --> 1:12:59.000 Okay, yeah, yeah, yeah, yeah, But some researchers were starting 1:12:59.040 --> 1:13:03.280 to ponder what it might be. Early experiments weren't showing 1:13:03.400 --> 1:13:06.639 much promise. But then in nineteen sixty four, a physician 1:13:06.720 --> 1:13:09.479 at a leprosy clinic was desperate to help one of 1:13:09.520 --> 1:13:14.000 his patients who had severe painful boils NL. If you 1:13:14.040 --> 1:13:15.040 remember what that stands for? 1:13:15.120 --> 1:13:19.080 Oh do I what is it? I do? But listeners don't. 1:13:19.160 --> 1:13:24.280 Probably it's erythema. No dose some lipprosum. 1:13:24.800 --> 1:13:30.799 Yeah, yea, so hugely painful, horrible boils. They're so painful 1:13:30.840 --> 1:13:33.320 and so uncomfortable that you can't sleep, you can't eat, 1:13:33.360 --> 1:13:38.439 they don't heal like it's horrific. And so he had 1:13:38.600 --> 1:13:42.360 he realized he had some leftover thlidamide that he hadn't 1:13:42.400 --> 1:13:44.400 thrown out yet and was like, you know what, here 1:13:44.479 --> 1:13:47.400 takes some of these. Maybe they'll help you sleep. And 1:13:47.479 --> 1:13:50.080 not only did the person actually get some sleep, but 1:13:50.240 --> 1:13:54.839 their boils healed like ye, they healed, which was almost 1:13:54.880 --> 1:13:59.200 unheard of. Yeah, And so then that one person turned 1:13:59.240 --> 1:14:01.760 into a study of like many more, and it was 1:14:01.760 --> 1:14:06.519 found to be extremely successful in treating NL So why 1:14:06.560 --> 1:14:09.320 this worked to help people with leprosy wouldn't become clear 1:14:09.560 --> 1:14:12.720 until nineteen ninety one, and then the litamide would be 1:14:12.720 --> 1:14:16.719 in the headlines again. At this time, the HIV AIDS 1:14:16.760 --> 1:14:20.080 pandemic was in full swing and there was still no 1:14:20.240 --> 1:14:24.200 widely accepted treatment for the virus. Enter the litamide, which 1:14:24.280 --> 1:14:29.320 acted to reduce TNF alpha to murnder crosis factor alpha, 1:14:29.680 --> 1:14:32.640 the cytokine found at high levels in people who are 1:14:32.800 --> 1:14:36.599 HIV positive. The litamide, because it was banned in the US, 1:14:37.800 --> 1:14:40.160 I was actually being smuggled into the country. 1:14:40.600 --> 1:14:41.120 Wow. 1:14:41.439 --> 1:14:44.439 And so the FDA decided to revisit this band drug 1:14:44.640 --> 1:14:47.920 and ultimately decided to legalize it, which is a very 1:14:47.960 --> 1:14:51.200 short sentence, but not a fast or easy decision. It 1:14:51.280 --> 1:14:56.320 was like a lot of contentious debate going on, and 1:14:56.400 --> 1:14:59.760 even after its legalization, the amplified side effects in people 1:14:59.800 --> 1:15:03.880 with HIV or AIDS who already had weakened immune systems 1:15:03.920 --> 1:15:07.080 meant that its popularity didn't last long for that, but 1:15:07.400 --> 1:15:10.400 it was found to be helpful in people with multiple myeloma. 1:15:11.600 --> 1:15:15.479 So Aaron earlier, you asked me if this episode is 1:15:15.520 --> 1:15:18.680 going to have any bright spots, so honestly, those are 1:15:18.680 --> 1:15:21.960 the only ones that I can really think of. I 1:15:22.080 --> 1:15:25.120 think there are like thousands of lessons to be learned 1:15:25.160 --> 1:15:30.639 from the story of the lidamide, but I think one 1:15:30.680 --> 1:15:33.760 of them is that I feel like we tell this 1:15:33.840 --> 1:15:36.200 story a lot to kind of, in a way, reassure 1:15:36.200 --> 1:15:39.519 ourselves that, you know, we've grown so much, we're doing 1:15:39.560 --> 1:15:41.800 so much better now, And I think that's valid. In 1:15:41.880 --> 1:15:46.519 many ways we are, but it still very much scares me. 1:15:46.680 --> 1:15:50.559 The whole bottom line over a human life, and I 1:15:50.560 --> 1:15:53.679 don't think that aspect has gone away at all, especially 1:15:53.720 --> 1:15:58.160 in light of like American healthcare and just how disgustingly 1:15:58.200 --> 1:16:03.800 abysmal it is in terms of like insurance companies, pharmaceutical companies, hospitals, 1:16:03.920 --> 1:16:05.960 like just this vicious cycle. 