WEBVTT - How cholera kills you and how we kill it 0:00:07.760 --> 0:00:11.119 How the extraordinaries. In a prior episode, we took a 0:00:11.360 --> 0:00:14.960 historic look at cholera, and just like before, you should 0:00:15.040 --> 0:00:18.400 keep in mind that cholera is a pretty awful disease, 0:00:18.920 --> 0:00:23.360 so we'll be discussing both disturbing symptoms and death. But 0:00:23.440 --> 0:00:26.760 today we're taking a more modern approach. We'll talk about 0:00:26.800 --> 0:00:30.920 what we've learned about how vibrio cholera goes about inducing 0:00:31.040 --> 0:00:35.160 catastrophic diarrhea, where these bacteria can be found when they're 0:00:35.159 --> 0:00:38.559 not wreaking havoc upon our intestines, and the methods we 0:00:38.680 --> 0:00:42.640 use to treat cholera. We'll also take a short foray 0:00:42.760 --> 0:00:47.120 through the colossally bad ideas we've had for treating cholera, 0:00:47.280 --> 0:00:52.400 because wow, we've tried out some really bad ideas. Welcome 0:00:52.600 --> 0:00:54.960 to Daniel and Kelly's Extraordinary Universe. 0:01:08.200 --> 0:01:11.760 Hi Daniel, I'm a particle physicist and I just installed 0:01:11.840 --> 0:01:13.880 bedezs and every toilet in my house. 0:01:14.480 --> 0:01:14.800 Hello. 0:01:14.880 --> 0:01:20.680 I'm Kelly Waiter Smith. I Uh, I feel like I 0:01:20.680 --> 0:01:21.720 didn't need to know that. 0:01:21.720 --> 0:01:24.520 Starting with the toilet and information at the very top. 0:01:24.600 --> 0:01:26.559 I don't feel like I needed to know that about your. 0:01:26.480 --> 0:01:28.120 Are we talking about diarrhea today? 0:01:28.680 --> 0:01:29.000 Sure? 0:01:29.240 --> 0:01:32.160 But that doesn't have to be connected to beidets. I 0:01:32.280 --> 0:01:35.160 encountered my first bidet when I lived in Davis, California, 0:01:35.200 --> 0:01:37.360 and I went to a sushi restaurant and I was like, 0:01:37.680 --> 0:01:42.039 what is this my Why do toilets need buttons? And 0:01:42.080 --> 0:01:45.839 then I was like, I pushed a button. I was like, whoa, whoa, 0:01:46.400 --> 0:01:48.160 And I don't know that I need a bidet in 0:01:48.200 --> 0:01:48.600 my house. 0:01:48.880 --> 0:01:51.120 I see, well, I just came back from two weeks 0:01:51.160 --> 0:01:55.040 in Japan and Korea, and so I experienced toilets with 0:01:55.120 --> 0:01:58.680 control panels, and I pressed that button and I went, whoa, whoa. 0:02:01.520 --> 0:02:04.080 I gotta say, this makes me wish we had we 0:02:04.080 --> 0:02:06.720 were releasing videos so that people can see the face 0:02:07.280 --> 0:02:09.120 that you made. Although maybe it's better we don't. 0:02:09.639 --> 0:02:12.800 No, yeah, exactly, everybody makes that face in private in 0:02:12.840 --> 0:02:14.960 the bidet, you know. And it turns out it's actually 0:02:15.000 --> 0:02:17.800 quite easy to turn your toilet into a bidet. 0:02:18.120 --> 0:02:20.440 Wow. Is the water heated or is it cold? 0:02:21.440 --> 0:02:24.240 Yes? Nice warm, toasty water, yes, exactly. 0:02:24.680 --> 0:02:26.880 Okay, So actually it was your trip to Asia that 0:02:26.960 --> 0:02:30.519 made you come home and add bidets to all your Okay, Yeah. 0:02:30.360 --> 0:02:32.800 I was like, wow, we are still using a very 0:02:32.919 --> 0:02:36.079 archaic form of this technology, it can be made much 0:02:36.080 --> 0:02:38.600 more pleasant. Why don't we do that? Oh my gosh, 0:02:38.680 --> 0:02:40.680 it's like eighty dollars, let's do it. 0:02:41.120 --> 0:02:43.679 Man. You know there are some people who are all like, man, 0:02:43.720 --> 0:02:48.560 it's a shame that cultures are homogenizing, and you're all like, no, 0:02:48.720 --> 0:02:51.639 this is great. We should be taking stuff from Asian cultures. 0:02:51.639 --> 0:02:54.200 We should be given stuff to them. They've got McDonald's. 0:02:54.200 --> 0:02:55.280 Why don't we have bidets? 