By the time paramedics removed Brianne Kiner from the ambulance and wheeled her into the e ER at Children's Hospital, Suzanne Kiner was doing all she could to hold herself together. Brianne was writhing in pain, and the diarrhea just kept coming, so did the blood. Suzanne was afraid to leave Brianne's side. It looked and sounded like her little girl was dying. Her breathing was rapid, she had deep pain in her chest,
her urine output had practically disappeared. Even her mental condition was deteriorating, and she was slurring her words when she tried to speak. When the hospital transferred Brianne to the ICU for round the clock observation, Suzanne wanted answers. The doctors informed her that Briann's stool culture had come back and definitely showed the presence of E. Coli O one five seven h seven, and her symptoms suggested she had hemolytic uremic syndrome. Shortly after arriving in the ICU, Brianne
suffered a seizure and stopped breathing. Doctor scrambled to resuscitate her. They gave her dilantin intravenously along with phenobarbital tubes were inserted in her chest. By the time doctors emerged to give Susanne an update, Brianne was in a coma. Suzanne had trouble swallowing. She wanted to scream, but all she could do was cry, WHOA yeah?
Did she survive?
She didhw Yes. So that first hand account is pieced together from a book called Poisoned, The True Story of the Deadly E. Coal I Outbreak that Changed the way Americans eat by Jeff Benedict. And it's about the outbreak of E. Cole I oh one five seven that you're going to hear a lot more about in nineteen ninety three. And Brienne was one of the children who was infected with E. Coli and she did survive, but she has had a lot of lingering problems because of this infection. Hi, I'm Aaron Welsh.
And I'm Erin omen Updyke.
And this is this podcast Will Kill You, And.
Today we're talking about E.
Coli E Coli.
Do you know I always raise my hands up when I say the disease that we're talking about, and no one can see except.
You, But I appreciate it.
Thank you, so so, today's a big one. It's a massive barin.
I did not realize that when we were like, let's do we call it?
Yeah, it's like it's well, yeah, we'll get into it. It's so big. It's so big. It's going to be a short episode though, don't worry.
Well to help us through this episode, I think it's time for quarantinis.
I think it's quarantini time. I have my first real quarantini in eleven months, yay, which feels quite exciting. What are we drinking today?
We are drinking the cookie Don't so and in the Cookie don't it's actually quite delicious.
It is. It's really tasty.
It is dark rum and chocolate liquore, Almaretto ice cream, ice chocolate syrup. You blend it and then you pour it into a glass that is rimmed with chocolate and crushed cookies.
It's so tasty.
It's really good. It's so good, it's like too good. I think.
Yeah. We'll post the full recipe for this quarantine as well as our non alcoholic Pussy Brita on all of our social media's and our website, so you can drink along with us.
Yes and it's called the cookie don't for reasons that I'm sure you'll go into Aaron.
Oh yeah, we'll talk all about it.
And I'm sure that everyone here can guess.
You can guess, yeah, cookie dough don't.
Yeah, it works. It works better if you read it. I think it does. We didn't think this went through.
It's still great. I like it.
Okay, So speaking of cookie dough and don't and whatever, Aaron, should we just get started?
I think so. We have merch check it out on our website, click on merch et cetera. Business. Let's do it, all right, cool, we'll take one quick break, all right. E Coli. I wrote that maybe this is the most important bacterial species we'll ever talk about, But I feel like that's overkill.
Well, I feel like a lot of people might have opinions about them.
They probably would, so I'm not going to make that statement, even though I just said it.
But it is massively important.
It is massively important. The thing about it is that E. Coli is everywhere. It's everywhere, and it's everything, and it causes almost every type of illness that you can think of. And we also use it in the lab to study every other disease pretty much. Equal is like the lab bacteria.
Oh and not just every other disease, but life itself all how life works.
Like literally, that's not an exaggeration.
Yeah. No, I'm going to talk about it.
Oh excellent. I can't wait because I'm not going to talk about it. O.
Good.
Oh. But we will get some of the basics out of the way first and then we'll talk about the diseases that equal I causes. Cool, perfect, Okay. So equal is a bacterium. It's a gram negative bacterium. So it's pink when we stain it on the microscope. That's what it means for the purposes of this podcast.
That's really the important takeaway is that a pink.
BacT pink little bacteria. If you're going to paint it color, you should choose it's rod shaped so it looks like a little tic tac. Okay, yeah, you have it in your mind now. For the most part, in our bodies, E. Coli is a normal and important component of our gut microflora. It's always there, and it's supposed to be there. It's part of a healthy microbiome. But this is this podcast will kill you. So that's not the ecoli that we're going to talk about today.
Nope, although we could talk a little bit about those guys.
Sure. Sure. So Aaron, when you think of the E. Coli that makes you sick, what do you think.
Of you mean, like, what symptoms and signs and stuff. Oh, I would say, well, after reading that first hand account, I would say bloody diarrhea, bloody diarrhea, and then also whatever hus is. But I was hoping you were going to tell me about that.
Don't worry, I'm going to Okay, Bloody diarrhea is the thing that probably comes to most people's minds when they think of E. Coli first, and that's because of just like you said, that oh one to five seven outbreak, which we'll talk about, you'll talk about, et cetera. Yeah, the diarrheagenic that's their official name. The diarrhegenic E Coli are probably the most infamous of the ecoalies that cause disease,
but they're not the only ones. So here's how I'm going to structure this biology section because E. Coli is so big. First, we're going to talk really quickly about what makes the pathogenic ecoali strains different than all of the normal ecoli or all of the non pathogenic ecoal i that live in our gut happily, okay, and then we'll talk about the non diarrheagenic ecoli just briefly, and then we'll talk poop cool.
Oh great, love talking poop met too.
