Speaker 1: I was born in a body very different to my
Speaker 1: brother and sister. The only difference was that with me,
Speaker 1: my mum took one tablet in the early stages of pregnancy,
Speaker 1: and that one tablet sealed my fate in life. Can
Speaker 1: you just imagine the delivery room. Instead of the usual
Speaker 1: congratulations you have a beautiful, bouncing baby girl, there would
Speaker 1: have been absolute, hushed silence and gasps of horror as
Speaker 1: I was born. I was whisked away into a corner
Speaker 1: of the room and Mum never saw me for three
Speaker 1: days because the doctors decided that I was too grossly
Speaker 1: deformed for her to love me. These doctors didn't know
Speaker 1: my mum, who was the most wonderful woman in the world,
Speaker 1: and knowing what she went through with me breaks my heart.
Speaker 1: She lives with so much guilt for taking that one tablet.
Speaker 1: How did the drug affect me? For starters, I have
Speaker 1: no arms. I have three little fingers attached to a
Speaker 1: little hand that basically comes out of the side of
Speaker 1: my shoulders. There was also heaps of internal damage done
Speaker 1: to my heart and lungs, which has resulted in numerous
Speaker 1: open heart operations, and I still have more in the pipeline.
Speaker 1: My childhood was, of course, very different to any other child.
Speaker 1: I didn't walk until I was nearly seven, and then
Speaker 1: I had to be carried everywhere until I had major
Speaker 1: heart surgery when I was twelve. Although they repaired my heart,
Speaker 1: I still get extremely tired very quickly. I can't walk far,
Speaker 1: and I can't walk up hills as I get breathless,
Speaker 1: so I never knew the joy of running and skipping.
Speaker 1: The bullying has been horrid, to say the least, and
Speaker 1: that's not just by other kids who are bad enough,
Speaker 1: but by adults who are just as bad, if not worse.
Speaker 1: I have had doctors look down on me and say
Speaker 1: I am worthless and that I would never amount to anything.
Speaker 1: I have had doctors poking and probing my body like
Speaker 1: a lab rat because my body is so different, with
Speaker 1: no compassion as to how they were treating me. One
Speaker 1: doctor told me I would never have friends because who
Speaker 1: would want to be friends with someone with no arms.
Speaker 1: It also amazes me how people think they have the
Speaker 1: right to say the most horrid things to me when
Speaker 1: I'm out in public. It's no wonder that there are days,
Speaker 1: even weeks, where I do not leave the safety of
Speaker 1: my house. The pain in my body is horrendous and
Speaker 1: extremely debilitating. I need knee and hip replacements, but have
Speaker 1: been told that I can't have them as mechanical ones
Speaker 1: don't bend the way I need my body to bend,
Speaker 1: just so that I can eat and drink. Feet weren't
Speaker 1: meant to be hands, but that is exactly how I
Speaker 1: must do everything since I have no arms thanks to
Speaker 1: the litamide. Can you imagine getting dressed and eating or
Speaker 1: cleaning your teeth with your feet every day? It is
Speaker 1: no wonder my body is falling apart thanks to the litamide.
Speaker 2: Oh my god, Erin, Yeah I know.
Speaker 1: That was Trisha's story from the Solidamide Group Australia dot com.
Speaker 1: It was excerpts from her story, and I'll post the
Speaker 1: link to where you can read her full story, along
Speaker 1: with other people's stories who have been affected by thelamide. So, yeah, Hi,
Speaker 1: I'm Erin Welsh and I'm Erin almond Updake and this
Speaker 1: is this podcast will kill you.
Speaker 2: So you've probably figured out by now that today we're
Speaker 2: talking about solidimide.
Speaker 1: We are indeed a little a.
Speaker 2: Little different type of episode for us. It's not a disease,
Speaker 2: per se that we're talking about, but rather a drug.
Speaker 1: Yeah. I guess the only other one like this that
Speaker 1: we've done is aspirin. But this is going to be
Speaker 1: a very different story than aspirin.
Speaker 2: Wait a second, we did something else that was weird
Speaker 2: that wasn't a crossover lead lead that's the one. This
Speaker 2: is not that.
Speaker 1: This is not that. No, no, yeah, although this is heartbreaking,
Speaker 1: as you heard and as you will continue to hear. Yeah, yeah,
Speaker 1: all right, Well we have a piece of business to
Speaker 1: take care of, Aaron.
Speaker 2: It is quarantiney time.
Speaker 1: It is not what are we drinking this week?
Speaker 2: This week, we're drinking David and Goliath.
Speaker 1: Yes we are, and it is named David and Goliath,
Speaker 1: as you will find out later in the episode, because
Speaker 1: of all of the epic struggles to bring the dangers
Speaker 1: of the lidamide to light and how it's been basically
Speaker 1: like one fight after another and you know, with some
Speaker 1: triumphs in there.
Speaker 2: But yeah, yeah, and so Aaron, what's in David and Goliath?
Speaker 1: Yes, yes, it has lemon cello homemade. I would like
Speaker 1: to brag a gin and sometime simple.
Speaker 2: Syrup, fabulous, delicious, love it.
Speaker 1: And we will post the full recipe for the quarantine
Speaker 1: as well as the non alcoholic place Rita on all
Speaker 1: of our social media channels as well as our website.
Speaker 1: This podcast will Kill You dot com?
Speaker 2: Yes, well, any other business that we need to attend
Speaker 2: to Aaron the usual.
Speaker 1: You know, we have merch check it out This podcast
Speaker 1: will Kill You dot Com. We have a good Reads list.
Speaker 1: You can also find that on the books tab on
Speaker 1: our website, and we also have a Bookshop affiliate program,
Speaker 1: so you can find all the books that we talk
Speaker 1: about on the podcast through those links.
Speaker 2: Perfect. Well, shall we dive right in into what's going
Speaker 2: to be a very depressing episode?
Speaker 1: I think that we should.
Speaker 2: Let's take a quick break first. I think soamide, which
Speaker 2: is a synthetic derivative of glutamate or glutenic acid. So
Speaker 2: thilidamide is a drug. Aaron. You're going to talk about
Speaker 2: kind of what it used to be prescribed for and
Speaker 2: in the history, and I'm going to talk about what
Speaker 2: we use it for today. Spoiler alert, it's still out there.
Speaker 2: But what I want to focus on for the biology
Speaker 2: section is just what the effects are when it's used
Speaker 2: in pregnancy, since that's kind of the majority of the
Speaker 2: history of this drug.
Speaker 1: Am I right, Yeah, yeah, it's a huge part of it.
Speaker 2: Right. So Thlidamide is what's called a teratogen, which means
Speaker 2: it's a drug or a substance that when it's ingested
Speaker 2: or used during pregnancy, it results in congenital defects or
Speaker 2: malformations in the developing embryo or fetus. Okay, So to
Speaker 2: talk briefly about something that I love to talk about
Speaker 2: and think about, embryologic development in all animals, not just
Speaker 2: in humans. There's a very distinct pattern of embryologic development
Speaker 2: that has been extremely well studied. So we know all
Speaker 2: of the steps like from two cells to four cells
Speaker 2: to eight cells, et cetera. We know the steps of development,
Speaker 2: especially in humans, like down to the days okay, like
Speaker 2: what's going to develop in what order?
Speaker 1: Yeah, it's actually kind of incredible the amount of detailed
Speaker 1: information that we have on that.
Speaker 2: It's so cool. If you want like some real detail,
Speaker 2: I found a great website. It's called like embryology dot
Speaker 2: au or something. It's an Australian website and it has
Speaker 2: pictures of like every single stage. It's very cool. WHOA, Yeah,
Speaker 2: So in humans, the first eight weeks of development post fertilization,
Speaker 2: which in pregnancy we call ten weeks just stational age.
Speaker 2: That is the embryologic phase of development. At the end
Speaker 2: of this phase, so eight weeks post fertilization, ninety percent
Speaker 2: of the anatomical structures that an adult human has have formed. Wow,
Speaker 2: isn't that incredible?
Speaker 1: Yeah, that's oh wild, It's so cool.
Speaker 2: So any substances that have an effect on the developing
Speaker 2: embryo this early in the process can result in really
Speaker 2: significant effects downstream, right, versus drugs that might have an
Speaker 2: effect later in pregnancy, when most of the structures are
Speaker 2: already developed. Okay, all right, So that's sort of the
Speaker 2: brief overview. So the syndrome that tholidimide causes if ingested
Speaker 2: during pregnancy is called tholidamide embryopathy. That's like the Google
Speaker 2: term if you want to find it. It just means
Speaker 2: a pathogenesis in the embryo due to tholidimide. Okay. So
Speaker 2: there are a huge range of effects that thalinimide can have.
Speaker 2: Some of them I think are very characteristic. Like you
Speaker 2: might you might already have in your head an image
Speaker 2: I know you do erin because you've been researching this,
Speaker 2: but listeners, you might have an image in your mind
Speaker 2: when you hear the word solidimide M. But there's a
Speaker 2: massive range anywhere from very very severe to minimal effects,
Speaker 2: and this does make it really difficult to know if
Speaker 2: the syndrome that you're seeing is from tholitimide or from
Speaker 2: something else. Yep. Yeah, So we'll talk about kind of
Speaker 2: what the most common ones are and what the ones
Speaker 2: that are very much associated with solitimide and not really
Speaker 2: associated with other things, and kind of focus on those.
Speaker 2: So thlinimide often induces what's called focomelia, which was a
Speaker 2: new term for me.
Speaker 1: Actually, that was a new term for me too.
Speaker 2: Yeah, So focomelia is a shortening of the limbs that's
Speaker 2: usually most prominent in the proximal which means like your
Speaker 2: upper arm bones and upper leg bones compared to your
Speaker 2: distal like your forearms or your calfs or whatever. So
Speaker 2: you can end up with either very very short limbs,
Speaker 2: or you can have just like the hand bones and
Speaker 2: feet bones that are more directly attached to the shoulder
Speaker 2: or hip girdle, and that would be focomelia, or you
Speaker 2: can end up with complete loss of limbs, which is
Speaker 2: called amilia. But what's bizarre is that solidimide can also
Speaker 2: be associated with like polydactyle, which means having extra digits I.
Speaker 1: Have, Like, I can feel the questions coming up, and
Speaker 1: I'm just suppressing though, so I'm gonna just let you finish.
Speaker 2: Okay, great, because I don't know if I'm gonna have
Speaker 2: the answer to your question, darreon, but I'm gonna try
Speaker 2: really hard. Okay. One of the things though, that sets
Speaker 2: thlitim embryopathy apart from other genetic causes of shortened or
Speaker 2: missing limbs, and I think this is again very interesting,
Speaker 2: is that the shoulder. So if you look at the shoulder,
Speaker 2: it tends to be very pointed. And this is because
Speaker 2: the clavical tends to be a bit longer, and where
Speaker 2: the clavical attaches to your scapula, that's called the a
Speaker 2: chromioclavicular joint. So that joint tends to be very prominent
Speaker 2: in cases of theldamide embryopathy. Interesting, whereas some genetic causes
Speaker 2: of shortened or loss of limbs, that shoulder tends to
Speaker 2: be more sloped rather than pointed.