0:02:55.639 --> 0:02:58.560 Yeah, I mean ask yourself this question. If you got 0:02:58.560 --> 0:03:01.000 peanut butter on a shag car, but would you just 0:03:01.040 --> 0:03:02.320 wipe it up with a piece of paper? 0:03:07.320 --> 0:03:08.600 No? No, I would. 0:03:08.880 --> 0:03:11.839 Well, Okay, there you go, there you go. I think 0:03:11.840 --> 0:03:13.519 we know the relevance of that example. 0:03:14.040 --> 0:03:16.440 Yes, we do. Thank you for choosing peanut butter and 0:03:16.680 --> 0:03:19.520 rooting peanut butter for me. I think it's time we 0:03:19.560 --> 0:03:20.560 move on, all. 0:03:20.520 --> 0:03:22.880 Right, and don't think about me next time you're having 0:03:22.880 --> 0:03:23.399 peanut butter. 0:03:24.040 --> 0:03:28.520 Thanks Daniel. Thanks all right. So in the last episode, 0:03:28.880 --> 0:03:31.760 we talked about the work that John Snow did to 0:03:31.800 --> 0:03:36.400 help us understand how cholera gets to people the fecal 0:03:36.720 --> 0:03:41.680 oral route passing through water into our mouths unfortunately, and 0:03:41.680 --> 0:03:43.480 today we're going to talk a little bit about the 0:03:43.520 --> 0:03:45.800 science that has been done in the one hundred plus 0:03:45.880 --> 0:03:49.240 years since to help us better understand what cholera is 0:03:49.280 --> 0:03:52.080 doing to our bodies and help us to treat people 0:03:52.160 --> 0:03:55.040 who have encountered the bacteria that causes cholera so that 0:03:55.040 --> 0:03:56.760 we can save their lives exactly. 0:03:56.840 --> 0:03:58.560 And so it's going to be a whole episode full 0:03:58.600 --> 0:03:59.960 of too much information. 0:04:00.520 --> 0:04:05.160 That is my specialty. Okay, So before we really dig in, 0:04:05.240 --> 0:04:08.000 I want to remind everybody that in the last Cholera 0:04:08.080 --> 0:04:11.280 episode I mentioned that we're actually in the middle of 0:04:11.320 --> 0:04:15.480 an ongoing cholera pandemic. And my sense is that most 0:04:15.520 --> 0:04:18.520 of us don't realize that because we're lucky enough to 0:04:18.839 --> 0:04:21.359 not have to hear about or deal with cholera on 0:04:21.400 --> 0:04:25.560 a daily basis. So I asked the extraordinaries, when did 0:04:25.640 --> 0:04:29.680 the most recent cholera pandemic, that is, the seventh cholera 0:04:29.800 --> 0:04:35.200 pandemic end? So let's go ahead and hear their answers. 0:04:35.760 --> 0:04:40.880 Cholera pandemic. I have no idea, Sorry, no answer, Kelly, 0:04:41.240 --> 0:04:45.360 I never heard of cholera pandemics. Please educate me on that. 0:04:46.080 --> 0:04:48.599 HI A bit of a guess, but I would reckon. 0:04:48.640 --> 0:04:54.200 The most recent cholera academic probably ended in the nineteen thirties, 0:04:54.480 --> 0:04:58.000 sometime after the end of the First World War. I 0:04:58.000 --> 0:05:01.000 don't remember any cholera event, so I'm going to say 0:05:01.040 --> 0:05:05.599 before I was born it ended nineteen sixty eight. 0:05:06.040 --> 0:05:08.839 If you asked like that, I would say it's ongoing. 0:05:09.040 --> 0:05:10.680 But I really don't have any idea. 0:05:11.200 --> 0:05:13.719 Just guessing here. In the nineteen twenties. 0:05:13.880 --> 0:05:18.679 Colera pandemic, and there's been several I have no idea 0:05:18.720 --> 0:05:20.520 when it ended, but I sure hope it was a 0:05:20.520 --> 0:05:23.440 while ago and that there are few possibilities of it 0:05:23.520 --> 0:05:27.680 coming back. But given the show, I'm a little bit concerned. 0:05:27.920 --> 0:05:30.320 Since there are still many parts in the world with 0:05:30.600 --> 0:05:35.680 questionable sanitization, I would guess like last year. Maybe my 0:05:35.760 --> 0:05:39.400 wild guess here is that the most recent cholera pandemic 0:05:39.600 --> 0:05:40.440 is still happening. 