This Podcast Will Kill You - Ep 31 Giardia: Gerardia

Episode Date: July 9, 2019

Giardia may be the most common intestinal parasite in the US and one of the most common worldwide, but did you know it was only in the last 40 years that it was officially recognized as a human pathogen?! In today’s episode, we’ll travel back to a time before humans knew microbes even existed to discover alongside Leeuwenhoek a whole new world of animalcules like giardia. We’ll find out how seeing these critters for the first time changed everything, and how long it has taken to recognize their impact on the globe. Plus, we’ll tell you all about how giardia gives you such bad poops. See omnystudio.com/listener for privacy information.

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Janice Torres here. And I'm Austin Hankwitz. We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio, in partnership with Intuit QuickBooks. We're back for season four to talk to some incredible small business owners. The big thing about working at tech is that it's ever evolving, ever changing. everyone's a rookie. That's how fast the industry is changing. So what I'm really excited about is to be part of that change. So listen on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. July 3rd, I woke that morning lethargic. The coffee didn't help my energy materialize, nor did it help clear away the clouds that had formed in my brain.

My functionability was so affected that at one point I was sitting at my desk holding my head in my hands. That was the moment home seemed like the best place for me to be. Something was wrong. Something was churning. That was the night the sickness hit. It reared its ugly head first by the expulsion of the contents of my stomach. I couldn't stop it from happening. Try as I may no deep breath would stay the sick. I was thwarted at every turn. Worship at the throne of the toilet god was inevitable. Dehydration became the scariest factor in this situation. I was losing more water than I could drink, partly because of the toilet god was inevitable. Partly because of the toilet god was inevitable. Dehydration became the scariest factor in this situation. I was losing the scariest. I was I had no desire to drink. I tried to work. I tried to eat. I slept on my sofa. I slept in my bed. I didn't get dressed. I barely ate. Sitting in my apartment alone, feeling the rumblings of my bowels, knowing that I was getting neither enough water nor nutrients was alarming. July 8th, Tuesday, a week since the beginning. Niagara rushed again. All the happiness and confidence that had been present on Monday got flushed right down the toilet. I was scared, but I thought I just had to keep

waiting. July 24th. I sent an email to my doctor's office pleading my case, begging for a spot in his busy schedule. Three weeks after life took a drastic turn towards Liquidville, I had an appointment. July 26th, Thursday. How was I going to catch the evacuating contents of my colon? bowl, bag, milk jug, milk chug with the top cut off, ew, a bag it was. Having finally figured out how to catch the liquid, I was ready. Now to the fun part. I was back on my knees at the throne, only this time I was armed with a spoon smaller than one used to feed a child its baby food. Thankfully, I only had to scoop about a quarter inch worth of waste into each vial. With a spoon that small, though, it took scoop after scoop, after scoop, after scoop.

July 29th, Sunday. I got a call from another doctor who works with my doctor. I'd been compromised. Small amounts of the parasite Gerardia had been found. A parasite. I had a parasite. After the initial shock, relief again washed over me. It was treatable with an antibiotic, and I could actually start it that day. August 5th, Sunday morning, I took the final dose of antibiotic. The party is over. Gerardia has left the building. As the host of a few human parties in my time, this was one of my least favorite. A host should have fun at their own party. But this party was full of selfish guests. They took and took and took from me, giving me nothing in return for my accommodations.

That's a very, you find the best first-hand accounts, Aaron. That one is one of my favorites, I think. It's amazing. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And where did that first-hand account come from, Aaron? So that came from a blog I found.

It's Michaelroar.blogspot.com. And it's from a August 2012 entry titled Giardia Ruined My Jolidia, which is an amazing title. It's a very good title. So, as you might have guessed, this week, we are. are covering Giardia. Yes, we are. The beautiful, beautiful protozoan parasite that will cause you to have horrible diarrhea. Yes. How fun. Wonderful. What a joy. This is kind of back to our standards in terms of disease, which I feel like we haven't done for a while, so I'm excited too. Like, it's a, it's a pathogen and it makes you sick, like our first season ones, you know?

I feel like we've been doing some off the wall crazy episodes lately. We did H. Pylori, which was along the same lines. That's true. That's true. No, it's hard to keep track. We have done a lot of sort of non-traditional format type ones. I'm very excited for this. I'm excited to hear all about how it works. I don't really know how it works. Oh, good. I can't wait to tell you. To honor Giardia, what are we drinking this week?

Our quarantini this week is Backpackers Delight. That's a good name. That's named because it is a very frequent infection in backpackers and many other people as well. But backpackers tend to get it from drinking contaminated streams. So make sure to filter your water people. What's in backpackers delight? In this beverage, we have coconut water, you know, to rehydrate you after all that diarrhea. Perf.

Pineapple juice because it's tasty with coconut water. ginger liqueur because that's good for your stomach, right? Vance. And vodka. Not good for your stomach. Not good to rehydrate you. But essential for our quarantini. Yes.

But our placebo rita does not contain alcohol and we will post the recipe to both the quarantini and the alcohol-free placebo-rita on our website and on our social media platforms. Yes, we will. So before we start on today's episode, I actually have two corrections. that I'd like to make that people emailed us about. So very quickly. One is from, I believe, our last episode or second to last episode on encephalitis. So in that, this is very embarrassing, Aaron. You mentioned that Robert De Niro, like, won the Academy Award, and I was like, oh, I'll fact check you. And I did that live during our recording of the episode, and I failed at fact

checking you. I did it incorrectly. Robert De Niro did not win Academy Award for Best Actor for Awakenings. But he was nominated. He was nominated. Thank you to true trivia nerd Amelia for writing to let us know. Thanks Amelia. Keeping us on the path. Oscar trivia nerd self-proclaimed. Okay. The other one is from our recent crossover with In Defense of Plants, where we talked about aspirin. So as I was talking about all the various effects of aspirin, one of the effects of aspirin is that it's an antipyretic or an anti-feber. So it reduces fever. And in the episode, I mentioned that this is due to its effects on vasodilation. I got over-excited.