Speaker 1: Are you going to tell me why this happens? What's
Speaker 1: the function?
Speaker 2: Come on, I don't know that I'm going to quite honestly,
Speaker 2: really it's it's not really okay anyways, can moving on? Okay, now,
Speaker 2: those are the biggest characteristic typical Okay, focomelia, amelia, this
Speaker 2: prominent shoulder joint. When limbs are affected, it tends to
Speaker 2: be the what's called pre axial, which is your thumb
Speaker 2: side and your big toe side. Those sides of your
Speaker 2: hands and feet are affected before your post axial, So
Speaker 2: your pinky finger and little toe side of your limbs.
Speaker 1: Okay, So does that mean like you would be more
Speaker 1: likely to have your pinky finger and your ring finger
Speaker 1: intact and not have the first three fingers.
Speaker 2: Yeah, so it means that you wouldn't have your pinky
Speaker 2: and ring finger affected without also having your thumb affected.
Speaker 1: Gotcha, So, like.
Speaker 2: It affects that first in the case of thlamide embryopathy,
Speaker 2: which is different than some other causes of limb defects.
Speaker 2: The other thing about solamide embryopathy that sets it apart
Speaker 2: from some other causes is that it's almost always bilateral,
Speaker 2: if not perfectly bilateral, like absolutely equal shortening of limbs,
Speaker 2: at least mostly bilateral, so you're not going to have
Speaker 2: complete unilateral effects okay, and this, Erin, I know your
Speaker 2: question is always why this makes sense? Okay, because this
Speaker 2: is something that's affecting a developing embryo, and embryos develop symmetrically,
Speaker 2: and this is a toxic insult to that developing embryo.
Speaker 2: So it's not going to preferentially affect one side or
Speaker 2: the other. Gotcha ha, At least I had one, all right.
Speaker 2: And the other thing about philidamide is that the upper
Speaker 2: limbs are affected before the lower limbs, so the same
Speaker 2: way that the thumb is affected before the pinkies. You
Speaker 2: won't have loss of portions of your lower legs without
Speaker 2: also having loss of portions of your upper limbs.
Speaker 1: Ah, okay, okay.
Speaker 2: Do you ask me why? Erin? Ask me why? Why?
Speaker 1: Erin? Why?
Speaker 2: Okay? We don't fully know, but here's a hypothesis. Philidimide
Speaker 2: as it turns out, has a very narrow rain in
Speaker 2: which it has effects. Between twenty and thirty six days
Speaker 2: post fertilization is the window in which the lidamide exerts,
Speaker 2: especially its most severe effects, right, So that would be okay,
Speaker 2: that would be days thirty four to fifty after a
Speaker 2: last menstrual period. So gestational age five to seven.
Speaker 1: Weeks okay, which is very early.
Speaker 2: It's very early. It also happens to coincide with what
Speaker 2: is often the peak of morning sickness, which is like
Speaker 2: weeks four to twelve.
Speaker 1: All of these are very pertinent details to the history.
Speaker 2: I know it. And it also is when the limb
Speaker 2: buds are forming and the upper limb buds begin to
Speaker 2: form around day twenty six post fertilization, and the lower
Speaker 2: limb buds start to form one to two days later, okay,
Speaker 2: and grow from proximal so from like humorous to distal
Speaker 2: to your hands. So, depending on exactly what day you
Speaker 2: would have taken solidimide and how long your exposure is,
Speaker 2: your downstream effects are going to vary. A shorter or
Speaker 2: earlier exposure might only affect one small portion, like just
Speaker 2: your humorous bilaterally versus prolonged exposure, which could then go
Speaker 2: on to affect the distal arm and the leg and
Speaker 2: the distal leg gotcha. Okay. Now, limbs are not the
Speaker 2: only thing that can be affected in philidimide. Philimide can
Speaker 2: also cause eye damage and ear damage, including what's called microphthalmia,
Speaker 2: which means small eyes or complete loss of eyes and ophthalmos.
Speaker 2: It can cause absence or reduction of the ear, and
Speaker 2: again this is going to most often be bilateral, so
Speaker 2: on both ears. It can cause cleft lip or cleft palate.
Speaker 2: It can cause issues with the developing vertebrae. It can
Speaker 2: cause damage to nerves, which can cause things like eye palsies,
Speaker 2: so where you can't move your eyes properly because the
Speaker 2: nerves to your eyes have been damaged. And of course
Speaker 2: it can affect literally any of the developing internal organs
Speaker 2: as well, so your heart, your gi tract, your kidneys,
Speaker 2: you name it. Okay, right, So that's a lot of things, right, Yeah,
Speaker 2: which makes sense. I warned you, right, you're affecting an early,
Speaker 2: very very early stage of development. Okay, But of course,
Speaker 2: the biggest question that we try to answer is why
Speaker 2: or how like, how does this happen? Why did these
Speaker 2: specific things happen? Honestly, we don't know.
Speaker 1: Still, still, there were at least hypotheses. I read a
Speaker 1: few of them.
Speaker 2: There's always hypotheses erin, but that doesn't mean we know.
Speaker 1: Okay, I know, But are there good hypotheses?
Speaker 2: Yes, there are three, Okay, there are three good hypotheses
Speaker 2: that have the most support. Okay, one of them is
Speaker 2: the inhibition of angiogenesis, and this is something that we
Speaker 2: know that philidamide does because it's part of why we
Speaker 2: use it as a drug in other contexts today. So
Speaker 2: what does that mean? Angiogenesis is the process of blood
Speaker 2: vessel formation. So thlidamide is known to disrupt the formation
Speaker 2: of blood vessels, and it's not a far stretch to
Speaker 2: see how this disruption in the development of blood vessels
Speaker 2: to your arms would then cause a disruption in the
Speaker 2: growth of those arms in an embryo. But then that
Speaker 2: leads to a question, why does it affect the limbs
Speaker 2: so much more often than internal organs? Does it? Who knows?
Speaker 2: Because right it definitely has large effects on internal organs
Speaker 2: as well, and your limbs are a lot more or visible,
Speaker 2: so you see those effects more than you might see
Speaker 2: some effects on internal organs. But there's also some evidence
Speaker 2: that this is getting very nitty gritty detail, but the
Speaker 2: blood vessels developing in the limbs of an embryo lack
Speaker 2: smooth muscle at that particular stage and development when it
Speaker 2: is susceptible tooth so litamide, and that seems to be
Speaker 2: what allows the litamide to have an effect. So vessels
Speaker 2: that have smooth muscle are more resistant tooth soltamide.
Speaker 1: And how how does that very among internal organs at
Speaker 1: that stage? Like are there some that have more smooth
Speaker 1: muscle or less?
Speaker 2: Yeah, most of the internal organs have smooth muscle on
Speaker 2: their vessels as embryos like during that stage of development,
Speaker 2: whereas the limbs are what don't right?
Speaker 1: But is there any variation within those or within the
Speaker 1: internal organs?
Speaker 2: Great question? Probably I don't know the answer to that.
Speaker 1: Okay, here's another question, and gosh, here maybe it's jumping
Speaker 1: the gun. But okay, how long does the litamide stay
Speaker 1: in your body? And like why that that window is
Speaker 1: so narrow?
Speaker 2: Still?
Speaker 1: But yeah, I don't get it.
Speaker 2: It's a very good question. So the half life of
Speaker 2: the litamite is actually very short. It's like five to
Speaker 2: seven hours, okay, So that means that it's pretty rapidly
Speaker 2: excreted from your body, all right, And the question as
Speaker 2: to why is it only that particular window is a
Speaker 2: really good one. A lot of studies have shown in rats,
Speaker 2: which I'm sure you'll talk about are not a great model,
Speaker 2: and also in humans earlier exposure. So before twenty days
Speaker 2: often results in spontaneous pregnancy loss. Okay, so then the
Speaker 2: effects necessarily exactly the effects have been so dramatic that
Speaker 2: the that embryo is no longer viable, whereas after that
Speaker 2: period of thirty six days post fertilization, it's not clear
Speaker 2: what the effects are in humans. In rats, later exposure
Speaker 2: can induce brain damage in the fetal rat, okay, but
Speaker 2: whether that happens with solidamide, it it's not at least
Speaker 2: clear from what we know about humans. That makes sense, okay,
Speaker 2: but that is all just angiogenesis. So that's just one hypothesis.
Speaker 2: We have a couple more, but luckily they're shorter because
Speaker 2: they're not as interesting or they're not as easy to
Speaker 2: explain at least. So another hypothesis is that philidamide induces
Speaker 2: the creation of free radicals. We've talked a lot about
Speaker 2: radical reactive oxygen species. Yeah, so philidamide does that, and
Speaker 2: so it's thought that that production can then cause damage
Speaker 2: that results in what we see. Not a ton more
Speaker 2: detail I can give you beyond that. And then the
Speaker 2: third one I'm going to give you even less detail
Speaker 2: on because it's beyond my scope of being able to explain.
Speaker 2: But we know a few of the molecular targets that
Speaker 2: philidimide interacts with. So the specific genes that pholidimide seems
Speaker 2: to have an interaction with these are seriblonde and SALL four.
Speaker 2: What's very interesting is that there is a genetic disorder
Speaker 2: associated with mutations in the gene sa L four that
Speaker 2: result in really similar phenotypes, so really similar limb defects
Speaker 2: that we see in soholidimide. But this is a genetic disorder,
Speaker 2: like a hereditary disorder. So it's like, that's kind of
Speaker 2: an appealing hypothesis in that way that maybe pholidimide is
Speaker 2: interacting with this gene somehow which is turning something on,
Speaker 2: turning something off that's causing these limb defects.
Speaker 1: Does that gene have an impact on angiogenesis?
Speaker 2: Good question, not that we know of. Okay, yeah, so
Speaker 2: that's a really good question because we know that theladamide
Speaker 2: has all these effects downstream, right. It has effects on nerves,
Speaker 2: it has effects on cartilage, it has effects on all
Speaker 2: these different things. But the real question is like what's
Speaker 2: the first like what is the first disruption that results
Speaker 2: in all these downstream effects? And that is what we
Speaker 2: don't fully understand yet.
Speaker 1: M hmm, Yeah, a lot to take in.
Speaker 2: Yeah, this is a lot, right, and it's depressing. That's
Speaker 2: what I have for you. I'm not going to talk
Speaker 2: about what we use the litamide for today until the
Speaker 2: current events section.
Speaker 1: Okay, good, I'll talk a little bit about it, but
Speaker 1: I bet you will.
Speaker 2: So, Aaron, where did we come up with this drug?
Speaker 2: What the heck we've already kind of elluded it's it
Speaker 2: was you in pregnancy. Tell me, why tell me all
Speaker 2: about it? I want to know everything.
