This Podcast Will Kill You - Ep 102 Arsenic: Paris Green with Envy

Episode Date: August 2, 2022

“The king of poisons,” “the poison of kings,” “inheritance powder.” As its various nicknames suggest, arsenic’s notoriety largely stems from its use as a murder weapon. But as we explore in this episode, the world of arsenic is much, much bigger than just as a plot device in an Agatha Christie novel, and it remains one of the most important environmental contaminants today. But how exactly does arsenic affect your body? When did people first start to use arsenic and for what purposes? Where does it have the most impact currently? And, of course, why was it so popular as a murder weapon? Tune in to hear the answers to these and many, many more questions about one of the most notorious poisons out there. See omnystudio.com/listener for privacy information.

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faintly at first. Her shoulders were shaken by a strong shuddering, and she was growing paler than the sheets in which her clenched fingers buried themselves. Her unequal pulse was now almost imperceptible. Drops of sweat oozed from her bluish face that seemed as if rigid in the exhalations of a metallic vapor. Her teeth chattered. Her dilated eyes looked vaguely about her, and to all questions, she replied only with a shake of the head. She even smiled once or twice. Gradually, her moaning grew louder. A hollow shriek burst from her. She pretended she was better, and that she would get up presently. But she was seized with convulsions and cried out, ah, my God, it is horrible. Then the symptoms ceased for a moment. She said,

seemed less agitated, and at every insignificant word, at every respiration, a little more easy, he regained hope. His colleague was by no means of this opinion, and as he said of himself, never beating about the bush, he prescribed an emetic in order to empty the stomach completely. She soon began vomiting blood. Her lips became drawn, her limbs were convulsed, her whole body covered with brown spots, and her pulsed slipped beneath the fingers like a stretched thread. like a harpstring nearly breaking. After this, she began to scream horribly. She cursed the poison, railed at it, and implored it to be quick and thrust away with her stiffened arms, everything that Charles, in more agony than herself, tried to make her drink.

Emma, her chin sunken upon her breast, had her eyes inordinately wide open, and her poor hands wandered over the sheets with that hideous and soft movement of the dying, that seems as if they wanted already to cover themselves with the shroud. Her chest soon began panting rapidly. The whole of her tongue protruded from her mouth. Her eyes as they rolled grew paler, like the two globes of a lamp that is going out, so that one might have thought her already dead, but for the fearful laboring of her ribs, shaken by violent breathing, as if the soul were struggling to free itself. Emma raised herself like a galvanized corpse, her hair undone, her eyes fixed, staring. She fell back upon the mattress in a convulsion. They all drew near. She was dead.

Ay, aye, aye, Aaron. Yeah. So that was heavily edited down from like the last chapter. Sorry for the spoilers, but the book has been out since the 1850s. Madame Bovary by Gustav LeBer. And yeah, the lead character dies of arsenic poisoning. Self-inflicted. Wow. Yeah. I have a question. Okay.

In that book, does she take arsenic for a long time? Or does she just like take a big dose of it? She takes a big dose of it from what I can tell. I attempted to read it, but I didn't start it early enough. And I gave up. Yeah, that's fair. But yeah, I'm excited to see. how the description there stacks up against what we know about arsenic poisoning from the biology

section. Yeah, me too, Aaron. So maybe not super close. Cool, cool, cool, cool, cool. I mean, come on, it's a novel. You have to allow some literary license, right? A hundred percent, yeah. Okay, let's dive in. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And today we're talking about arsenic, obviously. Obviously, it's going to be really interesting. There's a lot of fun trivia. I'm thrilled to learn about how it works. But first, should we, is it time? It's quarantini time. It is. What are we drinking this week? This week we're drinking the king. We're drinking the king. The actual king. The actual king. Arsenic is commonly known as the king of poisons and also the poison of kings.

Which I did not know and I really love. Yep. And so we just decided to keep it simple and keep it sweet with the king. The king. And what's in the king, Aaron? What's in the king is essentially a Midori sour. Fantastic. Yeah. We had to have something green because, as you'll learn, arsenic was used as a colorant for like different shades of green a lot during the 19th century. And yeah, Midori is hits, ticks that box. And very green. Yeah. And essentially a Midori sour is

Midori, lemon juice, lime juice, soda water. And we'll post the full recipe for the king as well as the non-alcoholic placebo-rita on our website, this podcast will kill you.com, as well as on all of our social media channels. On our website, this podcast will kill you.com. The things that you can find there are numerous. They include our merch and our bookshop.org affiliate account and our Goodbeats list, as well as Bloodmobile, our music, and transcripts for all of our episodes and all of the sources that we use in every episode.

You can find our Patreon. You can find, really, you name it. It's probably on our website. That's true. That's true. All right. I think that's all the business that we have. So can we get started?

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Quince.com slash this podcast. So, Aaron, when I started researching for arsenic, immediately right off the bat, I got really heavy Mercury vibes, meaning I was way out of my league and turns out that we don't have a lot of specifics, just like with Mercury. Okay. But I will tell you everything that I learned and then can't wait for your questions that I probably won't know the answer to. I can't wait to ask them.

I know. It's my favorite part. So arsenic is a metalloid. What is a metalloid? you may ask, because that's certainly what I asked, everyone, because chemistry really is something that makes me nervous. But I'm going to do my best, and it means that I'll explain it as if you know nothing, because we all know nothing. Let us go. A metalloid is not quite a metal and not quite a non-metal. When we look at the periodic table of elements. So I feel like most people probably have a

sense of what a metal is, even if you don't remember back to your high school chemistry class, like what the definition is. If you give somebody a chunk of something and say, is this metal or no, they'll be like, hmm, is it shiny? Is it solid? Does it look like metal? Et cetera. So those are the kinds of things that make a metal, a metal, right? They're generally shiny or metallic or lustrous. Metals are generally good conductors of heat and electricity. Non-metals can be anything, but in general they're not as good of conductors. They're less good than metals. And metalloids are somewhere in between. It turns out that there's no good consensus definition of what makes a metalloid a metalloid. It's not a very clear term, but it's still used in a lot of chemistry

textbooks. And the most common elements on the periodic table that are considered metalloids are boron, silicon, germanium, antimony, tellurium, and of course, arsenic. So arsenic is an element like carbon or lead or mercury. It just happens to be somewhere in between carbon and lead and mercury in that it's not a non-metal and not a metal. It's a metaloid. And much like carbon, arsenic, as it turns out, exists in what are called different allotropes. I learned so many interesting facts about arsenic. Aletropes, I have not come across that word, but I love it. Yeah, it's a really fun word. It basically means that it can form different crystalline structures that look differently. The same way, if you think of carbon atoms,

can form diamonds or graphite, right? Same atoms, different structure looks totally different. In the case of arsenic, there's gray arsenic, black arsenic, and yellow arsenic. And, Gray is the form that looks the most like a metal and tends to act the most like a metal. It can be a semiconductor, so that's very useful in a lot of industrial settings, which I'll get to. And arsenic is often used in metal alloys for that reason. And just like our friend and another element that we've talked about on this podcast, Mercury, arsenic also exists across the earth in various compounds, both organic compounds, like carbon-based compounds and inorganic or no-carbon-involved compounds.

And if you remember our mercury episode as well as our lead episode, which was a very long time ago now, the toxicity of elements like arsenic depends in part on what form we get exposed to, as well as, of course, whether we're being exposed to small amounts over long periods of time, like a chronic exposure or a big hefty dose all at once like an acute poisoning. And it turns out that with arsenic, this is very important. The type of arsenic that you're exposed to really determines the toxicity. And being not a chemist, I tried to not get too bogged down in oxidation states and valences. But it turns out that that's what's really important when it comes to arsenic. So the basics look like this. Arsenic is close to phosphorus on the periodic

table. And so in some forms, when it's oxidized in a certain way, it's called a pentavalent form. It's an inorganic form of arsenic. That's called arsenate. And it really can resemble phosphate, which is a form of phosphorus. And phosphate in our bodies is a pretty integral part of human biology. It's the P in our ATP, adenosine trifosate. And so much like with lead and mercury, what we see with arsenic is that the toxicity arises from its ability to mimic other compounds that our body normally uses and or its ability to hijack various enzymes or metabolic pathways because of these similarities. It's so interesting that it does that.