0:05:42.360 --> 0:05:45.640 I have no idea. I don't even know when it started. 0:05:46.240 --> 0:05:48.240 Maybe it hasn't ended yet. 0:05:48.560 --> 0:05:51.320 When did the most recent colera pandemic? And I don't know, 0:05:51.440 --> 0:05:53.440 but I think maybe it ended when they learned to 0:05:53.480 --> 0:05:55.799 treat the water that was causing a color. 0:05:56.200 --> 0:05:58.760 I don't know, but probably much more recently than one 0:05:58.760 --> 0:06:01.279 would guess maybe in the nineteen sixties. 0:06:01.720 --> 0:06:06.080 Okay, So as we sort of suspected not a lot 0:06:06.120 --> 0:06:08.360 of awareness that we're in the middle of a cholera 0:06:08.440 --> 0:06:11.440 pandemic because it's not really part of our lives if 0:06:11.480 --> 0:06:13.359 you happen to be living in a place, you know, 0:06:13.520 --> 0:06:15.200 like the United States, for example. 0:06:15.400 --> 0:06:18.960 So remind us Kelly, cholera. It's a virus, it's a bacteria, 0:06:19.279 --> 0:06:21.120 it's a pathogen. What is it? 0:06:21.120 --> 0:06:23.960 It is a bacteria. And so it is a bacteria 0:06:24.120 --> 0:06:27.680 that gets into the water. And for you to get cholera, 0:06:28.040 --> 0:06:31.440 you need to ingest a lot of it. So if 0:06:31.480 --> 0:06:35.600 you just sow, something like a million or maybe one 0:06:35.720 --> 0:06:38.760 hundred million need to be ingested for you to get sick, 0:06:39.000 --> 0:06:40.480 and Daniel. 0:06:40.480 --> 0:06:42.719 One hundred million, one hundred. 0:06:42.480 --> 0:06:45.440 Million, And so you might think, how would you accidentally 0:06:45.600 --> 0:06:48.520 ingest one hundred million cholera bacteria? Right? 0:06:48.680 --> 0:06:51.000 Is that like ten liters of cholera leased water. 0:06:51.240 --> 0:06:53.719 Now it turns out that in like a regular cup 0:06:53.800 --> 0:06:56.039 of water, you could have something like two hundred million 0:06:56.080 --> 0:06:58.880 cholera bacteria and you probably wouldn't detect them in there 0:06:58.920 --> 0:07:02.000 because they're pretty tiny and the glass like wouldn't look cloudy. 0:07:02.080 --> 0:07:04.120 So you probably wouldn't know, but if you. 0:07:04.040 --> 0:07:06.120 Put them under a microscope, you could probably see them. 0:07:06.200 --> 0:07:08.480 Or yeah, yeah, but you know, how often do you 0:07:08.480 --> 0:07:09.840 put your water under a microscope? 0:07:10.200 --> 0:07:12.960 Yeah? Never, never from now on? Always but never. 0:07:15.400 --> 0:07:17.920 All right, But so Daniel, like, you know, a million 0:07:17.960 --> 0:07:20.320 to one hundred million before you get sick. How do 0:07:20.360 --> 0:07:21.160 you think we know that? 0:07:22.160 --> 0:07:24.960 Because people tried it on themselves, not. 0:07:24.960 --> 0:07:29.960 Tried it on themselves, but tried it on prisoners. But 0:07:30.040 --> 0:07:34.560 the prisoners they signed consent forms. And so this was 0:07:34.800 --> 0:07:37.600 the experiment that I read was done on a prison 0:07:37.640 --> 0:07:41.120 population in Maryland, and they signed consent forms and they 0:07:41.200 --> 0:07:44.040 were told that they could stop the experiment at any time, 0:07:44.240 --> 0:07:46.800 and they were very carefully watched by physicians, and as 0:07:46.840 --> 0:07:49.280 soon as they started to show symptoms, they were you know, 0:07:49.360 --> 0:07:51.560 brought into an environment where they were treated very carefully 0:07:51.600 --> 0:07:53.360 and they were watched very carefully. This was done in 0:07:53.400 --> 0:07:54.080 the seventies. 0:07:54.280 --> 0:07:56.960 Wow, would that pass modern day i RB standards? 0:07:57.320 --> 0:08:01.120 So we actually do continue to infect people with cholera today, 0:08:01.120 --> 0:08:03.119 and we're going to talk about that later. 0:08:03.360 --> 0:08:05.840 Yeah, don't we know enough? We're still doing this to people. 