Vazodilation can produce like local heat production. So like if you get a cut and then you have heat, the cut feels hot. That kind of heat production can be from the vasodilation, but systemically, aspirin is even cooler in that prostaglandins in your brain, which aspirin blocks the production of, modulate the temperature center in your brain. So aspirin and other ensigns actually work by reducing the temperature set point in your brain or blocking the increase in it. and that's how they reduce fever. So that's actually a much cooler mechanism. And I'm really bummed that I didn't mention it in that episode. So thank you very much to Kelly for emailing about this.

Interesting. For anyone listening who has no idea what I'm talking about, that means you didn't listen to our aspirin episode. So you should go check it out. Hey. Okay. Is that all the business that we have? Yeah, I think so.

Well, then let's take a quick break and then get started on the biopi. Let's do it. Gerardia. Okay. First of all, there's only one R in Giardia. I know. I always call it Gerardia. It's like you're saying Gerardia Butler.

Gerardia. Geardia. Is that better? Yeah. It's like, I think it's the biology equivalent of saying nuclear. Okay, but I am always afraid that I'm going to do that, so I never say that word in public. Say it. No.

Girardia, okay? Beaver fever. That's what we're talking about today. So, geridiasis, which is the disease caused by Gerardia. Still doing it. Gerardia. Geardia. There we go.

Listen, it's fine. Gioridiasis is the most frequently diagnosed intestinal parasite in the United States. That's my first fact for you. It's a massive, massive disease worldwide. It's common among travelers. It's common across the globe. So let's talk about what it is. Yeah. First of all, it's a parasite. It's a protozoan, which means it's a single-celled organism. Protozoan is not a great word, but I used it. So there. It has three different names, three different species names that people call it, and it's all the same species, which is just, to me, the most annoying thing. Oh, my gosh. It made it very difficult to research. Yeah.

It has also changed throughout history multiple times. Oh, I'm not surprised about that at all. Yeah. So in medicine, they're more likely to call it Gerardia Lamblia. Yeah. But in the rest of everything other than, like, human medicine, it's Gerardia duodenalis or gerardia intestinalis. Or gerardia intestinalis, which is kind of funny because duodenum is just the first part of your intestine. So it's kind of like those are interchangeable. But anyways, Gerardia. I'm only saying one R, Aaron. It's never going to stop. I can't at this point. It's too late. It's a flagellate. So that means it has flagella, which we've talked about before, that they use to move and swim. Like a little tail.

A little tail. In fact, not just one little tail. Girardia. God, I did it again, didn't I? Giardia has four sets of flagella. So it actually has eight that it uses to swim around. And it has two adorable little nuclei that look like eyeballs. Gerardia is one of the cutest parasites of all time, in my opinion. I was just going to say, I think it is the cutest one.

done so far. It is, yeah. I think it's one of the top cutest ones ever because it really looks just like a little person's head. Yeah, they're so cute. Okay, so because this is a parasite, we get to talk about the life cycle. As far as parasites go, Gerardia has a very simple life cycle compared to a lot of parasites. It has two different life cycle forms. Inside of your intestine, it's called a trophazoid, and this is the form that looks like what I described. So it has two big old nuclei that look like eyes and eight floppy flagella that look like hair running off of it. So the trophazzoite form can swim through your intestine, stick on to your gut walls, and then they also divide by fission. So one trophazzoite can actually replicate and replicate and replicate,

all on its own. They also then form a cyst phase, and the cyst phase is what you're most likely to poop out and what ends up in the environment. You poop out trophazodes too, but the cis are really important in their life cycle because the cysts are very resistant to environmental stressors. So they can survive in water like ponds and rivers and storm drains and mountain streams for weeks to months. And then when an unsuspecting animal comes by to take a drink from that beautiful mountain spring, they're going to get a big old mouthful of gerardia cysts.

And then inside of your body or the animal's body, that cyst will then split and produce two trophazzoites and begin the cycle all over again. How cool, right? It's beautiful. And simple. I like it. It's simple. It's straightforward.

Another thing that's very cool about the cysts is that they're resistant to a lot of the common ways that we disinfect water, including chlorination and ozone nation or whatever you call it. Ozonification. But the chlorination is the chlorination that we use to treat the drinking water high enough to kill Giorgia? Nah, dude. You have to filter it or you have to boil it. Oh. Gerardia can live in your pool for up to like 45 minutes.

Not for a long time. Huh. Interesting. Yes. Mm-hmm. Mm-hmm. Mm-hmm. Mm-hmm. And when you're infected with it, you can poop out between one and 10 billion with a B cysts every time you poop. 10 billion is a lot of cysts.

It's a lot of cysts. And guess how many sists it takes to get you sick? Probably one. Well, usually about at least 10. Anyways. So that's why it's really, really common to get Gerardia from contaminated water sources. That's one of the most common ways that we think about the transmission of gerdia is from contaminated water. However, you can also get infected directly with trophazzoites, which you're also pooping out at the same time that you poop out cysts.

So other places that you can get infected are places that have a little bit less hygiene, like maybe daycare centers. which are one of the most common places that we see outbreaks in, for example, the United States. Tiny humans, poop their diapers, rub their hands in it, touch their friends' faces, everyone gets gerardia. I mean, we see a lot of GI things, parasites pathogens. Yeah, filthy tiny humans. Yes. Okay, so let's talk about the symptoms. Symptoms can range from absolutely nothing, entirely asymptomatic, just feeling normal, pooping out parasites without ever knowing that you're sick, to an acute illness that pretty much is self-limited, so you have diarrhea for a short time, and then you get better, to some pretty severe chronic infections that can result in things like weight loss and malnutrition.

Question. Yes. What proportion are asymptomatic versus symptomatic? That's a good question. I haven't found an exact number on that. And in the epidemiology section, we'll talk a little bit about why that's hard. But it does seem to be a pretty high proportion, and it depends on what strains of the parasite are circulating in the area. Because different strains are more likely to produce asymptomatic infections than symptomatic infections.

That's a good question. So the variability in presentation, like I said, is partially due to the virulence of the pathogen, like which one you end up getting infected with. But it also has a lot to do with your own host immune factor. So just something about you that makes you more likely to get a symptomatic infection. And then also the infectious dose. So how many of those cysts did you actually swallow? So let's talk about how it causes these symptoms, because I'm really excited about it.