It's one of my favorite things to talk about. Okay. So the main difference between the E. Coli hanging out in our guts happily right now and the E. Coli that made that little girl in the first hand account massively sick, or what are called virulence factors. We've talked about these before, right, I think so, I think so? Sure. Well, if you don't remember what a virulence factor is, it's basically just stuff things. Yeah, that clears it up, Things that a bacteria or a virus or a parasite makes
that helps it to cause disease in an organism. So let me give you some examples. Sometimes virulence factors allow for bacteria to attach to certain cells and colonize a new area in a host that they wouldn't be able to before.
Oh yeah, okay, like little velcrow, little velcro strips.
Sometimes it might be like a capsule kind of like an armor that allows it to evade a certain part of our immune response. That could be a virulence factor. It could be an endotoxin that the bacterium produces that also allows it to evade the immune system, or an exotoxin that it produces and sends out into our body and actually causes damage to other cells.
Cool.
Okay, So virulence factors are literally anything that a pathogen can make that makes it more virulent, aka makes you get sicker.
Cool sounds reasonable.
So these subtypes of E. Coli that are they're called different pathotypes because they are pathogenic, collectively have a couple of main virulence factors that allow them to get us sick. And those two things are different types of adhesons which allow them to adhere and colonize new areas, and toxins. Those are the two things that Ecoli tends to use to be able to invade new organs in our body
and make us sick in new ways. So another important thing about the virulence factors in E. Coli is that a large number of them are on plasmids, which we've talked about before. I think, right, oh, did we talk about it with cholera Maybe, because cholera definitely has plasmids anyways.
Plasmids are a little round pieces of DNA that bacteria can move from like one bacterium to another, they can like pass it off, and so basically this allows for ecoli to hand off virulence factors in like between different strains of bacteria, right, okay, Okay, that's like that's the whole pathogenesis. Like, that's how all of these ecoli have come to be, is just little changes in their toxins or their virulence factors or their adheson whatever that allows
them to make us sick. Okay, So what kinds of ways can ecoli make us sick? So many different ways? Yeah, all right. The two main kinds of disease that you can get from E. Coli besides diarrhea are urinary tract infections.
Oh yeah, did you try that? I think I did know that at one point. I don't know. It feels like a recovered memory. Yeah.
So these strains of ecoli are called you peck. So many ridiculous acronyms.
With no don't love. I don't love acronym you.
Peck is europathogenic ecoal i. Okay, okay, they're all like that. They're all like blah blah. Pathogenic ecoal i, they're really so they all end in PEC. Yeah, yeah, they're all mostly sometimes they're like hex. Well you'll see.
Heck and ecola, heck and e coli.
That's funny.
She sounds surprised.
She liked it. It was good. Okay. So the upeck, the europathogenic ecoal i, are strains of ecoli that are really good at attaching to our urinary tract walls. Okay, So they have adhesions that allow them to do that, and they are the most common cause by far of UTI's. So that means like, okay, right, like eighty percent of
UTI's or something like that are caused by ecole. And if you don't know what a UTI is, the symptoms generally are things like burning on urination, increase frequency meaning you have to pee way more often than normal, or urgency where you're like, if I don't pee right now, I'm on pima pants.
So that sounds a lot like gonrhea, Aaron, How are people going to distinguish between the two.
So another thing that upeck can cause ganeri prostatitis. No, but it is prostatitis, and gonorrhea is another common cause of prostatitis actually, so that's if it goes up the urethra far enough to invade the prostate. But then these strains of E. Coli can actually keep going up and then can also cause like pylonephritis, which is kidney infections as well, which is you can imagine more serious than only an bladder infection. Okay, so we covered three already.
We've got bladder infection, kidney infection, prostate infection, all from UPEC. Then we have the m neck. I don't know if you're supposed to say it like that, but these are the meningitis associated ecoli.
Ooh, that's right.
Yeah, So this is one of the most common causes of meningitis in neonates, so tiny babies. It can also cause meningitis in adults, but it's much less common compared to other causes.
Why.
I think that just other bacteria are better at colonizing the mining geese, and so you'd have to be pretty sick already or have a root of entry. So these strains of E. Coli are associated mostly with meningitis following like a neurosurgical procedure in ADU.
Oh okay, okay, yeah.
But what's really scary is that in neonates, this type of E. Coli infection has a fatality rate of like fifteen to forty percent.
Wow.
Yeah, it's really it's really gnarly, and it's also an extremely common cause overall adults and children of bacterial sepsis. So bloodstream infections, right, and that can actually be from any strain of E. Coli, not only the UPEC or m NEX strains. You can have any any way that ecoli can gets into your blood. Once it gets there, it's pretty good at estabel and infection.
Yikes.
Yeah, so so those are collectively you want another academ here?
Oh gosh, does end in heck er pecker?
Yeah it does?
What is it?
Okay, they're the xpecs.
I can't, I can't, I can't.
These are the those are the extra intestinal pathogenic equal ie.
Those we just talked about easy to remember, sure peck, XPEC eu peck. That's all we've learned so far. M neck Oh goodness, I can't.
Okay, now we get into the more fun ones. Oh yikes, Okay, the EPEX people are gonna hate me. So now we're going to talk about the ones that actually colonize your gut in a way that is bad. The taro pathogenic equal ie the most famous of which we've heard a little bit about already, and that is the entaro hemorrhagic ecoal i e heck.
Okay, So e hek is a form of epek. Yeah, bro, okay, it totally is. Do you want to know what gets even worse though? Aarin I even I, this is too much for even me.
Ehk is also called s tech or v tech. Uh why let me tell you why? I'm so glad you asked. Oh no, The enterohemorrhagic E. Coal i are the strains that cause bloody diarrhea. Okay, Entaro heemorrhagic, like hemorrhage means bleeding out and taro means your gut. Okay. So that's like a broad umbrella term that encompasses a number of different strains of E. Coli, all of which end up with symptoms like bloody diarrhea. Some of those strains produce a toxin called shiga toxin. Oh yeah, t s tech
siga toxin E. Coli. Some other strains produce a toxin that's really really similar to shiga toxin that is called suga like toxin oh, okay, or verotoxin vero toxin.
