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Speaker 1: How the extraordinaries. In a prior episode, we took a

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Speaker 1: historic look at cholera, and just like before, you should

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Speaker 1: keep in mind that cholera is a pretty awful disease,

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Speaker 1: so we'll be discussing both disturbing symptoms and death. But

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Speaker 1: today we're taking a more modern approach. We'll talk about

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Speaker 1: what we've learned about how vibrio cholera goes about inducing

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Speaker 1: catastrophic diarrhea, where these bacteria can be found when they're

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Speaker 1: not wreaking havoc upon our intestines, and the methods we

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Speaker 1: use to treat cholera. We'll also take a short foray

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Speaker 1: through the colossally bad ideas we've had for treating cholera,

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Speaker 1: because wow, we've tried out some really bad ideas. Welcome

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Speaker 1: to Daniel and Kelly's Extraordinary Universe.

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Speaker 2: Hi Daniel, I'm a particle physicist and I just installed

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Speaker 2: bedezs and every toilet in my house.

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Speaker 3: Hello.

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Speaker 1: I'm Kelly Waiter Smith. I Uh, I feel like I

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Speaker 1: didn't need to know that.

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Speaker 2: Starting with the toilet and information at the very top.

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Speaker 1: I don't feel like I needed to know that about your.

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Speaker 2: Are we talking about diarrhea today?

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Speaker 3: Sure?

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Speaker 1: But that doesn't have to be connected to beidets. I

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Speaker 1: encountered my first bidet when I lived in Davis, California,

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Speaker 1: and I went to a sushi restaurant and I was like,

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Speaker 1: what is this my Why do toilets need buttons? And

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Speaker 1: then I was like, I pushed a button. I was like, whoa, whoa,

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Speaker 1: And I don't know that I need a bidet in

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Speaker 1: my house.

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Speaker 2: I see, well, I just came back from two weeks

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Speaker 2: in Japan and Korea, and so I experienced toilets with

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Speaker 2: control panels, and I pressed that button and I went, whoa, whoa.

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Speaker 1: I gotta say, this makes me wish we had we

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Speaker 1: were releasing videos so that people can see the face

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Speaker 1: that you made. Although maybe it's better we don't.

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Speaker 2: No, yeah, exactly, everybody makes that face in private in

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Speaker 2: the bidet, you know. And it turns out it's actually

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Speaker 2: quite easy to turn your toilet into a bidet.

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Speaker 1: Wow. Is the water heated or is it cold?

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Speaker 2: Yes? Nice warm, toasty water, yes, exactly.

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Speaker 1: Okay, So actually it was your trip to Asia that

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Speaker 1: made you come home and add bidets to all your Okay, Yeah.

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Speaker 2: I was like, wow, we are still using a very

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Speaker 2: archaic form of this technology, it can be made much

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Speaker 2: more pleasant. Why don't we do that? Oh my gosh,

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Speaker 2: it's like eighty dollars, let's do it.

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Speaker 1: Man. You know there are some people who are all like, man,

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Speaker 1: it's a shame that cultures are homogenizing, and you're all like, no,

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Speaker 1: this is great. We should be taking stuff from Asian cultures.

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Speaker 1: We should be given stuff to them. They've got McDonald's.

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Speaker 1: Why don't we have bidets?

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Speaker 2: Yeah, I mean ask yourself this question. If you got

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Speaker 2: peanut butter on a shag car, but would you just

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Speaker 2: wipe it up with a piece of paper?

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Speaker 1: No? No, I would.

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Speaker 2: Well, Okay, there you go, there you go. I think

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Speaker 2: we know the relevance of that example.

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Speaker 1: Yes, we do. Thank you for choosing peanut butter and

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Speaker 1: rooting peanut butter for me. I think it's time we

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Speaker 1: move on, all.

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Speaker 2: Right, and don't think about me next time you're having

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Speaker 2: peanut butter.

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Speaker 1: Thanks Daniel. Thanks all right. So in the last episode,

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Speaker 1: we talked about the work that John Snow did to

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Speaker 1: help us understand how cholera gets to people the fecal

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Speaker 1: oral route passing through water into our mouths unfortunately, and

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Speaker 1: today we're going to talk a little bit about the

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Speaker 1: science that has been done in the one hundred plus

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Speaker 1: years since to help us better understand what cholera is

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Speaker 1: doing to our bodies and help us to treat people

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Speaker 1: who have encountered the bacteria that causes cholera so that

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Speaker 1: we can save their lives exactly.

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Speaker 2: And so it's going to be a whole episode full

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Speaker 2: of too much information.

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Speaker 1: That is my specialty. Okay, So before we really dig in,

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Speaker 1: I want to remind everybody that in the last Cholera

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Speaker 1: episode I mentioned that we're actually in the middle of

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Speaker 1: an ongoing cholera pandemic. And my sense is that most

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Speaker 1: of us don't realize that because we're lucky enough to

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Speaker 1: not have to hear about or deal with cholera on

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Speaker 1: a daily basis. So I asked the extraordinaries, when did

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Speaker 1: the most recent cholera pandemic, that is, the seventh cholera

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Speaker 1: pandemic end? So let's go ahead and hear their answers.

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Speaker 2: Cholera pandemic. I have no idea, Sorry, no answer, Kelly,

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Speaker 2: I never heard of cholera pandemics. Please educate me on that.

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Speaker 4: HI A bit of a guess, but I would reckon.

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Speaker 4: The most recent cholera academic probably ended in the nineteen thirties,

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Speaker 4: sometime after the end of the First World War. I

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Speaker 4: don't remember any cholera event, so I'm going to say

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Speaker 4: before I was born it ended nineteen sixty eight.

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Speaker 3: If you asked like that, I would say it's ongoing.

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Speaker 4: But I really don't have any idea.

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Speaker 2: Just guessing here. In the nineteen twenties.

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Speaker 3: Colera pandemic, and there's been several I have no idea

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Speaker 3: when it ended, but I sure hope it was a

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Speaker 3: while ago and that there are few possibilities of it

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Speaker 3: coming back. But given the show, I'm a little bit concerned.

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Speaker 2: Since there are still many parts in the world with

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Speaker 2: questionable sanitization, I would guess like last year. Maybe my

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Speaker 2: wild guess here is that the most recent cholera pandemic

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Speaker 2: is still happening.

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Speaker 4: I have no idea. I don't even know when it started.

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Speaker 2: Maybe it hasn't ended yet.

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Speaker 1: When did the most recent colera pandemic? And I don't know,

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Speaker 1: but I think maybe it ended when they learned to

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Speaker 1: treat the water that was causing a color.

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Speaker 2: I don't know, but probably much more recently than one

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Speaker 2: would guess maybe in the nineteen sixties.

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Speaker 1: Okay, So as we sort of suspected not a lot

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Speaker 1: of awareness that we're in the middle of a cholera

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Speaker 1: pandemic because it's not really part of our lives if

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Speaker 1: you happen to be living in a place, you know,

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Speaker 1: like the United States, for example.

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Speaker 2: So remind us Kelly, cholera. It's a virus, it's a bacteria,

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Speaker 2: it's a pathogen. What is it?

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Speaker 1: It is a bacteria. And so it is a bacteria

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Speaker 1: that gets into the water. And for you to get cholera,

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Speaker 1: you need to ingest a lot of it. So if

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Speaker 1: you just sow, something like a million or maybe one

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Speaker 1: hundred million need to be ingested for you to get sick,

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Speaker 1: and Daniel.

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Speaker 2: One hundred million, one hundred.

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Speaker 1: Million, And so you might think, how would you accidentally

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Speaker 1: ingest one hundred million cholera bacteria? Right?

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Speaker 2: Is that like ten liters of cholera leased water.

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Speaker 1: Now it turns out that in like a regular cup

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Speaker 1: of water, you could have something like two hundred million

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Speaker 1: cholera bacteria and you probably wouldn't detect them in there

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Speaker 1: because they're pretty tiny and the glass like wouldn't look cloudy.

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Speaker 1: So you probably wouldn't know, but if you.

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Speaker 2: Put them under a microscope, you could probably see them.

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Speaker 1: Or yeah, yeah, but you know, how often do you

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Speaker 1: put your water under a microscope?

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Speaker 2: Yeah? Never, never from now on? Always but never.

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Speaker 1: All right, But so Daniel, like, you know, a million

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Speaker 1: to one hundred million before you get sick. How do

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Speaker 1: you think we know that?

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Speaker 2: Because people tried it on themselves, not.

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Speaker 1: Tried it on themselves, but tried it on prisoners. But

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Speaker 1: the prisoners they signed consent forms. And so this was

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Speaker 1: the experiment that I read was done on a prison

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Speaker 1: population in Maryland, and they signed consent forms and they

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Speaker 1: were told that they could stop the experiment at any time,

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Speaker 1: and they were very carefully watched by physicians, and as

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Speaker 1: soon as they started to show symptoms, they were you know,

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Speaker 1: brought into an environment where they were treated very carefully

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Speaker 1: and they were watched very carefully. This was done in

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Speaker 1: the seventies.

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Speaker 2: Wow, would that pass modern day i RB standards?

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Speaker 1: So we actually do continue to infect people with cholera today,

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Speaker 1: and we're going to talk about that later.

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Speaker 2: Yeah, don't we know enough? We're still doing this to people.

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Speaker 1: We are still doing this to people. Wow, hold your

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Speaker 1: breath hold your cheeks. We're still gonna be talking about

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Speaker 1: this later.

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Speaker 2: So I just hope those poor people have access to

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Speaker 2: a bidet. Yeah, yeah, so they can feel clean and

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Speaker 2: fresh after.