Yes, me too. So the biggest symptom that you get with G.R. Diasis is diarrhea. You also get generalized abdominal pain, maybe distension, maybe it feels big. Maybe you get nausea and vomiting. You can definitely get that from infection with Gardia. Getting better. But diarrhea is the number one. So it turns out that we don't know everything about how it causes these symptoms.

But we do know a few things. So first of all, Giardia does not invade your intestine wall. So unlike something like hookworm that when it gets in is going to make a hole in your intestine and like actually punch through, Giardia doesn't do that. What it does is it has on its ventral surface, so on the opposite side of where the flagella are, it has this adhesive disc. So it uses its flagella to swim through your intestine up to the wall of your intestine, and then it uses this adhesive disc to just suction cup on to the wall of your intestine. And then do what? And then absorb your food, essentially, and just live and represent.

replicate. And they replicate by fission. So you don't need to have multiple parasites to replicate. They just replicate the way that bacteria do. They just divide. They don't sexually reproduce. There is some question as to whether they do sexually reproduce. They definitely do recombination, which is cool. Yeah. There's some really interesting articles that are like sex in the dark. Does you already have sex in the dark or something like that? It would be pretty dark in your intestine. Yeah. But so how long does an average Giardia infection last if untreated? It's hard to say because in some cases it can cause a really prolonged chronic infection. If you just have an acute infection, it'll probably resolve in a number of weeks.

But some people can be infected for months and months. Okay. So it's a very difficult thing to put like a straight number on. The incubation period, so the time from when you're first infected to when you start showing symptoms, is usually between one and three weeks. Okay. Okay. So once this parasite is attached onto your intestine wall,

they have a number of different mechanisms that, again, none of them are completely well understood, but these are the things that end up resulting in you having potentially massive diarrhea. So first is that they basically induce the cells, the epithelial cells lining your intestine to start undergoing apoptosis, which is cell suicide. That's bad news. I know. So they don't directly kill any of your cells, but somehow something that they're releasing

causes those cells to start undergoing apoptosis and essentially dying. So what that is going to do is increase the permeability of that epithelial cell layer. So normally the cells of your intestine, you can imagine, are very tightly packed because you only want certain things to pass through, right? You want to absorb nutrients, but leave a lot of stuff in your intestine. You want to absorb water, but not too much water, etc. It's a very fine balance, the whole process of digestion. So you're basically poking a bunch of holes by destroying these cells lining your intestine. On top of that, they flatten the microvilli. So microvilli are the protrusions.

on your intestinal wall that increase surface area to be able to absorb water and nutrients. If you flatten those, then you decrease the surface area, then you can't absorb that water and nutrient as well. So what that means is that in combination, when you have increased permeability and then you also have a decrease in the microvilli, you're completely messing up digestion, essentially, and absorption. What that means is, you're, is that you're going to end up with more stuff left in your intestine, and that's going to pull even more water out from your cells into your intestine instead of the other way. So that means that you're left with a watery stool, and that's what diarrhea essentially is, right? It's like

your food is passing through without actually getting absorbed. Does diarrhea have to be three times in 24-hour period? That's a very good question. No. There's no official definition on how you classify diarrhea. Usually we say three stools, three loose stools in 24 hours is when you can start being like, oh, I have diarrhea and not just like one bad poop or something like that. But it's not an official official definition. Okay. Yeah. On top of that, there have been studies that show that Gerardia increases the rate of transit through your intestine. So your food is moving faster. And if it's moving faster, then your body can't absorb everything that's in it. So that's another way that it can cause

diarrhea and malnutrition. Because if it's moving so fast that you can't absorb what's in there, boom, dude. No good. Hmm. I wonder if what you eat affects any of these things. Oh, what a good question. That's a very fun question. There's more. Okay. On top of all of that, there's some evidence that Giardia causes hyper-secretion of electrolytes. So on top of not allowing your intestine to properly absorb electrolytes and other things in your intestine, it causes the secretion of electrolytes from your cells into your intestine and wherever electrolytes go, water goes. So now you have even more water going from your body into your intestine instead of the other way around. It's definitely kicking you when you're down. It's not content to just like wring out your intestines a

little bit. It's like, no, completely dry. Completely dry. Burning some bridges there. Right. And so that's all of sort of the diarrhea-based things that Gardia does. Okay? Okay. Pretty cool. It's a lot. And we don't fully understand exactly how it happens, but it's easy to see how the few things that we do know can end up leading to maldigestion, so losing nutrients,

malabsorption, not being able to absorb these nutrients. So if you are not able to fight this parasite off and you have it chronically, it's easy to see how this can become a pretty serious infection that leads to poor nutrition. Yeah. Now, here's some things that I didn't really realize when I started researching this. In many cases, GRD is linked to later development of a whole host of diseases that we usually consider to be more autoimmune, like irritable bowel syndrome. Oh.

There's a pretty strong association between infection with geridea and irritable bowel syndrome. You also can get extra intestinal manifestations. So that means manifestations of this infection outside of your intestine, but not from the parasite. Because again, this parasite doesn't penetrate your intestine wall. So the parasite itself isn't traveling through your bloodstream and going anywhere else, but you can still get a ocular symptoms. You can get like eye infection type symptoms. You can get joint pains. You can get skin rashes from gerardia infection. Does it have some sort of surface protein that mimics human surface protein? You're so, so, I love this, Erin. I don't know if it mimics human

proteins, but there is thought that because the intestinal wall permeability is increased, antigens from gerardia are being sucked into your bloodstream and those are what's causing the extra intestinal manifestation so it's not the parasite itself but it's some of their surface protein that make it into your bloodstream how cool is that that's cool that's cool that's horrible I have a question about a symptom yes rotten egg burps yeah I heard you mentioned that earlier sulfur burps mm-hmm I didn't come across that as a thing in researching this. But, I mean, it's totally screwing up your gut.

