She turned her head from side to side with a gentle movement full of agony, while constantly opening her mouth as if something very heavy were weighing upon her tongue. At eight o'clock, the vomiting began again. Then she began to groan 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, she was seized with convulsions and cried out, ah, my god, it is horrible. Then the symptom ceased for a moment. She 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 pulse 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.
Aye, yeah, yea yi 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 eighteen fifties. Madame Bovary by Gustave Flaubert.
And yeah, the.
Lead character dies of arsenic poisoning self inflicted. Wow.
Yeah, I have a question, Okay that book. Does she take arsenic like 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? Maybe No, I mean, come on, it's a novel. You have to allow some literary license, right.
One hundred percent?
Yeah, Okay, let's let's dive in. Hi, I'm erin.
Welsh and I'm erin allman updight.
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 truvy. Yeah, I'm thrilled to learn about how it works. But first, should we is it time?
It can quarantin any 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.
Yeah, And so we just decided to keep it simple and keep it sweet with the King.
The King and what's in the King erin.
What's in the King is essentially a Madori sour, because yeah, we had to have something green, because, as you'll learn, arsenic was used as a colorant for like a different shades of Green a lot during the nineteenth century, and yeah, Madori is hits, Ticks that Box and Harry Green. Yeah, and essentially Immadori Sour is Majori lemon juice, limejuice, soda water.
And we'll post the full recipe for the King as well as the non alcoholic place Marita on our website This podcast will Kill You dot Com, as well as on all of our social media channels.
On our website This Podcast will Kill You dot Com. The things that you can find there are numerous. They include our merch and our bookshop dot 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?
I would love to right after this break. 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 lee. 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.
Okay, I can't wait to ask him.
I know. My favorite part so Arsenic is a meta. What is a metaloid? You may ask, because that's certainly what I ask everyone, because chemistry really is something that makes me nervous. But I'm gonna 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 metaloid 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 metaloid a metaloid. 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 metaloids 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.
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. 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 pentavalant 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 adentizene triphosphate, 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 is just happens to be extremely deadly.
Right exactly. It just 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's just it just happens to be there.
Yeah, it's 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 hydral 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, ar 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 thiols 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 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, 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 holds 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 your hand 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 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 talksins on this podcast, the dose determines the poison or whatever.
Right, well said, thank.
You, So our first hand 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 Bovriy 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 Yeah, the highlight is very much on all the chronics. 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 your friend you'll find it in there.
Well, what I found is 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 choleralike, 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 intestine eucosa. So you're losing a lot through your guts. And because of all these losses, you can end up seeing high potension, 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 vary. 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 gonna methylate you. Hey, you look kind of like a phosphate.
Poop poop, you know, right, Okay.
So it's not necessarily Yeah, I don't know, it's a 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 environment mental levels because it's like parts per billion and micrograms per et cetera. But sixty thousand parts per per billion, which is sixty thousand micrograms per liter.
I can't, I can't imagine. It's very difficult to visualize it is.
It is. That level is about ten thousand times higher than eighty percent of the drinking water in the US, for example. So it's like really really high doses, okay, but even much lower doses, like three hundred to thirty thousand 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 ten ten micrograms per liter or ten parts per billion. Okay, yeah, so that's the number. So we're talking about sixty thousand.
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 ten parts per billion, but still low, like between fifty and one hundred say, for example. So people who are exposed to this lower level but still high level of arsenic over a prolonged 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 hyper keratotic, which means that they are these little hard patches kind of 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 could through any way that you are exposed.
Right, it's not skin contact, 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 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 ganggreen.
Okay, it can.
Cause heart attacks, it can cause strokes, can cause a lot of different things. 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 increase 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 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 our cells. 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 cidoskeleton are our nerve axons. So arsenate 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 geon Beret 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 acetylcholon estrise. It can cause an increase coal energic crisis. It can honestly, honestly, you said, it can go anywhere and do anything. 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 effects. 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 gonna 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 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 two 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, 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 two one hundred 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, still birth, 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 you know 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 that have been associated with arsenic.