0:08:06.000 --> 0:08:08.680 We are still doing this to people. Wow, hold your 0:08:08.720 --> 0:08:11.840 breath hold your cheeks. We're still gonna be talking about 0:08:11.840 --> 0:08:12.320 this later. 0:08:12.400 --> 0:08:15.400 So I just hope those poor people have access to 0:08:15.440 --> 0:08:19.160 a bidet. Yeah, yeah, so they can feel clean and 0:08:19.200 --> 0:08:20.040 fresh after. 0:08:19.880 --> 0:08:22.280 Work, I guess in that. Yeah, I'm behind bidets in 0:08:22.320 --> 0:08:25.600 that situation, all right, Yeah, yeah, you're getting me on 0:08:25.640 --> 0:08:29.320 the same page. I guess so. But another thing that 0:08:29.360 --> 0:08:32.120 we learned from these this prison population is that actually 0:08:32.200 --> 0:08:36.720 it turns out cholera is really susceptible to acid. So like, 0:08:36.960 --> 0:08:40.120 if your stomach is particularly acidic at the moment, the 0:08:40.240 --> 0:08:43.080 cholera bacteria are much more likely to die. So even 0:08:43.120 --> 0:08:46.200 if you ingest something like one hundred million bacteria and 0:08:46.240 --> 0:08:49.880 your stomach is having like a particularly acidic day, you 0:08:50.000 --> 0:08:51.000 might not get cholera. 0:08:51.320 --> 0:08:54.640 Wow. So cholera is a bacteria. You got ingested billions 0:08:54.720 --> 0:08:56.480 of them. A lot of them die in your stomach. 0:08:56.800 --> 0:08:58.600 Where do they end up setting up camp? 0:08:58.840 --> 0:09:01.600 The small intestine? And I'll note now that when we 0:09:01.640 --> 0:09:04.880 do experiments with people to try to study cholera, we 0:09:04.960 --> 0:09:08.320 give them something that makes their stomach a more basic environment. 0:09:08.400 --> 0:09:10.960 So maybe you'll take some like sodium bicarbonate along with 0:09:11.000 --> 0:09:14.240 your cholera bacteria. Wow, so you ingest a bunch of them, 0:09:14.480 --> 0:09:17.679 and then they go through your stomach. Some of them survive, 0:09:17.840 --> 0:09:20.520 and then they get to your small intestine. The color 0:09:20.559 --> 0:09:23.560 of bacteria have a flagella, and so this is like 0:09:23.600 --> 0:09:27.440 a really long whip like appendage, and they use that 0:09:27.480 --> 0:09:30.800 flagella to try to get through the mucus that lines 0:09:30.840 --> 0:09:34.199 your small intestine. And so they like run into your 0:09:34.280 --> 0:09:37.439 mucus and they start shaking their butts and they're trying 0:09:37.440 --> 0:09:39.480 to get through the mucus so that they can get 0:09:39.520 --> 0:09:41.599 to the cells that line your intestine. 0:09:41.720 --> 0:09:44.200 But I thought the flagellum is like a propeller. You 0:09:44.200 --> 0:09:46.360 have it at the back to push you somewhere, like 0:09:46.440 --> 0:09:48.760 you know, like the motor on a boat, but here 0:09:48.760 --> 0:09:50.640 they're sort of like backing in. They're using it like 0:09:50.679 --> 0:09:51.079 a drill. 0:09:51.440 --> 0:09:54.679 No no, so they sorry, they run in headfirst. Oh yeah, 0:09:54.679 --> 0:09:56.760 and then they're using it to try to like corkscrew 0:09:56.800 --> 0:09:57.240 their way in. 0:09:57.360 --> 0:09:57.599 Got it. 0:09:57.720 --> 0:10:00.400 Yeah, Okay, So they keep going until they hit the 0:10:00.480 --> 0:10:04.680 cells of your intestine. And once they hit those epithelial cells, 0:10:05.080 --> 0:10:07.680 they sort of like cement themselves down and they start 0:10:07.679 --> 0:10:10.280 to replicate. And so now they've got these little batches 0:10:10.280 --> 0:10:13.360 that are replicating and they start producing. 0:10:12.880 --> 0:10:15.760 A toxin, and so they somehow know where to go, 0:10:16.040 --> 0:10:18.240 like they are looking for this. They're not just swimming 0:10:18.240 --> 0:10:20.160 in all random directions and the ones that end up 0:10:20.200 --> 0:10:22.720 there set up camp. They're like all heading in that direction. 