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Speaker 1: Work, I guess in that. Yeah, I'm behind bidets in

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Speaker 1: that situation, all right, Yeah, yeah, you're getting me on

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Speaker 1: the same page. I guess so. But another thing that

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Speaker 1: we learned from these this prison population is that actually

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Speaker 1: it turns out cholera is really susceptible to acid. So like,

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Speaker 1: if your stomach is particularly acidic at the moment, the

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Speaker 1: cholera bacteria are much more likely to die. So even

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Speaker 1: if you ingest something like one hundred million bacteria and

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Speaker 1: your stomach is having like a particularly acidic day, you

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Speaker 1: might not get cholera.

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Speaker 2: Wow. So cholera is a bacteria. You got ingested billions

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Speaker 2: of them. A lot of them die in your stomach.

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Speaker 2: Where do they end up setting up camp?

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Speaker 1: The small intestine? And I'll note now that when we

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Speaker 1: do experiments with people to try to study cholera, we

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Speaker 1: give them something that makes their stomach a more basic environment.

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Speaker 1: So maybe you'll take some like sodium bicarbonate along with

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Speaker 1: your cholera bacteria. Wow, so you ingest a bunch of them,

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Speaker 1: and then they go through your stomach. Some of them survive,

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Speaker 1: and then they get to your small intestine. The color

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Speaker 1: of bacteria have a flagella, and so this is like

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Speaker 1: a really long whip like appendage, and they use that

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Speaker 1: flagella to try to get through the mucus that lines

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Speaker 1: your small intestine. And so they like run into your

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Speaker 1: mucus and they start shaking their butts and they're trying

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Speaker 1: to get through the mucus so that they can get

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Speaker 1: to the cells that line your intestine.

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Speaker 2: But I thought the flagellum is like a propeller. You

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Speaker 2: have it at the back to push you somewhere, like

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Speaker 2: you know, like the motor on a boat, but here

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Speaker 2: they're sort of like backing in. They're using it like

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Speaker 2: a drill.

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Speaker 1: No no, so they sorry, they run in headfirst. Oh yeah,

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Speaker 1: and then they're using it to try to like corkscrew

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Speaker 1: their way in.

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Speaker 2: Got it.

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Speaker 1: Yeah, Okay, So they keep going until they hit the

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Speaker 1: cells of your intestine. And once they hit those epithelial cells,

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Speaker 1: they sort of like cement themselves down and they start

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Speaker 1: to replicate. And so now they've got these little batches

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Speaker 1: that are replicating and they start producing.

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Speaker 2: A toxin, and so they somehow know where to go,

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Speaker 2: like they are looking for this. They're not just swimming

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Speaker 2: in all random directions and the ones that end up

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Speaker 2: there set up camp. They're like all heading in that direction.

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Speaker 1: They are all heading in that direction.

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Speaker 2: Wow, that's a little creepy.

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Speaker 1: It is creepy. Yeah, Bacteria and viruses and things that

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Speaker 1: we might think of as not being very smart can

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Speaker 1: do pretty smart things.

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Speaker 2: They seem more like aware of the environment that I imagined.

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Speaker 2: Very cool. So then they start to replicate.

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Speaker 1: Yeah, so then they start to replicate, and while they're replicating,

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Speaker 1: they start producing a toxin. And this toxin is what

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Speaker 1: is massively the problem for cholera se. So this toxin

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Speaker 1: finds a way of like binding with your intestinal cells

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Speaker 1: and it gets taken up by your intestinal cells, and

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Speaker 1: when it's inside your intestine cells, it messes with your

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Speaker 1: cells and it starts to mess with your what we

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Speaker 1: call asmotic balance. But essentially, the way your body makes

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Speaker 1: sure that you are extracting water from the small intestine

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Speaker 1: to go into your body is by having different concentrations

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Speaker 1: of ions on either side of the inside of your

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Speaker 1: intestine and in your body.

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Speaker 2: So without getting too much into the chemistry, essentially you

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Speaker 2: want the water passing through the small intestines to be

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Speaker 2: less salty than the water in your body, so that

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Speaker 2: it then comes into your body to balance the salinity. Right,

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Speaker 2: isn't that the way it works?

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Speaker 1: Yep, that's exactly right. But then after this toxin gets

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Speaker 1: taken up by your body, that changes, and now your

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Speaker 1: intestine is saltier and the water in your body starts

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Speaker 1: getting dumped into your intestine and you start losing massive

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Speaker 1: amounts of water from your body, like we talked about

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Speaker 1: in the last episode.

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Speaker 2: And is this good somehow for the cholorobacteria. Are they

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Speaker 2: doing this in order to affect something which is positive

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Speaker 2: for them, or so that you'll have massive diarrhea which

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Speaker 2: spreads them or is this just like a random accidental

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Speaker 2: byproduct that they don't even care about.

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Speaker 1: So once you start losing this massive amounts of water,

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Speaker 1: the bacteria that have been replicating like crazy release themselves

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Speaker 1: from the outside of the cells and they get back

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Speaker 1: into the environments. And so in this way they managed

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Speaker 1: to get back out so they can go off and

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Speaker 1: infect someone else I see.

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Speaker 2: So it's definitely a part of their cycle. It's not

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Speaker 2: just an incidental thing.

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Speaker 1: It is easy to imagine how it could benefit the bacteria.

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Speaker 1: So I do think it seems to be a beneficial.

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Speaker 2: Thing that makes me feel better somehow, because if our

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Speaker 2: suffering and death was just like, well, we don't even

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Speaker 2: really care and we're accidentally doing this thing that kills you,

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Speaker 2: that would feel more tragic somehow.

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Speaker 1: Yeah, I guess, So I guess if no one's benefiting

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Speaker 1: from it, but I guess I don't. Maybe. But Okay,

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Speaker 1: so here's something that kind of blew my mind. And

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Speaker 1: maybe you already know this, given who you're married to,

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Speaker 1: and maybe I've just given away the punchline by saying that.

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Speaker 1: But these genes that produce the toxin, I want to

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Speaker 1: guess where they came from Mars Mars.

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Speaker 2: Wait wait, no, eight, there was a Katrina related clue here,

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Speaker 2: So it's gotta be a virus. Is it a virus?

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Speaker 1: It's a bacteria phage. Yeah, that's right, that's where well,

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Speaker 1: and you probably read the outline. So it looks like

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Speaker 1: there were two different bacteria phages that infected Vibrio cholera.

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Speaker 1: At some point. One of those bacteria phages I believe

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Speaker 1: gave the bacteria the ability to cling to the outside

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Speaker 1: of the intestinal cells so that they could like form

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Speaker 1: those mats and start replicating, and the other one gives

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Speaker 1: them the ability to make these toxins. And so without

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Speaker 1: this bacteria phage, Vibrio cholera would not be this like

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Speaker 1: human scourge that And did you catch that? I said

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Speaker 1: scourge right? I didn't say it right in the smallpox episode,

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Speaker 1: but I learn when the listeners write in lots of

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Speaker 1: emails about how I'm not pronouncing things right.

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Speaker 2: Gold star for Kelly makes everyone. But that's amazing that

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Speaker 2: this is virus power and it's like virus engineered. But

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Speaker 2: for those of you who don't remember, a lot of DNA,

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Speaker 2: including human DNA, is affected by viruses. Viral infections in

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Speaker 2: years past have altered our DNA, and some of our

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Speaker 2: essential functions come from DNA that essentially was injected into

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Speaker 2: the record by viruses, and that's true also for bacteria.

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Speaker 2: It's incredible.

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Speaker 1: It is incredible. But okay, so I feel like this

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Speaker 1: begs the question what was Vibrio cholera doing before these

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Speaker 1: viruses came along? And it turns out that this question

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Speaker 1: is really important for trying to figure out how you

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Speaker 1: can control cholera around the world, and it's also important

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Speaker 1: for trying to understand what colera is doing when it's

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Speaker 1: not in our body right. And so the answer is

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Speaker 1: that Vibrio cholera is a bacteria that you find in

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Speaker 1: aquatic ecosystems like all over the world. This is just

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Speaker 1: an aquatic bacteria that you find living on zoplankton, like copapods,

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Speaker 1: you find it living on like aquatic plants. This is

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Speaker 1: just an aquatic bacteria that is totally happy outside of

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Speaker 1: our bodies, living in aquatic ecosystems. You find it in

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Speaker 1: the Gulf Coast, you can find it in Lake Erie,

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Speaker 1: you can find it in the Ganges. It's just a

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Speaker 1: happy bacteria out there that every once in a while

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Speaker 1: ends up in a human body. So it looks like

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Speaker 1: there's lots of different strains of this bacteria. Some strains

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Speaker 1: don't have these toxin genes, so if you swallowed one

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Speaker 1: hundred million of them, nothing would happen. Other strains cause

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Speaker 1: some like tummy issues, but nothing on the level of

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Speaker 1: like cholera. But some of them cause pandemic cholera. And

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Speaker 1: so like there's lots of different Wow kinds of Fibrio

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Speaker 1: cholera that differ in how bad they are for us,

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Speaker 1: but you know they're out in our waterways.

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Speaker 2: So these were basically weaponized by these viruses. So the

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Speaker 2: story isn't this cholera infects you and uses you to

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Speaker 2: make more of it. It's this virus took over this

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Speaker 2: bacteria and instructed this bacteria to infect you to make

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Speaker 2: more of the bacteria, which in effect is making more

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Speaker 2: of the original virus DNA.

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Speaker 1: Yeah, I mean that sounds a bit more directed than

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Speaker 1: it probably, you know, actually.

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Speaker 2: Was I just wanted to make it sound like a

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Speaker 2: conspiracy theory so we can climb up the podcast charts.