Sure, so those two phrases are interchangeable, and yet they still give rise to two different acronyms. Three Oh, I'm sorry, yes, three yeah.
V tech s tech EHK. I think it's annoying, So I just go with EHK because it's the broadest one and it encompasses all of them.
Cool, I mean, I'm just rolling with it.
Yeah, all right, So let's talk about what this actually does inside of your body. This shiga toxin or suga like toxin. It's the same toxin that's produced by another bacteria, Shigella, which arguably might actually just be a subspecies of Ecoli.
Okay, yeah, so I'm glad. Yeah, I talk a little bit about it.
But yeah, yeah, it's basically it. Basically they are so closely related it might as well be a subspecies. It's also possible that equoali oh one to five seven should actually be a Shagella.
It's like some Ecoli strains should be Shigella and some Shagella strains should be Ecoli.
Yes, is yeah what I wrote?
Okay, Yeah, anyway, that blew my mind, by the way.
Yeah, yeah, so they all produce this toxin that the bacteria can then release that causes damage directly to the mucosa of your intestine. These bacteria tend to colonize in your large intestine, in your colon, and when they release this toxin, they can cause perforation of your intestine. They can cause necrosis, so they can cause your your colon to actually die in places, and this is what results in the bloody stools that you see in enterohemorrhagic equali infections.
Question about this unless you're going to cover this in the poop section.
Oh we're in the poop section girl.
Oh great, okay, okay, I thought so. I didn't want to get my hopes up in case we weren't. So bloody diarrhea doesn't mean red blood in your poop.
Great, question, it can, and in this case it probably does.
Okay.
It all depends on where you're bleeding from. Yeah, So the higher up you bleed in your GI tract, the more black your stool is going to look when you poop it out right. The lower down you're bleeding, the more bright red this blood is going to be.
But soose S tech V tech et cetera. Whatever, ones that actually cause the hemorrhage. E heck, cause the hemorrhage in your gut. That can that can produce any shade of bloody diarrhea.
Yeah yeah, because they colonize your colon, and your colon is pretty big and large. So if they're colonizing closer to no erin, I'm gonna get my, oh my anatomy. If they're colonizing closer to the left side where the outlet is, then it might be more bright red blood. If they're colonizing closer to the start of your colon, it might be a darker color.
Okay. In any case, seek medical attention. Yeah rah, Unless you ate beats the night before.
Unless you unless it's beats. I feel like we've had so many good title possibilities already.
Well, I also feel like we've mentioned beats on a couple other podcasts or a couple of other episodes before ECOLI.
Unless it's beats. Unless it's beats, okay, beats by beats. Okay. So that's the damage that this toxin and that this bacteria causes in your colon where it's actually colonizing. But what's really really dangerous about these enterohemorrhagic equali is that the toxin can actually leave the intestine and get into your bloodstream. If that happens, it can make it all the way to the kidneys, where it causes inflammation in the kidneys that can end up causing kidney failure.
Yikes.
And then what it also does is it it causes damage in your small blood vessels that then leads to small clots forming inside of your blood vessels, like little teensy tiny clots that when your blood then passes over these clotted chunks in your blood vessels, it shears your red blood cells.
Oh my goodness.
Right, And so this is what's called a hemolytic anemia because your red blood cells are literally bursting open. Whoa, because they're traveling over these tiny microclots. And those clots are formed by platelets. So now all your platelets in your blood are being used up. So the three main signs that you see are renal failure, kidney failure, this hemolytic anemia, and thrombocytopenia, which means your your platelet count is low. And that collectively is what's known as hemolytic
uremix syndrome. Oh wasn't that.
Okay, Wow, So I have a question, Okay, how does it does it benefit ecoali to produce this toxin in terms of their replication or in terms of their ability to colonize new areas? Like why do they Why do some strains produce this toxin and some don't? Does it give them some sort of fitness advantage?
That's a really really good question. I don't fully know the answer to that, but what I can tell you is that a lot of these strains of E. Coli, especially like oh one five seven, are naturally found in the guts of ruminants like cows and cheap So I wonder if it provides a fitness advantage in those environments in some way. M right, like guts, the guts of cows are bananas, They're like have five stomachs and stuff.
So I know, what if the microfloor is totally different at each one of them.
Oh, it probably is, I know.
But like there's probably a study out there, but but we just haven't read it.
Isn't that veterinarians going to be like, you guys, let me tell you tell us we want to not Yeah, we want to know. That's a really good question. Though, because yeah, the toxins are expensive for bacteria to produce, so presumably in some way it has to be. You would think, because these strains are so prevalent, you would think that, yeah, it does cause some kind of fitness advantage. Probably,
great question. So yeah, that's uh. That is the enterohemorrhagic ecoalize, the most famous of which is E. Coli one five to seven H seven specific, let's just call it. That's what I do for most of it. Yeah, this is what causes outbreaks very often, but it also causes tons of infection across the globe and in the US that isn't outbreak associated, so we actually often never know what the source of infection is. But in general, you get
sick between one and three days. You'll start having this diarrhea that's often bloody within one to three days after exposure, although it can be as long as ten and about five to ten percent of people that get infected with EHK will end up getting hemolytic uremic syndrome.
Wow, I didn't know it was that high.
The thing is that number varies a lot based on age, so in kids it's potentially even higher, especially in very young children. But in adults, that number is quite a lot less, so on balance. Yeah, so that's the entero haemorrhagic. There's one last kind of poop that I'd like to talk about before we're done here.
Wonderful.
So there's another strain of ecoli called e tech.
Do we not talk about E tech already?
No? No, we haven't. We've had EHC and now we have.
E tech extraterrestrial ecola.
Very very good. Guess so close. Entaro toxogenic okay, okay? And taro so toxogenic.
Yeah, it has toxin and it's in your gut, and it's somehow different than shigella or than schiga toxin.
Yes, exactly, that's exactly right. This is another kind of toxin, and specifically, this type of toxin is more similar to a toxin produced by Vibrio cholera.