0:10:23.080 --> 0:10:24.640 They are all heading in that direction. 0:10:24.760 --> 0:10:26.840 Wow, that's a little creepy. 0:10:27.040 --> 0:10:29.640 It is creepy. Yeah, Bacteria and viruses and things that 0:10:29.679 --> 0:10:34.040 we might think of as not being very smart can 0:10:34.080 --> 0:10:35.480 do pretty smart things. 0:10:35.640 --> 0:10:38.239 They seem more like aware of the environment that I imagined. 0:10:38.760 --> 0:10:40.800 Very cool. So then they start to replicate. 0:10:41.000 --> 0:10:44.040 Yeah, so then they start to replicate, and while they're replicating, 0:10:44.080 --> 0:10:47.400 they start producing a toxin. And this toxin is what 0:10:47.520 --> 0:10:51.320 is massively the problem for cholera se. So this toxin 0:10:51.880 --> 0:10:54.760 finds a way of like binding with your intestinal cells 0:10:54.760 --> 0:10:58.600 and it gets taken up by your intestinal cells, and 0:10:58.640 --> 0:11:02.000 when it's inside your intestine cells, it messes with your 0:11:02.000 --> 0:11:04.160 cells and it starts to mess with your what we 0:11:04.200 --> 0:11:07.040 call asmotic balance. But essentially, the way your body makes 0:11:07.040 --> 0:11:10.360 sure that you are extracting water from the small intestine 0:11:10.440 --> 0:11:14.680 to go into your body is by having different concentrations 0:11:14.720 --> 0:11:17.559 of ions on either side of the inside of your 0:11:17.559 --> 0:11:18.880 intestine and in your body. 0:11:19.000 --> 0:11:22.560 So without getting too much into the chemistry, essentially you 0:11:22.559 --> 0:11:25.200 want the water passing through the small intestines to be 0:11:25.320 --> 0:11:28.560 less salty than the water in your body, so that 0:11:28.960 --> 0:11:31.960 it then comes into your body to balance the salinity. Right, 0:11:32.080 --> 0:11:32.959 isn't that the way it works? 0:11:33.040 --> 0:11:36.040 Yep, that's exactly right. But then after this toxin gets 0:11:36.080 --> 0:11:39.680 taken up by your body, that changes, and now your 0:11:39.840 --> 0:11:42.960 intestine is saltier and the water in your body starts 0:11:42.960 --> 0:11:46.800 getting dumped into your intestine and you start losing massive 0:11:46.800 --> 0:11:49.200 amounts of water from your body, like we talked about 0:11:49.440 --> 0:11:50.560 in the last episode. 0:11:50.640 --> 0:11:54.160 And is this good somehow for the cholorobacteria. Are they 0:11:54.200 --> 0:11:56.959 doing this in order to affect something which is positive 0:11:56.960 --> 0:11:59.600 for them, or so that you'll have massive diarrhea which 0:11:59.640 --> 0:12:02.920 spreads them or is this just like a random accidental 0:12:02.960 --> 0:12:04.640 byproduct that they don't even care about. 0:12:04.720 --> 0:12:07.080 So once you start losing this massive amounts of water, 0:12:07.200 --> 0:12:10.439 the bacteria that have been replicating like crazy release themselves 0:12:10.440 --> 0:12:14.240 from the outside of the cells and they get back 0:12:14.280 --> 0:12:17.319 into the environments. And so in this way they managed 0:12:17.360 --> 0:12:19.160 to get back out so they can go off and 0:12:19.160 --> 0:12:20.880 infect someone else I see. 0:12:20.880 --> 0:12:22.600 So it's definitely a part of their cycle. It's not 0:12:22.679 --> 0:12:23.880 just an incidental thing. 0:12:24.200 --> 0:12:27.800 It is easy to imagine how it could benefit the bacteria. 0:12:27.920 --> 0:12:30.720 So I do think it seems to be a beneficial. 0:12:30.160 --> 0:12:32.880 Thing that makes me feel better somehow, because if our 0:12:33.000 --> 0:12:35.960 suffering and death was just like, well, we don't even 0:12:35.960 --> 0:12:38.840 really care and we're accidentally doing this thing that kills you, 0:12:39.280 --> 0:12:41.079 that would feel more tragic somehow. 