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Speaker 1: Oh not, yes, okay, that I agree. That is exactly

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Speaker 1: what happened, Daniel. This bacteria phage was out to get us,

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Speaker 1: and through Vibrio cholera, it has achieved its goal.

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Speaker 2: Probably was engineered by the CIA, wasn't it.

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Speaker 1: Yeah? No, I know, right, like, yeah, the exploding cigars

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Speaker 1: for Castro didn't work, and so they were like, let's

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Speaker 1: go after a Vibrio cholera.

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Speaker 2: So no, I don't think a CIA is pulling the strings.

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Speaker 2: I think it probably is. Virus viruses control the world.

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Speaker 1: Yeah, yeah, well, so I think we don't really understand

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Speaker 1: what the bacteria phage was doing with this toxin before

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Speaker 1: it got into the bacteria or you know, so we

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Speaker 1: don't really understand all of the steps and why they happened.

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Speaker 1: But we're you know, we're working on trying to understand that.

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Speaker 1: But it does appear that, yes, this bacteria phage is

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Speaker 1: what essentially gave cholera the ability to be this whole

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Speaker 1: scourge upon humanity. And here we are, all.

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Speaker 2: Right, So I ingest like a cup of fluid with

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Speaker 2: like one hundred million collar bacteria in it, and then

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Speaker 2: they colonize my lower intestine. They make lots more of themselves?

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Speaker 2: How many come out the other end? Like I'm a

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Speaker 2: color of factory. Now, how big a multiplier am I?

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Speaker 1: You could produce like a trillion cholera bacteria with a

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Speaker 1: tea with a t yep, and you can release something

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Speaker 1: like twenty liters of fluid with about of cholera. I know,

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Speaker 1: just an incredible about flu Yes, flu Well, I mean

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Speaker 1: you're vomiting also, so the.

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Speaker 2: Fluid smelling rice filled fluid, right.

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Speaker 1: Yep, yep, it's pretty unpleasant. And so you know, so

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Speaker 1: you can see how this is a great route for

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Speaker 1: cholera to reproduce itself and get back into the environment

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Speaker 1: in large quantities.

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Speaker 2: Wow, if I'm doing my math right, one hundred million

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Speaker 2: to a tillion, that's a factor of ten thousand. So

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Speaker 2: every individual can ten thousand x the cholera population.

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Speaker 1: Yeah, but you know, if you have good sanitation and

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Speaker 1: all of those fluids from either end end up in

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Speaker 1: a good sanitation facility and they get treated appropriately, then

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Speaker 1: it's a dead end. And so sanitation makes a huge

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Speaker 1: difference here, so to me, like you know, good sewer

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Speaker 1: systems are one of the most amazing things that humanity

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Speaker 1: has ever done. And you might understand now why I

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Speaker 1: don't get invited to a lot of parties, but I'm

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Speaker 1: very excited about sewers.

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Speaker 2: And so why do people die of cholera? The toxin itself?

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Speaker 2: Does it do more than just make you put out

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Speaker 2: twenty leaders or is it dumping twenty leaders of fluid?

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Speaker 2: It kills you.

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Speaker 1: It's dumping twenty leaders of fluid that kills you. That's

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Speaker 1: all it's got to do. At that point, your blood

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Speaker 1: becomes super thick, your organs shut down because you just

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Speaker 1: can't get oxygen and stuff to all the places it

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Speaker 1: needs to go, and you go into a coma and

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Speaker 1: die usually.

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Speaker 2: Yeah.

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Speaker 1: Wow, all right, so now we know what the color

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Speaker 1: of bacteria are doing. Let's take a break, and when

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Speaker 1: we get back, let's start with the history of treatments

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Speaker 1: and begin with some of the less good treatments we've

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Speaker 1: tried throughout the history of time.

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Speaker 2: All right, we're back, and we were talking about cholera,

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Speaker 2: a disease that makes people produce twenty liters of fluid

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Speaker 2: out the north and the south ends of the body

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Speaker 2: on average.

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Speaker 1: Ish.

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Speaker 2: Yeah, and we've done a deep dive on the pandemics

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Speaker 2: and now we understand the biochemistry of cholera, how it

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Speaker 2: affects you. So let's talk about the good side of it,

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Speaker 2: developing treatments. How did we start to make this better?

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Speaker 1: Well, I'm going to start on the bad side of

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Speaker 1: treatments first. So, well, I was reading about the history

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Speaker 1: of cholera. There was this book that kept coming up

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Speaker 1: and it was Cholera It Causes Symptoms, Pathology Treatment by

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Speaker 1: Robert's Bartholow. And Bartholow was a physician in the United

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Speaker 1: States who was a physician through two cholera pandemics, and

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Speaker 1: people thought of him as an expert, and so I

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Speaker 1: was like, okay, well let's read what the expert was

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Speaker 1: saying in eighteen ninety three. And so when I got

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Speaker 1: to the treatment section, I found myself saying out loud

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Speaker 1: many times, oh.

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Speaker 2: No, oh no, didn't. It wouldn't.

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Speaker 1: So okay, So here's bad idea number one. Okay, okay,

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Speaker 1: so quick background they knew at this point. So this

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Speaker 1: is eighteen ninety three. So Roberts totally believed the cholera

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Speaker 1: was caused by vibrio cholera. He knows that it's a

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Speaker 1: bacteria that you're drinking it, it's in your gut. He's

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Speaker 1: on board with that.

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Speaker 2: You had the germ theory already.

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Speaker 1: He had the germ theory already. Not everybody was on

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Speaker 1: board with it at the time, but Bartholow was. So

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Speaker 1: he's like, all right, so here's the idea. You've got

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Speaker 1: these bacteria in your gut and they're gonna give you cholera.

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Speaker 1: If you are early in a case of cholera and

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Speaker 1: you just got it, maybe the solution, and hear me out,

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Speaker 1: is to give someone diarrhea. What to wash out the bacteria.

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Speaker 2: Oh, and it's like no.

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Speaker 1: But if twenty liters of fluids washing through your intestines

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Speaker 1: doesn't get rid of the bacteria. Yeah, And so the

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Speaker 1: idea was, if you start the diarrhea early, you'll flush

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Speaker 1: the bacteria out before the collar it can get worse.

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Speaker 1: And so you'd give people castor oil to induce diarrhea

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Speaker 1: and then you'd try to stop the diarrhea later on.

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Speaker 1: And needless to say, this just started dehydrating people before

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Speaker 1: the collar had a chance to dehydrate them further. So

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Speaker 1: this not a good idea.

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Speaker 2: Yeah, this is like there's a leak in the water tank,

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Speaker 2: so let's blow a hole in the water tank.

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Speaker 1: Yes, exactly right. And the word that they use for

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Speaker 1: the diarrhea inducing medications were eliminates, and which I had

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Speaker 1: never heard before, and so I that made me chuckle

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Speaker 1: a little before I went back to feeling awful for

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Speaker 1: the people who were being induced to have diarrhea before

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Speaker 1: they were subsequently killed by diarrhea.

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Speaker 2: And you know, in the defense of these folks, like

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Speaker 2: there are some successful treatments which on the surface sound insane.

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Speaker 1: Yeah, yep, yeah, you know.

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Speaker 2: Like drilling holes in people's skulls can sometimes relieve headaches.

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Speaker 1: Relieve the pressure. Yeah, yeah, yeah, yeah, you know totally.

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Speaker 2: So science is bizarre. If you don't have a fully

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Speaker 2: working model of how the body works, it's basically a

437
00:22:33,359 --> 00:22:35,840
Speaker 2: Rube Goldberg machine and we're just mashing on the levers.

438
00:22:35,960 --> 00:22:38,120
Speaker 2: You never really know what's going to work.

439
00:22:38,240 --> 00:22:39,840
Speaker 1: That's right. Well, and then in the past, we've given

440
00:22:39,840 --> 00:22:42,359
Speaker 1: people malaria to cure late stage syphilis.

441
00:22:42,440 --> 00:22:44,400
Speaker 2: Yeah exactly, and it worked, and.

442
00:22:44,359 --> 00:22:47,320
Speaker 1: It worked in some cases. Other cases it killed them.

443
00:22:47,359 --> 00:22:50,240
Speaker 1: But yes, we have done crazy things that have worked

444
00:22:50,240 --> 00:22:52,080
Speaker 1: in the past. So you know, you try stiff in.

445
00:22:52,080 --> 00:22:54,960
Speaker 2: The defense of bad idea number one, make them poop more.

446
00:22:55,160 --> 00:22:55,600
Speaker 1: That's right.

447
00:22:55,840 --> 00:22:57,600
Speaker 2: I can't believe I ended up on that side of

448
00:22:57,600 --> 00:22:58,520
Speaker 2: this conversation.

449
00:22:58,800 --> 00:23:02,200
Speaker 1: Oh, you know, it's good that defending outside the box

450
00:23:02,280 --> 00:23:03,320
Speaker 1: thinking they're something.

451
00:23:03,880 --> 00:23:07,400
Speaker 2: I just I'm always fascinated on these historical journeys, trying

452
00:23:07,400 --> 00:23:09,280
Speaker 2: to get in the minds of the people there, because

453
00:23:09,280 --> 00:23:12,199
Speaker 2: it's easy to judge them given our level of knowledge

454
00:23:12,240 --> 00:23:15,360
Speaker 2: and our understanding and our mode of thinking. But it's

455
00:23:15,400 --> 00:23:17,520
Speaker 2: another thing to try to get yourself in their heads

456
00:23:17,560 --> 00:23:19,720
Speaker 2: and wonder, like, what did they know? What's this reasonable?

457
00:23:19,760 --> 00:23:23,040
Speaker 2: Given what they understood, would I really have done something different?