1:16:06.400 --> 1:16:10.760 I think another thing that concerns me is that the 1:16:10.880 --> 1:16:14.360 lessons that I feel like I have been taught from 1:16:14.400 --> 1:16:17.840 the solidamide story in classes that I have taken are 1:16:17.880 --> 1:16:20.559 not the lessons that I am taking away from this 1:16:20.640 --> 1:16:25.360 discussion with you. Yeah, so that is concerning to me. 1:16:26.200 --> 1:16:32.639 I agree, well, Aaron, what's going on with the Littlemie today. 1:16:32.680 --> 1:16:35.040 I don't know how else to end this really depressing 1:16:35.200 --> 1:16:35.960 history section. 1:16:36.400 --> 1:16:38.559 Do we even want to talk about it? 1:16:39.080 --> 1:16:39.680 I think we do. 1:16:40.920 --> 1:17:16.080 It's gonna be okay, let's take a quick break. Okay, 1:17:16.200 --> 1:17:22.920 all right, So, like you mentioned, aaron, solimid hasn't disappeared, 1:17:24.400 --> 1:17:26.719 and I have written in my notes that that's actually 1:17:26.800 --> 1:17:29.120 a good thing, and it is a good thing because 1:17:29.160 --> 1:17:32.080 it's a very useful drug, as it turns out, for 1:17:32.240 --> 1:17:36.760 a number of disorders. But now, after you told me 1:17:36.800 --> 1:17:39.040 this story, in my pit of my stomach, I'm like, 1:17:39.080 --> 1:17:40.639 do you know what it just means that the drug 1:17:40.640 --> 1:17:43.680 companies are still making money off of this drug, you know, like, 1:17:44.040 --> 1:17:46.559 don't worry, we found another use for it. It's that's 1:17:46.600 --> 1:17:50.040 what drug companies do with every drug. They're like, oh, gaba, 1:17:50.080 --> 1:17:52.280 pendin doesn't work great as a seizure med but hey, 1:17:52.479 --> 1:17:59.240 it works for peripheral oropathy, you know, right, Okay, sorry, anyways, 1:18:00.200 --> 1:18:03.080 let's talk about it. And I also want to clarify something. 1:18:04.040 --> 1:18:06.280 So in the biology section, when I was talking about 1:18:06.280 --> 1:18:09.800 how we don't fully understand the mechanisms of thlidamide, that 1:18:09.960 --> 1:18:14.439 is true, but it's more true for the mechanisms of 1:18:14.640 --> 1:18:19.520 thlidamide embryopathy than it is true for the mechanisms of thlidamide, 1:18:20.160 --> 1:18:22.840 not in the fetus, if that makes sense. Yeah, okay, 1:18:23.040 --> 1:18:27.000 So the part about the inhibition of angiogenesis, we know 1:18:27.120 --> 1:18:30.240 that that's what thlidimide does. What we don't know is 1:18:30.280 --> 1:18:32.879 exactly how that causes the congenital defects. 1:18:33.200 --> 1:18:33.800 Gotcha. 1:18:33.920 --> 1:18:37.840 And like you mentioned, tholiimide is an inhibitor of TNF 1:18:37.880 --> 1:18:41.880 alpha tumoricrosis factor alpha. So those are kind of two 1:18:41.960 --> 1:18:45.120 of the biggest ways that we know that thlidamide works 1:18:45.640 --> 1:18:48.720 in the ways that we use it, like in adults 1:18:48.840 --> 1:18:53.120 and children that are not pregnant. Okay, mm hmm. So 1:18:53.479 --> 1:18:57.200 what do we use it for today? It's been studied 1:18:57.280 --> 1:19:01.760 at least peripherally in a really wide range of conditions, 1:19:02.000 --> 1:19:05.360 but there are a few conditions that it's like really 1:19:05.600 --> 1:19:08.839 more commonly used for and like more associated with today. 