Speaker 1: Oh man, let's take a short break first.
Speaker 3: Okay.
Speaker 1: I think most people have heard of thelidamie before and
Speaker 1: its association with congenital defects. And the story that I
Speaker 1: remember learning in college was brief, like, in the nineteen sixties,
Speaker 1: a drug was developed that ended up causing these really
Speaker 1: severe congenital abnormalities, and when that link was discovered, it
Speaker 1: was pulled from.
Speaker 2: The market, Right, That's the story we heard.
Speaker 1: Yeah, and it was used I think as like a
Speaker 1: teaching moment of how a medication can have enormous unforeseen
Speaker 1: side effects and to represent just how far we've come
Speaker 1: in terms of our policies for drug regulation. And safety,
Speaker 1: almost like a cautionary tale about the price of progress.
Speaker 2: Yeah, and animal studies. I remember learning it in the
Speaker 2: context of animal studies. Mm hmm.
Speaker 1: That's a huge component to this.
Speaker 3: Yeah.
Speaker 1: But as it turns out, the story of the Litamyde
Speaker 1: is much much deeper than that. It always is, Erin,
Speaker 1: and I just have to say that. You know, like,
Speaker 1: we've been doing this podcast for three years now, we're
Speaker 1: going on our fourth year. Yeah, and you'd think that
Speaker 1: after reading about all of the various accounts of horrible
Speaker 1: unethical things that people do, I would cease to be
Speaker 1: shocked at some point.
Speaker 2: Oh no, Erin, but no.
Speaker 1: So with that to set the tone, let's get started.
Speaker 2: I'm sorry, okay, all right, deep, all right.
Speaker 1: Let's begin with an origin story, that of Kemi Grunenthal,
Speaker 1: the company that created the Linnamide Grunental. I'm just shortening
Speaker 1: it to that from this point on, I was created
Speaker 1: in West Germany in nineteen forty six, the year after
Speaker 1: World War two ended. And who better to staff a
Speaker 1: pharmaceutical company than a bunch of convicted mass murderers and
Speaker 1: war criminals.
Speaker 2: Oh oh, like the uh Nuremberg.
Speaker 1: Yeah, Basically it was like Nuremberg was like a a hiring,
Speaker 1: Yeah hiring.
Speaker 2: It turns out yeah cool, great, awesome.
Speaker 1: So convicted of mass murder, slavery, and crimes against humanity
Speaker 1: at the Nuremberg trials, Nazee Otto Ambrose actually ended up
Speaker 1: as the chair of Grunenthal's supervisory board and oversaw the
Speaker 1: production of the LDAMIDE.
Speaker 2: I already hate this story erin.
Speaker 1: I know it's really it's all downhill from here. Great
Speaker 1: m hm, but it's important to know. I feel like
Speaker 1: this is this is such an important story and it's
Speaker 1: been so underreported throughout its history. We've shortened it to
Speaker 1: this very tight little narrative, and I was shocked to
Speaker 1: read about all of the stuff that's like beneath the surface.
Speaker 1: So with that, so, before Otto Ambrose landed this position
Speaker 1: at Greenenthal, he had worked on chemical weapons and nerve agents.
Speaker 1: He had used slave labor from those imprisoned at Auschwitz,
Speaker 1: and was also involved in having another concentration camp built
Speaker 1: that was closer for convenience for his work. After serving
Speaker 1: three years of his eight year sentence, he was granted
Speaker 1: clemency by the US. He promptly landed that position at Grenental.
Speaker 1: Great another war criminal and murderer that found a job
Speaker 1: at Grunental was Heinz Baumbcotter, an SS doctor at a
Speaker 1: concentration camp outside Berlin where he would oversee executions, pick
Speaker 1: up people for gas chamber, and dabble heavily in medicalized
Speaker 1: torture using injections, explosives and chemicals. He too was convicted
Speaker 1: of these crimes and was actually sentenced to life, but
Speaker 1: was led out in eight years and immediately found a
Speaker 1: job at Grunenthal as a salesperson. And those weren't the
Speaker 1: only ones. There was also Ernst gunther Schenck, another SS doctor,
Speaker 1: and Martin Stemler, a Nazi who wrote copious amounts on
Speaker 1: how German people were racially superior, and he actually ended
Speaker 1: up head of Grunenthal's pathology department. And in general, it
Speaker 1: should be said that Grunenthal was no special case of
Speaker 1: hiring Nazi war criminals. In general, they actually found work
Speaker 1: pretty easily after their conviction, including in the US for instance,
Speaker 1: on research projects. But the question is what role did
Speaker 1: these Nazis play in the development and motion of the
Speaker 1: lidamide And for the names that I've already listed, it
Speaker 1: actually doesn't seem like they played much of a very
Speaker 1: active role, perhaps in sales or the general overseeing of
Speaker 1: the development. But there's one more name that I haven't
Speaker 1: yet mentioned, okay, and that's Heinrich Muchter. Also, I'm sorry
Speaker 1: if I'm horribly mispronouncing all of these names, all of them.
Speaker 2: You mean you don't speak German?
Speaker 1: I do not, and I probably should consult someone who
Speaker 1: speaks German to talk about these names. But well, here
Speaker 1: we are. During World War Two, Muchter worked in Poland
Speaker 1: as the deputy head of the Institute for Virus and
Speaker 1: Typhus Research, where he was involved in countless instances of
Speaker 1: medicalized torture. After the war, he fled Poland and the
Speaker 1: criminal charges that he faced there, and immediately was given
Speaker 1: a job at Grunenthal, and not just any job, but
Speaker 1: the director of research and development. He was also promised
Speaker 1: a percentage of sales in addition to his salary. Sales
Speaker 1: which would later include the Litamide. The Litamide would make
Speaker 1: Muchter incredibly wealthy. In nineteen sixty one, which spoiler was
Speaker 1: the last year that it was sold, Mucter's bonus was
Speaker 1: twenty two times his actual salary. What mm hmm, okay,
Speaker 1: So why did I spend so much time just now
Speaker 1: on the Nazi backgrounds of the people working or running
Speaker 1: the show at Grunenthal. Why it's because later on I
Speaker 1: know that you'll be asking, whether literally or rhetorically, just
Speaker 1: like I did, how could this happen? How could a
Speaker 1: company be so without morals? And when a company is
Speaker 1: comprised of people who are accustomed to a complete disregard
Speaker 1: for humanity and human life, as well as a culture
Speaker 1: of extreme respect for authority, you basically have a recipe
Speaker 1: for criminal negligence. Not I should note that it takes
Speaker 1: Nazis to be greedy or a moral or to put
Speaker 1: the bottom line above human lives, But in this case,
Speaker 1: I do think it's an important part of the background.
Speaker 1: So now let's get to the medical context in which
Speaker 1: the litamide was developed and introduced. So throughout the first
Speaker 1: half of the twentieth century, the use of barbiturates had
Speaker 1: steadily risen, especially in Europe, North America and Australia, and
Speaker 1: with this rise also came recognition of the dangers that
Speaker 1: barbiturates carry, such as addiction, overdose, and respiratory system suppression,
Speaker 1: and the growing awareness of this meant that the market
Speaker 1: was ripe for a safer alternative, especially when it came
Speaker 1: to sleep aids. So when grunental doctors on the hunt
Speaker 1: for a new antibiotic stumbled upon the litamide, who structure
Speaker 1: closely resembled that of barbiturates, they were hopeful it might
Speaker 1: act as a sedative and hypnotic. The next step was
Speaker 1: simply to test it out. Rats were supposedly given doses
Speaker 1: of the drug and observed for sleepiness as compared to
Speaker 1: non drugged rats, and the scientists came to the conclusion that, yes,
Speaker 1: this drug did have a sedative effect, which is interesting
Speaker 1: considering that no sleep was actually observed in the animals
Speaker 1: and no one was able to replicate the experiments.
Speaker 2: That's what.
Speaker 1: So it has something to do with something called a
Speaker 1: jiggle cage, and I'm not going to go into it,
Speaker 1: but basically it measures like the amount of like jiggle
Speaker 1: that the rats are, like movement that the rats would make,
Speaker 1: and the less movement they think they they figured translated
Speaker 1: into a more sedative effect.
Speaker 2: Right, So the rets just weren't moving around, but they
Speaker 2: weren't necessarily sleeping.
Speaker 1: Yeah, and it doesn't really hold up. No one could
Speaker 1: ever replicate it, so there's no telling what really wanted on.
Speaker 1: Additional experiments continued testing the safety of the drug, and
Speaker 1: the company gave it an A plus plus. Apparently there
Speaker 1: was no amount of drug that they could give the
Speaker 1: rats that would kill them.
Speaker 2: Okay, that we just know is false, because you can
Speaker 2: kill a rat with water.
Speaker 1: Okay, uh huh, I know, I know. But just because
Speaker 1: you don't instantly die from the drug doesn't mean that
Speaker 1: there won't be short or long term side effects. Right
Speaker 1: and crucially, no studies were conducted on the safety of
Speaker 1: the drug in pregnant animals, remember that, So rather than
Speaker 1: test animals pregnant or not for side effects, best to
Speaker 1: move on right to humans right naturally, And since we
Speaker 1: know that the company makeup at the time was at
Speaker 1: least in part Nazi, why not resort to what's familiar
Speaker 1: e g. Medicalized torture. So, for example, forty developmentally disabled
Speaker 1: children were given doses of the lidamide to twenty times
Speaker 1: that of the recommended dose for an adult, all without
Speaker 1: the parents' knowledge. Of course, two of the children died
Speaker 1: and one lost their sight. The doctor in charge of this,
Speaker 1: doctor Lange, said there's no way that the deaths were
Speaker 1: attributable to thlidamide.
Speaker 3: O my.
Speaker 1: Uh huh. And hidden among all of these glowing reports
Speaker 1: of the super safe and effective new sedative, some warning
Speaker 1: bells were going off. One doctor who had been given
Speaker 1: samples of the drug discontinued use because there appeared to
Speaker 1: be nerve damage after extended use, and another because it
Speaker 1: caused slight constipation in his patience, which I really appreciate.
Speaker 1: He's just like some people can't poop you well, backed up, well,
Speaker 1: and a lot of And his justification for this was that, like,
Speaker 1: you know what, this is not a life saving drug,
Speaker 1: This is not an essential drug. This is simply like
Speaker 1: an above and beyond and if it's causing discomfort, then
Speaker 1: there's no to give it.
Speaker 2: Can I ask you again what year this was? That?
Speaker 2: Like the already doctors had access to this drug.
Speaker 1: So in nineteen fifty four is when the littamide was
Speaker 1: discovered or developed. In a nineteen fifty seven it was
Speaker 1: released for public consumption. Okay, wow, so with three years, yeah, yeah,
Speaker 1: which is very fast in today's standards.
Speaker 3: Right.