0:12:41.400 --> 0:12:43.640 Yeah, I guess, So I guess if no one's benefiting 0:12:43.720 --> 0:12:48.640 from it, but I guess I don't. Maybe. But Okay, 0:12:48.640 --> 0:12:51.360 so here's something that kind of blew my mind. And 0:12:51.440 --> 0:12:54.080 maybe you already know this, given who you're married to, 0:12:54.160 --> 0:12:56.640 and maybe I've just given away the punchline by saying that. 0:12:57.000 --> 0:13:00.280 But these genes that produce the toxin, I want to 0:13:00.280 --> 0:13:03.560 guess where they came from Mars Mars. 0:13:03.640 --> 0:13:05.840 Wait wait, no, eight, there was a Katrina related clue here, 0:13:06.000 --> 0:13:08.760 So it's gotta be a virus. Is it a virus? 0:13:08.840 --> 0:13:13.400 It's a bacteria phage. Yeah, that's right, that's where well, 0:13:13.440 --> 0:13:15.800 and you probably read the outline. So it looks like 0:13:15.840 --> 0:13:20.079 there were two different bacteria phages that infected Vibrio cholera. 0:13:20.120 --> 0:13:23.320 At some point. One of those bacteria phages I believe 0:13:23.400 --> 0:13:27.120 gave the bacteria the ability to cling to the outside 0:13:27.120 --> 0:13:29.280 of the intestinal cells so that they could like form 0:13:29.320 --> 0:13:33.040 those mats and start replicating, and the other one gives 0:13:33.040 --> 0:13:36.560 them the ability to make these toxins. And so without 0:13:36.640 --> 0:13:41.200 this bacteria phage, Vibrio cholera would not be this like 0:13:41.360 --> 0:13:43.920 human scourge that And did you catch that? I said 0:13:43.920 --> 0:13:46.840 scourge right? I didn't say it right in the smallpox episode, 0:13:46.840 --> 0:13:49.880 but I learn when the listeners write in lots of 0:13:49.880 --> 0:13:52.079 emails about how I'm not pronouncing things right. 0:13:52.880 --> 0:13:56.920 Gold star for Kelly makes everyone. But that's amazing that 0:13:56.960 --> 0:14:00.079 this is virus power and it's like virus engineered. But 0:14:00.160 --> 0:14:02.480 for those of you who don't remember, a lot of DNA, 0:14:02.559 --> 0:14:07.160 including human DNA, is affected by viruses. Viral infections in 0:14:07.520 --> 0:14:10.679 years past have altered our DNA, and some of our 0:14:10.760 --> 0:14:14.839 essential functions come from DNA that essentially was injected into 0:14:14.880 --> 0:14:17.840 the record by viruses, and that's true also for bacteria. 0:14:17.840 --> 0:14:18.520 It's incredible. 0:14:18.720 --> 0:14:20.480 It is incredible. But okay, so I feel like this 0:14:20.520 --> 0:14:25.360 begs the question what was Vibrio cholera doing before these 0:14:25.440 --> 0:14:28.240 viruses came along? And it turns out that this question 0:14:28.400 --> 0:14:30.640 is really important for trying to figure out how you 0:14:30.680 --> 0:14:35.240 can control cholera around the world, and it's also important 0:14:35.240 --> 0:14:37.680 for trying to understand what colera is doing when it's 0:14:37.720 --> 0:14:39.960 not in our body right. And so the answer is 0:14:40.000 --> 0:14:43.600 that Vibrio cholera is a bacteria that you find in 0:14:43.680 --> 0:14:47.600 aquatic ecosystems like all over the world. This is just 0:14:47.760 --> 0:14:52.760 an aquatic bacteria that you find living on zoplankton, like copapods, 0:14:52.840 --> 0:14:56.160 you find it living on like aquatic plants. This is 0:14:56.280 --> 0:14:59.720 just an aquatic bacteria that is totally happy outside of 0:14:59.760 --> 0:15:03.320 our bodies, living in aquatic ecosystems. You find it in 0:15:03.400 --> 0:15:06.840 the Gulf Coast, you can find it in Lake Erie, 0:15:06.920 --> 0:15:09.560 you can find it in the Ganges. It's just a 0:15:09.600 --> 0:15:12.200 happy bacteria out there that every once in a while 0:15:12.880 --> 0:15:14.400 ends up in a human body. So it looks like 0:15:14.440 --> 0:15:17.400 there's lots of different strains of this bacteria. Some strains 0:15:17.400 --> 0:15:20.680 don't have these toxin genes, so if you swallowed one 0:15:20.760 --> 0:15:24.720 hundred million of them, nothing would happen. Other strains cause 0:15:24.880 --> 0:15:29.400 some like tummy issues, but nothing on the level of 0:15:29.480 --> 0:15:34.000 like cholera. But some of them cause pandemic cholera. And 0:15:34.040 --> 0:15:37.360 so like there's lots of different Wow kinds of Fibrio 0:15:37.480 --> 0:15:39.920 cholera that differ in how bad they are for us, 0:15:40.240 --> 0:15:42.000 but you know they're out in our waterways. 