Because we talk about infectious diseases primarily on the podcast, although maybe not as much anymore, we think of these pathogens as striving to reproduce and survive. And that's why they cause infection. That's why they make us sick. But with arsenic, it's just like here's this inert thing that just happens to be extremely deadly. Right. Exactly. It just happens to have an effect in our bodies because it's similar to things that our body actually needs and uses. But not because we need it in any way. And it just happens to be there. Yeah. Oh, it's very interesting. Yeah. I know. So that's one way.

that arsenic can exert its toxicity when it's in its oxidized pentavalent form. Another, probably even more common and more toxic form of arsenic, is called arsenite. And this is the trivalent form. This is what happens when arsenic is in a reducing environment. And this, in a very similar way, disrupts a number of our biological processes, but not by mimicking phosphate in this case, but by having a high affinity for what are called thiols or self-hydro groups, so sulfur and hydrogen, turns out that our body has a lot of proteins and enzymes that have these sulfur hydrogen groups on them that are really integral to things like, I don't know, our citric acid cycle, which makes ATP to power our cells, and a whole host of other very basic and important metabolic functions.

So that's kind of the most basic look at arsenic. And in terms of whether it happens to mimic thyls or phosphate, that just is in the way that it's formed these... It's basically just depends on which form of arsenic you're exposed to. Okay. And which form you're exposed to will depend on what that arsenic is doing in the environment, whether it's a high oxygen environment or a low oxygen environment, blah, blah, blah. And that is all, all of those are inorganic forms of arsenic. Organic arsenic, organic compounds that contain arsenic, can be found in really high concentrations

in things like shellfish. But it turns out, if we get exposed to arsenic that's already bound to organic compounds, we actually don't see a lot of effects from it. It actually is very non-toxic, which is interesting and different than what we saw in Mercury, which I think is just fascinating. Yeah. And these different forms of arsenic and the different things they mimic and all of that, that must lead to different symptoms if it's disrupting different parts, or is it because it's all kind of in the same pathway? So let's get into that, shall we? Let's get into the symptoms and then maybe it'll kind of get. at that question. Okay. So when we encounter arsenic in any of these various forms, we generally absorb it into our bloodstream and it goes to anywhere in our body, but it's often stored in places like our liver, our heart, our lungs, our kidneys are really important for excreting arsenic.

It can also be found in our skin. Really, it's everywhere. And our bodies have a lot of enzymes that actually function to break down arsenic, to metabolize it into a form that we can then excrete it. But it turns out that one of these forms, which is known as methyl arsenite or monomethyl arsenite, blah, blah, blah, this form is also very toxic. So our bodies are dealing with arsenic by, quote, breaking it down, methylating it, really. But then that is also toxic. So it doesn't just get rid of it automatically. So then what happens to it? It builds up in our bodies and causes all these symptoms that I'm about to talk about. Oh, oh, oh, okay. Yeah. So it acts just like arsenic, even though organic arsenic from a shellfish doesn't. Weird. I know. It's so bizarre.

So we get exposed to arsenic generally via food or water. So contamination of food sources and drinking water from arsenic, which comes from, honestly, anywhere. Like, it's found in the soil. It is ubiquitous across this earth, although, as we'll see later on, it's certainly not evenly distributed across the globe, but it can be found in groundwater kind of worldwide. And oral root, so ingesting it, is the primary way that people get exposed. In industrial settings, you can get exposed via inhalation. And it's unclear whether you can really absorb much of it through your skin. It seems like mostly no. But if you're handling it all day, all the time and you have it on your skin, you can potentially then ingest it from your hands. But everyone is being exposed to arsenic

at least some level. So let's talk about what we see in terms of symptoms, because as with everything we've talked about in terms of toxins on this podcast, the dose determines the poison or whatever, right? Well said. Thanks. I tried. So our firsthand account perhaps described an acute arsenic poisoning episode. And I say perhaps because Aaron, that firsthand didn't sound like what I'm about to describe. That's so funny because when I came across it in a book I read about arsenic for this episode, it was like, yeah. And then, you know, in Madame Bovary, it's actually a very excellent example of what arsenic poisoning is like. How fascinating. Maybe I just, I will say that most of the papers that I read really did not focus on acute arsenic poisoning. It was more chronic. That makes sense.

The highlight is very much on all the chronic. So maybe I just didn't find good enough, like, old-timey descriptions of arsenic poisoning. I mean, just pick up basically any Agatha Christie novel and you'll find, you'll find it in there. Well, what I found is that. That arsenic poisoning in some ways can look a lot like a lot of other poisonings in that within a matter of minutes to hours after ingestion, you have intense abdominal pain. You have a lot of GI symptoms. A lot of abdominal pain, vomiting, diarrhea. The diarrhea can actually be very profound. I saw it described as cholera-like. If you remember back to that episode. So that's like a rice water, just like pure water stool. and basically in high enough doses, this arsenic is kind of just ripping its way through your intestinal mucosa. So you're losing a lot through your guts. And because of all these losses, you can end up seeing hypotension, so drops in your blood pressure, which can be from dehydration and volume loss from this profuse GI losses. This can then cause electrolyte abnormalities because you're losing your electrolytes

through your diarrhea, through your vomiting. And that can cause your heart to stop functioning properly because without the right balance of electrolytes, your heart can't send the signals that it needs to to beat in sync. So then you can have death because of arrhythmias if you have a high enough exposure. There also can be a lot of neurologic symptoms. But from what I read, usually, though not always, the neurologic symptoms tend to happen more like weeks, days or weeks after exposure can cause things like numbness, tingling, muscle cramping, a lot of different neurologic effects. But these tend to not be as acute onset as the GI effects.

And these neurological symptoms are part of the acute thing. It's just part of the recovery phase? Not necessarily recovery, but there also can be seen in more like subacute. So maybe you're exposed to like kind of high doses for a number of days in a row or something like that. And you can even see them after very, very long-term exposures. So it's kind of just like arsenic is having its effect on your nervous system, which we'll talk about in more detail. But it's happening kind of all at once after that exposure, once it's made its way into your nervous system. Right. Okay. What's the half-life of arsenic in the body? Great question. It can. It can. It tends to be on the order of many hours to a few days, like two to four days. That's for the

inorganic forms. But once it's methylated in our bodies, once our body tries to break it down, it can actually persist for a bit longer. Interesting. Yeah. Interesting that like our bodies, like what is the benefit of our bodies actually breaking down arsenic? Well, that's a very good question. I think it seems to make it easier to excrete via our kidneys. Okay. However, it also can have bad effects on our kidneys. Yeah. And I think it's probably in part just our body's natural reaction to stuff that gets absorbed, right? Our body methylates things. It sees something and it's like, I'm going to methylate you. Hey, you look kind of like a phosphate, boop, you know? Right. Okay. So it's not necessarily, yeah, I don't know. It's a good, it's a good question. So that's kind of the acute phase. From what I read, acute poisoning, especially at high enough doses to result in death, tends to happen at levels very, very high. So I hate environmental levels because it's like parts per billion and micrograms per, etc. But, um, so. Um,

60,000 parts per billion, which is 60,000 micrograms per liter. I can't imagine it's very difficult to visualize. It is. It is, that level is about 10,000 times higher than 80% of the drinking water in the U.S., for example. So it's like really, really high doses. Okay. But even much lower doses, like 300 to 30,000 parts per billion, could cause pretty

significant effects, right? Like make you feel pretty sick. Right. But there is a level as a safe level because our body will methylate it and kind of kick it out of our systems and excrete it. Right. The World Health Organization has the kind of provisional level of arsenic in drinking water, which is the most like ubiquitous source. And so the one that's the most has, has that level attached to it is 10, 10 micrograms per liter or 10 parts per billion. Okay. Yeah. So that's the number. So we're talking about 60,000. Like, that's a lot.