Oh 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 Like, yeah, it's it is 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 that's arsenic arin 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 kulation therapy, especially if someone is exposed to very large amounts of arsenic. And what culation 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 wait it 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 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 cofactor 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 Aaron, speaking of connections, how did people connect the dots? Like, how did 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. 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 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 a mass wealth and power in fifteenth century Italy. Alongside Arsenic's potential for
murder is also, of course, it's 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. As I read more, I realize just how intertwined these roles of arsenic all are.
For instance, the rise of arsenic as a murder weapon in the eighteen hundreds 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 coloran. So let's get started on this rich history of arsenic.
Oh, 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, and typically you won't find arsenic in its elemental form in nature, it exists in over one hundred and fifty 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, in 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. So you talked about how we have a gene that is like
a methyl transferrase, right, it adds methyls 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 as three MT if you're curious, it's the arsenic plus three oxidation
state methyl transferrase 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.
Fascinating, 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, I think 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 seven thousand 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 thirty three hundred 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 metaloids. Okay, most metals aren't just hanging out there in their pure form. They often co occur with other things like personic 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 gonna 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 metal workers represents the very first occupational exposure.
Huh wow, bold claim.
It is a bold claim, But I mean, if you were smelting and 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. The Greek god of smiths, Hephaestus, 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 and recognition of.
That I love that air, whether or not.
Have faced this 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 arsenecon, 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 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, ulcer's cough, shortness of breath.
And so on.
Does it all?
Does it all? The first exposures to arsenic may have been of an occupational 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. There are two qualities that would make them pretty poor murder tools, at least if you wanted to get away with it.
Okay, aarin.
Arsenic trioxide, or white arsenic or rat spain. On the other hand, those are all names for the same thing. Is a powder that dissolves in water, is colorless and tasteless. Aarin Does it get better than that? Yeah?
No, not when you're trying to murder somebody.
M h.
This 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 Wolf, Spain 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 fourteen hundreds and fifteen hundreds thanks to the Borges, who were the Borges. Someone might ask.
I remember learning about the Borges.
In what class history?
No? I remember, and 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 Borges are a very dramatic and titillating part of history. So this was this family who super wealthy, super powerful, and whose name became synonymous with greed, adultery, theft, and murder, specifically murder via arsenic.
Ooh, I love it.
The Borges 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. My gosh, their signature poison La Cantarella was mostly arsenic, and they especially the siblings Cesaire and Lucrezia Borgia, whose father, by the way, was Pope Alexander the sixth, like the Pope Wait what the Pope? Yeah?
Had kim okay, 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 now think that a lot of these rumors about the Borges 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 Borges were definitely responsible for putting arsenic on the map as a murder weapon,
but they were merely just the first. After the Borges, Arsenic pops up more and more in stories like the one of Julia Tofana from Naples in the seventeenth century, who sold her signature arsenic poison Aqua Tofana to dozens of people. Or Hrona Maspara, who also sold poison and started a poisoning society in Rome in the mid sixteenth 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 sixteenth 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 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. But 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 a in movies and things. That's still like the trope, like poison is 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 seventeen hundreds, 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 to 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 their breakdown, according to the study. Interesting, and when anyone used poison, they grew more and more likely to reach for the bottle of arsenic. Let's talk about why, and to do that, let's head to the
eighteen hundreds. The nineteenth century has been called the arsenic century, but not because everyone in their neighbor was poisoning everyone else in 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 likes 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 mimicry, 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 eighteen hundreds, 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 US around the seventeen sixties or so and lasted until the eighteen twenties eighteen forties, 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 eighteen hundreds that mining for arsenic specifically really took off. The list of things that you could use arsenic four seemed endless, and the arsenic industry in minds 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 Shiel's Green. Wallpapers were full of the stuff.
Question.
Uh huh.
You know the book Goodnight Moon. Yeah, the walls are green. Uh huh is that Paris green?