Oh yeah, so.
It's not the same toxin, but it's very similar. So you can imagine that the diarrhea that you have with this type is more similar to cholera diarrhea, which is what.
Aerin rice water stool.
Exactly. So this is a watery diarrhea, not a bloody diarrhea. Okay, is that cool?
Yes? I mean cool is maybe that's the word I would choose.
I think it's pretty cool. I mean it's actually not cool because etech, as it turns out, is the cause of what's often called traveler's diarrhea. Oh, yes, that's etech. Which what that means is that etech is an extremely important cause of diarrhea in children in developing countries, so second only to like rotavirus, and probably up there in competition with rotavirus for the most important diarrheal disease. Okay,
in the developing world. So it's a huge cause of morbidity immortality, and it's a watery diarrhea, so it's not bloody, but you're losing so much water that you then can end up dying from dehydration. Right, Okay, there are other enteropathogenic ecal eyes. I'm too big of a topic. I know,
we're not going to talk about them. Quite honestly, we don't know as much about them, and we don't have time and etc. If you want all of the nitty gritty details of all these different pathotypes, there was a great Nature review from two thousand and four that I read that goes into way too much detail, and that will be posted on our website. So great, that's the biology of ekoli Aaron, beautiful, thank you, thank you. I made it myself. So tell me how the heck did
it get here? Where did this thing come from? And why does some strains just want to kill us? Oh?
Great questions. First, let's take a little break. I think that for most people the words e coli bring to mind these images that you kind of just went over and described this writhing gut, bloody diarrhea, just doubled over in the bathroom, trying to hang on. And a smaller subset may also think of ecolai's role as a model organism in the lab.
That's what I think of, if we're honest.
Have you worked with E coli before in the lab?
Yes, I used it during my master's a lot. And also because we use it as a water quality indicator, so I've worked with ekoi a lot actually in the past.
Yeah, it's a stinky colonizer. Yeah, it's not all good when you crite those big cultures smell so bad. It's really bad. But I think that those two roles you know this like super pathogenic one and also this lab model organism account for a tiny amount of the amazing diversity of E.
Coli.
Oh cool, because I mean A cola is found all over the earth. Oh yeah, inside people and animals and stuff, and also outside of them, which is.
Why it makes for a terrible water quality indicator. Right, yeah, I was actually good point, yes, thank you.
And also they're incredibly numerous. So Carl Zimmer estimated in his book about E. Cola, which was great, by the way, he estimated that there are about one hundred billion billion E. Coli on Earth, which is not a number I can comprehend, and I don't know if anyone can comprehend it. Please let us know. These bacteria are among the top, if not the very top, most studied organisms on the planet.
Research on Ecoli has led to Nobel prizes, to genetic engineering, to insights into evolution and cellular biology how genes work. And there could really be an entire podcast series on the contributions of Ecoli to our understanding of how life works. So let's start at the beginning, and to do that, we have to go so far back, so so far back before humans were even humans, because E. Coli has been with us for as long as we've been a species.
And way before, and probably caused occasional food borne illnesses during that long relationship. But until microscopy and microbiology emerged, it's hard to pinpoint exactly what might have caused the fatal diarrhea of this or that person and be able to conclusively say that it was ecoli. So this is more. This history is less. These are the pandemics of E. Coli and more. Yeah, more, you're about to find out.
So humans first learned about the existence of E. Coli when in eighteen eighty five a German pediatrician named theatre escherish Which did we even say, Oh.
My god, no, because do you know what I can't pronounce it and I didn't want another gr dam situation.
Well, okay, Becauseishia Escherishia.
I have never attempted to pronounce that word in my life.
I don't. I mean, I've tried to do it, but I don't. I mean it's an attempt, of course. But I remember my micro tea, my micro professor in undergrad saying that one of his friends, who was also a microbiologist, gave their daughter the middle name of Escherishia because he thought it was so beautiful. Wow, weird anyway. Okay, So, anyway, Theodore Esherish was looking at baby poop under the microscope
and noticed a bunch of rod shaped bacteria. And he the reason he was looking at baby poop is because he had been waging a full on war against diarrhea, believing it to be one of the biggest killers of infants under his care.
And he was right, totally trite. Yeah, yeah, for sure.
He was looking under the scope to try to see if he could figure out what's good bacteria and what's bad bacteria? Wow, which I think yeah, eighteen eighty five forward thinker. Yeah. And so he would look for bacteria in both healthy and unhealthy children and say, okay, what can I find in just the unhealthy ones versus what
do I find him both? And he found E. Coli in both, and so he didn't really consider it to be that interesting of a finding, but he published it anyway, and absolutely no one took note of it.
Shocker, right.
And the original name, which was much easier to pronounce, was Bacterium coliinus, so common bacteria of the colon wow. Yeah. But seven years after his death in nineteen eighteen, scientists renamed it after him. Oh, Okay, So just a few years after that, a biochemist named Edward Tatum. I don't know, I really want to know if he's related to Channing.
Mister Channing.
Yeah, Edward Tatum started to culture a strain of E. Coli, the K twelve strain if you're curious in the lab and the K twelve. This K twelve strain that's so popular for lab work today was isolated from a dude who had diphtheria and was living in California in the early nineteen hundred. So what Yeah, he.
Hadthera and just happened to have this strain of E.
Col I. Don't really know the full story, but yeah, I assume that's because this is a harmless strain, like this is a nonpathogenic strain.
Yeah.
Right. So Tatum had recently gotten super interested in the very new field of genetics, because this is the early nineteen hundreds, and he had actually worked with Thomas Hunt Morgan and George Beetle, which like two of the biggest pioneers in the field, and up until this point of time, genetics had mostly been studied using things like fruit flies and bread mold, which were more complex in some ways than bacteria, particularly in that they had sex like gene
exchange or were known to Tatum wanted to see whether bacteria like E. Coli also followed the one for every one gene for every enzyme rule that had been the pattern he discovered in mold. And he chose E. Cola because it has very few requirements in the lab, grows rapidly and produces visible colonies, which is useful for monitoring what exactly is going on. And he blasted E. Coli with X rays, managing to produce a few mutants, which
gave this huge indication bacteria have genes. Because if you blast something with X rays and then there are mutations that happen and there are differences in the bacteria after that, then that shows that these things have changed based on how they.