458
00:23:23,320 --> 00:23:25,439
Speaker 1: Yeah? Yeah, Well, so you know what, let's jump to

459
00:23:25,600 --> 00:23:27,960
Speaker 1: what I had listed as bad idea number three because

460
00:23:27,960 --> 00:23:30,399
Speaker 1: I feel like it kind of goes with the argument

461
00:23:30,440 --> 00:23:33,600
Speaker 1: you're making right now. So okay, So bad idea number

462
00:23:33,600 --> 00:23:37,040
Speaker 1: three was sort of built on this idea that if

463
00:23:37,080 --> 00:23:40,720
Speaker 1: you made someone's stomach more acidic y, you could fight

464
00:23:40,760 --> 00:23:43,720
Speaker 1: the cholera. And I don't know that they actually understood

465
00:23:43,760 --> 00:23:48,159
Speaker 1: at the time that stomach acidity did kill cholera bacteria,

466
00:23:48,240 --> 00:23:51,200
Speaker 1: but they were onto something and so sounds reasonable, yes,

467
00:23:51,240 --> 00:23:56,399
Speaker 1: and so they would give people various acidic solutions and

468
00:23:56,440 --> 00:23:58,600
Speaker 1: have them drink it, and you know, it did turn it.

469
00:23:58,680 --> 00:24:02,360
Speaker 1: We did discover later on through controlled experiments that acidic

470
00:24:02,400 --> 00:24:06,640
Speaker 1: stomachs were good for killing bacteria, and so that that

471
00:24:06,760 --> 00:24:13,480
Speaker 1: was a reasonable treatment. But then some prodigy decided, what

472
00:24:13,760 --> 00:24:19,800
Speaker 1: if we instead injected the acid under someone's skin. And

473
00:24:19,960 --> 00:24:22,800
Speaker 1: I'm not sure what the thought was there, because I get,

474
00:24:22,920 --> 00:24:26,040
Speaker 1: you know, going after the bacteria in the intestine. But

475
00:24:26,320 --> 00:24:30,280
Speaker 1: it turns out injecting sulfuric acid under the skin quote

476
00:24:30,800 --> 00:24:32,520
Speaker 1: caused colossal gangreen.

477
00:24:33,240 --> 00:24:33,640
Speaker 2: Wow.

478
00:24:34,720 --> 00:24:37,720
Speaker 1: Yes, so that's that's essentially when the tissues die.

479
00:24:37,920 --> 00:24:40,240
Speaker 2: How many people did they inject this in before they

480
00:24:40,240 --> 00:24:43,160
Speaker 2: decided maybe this isn't a go to treatment.

481
00:24:43,280 --> 00:24:45,040
Speaker 1: I don't think it was a lot. I hope it

482
00:24:45,119 --> 00:24:49,480
Speaker 1: wasn't a lot, but it was some. So that's not great.

483
00:24:49,880 --> 00:24:53,000
Speaker 2: Yeah, yeah, because gangreen does not seem like a fun

484
00:24:53,080 --> 00:24:53,800
Speaker 2: thing to have.

485
00:24:54,080 --> 00:24:58,840
Speaker 1: On top of cholera, right right, yeah, right, yeah, So okay,

486
00:24:59,160 --> 00:25:02,280
Speaker 1: that there's a idea. All right, So the last bad

487
00:25:02,320 --> 00:25:04,920
Speaker 1: idea before we get to the good ideas. The last

488
00:25:04,920 --> 00:25:11,520
Speaker 1: bad idea is what was called tero lysis or no enteroclysis,

489
00:25:12,320 --> 00:25:15,439
Speaker 1: And the idea here is that maybe it would be

490
00:25:15,480 --> 00:25:19,240
Speaker 1: helpful if you rinsed off the intestines from the inside

491
00:25:19,600 --> 00:25:22,880
Speaker 1: with a chemical. And so they took a long tube

492
00:25:23,400 --> 00:25:26,560
Speaker 1: that was connected to a bag with a solution of tannins,

493
00:25:26,600 --> 00:25:29,440
Speaker 1: which are like some chemicals that plants make, and they

494
00:25:30,160 --> 00:25:33,160
Speaker 1: inserted the tube up the rear end as far as

495
00:25:33,160 --> 00:25:35,480
Speaker 1: it would go, and then they squeezed the bag to

496
00:25:35,520 --> 00:25:37,639
Speaker 1: try to rinse the inside of the intestines off with

497
00:25:37,680 --> 00:25:41,000
Speaker 1: these chemicals to try to essentially dislodge the bacteria and

498
00:25:41,119 --> 00:25:42,080
Speaker 1: sort of kill them.

499
00:25:42,160 --> 00:25:44,800
Speaker 2: So this is a tannin anema. Basically, this is.

500
00:25:44,920 --> 00:25:48,520
Speaker 1: A tannin anima. I guess I'm going to admit now

501
00:25:48,880 --> 00:25:52,720
Speaker 1: that I am not super familiar with how enemas are conducted.

502
00:25:52,920 --> 00:25:56,919
Speaker 1: I am not aware of them being attached to like

503
00:25:56,960 --> 00:25:59,720
Speaker 1: a hose. I thought it was more of I won't

504
00:25:59,720 --> 00:26:02,080
Speaker 1: go into too much detail anyway, this sound I don't.

505
00:26:01,920 --> 00:26:05,160
Speaker 2: Think it's that complicated, Kelly. I think you're maintaining an

506
00:26:05,200 --> 00:26:07,040
Speaker 2: ignorance untentionally.

507
00:26:07,080 --> 00:26:10,000
Speaker 1: I thought it was just just stuck a like pouch

508
00:26:10,119 --> 00:26:13,480
Speaker 1: up there and then that's done. Isn't that? Isn't that

509
00:26:13,520 --> 00:26:15,840
Speaker 1: the end? There's no like tube and you won't rinse

510
00:26:15,880 --> 00:26:19,840
Speaker 1: the inside. That's enemas. Aren't that complicated? Are they? Have?

511
00:26:19,920 --> 00:26:23,760
Speaker 2: You have I answer your questions? Never?

512
00:26:23,760 --> 00:26:24,000
Speaker 3: Fine?

513
00:26:24,000 --> 00:26:27,600
Speaker 1: Never fine? Okay? Point is point is they used to

514
00:26:27,640 --> 00:26:32,200
Speaker 1: rinse out people's intestines while they were suffering from uh cholera.

515
00:26:32,720 --> 00:26:36,560
Speaker 2: Why tannins though, Like I understand, the idea is to

516
00:26:36,920 --> 00:26:39,440
Speaker 2: rinse it out, maybe do something to reduce the bacteria.

517
00:26:39,520 --> 00:26:41,600
Speaker 2: But they have a theory that tannins we're going to

518
00:26:41,600 --> 00:26:42,560
Speaker 2: impact the bacteria.

519
00:26:43,119 --> 00:26:48,760
Speaker 1: So I have recently started keeping this amazing to me

520
00:26:49,400 --> 00:26:54,560
Speaker 1: timeline of medical advances, and it wasn't until nineteen twenty

521
00:26:54,640 --> 00:26:59,080
Speaker 1: eight that Alexander Fleming discovers penicillin. Yeah, and so this

522
00:26:59,280 --> 00:27:02,359
Speaker 1: is around eighteen ninety three, and so we didn't really

523
00:27:02,400 --> 00:27:06,280
Speaker 1: have antibiotics at that point, and so I don't know,

524
00:27:06,320 --> 00:27:08,520
Speaker 1: I'm guessing tannin's were just they were like, I don't know,

525
00:27:08,600 --> 00:27:12,000
Speaker 1: those things like kill stuff, and they're just kind of

526
00:27:12,000 --> 00:27:14,320
Speaker 1: they seem like the kind of thing that might make

527
00:27:14,440 --> 00:27:17,879
Speaker 1: an intestine inhospitable. So I'm not really sure what the

528
00:27:17,880 --> 00:27:19,120
Speaker 1: thinking was for tannins.

529
00:27:19,680 --> 00:27:22,359
Speaker 2: I mean, because if they're just guessing, you think maybe

530
00:27:22,359 --> 00:27:24,320
Speaker 2: they would try a few things. They're like, oh, let's

531
00:27:24,320 --> 00:27:26,720
Speaker 2: put in some cayenne pepper or something.

532
00:27:26,760 --> 00:27:28,679
Speaker 1: There was more than one thing that they were trying.

533
00:27:29,560 --> 00:27:34,840
Speaker 1: Tannic acid is those are tannins, right, tannic acid dear,

534
00:27:35,160 --> 00:27:37,840
Speaker 1: Neither one of us know they were putting stuff in

535
00:27:38,040 --> 00:27:41,600
Speaker 1: people's intestines, raising it out. So anyway, bad answer?

536
00:27:41,720 --> 00:27:43,560
Speaker 2: Did that make things worse or have no effect?

537
00:27:43,800 --> 00:27:47,600
Speaker 1: So Barthelow, the author of this book, seemed pretty convinced

538
00:27:47,600 --> 00:27:50,200
Speaker 1: that this was a good method. But here's the thing.