0:15:42.440 --> 0:15:46.520 So these were basically weaponized by these viruses. So the 0:15:46.560 --> 0:15:50.440 story isn't this cholera infects you and uses you to 0:15:50.480 --> 0:15:53.480 make more of it. It's this virus took over this 0:15:53.560 --> 0:15:57.080 bacteria and instructed this bacteria to infect you to make 0:15:57.160 --> 0:15:59.720 more of the bacteria, which in effect is making more 0:15:59.800 --> 0:16:01.720 of the original virus DNA. 0:16:02.040 --> 0:16:04.200 Yeah, I mean that sounds a bit more directed than 0:16:04.240 --> 0:16:06.479 it probably, you know, actually. 0:16:06.240 --> 0:16:07.600 Was I just wanted to make it sound like a 0:16:07.640 --> 0:16:10.720 conspiracy theory so we can climb up the podcast charts. 0:16:10.880 --> 0:16:13.440 Oh not, yes, okay, that I agree. That is exactly 0:16:13.440 --> 0:16:16.280 what happened, Daniel. This bacteria phage was out to get us, 0:16:16.280 --> 0:16:19.320 and through Vibrio cholera, it has achieved its goal. 0:16:19.760 --> 0:16:22.000 Probably was engineered by the CIA, wasn't it. 0:16:22.600 --> 0:16:25.640 Yeah? No, I know, right, like, yeah, the exploding cigars 0:16:25.640 --> 0:16:28.040 for Castro didn't work, and so they were like, let's 0:16:28.040 --> 0:16:29.320 go after a Vibrio cholera. 0:16:29.800 --> 0:16:34.960 So no, I don't think a CIA is pulling the strings. 0:16:35.000 --> 0:16:37.840 I think it probably is. Virus viruses control the world. 0:16:38.120 --> 0:16:41.720 Yeah, yeah, well, so I think we don't really understand 0:16:41.800 --> 0:16:44.720 what the bacteria phage was doing with this toxin before 0:16:44.760 --> 0:16:47.080 it got into the bacteria or you know, so we 0:16:47.080 --> 0:16:49.840 don't really understand all of the steps and why they happened. 0:16:50.120 --> 0:16:52.480 But we're you know, we're working on trying to understand that. 0:16:52.840 --> 0:16:55.920 But it does appear that, yes, this bacteria phage is 0:16:55.960 --> 0:16:59.920 what essentially gave cholera the ability to be this whole 0:17:00.320 --> 0:17:03.200 scourge upon humanity. And here we are, all. 0:17:03.160 --> 0:17:06.000 Right, So I ingest like a cup of fluid with 0:17:06.080 --> 0:17:09.000 like one hundred million collar bacteria in it, and then 0:17:09.040 --> 0:17:12.080 they colonize my lower intestine. They make lots more of themselves? 0:17:12.400 --> 0:17:15.000 How many come out the other end? Like I'm a 0:17:15.080 --> 0:17:17.760 color of factory. Now, how big a multiplier am I? 0:17:18.280 --> 0:17:22.240 You could produce like a trillion cholera bacteria with a 0:17:22.280 --> 0:17:26.080 tea with a t yep, and you can release something 0:17:26.119 --> 0:17:29.240 like twenty liters of fluid with about of cholera. I know, 0:17:29.320 --> 0:17:31.959 just an incredible about flu Yes, flu Well, I mean 0:17:32.000 --> 0:17:33.680 you're vomiting also, so the. 0:17:33.680 --> 0:17:36.760 Fluid smelling rice filled fluid, right. 0:17:36.680 --> 0:17:39.960 Yep, yep, it's pretty unpleasant. And so you know, so 0:17:40.040 --> 0:17:43.199 you can see how this is a great route for 0:17:43.440 --> 0:17:46.160 cholera to reproduce itself and get back into the environment 0:17:46.240 --> 0:17:48.000 in large quantities. 