Speaker 1: And so at this point the scientists at Grunenthal still
Speaker 1: weren't sure how the drug actually worked on a molecular level,
Speaker 1: which seems like we still don't truly know, but.
Speaker 2: Still aren't so can't fault him for that one single
Speaker 2: tiny thing.
Speaker 1: Nor did they know how long it stayed in the body.
Speaker 1: But none of this slowed the enthusiasm for the drug,
Speaker 1: and the litamide was launched in Germany in October of
Speaker 1: nineteen fifty seven under the name Kontragen, with hundreds of
Speaker 1: thousands of ads and letters directed towards doctors and pharmacists.
Speaker 2: Wow.
Speaker 1: Its biggest selling point was its absolute safety a toxicity,
Speaker 1: and this hype machine worked far outside the German borders
Speaker 1: as well. The pharmaceutical companies all over the world fought
Speaker 1: to license this wonder drug for sale in their country.
Speaker 1: So one of these companies was Distiller's Biochemical, which was
Speaker 1: an offshoot of Distillers, which sold some of the most
Speaker 1: recognizable liquor brands around the world. It was based in
Speaker 1: the UK, and Distillers won the bid to sell the
Speaker 1: linamide under the brand name dist of All in the
Speaker 1: UK and then also in Australia the year later in
Speaker 1: nineteen fifty nine, opting to have Grenenthal continue producing the
Speaker 1: drug while they would just package it and sell it
Speaker 1: under their name. Advertising for the litamide under any of
Speaker 1: its brand names almost solely consisted of assurances of its
Speaker 1: absolute safety.
Speaker 2: And sorry, at this point, it's marketed just as a
Speaker 2: sedative that is safer than barbituates.
Speaker 1: Yes, so it began just to be so that was
Speaker 1: how it was promoted to doctors, and then doctors sort
Speaker 1: of prescribed it for any manner of like sleep aid,
Speaker 1: sedative for people of varying age, like it just became
Speaker 1: sort of this like cure all type of drugging. And
Speaker 1: it also was not prescription. It was over the counter.
Speaker 2: Uh oh mm hm, oh, okay, I didn't know that, okay,
Speaker 2: m hmm. Yeah.
Speaker 1: So one ad that is very unsettling in light of
Speaker 1: all that would happen and all we know now showed
Speaker 1: a small child on a stool rummaging through the medicine cabinet.
Speaker 1: It's a picture of him and this kid has in
Speaker 1: his hands an unlabeled bottle, with the implication that there's
Speaker 1: about to be a horrible overdose of some drug. But
Speaker 1: then the ad makes it clear that it's actually dist
Speaker 1: of all, with the quote this child's life may depend
Speaker 1: on the safety of dist of all.
Speaker 2: Oh that's bad, is that not?
Speaker 1: That's bad, horrible, but because it was at least superficially
Speaker 1: safer than barbiturates, a point that sales rep were urged
Speaker 1: to hammer on over and over again, it really grew
Speaker 1: in popularity. In some places, sales of the litamide were
Speaker 1: second only to aspirin.
Speaker 2: Wow, which, like our hitty, We've talked about the problems there.
Speaker 1: We've talked about how popular aspirin was and some of
Speaker 1: the problems with aspirin.
Speaker 3: Wow.
Speaker 2: Though, Wow second to aspirin.
Speaker 1: And by nineteen sixty it was the best selling sleeping
Speaker 1: pill in Germany.
Speaker 2: Wow.
Speaker 1: A liquid form was advertised as being a great sedative
Speaker 1: for children.
Speaker 2: Why are you sedating your children? Oh? Stop it?
Speaker 1: And it gets worse because it had the nickname cinema
Speaker 1: juice or the baby sit because parents could just drug
Speaker 1: their kids with the littamide and go off to the
Speaker 1: movies and not have to worry about them.
Speaker 2: Mike, do not drug your child to sleep. Cinema juice.
Speaker 1: Yeah. So, despite being hailed as this incredibly safe drug,
Speaker 1: reports of some side effects of the lidamine started to
Speaker 1: trickle in, not of congenital defects or still births or miscarriages,
Speaker 1: but rather peripheral nerve damage. Doctors began to bring these
Speaker 1: reports to Grunental, and in response, Grunenthal did not pull
Speaker 1: the drug from the market, nor did they further investigate
Speaker 1: these claims or run any additional experiments to see what
Speaker 1: might be going on. Rather, they lied, they denied, and
Speaker 1: they spied. Ooh. Grunenthal hired a PI to follow around
Speaker 1: the doctors that made these complaints because they were convinced
Speaker 1: that a rival pharmaceutical company such as Bayer was behind
Speaker 1: it all. Wow, there's absolutely no truth to this. By
Speaker 1: the way, the little mind does cause nerve damage.
Speaker 2: Yeah, that's like the number one side effect that causes
Speaker 2: it to be discontinued in use today.
Speaker 1: Mm hmm. And this PI even followed the victims of
Speaker 1: nerve damage to see whether they would seek compensation, and
Speaker 1: he gathered dirt on both patients and doctors involved in
Speaker 1: these reports.
Speaker 2: Wow.
Speaker 1: Uh huh. When one Grunental rep went to sell more
Speaker 1: thalidamide to a psychiatric wing and a hospital, he heard
Speaker 1: no reports of nerve damage, and he attributed this to
Speaker 1: a lack of reporting, writing in a letter to his
Speaker 1: boss's quote, maybe the idiots are happy when there's tingling.
Speaker 1: Uh huh, and another employee one uped this despicable remark
Speaker 1: by suggesting that the lidamide be combined with other ingredients
Speaker 1: so that the nerve damage could be blamed on those
Speaker 1: compounds instead. What uh huh, this is real, This really happened.
Speaker 2: So then they're like, yes, sure, whatever, it causes nerve damage,
Speaker 2: but like that doesn't Oh my god, erin, I know.
Speaker 1: I know. Just breathe. You have to just practice, like
Speaker 1: focus on your breathing during this.
Speaker 2: I don't know if I can do that. You're just
Speaker 2: gonna hear like a for the background of this whole episode.
Speaker 2: No one's gonna want to listen.
Speaker 1: Yes. So, so, while while internally Grunental began to more
Speaker 1: closely watch the drug, they at no point made any
Speaker 1: public announcement regarding it, fighting any pressure to put a
Speaker 1: warning on the bottle or make it prescription only. And
Speaker 1: Grunenthal wasn't the only one to be receiving these reports either.
Speaker 1: Distillers the licensee in the UK and Australia had learned
Speaker 1: of potential nerve damage and immediately slapped a warning label
Speaker 1: on its packaging. They asked Grunental about the nerve damage,
Speaker 1: and they were assured that it was only in very
Speaker 1: rare cases and they cleared up quickly. Also not true.
Speaker 1: Some nerve damage was permanent, if not like the majority
Speaker 1: of it. But then another concern came to light. Distillers
Speaker 1: had been developing a liquid version of the lidamide, similar
Speaker 1: to the cinema juice that Grunenthal had made, and they
Speaker 1: were in the process of running some preliminary tests using
Speaker 1: animals rats I think in particular, when some disturbing results
Speaker 1: came to light. The animals were dying at like not
Speaker 1: very high doses, and apparently the liquid was much more
Speaker 1: toxic than the pill form, and so these claims of
Speaker 1: extreme safety were unfounded.
Speaker 2: And that's the one you're giving to babies so you
Speaker 2: could go watch a movie.
Speaker 1: And the company brought their concerns and these results to Grunentol,
Speaker 1: who assured them that they had run similar tests but
Speaker 1: no animals had died, suggesting that it might be due
Speaker 1: to a difference insensitivities between German and English mice.
Speaker 2: That what come on, I know.
Speaker 1: I know. So this logic, if you can even call it, that,
Speaker 1: we cannot shaky to begin with. It completely falls apart
Speaker 1: with the first published report of nerve damage in connection
Speaker 1: with the litamide, titled is the Litamide to Blame? And
Speaker 1: written by Scottish doctor Leslie Florence, published in the British
Speaker 1: Medical Journal in December of nineteen sixty. Immediately following this publication,
Speaker 1: tons of doctors wrote to Florence saying that they had
Speaker 1: seen the same thing in their patients, and his letter
Speaker 1: was a pivotal moment in the history of the litamide
Speaker 1: because it not only created the momentum that would increase
Speaker 1: scrutiny of the super safe drug, but it also played
Speaker 1: a huge role in one of the biggest triumphs of
Speaker 1: drug regulation or oversight. At this time early nineteen sixty one,
Speaker 1: the litamide was a big hit in the countries where
Speaker 1: it's pretty was licensed, but there was still one big
Speaker 1: untapped market, the United States. Grunenthal had been working with
Speaker 1: its US licensee for over a year to try to
Speaker 1: get the drug on the market in the US. In
Speaker 1: anticipation of the eventual approval, they had stockpilot the litamide
Speaker 1: and they were basically all ready to go except for
Speaker 1: one thing FDA approval. FDA Medical Officer and mdphd I
Speaker 1: believe Francis Oldham Kelsey had raised a list of questions
Speaker 1: and concerns about the drug, and none of the answers
Speaker 1: that she was ever given made her any more assured
Speaker 1: in the safety of the litamide, and the hopeful licensee company,
Speaker 1: Richardson Merrill, was not used to not getting their way,
Speaker 1: and so they essentially harassed her. They complained to her
Speaker 1: boss to try to get someone else on the case,
Speaker 1: and they made like over fifty contacts to her, which
Speaker 1: was like, highly against regulation. There wasn't supposed to be
Speaker 1: any contact between like the medical officer and the drug company.
Speaker 1: They weren't even supposed to know who she was, like, oh,
Speaker 1: her name, but her boss gave them not only her
Speaker 1: name but her phone number, which is, oh my god, bizarre.
Speaker 1: So anyway, so Kelsey was already feeling super suspicious of
Speaker 1: the company's demands when in early nineteen sixty one, she
Speaker 1: stumbled across Leslie Florence's article about the lidamite and nerve damage,
Speaker 1: something that the US licensee rep had failed to mention.
Speaker 1: So she called a meeting to basically call them out.
Speaker 1: She was like, all right, let's have a meeting. So
Speaker 1: is there something you're not telling me? They're like, no, no,
Speaker 1: everything's great, Like this drug is the best thing that's
Speaker 1: ever been invented. And she's like, what about this paper
Speaker 1: And they're like, oh no, it's it's nothing like that.
Speaker 1: That's just whatever, you know, And she was like, Okay,
Speaker 1: here's a list of questions that I need thorough answers
Speaker 1: for scientifically supported. Among these questions were what were the
Speaker 1: long term side effects, how and when did nerve damage occur?
Speaker 1: What levels led to overdose? And the new one, which
Speaker 1: hadn't really been asked that much before, was was the
Speaker 1: litamide safe during pregnancy?
Speaker 3: Yeah.