That's a lot. That's a lot. It's a lot more. But that's kind of the acute poisoning. It's pretty rare nowadays. What's much more common is that someone is exposed to levels that are higher than that 10 parts per billion, but still low, like between 50 and 100, say, for example. So people who are exposed to this lower level but still high level of arsenic over a pro, long period of time, one of the most characteristic things that we can see is pigmentation changes

in the skin, which is fascinating. You get these little patches of skin that can be darker or lighter than your underlying skin tone. And these patches are hyperkeratotic, which means that they are these little hard patches, kind of like a wart almost, like a little stuck-on patch of skin. And this is caused by your skin actually proliferating in a very abnormal way. And these lesions are precursors to various skin cancers. Oh, and so the skin cancer that's associated with arsenic is not just through direct contact on your skin, but through any way that you are exposed. Right. It's not skin contact. Gotcha.

It is ingestion or inhalation, but it goes and is absorbed through your whole body and causes these changes. in your skin. And you wouldn't expect to see this with an acute case? Not as far as I could tell, because it takes time for your skin to, like, react to it. Gotcha. Right. Long-term ingestion can also cause cardiovascular disease. It can cause something that is called Blackfoot disease. It's a very severe form of vascular disease in the feet where the vascular system becomes so severely compromised that you basically lose circulation to your feet and then develop gangrene. Okay. It can cause heart attacks. It can cause strokes. It can cause a lot of different things. Mm-hmm.

So I wanted to try and get a little bit more into the nitty-gritty of why it's causing specifically heart attacks, specifically vascular disease. So let me attempt. So I said that this is an element that can affect our enzymes and how our enzymes function. So a lot of what we know about the effects of arsenic in our body are what we think it's doing to various specific enzymes in the systems that we see effects. So for example, cardiovascular damage. We know from epidemiological studies that arsenic can cause some pretty severe cardiovascular damage. It seems like the way it mostly does this is actually by increasing reactive oxygen species. and inducing our cells to synthesize a bunch of inflammatory cytokines and a whole host of other largely reactive oxygen-mediated enzymes and effects.

And so the end result is that this arsenic is turning on a bunch of stuff that damages the lining of our blood vessels, that damages that endothelium. And so that's what ends up causing these cardiovascular complications like heart attack. It can cause increased blood pressure because that damage, first of all, is going to damage our blood vessels. But then it also affects enzymes that cause vasoconstriction. So it causes our blood vessels to go get smaller and smaller and smaller, which increases the pressure in our blood vessels. It can do anything. It can.

And then in our nervous system, because it's going to get there eventually, this is something that can cross our blood brain barrier. in our brain, again, we think it's related to oxidative stress, increased in reactive oxygen, but it can alter the metabolism of various neurotransmitters. So over long periods of time, exposure to arsenic can result in impaired memory or poor concentration. Arsenic also causes the cytoskeleton of our cells, like the literal kind of bones that form ourselves. they're not bones, but it's called the cytoskeleton. It can cause that to be disrupted, to basically not be as strong or form in the correct way. And one of our types of cells that really rely on our cytoskeleton are our nerve axons.

So arsenic causes the axons of our nerves to degrade, which leads to things like neuropathy, which we talked about a little bit already. This can look kind of like a Gian-Barray-type neuropathy. Interesting. Okay. It can also arsenic lead to degradation of specific groups of neurons in our brains, like, for example, our dopamine-producing neurons. So this can cause a syndrome that looks a lot like Parkinson's. Is it targeted in that way, or are those just the types of neurons that are, like,

somehow more susceptible? Right, exactly, because it's not just those. It can also decrease activity. of things other than dopamine like acetylcholine estuase. It can cause an increase colonergic crisis. It can honestly, honestly, you said it can go anywhere and do anything. Yeah. That's accurate.

Okay. It also affects our kidneys, even though our kidneys are what is going to be excreting this arsenic eventually. As our kidneys are excreting this arsenic, they can also get hammered by the effect. and then that can have even more of an effect on our blood pressure because it's disrupting our kidney's ability to regulate our blood pressure, which, by the way, your kidneys do that for you. Finally, maybe not finally, because I'm going to keep going. But another thing that I think is so fascinating is that exposure to arsenic at higher levels can also cause diabetes, like very specifically diabetes. I know, your face.

Yeah, what? Uh-huh. Okay. So this we have a more specific answer for. It turns out that arsenic decreases the expression of a transcription factor that results in us having increased resistance to insulin, right? Basically causing type 2 diabetes. And then on top of that, it slows down the metabolism of glucose because of its effects on ATP, right? Because of the way that it interacts with our metabolic cycles that produce. ATP, it disrupts that process. And so it interferes with ATP dependent insulin secretion. So now we're secreting less insulin and we're resistant to insulin, boom, diabetes. That is incredible. It's so overwhelming. Yeah. Yeah. I mentioned Blackfoot disease. This is something that is a cardiovascular complication in a way because it's your vascular system just in your feet. And it's actually unclear if this is just arsenic or if this is something more. It has been seen in Taiwan very strongly in association with exposure to arsenic, but it hasn't been seen outside of

Taiwan with exposure to arsenic. So there's a question, is it in combination with malnutrition? Is it something else? And the reason I bring this up is because I think it highlights one of the big problems with trying to get at the exact effects of arsenic exposure. Not only is it going anywhere and everywhere and affecting over 200 different enzymes potentially in our bodies, but it's also something that we're being exposed to to various degrees in combination with so much else in the environment. So it's never going to be an individual-only exposure, arsenic alone. Just a couple more. Arsenic does cross the placenta the same way that it crosses the blood-brain barrier,

so it can have a lot of detrimental effects on the fetus. It can cause spontaneous abortion, stillbirth, preterm birth. There is some suggestion that exposure to arsenic in utero might be associated with increased cancer risk later in life, but that's a little unclear. But we do know that arsenic is a carcinogen. And what I think is so interesting about arsenic as a carcinogen, arsenic as something that causes cancer, is that, We do not know the cellular mechanisms of this. But this is one of the strongest associations, especially when it comes to skin cancer, as well as bladder cancer, lung cancer, various other cancers. So we don't know the exact mechanism of like that abnormal skin growth or cellular growth on your skin.

Or is it just like inflammation? Yeah, it's a good question. It seems like arsenic activates various transcription factors and induces, like, changes the expression of genes that are involved in cell growth and proliferation or transformation. And so that is then leading you to cancer. Why does it do this in the skin so specifically, we don't know. How is it doing it in the skin so specifically? We don't know. And the same is true for other cancers like lung cancer and bladder cancer.

cancer that have been associated with arsenic. Wow. I know. Interesting. I don't know if that was like way too much or not enough, but it feels like a lot. I mean, it's a lot, but I think that that's just also the nature of arsenic. Yeah. It has profound effects throughout your body.

And how much variation is there in terms of susceptibility, like children versus adults or, yeah, anything? else like that? Great question. Children generally are more susceptible to things like toxins than adults because lower amounts are going to cause an effect on children because they're smaller, because their metabolism is such that that's going to be the effect. But other than that, I don't have a lot of very specifics in terms of like who is exposed the most or anything like that. Okay. So that's, Um, that's arsenic, Erin. Was that, that was a lot. How do you treat arsenic poisoning?