When was Goodnight Moon written?
Ah? I don't know. It's been around since my mom was little, so before the late nineteen fifties.
I feel like it was. It's been around since the nineteen Yeah, I feel like no, it would Okay, 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 eighteen hundreds.
How fast eighteen hundreds?
Yeah, okay, I'm gonna 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, absorbing it maybe into your skin, maybe not. Yeah, there's a comic from eighteen sixty two 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 Mind, 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 there you can still get, actually, William Morris designs and all kinds of things. He was
all about the arsenic huh. 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 seem 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 what could be both probably both. Arsenic could also appear in candles, soap books, glass and glassware, paint,
stuffed animals, paper and packaging, fly papers, lamp shades. 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 fit 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 pine 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, Christmas tree ornaments, and children's stuffed animals. No less were often arsenical, and the money used to purchase all of these products was itself sometimes contaminated.
How fascinating aaron I it is.
I had no idea how the extent to which arsenic was in every day items.
I've 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 and 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 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 found something that like makes that color like, it's gonna 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 mines 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 shocking and intentionally But there was also a pretty infamous incident in eighteen fifty eight when an English sweet maker named Joseph Neil accidentally arsenic poisoned about two hundred people and twenty 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 this sweet maker 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 adding these other things. How could you have lived in the late seventeen hundreds and eighteen hundreds and not been exposed to arsenic like high levels of arsenic. Yeah, in the nineteen fifties, some hair samples of Napoleon, who died in eighteen twenty one 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?
I would love that. But Napoleon's hair was tested in the nineteen fifties 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 I'm sure probably because the other thing, too is that it's like, that's a great, that's 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 him severe illness and especially death, because there was definitely arsenic in the wallpaper on his living room walls, and also was probably arsenic in everything, just everything.
Yeah, and he's candy. I'm sure Napoleon ate candy. I feel like he had to have 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 minds. Yeah, every step along the way, from the dust inside the mines to the toxic gases produced in the smelting process to the packaging of the arsenic for future sale, workers were exposed to outrageous amounts of arsenic and many mind 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 minds making people sick. So they began an investigation into the health effects of arsenic minds, 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 a mine, 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.
Totally. 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 flag wallpaper. By the eighteen fifties, 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 thirteen.
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 nineteenth 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 diyes. 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 and 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 chalk full of arsenic.
Yeap, 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 spread, but the US, 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 US, and so they finally agreed to lower arsenic spraying levels, but only on apples that were to be exported.
Oh cool like that.
Yeah, it's awesome. Yeah, 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 nineteenth century. The arsenic based soap that somebody came up with was the soap 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 in the animal once you skinned it or something.
That's that's what it seems like.
Yeah, like thet I have literally never thought about what it takes to taxidermy preserve an animal.
But that could be a fun episode, it could.
Be And that kind of makes sense that they would use something gnarly mm hmm.
Yeah, it does. And during the nineteenth century was this huge time for natural history and taxidermy, as people traveled to new places and brought back animals specimens to fill museums. You have collections, collections, collections, and its legacy lasts today. For people who work on these historical collections in museums, they have to take special precautions to make sure that they're not being continually exposed to these arsenics and specimens.
Wow.
Yeah. And the success of arsenic and taxidermy led to it being used also in embalming starting in the early nineteenth 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 Pump 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 arsen 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 and water can be given over time to mimic a chronic illness, and importantly during a good chunk of the seventeen hundreds and eighteen hundreds was super easy
to obtain. In England. Until eighteen fifty one, 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 twentieth century. It was bad, 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 like to explain why it would be called that, but I'll just briefly mention one, which is that one of the signers of the US Declaration of Independence, George Wythe, 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 yeah, 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 two two thousand and three mass poisoning of churchgoers in Maine, then I will recommend the book King of Poisons by
John Pariscandala. 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 eighteen hundreds. There's an asterisk that I have here because there is one case in England in the seventeen fifties where a chemist claimed to successfully test for arsenic, but it's not clear what whether he actually did it and if it did anything. And the accused of woman who allegedly poisoned her father for preventing her elopement to an already married dude was convicted despite of this non specific and probably useless test and she was hanged.