Speaker 1: For more than six months, the company continued to fight
Speaker 1: for the license in the US, but still Kelsey held
Speaker 1: her ground. She felt that their answers were not satisfactory.
Speaker 1: The drug would remain off the shelves in the US,
Speaker 1: and when it was finally revealed that the littamide greatly
Speaker 1: harmed the fetus if taken during pregnancy, Francis Kelsey's role
Speaker 1: in preventing its licensing in the US earned her a
Speaker 1: great fame. However, there is a dark side to the
Speaker 1: story in the US. Even though thlidomide was never officially
Speaker 1: for sale here, millions of samples were sent out across
Speaker 1: the US by the hopeful licensee Richardson Merril. To do this,
Speaker 1: they exploited some loopholes to get the drug into the
Speaker 1: hands of doctors all over the US in promotional events
Speaker 1: masquerading as clinical trials. Over two point five million pills
Speaker 1: were handed out to more than twelve hundred doctors, which
Speaker 1: gave them to around twenty thousand people.
Speaker 2: Wow.
Speaker 1: Richardson Merrill rep. Doctor Pogue. I think that's how you
Speaker 1: say it. Ghost wrote an article under the name of
Speaker 1: a Cincinnati GP and submitted it to the American Journal
Speaker 1: of Obstetrics and Gynecology stating how wonderfully the drug worked
Speaker 1: and how safe it was for the fetus or newborn,
Speaker 1: but no studies had actually been done, but it got
Speaker 1: published anyway. This GP, by the way, was no stranger
Speaker 1: to this practice of like putting his name on an
Speaker 1: article that he didn't write, and he continually denied any
Speaker 1: wrongdoing in this.
Speaker 2: Wow.
Speaker 1: Four months passed after the news of the link between
Speaker 1: the lidamide and congenital defects before Richardson Merrill finally told
Speaker 1: the doctors involved in these quote unquote studies to stop
Speaker 1: their research and return all the remaining samples, four months
Speaker 1: after it had been pulled from German markets.
Speaker 2: Four months after it had been pulled from German markets.
Speaker 1: When the extent of their deceit and for shady behavior,
Speaker 1: I mean that's like not inadequate, it's not adjective, but yeah,
Speaker 1: when it was discovered, the FDA pushed for Richardson Merrill
Speaker 1: to face criminal charges, which of course they didn't. Okay,
Speaker 1: So I wanted to tell that part about the US
Speaker 1: and one big chunk, so I skipped ahead a little bit.
Speaker 1: So now it's backtracked to before the link between the
Speaker 1: littamide and congenital abnormalities was uncovered.
Speaker 2: Yeah, like more detail please?
Speaker 1: Yeah? So okay. So, alongside its success as an extremely
Speaker 1: popular sleeping aid, the littamide was also freely handed out
Speaker 1: as a treatment for morning sickness, uncontrolled vomiting, and pregnancy
Speaker 1: and just general anxiety for pregnant.
Speaker 2: People because you know those hysterical pregnanty.
Speaker 1: The hysterical pregnant people. In some instances it was specifically
Speaker 1: advertised for those uses. In one distiller's brochure, they claimed
Speaker 1: that quote, it is with absolute safety that dist of
Speaker 1: all can be administered to pregnant or breastfeeding women without
Speaker 1: any adverse effects on the mother or the child. The
Speaker 1: reports of nerve damage associated with the drug led to
Speaker 1: its starting to require a prescription in some countries, and
Speaker 1: it also prompted additional questions about the safety of the drug,
Speaker 1: especially as it related to pregnancy. Grunenthal, of course, was
Speaker 1: quick to dismiss and mislead any and all inquiries. For instance,
Speaker 1: when one pharmacist wrote to the company in November nineteen
Speaker 1: sixty on the suspicion that the drug had caused birth
Speaker 1: defects in one of his patients, they replied immediately, dear
Speaker 1: mister pharmacist, based on all observations and findings on hand
Speaker 1: to date, in particular from gynecological departments, we can negate
Speaker 1: any causal connection. To date, not a single indication exists
Speaker 1: at all to suggest that a human or animal, irrespective
Speaker 1: of age, could suffer any form of liver damage through kontragen.
Speaker 1: We therefore feel safe in assuming that the liver damage
Speaker 1: diagnosed shortly after the birth of the baby you are
Speaker 1: referring to is not to be connected with the mother's
Speaker 1: contragen use. They didn't ask questions about the mother. They
Speaker 1: didn't investigate these claims further or ask a hospital about
Speaker 1: any increase in congenital malformations. They just denied. They asked
Speaker 1: an ob to use the drug and report on its findings.
Speaker 1: This doc gave the little Mine exclusively to breastfeeding mothers.
Speaker 1: He refused to give it to pregnant people, and reported
Speaker 1: that it appeared safe to both mother and baby. Bits
Speaker 1: and pieces of his report were misleadingly used in an
Speaker 1: advertising letter that Grunenthal sent to German doctors. Quote, dear doctor,
Speaker 1: during pregnancy and lactation, the female organism is subject to
Speaker 1: particular stresses. The female organism, female.
Speaker 2: Organism ross is disgusting.
Speaker 1: Okay, I'll continue. Sleeplessness, inner unrest, and tiredness are recurring complaints.
Speaker 2: Inner unrest does that mean? Like? What what does that mean?
Speaker 1: Oh?
Speaker 2: I'm gonna lose it.
Speaker 1: I know this is this is definitely the most rage
Speaker 1: inducing episode like we've had in a very long time.
Speaker 1: It is there for often necessary to prescribe a sedative
Speaker 1: and hypnotic, which is harmless to mother and baby. When
Speaker 1: the Obie docs saw this letter, he was appalled by
Speaker 1: how they had misconstrued his words to indicate that the
Speaker 1: drug had also been tested to be safe and pregnant people.
Speaker 1: I don't know if he took issue with the female
Speaker 1: organism or inner unrest part.
Speaker 2: He probably didn't, quite honestly, he was an OBI in
Speaker 2: the fifties. I don't know. Maybe he did. I shouldn't assume,
Speaker 2: but we'll never know.
Speaker 1: I think that's the bottom line. In February nineteen sixty one,
Speaker 1: a pharmaceutical firm reached out to Grunenthal to ask whether
Speaker 1: there were any data on the safety of the drug
Speaker 1: for fetuses, because they wanted to develop it as a
Speaker 1: potential way to prevent miscarriages.
Speaker 2: I know, oh horrifying.
Speaker 1: Grunental responded that they had never done any experiments, but
Speaker 1: they could prove useful even though they're there's been nothing
Speaker 1: so far to make them doubt it's absolute safety. They
Speaker 1: never took it upon themselves to run the experiments and
Speaker 1: to look directly at the link. Ever, when a finished
Speaker 1: doctor asked them three straightforward direct questions. One does the
Speaker 1: lidamide cross the placenta? Answer not known? Two? Can't the
Speaker 1: litamide have a damaging effect on the fetus? Answer improbable? Three?
Speaker 1: In what part of the body is the litamide broken
Speaker 1: down answer, probably by the liver. What yeah, this.
Speaker 2: Wasn't made things up, and then didn't even answer like,
Speaker 2: it's also it's not even the liver.
Speaker 1: This was in July of nineteen sixty one, so the
Speaker 1: drug had been out for four years at this point
Speaker 1: and had been developed seven years earlier. They had ample
Speaker 1: opportunity to do all kinds of studies, and not to
Speaker 1: mention that they had received reports a possible link between
Speaker 1: the lidamide and congenital defects as early as August nineteen
Speaker 1: fifty eight.
Speaker 2: That's like a year after it was out.
Speaker 1: Right, which, yeah, just as with the peripheral nerve damage.
Speaker 1: Though while their outward position was deny internally, Grunenthal began
Speaker 1: looking into the matter. Fears and alerts continued to pile
Speaker 1: up during nineteen sixty one. By the summer, Grunental employees
Speaker 1: refuse to take the drug because of the side effects,
Speaker 1: and Mucht himself said he would not prescribe it if
Speaker 1: he were a doctor. He was like, I would not
Speaker 1: prescribe the drug. It's not safe, but we're going to
Speaker 1: keep selling it. The company's own lawyers were like, wow,
Speaker 1: you didn't do any experiments. There's no way that the
Speaker 1: insurance company is going to cover you. Don't go to trial,
Speaker 1: just settle your screwed. What would it take for there
Speaker 1: to be some oversight, some looking into these claims. Well,
Speaker 1: one thing's for sure, it wasn't going to be done
Speaker 1: by Grunenthal. The two main people involved in uncovering the
Speaker 1: link between the litamide and congenital defects were an Australian
Speaker 1: ob named William McBride and a German doctor named vidukind
Speaker 1: I hope that's right. Lens McBride is typically credited as
Speaker 1: the first person to recognize that the litamide was at
Speaker 1: the root of an epidemic of congenital abnormalities, although later
Speaker 1: he would face his own controversy when it was real
Speaker 1: that he had fabricated some of his research results and
Speaker 1: he would be stripped of his medical license.
Speaker 2: Why are all these humans?
Speaker 3: I know?
Speaker 1: I know?
Speaker 2: So?
Speaker 1: He had also been giving his patients the lidamide at
Speaker 1: the request of distillers, and when he delivered three babies
Speaker 1: in short succession that all had severe congenital defects, some
Speaker 1: very similar to one another, he immediately suspected that's something
Speaker 1: specific was causing these and eventually, though not as soon
Speaker 1: as you might think. He landed on the linamide, and
Speaker 1: he brought his suspicions to the sales rep who passed
Speaker 1: on his concerns, which were dismissed as having no basis.
Speaker 1: In fact, this was in June nineteen sixty one. McBride
Speaker 1: took it upon himself to see if he could induce
Speaker 1: some of these congenital abnormalities in an animal experiment involving
Speaker 1: guinea pigs and mice. But he didn't use a control
Speaker 1: group and didn't compare doses. He simply looked for malformations
Speaker 1: similar to the ones that he had observed in humans,
Speaker 1: and he didn't find any, and so a seed of
Speaker 1: doubt was planted.
Speaker 2: This is what happens if you don't have a lot
Speaker 2: of training and research study design.
Speaker 1: Yeah, very true. And still though for months he continued
Speaker 1: to run these experiments and to ask distillers to look
Speaker 1: into the matter and even to pull the drug until
Speaker 1: additional testing was done.
Speaker 2: That's a very reasonable request.
Speaker 1: It is, But they didn't listen. They didn't they didn't
Speaker 1: take him up on that. And over in Germany, around
Speaker 1: the same time that McBride was developing his own suspicions
Speaker 1: about the lidamide lens vidukin Lens was beginning to notice
Speaker 1: an unusual increase in congenital defects when a man whose
Speaker 1: wife and sister both gave birth to babies with very
Speaker 1: similar congenital abnormalities.
Speaker 2: And that's weird your wife and your sister. No, maybe
Speaker 2: it's not that weird.