Oh, such a good question. It's not super easy to do. There are a variety of different compounds that you can use for what's called chelation therapy, especially if someone is exposed to very large amounts of arsenic. And what chelation therapy does is basically bind the arsenic and then allow your body to excrete it without having to metabolize it, et cetera. So basically just helping your body get rid of it quicker. But otherwise, you just waded out and try to not be further exposed and then treat whatever complications have arisen. I thought I also read something about folate, which I

thought was fascinating because we just researched folate and how higher levels of folate are recommended for like long-term more chronic exposure to arsenic. But I don't know why. I wonder, I mean, I don't either, but most likely it has to do with the fact that we talked about how important folate is as a co-factor in all of these various metabolic processes. So it's probably just trying to displace arsenic in a way, not directly, but allowing ourselves to continue their metabolic processes despite the exposure to arsenic. That makes sense. Right. Oh, that's interesting, though. I know.

Connections. Yeah. They're all around us. So, Erin, speaking of connections, how did people connect the dots? Like, had they figure out what arsenic was and then figure out that it's such a great killer of people? I will try to answer those right after this break. Anyone who works long hours knows the routine.

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Aw, see, Pop-P trusts you. I think we should call it, doctor. Connecting homeowners with skilled pros for over 30 years. Angie, the one you trust, to find the ones you trust. Find pros for all your home projects at Angie.com. Like we talked about earlier, arsenic is often called the king of poisons and the poison of kings. It is perhaps the most infamous and famous of all poisons and the one most synonymous with murder. And it could be said that the history of all intentional poisonings is really the history of arsenic.

What? What? Uh-huh. Why? It was so, well, we'll get to it. We'll get to it. And you'll see that it does make sense as an intentional, as an intentional agent of poison.

And as I'll also talk about later on, arsenic does deserve this notoriety. But like with all poisons that we've covered on the podcast, there is so much more to this chemical than just its role as a plot device in an Agatha Christie novel, or it's used by the Borgias to amassie. wealth and power in 15th century Italy. What?

Alongside arsenic's potential for murder is also, of course, its potential for healing. It has been considered an important medical substance for years, though whether it was more harmful than helpful is in question for much of that time. And it's still in use today as a treatment for some cancers, which is pretty awesome. But the other enormously important side of arsenic is what happens when you come into contact with arsenic unintentionally, whether through occupational exposure, environmental exposure, or through drinking water that is expected to be safe and clean. And these three main faces of arsenic, as an intentional poison, as a historically questionable

but present-day effective medicine, and as an environmental contaminant, are the three themes that kind of make up this history section. And initially, I was going to split up the discussion along those lines. First, I talk about arsenic and murder, and then I talk about arsenic and medicine, and so on. But as I read more, I realized just how intertwined these roles of arsenic all are. For instance, the rise of arsenic as a murder weapon in the 1800s in Britain and its inclusion among many patent medicines came about because it was more available from mining, which, of course, led to more occupational exposure as well as environmental exposure when it was used as, for instance, a dye, a colorant. So let's get started on this rich history of arsenic.

Ooh, I can't wait. Like you said, Aaron, arsenic occurs naturally all over the world, with apparently a good deal of it coming from volcanoes, like in its natural form. Yeah. Yeah. And typically, you won't find arsenic in its elemental form in nature. It exists in over 150 different minerals and is usually found as a sulfide compound, commonly Railgar or Orpiment. I'm not sure if I'm saying those right, probably not. And although arsenic is widely distributed, like we mentioned, it's not necessarily evenly distributed. And mining has played a

big role in both the uneven distribution of arsenic in the environment, as well as the high concentrations that we see in the soil, the water, and the air of some regions. But even before mining and industry unloaded tons of arsenic everywhere, some humans lived in naturally arsenic-rich environments, and their constant exposure may have left a genomic signature. Stop it. So you talked about how we have a gene that is like a methyl transferase, right? It adds methals to whatever. And this gene is really important in metabolizing arsenic so that we can excrete it safely. There is some very cool research looking at this gene, which is called AS3MT. If you're curious, it's the arsenic plus three oxidation state methyl transferase gene.

And this research has found that in some populations that have historically lived in areas with high arsenic concentration in drinking water, particularly in some parts of the Andes in South America, it seems that you're more likely to see a protective version of this gene, one that helps with more efficient arsenic metabolism. So you can be exposed to higher levels of arsenic without getting as sick as you would without that version. Which is so cool. And I think that this is one of the earliest or one of the only known examples of humans adapting to toxins. Yeah. It's so cool. How interesting. Also, there is evidence of high arsenic exposure that's been found in remains of people who lived in the Atacama Desert in Chile around 7,000 years ago.

So yeah, I mean, humans have been exposed to arsenic for a very long time, even before mining. which isn't to say that mining hasn't played possibly the largest role in exposure nowadays and historically. But when did humans start noticing the negative health effects of arsenic? Probably as soon as we started working with the stuff, which was around the Bronze Age, which began 3,300 BCE. The Bronze Age is called this because it's when people began to create, guess what? Bronze. Yeah, and what's bronze? Bronze. Bronze is an alloy consisting mostly of copper along with tin and sometimes other non-metals or metalloids.

Okay. Most metals aren't just hanging out there in their pure form. They often co-occur with other things like arsenic. And an observant smelter would have noticed that what you find with your copper naturally could influence the quality of the alloy that you produced. How strong it was, how durable it was, et cetera. And arsenic and copper happened to be a great combo, which is something that you would be like, I'm storing that little fact away for later because I'm going to have better bronze than the other person. Yeah. And this observant smelter would have also probably noticed that when they did their smelting with this combo, the oven was full of noxious fumes.

And the more they worked with it, the worse they felt. Yeah, because the fumes are pretty bad. Pretty bad. They also may have noticed that smelters tended to not live quite as long as their non-smelting buddies. One paper I read suggested that arsenic poisoning in metalworkers represents the very first occupational exposure. Huh. Wow. Bold claim. It is a bold claim, but I mean, if you were smelting, you would come into contact with arsenic almost immediately. I mean, I'm sure we could make arguments for other occupational exposures.

There are many different occupational. In any case, people have been exposed to arsenic in an occupational setting for a long time. Yeah. The Greek god of Smiths, Hephaestis, and his Roman counterpart Vulcan, are often depicted as limping and kind of hunched over. And there's been this long debate over what might be the cause of that limp. Some people have speculated it's because Smiths were known to suffer the ill effects of working with toxic metals such as lead and arsenic. and so he was depicted with a limp in recognition of that. I love that, Erin.

Whether or not Hephaestus limp was supposed to represent arsenic poisoning, humans have been aware of arsenic in its various forms for centuries. Take the etymology of the word, for instance, which starts somewhere around the Persian word, Zarnik, which means yellow orpiment, which is this brightly colored compound of arsenic and sulfur. Zarnik was then translated into the Greek word arsenicon, which was related to another Greek word arsenicos, meaning masculine or potent. And eventually that became arsenic. So like that is a kind of, and that's only a little bit of a snippet of the etymology. So I think that kind of is a good indication that not only was arsenic widely known in many parts of like the ancient world, it was also known in the ancient world for a very long time.

arsenic in its many forms was used in the ancient world not just to make copper alloys but also as a hair remover for leather working or to create a silvery surface on mirrors and statues as a dye or cosmetic or as a medication for all sorts of things lice infestation abscesses constipation tuberculosis ulcers cough shortness of breath and so on does it all does it all the first exposures to arsenic may have been of an occupational nature, but the growing range of uses for arsenic meant that anyone was at risk. And some scholars think that arsenic poisoning in the ancient world was incredibly, unbelievably widespread. Not necessarily poisoning in the murderous sense, however, the most common forms of arsenic that people worked with, this real gar and orpiment, which I have mentioned before, are, insoluble and brightly colored. Which are two qualities that would make them pretty poor murder tools, at least if you wanted to get away with it. Okay, Aaron.