0:17:48.280 --> 0:17:50.640 Wow, if I'm doing my math right, one hundred million 0:17:50.680 --> 0:17:53.360 to a tillion, that's a factor of ten thousand. So 0:17:53.440 --> 0:17:57.360 every individual can ten thousand x the cholera population. 0:17:57.880 --> 0:18:00.040 Yeah, but you know, if you have good sanitation and 0:18:00.200 --> 0:18:05.159 all of those fluids from either end end up in 0:18:05.200 --> 0:18:08.080 a good sanitation facility and they get treated appropriately, then 0:18:08.119 --> 0:18:10.560 it's a dead end. And so sanitation makes a huge 0:18:10.600 --> 0:18:13.359 difference here, so to me, like you know, good sewer 0:18:13.400 --> 0:18:16.320 systems are one of the most amazing things that humanity 0:18:16.320 --> 0:18:19.000 has ever done. And you might understand now why I 0:18:19.000 --> 0:18:23.440 don't get invited to a lot of parties, but I'm 0:18:23.560 --> 0:18:25.080 very excited about sewers. 0:18:25.440 --> 0:18:28.920 And so why do people die of cholera? The toxin itself? 0:18:29.000 --> 0:18:31.080 Does it do more than just make you put out 0:18:31.119 --> 0:18:33.679 twenty leaders or is it dumping twenty leaders of fluid? 0:18:33.680 --> 0:18:34.199 It kills you. 0:18:34.480 --> 0:18:37.120 It's dumping twenty leaders of fluid that kills you. That's 0:18:37.119 --> 0:18:39.040 all it's got to do. At that point, your blood 0:18:39.080 --> 0:18:41.679 becomes super thick, your organs shut down because you just 0:18:41.680 --> 0:18:43.639 can't get oxygen and stuff to all the places it 0:18:43.680 --> 0:18:45.960 needs to go, and you go into a coma and 0:18:46.000 --> 0:18:46.639 die usually. 0:18:46.800 --> 0:18:47.280 Yeah. 0:18:47.320 --> 0:18:51.120 Wow, all right, so now we know what the color 0:18:51.160 --> 0:18:53.560 of bacteria are doing. Let's take a break, and when 0:18:53.600 --> 0:18:56.360 we get back, let's start with the history of treatments 0:18:56.480 --> 0:19:00.240 and begin with some of the less good treatments we've 0:19:00.280 --> 0:19:02.119 tried throughout the history of time. 0:19:22.840 --> 0:19:24.919 All right, we're back, and we were talking about cholera, 0:19:25.040 --> 0:19:28.320 a disease that makes people produce twenty liters of fluid 0:19:28.480 --> 0:19:31.159 out the north and the south ends of the body 0:19:31.800 --> 0:19:32.680 on average. 0:19:32.960 --> 0:19:33.520 Ish. 0:19:33.600 --> 0:19:37.720 Yeah, and we've done a deep dive on the pandemics 0:19:37.800 --> 0:19:41.280 and now we understand the biochemistry of cholera, how it 0:19:41.320 --> 0:19:43.720 affects you. So let's talk about the good side of it, 0:19:43.840 --> 0:19:47.119 developing treatments. How did we start to make this better? 0:19:47.640 --> 0:19:49.720 Well, I'm going to start on the bad side of 0:19:49.720 --> 0:19:53.600 treatments first. So, well, I was reading about the history 0:19:53.640 --> 0:19:55.760 of cholera. There was this book that kept coming up 0:19:56.119 --> 0:20:00.880 and it was Cholera It Causes Symptoms, Pathology Treatment by 0:20:01.000 --> 0:20:05.160 Robert's Bartholow. And Bartholow was a physician in the United 0:20:05.200 --> 0:20:09.320 States who was a physician through two cholera pandemics, and 0:20:09.400 --> 0:20:11.760 people thought of him as an expert, and so I 0:20:11.800 --> 0:20:13.639 was like, okay, well let's read what the expert was 0:20:13.640 --> 0:20:16.159 saying in eighteen ninety three. And so when I got 0:20:16.200 --> 0:20:19.480 to the treatment section, I found myself saying out loud 0:20:19.560 --> 0:20:21.119 many times, oh. 0:20:21.080 --> 0:20:26.080 No, oh no, didn't. It wouldn't. 0:20:26.600 --> 0:20:31.320 So okay, So here's bad idea number one. Okay, okay, 0:20:31.400 --> 0:20:33.720 so quick background they knew at this point. So this 0:20:33.760 --> 0:20:37.159 is eighteen ninety three. So Roberts totally believed the cholera 0:20:37.280 --> 0:20:39.720