Write their DNA has been affected.
Yeah, that was a huge finding. But did that matter that much? Did the fact that bacteria had genes matter that much if the bacteria couldn't reproduce sexually. Yeah, And so from these findings, another guy named Joshua Letterberg, who was twenty one years old, just wanted to say this, Yeah, I know that hurts.
Don't tell me that He got like the Nobel Prize.
Oh my, he did, okay, So Joshua Letterburg decided he would look for bacteria sex. So he was just convinced that people weren't looking hard enough, and he found it. So he found Ecola mutants could exchange genes somehow, And from this monumental discovery that led to basically the amount of research is on. You can't count the number of like findings or new laws of biology or whatever, all
these discoveries. These three dudes, So Letterberg, Tatum, and Beetle were given the Nobel Prize in nineteen fifty.
Eight, and he was twenty one.
He was twenty one, not in nineteen fifty eight, but he was twenty one when we discovered bacteria sex.
Yeah, well to I mean, he's great.
Come on, come on, it's never too late. It's never too late.
No, that's true, it's not.
Studying E. Coli would lead to other huge advancements, such as discovering that viruses had genetic material, which was learned by looking at the bacteria phases of E.
Coli.
It would also help to show conclusively that genes are made of DNA, which overturned the long held hypothesis that DNA was made of proteins, and it even helped to reveal the structure of DNA in what apparently is known as the most beautiful experiment in biology. And I'm not going to get into the details of it, but it has to do with like nitrogen and different weights and lots of centrifugion. If you want to know more, read the book Microcosm by Carl Zimmer. It keeps going though.
Ecol I also helped to show how DNA was made up of codons and how these codons match to certain amino acids. By studying Ecoli, scientists were learning about the rules that govern life itself and even what it means to be alive. It's amazing. It's amazing. Ecoli has thousands of genes, and scientists have a pretty good idea, if not exactly the idea, of what each of those genes do. Basically, you knock a gene out and you see what happens.
And by fiddling with these mutant varieties be Coli, researchers also figured out the genes can be turned off and turned on, that they don't work in isolation, but are rather connected like a circuit board. Ecoli has been subject to the whim of so many researchers who wanted to see if it could be grown at extremely high temperatures or super low levels of food, or infected with tons
of viruses. And what the scientists observed over and over again was evolution at work on a timescale that no one had thought was possible, even though now it kind of maybe seems.
Obvious antibiotic resistance and all that exactly, Yeah, yeah. E.
Coli was used in genetic engineering starting in the nineteen seventies, when it caused quite a stir and now no one thinks twice, but people started using it for insulin production, which led to this huge industry which was fueled initially by controversy and then by demand. Doctors sometimes would give
or still give. I don't know, you tell me a strain of E. Coli called a zero thirty four slash eighty six to premature infants that don't have fully formed intestines because it helps them protect against nasty gut pathogens.
I don't know if they steal do that, but that's genius. Because babies get colonized with ecolai in like minutes, like oh after bears. It's amazing.
It's amazing. And so this this particular like helpful strain or whatever. Some of its genes code for things that directly fight the weapons of strains like oh, one to five seven, stop it. Yeah, this is like a total role reversal. Usually you're the one telling me about this strain differences.
I love it.
Okay, Okay, just a couple more cool bits about E. Coli before the history of the pathogenic one the poop.
Yes.
E Coli can sense each other.
Oh yeah, Oh, I'm so glad you're talking about this.
It's amazing. Okay. So a group of researchers least E. Coli labeled with a glowing protein into a maze and wanted to see how they would move and what would happen. And at first, so you could trace these individual cells. Right at first, everything was random, but then eventually the researchers saw a pattern emerge. The bacteria were moving towards other bacteria, and soon there was this giant cluster of E. Coli just hanging out. Okay, so it turns out you're
doing a very happy dance. It turns out that Ecoli shoots out serene in its waist and other Ecoli might use that as a sensing mechanism to find other E.
Coli.
Once they're all together, they might even change their behavior, so instead of having their normal flagellum, they grow a giant one that gets tied up with other flagella, creating a rat king of E. Cola.
Oh my gosh, ecolid like bacteria having behavior is one of the coolest things.
And this whole rat king whatever like tails are flagellatide, Yeah, helps them move as a group across a petri dish or maybe even your intestinal wall.
Definitely your intestinal wall.
It's amazing. It's amazing, dude. Okay. Even though now I think most of us think of E. Coli as this deadly food born terror, For several decades after its description and even after its use in a lab as basically the thing that revealed all secrets of life, people weren't aware of how sick it could make you. So it wasn't until nineteen forty five that the link between E. Coli and horrific gastintestinal disease was really conclusively made. Have you ever heard of summer diarrhea?
No? I know? In was it the poly episode we talked like about closing down pools and things. But summer diarrhea no.
Yeah, so this was like a known phenomenon as something called summer diarrhea. So if you go to Google scholar you can find reports of now analysis of what the summer diarrhea was and writings or whatever, but also in like reports from the early nineteen hundreds. So every summer, kids and infants in industrialized countries would get super sick
with diarrhea, often bad enough to kill them. So it was this very seasonal trend of diarrhea and a British pathologist named John Bray decided to hunt for whatever pathogen might be causing this using antibody tests. He found that while only four percent of the healthy kids responded to the E. Cola antibody test like they were positive, ninety five percent of sick kids did. Huh, And so then he went. He would go on to describe this strain and several more that were pathogenic to humans.
Interesting.
Okay, so now here's the part that you've probably been waiting for. Maybe, yes, I don't know, maybe you've enjoyed all of this.