539
00:27:50,320 --> 00:27:53,880
Speaker 1: If you are dying from cholera, you probably don't want

540
00:27:53,880 --> 00:27:56,720
Speaker 1: to sit through this procedure, especially when it turns out

541
00:27:57,640 --> 00:28:04,600
Speaker 1: that what works is very simple. It is rehydration. And

542
00:28:04,720 --> 00:28:09,399
Speaker 1: Bartholow notes that there's this guy named Latta who in

543
00:28:09,520 --> 00:28:12,920
Speaker 1: eighteen thirty one was saying, hey, y'all, if you just

544
00:28:13,160 --> 00:28:17,520
Speaker 1: use this intravenous infusion of fluids that have some like

545
00:28:17,560 --> 00:28:22,440
Speaker 1: electrolytes in them, they seem to survive. And Bartholow is like, yeah, okay,

546
00:28:22,440 --> 00:28:25,400
Speaker 1: So if you give them a bunch of fluids intravenously

547
00:28:25,680 --> 00:28:27,359
Speaker 1: or you just make them drink it, if they're able to,

548
00:28:28,040 --> 00:28:30,520
Speaker 1: they perk up and they seem like they're in such

549
00:28:30,560 --> 00:28:32,840
Speaker 1: a good mood. But it's temporary because then they get

550
00:28:32,880 --> 00:28:34,920
Speaker 1: diarrhea and they throw up, and then they don't feel

551
00:28:34,920 --> 00:28:37,159
Speaker 1: good again, and it just kind of feels like you

552
00:28:37,240 --> 00:28:39,600
Speaker 1: have to keep doing this over and over again, and

553
00:28:39,640 --> 00:28:45,160
Speaker 1: that's frustrating, and so they abandoned this technique until like

554
00:28:45,280 --> 00:28:48,280
Speaker 1: nineteen fifteen when this new physic, when this physician named

555
00:28:48,360 --> 00:28:51,840
Speaker 1: Rogers is like, hey, y'all, actually this rehydration thing, like

556
00:28:52,400 --> 00:28:55,600
Speaker 1: this is the thing that works. All of those fluids

557
00:28:55,600 --> 00:28:58,080
Speaker 1: that they're losing, you just need to put them back.

558
00:28:58,520 --> 00:29:01,520
Speaker 1: And then everybody's okay, and Daniel, you have a story

559
00:29:01,560 --> 00:29:02,440
Speaker 1: about this, right.

560
00:29:03,960 --> 00:29:07,280
Speaker 2: Yeah, key to this rehydration technique is getting the like

561
00:29:07,480 --> 00:29:11,080
Speaker 2: salt and sugar balance of the rehydration correct, so the

562
00:29:11,160 --> 00:29:14,080
Speaker 2: things are actually absorbed and you don't end up like

563
00:29:14,120 --> 00:29:18,280
Speaker 2: stealing more fluids. And what works best is a particular

564
00:29:18,440 --> 00:29:21,239
Speaker 2: mix not just like salty water. We're also having some

565
00:29:21,280 --> 00:29:24,960
Speaker 2: sugar in there. And a guy I know here, Jonas Schultz,

566
00:29:24,960 --> 00:29:28,000
Speaker 2: who's a particle physicist, his brother Stanley Schultz, is the

567
00:29:28,040 --> 00:29:31,280
Speaker 2: guy who figured out like exactly the right balance of

568
00:29:31,320 --> 00:29:34,120
Speaker 2: salt and sugar and the chemistry for why that works.

569
00:29:34,680 --> 00:29:37,920
Speaker 2: And so now we understand exactly like how to sweeten

570
00:29:38,000 --> 00:29:40,800
Speaker 2: and salty that water so that when you rehydrate people

571
00:29:41,080 --> 00:29:43,720
Speaker 2: they absorb and keep as much of that water as possible.

572
00:29:43,880 --> 00:29:48,840
Speaker 1: That's amazing and so like. Whereas previously cholera was pretty

573
00:29:48,920 --> 00:29:53,440
Speaker 1: darn fatal, these days, if you use the appropriate rehydration technique,

574
00:29:53,840 --> 00:29:56,920
Speaker 1: we expect that you only lose about one percent of

575
00:29:56,960 --> 00:30:01,440
Speaker 1: patients who come in with cholera. You lose, of course,

576
00:30:01,480 --> 00:30:04,720
Speaker 1: ideally you lose no one, but the one percent that

577
00:30:04,760 --> 00:30:07,600
Speaker 1: you lose tend to be people who had some other

578
00:30:07,680 --> 00:30:10,440
Speaker 1: issues going on and the cholera just sort of was

579
00:30:10,480 --> 00:30:12,800
Speaker 1: more than their body could take. But for most people,

580
00:30:12,800 --> 00:30:14,400
Speaker 1: if you can get the fluids back, they survive.

581
00:30:14,680 --> 00:30:16,920
Speaker 2: So that's why I asked earlier, like what is it

582
00:30:16,960 --> 00:30:19,160
Speaker 2: that kills you? And if it's just really the loss

583
00:30:19,160 --> 00:30:22,560
Speaker 2: of fluids, then yeah, it seems very straightforward to say, well,

584
00:30:22,640 --> 00:30:24,960
Speaker 2: let's just prevent you from losing those fluids or replace

585
00:30:25,000 --> 00:30:28,120
Speaker 2: them as they exit. But then the other question, of course,

586
00:30:28,200 --> 00:30:29,680
Speaker 2: is like how long do you have to do this for?

587
00:30:30,200 --> 00:30:34,280
Speaker 2: Does the body eventually kill the bacteria without any external assistance,

588
00:30:34,320 --> 00:30:36,720
Speaker 2: without penicillin, if you can just sort of survive long

589
00:30:36,840 --> 00:30:37,600
Speaker 2: enough for it to do that.

590
00:30:37,920 --> 00:30:39,960
Speaker 1: Yes, that is the case. Every once in a while

591
00:30:40,000 --> 00:30:42,240
Speaker 1: they will give people antibiotics to try to speed the

592
00:30:42,280 --> 00:30:44,640
Speaker 1: process up, but in a lot of cases they don't

593
00:30:44,680 --> 00:30:47,520
Speaker 1: even give people antibiotics, and eventually your body clears it

594
00:30:47,560 --> 00:30:50,000
Speaker 1: out and you will be fine.

595
00:30:50,360 --> 00:30:53,040
Speaker 2: And that's fascinating because then everybody gets what they want, right,

596
00:30:53,080 --> 00:30:55,440
Speaker 2: Like the cholera still got to do their thing and

597
00:30:55,480 --> 00:30:58,480
Speaker 2: make more cholera and exit your body in twenty liters

598
00:30:58,520 --> 00:31:00,680
Speaker 2: of discusting fluid. Do you survive?

599
00:31:01,160 --> 00:31:03,239
Speaker 1: Yeah? I don't think the World Health Organization is like

600
00:31:03,320 --> 00:31:06,720
Speaker 1: making their recommendations based on trying to make everyone happy,

601
00:31:06,760 --> 00:31:09,560
Speaker 1: including the one trillion cholera that we're produced by an infection,

602
00:31:10,120 --> 00:31:12,760
Speaker 1: and I don't think the cholera are happy if they

603
00:31:12,880 --> 00:31:15,959
Speaker 1: end up in like a modern sanitation system. But yeah, so,

604
00:31:16,040 --> 00:31:18,959
Speaker 1: I mean, the World Health Organization says you need water,

605
00:31:19,240 --> 00:31:23,200
Speaker 1: sanitation and hygiene. The acronym there is wash with the

606
00:31:23,240 --> 00:31:27,320
Speaker 1: water providing the W and the A loving it. And

607
00:31:27,400 --> 00:31:29,520
Speaker 1: you know, if you have these things, you can usually

608
00:31:29,600 --> 00:31:32,640
Speaker 1: keep cholera out of your population. And then with this

609
00:31:32,840 --> 00:31:35,960
Speaker 1: oral rehydration solution, you can treat anyone who does happen

610
00:31:36,000 --> 00:31:36,880
Speaker 1: to get cholera.

611
00:31:37,120 --> 00:31:39,280
Speaker 2: And so these days, if you have any get cholera,

612
00:31:39,400 --> 00:31:41,960
Speaker 2: it's still the go to treatment is basically just an

613
00:31:42,000 --> 00:31:43,000
Speaker 2: infusion of fluids.

614
00:31:43,200 --> 00:31:47,640
Speaker 1: Yeah, an infusion of fluids. Sometimes you'll get antibiotics, but yes,

615
00:31:47,720 --> 00:31:50,680
Speaker 1: just trying to replace those fluids is what happens.

616
00:31:50,960 --> 00:31:53,000
Speaker 2: But it has to be quick, right because color can

617
00:31:53,080 --> 00:31:54,440
Speaker 2: kill you in like twelve hours.

618
00:31:54,800 --> 00:31:57,440
Speaker 1: Yes, yeah, yeah, you want to get to a hospital immediately.

619
00:31:58,680 --> 00:31:58,880
Speaker 3: Yeah.

620
00:31:59,520 --> 00:32:02,920
Speaker 2: It's amazing sing when like minutes or hours matter for

621
00:32:03,240 --> 00:32:05,080
Speaker 2: outcomes in these medical decisions.

622
00:32:05,400 --> 00:32:06,680
Speaker 1: Yeah, scary, it is.

623
00:32:06,760 --> 00:32:08,640
Speaker 2: All right, let's take a break and when we come back,

624
00:32:08,720 --> 00:32:10,880
Speaker 2: we'll learn about how we're going to prevent people from

625
00:32:10,880 --> 00:32:33,960
Speaker 2: getting cholera in the first place. All right, we're back,

626
00:32:34,080 --> 00:32:36,000
Speaker 2: and now we're going to talk about something which is

627
00:32:36,240 --> 00:32:39,480
Speaker 2: unfortunately controversial these days vaccines.