Yeah, I just wondered what specifically would be causing the sulfur smell from that. Yeah, that's a good question. I don't know. Huh. The good news about this parasite is that it's pretty easy to treat. Yeah. You basically just go on a course of antimicrobials, usually metronidazol or nitazoxinide, another, just there's a couple different classes of

antimicrobials that we can use that are very effective so far at treating it. The problem is reinfection is really, really common, especially if the reason that you got infected in the first place was that sanitation isn't great where you live or something like that. If you got infected while you were out backpacking, you're probably less likely to get reinfected once you clear that infection. But anyways, I'll talk a little bit more about that all in the epidemiology section. But anyways, that's the biology of Giardia. I like it. On the surface, straightforward, but I think there's a little bit more interesting things going on. Yeah, and it seems like there's very, very cool research being done on figuring out exactly how this pathogen ends up causing all these different

manifestations and exactly how it's affecting all the different cell layers in your intestine. It's very cool. We at this point don't even know exactly how it adheres. We know there's a bunch of different proteins that are interacting on that ventral disc to suction it on, but still. Well, it's surprising that it's sort of an up-and-coming field of research, considering that it's so widespread. Yeah. Yeah. Shall we take a quick break? And then I want to you to tell me all about how we got here and where the heck this parasite came from. Okay, I'll do. I'll try my best. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs

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now available in Canada too. That's Q-U-I-N-C-E dot com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. Before I get started, I just want to admit that when I was research, researching this history, I had a bit of a tough time, and you know this because I complain to you in excess. I wouldn't say excess. Well, I did complain about it, yeah, which is nice to have this be something to complain about instead of many other things. But it shows that my life is pretty good. But the thing is that there isn't a super cut and dry history of Giardia in humans. which is strange to me because it is one of the most prevalent waterborne infections and causes of diarrhea around the world today

and has probably held that title for centuries. Giardia doesn't have the glitz and glam of a pathogen like cholera. It's more of a background parasite, always kind of causing a bit of trouble here and there, but rarely headline worthy. I just love glitz and glam of cholera. Fantastic. Has anyone said that about cholera before?

Not until this podcast. That's why we're here. Yeah. But the history of Giardia can be condensed pretty much into a few sentences. Oh, okay. And in most of the papers that I skimmed, that's all that it was. But that wouldn't really make for a very good podcast episode, in my opinion. So I kept digging deeper.

And as I dug more and more into the history of Giardia, I found that it was part of a larger story that I could tell, one about a new way to see the world. Ooh. Okay. Just bear with me. I hope this is okay. I love it already. Gardia was first described in 1681 by the famous Antony von Lavinhook when he was examining his diarrheal poop under a microscope of his own making.

Yeah, that's the kind of guy he was. I think he would have been a fan of TPWKY. We would have been friends for sure, yeah. Possibly. And so this isn't the first time that we've come across Lavin Hook during the podcast. And I remember this because every time I talk about him, I have to try to figure out how to say his name. And I end up just crossing my fingers and hoping for the best. But mostly when I've mentioned Lavin Hook, it's just been in passing.

So this guy named Lavin Hook saw this thing. and then I would move on to another part of the history. But for this episode, I really wanted to go more into this period of science, and what a critical role the microscope played in the development of many different scientific fields, and even more importantly, maybe, or more interestingly, our perception of the world. On the surface, Anthony Van Lavenhook may not have been the person you would have predicted would discover and develop a new way to see the world. He was born in 1632 in Delft in what was then the Dutch Republic.

He was a cloth merchant and a bureaucrat for most of his life. And throughout a lot of his life, he didn't really seem preoccupied or even that much interested in the natural world. It was only later that he started to dabble in lens making and maps and collecting of odd specimens and having a curiosity's cabinet, which was, by the way, all the raid. of course. In the Dutch Republic in the mid-1600s. A curiosity's cabinet? Of course. Yes.

Yes. I want a curiosity's cabinet. I'm getting there. Okay. One warm August day in 1674, Lavinhook was relaxed and maybe a tad restless, though. Now that he was retired and no longer had his thread counts to keep him occupied, he had turned his sights toward natural science pursuits,

which often pulled him out. outside into the sun. On this particular August day, he does something extraordinary, something that would go on to revolutionize our understanding of the world around us. He had taken some water from a lake that was a couple hours walk away, and he put it in a lens and tube mechanism that he had made himself, an early microscope. Even though the lake was cleaned, or at least believed to be clean by the people who lived near the lake, the drop. of lake water that he examined is teeming with life not visible to the human eye on its own. The motion of these animal cules and the water was so swift and so various, downwards and roundabout,

that I confess I could not but wonder at it, he said, about this, lake water. This marks the first time in history, probably, that humans had gotten a glimpse of an entirely new world, not visible to the naked eye. Discoveries like this don't often happen in isolation, although they're often told in that way. There's almost always some kind of build-up that has made it the right time and place for a particular development to take place,

or at least that's how we can see it in retrospect. So, in this case, what was going on in the world in 1674 that had set the stage for Lavinhook's discovery? So at the time that Leavenhook was looking through his microscope at this previously undiscovered world, the scientific world was undergoing something of a revolution, and maybe more accurately was being born. Whereas in the past, it was enough for someone to rely on the words or the writings of those ancient philosophers who had come before. The trend was shifting towards emphasis on data that you obtained empirically. through observations. And this often meant personally observing the phenomenon that you were interested in,

then publishing your observations, and then having other people independently confirm what you had seen. But these people, who were not yet called scientists, needed tools that would enable them to accurately measure whatever it was they were interested in and produce consistent results across other observers. And as we know, necessity is the mother of invention. And during the 17th century, a lot of invention happened. So all kinds of empirical tools were developed that expanded the realm of human observation. The thermometer, the barometer, the pendulum clock, the telescope, the microscope, these things were all either invented or developed to the point where they were in almost wide use.

That's so cool. It's so cool. And these, because these tools also, they turned these personal experiences, into impersonal numbers. The subjectivity in describing natural events decreased, but the words that were used to describe these observations became more specific and more relatable across cultures and languages. Oh, wow. I never even thought about that aspect of it. Yeah, it really did sort of flatten the globe, I guess, or in terms of advancing knowledge and saying, to be able to say how hot is it, it's pretty hot, or it's this many degrees, although here I am, you know,

Celsius and Imperial. That's okay. We won't get into. We have calculators now. Yeah, exactly. We have Google for that. This fascination with empiricism extended beyond those that were studying mathematics or geography or the natural world.