I have enjoyed all of this.
Okay, good enter oh one five seven h seven, don't, don't, don't, although we can't say for sure. Oh, one five seven seems to be a pretty recent arrival. It's like nineteen seventy five to.
Be that's super recent.
Yeah, No, samples can be found before then.
Fascinating.
It first made headlines in early nineteen eighty two in Medford, Oregon, and later that same year in Traverse City, Michigan. The source was under cooked burgers at McDonald's, and then it went quiet for about ten years until the infamous nineteen ninety three Jack in the Box outbreak. JTV baby, I've never had Jack in the Box? Do they not have it out east now or like, I don't know past the Mississippi River.
Oh interesting, Yeah, JTV man.
There have been dozens of one to five seven outbreaks all over the world since its first appearance, and I could probably go into each one of them to talk about the source of infection and the lessons learned. But I'm just going to focus on the nineteen ninety three Jack in the Box outbreak in the western US because this is probably the most famous.
Food born or E.
Coli outbreak in the US. It's pretty it's massive.
Everyone still talks about it.
Yeah, I mean it put ekoli like in as a popular phrase or like a known phrase to people.
Yeah, totally.
It resulted in landmark personal injury lawsuits, increased oversight of food production, and widespread public awareness of this deadly pathogen which you know, burgers used to be safe before this, maybe some worms. It started around Christmas nineteen ninety two, when six year old Lauren Rudolph was rushed to the er in San Diego after having bloody diarrhea. After a
few days of battling the illness, she passed away. And in January nineteen ninety three, doctors at Children's Hospital in Seattle started noticing an unusual number of kids with hemolytic uremix syndrome, which is that thing you described. And this set off some alarm bells because you don't really see that number of cases very often. It's not it's pretty.
Rare, right, yeah.
And so the high number of HUS cases, which is the hemo hemolytic urimi syndrome, I'm just gonna call it HUS, it pointed towards an E. Coli outbreak, But those usually happen in the summer, So where could these cases be coming from? These children weren't connected to one another in any way like that at daycare or something like that.
But there must have been a shared source somewhere. Epidemiologists that were assigned to the case did their thing, asking parents about their lives, their movement patterns, what food they ate at home, where they ate, and eventually a likely culprit emerged, Jack in the Box the Nations. Did you know it was the nation's oldest fast food chain.
No, I did not know that it beat.
Out McDonald's by like a couple of months. Huh. Anyway, they so, Jack in the Box had recently been having this big promotion for their monster burger so good it's scary, just like in retrospect, not a great not glareat.
They don't make that burger anymore.
No, I don't think so. Yeah, the pr campaign to get Jack in the Box to not fold as a company is pretty I think also Landmark.
Yeah, there's like that's a whole podcast in and of itself.
I feel like, oh, for sure. So the president of Jack in the Box, Bob NuGen, when notified that the company might be the source of this horrible outbreak, he immediately stole all of the restaurants in the affected areas from serving their burgers and destroyed the possibly contaminated batches of beef.
Wow.
Yeah, oh was he acted as fast as he I think it seemed like as fast as you could.
Yeah, that's awesome.
And he did all this without being entirely convinced that it was the beef that was Jack in the Box in the first place.
But I mean, but you have dead kids, so it's like exactly, yeah.
Well, and everyone was very like a lot of the people who were at Jack in the Box, I think were felt awful, Like, yeah, were very very troubled by I can't even imagine by their yeah yeah, what they're inactions I think had done. And so people knew at this time. People knew that undercooked chicken could be a problem in terms of salmonella, but no one really had heard of outbreaks of food poisoning associated with beef. It was a new thing at that point, or at least
it seemed to be, according to this book. And so even though there had been this Ekoli outbreak just ten years before the Jack and Box, the one that was in McDonald's, it had gotten quietly buried, and so McDonald's wasn't really named And so When Washington State epidemiologist John Kobayashi told Bob Nugent, the president of Jack in the Box, that this horrible outbreak affecting all of these kids was likely tied to E. Coli contaminated burgers, NuGen was like,
what so, even though that contaminated beef had been stopped, it was too late for a lot of people, mostly children. By the end of the epidemic, seven hundred and thirty two people were infected with E. Coli.
Seven hundred and thirty two confirmed.
Confirmed whoa all traced back to Jack in the Box restaurants in Washington, Idaho, Nevada, Nevada. How do you say? I say Nevada, and I know that's wrong, so I need to say it properly. Nevada, Nevada and California.
Yeah, please leave that in because it's the funniest thing I've ever heard people. A lot of people say Nevada, Nevada. But the way that you went Nevada, Nevada.
Because I knew it was wrong as soon as it left my mouth. Embarrassing. Oh God. Avoiding these restaurants wasn't enough, though. One of the four children who died during the outbreak, was seventeen month old Riley Dettweiler, and he contracted E. Coli from a friend in daycare who had picked up the bacteria from a burger. Oh, there were two other children who died, Selina Shribbs and Michael Nole. And all of the kids who died from this outbreak were younger six years or younger.
Ah, those babies, yeah, I ough. Yeah.
Even if you were fortunate to survive the initial infection, many people over one hundred experience long term side effects from the infection. Viously, with so much tragedy and suffering experience as a result of this epidemic, people wanted answers to questions like how did this happen? And how can we make sure this doesn't happen again. The first question, how did this happen? Actually ended up being fairly easy
to answer. So in nineteen ninety three, the federal regulations for the temperature for cooking beef were one hundred and forty degrees fahrenheit sixty degrees celsius.
Oh.
Okay, however, so one hundred and forty degrees keep that in your head. And Washington, the state law was actually one hundred and fifty five degrees sixty eight point three degrees celsius. This regulation was, which was different than than the federal regulation higher temperature, was put in place by the same epidemiologist John Kobyashi that I mentioned earlier, and because he was aware of the danger that E coli posed.
Wow, way to go.