1:19:09.600 --> 1:19:12.599 So we'll kind of just like run through them all 1:19:12.680 --> 1:19:15.120 and then focus a little bit on the two or 1:19:15.200 --> 1:19:19.000 three biggest ones. Okay, m hm. So it has been 1:19:19.120 --> 1:19:22.200 used for the treatment of Crone's disease, which I think 1:19:22.280 --> 1:19:28.639 is fascinating. How does that work, don't I don't know? Okay, 1:19:30.680 --> 1:19:33.439 But what's even more interesting is that I found a 1:19:33.479 --> 1:19:37.320 paper that it's it was used in children with Crohn's 1:19:37.360 --> 1:19:41.960 disease that were also infected with tuberculosis. So you can't 1:19:42.080 --> 1:19:45.479 use other like forms of therapy in those kids because 1:19:45.479 --> 1:19:48.040 it would increase the tuberculosis load. 1:19:48.920 --> 1:19:53.240 Oh, because it would be immunosuppressive exactly right. 1:19:53.560 --> 1:19:59.599 Yeah, so yeah, super interesting. It's not super well studied 1:19:59.640 --> 1:20:02.439 in chro in general, and it's not like a first 1:20:02.439 --> 1:20:06.679 line therapy, but in refractory chrones it has been used. 1:20:08.000 --> 1:20:12.360 It's also used to treat graft versus host disease, which 1:20:12.439 --> 1:20:15.440 is what happens when you get a bone mirror transplant 1:20:15.479 --> 1:20:19.479 and the donor marrow starts attacking the recipient's owned cells, 1:20:19.520 --> 1:20:25.759 which is a really common complication of bone marrow transplantation. Okay, 1:20:26.400 --> 1:20:28.760 don't ask me how that works because I'll explain it 1:20:28.800 --> 1:20:33.320 in a minute. And then two of the kind of 1:20:33.479 --> 1:20:36.599 most common uses are the ones that you mentioned aaron, 1:20:36.760 --> 1:20:43.360 multiple myeloma, and leprosy, okay, and specifically Erythema nodosum leprosum. 1:20:43.520 --> 1:20:48.479 That's not actually leprosy, but it's an autoimmune reaction to 1:20:48.680 --> 1:20:55.400 infection with Microbacterium lepre So. Multiple miloma is a type 1:20:55.439 --> 1:21:00.000 of blood cancer that specifically affects your plasma cells, which 1:21:00.160 --> 1:21:02.760 like the mature form of B cells. Okay, check our 1:21:02.800 --> 1:21:06.200 vaccines episode if you want more. Okay. So, your plasma 1:21:06.200 --> 1:21:10.599 cells normally make antibodies. So it's like, how on earth 1:21:10.880 --> 1:21:16.240 can this treat a blood cancer? Essentially it doesn't make sense. Well, 1:21:16.600 --> 1:21:22.920 it turns out that multiple myeloma is associated, like most cancers, 1:21:23.120 --> 1:21:29.120 with an increase in angiogenesis. Okay, And so the effect 1:21:29.280 --> 1:21:33.080 that solidimide has on a couple of specific growth factors 1:21:33.240 --> 1:21:39.000 that are associated with angiogenesis fibroblast growth factor and vascular 1:21:39.160 --> 1:21:44.960 endothaleal growth factor so FGF and VEGF, as well as 1:21:45.040 --> 1:21:50.320 its effects on TNF alpha. Those things all combined are 1:21:51.160 --> 1:21:54.040 how it has its effects on a multiple myeloma which 1:21:54.080 --> 1:21:59.040 is associated with an increase in angiogenesis. Now, a logical 1:21:59.120 --> 1:22:01.600 question you might ask me, Aaron, is can this be 1:22:01.720 --> 1:22:02.879 used in any cancer? 1:22:03.439 --> 1:22:06.800 You're just preempting all of my questions, sarh. 1:22:07.120 --> 1:22:10.200 Yeah. The answer is it has been studied in a 1:22:10.320 --> 1:22:14.719 number of other cancers, but it's not as well studied. 1:22:15.960 --> 1:22:18.800 And I think what it boils down to is that 1:22:18.840 --> 1:22:21.760 for a lot of other cancers, we have better treatments, 1:22:22.320 --> 1:22:26.240 whereas multiple myeloma is something that before this we really 1:22:26.240 --> 1:22:30.160 didn't have anything. So thilinide was kind of like revolutionary 1:22:30.200 --> 1:22:33.720 in that way. And graft versus host it's kind of 1:22:33.760 --> 1:22:37.720 the same thing, right, So it's inhibiting those cytokinds associated 1:22:37.720 --> 1:22:44.360 with the inflammatory response, right. So yeah, and then erethoma 1:22:44.400 --> 1:22:50.720 nodosum leprosum. Again, this is an immune mediated reaction to 1:22:51.320 --> 1:22:56.680 infection with the bacteria. So by suppressing that inflammation somehow, 1:22:57.000 --> 1:23:04.080 thilinomide works really well to treat that disorder. Now do 1:23:04.120 --> 1:23:08.360 you want some depression to end this depressing episode? 