Arsenic trioxide or white arsenic or Ratsbane, on the other hand, those are all names for the same thing, is a powder that dissolves in water, is colorless and tasteless. Aaron. Does it get better than that? No, not when you're trying to murder somebody. This form of arsenic, this arsenic trioxide or white arsenic, was known to the ancient world, as were the means of producing it. But it didn't seem to be the top pick for intentional poisonings in ancient Greece or Rome. That honor would go to Wolfsbane and Hemlock. It was probably used here and there, such as by Agrippina the Younger and her son Nero to

get him to the coveted position of Emperor of Rome. But it really only began to gain notoriety in the 1400s and 1500s thanks to the Borgias. Who were the Borgias, someone might ask? I remember learning about the Borgias. In what class? History. No, I remember in, I'm pretty sure it was eighth grade European history. Does that sound right? Yeah, I mean, I feel like that would be right. I mean, the Borgias are a very dramatic and titillating part of history. So this was this family who's super wealthy, super powerful and whose name became synonymous with greed, adultery, theft, and murder, specifically murder via arsenic. Ooh, I love it. The Borgias were said to collect and store poisons like wine, having like a poison cellar instead of a wine cellar. They would experiment with different combinations until they found one that they liked. Oh, my gosh.

Their signature poison, La Cantarella, was mostly arsenic. And they, especially the siblings Cesare and Lucrezia Borgia, whose father, by the way, was Pope Alexander the Sixth, like the Pope. Wait. What? The Pope? Yeah. Had kids? Mm-hmm.

Mm-hmm. Mm-hmm. And these siblings supposedly fed it to anyone who stood in their way. and it seems like there were a lot of people who stood in their way. Okay. But I do want to add that many historians nowadays think that a lot of these rumors about the Borgias were exaggerated by contemporary critics. And Lucrezia may have been more of a victim of her family rather than the infamous poisoner that she was painted to be. But regardless of where the truth lies, the Borgias were definitely responsible for putting arsenic on the map as a murder weapon.

But they were merely just the first. After the Borgias, arsenic pops up more and more in stories like the one of Julia Tofana from Naples in the 17th century who sold her signature arsenic poison Aquatofana to dozens of people. Or Hirona Masparra, who also sold poison and started a poisoning society in Rome in the mid-16th century where she taught women how to poison their husbands. Oh my gosh. Allegedly. And of course, I have to mention Catherine de Medici, Queen Consort of France in the 16th century, who is said to have studied poisons extensively,

including arsenic, and brought the art of poisoning, especially for political gain, from Italy to France. And already a pattern emerges with these stories of famous arsenic poisoners. they were all women. Granted, they were also mostly all from Italy, which did have a reputation for a while as a place with a lot of poisoners, in part maybe because there was for a period of time an entire branch of the Venetian government apparently dedicated to poisonings and you could get a job as a professional poisoner. Wait, wait, wait, wait. Not like to investigating poisonings or like something like that was just like to point to the point.

To poison. To poison people. Yeah. How fascinating. I just love learning this history that I once probably heard some of. There's just so much to arsenic. There's so much. And it's like this is such a brief tour, even though this is a long section.

This is such a surface level tour. I love it. And of course, neither of these stereotypes were true. Right. Right. Like it's not like people were only poisoning in Italy. Right. people and of course women weren't the only ones poisoning.

Yeah. But that didn't stop them from being perpetuated. I feel like that's still like in movies and things. That's still like the trope. Like poison is a woman like on CSI or bond order. Like you still hear that as like a trope. Yep. Yep.

And there was a study of murders in Victorian England, which by the way had fully embraced arsenic as a murder weapon by the late 1700s. And this study showed that cases of poisonings were actually fairly evenly split across genders, but that poisonings represented a smaller proportion of murder styles for men who were much more likely to use violent means of murder and were more likely to murder overall. So if that makes sense. So when women did murder, even though they took up a smaller proportion of all murders, they were more likely to use poison in the case. their breakdown according to the study. Okay. Interesting.

And when anyone used poison, they grew more and more likely to reach for the bottle of arsenic. Let's talk about why. Yeah. And to do that, let's head to the 1800s. The 19th century has been called the arsenic century, but not because everyone and their neighbor was poisoning everyone else and their neighbor with arsenic, or rather not just because that. intentional poisoning via arsenic was a really popular choice during this time, in part because the

symptoms of arsenic poisoning could mimic several infectious diseases that were super common around this time, or even just other diseases. Yes, okay, I love this. Yeah, like cholera, right? So you talked about how it's like these GI symptoms are like cholera. That's pretty handy if you're trying to murder someone during a cholera outbreak. Sure is, yeah. But also, not just because of this mimic.

agree, but because arsenic was really easily accessible. You could just buy it at the local grocers, the pharmacy, anywhere. But the vast majority of people who became exposed to arsenic during the 1800s and a whole lot of people got exposed did so because of their job or simply because they were eating, breathing, and living among the poisonous stuff. During the Industrial Revolution, which started in Great Britain and the U.S. around the 17th, 60s or so and lasted until the 1820s, 1840s, the demand for metals grew and grew in order to build these new buildings or build these new machines. And of course, to get new metals, you have to mine. At first, it seems like arsenic, specifically this super toxic white arsenic, arsenic trioxide,

was mainly a byproduct during the smelting of other metals. People had, of course, recognized its value on its own for a long time, but it wasn't until the 1800s that mining for arsenic specifically really took off. The list of things that you could use arsenic for seemed endless, and the arsenic industry in mines to produce this stuff grew and grew. For instance, it began to be used as a bright green colorant. It went by the names Paris Green or Shields Green. Wallpapers were full of the stuff. Question. Uh-huh.

You know the book Good Night Moon? Yeah. The walls are green. Uh-huh. Is that Paris Green? When was Good Night Moon written? I don't know. It's been around since my mom was little, so before the late 1950s.

I feel like it was, it's been around since the 19th. Yeah, I feel like no. It would, it's unlikely to have been at that point, Paris Green, unless they were living in a house that hadn't been updated since the mid-1800s. How fascinating. Yeah. Okay. I'm going to have to Google this.

Yeah, you should definitely Google wallpapers that have Paris green in them. Okay. Because some of them are really beautiful. But it wasn't just wallpapers either. This arsenic green was used in artificial flowers, which were often in decorations for hats or dresses. And the gowns themselves were often dyed with arsenic colorant. Oh, no.

So you can imagine. someone in an arsenic dress, dancing and swirling around, not knowing that arsenic was being discharged with every move. And you're breathing it in, you're shedding it on the floor, you're absorbing it maybe into your skin, maybe not. Yeah, there's a comic from 1862 about this that's titled The Arsenic Waltz. And speaking of like just discharging arsenic everywhere, let's talk about the wallpapers. Even though wallpaper producers tried to downplay any risk that their arsenic wallpapers posed, such as the famous designer William Morris, who, by the way, was a big investor in the Devon Great Consul's Arsenic Mine, which was the biggest source of arsenic in the world. So this is like the head honcho, most beautiful wallpaper designs you've ever seen.

You can still get actually William Morris designs and all kinds of things. things. He was all about the arsenic. And even though there was all this downplaying of the risks, reports just kept pouring in of people that would become really sick after wallpapering their room. And the only time they would get better was moving out of the room or taking down the wallpaper. And children, of course, seemed to be especially at risk, crawling around on floors that were coated with a dusting of arsenic from the green wallpaper. And just licking. everything. Licking everything. Yeah. Putting, yep, yep. And this is actually still, arsenic wallpapers is still a problem,

of course, in places that are being renovated or like going back through, just like we talked about with anthrax, I think, because they used to use anyway. I can't remember what it was. Or lead? Could be both. Probably both. Arsenic could also appear in candles, soap, books, glass and glassware, paint, stuffed animals, paper and packaging, fly papers, lampshades. I mean, the list goes on and on and on. And so it's pretty easy to see how you could be exposed on a daily basis. Yeah. But let me read you this quote about arsenic during the Victorian era to finish out the picture. So this is from the medical historian James Wharton. Quote, a great deal of it was introduced purposely into many of the components of everyday life, with the result that people

took it in with fruits and vegetables, swallowed it with wine, inhaled it from cigarettes, absorbed it from cosmetics, and imbibed it even from the pint glass. The substance was present in a broad assortment of household items from candies and candles to cookware, concert tickets, and preserved partridge heads used to ornament ladies' headdresses. Oh my gosh. Christmas tree ornaments and children stuffed animals. no less were often arsenical, and the money used to purchase all of these products was itself sometimes contaminated. How fascinating, Erin. I had no idea how the extent to which arsenic was in everyday items. I would never have guessed, never have guessed that. I know, I know. And I don't know if you,

if the word candy popped out to you in that quote because it did to me because what on earth? I love candy. Uh-huh. Well, the candy thing refers to the use of arsenic as a dye to make candies green. So I just Googled Paris Green real quick. It's a gorgeous color. Oh, it really is. It's beautiful.