628
00:32:40,520 --> 00:32:45,360
Speaker 1: Yes, yes, unfortunately controversial and also in this case a

629
00:32:45,360 --> 00:32:47,640
Speaker 1: little bit hard to study. So it turns out that

630
00:32:47,760 --> 00:32:51,520
Speaker 1: cholera is one of those diseases that acts differently in

631
00:32:51,680 --> 00:32:54,680
Speaker 1: humans than it does in a lot of animals. So

632
00:32:54,720 --> 00:32:57,800
Speaker 1: it's been hard to have animal models because, for example,

633
00:32:57,920 --> 00:33:02,240
Speaker 1: if you give cholera to an animal like a rabbit,

634
00:33:02,920 --> 00:33:07,920
Speaker 1: they don't produce the massive quantities of diarrhea that humans produce.

635
00:33:08,400 --> 00:33:10,840
Speaker 1: And so if you are testing out a vaccine on

636
00:33:11,080 --> 00:33:14,760
Speaker 1: a rabbit, for example, you don't necessarily get the information

637
00:33:14,840 --> 00:33:17,560
Speaker 1: that you want from studying a rabbit that you would

638
00:33:17,600 --> 00:33:20,560
Speaker 1: get from studying a human, for example, because it's just

639
00:33:20,560 --> 00:33:21,400
Speaker 1: not doing the same thing.

640
00:33:21,400 --> 00:33:23,160
Speaker 2: To rabbits, even proportionally.

641
00:33:23,440 --> 00:33:25,000
Speaker 1: Even proportionally, that's right.

642
00:33:25,120 --> 00:33:27,040
Speaker 2: And do we understand what's going on in the rabbit

643
00:33:27,120 --> 00:33:29,160
Speaker 2: small intestine that makes it respond differently.

644
00:33:29,840 --> 00:33:33,600
Speaker 1: We've done some research to understand a bit about why

645
00:33:33,680 --> 00:33:36,120
Speaker 1: it differs in rabbits versus why it differs in humans.

646
00:33:36,120 --> 00:33:38,480
Speaker 1: To be honest, I didn't dig into that part too much,

647
00:33:38,880 --> 00:33:41,080
Speaker 1: but at the end of the day, rabbits don't tell

648
00:33:41,160 --> 00:33:44,040
Speaker 1: us everything we need. We've learned some great stuff from

649
00:33:44,080 --> 00:33:47,280
Speaker 1: rodents that's been super helpful, but not everything we need

650
00:33:47,560 --> 00:33:50,640
Speaker 1: will be able to come from rabbits. And another thing

651
00:33:50,680 --> 00:33:54,360
Speaker 1: that's difficult, so we had talked about in the prior

652
00:33:54,440 --> 00:33:57,760
Speaker 1: segment the fact that vibrio cholera has a lot of

653
00:33:57,760 --> 00:34:03,160
Speaker 1: different strains that act differently, the strains that cause pandemics.

654
00:34:03,640 --> 00:34:05,560
Speaker 1: There is a lot of them. So you know how

655
00:34:05,560 --> 00:34:08,560
Speaker 1: every season you go and you get the flu vaccine

656
00:34:08,719 --> 00:34:11,560
Speaker 1: because there's a different strain of the flu that's going around.

657
00:34:12,280 --> 00:34:16,040
Speaker 1: Cholera isn't really that different. It doesn't have a different

658
00:34:16,080 --> 00:34:19,880
Speaker 1: strain every year, but there are something like five or

659
00:34:19,960 --> 00:34:22,680
Speaker 1: six different pandemic strains, and you do need to keep

660
00:34:22,680 --> 00:34:24,560
Speaker 1: an eye on it over time, because every once in

661
00:34:24,600 --> 00:34:27,719
Speaker 1: a while, a new pandemic strain will sort of pop up,

662
00:34:28,320 --> 00:34:30,759
Speaker 1: and now you need to worry about trying to include

663
00:34:30,840 --> 00:34:34,960
Speaker 1: that strain in the vaccines. And if you're vaccinated against,

664
00:34:35,360 --> 00:34:38,280
Speaker 1: you know, one of the six strains that might protect

665
00:34:38,320 --> 00:34:41,279
Speaker 1: you against a subset of the other strains, but not

666
00:34:41,400 --> 00:34:44,040
Speaker 1: all of them. And so when you're creating a vaccine,

667
00:34:44,080 --> 00:34:46,799
Speaker 1: you need to have multiple strains in there. And this

668
00:34:46,880 --> 00:34:49,640
Speaker 1: isn't totally foreign. Like when I went to go get

669
00:34:49,719 --> 00:34:51,440
Speaker 1: the flu shot this year, I think there were three

670
00:34:51,560 --> 00:34:55,400
Speaker 1: different flu strains in that flu shot to protect me against,

671
00:34:55,440 --> 00:34:57,839
Speaker 1: you know, the most likely strains that I'll encounter this year.

672
00:34:58,360 --> 00:35:01,319
Speaker 1: And so we do do a of different strains in

673
00:35:01,360 --> 00:35:05,440
Speaker 1: the cholera vaccines, and interestingly that we also try to

674
00:35:05,520 --> 00:35:11,040
Speaker 1: include subunits of the toxin that cholera produces because our

675
00:35:11,080 --> 00:35:15,120
Speaker 1: body also produces like antibodies to stop the toxin from

676
00:35:15,160 --> 00:35:17,359
Speaker 1: binding to our intestines.

677
00:35:17,560 --> 00:35:21,280
Speaker 2: Wow, fascinating, And so how do we go about making

678
00:35:21,320 --> 00:35:24,680
Speaker 2: this vaccine? Like do we inject it in humans and

679
00:35:24,760 --> 00:35:28,279
Speaker 2: look at the antibodies and then use those antibodies somehow?

680
00:35:28,760 --> 00:35:31,879
Speaker 2: Is it just those antibodies? How does this vaccine work?

681
00:35:31,960 --> 00:35:36,040
Speaker 1: Yeah, So the way that we test these vaccines is

682
00:35:36,600 --> 00:35:39,160
Speaker 1: different than the way we test a lot of other vaccines.

683
00:35:39,160 --> 00:35:41,640
Speaker 1: So I think that the way that I most often

684
00:35:41,719 --> 00:35:45,359
Speaker 1: think of how we test vaccines is that we give

685
00:35:45,360 --> 00:35:48,719
Speaker 1: the vaccine to a large population of volunteers, and then

686
00:35:48,880 --> 00:35:52,120
Speaker 1: we track those volunteers as they go about their lives,

687
00:35:52,200 --> 00:35:54,880
Speaker 1: and then after like three or four months or some

688
00:35:54,960 --> 00:35:57,000
Speaker 1: maybe half a year or something some amount of time,

689
00:35:57,440 --> 00:35:59,880
Speaker 1: we ask them to report back and say, you know,

690
00:36:00,080 --> 00:36:03,680
Speaker 1: for example, you got the COVID vaccine six months later,

691
00:36:03,760 --> 00:36:05,920
Speaker 1: can you let us know did you get COVID or not?

692
00:36:06,520 --> 00:36:08,120
Speaker 1: And then we look and we say, okay, for the

693
00:36:08,160 --> 00:36:12,280
Speaker 1: people who got the placebo, what percent of them got COVID?

694
00:36:12,400 --> 00:36:15,480
Speaker 1: And the people who got the actual COVID vaccine, what

695
00:36:15,600 --> 00:36:18,240
Speaker 1: percent of them got COVID? And you hope the percent

696
00:36:18,280 --> 00:36:20,760
Speaker 1: that got the actual vaccine is lower than the percent

697
00:36:20,840 --> 00:36:23,680
Speaker 1: that got the place ebo, which is, you know, maybe

698
00:36:23,719 --> 00:36:26,120
Speaker 1: like a solution of saline and not actually the vaccine.

699
00:36:27,080 --> 00:36:31,360
Speaker 1: What we do with something like cholera often is we

700
00:36:31,360 --> 00:36:33,120
Speaker 1: we know that cholera is the kind of thing where

701
00:36:33,160 --> 00:36:36,120
Speaker 1: if you have somebody in a medical setting and they

702
00:36:36,160 --> 00:36:40,440
Speaker 1: are healthy to begin with, if you treat them, you

703
00:36:40,520 --> 00:36:43,839
Speaker 1: can make sure that they will survive, and so you

704
00:36:43,880 --> 00:36:48,879
Speaker 1: can do a much faster trial if you essentially give

705
00:36:48,920 --> 00:36:53,279
Speaker 1: people the vaccine, give some people a placebo, you know,

706
00:36:53,480 --> 00:36:57,319
Speaker 1: like a solution of saline, and then you give everybody

707
00:36:57,880 --> 00:37:02,640
Speaker 1: a hundred million cholera bacteria, because then you can control

708
00:37:02,719 --> 00:37:06,960
Speaker 1: how strong of a dose everybody's getting and what strains

709
00:37:06,960 --> 00:37:10,359
Speaker 1: of cholera they're being exposed to, and so that tends

710
00:37:10,440 --> 00:37:12,359
Speaker 1: to be what we do. And so what what we'll

711
00:37:12,400 --> 00:37:15,840
Speaker 1: do is we'll try to pick strains of cholera that

712
00:37:15,880 --> 00:37:19,120
Speaker 1: we think are the most likely to be a problem

713
00:37:19,160 --> 00:37:22,680
Speaker 1: in a particular region at a particular time. We will

714
00:37:22,840 --> 00:37:25,479
Speaker 1: kill them. So usually what we're doing is like oral

715
00:37:25,560 --> 00:37:30,200
Speaker 1: vaccines of killed cholera cells, and then we will set

716
00:37:30,280 --> 00:37:33,799
Speaker 1: up a facility where people will volunteer. First, we'll do

717
00:37:33,920 --> 00:37:36,560
Speaker 1: tests to make sure that everybody's healthy, and then they

718
00:37:36,560 --> 00:37:39,480
Speaker 1: will either get the vaccine or a placebo, and then

719
00:37:39,480 --> 00:37:41,759
Speaker 1: they'll get exposed to the kind of cholera that we

720
00:37:41,800 --> 00:37:44,480
Speaker 1: think they're going to encounter. You know, in the areas

721
00:37:44,480 --> 00:37:47,239
Speaker 1: that we're worried about, are these prisoners, Uh No, I don't.