1:23:08.920 --> 1:23:11.160 I mean, I think I can guess what it is. 1:23:11.720 --> 1:23:18.439 Yeah, Okay, so the congenital effects of tholidamide are not gone. No, 1:23:20.080 --> 1:23:23.439 I couldn't find sort of exact numbers on like what 1:23:23.560 --> 1:23:29.960 the epidemiology is worldwide. In most countries, philidamide is very 1:23:30.000 --> 1:23:35.519 tightly regulated because of its effects, its tyotogenic effects, so 1:23:35.760 --> 1:23:38.720 it's only given you know, it's given under like in 1:23:38.760 --> 1:23:41.320 the US, it's called the Class X drug, which means 1:23:41.360 --> 1:23:47.360 it's completely one, absolutely contraindicated in pregnancy. Generally Class X 1:23:47.479 --> 1:23:51.439 drugs if you are a person of reproductive age. You 1:23:51.520 --> 1:23:54.360 generally have to ensure that you're not going to become 1:23:54.400 --> 1:23:56.360 pregnant if you're going to use this drug, and so 1:23:56.400 --> 1:24:00.559 there's like a lot of regulation with that. Gotcha, Okay, 1:24:01.200 --> 1:24:03.719 And this is not just people with uteruses actually, because 1:24:03.720 --> 1:24:06.679 the litamide can be transmitted in the semen as well. 1:24:06.760 --> 1:24:08.920 So I was wondering if you were going to bring 1:24:09.000 --> 1:24:09.320 that up. 1:24:09.439 --> 1:24:12.599 Yeah, So it's anyone of reproductive age. It's it's obviously 1:24:12.760 --> 1:24:15.400 most severe if you are a person with a uterus 1:24:15.400 --> 1:24:18.879 who becomes pregnant while you're using it, but it's anyone 1:24:18.880 --> 1:24:22.200 of reproductive age because it can be transmitted in the 1:24:22.240 --> 1:24:25.960 semen as well. But one place that there is some 1:24:26.000 --> 1:24:29.680 good data on kind of the numbers of babies that 1:24:29.720 --> 1:24:34.160 are being born with soldamite exposure today is Brazil, and 1:24:34.200 --> 1:24:36.840 that's largely because, first of all, there's groups that are 1:24:36.920 --> 1:24:40.000 actively studying it and doing active surveillance for it, but 1:24:40.120 --> 1:24:44.760 also because leprosy is common in Brazil compared to a 1:24:44.800 --> 1:24:47.920 lot of other countries. So I think I saw there 1:24:47.920 --> 1:24:52.320 are about twenty four thousand cases of multibaselar leprosy, which 1:24:52.360 --> 1:24:56.280 is the kind that is associated with this arithema nodosum 1:24:56.360 --> 1:25:00.080 leprosim that are diagnosed annually in Brazil, and so so 1:25:00.160 --> 1:25:02.920 this study was looking at what the birth rate of 1:25:03.280 --> 1:25:08.080 tholdimide embryopathy was and they found that in the period 1:25:08.120 --> 1:25:10.960 from two thousand to two thousand and eight, that rate 1:25:11.000 --> 1:25:15.960 has actually increased compared to the previous decades. So it's 1:25:16.000 --> 1:25:19.879 now three point one per ten thousand live berths compared 1:25:19.880 --> 1:25:22.679 to about one point nine per ten thousand live births 1:25:22.840 --> 1:25:26.240 from nineteen eighty two to nineteen ninety nine. What's going on, 1:25:27.160 --> 1:25:30.000 It's not clear, and this study really couldn't get a 1:25:30.000 --> 1:25:33.920 good handle on it. Thiltamide is tightly regulated in Brazil, 1:25:34.479 --> 1:25:39.439 but you know, leprosy is also still a problem there, 1:25:39.640 --> 1:25:43.040 and so the study also reported that med sharing might 1:25:43.080 --> 1:25:46.160 also be contributing. So if we're not getting a handle 1:25:46.240 --> 1:25:50.960 on who exactly is taking tholidamide and if people also 1:25:51.439 --> 1:25:53.720 the other thing is that leprosy tends to happen in 1:25:53.840 --> 1:25:56.800 very rural areas, in very remote areas where people might 1:25:56.880 --> 1:26:02.720 not have as much knowledge about polimide. But