Speaker 1: Well, so at first she was like, is it genetic?
Speaker 1: Is it something with that? But then as the head
Speaker 1: of a children's clinic at Hamburg University, he recognized that
Speaker 1: these were not only like probably not linked to genetics,
Speaker 1: but that they were incredibly rare. Right, these were ones
Speaker 1: that you would see every like, I don't know how
Speaker 1: many years, two in short succession. Was like red flag,
Speaker 1: something's going on. Yeah, yeah, And so he was like, okay,
Speaker 1: I'm I want to see whether there's a common factor
Speaker 1: between this, and in his research he learned that there
Speaker 1: were several more children that had been born with the
Speaker 1: same deformities like in his area. And then he was like, okay,
Speaker 1: now it's time for like full on detective work. So
Speaker 1: he launched this investigation, calling doctors around the country and
Speaker 1: digging through medical reports and newspapers. By his estimate, in
Speaker 1: the last couple of years there were two hundred times
Speaker 1: more congenital defects than usual. Whoa can you imagine tallying
Speaker 1: those numbers with like the dawning horror? Oh my, Yeah.
Speaker 1: He was convinced that there was a single element that
Speaker 1: was causing this.
Speaker 2: Uh huh.
Speaker 1: He thought maybe detergent, maybe something else, nuclear falloup, maybe
Speaker 1: some sort of other like face lotion was one of
Speaker 1: the things, I think, But eventually he land on the
Speaker 1: lidamide after asking detailed drug histories of the mothers that
Speaker 1: he interviewed. He brought this evidence to Grunenthal and asked
Speaker 1: that the littam I'd be withdrawn from sale. The company
Speaker 1: was like, all right, yeah, yeah, sure, we can talk
Speaker 1: about it, and he was like, that's not good enough.
Speaker 1: So he sent an express letter that declared that he
Speaker 1: thought it was irresponsible to quote wait for the strict
Speaker 1: scientific proof. I consider it necessary to withdraw the drug
Speaker 1: immediately from the market until its innocuousness as a tarratogenic
Speaker 1: agent in man is proved with certainty reasonable a reasonable, like.
Speaker 2: The most basic of reasonable.
Speaker 1: And so he like, you know, he forced them to
Speaker 1: have a meeting with him and in the meeting, they
Speaker 1: simply tried to discredit his research and then later threatened
Speaker 1: him with legal action. Irony of all ironies. Grunenthal then
Speaker 1: appear to try to start a smear campaign against Lens
Speaker 1: by saying, isn't this the son of the Nazi eugenicist
Speaker 1: Fritz Lens? What? Just like my what?
Speaker 2: What?
Speaker 1: But Lens wouldn't let it drop. Even when faced with
Speaker 1: Lens's detective work and reports from distillers of six babies
Speaker 1: who died from complications after their mother took the litamide,
Speaker 1: they refused to stop sales. They said, We'll let the
Speaker 1: doctors know what Lens thinks of the litamide, but that's it.
Speaker 1: But then a newspaper article appeared that shared Lens' findings
Speaker 1: and said that a popular sleeping pill not naming the
Speaker 1: litamide outright or Kuntergen, was responsible for a huge increase
Speaker 1: in birth defects. And that was the final straw for
Speaker 1: Grunental and the litamide.
Speaker 2: So it took a newspaper article like it took public opinion,
Speaker 2: Essentiallykelly Yes.
Speaker 1: It would finally be withdrawn from the market on November
Speaker 1: twenty sixth, nineteen sixty one, which was eleven days after
Speaker 1: Lenz first brought his findings to the company. But they
Speaker 1: had known about it before then, Let's not make that mistake,
Speaker 1: of course, not to mention the nerve damage.
Speaker 2: Yeah.
Speaker 1: Despite these enormous revelations, the media was a bit slow
Speaker 1: to pick up the story outside of Germany, in part
Speaker 1: because the involved companies discouraged local coverage, and distillers had
Speaker 1: to approach to Grunenthal to be like, hey, this guy
Speaker 1: McBride is saying that the littamide might be causing congenital defects.
Speaker 1: Do you know anything about this? And Grunental replying, oh, yeah, yeah,
Speaker 1: we're pulling the drug from the market. What so should
Speaker 1: we do that too, Like, yeah, you should do that.
Speaker 1: And I should note that although the littamide was pulled
Speaker 1: from the shelves in Germany in November nineteen sixty one,
Speaker 1: in many other countries it remained on the shelves for
Speaker 1: months after this connection had been made.
Speaker 2: Jeez.
Speaker 1: Some companies said, oh, you know, we'll sell what we've
Speaker 1: got and then we'll pretend like we ran out of stock.
Speaker 1: Literally it continued in some places, I think Japan, it
Speaker 1: was sold for months and months and months after like
Speaker 1: just absolutely. I can't wrap my brain around this.
Speaker 2: I can't either, I literally. I mean it's because the
Speaker 2: bottom line is money, right, right, mm hmm, that's it.
Speaker 1: Okay, Yeah, this is a very disheartening episode.
Speaker 2: I'm sorry, it really is so.
Speaker 1: But you know, even when the dangers of the drug
Speaker 1: began to come to light, Grinental didn't acknowledge their wrongdoing. Instead,
Speaker 1: they promised to fight for the lidamide quote to the last,
Speaker 1: with all measures. Within a few days of pulling the
Speaker 1: drug from the market, they started working on their legal
Speaker 1: defense strategy, no knowing that many legal battles lay ahead
Speaker 1: of them. In nineteen sixty seven, nine Grunental executives faced
Speaker 1: criminal charges, including negligent homicide in Germany. And if you
Speaker 1: thought you couldn't be any more disgusted by this company,
Speaker 1: I'm sorry to say that you were wrong. God, Aaron,
Speaker 1: I know because I'm about to tell you some of
Speaker 1: their defense strategies. Number One, they insisted that there was
Speaker 1: no evidence that the litamide cause nerve damage or fetal malformations,
Speaker 1: finding doctors who would actually support that claim. Number Two,
Speaker 1: that even if the litamide caused these supposed defects, a
Speaker 1: fetus has no legal rights in Germany, so it wasn't
Speaker 1: against the law to damage a fetus.
Speaker 2: I'm sorry. Oh okay, uh huh.
Speaker 1: Number three, there were many other compounds that were far
Speaker 1: more likely to be responsible, including detergents, nuclear fallout, and television.
Speaker 2: Rays yep, those television rays.
Speaker 1: Number four, that the tholidamide actually helped save those babies
Speaker 1: who would otherwise have not survived.
Speaker 2: Okay, that just literally doesn't make any sense.
Speaker 1: M They were like, oh, well, they would have. They
Speaker 1: would have like either died or been still born or
Speaker 1: miscarried or whatever. But the the litamide actually allowed them
Speaker 1: to survive. With those with those fetal malformations.
Speaker 2: That okay, mm hmm.
Speaker 1: And number five the most appalling, that the congenital defects
Speaker 1: were actually caused by the mothers themselves in botched abortion attempts. Yeah,
Speaker 1: this was one of their defense strategies. I wrote down
Speaker 1: a few adjectives and then I ran out like deplorable, disgusting, despicable,
Speaker 1: Like I don't know what else. There's there aren't words.
Speaker 2: I don't have any word. There aren't words. What.
Speaker 1: There's no way that this company would not held accountable
Speaker 1: for their actions. Right, ugh, wrong, wrong, the trial dragged
Speaker 1: on and on and on, and after three years of
Speaker 1: tedious proceedings, the trial ended with basically a slap on
Speaker 1: the wrist for Grunental and German law forbade them from
Speaker 1: being further prosecuted. For decades, they admitted no wrongdoing, even
Speaker 1: at times playing the victim. How this unforseeable tragedy has
Speaker 1: haunted the Wertz family, who still owns Grunental, which is
Speaker 1: still an operating company by the way, for years, Aaron,
Speaker 1: I know this is a tough one.
Speaker 2: Yeah, it really is.
Speaker 1: According to CBC, an estimated twenty four thousand babies worldwide
Speaker 1: were born with the lidamide induced malformations, with an additional
Speaker 1: one hundred and twenty three thousand still births and miscarriages. Wow,
Speaker 1: and those are conservative estimates.
Speaker 3: Yeah.
Speaker 1: The story of the legal battles for compensation for those
Speaker 1: babies now adults affected by the litamide is an entire
Speaker 1: podcast in and of itself, not just an episode, And
Speaker 1: while I won't go into a ton of detail, I
Speaker 1: will of course recommend further reading. The long and short
Speaker 1: of it is that any sort of justice has either
Speaker 1: been long delayed or denied entirely. It has been an
Speaker 1: upward battle every step of the way, with incredible obstacles.
Speaker 1: For example, in England there was a press gag for years,
Speaker 1: so the story of distillers and the litamide could not
Speaker 1: be written about for years and years and years. Yeah,
Speaker 1: it's really interesting.
Speaker 2: How can you even do that?
Speaker 1: So there's a whole documentary that I'll recommend that goes
Speaker 1: into it in great detail. It's called Attacking the Devil.
Speaker 2: What.
Speaker 1: Yeah, it has to do with not biasing a court
Speaker 1: case essentially by public opinion or whatever.
Speaker 2: Because it was still in a court case was.
Speaker 1: Still but like once that court case starts, then it's
Speaker 1: a press gag until it's over. But that gag, that
Speaker 1: press gag prevented the public support that may have led
Speaker 1: to more accountability and actually adequate compensation rather than like
Speaker 1: the extremely i mean shockingly paltry pensions that they received.
Speaker 1: And since then there's been a lot more like struggle
Speaker 1: and fight. I mean, just like the story is ongoing.
Speaker 1: I think this is another big aspect of it. But
Speaker 1: also you know, in this of course, just like the
Speaker 1: name of our quarantine suggests, there are a lot of
Speaker 1: incredible people that have stood up against these pharmaceutical companies
Speaker 1: and saying, you know what, no, like you will be
Speaker 1: held accountable. You're going to like help us at the
Speaker 1: very least we can't we can't get the lives that
Speaker 1: we could have had back. You were going to help us,
Speaker 1: like live as comfortably as possible. You know that's and
Speaker 1: I think that's yeah. So there are still people continuing
Speaker 1: this fight today. In August twenty twelve, Grunenthal's chief executive,
Speaker 1: Harold Stock, gave the first and only public apology, if
Speaker 1: it can be called that, on behalf of the company,
Speaker 1: at the unveiling of a statue of a victim of
Speaker 1: the lidamide quote. We ask that you regard our long
Speaker 1: silence as a sign of the silent shock that your
Speaker 1: fate has caused us.
Speaker 2: What m h are you that's not even close to
Speaker 2: an apology.
Speaker 1: No, no, Before I wrap up with the story of
Speaker 1: the little Mites comeback, I want to address one line
Speaker 1: of defense that was used by both Grunenthal and Distillers
Speaker 1: to absolve them of any guilt.