This time, so like the mid-1600s, the 1600s, the 1700s, the 1700s, was a time. of the observation of recording, surveyors would map the land while astronomers map the sky, and painters use camera obscuras to record scenes from life, while natural historians recorded the plants and animals around them. In this time, also, the boundary between artist and scientist was thin. So some of those that considered themselves catalogers of the natural world had been trained in painting or drawing, because how else could you relay what you were seeing or observing? Right.

And Dutch artists, in particular, were becoming more detail-oriented, with the tendency for art during this time to be more about what is directly observed, rather than telling a story or idealizing a person or place by ignoring or glossing over the flaws. This general focus on recording and realism during this time is, I think, a really important part of the story of microscopy. Because for the first few decades of its existence,

the microscope was primarily used to demonstrate the wonders of the natural world. Look at this super cool grasshopper. Look at this tiny mite living in your cheese. This animal keel. What does he call them? Animal cure. Animal cure. And while telescopes shortened distance, bringing far away things closer to the eyes,

those things were already generally known to humans, just far away. You could see that that star or that planet or that tree was there, but if you looked out of the telescope, it's closer. But microscopes, on the other hand, revealed this whole new world. And this, I feel like, would have completely shifted the perception of the natural world and what role humans play in that. Oh, yeah. It's really hard to imagine.

It blows my mind. quite honestly. It's impossible. It really is unimaginable, like, to wonder at what that would be like today. It would be like discovering that we live in the teardrop of a giant. I don't know. I feel like it, I mean, this is not as extreme, but I feel like it was how I felt the first time I ever went scuba diving. Mm.

I, like sitting at the bottom of a kelp forest and looking up, you realize. just how like it's an entirely different world and I feel like it's a similar you're looking if you have no concept that things this small exist and then you look in a drop of water and you see this it's like yeah yeah that's the closest I can come I've read before that people who go to space astronauts and then they look down at the earth that their perception of of world of life of human of humanity is forever changed by that in a way that's, yeah, that you can't imitate or mimic. And I kind of wonder whether that was, it was similar to that being some of the first people to say, oh, like, there's a whole new world here and not just being told or seeing pictures of it.

I can't stop singing a whole new world every time you say it, by the way. Every single time. It's amazing. Yeah. But yeah, these microscopes could reveal the tiny, tiny, tiny little intricacy of a flea's leg and how beautiful it could be to look at a spider's eye. It's amazing.

It's incredible. Robert Hook was one of the first people to develop or to use the microscope in observation. And he had this groundbreaking book called Micrographia, Micrographia, that displayed the exteriors of these tiny creatures or of everyday objects, magnified to sizes never before seen. And he had a foldout of a flea, for instance. Oh, yeah, I've seen that. I've seen that. It's incredible. Yeah. I want to get that coffee table book. Yes. I wonder if they make it. But the simple description of these things soon wasn't seen as enough. Some people were like, okay, these microscopes are incredibly powerful tools that should be used to explore the

inner workings of both living and non-living things. How do things work? Yeah. Just to use them only on making pretty drawings, seemed like a waste to a lot of people. Okay. So Lavinhook would not have been unfamiliar with microscopes or at least magnification using lenses because as a cloth merchant, he had to inspect his fabric for thread count. So it makes sense that he would have maybe tried experimenting with lenses, especially considering the trend that had swept society because people were obsessed, fascinated by lenses. Oh, that is so funny. They wanted to look at the mites crawling in their bread, the fleas on their dogs, anything and everything.

By the mid-1600s, you could find lens stores in every marketplace. And wearing glasses, even if you didn't need them, could be considered fashionable. Okay, that's still fashionable today, isn't it? So nothing has changed. Lens crafting varied in technique and quality and imperfections in the glass led many people, including Levin Hook, to experiment with making lenses of their own. After retiring from the cloth trade, Lavin Hook started to venture into lens crafting,

first with bead lenses, which is where you melt the end of a glass rod over a flame, and then you draw out a thread of glass cutting off the end when it becomes a bubble. What? Yep. And so from these bead glasses, you could make powerful lenses,

but with very short focal lengths. Huh. And because you were using flame to create them, you were going to make a lot of duds before getting a new one. Okay. So after bead lenses, Leavenhook moved unto grinding and blowing glass. His obsession or patience, maybe, or maybe it was both, rewarded him, and his microscopes ended up being some of the best known during this time.

In his life, he made loads of microscopes of varying magnification and construction and quality, an estimated 566 total. Wow. Of which, sadly, only nine survive, eight with lenses. I thought I remembered you saying that. Like, he's got a whole cabinet full somewhere that just disappeared from... Yep, it disappeared. He left it to the Royal Society after his death,

and somebody went to look at it in the mid-1800s, and then the Royal Society was like, we don't know where it is. That's the most depressing. Anyone who's thrifting or antique hunting in England, I think, is where the cabinet was last seen. Keep an eye. Yeah, man. I think a lot of the other ones to the glass tubes were melted down, not the glass tubes, the gold tubes were melted down for gold. Oh. Yeah.

But of those surviving lenses, of the eight ones that have lenses, the magnification range from 69 times, the magnification range from 69 times. to 266 times. What? But he may have achieved even higher magnification up to 500 times. That's bananas. He was probably the first person to see bacteria. He saw some on peppercorns. Wow.

I had no idea that he, wow. Yeah. 225 is a lot already. I know. It's amazing. That is very cool. So Hook had shown. shown the world this beauty and intricacy of things that humans already knew to exist,

like the foldout flee, but Lavin Hook would reveal a whole new world, a brand new world. I'm just going to keep saying whole new world. A whole new world. There we go. That previously had been completely unknown. And he started out like Hook, observing visible things in miniature, but when he stuck some lake water under his scope is when he discovered that this microscopic, teeming life that was present in not just lake water but rainwater and everything else.

It's hard to say whether even Lavinhook realized at first the magnitude of his discovery. He published his observations, but they were buried around 20 pages in his manuscript on other microscopic observations of things like the working of the eye. And so his description of this new unseen world wasn't met with much acclaim. And he kept sort of writing in with new observations saying, oh, remember when I found this like tons of microscopic life and rainwater? They were very small. They were very small. And finally, he was like, wait, did no one read this?