It's like such a green, green, green. Yeah. So I get it. I mean, I'm not advocating. for it. But like, I get how once you've found something that, like, makes that color, like, it's going to be a high bar to stop using it because it's going to make you a lot of money. Right, exactly. And that's what that's the thing is that there were so many minds now devoted to arsenic. And so it was just like, let's find what else we can use this for. But yeah, the arsenic in candies was, was shocking.

And gross. Intentionally. But there was also a pretty interesting. infamous incident in 1858 when an English sweetmaker named Joseph Neal accidentally arsenic poisoned about 200 people and 20 of them died. So what happened was that it was really common practice at the time to fill out candies with like tasteless inert substances. What? To kind of, yeah, to be like, I'm going to add a little bit of sugar, you know, just to kind of fill it out a little bit more. Save money. And one of these substances was called daft, which seems like it was probably mostly plaster of Paris. And the sweetmaker mistook white, which sounds gross enough on its own, but the sweetmaker mistook white arsenic for this daft stuff and poisoned a massive batch of his candies. Oh, no.

Yeah, so it was just with white arsenic. Oh, goodness gracious. But even if you avoided these tainted candies or any these other things, how could you have lived in the late 1700s and 1800s and not been exposed to arsenic? Like high levels of arsenic. Yeah. In the 1950s, some hair samples of Napoleon, who died in 1821, of stomach cancer, supposedly. This is like the fourth time Napoleon has been mentioned this season. I know. I was just going to say, like, can we put a compilation together of every time that you mentioned Napoleon? Yeah, I would love that. But Napoleon's hair was tested in the 1950s and found to contain high amounts of arsenic,

which led some people to conclude that he died of intentional arsenic poisoning. What? What? I feel like another episode, you said he died from a different thing that we talked about. I'm sure. Probably. Because the other thing, too, is that it's like, that's a great. That's a very fun and interesting hypothesis, and it could be true.

But I think there's some debate over whether it was intentional and whether there were high enough levels to actually cause some severe illness and especially death. Because there was definitely arsenic in the wallpaper on his living room walls. And also it was probably arsenic in everything. Everything. Just everything. Yeah, and his candy. I'm sure Napoleon ate candy. I feel like he had to have.

You had to have a sweet tooth. But even if Napoleon wasn't around enough arsenic for it to kill him or make him seriously ill, plenty of other people were, especially those working directly with a substance. Let's start right at the source, arsenic mines. Yeah. Every step along the way, from the dust inside the mines to the toxic gas is produced in the smelting process to the packaging of the arsenic for future sale, workers were exposed to outrageous amounts of arsenic. And many mine employees became too sick to work,

which led to an increase in applications to the government under the poor laws, which made the government wonder whether there might be something about these mines making people sick. So they began an investigation into the health effects of arsenic mines, and surprise, surprise, they found that there was no ventilation or protection and that continuous exposure was really dangerous, especially also in terms of lung cancer. Yes. They found. Yeah, because in mind, you're being exposed to it primarily via inhalation rather than ingestion.

And so it's going straight to your lungs and causing damage there, hence the lung cancer. Right. Despite this, nothing was really done about it. Yeah, I'm not surprised based on this podcast. And this is a common theme in the history of arsenic that we'll see repeated time and time again. Like wallpaper. By the 1850s, people had grown suspicious of arsenic-laced wallpaper and demanded investigations into just how much of a risk it actually posed, starting with the wallpaper factories. Unsurprisingly, these investigations turned up tons of health problems.

in these crowded and poorly ventilated factories where this wallpaper was produced. Factories, which I might add, were mostly staffed by children. Oh, no. The majority of the workers that would actually paint the wallpaper were children, and over half of these children were under the age of 13. Oh, no. But even though these investigations confirmed what many people had already suspected, no changes were really made to the manufacturing process to try to reduce exposure.

If someone did get sick from arsenic exposure in one of these factories, it was usually blamed on the worker. Oh, you didn't clean your hands well enough. Or, oh, you shouldn't have licked your paintbrush, which was reminiscent of the radium girls, right? Yeah. And of course, wallpaper production was just one of many industries where arsenic was commonly used. Another one was the artificial flower trade. This was actually a booming industry in the 19th century, where workers who were primarily young, economically disadvantaged women, would spend all day in crowded rooms, decorating hats and dresses with these artificial flowers and leaves and fruits, many of which had been dyed this beautiful green, this beautiful Paris green or Shields Green, with these green arsenic dyes. The business owners weren't required to tell their employees that they were working with a potentially deadly substance or give any safety guidelines on how to handle it.

Or if those requirements did exist, because eventually they did in some places, they weren't really enforced. The attitude at the time was, well, if you didn't want to work with arsenic-laced flowers, then find another job. Oh, my goodness gracious. Yeah, it's classic. completely ignoring that many workers didn't have this luxury of choice. Besides proving useful in decorating hats and walls with its vivid green color, arsenic was also found to be a stellar pesticide. And naturally, it was used everywhere.

Tobacco, for a long time, absolutely chalkful of arsenic. Yep, I read that, yeah. Yeah. Grains used in beer, an outbreak of arsenic poisoning, in England from tainted beer finally prompted them to put a limit on how much arsenic you could spray, but the U.S., which was a much bigger user of arsenic, lagged far behind. Not surprising. At least until a British family got arsenic poisoning from apples that had been imported

from the U.S. And so they finally agreed to lower arsenic spraying levels, but only on apples that were to be exported. Oh, cool. Love that. Yeah. Yeah, it's awesome. And I'm curious, I'm very curious to hear we stand in terms of arsenic use in agriculture today

because I know that so much land is contaminated with arsenic either in soil or groundwater because of how much it was used as a pesticide in the past. And not just to spray crops, but also to protect sheep from pests, which probably harmed the sheep as much as it did the worker, who had to hold this wriggling animal in this arsenic solution and press it into the wool of the sheep with their bare arms for hours and hours every single day. And many of these people eventually developed skin cancer from this constant exposure to arsenic, of course. Arsenic was used extensively in taxidermy in the 19th century.

The arsenic-based soap that somebody came up with was the soap. It was the first one to actually, that actually seemed to work and not just leave you with a rotting carcass. Like it used to clean the animal once you skinned it or something? That's what it seems like. Yeah. Yeah. I have literally never thought about what it takes to taxidermy preserve an animal. That could be a fun episode.

It could be, and that kind of makes sense that they would use something gnarly. Yeah, it does. And during the 19th century was this huge time for natural history and taxidermy as people traveled to new places and brought back animal specimens to fill museums. You just have collections, collections, collections, and it's legacy last today for people who work on these historical collections in museums, right? They have to take special precautions to make sure that they're not being continually exposed to these arsenic specimens.