Speaker 2: Why it's just going to make me angrier.
Speaker 1: I know, I know. And this line of defense well, well,
Speaker 1: so it's important because this line of defense has been
Speaker 1: misused in the narrative of the lidamide that is often told.
Speaker 1: So the story of the litamide often places the drug
Speaker 1: at the center of drug testing reform, particularly in ensuring
Speaker 1: a drug safety during pregnancy. Yes, and to be fair,
Speaker 1: the enormous media attention given to that the litamide tragedy
Speaker 1: did bring increased scrutiny to drug testing and awareness and
Speaker 1: regulation and about how what might be safe for a
Speaker 1: pregnant person might not be safe for a fetus. But
Speaker 1: the whole oh, we didn't test the drug in pregnant
Speaker 1: animals because it just wasn't done at the time. And
Speaker 1: you know, at the time, no one knew that a
Speaker 1: drug could affect the fetus and not the mother. Like
Speaker 1: that doesn't fly one little bit. So let's not pretend
Speaker 1: like that's what's going on. Because when the litamide was developed,
Speaker 1: there were plenty of drug companies that were testing their
Speaker 1: rugs on pregnant animals to ensure its safety in the fetus,
Speaker 1: because people had long observed that some drugs may be
Speaker 1: toxic to a fetus but not the person carrying the fetus.
Speaker 2: Okay, and here's another thing, Arin, because I feel like
Speaker 2: when I learned this story it was this story. It
Speaker 2: was what I remember was that it was like, oh,
Speaker 2: we even tested it in some animal models, but in
Speaker 2: a lot of mammalian animals that we often use for
Speaker 2: testing drug testing, it doesn't cause those effects in the fetus.
Speaker 2: So they're like, we just didn't know, and so it's
Speaker 2: like the importance of using the correct animal model. That's
Speaker 2: the context that I remember learning the filidamide story is
Speaker 2: like choosing the quote correct animal model for doing these
Speaker 2: studies in but like, this is so far, so far
Speaker 2: beyond that.
Speaker 1: Oh, it's so far beyond that. And also like, I
Speaker 1: do you think that is part of it? Like that
Speaker 1: was sort of something that brought to light the fact
Speaker 1: that you know, it further illustrated differences between some mammal
Speaker 1: species and humans and how you can't necessarily make a
Speaker 1: connection between those. But the lidamide still does affect rats
Speaker 1: during pregnancy, and so it.
Speaker 2: Doesn't cause the same defects that we see. There isn't
Speaker 2: a good mammalian model for the limb defects that we
Speaker 2: see in mammals.
Speaker 1: So I think there actually were some pregnant rats included
Speaker 1: in some of the studies, and there was note taken
Speaker 1: of the fact that there was an overall reduced litter size,
Speaker 1: which should be a red flag for all. And secondly,
Speaker 1: the rats were found to have resorption scars on their uterus,
Speaker 1: which happens when a fetus develops and then dies or
Speaker 1: like doesn't make it to like birth right.
Speaker 2: So there were red flags even if there weren't the
Speaker 2: exact like congenital abnormality these that were seen in humans.
Speaker 1: But then after the link between congenital defects and the
Speaker 1: littamide came to light, a researcher at Distillers was like, okay,
Speaker 1: we need to do some studies to see whether this
Speaker 1: is like happening in animal models, you know, realizing like, oh,
Speaker 1: we should have done this a long time ago. And
Speaker 1: he tested the drug on rabbits and voila, like it
Speaker 1: was very similar to what they were seeing in humans.
Speaker 1: Like there were congenital defects. It was some New Zealand
Speaker 1: white rabbit or something like that species. Weird, okay, So anyway,
Speaker 1: that defense, like all of their defenses, does not hold
Speaker 1: any water. All right, the final section come back. So
Speaker 1: when the littamide was pulled off the market in nineteen
Speaker 1: sixty one, its mechanism of action was still unknown, and
Speaker 1: I wrote that not knowing that we still don't know it.
Speaker 2: I mean we know a lot more.
Speaker 1: Okay, yeah, yeah, yeah, yeah, But some researchers were starting
Speaker 1: to ponder what it might be. Early experiments weren't showing
Speaker 1: much promise. But then in nineteen sixty four, a physician
Speaker 1: at a leprosy clinic was desperate to help one of
Speaker 1: his patients who had severe painful boils NL. If you
Speaker 1: remember what that stands for?
Speaker 2: Oh do I what is it? I do? But listeners don't.
Speaker 2: Probably it's erythema. No dose some lipprosum.
Speaker 1: Yeah, yea, so hugely painful, horrible boils. They're so painful
Speaker 1: and so uncomfortable that you can't sleep, you can't eat,
Speaker 1: they don't heal like it's horrific. And so he had
Speaker 1: he realized he had some leftover thlidamide that he hadn't
Speaker 1: thrown out yet and was like, you know what, here
Speaker 1: takes some of these. Maybe they'll help you sleep. And
Speaker 1: not only did the person actually get some sleep, but
Speaker 1: their boils healed like ye, they healed, which was almost
Speaker 1: unheard of. Yeah, And so then that one person turned
Speaker 1: into a study of like many more, and it was
Speaker 1: found to be extremely successful in treating NL So why
Speaker 1: this worked to help people with leprosy wouldn't become clear
Speaker 1: until nineteen ninety one, and then the litamide would be
Speaker 1: in the headlines again. At this time, the HIV AIDS
Speaker 1: pandemic was in full swing and there was still no
Speaker 1: widely accepted treatment for the virus. Enter the litamide, which
Speaker 1: acted to reduce TNF alpha to murnder crosis factor alpha,
Speaker 1: the cytokine found at high levels in people who are
Speaker 1: HIV positive. The litamide, because it was banned in the US,
Speaker 1: I was actually being smuggled into the country.
Speaker 2: Wow.
Speaker 1: And so the FDA decided to revisit this band drug
Speaker 1: and ultimately decided to legalize it, which is a very
Speaker 1: short sentence, but not a fast or easy decision. It
Speaker 1: was like a lot of contentious debate going on, and
Speaker 1: even after its legalization, the amplified side effects in people
Speaker 1: with HIV or AIDS who already had weakened immune systems
Speaker 1: meant that its popularity didn't last long for that, but
Speaker 1: it was found to be helpful in people with multiple myeloma.
Speaker 1: So Aaron earlier, you asked me if this episode is
Speaker 1: going to have any bright spots, so honestly, those are
Speaker 1: the only ones that I can really think of. I
Speaker 1: think there are like thousands of lessons to be learned
Speaker 1: from the story of the lidamide, but I think one
Speaker 1: of them is that I feel like we tell this
Speaker 1: story a lot to kind of, in a way, reassure
Speaker 1: ourselves that, you know, we've grown so much, we're doing
Speaker 1: so much better now, And I think that's valid. In
Speaker 1: many ways we are, but it still very much scares me.
Speaker 1: The whole bottom line over a human life, and I
Speaker 1: don't think that aspect has gone away at all, especially
Speaker 1: in light of like American healthcare and just how disgustingly
Speaker 1: abysmal it is in terms of like insurance companies, pharmaceutical companies, hospitals,
Speaker 1: like just this vicious cycle.
Speaker 2: I think another thing that concerns me is that the
Speaker 2: lessons that I feel like I have been taught from
Speaker 2: the solidamide story in classes that I have taken are
Speaker 2: not the lessons that I am taking away from this
Speaker 2: discussion with you. Yeah, so that is concerning to me.
Speaker 1: I agree, well, Aaron, what's going on with the Littlemie today.
Speaker 1: I don't know how else to end this really depressing
Speaker 1: history section.
Speaker 2: Do we even want to talk about it?
Speaker 1: I think we do.
Speaker 2: It's gonna be okay, let's take a quick break. Okay,
Speaker 2: all right, So, like you mentioned, aaron, solimid hasn't disappeared,
Speaker 2: and I have written in my notes that that's actually
Speaker 2: a good thing, and it is a good thing because
Speaker 2: it's a very useful drug, as it turns out, for
Speaker 2: a number of disorders. But now, after you told me
Speaker 2: this story, in my pit of my stomach, I'm like,
Speaker 2: do you know what it just means that the drug
Speaker 2: companies are still making money off of this drug, you know, like,
Speaker 2: don't worry, we found another use for it. It's that's
Speaker 2: what drug companies do with every drug. They're like, oh, gaba,
Speaker 2: pendin doesn't work great as a seizure med but hey,
Speaker 2: it works for peripheral oropathy, you know, right, Okay, sorry, anyways,
Speaker 2: let's talk about it. And I also want to clarify something.
Speaker 2: So in the biology section, when I was talking about
Speaker 2: how we don't fully understand the mechanisms of thlidamide, that
Speaker 2: is true, but it's more true for the mechanisms of
Speaker 2: thlidamide embryopathy than it is true for the mechanisms of thlidamide,
Speaker 2: not in the fetus, if that makes sense. Yeah, okay,
Speaker 2: So the part about the inhibition of angiogenesis, we know
Speaker 2: that that's what thlidimide does. What we don't know is
Speaker 2: exactly how that causes the congenital defects.
Speaker 1: Gotcha.
Speaker 2: And like you mentioned, tholiimide is an inhibitor of TNF
Speaker 2: alpha tumoricrosis factor alpha. So those are kind of two
Speaker 2: of the biggest ways that we know that thlidamide works
Speaker 2: in the ways that we use it, like in adults
Speaker 2: and children that are not pregnant. Okay, mm hmm. So
Speaker 2: what do we use it for today? It's been studied
Speaker 2: at least peripherally in a really wide range of conditions,
Speaker 2: but there are a few conditions that it's like really
Speaker 2: more commonly used for and like more associated with today.
Speaker 2: So we'll kind of just like run through them all
Speaker 2: and then focus a little bit on the two or
Speaker 2: three biggest ones. Okay, m hm. So it has been
Speaker 2: used for the treatment of Crone's disease, which I think
Speaker 2: is fascinating. How does that work, don't I don't know? Okay,
Speaker 2: But what's even more interesting is that I found a
Speaker 2: paper that it's it was used in children with Crohn's
Speaker 2: disease that were also infected with tuberculosis. So you can't
Speaker 2: use other like forms of therapy in those kids because
Speaker 2: it would increase the tuberculosis load.
Speaker 1: Oh, because it would be immunosuppressive exactly right.
Speaker 2: Yeah, so yeah, super interesting. It's not super well studied
Speaker 2: in chro in general, and it's not like a first
Speaker 2: line therapy, but in refractory chrones it has been used.
Speaker 2: It's also used to treat graft versus host disease, which
Speaker 2: is what happens when you get a bone mirror transplant
Speaker 2: and the donor marrow starts attacking the recipient's owned cells,
Speaker 2: which is a really common complication of bone marrow transplantation. Okay,
Speaker 2: don't ask me how that works because I'll explain it
Speaker 2: in a minute. And then two of the kind of
Speaker 2: most common uses are the ones that you mentioned aaron,
Speaker 2: multiple myeloma, and leprosy, okay, and specifically Erythema nodosum leprosum.