Wow.
Anyway, The first actual test for arsenic in cases of poisoning was developed in the eighteen thirties 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, 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 regard 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 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 it's unclear, Okay. Even after the laws restricting the sale of arsenic were passed in England in eighteen fifty one, like I said, people continue 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, that switches a lot. Also, I just love Agatha Christie so much. Our first hand account, of course, was taken from Madame Bovary, published in eighteen fifty six, 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 nineteen forties. 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 at a long 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 and seue 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 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 or I know, or my favorite, taking small amounts of arsenic to build up an immunity. A la princess bride and iakane powder, and this building an immunity to arsenic may be based on the so called arsenic eaters of Steia, 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, and this rumor, this legend grew really really
famous in like the eighteen hundreds. 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 nineteenth century, when people were either poisoning their spouse or grandparent with the stuff, inhaling it while working in the minds, 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 twentieth century. But that's certainly not the end of arsenic 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 twentieth century saw arsenic being developed, but not extensively, deployed as a chemical weapon during World War One, in the form of something called lewisite, which is also how I believe we started to develop treatment for arsenic poisoning
in anticipation of its use as a weapon. The twentieth century also saw the emergence of arsenic as a truly effective medicine, first as a treatment for tripanisimiasis, then the first effective treatment for syphilis in the form of salvarsan, and later as a treatment for a certain type of
leukemia called acute promylocidic leukemia. And arsenic is to this day a hugely important and prevalent environmental contaminant and erin 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 that
highest risk is in Bangladesh and West Bengal. There in the nineteen seventies, 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 tubewells to tap into cleaner water from the Himalayas. A bunch of international organizations got involved, and by two thousand there were close to eleven million tubewells in these regions, providing water to ninety seven percent of rural residence, and
water borne illness and infant mortality dropped tremendously. But about ten years after this well building program really ramped up in the early nineteen eighties, 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 twelve hundred cases from sixty one 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, Erin, 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, 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 wow, yeah. So groundwater contaminated with arsenic is a massive problem worldwide, with an estimated, according to the World Health Organization, one hundred and forty million people in fifty 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 ten parts per billion or ten micrograms per leader. So one hundred and forty million people in fifty 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 air that have the highest values that we've found in some areas in Bangladesh, drinking water has as much as eight hundred micrograms per leeter or eight hundred parts per billion of arsenic, which is so high. 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 twenty twelve, but then it was estimated that over thirty nine million people in Bangladesh specifically were exposed to levels over that ten micrograms per leeter in their drinking water, and nineteen million people were exposed to levels above fifty micrograms per later or fifty parts per billion, which is a lot higher than what our minimums should be or maximum. Yeah, and in one area of Bangladesh, an estimated twenty one percent of
deaths were actually attributed to arsenic poisoning. Twenty one percent.
Of deaths, twenty one percent.
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, et cetera. 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 anti fungal h so treated lumber is generally treated with arsenic.
Interesting, I would 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 potential effects. And so it seems like from what I can gather and from the papers 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 hydrals, it can mimic phosphate. Because there is such interactions between exposure to arsenic and exposure to so many other things or things like malnutrition, et cetera, 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 ten parts per billion, fifteen 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 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 erin, 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. 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 groundwater 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 that's a nutshell of arsenic current events sarin.
I mean, there's it's a complicated topic because because its distribution is so uneven, and it seems like even we just don't have a good handle 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 anacondomine 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 have several. I'm going to shout out two in particular, one by Apata and Pfeifer from twenty nineteen 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 pariscandala all 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 twenty eleven 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 US. We will post the full list of our sources from this episode and everyone of our episodes on our website this podcast will Kill You dot Com under the episode STAB.
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Yeah, truly. Well until next time, wash your hands.
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