the other 1:26:02.800 --> 1:26:07.080 thing is that the history that you told Aaron is 1:26:07.200 --> 1:26:10.960 not in the distant past, no, And I think that's 1:26:11.000 --> 1:26:14.320 another thing that you know, when we learned about tholidamide 1:26:14.320 --> 1:26:18.240 in school multiple times, you know, they show these black 1:26:18.280 --> 1:26:20.599 and white pictures and it makes it seem like this 1:26:20.800 --> 1:26:26.280 was so long ago, but it wasn't. This was like 1:26:26.400 --> 1:26:34.439 our parents' generation, right absolutely, And so babies that were 1:26:34.479 --> 1:26:40.280 born with anomalies or congenital defects due to thlamite exposure 1:26:40.360 --> 1:26:44.320 are now adults living with these effects, and there are 1:26:44.400 --> 1:26:47.160 thousands of them across the globe. I think the estimate 1:26:47.200 --> 1:26:51.800 I saw was about three thousand people living from like 1:26:51.880 --> 1:26:57.880 that nineteen sixties cohort of tholtamide exposure, and there are 1:26:58.000 --> 1:27:01.000 a number of support groups. I think the Internet has 1:27:01.040 --> 1:27:03.400 been wonderful for this and that people have been able 1:27:03.439 --> 1:27:06.519 to find other survivors and kind of connect with them, 1:27:06.880 --> 1:27:09.640 And there are a ton of different support networks and 1:27:09.720 --> 1:27:13.880 things across the globe in every different country where there 1:27:13.920 --> 1:27:18.320 are theletomide survivors and so now these are adults that 1:27:18.360 --> 1:27:20.880 are living with these quality of life issues. And there 1:27:20.960 --> 1:27:23.160 is a really interesting paper that came out last year 1:27:23.200 --> 1:27:27.440 that kind of specifically looked at this in UK, theiletomide Survivors, 1:27:27.560 --> 1:27:29.920 So we'll definitely link to that on the website as well. 1:27:30.439 --> 1:27:33.360 Awesome. Yeah, so I think that's really important to remember. 1:27:33.400 --> 1:27:38.400 This is this is not history, this is like it's 1:27:38.439 --> 1:27:39.360 still happening. 1:27:39.720 --> 1:27:43.760 Yeah, it is absolutely show we cite our sources so 1:27:43.800 --> 1:27:46.439 that people can do more reading and learn even more 1:27:46.520 --> 1:27:48.280 about this horrible tragedy. 1:27:48.600 --> 1:27:53.599 Absolutely. But actually, you know what I realized is that 1:27:53.960 --> 1:27:57.920 throughout that super long history section there's one thing that 1:27:58.000 --> 1:28:02.520 I completely forgot to mention or touch on, which is etymology. 1:28:03.280 --> 1:28:06.240 But not of the lidimide, because we've talked about that. 1:28:06.320 --> 1:28:08.920 It's just like a shortening of its super long chemical name, 1:28:09.720 --> 1:28:14.160 but of teratogen. Aaron, do you know what tiatogen the 1:28:14.200 --> 1:28:14.840 origin is? 1:28:15.280 --> 1:28:19.160 Oh my gosh no, And I've never even thought about it. 1:28:20.280 --> 1:28:23.400 Yeah, I didn't realize it until I think I was 1:28:23.439 --> 1:28:26.559 reading one of these accounts or it was in a documentary. 1:28:26.640 --> 1:28:30.280 And it surprises me that it is still used because, 1:28:30.479 --> 1:28:33.439 let me tell you, so, the word territology had been 1:28:33.479 --> 1:28:37.240 around since the eighteen hundreds, meaning like basically any sort 1:28:37.280 --> 1:28:41.519 of irregularity during any developmental process, so whether it was 1:28:41.600 --> 1:28:45.599 like in the womb or during puberty, not just humans 1:28:45.600 --> 1:28:49.639 but also plants or whatever. But tatagen was coined really 1:28:49.680 --> 1:28:52.040 only or started to be used really only in nineteen 1:28:52.120 --> 1:28:55.000 fifty nine. But both of these share the same root, 1:28:55.200 --> 1:28:59.519 which is from the Greek tirato, meaning marvel or monster 1:29:00.240 --> 1:29:07.040 what and so literally Taratagen has monster in the name. 1:29:07.760 --> 1:29:10.240 Yeah, but I mean, and I would assume jen is 1:29:10.280 --> 1:29:14.000 like general, like it generates it or something, right, right, right, 1:29:14.080 --> 1:29:17.719 generating monsters. Wow, that's awful. 