Wow. Yeah. And the success of arsenic and taxidermy led to it being used also in embalming, starting in the early 19th century. But it didn't last too long as an embalming agent for two reasons. One was that people were worried about the negative health impacts

of working so closely with the substance. Side note, John Snow of Broad Street, and cholera epidemic fame, published a letter in a British medical journal in which he described the dangers of working with cadavers because of their toxic arsenic embalming contents. Huh. Yeah. But the other reason that arsenic and embalming was short-lived was that if you used arsenic to preserve a body, how would you be able to tell whether that person had been murdered using arsenic?

You couldn't. And this was a problem because people were certainly still. committing murder with the stuff. How interesting. As I mentioned, white arsenic tasteless, colorless, dissolves in water can be given over time to mimic a chronic illness. And importantly, during a good chunk of the 1700s and 1800s, was super easy to obtain. In England, until 1851, there were no legal restrictions on the sale of poisons. So you could pop down to the corner store.

for some arsenic-based rat poison or head over to the pharmacists and pick up Fowler's solution, which was a medication whose featured ingredient was arsenic. And it was also used, like, well into the 20th century. It was bad news, yeah. So, of course, people used arsenic for murder. One of arsenic's nicknames was inheritance powder. Oh, my gosh. There are many stories that I could explain why it would be called that,

but I'll just briefly mention one, which is that one of the signers of the U.S. Declaration of Independence, George Wyth, was likely poisoned along with two of his employees by his grandson because he had threatened to cut him out of his will. Oh, my. Juicy. Family dramas. And as much as I'd like to go through a long list of all of the famous arsenic murder cases, I'm only going to mention a few that played a role in the development of a test for arsenic. However, if you are interested in reading more about these other infamous cases, such as a town in Hungary, where dozens of arsenic murders happened over the course of decades, like dozens and dozens, or the 2003 mass poisoning of churchgoers in Maine, then I will recommend the book King of Poisons by John Periscandala.

another attractive feature of arsenic as a poison for much of its history was that you couldn't test for it. You couldn't say, Your Honor, this was clearly a case of arsenic poisoning and not cholera as the defendant claims, or whatever you would say. Of course, people still got convicted based on witness testimony or a confession, or a coerced confession, but the scientific proof of arsenic poisoning would have to wait until the 1800s. There's an asterisk that I have here because there is one case in England in the 1750s where a chemist claimed to successfully test for arsenic. But it's not clear whether he actually did it and if it did anything. And the accused, a woman who allegedly poisoned her father for preventing her elopement to an already married dude, was convicted despite of this nonspecific and probably useless test and she was hanged. Wow.

Anyway, the first actual test for arsenic in cases of poisoning was developed in the 1830s by an English chemist named James Marsh. And Marsh had been called on to try to test for arsenic in a case of suspected poisoning, where a grandson was accused of murdering his grandfather by slipping some arsenic into the coffee. See, it's like, it's a common. It happened a lot. happened a lot. And Marsh was able to produce a yellow precipitate from the stomach contents of the dead man, which was characteristic of arsenic. But the jury was not convinced. And the defendant was acquitted. Later on, he did admit that he actually murdered his grandfather. Wow. And so Marsh, this chemist, was really frustrated by the acquittal and also by the jury's kind of disregard

for his test. He was like, it was clearly arsenic poisoning. What do I have to do to convince you that this is a reliable test that you should use? And so that's what he devoted his time to. He wanted to try to make a new and improved and reliable test for arsenic. And he did it. And I won't go into the how of the Marsh test because it's probably confusing and beyond my chemical knowledge scope for sure. But the important thing was that it was. worked and that it could be reproduced in other labs. Later improvements made arsenic even more easily detected, either by making this test better or building a new test from scratch. But did these tests do anything to affect the rate of poisonings? I'm going to guess no. Yeah. I mean,

it's unclear. Okay. Even after the laws restricting the sale of arsenic were passed in England in 1851, like I said, people continued to use it as a weapon, mostly because these laws were really difficult to enforce. By the time that intentional arsenic poisonings were on the decline, they had already left their mark in public consciousness and pop culture. When I think arsenic, I think Agatha Christie, I think murder she wrote, I think old cozy murder mystery books, which is like one of my favorite genres of books. As somebody tallied the different poisons used in works of detective fiction, and arsenic came in third. Wow.

Behind cyanide and mushrooms. Yep, okay. Mm-hmm. And in Agatha Christie's books alone, arsenic is mentioned either as a plot point or suspected poisoning or just in passing in nearly a quarter of her novels. Wow. It switches a lot. Also, I just love Agatha Christie so much.

Our first-hand account, of course, was taken from Madam Bovary, published in 1856, also featuring arsenic heavily. I just finished a couple days ago, we have always lived in the castle by Shirley Jackson, who also wrote The Lottery and Haunting of Hill House. And arsenic is a main character in We Have Always Lived in the Castle, which is, by the way, such an amazing book. I loved it so much. Okay. Put it on my list. And I also have to mention arsenic and old lace, which is a play later made into a movie in the 1940s. The premise is absolutely absurd.

These two old sisters rent out a room to elderly men that have no friends and no family, and then the sisters poison them out of kindness. Out of kindness. Out of kindness. And their poison of choice was not just arsenic. It was a blend, but arsenic was heavily featured along with strychnine and just a pinch of cyanide in some elderberry wine. And then the sister's nephew finds the bodies and chaos and hijinks ensue. And it's fun times.

It's based on a true story, by the way, of like someone who owned a boarding house and would do this. I feel like boarding house murders are a thing I have read a lot about. Oh, for sure. Yeah. For sure. I also love not just how often arsenic appears in books and movies, but how creative some of its uses are, like a murderer infusing candles with arsenic so that when they were lit, they would poison the intended victim. Wow.

I know. Or my favorite, taking small amounts of arsenic to build up an immunity, a la Princess Bride and Iocaine powder. And this building an immunity to arsenic, may be based on the so-called arsenic eaters of Styria, which is a state in southeastern Austria. So people in this region would allegedly eat small amounts of arsenic to make their skin look better or to be better able to climb at high altitude. What?

And this rumor, this legend, grew really, really famous in like the 1800s. Huh. Did they actually exist, these arsenic eaters? Hard to say. But whether or not they were real, their legend had tremendous influence on the use of arsenic in the 19th century, when people were either poisoning their spouse or grandparent with the stuff, inhaling it while working in the mines, ingesting it with their candy, or absorbing it from their wallpaper or cosmetics. Eventually, the prevalence of arsenic in commercial goods or as a murder weapon started to decline in the 20th century. but that's certainly not the end of arsenic's story. And don't worry, I'm nearly done.

Sticking with the three themes of arsenic as an intentional poison, a medicine, as an environmental contaminant, the 20th century saw arsenic being developed but not extensively deployed as a chemical weapon during World War I in the form of something called leucite, which is also how I believe we started to develop treatment for arsenic poisoning in anticipation of its use as a weapon. The 20th century also saw the emergence of arsenic as a truly effective medicine, first as a treatment for tripanosomiasis, then the first effective treatment for syphilis in the form of salvar san, and later as a treatment for a certain type of leukemia called acute pro-mylocytic leukemia. And arsenic is to this day a hugely important and prevalent

environmental contaminant. And Aaron, I'm sure you'll talk more about this, but arsenic in drinking water poses a threat to tens of millions, maybe hundreds of millions of people around the world today. And although it's a global problem, one of the areas at highest risk is in Bangladesh and West Bengal. There, in the 1970s, a huge initiative was started to try to improve the water supply and reduce illness and death from waterborne pathogens. And so one solution proposed was to use tube wells to tap into cleaner water from the Himalayas. A bunch of international organizations got involved, and by 2000, there were close to 11 million tube wells in these regions providing water to 97% of rural residents.

And waterborne illness and infant mortality dropped tremendously. But about 10 years after this well-building program really ramped, up in the early 1980s is when a dermatologist noticed arsenical dermatosis in a patient, and he linked it to the water from the tube well. This turned out to not just be a one-off, but the beginning of one of the largest scale arsenic poisonings in the world. In the next four years after this first case, this doctor alone identified over 1,200 cases from 61 villages, And since arsenic poisoning can take a while to show up with its long-term exposure, chronic exposure, the extent of the poisoning was not realized until much later on.