Probably not. No one makes it 20 pages in, Antony. Uh-uh. Come on, man. After his repeated writings, people finally did start to take notice of what he had said. And they were like, yeah, really? Come on. It was, there was a little bit of disbelief happening. Because Leavenhook was describing a world that was unimaginably small. He was describing living creatures 10,000 times smaller than the smallest thing perceivable by the naked eye. Geez. It sounded like a fanciful story made up by a very creative and bored person.

I'm an retired dude. Yeah. The credibility of his findings also wasn't helped by his extreme possessiveness of his instruments. He was famous for jealously guarding the secrets of how he made his powerful microscopes. And this was super frustrating to the Royal Society who had no patience for people obscuring the methods behind their discoveries, acting like magicians. And that's, I think, reasonable. Yeah.

Because how can you take someone at their word who claims that the water you drink, the rain that falls, contains billions, trillions of small animals invisible to the naked eye? Right. It sounds absurd. And they won't tell you how they made the thing in order to look at it. Right. Yeah. Yeah.

And he, you know, he recognized that this was standing in the way of the world. of the world accepting his immense discovery, but he was too stubborn to do anything about it. So what he did was he was like, all right, now you all can come here to look through the lens for yourselves. And they were like, we're not going to do that, man. We're in England. We're not going to go all the way to Delft.

It's not that far. And then so he was like, okay, fine. Stay there. Don't come here. He got people to write, like, to sign affidavits. saying that they had seen this in his scopes. And they were like, okay, it's a little bit better, but we're still not content. So then the Royal Society was like, all right, we just need somebody else to do this.

So then they pulled Robert Hook away from his workings of circulatory systems and respiratory systems because Hook had by now moved on from microscopy. Okay. And they were like, okay, Bob, will you try to replicate these findings? Bob. Bob, can you help us out here? And Bob did. So he did eventually, after a little bit of trying, find these animal cules that Leavenhook had supposedly seen.

So that was pretty big step. Yeah. His world was confirmed. And this discovery caused this major shift. Once it was confirmed by Hook, it was reported widely. and it caused this major shift in human perception, because suddenly the world both grew and shrank. Yeah.

Some people were comforted by it, taking it as evidence of a divinely created world, while others took a more nihilistic view. Oh. Yeah. For his part, Lavin Hook didn't stop at examining lake water or rainwater. Once he had gotten a glimpse of those microscopic worlds teeming with life,

there was no substance off limits. He looked at his own blood, urine, tooth plaque, pus, gunk from between his toes after not taking off his stockings for two weeks. That's pretty gross, man. Isn't that gross? He also looked at earwax, semen, and of course, his own feces. Who? Which is, of course, where he first spotted his sweet little gerdia. One of the things that I think is really fascinating about the development of microscopy is how long it seemed to take for people to make the connection between the little microscopic animal cules seen in sources of drinking water and diarrheal disease.

Yeah. Even Lavinhook was so fond of his little animal cules that he would never have accused them of causing the diarrhea in which he found Giardia. That's very adorable. He loved them. They were like pets. in his poop. Yes. He loved, I mean, he loved the ones in rainwater.

He loved the ones, he missed them when he went away. That's very adorable. Yeah. Okay. So going into Giardia a little bit now, it took almost 200 years after Lavinhook first observed Gyardia in 1681 for it to get an official name. Wow. And even then, it would be another 100 years or so before it was officially recognized as

actually causing disease in humans. Does that mean we're talking about the 1900s? Yes. What? Yeah. So in 1859, Villum Dusan Lambl, I probably said that wrong, was a Czech scientist, and he was examining the stool of a child, found it teeming with Giardia protozoa. He called them circumonus intestinalis, but the name eventually was changed to Giardia Lamblia

to honor Lamble and Alfred Gyard, who. who also described the parasite. So to put the official discovery of Giardia in 1859 into our history of disease timeline, that happened just a few years after the infamous Broad Street cholera epidemic in London. And as we remember from that cholera episode, the theory of myasma was in full swing at that time.

Of course, over the next few decades, people would use microscopes to develop the field of germ theory linking a parasite or pathogen to the site of infection. And microscopes were also used to develop so many other fields, both in biology, in chemistry, in physics, and everything. They've been amazing. I don't know why I was expecting that since it's a parasite, it somehow would have been earlier. But I mean, it's still, I mean, it's still microscopic.

It's still, you know, it's like malaria. It's like, yeah. Well, it's still microscopic, but even when it was recorded and given a name in 1859, it was still just seen as an organism. Right. Not necessarily a parasite. Yeah. God, that is so interesting. And I think so, yeah, I was thinking about this and I'm like, well, okay, that seems like one of the easiest links to uncover between microbe and disease.

Yeah. But it didn't seem like it got a lot of focus. And maybe that's because it was almost ever present and didn't necessarily cause a lot of obvious mortality or epidemics, even though it did cause occasional epidemics. Yeah. And if you can have just, I mean, probably everyone was infected with it. So you're testing everyone's poop and not everyone is having diarrhea. You're still going to see jaradia in everyone's poop. So you wouldn't think. Yeah, yeah, that makes sense. So it's a little bit of a harder, yeah. And there were some researchers in the early 1900s that claimed that GRD was a common cause of diarrhea, and they had conducted experiments on both humans and animals

to observe the effects of the infection, and they also had recorded their observations of GR. Diocese and English soldiers in like World War I, I think. But interest in the parasite seemed to wane throughout the 20th century. So the WHO officially declared it a human pathogen. or parasite in 1981, but it wasn't officially recognized as fulfilling all the postulates until 1987. And even after that, it was still debated whether some cases of disease could be attributed to the parasite. Yeah. That's like our lifetime. I'm surprised. I can't even wow. And this decline in interest, I think, was possibly maybe due to the massive reduction in waterborne infections throughout the developed world as water filtration increased.

So I couldn't really find any good numbers for global prevalence of GRDA throughout history. And that's maybe because it was only recently recognized as a human parasite. And possibly because it dropped off in places that had the highest amounts of research funding. But even though I can't give you hard numbers, I can make some guesses, which is a statement that the 17th century Dutch society would have hated. It's very non-imperical. Giardia has probably infected humans for millennia, as is evidenced by its global distribution,

and prevalence likely increased as humans settled and population density increased. As water treatment and filtration became more widespread in the first half of the 20th century, cases of intestinal diseases declined in many places, as did mortality from waterborne diseases. So, for instance, in 1900, if you lived in the U.S., you had a one in 20 chance of dying of a gastrointestinal infection before you were 70 years old. Whoa.