He chose one hundred and fifty five degrees fahrenheit because that was the temperature required to kill E coli. Whoa Jack in the Box in Washington was notified of this new regulation, but for whatever reason, didn't change their practices. They followed the federal regulation of one hundred and forty degrees. So, yeah, a lot of the cases probably could have been prevented if they had followed Washington state law. But Jack in the Box argued that they weren't completely responsible for a
contaminated product. The screening regulations for E coli and beef weren't what they are today, Like, people didn't really screen that much for them.
They Oh, I should have had Matt kmet Co on this episode. Oh my god, you're right what he does.
It's so true.
Shout out Matt.
And so researchers were desperately trying to figure out where the strain came from and how to prevent it from getting into the food supply. And that's something that's way easier said than done, because it was found in around twenty eight percent of cows, and probably that number has jumped since this book was written. And so basically what happens is that during the slaughtering process, if a cow's colon is cut, that E Coli that's in the gut can that escape and basically all the meat is all
blended together that oh like ground together? Yeah, that one to five seven can travel through literal tons of beef.
Yeah, that's so gross, horrific.
Proper cooking will kill the bacteria, but if a few escape, then there you go.
And do you know the infectious dose for E. Coli is like as little as ten organisms.
I remember that from micro Yeah, so that's how the E. Coli got into the beef. But how do you make sure it doesn't happen again? That's a much trickier issue, and probably because we've had several outbreaks since then, it's obviously tricky. So there are several stages of food prep that could have been improved. First, there's the beef industry itself.
Clean up that process, maybe don't allow dropped carcasses to be incorporated, maybe cleaning the floor on which they are dropped, maybe following a one cow, one burger practice, which isn't what happens.
I need to not think about it, or I'll never eat another burger again in my life.
So well, it's it's funny that you said that, because that was my exact response when I read this in Carl Zimmer's book. And then the next paragraph is, and if you're vegetarian, don't feel so smug or something like that, like you're not escaping it either, because cows poop on crops.
And then the most of the outbreak, not most, but a large number of the outbreaks recently have been in lettuce and spinachar Yeah.
No cookie dough. We call it cookie like the title of our quarantine Cookie don't because raw flower is how people have gotten sick for the coal. I also, yeah, okay, but then there are also these restaurant quality control improvements that could be made cooking the beef at the temperature that actually kills e coal. I. So this, this Yekuli outbreak is notable not just because of its size, but because of the changes it led to in the food
industry and the government oversight of it. So it really did. It was like a huge, huge deal, and a lot of people who work in food safety are today still very unsatisfied by how it's done. And that's kind of a fair point, considering that outbreaks continued to happen, all right, so you know, back to the whole vegetables are not necessarily safe. There was a nineteen ninety seven outbreak of oh one to five seven in Japan from tainted Radish sprouts that made twelve thousand people sick.
Oh my what Yeah, three.
Of whom died twelve thousand. September two thousand and six. In the US, there was an oh one to five seven outbreak in Spinach that made two hundred and five people sick. That same year, let us at Taco Bell made seventy one people sick. Like you could just go on and on and on. Yeah, So I could go on and on and on and on about all these different outbreaks, but I'm not going to this. Instead, Aaron, I want you to tell me where do we stand today with E Coli?
I can't wait to all right, E Coli. Today it's everywhere, yeah, yeah, it's still everywhere. It causes so many different diseases. It's really hard to do an epidemiology section on this because like, what where do you even begin? I don't know. Let's start. Let's start where you left off with the inflammatory, bloody
e heck food born outbreaks. Just looking over the last ten ish years, which is basically where you left off around two thousand and six two thousand and seven, there have been pretty much between one and four multi state outbreaks of like EHK, really bad bloody diarrhea E coli every year, wow much And each of these multi state outbreaks, the multi state outbreaks are the only ones that are reported,
like easily accessible on the CDC website. You can go to every state health department and probably find a handful of outbreaks that were just contained to one single state. But of these multi state outbreaks, they range in size from like eighteen or twenty cases on the low end to over two hundred cases on the high end. And every year, from each of these cases, a handful of people are hospitalized and end up getting hemolytic uremic syndrome.
Most years there aren't any deaths related to this, but every other year or so there's a bad outbreak and there are some deaths associated with this, so to put some numbers on that, from the last couple of years. So far in twenty nineteen, there have been two hundred and sixty three cases in three multi state outbreaks associated with ground bison also flower oh aka cookie, dow yeap, and ground beef. Of these two hundred and sixty three cases,
fifty of them were hospitalized. Nobody died so far in twenty nineteen. Twenty eighteen was a little worse, although twenty nineteen is not over yet. There were three outbreaks with two hundred and ninety cases but one hundred twenty seven hospitalizations. And that's because two of those outbreaks were actually one five to seven. Oh yeah. So these are just all of the e HEK or s tech whatever you call it, outbreaks. Not all of those are oh one five to seven.
And it turns out that one five seven is more likely to cause hus than some of the other e hex strains.
Just based on the amount of shiga toxin or what.
Yeah, or just the specific subtype of that siga toxin okay, yeah, right, or sugar like toxin. It's just more likely to end up causing hus So the years that you have oh one to five to seven outbreaks tend to be worse in terms of the number of people hospitalized and the number of deaths. But that's just the outbreaks from The vast majority of ECK cases are actually not outbreak associated. They're just individuals who end up getting sick and maybe
end up in the hospital. So in twenty sixteen there were over fifty four hundred cases of EHEK reported.
Wow. Yeah, that's like twenty times higher than.
The outbreak numbers. Yeah, the vast majority of people they aren't actually part of an outbreak, which means that you never actually figure out where their infection came from.
Oh gotcha.