722
00:37:47,520 --> 00:37:50,719
Speaker 1: I haven't seen. The prisoner experiment was from the seventies.

723
00:37:51,760 --> 00:37:56,120
Speaker 1: I think these days they're probably you know, college kids

724
00:37:56,280 --> 00:37:58,279
Speaker 1: who are who are volunteering.

725
00:37:58,960 --> 00:38:00,960
Speaker 2: We'd need a few hundred bucks and have a day

726
00:38:00,960 --> 00:38:05,319
Speaker 2: to spend over the toilet. But I'm wondering you're saying

727
00:38:05,360 --> 00:38:08,160
Speaker 2: we do this for cholera because we're confident that anybody

728
00:38:08,160 --> 00:38:10,719
Speaker 2: who gets it they will recover, And so it's not

729
00:38:10,920 --> 00:38:13,520
Speaker 2: really dangerous to give people the disease, and therefore it's

730
00:38:13,520 --> 00:38:17,440
Speaker 2: a very useful way to directly study whether the vaccine

731
00:38:17,520 --> 00:38:20,280
Speaker 2: saves them or prevents the disease. So is that only

732
00:38:20,320 --> 00:38:22,880
Speaker 2: true for diseases where we're very confident that we can

733
00:38:22,920 --> 00:38:24,680
Speaker 2: save people. That's why we don't do this for the flu.

734
00:38:24,760 --> 00:38:27,040
Speaker 2: We don't give people the flu vaccine and then intentionally

735
00:38:27,040 --> 00:38:30,040
Speaker 2: inject them with the flu because as a higher mortality rate.

736
00:38:30,080 --> 00:38:34,200
Speaker 1: We're careful with things like respiratory illnesses. I do think

737
00:38:34,200 --> 00:38:38,520
Speaker 1: we've done some challenge trials on influenza, but on very

738
00:38:38,600 --> 00:38:42,359
Speaker 1: healthy volunteers. I'm sure that this was implied in what

739
00:38:42,400 --> 00:38:45,000
Speaker 1: you said. But like you know, we for cholera, we

740
00:38:45,120 --> 00:38:47,080
Speaker 1: only know we can save people because they are like

741
00:38:47,280 --> 00:38:51,280
Speaker 1: already in a hospital. Like you know, you wouldn't yeah, yeah,

742
00:38:51,320 --> 00:38:54,040
Speaker 1: you wouldn't test this out Like in the field where

743
00:38:54,120 --> 00:38:56,400
Speaker 1: somebody got cholera, you'd have to drive them two hours

744
00:38:56,400 --> 00:38:57,480
Speaker 1: to a hospital or something.

745
00:38:57,520 --> 00:38:59,840
Speaker 2: Call us if you feel anything, right, are already in

746
00:38:59,840 --> 00:39:00,680
Speaker 2: the Yeah, we're right.

747
00:39:00,960 --> 00:39:03,600
Speaker 1: These are under conditions that are very controlled, and you

748
00:39:03,640 --> 00:39:05,760
Speaker 1: know you could very quickly get them to safety.

749
00:39:06,080 --> 00:39:07,680
Speaker 2: But is the mortality zero?

750
00:39:08,400 --> 00:39:13,799
Speaker 1: There was one instance where somebody had a cardiac thing

751
00:39:14,120 --> 00:39:17,400
Speaker 1: happen and this was over I think thirty years of

752
00:39:17,440 --> 00:39:21,440
Speaker 1: experiments where these controlled studies challenge studies have been done,

753
00:39:21,440 --> 00:39:23,319
Speaker 1: and I'm pulling this number from my head, and that

754
00:39:23,400 --> 00:39:26,920
Speaker 1: might have been from challenge studies. So these kinds of

755
00:39:26,960 --> 00:39:30,919
Speaker 1: trials are called challenge trials, and that might have been

756
00:39:30,960 --> 00:39:36,040
Speaker 1: for all challenge trials, including studies that weren't just cholera,

757
00:39:36,080 --> 00:39:38,759
Speaker 1: because this has been done on other diseases too. So

758
00:39:39,040 --> 00:39:44,320
Speaker 1: this technique has very high success because folks are really

759
00:39:44,440 --> 00:39:48,080
Speaker 1: cautious when they do it, But we have still had

760
00:39:48,239 --> 00:39:51,520
Speaker 1: quite a bit of difficulty when we go to use

761
00:39:51,640 --> 00:39:55,040
Speaker 1: colera vaccines in the field. So just because you have

762
00:39:55,120 --> 00:39:59,160
Speaker 1: tested a colera vaccine I don't know, for example, in London,

763
00:40:00,120 --> 00:40:02,799
Speaker 1: doesn't necessarily mean that when you go to use the

764
00:40:02,840 --> 00:40:06,680
Speaker 1: color vaccine in children in India, you know, in an

765
00:40:06,680 --> 00:40:10,680
Speaker 1: area where cholera pops up quite a bit, it doesn't

766
00:40:10,719 --> 00:40:12,879
Speaker 1: mean that immune systems are going to do the same thing.

767
00:40:13,080 --> 00:40:16,200
Speaker 1: So you know, for example, maybe if you're I don't know,

768
00:40:16,239 --> 00:40:20,360
Speaker 1: a teenager in India, you have encountered the cholera bacteria

769
00:40:20,440 --> 00:40:23,680
Speaker 1: before and so your immune system might respond differently whereas

770
00:40:23,719 --> 00:40:26,600
Speaker 1: like a college kid in London has probably never encountered

771
00:40:26,640 --> 00:40:30,680
Speaker 1: the color of bacteria before. Additionally, they have different microbiomes

772
00:40:30,680 --> 00:40:33,919
Speaker 1: and I've seen papers indicate that that could matter. And

773
00:40:34,080 --> 00:40:39,080
Speaker 1: kids in India probably have some different intestinal parasites than

774
00:40:39,200 --> 00:40:42,680
Speaker 1: kids in London and that could impact how bodies respond

775
00:40:42,760 --> 00:40:46,360
Speaker 1: to things like vaccines. And so we're finding that sometimes

776
00:40:46,360 --> 00:40:50,440
Speaker 1: in challenge trials, what you see doesn't always match what

777
00:40:50,480 --> 00:40:53,200
Speaker 1: you see in the field when you're giving it to

778
00:40:53,520 --> 00:40:57,040
Speaker 1: two communities. So challenge trials still seem useful, but we

779
00:40:57,120 --> 00:40:59,120
Speaker 1: don't always see exactly what we expect.

780
00:40:59,360 --> 00:41:02,080
Speaker 2: And who takes this vaccine. Is it only for people

781
00:41:02,080 --> 00:41:05,600
Speaker 2: who are living in cholera endemic regions and people traveling

782
00:41:05,640 --> 00:41:09,400
Speaker 2: there or is everybody get it? Have I been vaccinated

783
00:41:09,440 --> 00:41:10,040
Speaker 2: against cholera?

784
00:41:10,160 --> 00:41:13,120
Speaker 1: Well, it depends have you traveled to an area where

785
00:41:13,200 --> 00:41:14,160
Speaker 1: cholera is endemic?

786
00:41:14,239 --> 00:41:15,640
Speaker 2: I don't think so. I've ever been to India.

787
00:41:15,760 --> 00:41:19,160
Speaker 1: Well, you know, it's also in South America and Africa.

788
00:41:19,480 --> 00:41:21,200
Speaker 2: I've been to South America and I definitely got some

789
00:41:21,320 --> 00:41:22,120
Speaker 2: vaccines for that.

790
00:41:22,239 --> 00:41:26,600
Speaker 1: So maybe maybe I've gotten the yellow fever vaccine before,

791
00:41:27,080 --> 00:41:29,359
Speaker 1: but I think but I don't think I've ever gotten

792
00:41:29,360 --> 00:41:31,879
Speaker 1: the color of vaccine. Most people have probably haven't gotten

793
00:41:31,920 --> 00:41:33,920
Speaker 1: the color of vaccine. If you traveled to an area

794
00:41:33,960 --> 00:41:37,400
Speaker 1: where cholera is endemic, you might have gotten the vaccine,

795
00:41:37,440 --> 00:41:41,720
Speaker 1: and challenge trials were used to develop the traveler's version

796
00:41:41,960 --> 00:41:44,520
Speaker 1: of the colera vaccine. And if you live in an

797
00:41:44,520 --> 00:41:48,040
Speaker 1: area where cholera is common, you and your kids may

798
00:41:48,040 --> 00:41:50,560
Speaker 1: have had the color of vaccine. And actually, if any

799
00:41:50,560 --> 00:41:52,440
Speaker 1: of our listeners want to write in and let us

800
00:41:52,480 --> 00:41:54,080
Speaker 1: know if they got the color of vaccine, I'd be

801
00:41:54,080 --> 00:41:57,040
Speaker 1: interested in hearing about that. But you need to get

802
00:41:57,040 --> 00:41:59,920
Speaker 1: the color of vaccine pretty often. So even if you

803
00:42:00,960 --> 00:42:05,000
Speaker 1: get cholera in real life, the immunity that your body

804
00:42:05,080 --> 00:42:09,480
Speaker 1: provides doesn't last for a lifetime. Like if you get

805
00:42:09,560 --> 00:42:13,120
Speaker 1: cholera and it's like a mild case, your immunity might

806
00:42:13,200 --> 00:42:15,279
Speaker 1: last for like three years. I've read one source that

807
00:42:15,400 --> 00:42:17,319
Speaker 1: said a really bad case of cholera can give you

808
00:42:17,320 --> 00:42:20,600
Speaker 1: immunity for ten years. But after that, your immune system

809
00:42:20,680 --> 00:42:23,759
Speaker 1: kind of forgets what colera looks like, which seems like

810
00:42:23,800 --> 00:42:27,839
Speaker 1: a bad plan. And so you need to get immunized regularly.