And really, you could argue that we still don't necessarily have a good handle on it even today, since the wells are still being used in many places. So this is my quick segue here. But speaking of today and what's happening today, Aaron, Can you tell me what we know about arsenic poisonings or arsenic in medicine or arsenic in the environment these days? I would love to. Let's take a quick break first and then we'll get into it. So the World Health Organization actually lists arsenic. And this blew my mind, but after that whole history section, I feel like this makes a lot of sense. it lists arsenic as the most significant chemical contaminant in drinking water globally, period, the most significant one, arsenic.

Yeah. Yeah. I believe it now. I know, exactly. Like when I read that, I was like, what? And then the history and I was like, well. Yeah. So groundwater contaminated with arsenic is a massive problem worldwide with an estimated, according to the World Health Organization, 140 million people in 50 countries that are currently drinking water, exposed to drinking water,

at levels well above what is considered the World Health Organization still listed as the kind of provisional guideline, meaning they're still looking at this to see if this is actually the best guideline, but it's been the guideline for a while now. and that is 10 parts per billion or 10 micrograms per liter. So 140 million people in 50 countries are drinking water that is well above that. How high above that can really, really vary. Like you mentioned, Aaron, Bangladesh has some of the areas that have the highest values that we've found. In some areas in Bangladesh, drinking water has as much as 800,

per liter or 800 parts per billion of arsenic, which is so high. Yeah. But in a lot of various rivers streams and other freshwater sources, in various environmental studies have found as high as several thousand parts per billion. It just doesn't necessarily mean that that's in the drinking water. But the good news is that especially in Bangladesh, where we know these levels have been so high, a lot of progress has been made to try and reduce the number of people that are being exposed. The World Health Organization's most up-to-date numbers are unfortunately still rather

old. They're from about 2012. But then it was estimated that over 39 million people in Bangladesh specifically were exposed to levels over that 10 micrograms per liter in their drinking water, and 19 million people were exposed to levels above 50 micrograms per liter or 50 parts per billion, which is a lot higher than what our minimum should be or maximum should be. Right. Yeah. And in one area of Bangladesh, an estimated 21% of deaths were actually attributed to arsenic poisoning. 21% of deaths. 21%?

I know. It's so much higher than I realized. Yeah. Yeah. Globally, mostly the... sources still are just various environmental sources. Arsenic is found in rock, in volcanic ash, like you said, but anthropogenic sources like mining, the burning of fossil fuels, working in industries like alloy making, etc. Arsenic containing pesticides are not really used in the US

very much anymore. They're not from what I can tell completely eliminated, but the use of them has declined significantly. Arsenic is still used in treating lumber. That's one of the main areas that it's still used as a sort of pesticide. It's for like an antifungal. So treated lumber is generally treated with arsenic. Interesting. I did not know that. Yeah. Yeah. So wash your hand. That's why they always say to wash your hands after you're working with treated lumber. It's not necessarily the exposure via your hands, but just, you know, how much it's easy to get that on your face or mucus membranes after handling it. And one thing that I kind of really was trying to get a handle on in addition to those

numbers that I mentioned, which weren't really that satisfying to me when I was trying to get a sense of like the global state of arsenic epidemiology or whatever I usually do in this section is that the vast majority of papers that I found, even the ones that were like seemed from the title that they were going to be talking about the epidemiology of chronic arsenic or of arsenic exposure, most of these papers were actually more focused on the mechanistic underpinnings. Like, here's what you should understand about the mechanistic effects if you want to study the relationship of arsenic and its various, you know, potential effects. And so it seems like from what I can gather and from the paper,

that we're trying to kind of assess the state of arsenic knowledge. The biggest thing that researchers are really trying to get a better handle on are some of these very specific mechanisms to explain the health effects that I talked about in the biology section. Because as much as we know, okay, it can affect these various enzymes, it can react with thiols and self-hydroles. It can mimic phosphate. Because there is such interactions between exposure to arsenic, and exposure to so many other things or things like malnutrition, etc. A lot of the epidemiological studies can result in mixed results, especially when you're looking at very low levels of arsenic exposure.

So we know all of those health effects from very high levels of exposure, but when we get down to the like 10 parts per billion, 15 parts per billion, five parts per billion, the data becomes a lot less clear. and it seems like a lot of that is because we don't fully understand the effects that arsenic is having on our bodies. So a lot of the research seems to be focusing on that, especially at lower levels of exposure. Like if we can understand specifically what does arsenic do when it gets into our body and how much does it take to cause that in various people, then you can have more data to say, no, this really is an acceptable level and this level is not. not acceptable at all, if that makes sense.

Yeah, yeah. So that is kind of what I researched, at least when it comes to arsenic. I tried to look into arsenic in rice, because I don't know about you, Aaron, but when I think of arsenic poisoning, I think of rice. Yeah. And I actually didn't even know why in my brain I had that association. Yeah. But arsenic is something, it is ubiquitous, but one of the reasons that it can be found in

relatively high levels in rice and in things like rice cereal, which for a while was touted as like, the best thing to feed your baby, rice cereal, is because of the way that rice is grown and harvested. So it's not necessarily rice specific, but it's the way that rice is grown, which is often under flood irrigation. And so in places where you want to be able to grow rice during the dry season, where you don't have as much rainfall, if ground, water is used for that flooding, groundwater can contain a lot of arsenic. And on top of that, the way that rice grows in this flood irrigation happens to be really good conditions for arsenic to be in that form of arsenite, the reduced form, which is very toxic and bioavailable. And so

it's easily taken up in the rice and accumulates in the rice in high levels. And then when you dry that rice out, pulverize it, and concentrate it into something like a baby cereal where you're exposed to a lot more rice than you would be if you were just eating a bowl of rice, then it's even more concentrated. And so that's how you end up with high levels of arsenic potentially in something like rice or a rice cereal. Okay. It's not rice isn't the bad guy. Right, right. But yeah, that's a nutshell of arsenic current events. I mean, there's, it's a complicated topic because, because its distribution is so uneven and it seems like we just don't have a good handle on, on everything. No.

Which is kind of, yeah. Kind of a little scary. And kind of scary and all of those things. Yeah. But I feel like we covered a lot of ground in this episode. And I just also wanted to say that if I left out your favorite arsenic trivia or favorite arsenic movie or book or whatever, like maybe you wanted to talk about the anacondamine in Montana or how arsenic was used in dentistry forever, please share it on the social media post announcing this episode's release or wherever you want to share it because we'd love to hear more about arsenic.

I love it. Well, should we do sources? Let's do sources. I had several. I'm going to shout out two in particular. One by Apata and Pfeiffer from 2019 is about the evolution of that variant of that arsenic metabolism gene. That's a really interesting one.

And then for the big history section, mostly I used a book called King of Poisons by John Periscandola, all about arsenic. I had a number of papers that have so much more detail on what we know about the mechanisms of arsenic and its effects on our body. A couple that I'll shout out, one from toxicology International from 2011. That was just called mechanisms pertaining to arsenic toxicity. And then there was actually a great Department of Health and Human Services, like very comprehensive. It was called the toxicologic profile for arsenic. and it was from the Agency for Toxic Substances and Disease Registry.

And that's really comprehensive and also has some data about what the state of arsenic is in the world and in the U.S. We will post the full list of our sources from this episode and every one of our episodes on our website. This podcast will kill you.com under the episodes tab. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the Exactly Right Network. And thank you to you, listeners. We hope that you liked this one. I think I did.

I loved it, actually. I really liked it. Yeah. Thanks for listening. And a special thank you to our patrons for supporting us on Patreon. We can't tell you how much it means to us. Yeah, truly. Well, until next time, wash your hands.

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