And that's the other important part of it. The only time you can identify an outbreak is if you have multiple people coming to the same hospital, or at least reporting to the same health district, so that someone can pick up on the fact that there's a number of cases happening. Right, If just one person comes, or even a couple people come but to different hospitals that somehow don't end up talking to each other, there's an outbreak
going on, perhaps, but you'll never know about it. You just have a handful of cases, right, that makes sense. That makes sense, okay, So yeah, and then, like you mentioned that happened in the nineteen ninety three outbreak, about ten to twenty percent of cases can actually end up in what's called like a secondary attack, where people pass on that one to five seven or that ehex strain to somebody else in a daycare facility, changing diapers, nursing homes,
et cetera. So yeah, ehek is gnarley. Yeah, but again, that's not the only ecola out there.
Great, there's the one that makes you have watery diarrhea instead of bloody diarrhea.
So let's talk about that one real quickly, right. So, e tech is what you were mentioning. The enterotoxogenic ecoli is a hugely important cause of morbidity and mortality worldwide, especially for infants and children. So there's a lot of interest in developing a vaccine for something like ETECH because we're talking millions of children every year that are affected by this and potentially dying as a result of it. There are some candidates in trials that seem promising, but
nothing so far as licensed. You're going to see that for all the different things. Okay, great, yeah, cool. The other big type of E. Coli is, of course, the europathogenic ecoli, the UPEX. There's also a lot of interest in developing a vaccine for these because eighty percent of all UTIs are caused by E. Coli, and recurrent UTIs are really really common, so getting one UTI puts you at very high risk of getting a second UTI in a short period of time. So there's a lot of
people working on vaccines for the various types of UPEX. Uh, there's not really a lot promising so far.
Quite honestly, they have anything promising about this section.
No, it ends on the worst note possible. So great, Yeah, yeah, yeah, it's so true. Uh. But yeah, it turns out that UTIs are a massive financial burden.
Oh that makes sense.
Yeah, Like three and a half billion dollars a year in the US alone is spent on UTIs.
Three and a half billion dollars. Yeah, dude, Well what about other countries that don't have is outrageous healthcare situation?
Good, good point, good point. But still, it's like eleven million doctors' visits in the US every year and two million emergency room visits for ugs alone. Wow.
Okay, So even though like those numbers sensive for understanding more than I do with money.
It makes sense. So yeah, there, but there are a lot of there is a lot of work going on on etech on UPEC and even on the ex so the enterohemorrhagic ecoli. There are people trying to come up with vaccines for all of these strains, but it's proving to be pretty elusive, which isn't that surprising considering how ubiquitous equoali is and how we have co evolved with it for so like literally the entire time that we've existed as humans.
I mean, because yeah, also they're it's part of our normal microflora, so you'n't have to attack it from a different angle and if you did, like the suga sugar or shiga like toxin. But because we have vaccines that are based on toxins.
Yeah, and that's exactly what most of these vaccines do. They're either component vaccines or they're toxoid vaccines, which are inactivated forms of a toxin essentially, And so that's exactly what people are trying to do, is to target the things that make these pathotypes different than our normal microflora. We just haven't been able to come up with one so far that produces a good immune response in humans to actually be protective, if that makes sense. That yeah, okay, yeah.
And the other thing that's really scary is that antibiotic resistance is on the rise for ecoli in general, but especially for ecoli that tend to cause sepsis, so bacteremia, blood born infections, and.
Those are most common in a hospital setting.
They're very for surgery. Yeah, they're very common in hospital settings. They can happen also in babies, not just the meningitis, but just blood born infections in general. And from what I saw in the paper that I will post on our website, from two thousand to two thousand and nine, the rates of antibiotic resistant ecoli have risen about three hundred percent from two thousand to two thousand and nine. What Yeah, three hundred percent rise.
It's really bad.
And the numbers that I saw were that ecoli sepsis. So sepsis from ecoli in two thousand and one was estimated to have caused forty thousand deaths in the US, but in twenty fourteen that number may have been as high as eighty five thousand.
What?
Yeah, what. Ecola is a very common cause of sepsis, and sepsis is a very high mortality rate. So these are estimate numbers.
Right, But that's so many people, I know.
Yeah, it's really scary.
Oh my gosh.
Oh no, that's the end. Oh Aaron, it's literally the end. That's where my page ends. May have been as high as eighty five thousand.
Great, okay, so good night everyone sleep Well I'm sorry. Okay, so not very much good news for ecola.
Yeah, I should have organized that to be a happier ending, But I mean we could end it with the happiness that there is so much cool research going on using E. Coli in a lapse setting to develop other vaccines and cool stuff, and maybe things.
Will get better somehow.
Yeah. I mean there's people working on it. There are people out there trying really hard to make these vaccines happen, et cetera.
Maybe looking back, these will be the dark days. Well they kind of are the dark days.
But right now it's pretty dark days.
We're in some weird timeline. Okay.
Yeah, so but yeah, that's E coli?
What is This was a massive topic.
Yeah, we just barely even scratched the surface of that augur plate. Let me tell you, Oh, I really like that. Thank you. I just came up with it. I didn't even plan that.
Mm hmm. She checks her notes.
Do I say this joke?
Check?
All right?
Well, I guess on these really sad notes. Should we discuss sources?
Yes, let's so.
I read. I read a couple of books. One is called Microcosm E. Coli and the New Science of Life, and that's by Karl Zimmer. I loved it, really fascinating a lot about the lab researchedn on Equali and how it's provided answers to evolution. Then I also read a book about the nineteen ninety three Jack in the Box outbreak called Poisoned, The True Story of the deadly equal I outbreak that changed the way Americans eat. That's why Jeff Benedict I can't necessarily recommend this book.
That's all I'll say about it, Okay.
And then I also watched a New York Times retro report that was like a new study report on the nineteen ninety three outbreak. And I'll also post a few more articles that I read.
Awesome. I will post all of the articles that I read, which included that really intense Nature Reviews microbiology paper if you want the deets on equopathotypes, and then a bunch of reviews about the current status of various vaccines and things. All of these will be on this podcast will Kill You dot com. Under the episodes tab, you can find the sources for this and all of our episodes.
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And with that, please wash your hands and cook your meat.
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