Speaker 2: That's not actually leprosy, but it's an autoimmune reaction to
Speaker 2: infection with Microbacterium lepre So. Multiple miloma is a type
Speaker 2: of blood cancer that specifically affects your plasma cells, which
Speaker 2: like the mature form of B cells. Okay, check our
Speaker 2: vaccines episode if you want more. Okay. So, your plasma
Speaker 2: cells normally make antibodies. So it's like, how on earth
Speaker 2: can this treat a blood cancer? Essentially it doesn't make sense. Well,
Speaker 2: it turns out that multiple myeloma is associated, like most cancers,
Speaker 2: with an increase in angiogenesis. Okay, And so the effect
Speaker 2: that solidimide has on a couple of specific growth factors
Speaker 2: that are associated with angiogenesis fibroblast growth factor and vascular
Speaker 2: endothaleal growth factor so FGF and VEGF, as well as
Speaker 2: its effects on TNF alpha. Those things all combined are
Speaker 2: how it has its effects on a multiple myeloma which
Speaker 2: is associated with an increase in angiogenesis. Now, a logical
Speaker 2: question you might ask me, Aaron, is can this be
Speaker 2: used in any cancer?
Speaker 1: You're just preempting all of my questions, sarh.
Speaker 2: Yeah. The answer is it has been studied in a
Speaker 2: number of other cancers, but it's not as well studied.
Speaker 2: And I think what it boils down to is that
Speaker 2: for a lot of other cancers, we have better treatments,
Speaker 2: whereas multiple myeloma is something that before this we really
Speaker 2: didn't have anything. So thilinide was kind of like revolutionary
Speaker 2: in that way. And graft versus host it's kind of
Speaker 2: the same thing, right, So it's inhibiting those cytokinds associated
Speaker 2: with the inflammatory response, right. So yeah, and then erethoma
Speaker 2: nodosum leprosum. Again, this is an immune mediated reaction to
Speaker 2: infection with the bacteria. So by suppressing that inflammation somehow,
Speaker 2: thilinomide works really well to treat that disorder. Now do
Speaker 2: you want some depression to end this depressing episode?
Speaker 1: I mean, I think I can guess what it is.
Speaker 2: Yeah, Okay, so the congenital effects of tholidamide are not gone. No,
Speaker 2: I couldn't find sort of exact numbers on like what
Speaker 2: the epidemiology is worldwide. In most countries, philidamide is very
Speaker 2: tightly regulated because of its effects, its tyotogenic effects, so
Speaker 2: it's only given you know, it's given under like in
Speaker 2: the US, it's called the Class X drug, which means
Speaker 2: it's completely one, absolutely contraindicated in pregnancy. Generally Class X
Speaker 2: drugs if you are a person of reproductive age. You
Speaker 2: generally have to ensure that you're not going to become
Speaker 2: pregnant if you're going to use this drug, and so
Speaker 2: there's like a lot of regulation with that. Gotcha, Okay,
Speaker 2: And this is not just people with uteruses actually, because
Speaker 2: the litamide can be transmitted in the semen as well.
Speaker 1: So I was wondering if you were going to bring
Speaker 1: that up.
Speaker 2: Yeah, So it's anyone of reproductive age. It's it's obviously
Speaker 2: most severe if you are a person with a uterus
Speaker 2: who becomes pregnant while you're using it, but it's anyone
Speaker 2: of reproductive age because it can be transmitted in the
Speaker 2: semen as well. But one place that there is some
Speaker 2: good data on kind of the numbers of babies that
Speaker 2: are being born with soldamite exposure today is Brazil, and
Speaker 2: that's largely because, first of all, there's groups that are
Speaker 2: actively studying it and doing active surveillance for it, but
Speaker 2: also because leprosy is common in Brazil compared to a
Speaker 2: lot of other countries. So I think I saw there
Speaker 2: are about twenty four thousand cases of multibaselar leprosy, which
Speaker 2: is the kind that is associated with this arithema nodosum
Speaker 2: leprosim that are diagnosed annually in Brazil, and so so
Speaker 2: this study was looking at what the birth rate of
Speaker 2: tholdimide embryopathy was and they found that in the period
Speaker 2: from two thousand to two thousand and eight, that rate
Speaker 2: has actually increased compared to the previous decades. So it's
Speaker 2: now three point one per ten thousand live berths compared
Speaker 2: to about one point nine per ten thousand live births
Speaker 2: from nineteen eighty two to nineteen ninety nine. What's going on,
Speaker 2: It's not clear, and this study really couldn't get a
Speaker 2: good handle on it. Thiltamide is tightly regulated in Brazil,
Speaker 2: but you know, leprosy is also still a problem there,
Speaker 2: and so the study also reported that med sharing might
Speaker 2: also be contributing. So if we're not getting a handle
Speaker 2: on who exactly is taking tholidamide and if people also
Speaker 2: the other thing is that leprosy tends to happen in
Speaker 2: very rural areas, in very remote areas where people might
Speaker 2: not have as much knowledge about polimide. But the other
Speaker 2: thing is that the history that you told Aaron is
Speaker 2: not in the distant past, no, And I think that's
Speaker 2: another thing that you know, when we learned about tholidamide
Speaker 2: in school multiple times, you know, they show these black
Speaker 2: and white pictures and it makes it seem like this
Speaker 2: was so long ago, but it wasn't. This was like
Speaker 2: our parents' generation, right absolutely, And so babies that were
Speaker 2: born with anomalies or congenital defects due to thlamite exposure
Speaker 2: are now adults living with these effects, and there are
Speaker 2: thousands of them across the globe. I think the estimate
Speaker 2: I saw was about three thousand people living from like
Speaker 2: that nineteen sixties cohort of tholtamide exposure, and there are
Speaker 2: a number of support groups. I think the Internet has
Speaker 2: been wonderful for this and that people have been able
Speaker 2: to find other survivors and kind of connect with them,
Speaker 2: And there are a ton of different support networks and
Speaker 2: things across the globe in every different country where there
Speaker 2: are theletomide survivors and so now these are adults that
Speaker 2: are living with these quality of life issues. And there
Speaker 2: is a really interesting paper that came out last year
Speaker 2: that kind of specifically looked at this in UK, theiletomide Survivors,
Speaker 2: So we'll definitely link to that on the website as well.
Speaker 1: Awesome. Yeah, so I think that's really important to remember.
Speaker 1: This is this is not history, this is like it's
Speaker 1: still happening.
Speaker 2: Yeah, it is absolutely show we cite our sources so
Speaker 2: that people can do more reading and learn even more
Speaker 2: about this horrible tragedy.
Speaker 1: Absolutely. But actually, you know what I realized is that
Speaker 1: throughout that super long history section there's one thing that
Speaker 1: I completely forgot to mention or touch on, which is etymology.
Speaker 1: But not of the lidimide, because we've talked about that.
Speaker 1: It's just like a shortening of its super long chemical name,
Speaker 1: but of teratogen. Aaron, do you know what tiatogen the
Speaker 1: origin is?
Speaker 2: Oh my gosh no, And I've never even thought about it.
Speaker 1: Yeah, I didn't realize it until I think I was
Speaker 1: reading one of these accounts or it was in a documentary.
Speaker 1: And it surprises me that it is still used because,
Speaker 1: let me tell you, so, the word territology had been
Speaker 1: around since the eighteen hundreds, meaning like basically any sort
Speaker 1: of irregularity during any developmental process, so whether it was
Speaker 1: like in the womb or during puberty, not just humans
Speaker 1: but also plants or whatever. But tatagen was coined really
Speaker 1: only or started to be used really only in nineteen
Speaker 1: fifty nine. But both of these share the same root,
Speaker 1: which is from the Greek tirato, meaning marvel or monster
Speaker 1: what and so literally Taratagen has monster in the name.
Speaker 2: Yeah, but I mean, and I would assume jen is
Speaker 2: like general, like it generates it or something, right, right, right,
Speaker 2: generating monsters. Wow, that's awful.
Speaker 1: Isn't that horrible?
Speaker 2: We need a new word.
Speaker 1: I mean, I feel, you know, it's it's a word
Speaker 1: that right now, it's it's so deeply you know, embedded
Speaker 1: in medical literature and education.
Speaker 4: But it's kind of like wow, yeah, yeah, that's I
Speaker 4: don't know, I don't know what else to say about that,
Speaker 4: but I was I was dismayed to find that out.
Speaker 2: Wow. I am never going to forget that. Aaron, Yeah,
Speaker 2: you good.
Speaker 1: Wow, You're welcome. So yeah, anyway, back to sources. So, uh,
Speaker 1: I read a few books for this. So one is
Speaker 1: Suffered the Children by the Sunday Times Insight team in
Speaker 1: London and that was published in nineteen seventy nine. The
Speaker 1: second one was Dark Remedy The Impact of the Litamide
Speaker 1: and its Revival as a Vital Medicine by Trent Stevens
Speaker 1: and Rock Brinner from two thousand and nine, and finally
Speaker 1: Silent Shock The Men behind That, the Littamyde scandal and
Speaker 1: an Australian Family's Long Road to Justice by Michael Magazanik
Speaker 1: that was from twenty fifteen. And then finally there's a
Speaker 1: documentary called Attacking the Devil and that follows pretty closely
Speaker 1: the suffer the Children's story, so more about the fight
Speaker 1: to get UK families justice from distillers. Yeah, and so
Speaker 1: in addition to the first hand account that I read,
Speaker 1: as I mentioned, there are many other personal stories on
Speaker 1: that website and I'll post a link to that. But
Speaker 1: also as I was doing the research for this episode,
Speaker 1: I also found that the Welcome Library did an oral
Speaker 1: history project for people who have been affected by thaltamide
Speaker 1: and they have excerpts from the interviews on their SoundCloud
Speaker 1: account and also just more information on their website, so
Speaker 1: I'll post a link to those sources as well.
Speaker 2: Excellent and I had a number of different articles both
Speaker 2: about sort of the congenital effects of the litamide as
Speaker 2: well as what we use the litamide for today in
Speaker 2: terms of treatment. We'll post the full list of all
Speaker 2: of our sources for this episode, and you can find
Speaker 2: them from every single episode on our website, This podcast
Speaker 2: will Kill You dot Com under the episodes tab.
Speaker 1: Thank you to Bloodmobile for providing the music for this
Speaker 1: episode and all of our episodes, and.
Speaker 2: Thank you to you listeners. This was a pretty depressing episode,
Speaker 2: but we think it's a pretty important topic, so we
Speaker 2: really appreciate you sticking with us and making it through
Speaker 2: this episode.
Speaker 1: Absolutely. We hope you got something out of it. Yeah yeah, okay,
Speaker 1: Well with that, wash your hands
Speaker 2: You filthy animals.