811
00:42:28,000 --> 00:42:31,439
Speaker 1: And if your immune system only remembers an actual case

812
00:42:31,480 --> 00:42:34,080
Speaker 1: of cholera for three to ten years. Probably that's the

813
00:42:34,080 --> 00:42:36,319
Speaker 1: best we can do with a vaccine, which means you

814
00:42:36,360 --> 00:42:38,920
Speaker 1: need to get vaccinated regularly, which is hard because a

815
00:42:38,920 --> 00:42:41,640
Speaker 1: lot of areas where cholera is endemic are areas where

816
00:42:41,640 --> 00:42:44,800
Speaker 1: you don't have good sanitation, and those are also areas

817
00:42:44,800 --> 00:42:47,080
Speaker 1: where it's probably hard to get vaccines, especially if for

818
00:42:47,080 --> 00:42:49,560
Speaker 1: the vaccines need to be refrigerated, and so there are

819
00:42:49,600 --> 00:42:52,239
Speaker 1: areas where it's hard to get vaccines to people regularly,

820
00:42:52,560 --> 00:42:55,680
Speaker 1: and so we don't currently have vaccines that we feel

821
00:42:55,719 --> 00:42:59,960
Speaker 1: like amazing about. Research on cholera vaccines continues because we

822
00:43:00,080 --> 00:43:03,000
Speaker 1: would like to have even better cholera vaccines.

823
00:43:03,360 --> 00:43:06,840
Speaker 2: And is there a campaign to eradicate cholera like we

824
00:43:06,880 --> 00:43:10,080
Speaker 2: did for smallpox or is that impossible because cholera is

825
00:43:10,160 --> 00:43:12,719
Speaker 2: happy to live in the environment even if we got

826
00:43:12,760 --> 00:43:13,760
Speaker 2: it out of all of the people.

827
00:43:14,360 --> 00:43:18,680
Speaker 1: I think that the goal is to reduce cholera. I

828
00:43:18,800 --> 00:43:22,279
Speaker 1: don't think it would be reasonable to try to eradicate

829
00:43:22,360 --> 00:43:27,040
Speaker 1: cholera entirely because it can live in the environments without us,

830
00:43:27,080 --> 00:43:29,560
Speaker 1: Like I just I don't see how you would how

831
00:43:29,600 --> 00:43:30,640
Speaker 1: you would do that, And.

832
00:43:30,640 --> 00:43:33,280
Speaker 2: Because it's out in the environment and there's viruses out there.

833
00:43:33,480 --> 00:43:36,920
Speaker 2: There must be constantly new versions of it, and it's mutating,

834
00:43:36,960 --> 00:43:40,440
Speaker 2: and there's gazillion's uncountable number of these things floating in

835
00:43:40,520 --> 00:43:44,320
Speaker 2: every lake, one mutation away from being the next pandemic.

836
00:43:44,600 --> 00:43:46,839
Speaker 1: Yes, right, yeah, And you know, even if we had

837
00:43:46,840 --> 00:43:50,200
Speaker 1: a perfect vaccine tomorrow, the week after that, you could

838
00:43:50,320 --> 00:43:53,799
Speaker 1: have horizontal gene transfer and you know, the genes for

839
00:43:53,840 --> 00:43:56,040
Speaker 1: the toxin could be passed to a new strain of cholera,

840
00:43:56,160 --> 00:43:59,680
Speaker 1: and that's the next pandemic. So you need constant surveillance

841
00:43:59,719 --> 00:44:01,600
Speaker 1: to try to understand this stuff, which is why it's

842
00:44:01,640 --> 00:44:05,600
Speaker 1: really important that we fund organizations like the World Health Organization,

843
00:44:06,239 --> 00:44:08,040
Speaker 1: which the United States pulled out of.

844
00:44:08,600 --> 00:44:11,400
Speaker 2: And so who does this research? I mean, doesn't sound

845
00:44:11,520 --> 00:44:15,240
Speaker 2: like there's a lot of money in cholera vaccines since

846
00:44:15,320 --> 00:44:18,719
Speaker 2: the places where color is endemic tend to be poorer countries.

847
00:44:19,120 --> 00:44:21,239
Speaker 2: You don't have a whole lot of cholera happening to

848
00:44:21,320 --> 00:44:24,760
Speaker 2: like US senators for example. And so who is funding

849
00:44:24,800 --> 00:44:25,400
Speaker 2: this research?

850
00:44:25,400 --> 00:44:28,880
Speaker 1: If anybody, cholera research is funded by you know, the

851
00:44:28,920 --> 00:44:32,239
Speaker 1: World Health Organization wants there to be cholera vaccines. There's

852
00:44:32,320 --> 00:44:36,640
Speaker 1: money from government organizations like the National Institute of Health.

853
00:44:36,680 --> 00:44:40,200
Speaker 1: There's I think there's US companies that make color of

854
00:44:40,280 --> 00:44:43,279
Speaker 1: vaccines to sell to you know, tourists in the US

855
00:44:43,320 --> 00:44:46,440
Speaker 1: who want to go and you know, there's lots of

856
00:44:46,480 --> 00:44:49,440
Speaker 1: people living in areas where color is endemics. So if

857
00:44:49,440 --> 00:44:52,200
Speaker 1: you could sell the vaccine, you know, you can probably

858
00:44:52,200 --> 00:44:53,880
Speaker 1: make some money, although you probably can't sell it for

859
00:44:53,920 --> 00:44:58,040
Speaker 1: too much. There's philanthropic organizations and government organizations funding this

860
00:44:58,120 --> 00:44:58,800
Speaker 1: kind of research.

861
00:44:59,120 --> 00:45:01,840
Speaker 2: Yeah, not everyth happens from a profit mode of y'all.

862
00:45:02,120 --> 00:45:05,800
Speaker 1: Yes, that's right. This research is super important. The seventh

863
00:45:05,880 --> 00:45:08,400
Speaker 1: cholera pandemic, as we said in the last episode, is

864
00:45:08,480 --> 00:45:12,880
Speaker 1: still happening right now. The next cholera pandemic could start

865
00:45:12,920 --> 00:45:15,879
Speaker 1: at any time. Cholera pandemics can overlap. If a new

866
00:45:15,920 --> 00:45:19,000
Speaker 1: strain pops up and starts spreading around the world, seven

867
00:45:19,040 --> 00:45:20,759
Speaker 1: and eight could be happening at the same time.

868
00:45:21,520 --> 00:45:24,880
Speaker 2: And I'm grateful that there's continued funding for research into

869
00:45:25,040 --> 00:45:29,640
Speaker 2: technological developments in advanced bidets. As I traveled around Japan,

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00:45:29,680 --> 00:45:32,080
Speaker 2: I discovered, ooh, some of these have music. Ooh, this

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00:45:32,120 --> 00:45:35,319
Speaker 2: one has a strong deodorizer button you can press. What

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00:45:35,360 --> 00:45:35,840
Speaker 2: does that do?

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00:45:37,360 --> 00:45:41,759
Speaker 1: Okay? All right? I'm grateful for good sanitation systems, and

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00:45:41,920 --> 00:45:45,359
Speaker 1: i am grateful to organizations that are trying to bring

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00:45:45,520 --> 00:45:49,200
Speaker 1: good sanitation systems to communities that don't have them yet,

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00:45:49,600 --> 00:45:54,080
Speaker 1: because that you know, vaccines are great, but sanitation systems

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00:45:54,080 --> 00:45:56,920
Speaker 1: that keep people from getting poop in their water, yes,

878
00:45:57,320 --> 00:45:59,680
Speaker 1: is probably a better long term solution.

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Speaker 2: You're so much more wholesome than i am, Kelly.

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00:46:04,160 --> 00:46:06,560
Speaker 1: I'm glad that the day is bringing you so much joy.

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00:46:07,360 --> 00:46:09,680
Speaker 2: Hey, it's the small pleasures in life, that's right. Anyway,

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Speaker 2: Today it's been a great pleasure learning about colera. Thank you,

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00:46:12,200 --> 00:46:16,040
Speaker 2: Kelly for this deep dive into the experience of calera,

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00:46:16,320 --> 00:46:18,600
Speaker 2: how we treated it, and how we continue.

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00:46:18,160 --> 00:46:28,319
Speaker 1: To Thanks for listening. Daniel and Kelly's Extraordinary Universe is

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00:46:28,360 --> 00:46:31,400
Speaker 1: produced by iHeartRadio. We would love to hear from you,

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00:46:31,640 --> 00:46:32,680
Speaker 1: We really would.

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00:46:32,840 --> 00:46:35,560
Speaker 2: We want to know what questions you have about this

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00:46:35,760 --> 00:46:37,440
Speaker 2: Extraordinary Universe.

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Speaker 1: back to you.

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00:46:44,200 --> 00:46:47,719
Speaker 2: We really mean it. We answer every message. Email us

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00:46:47,760 --> 00:46:50,840
Speaker 2: at Questions at Danielandkelly dot org, or.

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00:46:50,840 --> 00:46:52,960
Speaker 1: You can find us on social media. We have accounts

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Speaker 1: on x Instagram, Blue Sky, and on all of those platforms.

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Speaker 1: You can find us at D and Kuniverse.

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