That's a lot. By 1940, that was a 1 in 3,33 chance. And in 1990, a 1 in 2 million chance. Wow. But for much of the world, the risk of dying of a waterborne disease remains staggeringly high. and Giardia remains one of the most common infections and causes of morbidity out there. So, Erin, tell me exactly what we're dealing with in Giardia today. I'd love to. We'll take one more quick break.

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Not compatible with any other offers. Zero percent APR financing for 60 months equals 1667 per month per 1,000 financed for well-qualified buyers through Stalantis financial services regardless of down payment. Not all customers will qualify. Contact dealer for details. Offer ends 3-2. It's funny that you said you couldn't find good numbers on Gardia throughout history because I couldn't find good numbers on GERDIA today. What's the deal?

End of our episode, just kidding. This is the most slept on parasite out there. So this is a disease that is so widespread that on the World Health Organization website page about G.R. Diasis, it just says distribution, colon, Worldwide. Wow. Like legit, that's what it says. So, according to the CDC, nearly 2% of adults and 6% to 8% of children in developed countries will be infected at some point in their lives with Giardia.

And nearly 33% of people living in developing countries will have been infected at some point in their lives. And we still don't exactly know how. how it causes disease. Well, apparently it was like 30 years ago that we decided we'll call it a human pathogen. So when you hear that, it's not that surprising. That's, yeah, that is, that's true. Yeah. Wow. So it's by a long shot, the most common human intestinal parasite diagnosed in the U.S. I did find a few numbers in one, one of the papers that I read reported at least a few numbers. So I'll give those to you. Between 2006 and 2008, in the U.S., there were at least 20,000 cases reported annually, and the estimated actual number

was closer to 2 million. And that's in the U.S. Okay. And for you, in Finland, in Finland, Norway, and Sweden, again, in like the mid-2000s, they estimated that for every single case that was reported, there were likely between 250 and 850 actual cases. that went unreported. Wow.

Yeah. And then throughout Europe, the numbers really vary, like, hundreds to thousands to tens of thousands reported every year. So we just absolutely do not have a good handle on how many people are actually infected at all. It's a real tip of the iceberg situation. And here's where it gets even more fun and even more tip of such a large iceberg, Aaron. Okay.

This was thrilling to get to read. one of the biggest things that we absolutely do not have a handle on that we're still trying to figure out is in regards to how much overlap there is between cycles of this disease between cycles let's talk about it so yes as it turns out there are several distinct cycles in which we can identify that gerdia circulates there's wildlife cycles So wildlife, poop in the wild, and infect other wildlife. Okay? That's a wildlife cycle of disease.

There's livestock cycles where livestock on a farm, poop on that farm and infect all the livestock on that farm. That's a livestock cycle. There's domestic animal cycles, like dogs and cats infecting each other. And then there's human cycles where humans poop and infect each other. the question that we don't know is how much overlap is there between these cycles and what kind of overlap is it? Are things being directly transmitted between wildlife and humans? Is it all waterborne transmission between wildlife and humans?

Is it more cycling between livestock and humans or between humans and livestock? which direction do these spillovers occur? And are there distinct species or subspecies of Gerardia being transmitted between these different groups or is it all the same parasite? We have no idea, Aaron. But I imagine that there's work being done on geographical variance or subspecies or whatever. Yeah. There's very, very cool work being done on the molecular,

of Giardia. It's very cool. A couple of questions real quick. Because you mentioned wildlife and livestock, what do we know about the prevalence in, I know that this is a huge question, but like, in general, is there much known about the prevalence of Gartia in wildlife or different wildlife species? Everyone calls it beaver fever. We can't get through the episode without saying beaver fever. Yeah. And so what is the actual prevalence in beavers? And then second question, or 15th, question. What about livestock? Are pigs more likely than cows? Are chickens more likely than goats? Where? Erin, you're asking all the right questions. You're 100% asking all the right questions. I don't have the answers to all of them. Aaron. Livestock are affected at very high rates in general.

And a lot of times, if you end up with one, for example, infected cow on a farm, then you're likely to have every single cow infected on that farm. So that's livestock. It's very, very common among livestock. How common it is among wildlife, totally varies and depends on what type of wildlife you're talking about and where they are. I mean, because again, this is a disease, this is a parasite that's found across the entire globe. Are there any species that don't get infected when exposed? Oh, good question. Don't know. Okay. Yeah. Don't have no idea. The other thing is. is we have no, we don't have a good grasp on whether it's distinct species or subspecies of

Gerardia parasite being transmitted among wildlife and livestock and humans. I know I keep saying it with two hours. Just leave it. I just keep thinking Gerardia bell. Every time I see your face, I know I've said it wrong. I'm trying to poker face this, but I can't. You're failing at a poker face. But there is a lot of molecular epidemiology work being done to try and figure this out because WHO has classified this as a zoonotic pathogen, which means that you would expect that most of the transmission happens in a zoonotic pathogen between wildlife or other animals and humans. But in many cases, that doesn't seem to be the case. And it might even be more likely that humans are actually infecting wildlife at just as high, if not higher rates,

then wildlife end up infecting humans. Mm-hmm. Mm-hmm. It's so cool. So while there's no doubt that Giardia can be a zoonotic disease, we don't know how frequently it's actually zoonotic versus just a human disease that circulates among human populations. Also, quick question.

What's the opposite of zoonotic? Is it anthroponautic? Anthroponotic. Fact-checked, me. I'm doing it. Thank you. Anthroponosis, yeah. Anthroponoses.