1:29:18.160 --> 1:29:19.160 Isn't that horrible? 1:29:19.760 --> 1:29:20.719 We need a new word. 1:29:21.760 --> 1:29:23.360 I mean, I feel, you know, it's it's a word 1:29:23.400 --> 1:29:26.440 that right now, it's it's so deeply you know, embedded 1:29:26.520 --> 1:29:29.799 in medical literature and education. 1:29:30.040 --> 1:29:36.120 But it's kind of like wow, yeah, yeah, that's I 1:29:36.200 --> 1:29:37.760 don't know, I don't know what else to say about that, 1:29:37.800 --> 1:29:41.320 but I was I was dismayed to find that out. 1:29:42.120 --> 1:29:46.280 Wow. I am never going to forget that. Aaron, Yeah, 1:29:46.439 --> 1:29:46.760 you good. 1:29:46.800 --> 1:29:53.200 Wow, You're welcome. So yeah, anyway, back to sources. So, uh, 1:29:53.280 --> 1:29:56.479 I read a few books for this. So one is 1:29:56.479 --> 1:30:00.160 Suffered the Children by the Sunday Times Insight team in 1:30:00.200 --> 1:30:03.680 London and that was published in nineteen seventy nine. The 1:30:03.720 --> 1:30:06.479 second one was Dark Remedy The Impact of the Litamide 1:30:06.520 --> 1:30:09.400 and its Revival as a Vital Medicine by Trent Stevens 1:30:09.400 --> 1:30:12.559 and Rock Brinner from two thousand and nine, and finally 1:30:12.720 --> 1:30:15.439 Silent Shock The Men behind That, the Littamyde scandal and 1:30:15.479 --> 1:30:19.960 an Australian Family's Long Road to Justice by Michael Magazanik 1:30:20.560 --> 1:30:23.200 that was from twenty fifteen. And then finally there's a 1:30:23.200 --> 1:30:27.240 documentary called Attacking the Devil and that follows pretty closely 1:30:27.439 --> 1:30:30.639 the suffer the Children's story, so more about the fight 1:30:30.800 --> 1:30:38.120 to get UK families justice from distillers. Yeah, and so 1:30:38.680 --> 1:30:42.519 in addition to the first hand account that I read, 1:30:42.960 --> 1:30:45.800 as I mentioned, there are many other personal stories on 1:30:45.840 --> 1:30:48.479 that website and I'll post a link to that. But 1:30:48.680 --> 1:30:51.680 also as I was doing the research for this episode, 1:30:52.160 --> 1:30:56.679 I also found that the Welcome Library did an oral 1:30:56.760 --> 1:31:00.880 history project for people who have been affected by thaltamide 1:31:00.920 --> 1:31:06.080 and they have excerpts from the interviews on their SoundCloud 1:31:06.120 --> 1:31:09.600 account and also just more information on their website, so 1:31:09.760 --> 1:31:12.519 I'll post a link to those sources as well. 1:31:12.720 --> 1:31:17.320 Excellent and I had a number of different articles both 1:31:17.320 --> 1:31:21.840 about sort of the congenital effects of the litamide as 1:31:21.880 --> 1:31:24.920 well as what we use the litamide for today in 1:31:25.000 --> 1:31:29.080 terms of treatment. We'll post the full list of all 1:31:29.120 --> 1:31:31.880 of our sources for this episode, and you can find 1:31:31.920 --> 1:31:34.839 them from every single episode on our website, This podcast 1:31:34.920 --> 1:31:37.599 will Kill You dot Com under the episodes tab. 1:31:38.320 --> 1:31:41.559 Thank you to Bloodmobile for providing the music for this 1:31:41.640 --> 1:31:44.200 episode and all of our episodes, and. 1:31:44.240 --> 1:31:48.680 Thank you to you listeners. This was a pretty depressing episode, 1:31:49.040 --> 1:31:52.840 but we think it's a pretty important topic, so we 1:31:52.880 --> 1:31:55.720 really appreciate you sticking with us and making it through 1:31:55.720 --> 1:31:56.640 this episode. 1:31:56.920 --> 1:32:02.000 Absolutely. We hope you got something out of it. Yeah yeah, okay, 1:32:02.080 --> 1:32:04.320 Well with that, wash your hands 1:32:04.600 --> 1:32:05.760 You filthy animals.