Yep, there we go. Perfect. So, we don't know fully. I will post a link on our website to two very great reviews, one from 2004, another from 2011, that dive really deeply into this. We don't have time in this episode to dive into all the different subgroups and subspecies and whether there should be multiple species of gerardia giardia duodenalis or not etc etc but what i do want to say is it seems as though at

this point a lot of the transmission and a lot of the outbreaks that we see in humans happen between humans human to human transmission so while things like drinking surface groundwater from a mountain stream is absolutely a risk factor for getting G.R. Diasis, it's not like we can just blame it on the beavers. Don't blame it on the beavers. It's equally possible that that water has been contaminated by humans or domestic or livestock animals. Isn't that just so cool? That's very interesting. It makes so much more sense to me knowing that it's been so recent that people have even been recognizing this as a disease because I was like, how do we know so little about the molecular epidemiology and like the distribution of this disease among wildlife and livestock and what species

or subspecies are affecting humans versus wildlife? Like it's bananas to me that we know so little, but there's very, very cool research being done on it. Yeah, good. The other big field of research right now is in vaccines. So there does exist already, licensed vaccine for dogs and cats, but it's not great. It doesn't work very well, as it turns out. It decreases the shedding of cysts in the stool of dogs, but it doesn't actually prevent infection or reduce symptoms of the disease. So it's kind of, if you're talking about giving it to your pet dog, it's not, doesn't seem to actually be that helpful. Hmm. Okay. But that just means that there's room for new research. I found a very cool study that was published in 2016. It was a

massive, massive study. Sometimes I look at these and I'm like, good Lord, you put like six years worth of work into one paper. Hoof. Yeah, but it was nature. So, you know, yeah. So this group developed a vaccine, a component vaccine that was actually a vaccine against the human genotypes that are more common among humans than dogs and cats. Okay. And it was a component vaccine, so just the surface proteins, not an entire killed parasite, which is what the vaccine that's for dogs is today. So in this paper, they showed that this vaccine could both stimulate an immune response in puppies and kittens, so actually stimulated their immune system to develop antibodies, that this immune response was actually protective against infection with gerda. So they exposed the puppies and kittens

to gerda. And then they vaccinated dogs and cats in a community. And they found that it protected the puppies and kittens, the dogs and cats in that community from infection. So over time, infection was less in the dogs and cats that were vaccinated. In fact, none of the dogs and cats that were vaccinated ended up getting infected after two years. Whoa. That's great. Yeah. On top of that, they tested children in that community, and infection in children in that area decreased over that time period as well. So in this paper, they were suggesting that vaccinating dogs and cats against this specific species or subspecies, this specific genotype of Gerardia could actually help potentially prevent the spread of disease in humans even. Huh. Based on a lot of the other molecular epidemiology studies, it seems like that's very context dependent because in a lot of communities, there's actually very little overlap between the genotypes

of gerardia that circulate among dogs and those that circulate among humans. So it would really depend on, so where they did this study in Argentina, that happened to be true. But in another community, it very well may not be. But it's still very cool. Huh. So, and again, I'll post the link to that study as well, of course. So about the widespread prevalence of Giardia and how problematic it is for nutrition and just overall health, what are the kind of secondary outcomes associated in like in terms of dally's or anything else like that? So I couldn't find numbers on that. A lot of it, a lot of the studies on Gerardia that look more at that, Gerardia becomes more important in cases of co-infection. So when you have areas where you have really high rates of

co-infection with gerardia and things like hookworm or other intestinal worms, that's when you see worse outcomes for people in terms of nutrition and malnutrition and things like that. But just looking at gerardia alone, there's not a ton of great epitata that I was able to find. Okay. Interesting. Yeah. Yeah. So yeah, that's. Pretty much geridiasis in a nutshell. How about it? How about it? Don't swim in a pool if you have diarrhea, please.

That's what I gleaned from all of them. I have one more question for you. Okay. How scared should we be of gerida? I think we should be scared that we know so little about it. Gosh. Oh, I like that. Okay. Maybe it's another H. Pylori.

Yeah, it could be. It really could be. Like, who knows what this thing has been doing in our guts for so long? Clearly, we have no idea. Causing lactose intolerance in all kinds of people. And all kinds of things, IBS, etc. Cool. That was fun.

Cool. That was fun. Okay, sources. I'm going to mention a couple of books that I read. One is called Drinking Water, A History by James Salzman. And the other one is called Eye of the Beholder, Johann's Vermeer, Anthony von Leavenhook, and the Reinvention of Seeing. But that's by Laura Snyder.

So if you just Google Eye of the Beholder, you're going to get a lot of bodice-ripping romance novels. You have to put in Leavenhook or Vermeer. But this book was really interesting because it dove into both art history and the history of microscopes. And it was just a really sort of big picture history book. I really enjoyed it. So Melissa Alman, if you're listening, you should read it. You'll love it. Yes, Melissa, please.

And then I've read some articles that I'll post the links to on our website. Yep, as always, we'll post the links to all of our sources on our website. This podcast will kill you.com. You can find our sources from this and all of our episodes. Thank you all for listening. Yeah. We really appreciate it. Thank you also to Bloodmobile for the music in this episode and all of our episodes.

and stay tuned because you are going to get a wonderful song that if you listen to the hookworm episode you've heard before. Parasite love song is going to play us out. It's the best. Thank you so much to Merrimack Valley Girl for letting us play it again. And you can find her website at merrimackvalley girl.com and she also has an Instagram. M-E-R-A-M-C-Valley Girl. All right. Until next time, wash your hands. You filthy animals. Can I live without you, not even for a day.

Please don't try to push me out. Please just let me stay. It's a miracle I found you. Introductions were not forced. Fate brought us together. Let nature take her course. You tried to avoid me But my instincts were too good

Your defense is now arising But I knew that they would I never want to hurt you I don't want to make you bleed Do you understand me Do you know that I have need Have you ever felt so wanted I may be a fluke

Our support may not be mutual but please do not rebuke. You're a giver, I'm a taker, but relations can evolve. I'll adapt to stay with you, our problems can be solved. Oh, what do I love about you? You're such a lovely host.

You're beautiful and rich inside where it counts the most. I promise I won't cheat on you. Please just let me stay. I cannot live without you I want you out you make me sick For lousy and you make me sick Also I just want to say

You are my mother Because you managed to fit in art history And microscope history In like the same sentence Listen I read a great book I'll shout it out at the end Okay

I'll say Melissa you should listen to this Or you should read this She'll be like, Aaron, I've already read it. I'm just kidding. Probs. We're friends on Goodread, so maybe she's already seen that I've read it, and then she'll add it to her Goodreads. I love it. This is Bethany Frankel from Just Be with Bethany Frankel.

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