1 00:00:00,080 --> 00:00:02,800 Speaker 1: Howdy friends, Just a heads up that we're talking about 2 00:00:02,800 --> 00:00:06,279 Speaker 1: parasites again, and as you're probably aware of by now. 3 00:00:06,440 --> 00:00:07,680 Speaker 2: That can get pretty gross. 4 00:00:08,119 --> 00:00:10,360 Speaker 1: Also, it's kind of upsetting to hear about parasite life 5 00:00:10,400 --> 00:00:12,720 Speaker 1: cycles and the effects of parasites on our health. I 6 00:00:12,760 --> 00:00:15,200 Speaker 1: get that today we're going to be talking about malarias 7 00:00:15,280 --> 00:00:18,120 Speaker 1: just a semiasis and hookworm, So decide if those are 8 00:00:18,120 --> 00:00:19,840 Speaker 1: topics you are prepared. 9 00:00:19,480 --> 00:00:21,280 Speaker 2: To hear about. All Right, here we go. 10 00:00:29,320 --> 00:00:32,240 Speaker 1: According to the World Health Organization, in twenty twenty three, 11 00:00:32,400 --> 00:00:35,800 Speaker 1: about two hundred and sixty three million people were infected 12 00:00:35,840 --> 00:00:39,080 Speaker 1: by malaria, of which five hundred and ninety seven thousand 13 00:00:39,159 --> 00:00:42,440 Speaker 1: passed away from this disease. Most of these deaths happened 14 00:00:42,479 --> 00:00:45,600 Speaker 1: in Africa, in seventy six percent of the deaths or 15 00:00:45,720 --> 00:00:49,320 Speaker 1: children under five. You might remember from a past episode 16 00:00:49,479 --> 00:00:52,080 Speaker 1: that we were able to create a vaccine for smallpox, 17 00:00:52,440 --> 00:00:55,480 Speaker 1: and that that vaccine was used to wipe smallpox off 18 00:00:55,520 --> 00:00:59,200 Speaker 1: the face of the planet, saving humanity from this ancient scourge. 19 00:00:59,520 --> 00:01:01,920 Speaker 1: And yeah, thanks to all who wrote in. I pronounce 20 00:01:01,960 --> 00:01:05,200 Speaker 1: the word correctly. Now we also have vaccines for other 21 00:01:05,240 --> 00:01:11,880 Speaker 1: bacterial and viral infections like polio, chicken pox, human papilloma virus, COVID, nineteen, measles, mumps, 22 00:01:11,880 --> 00:01:15,720 Speaker 1: et cetera. With the exception of some tricky viruses like 23 00:01:16,000 --> 00:01:19,000 Speaker 1: HIV which hide in our immune cells, We've had a 24 00:01:19,000 --> 00:01:22,600 Speaker 1: lot of success making vaccines for viral and bacterial infections, 25 00:01:23,120 --> 00:01:26,160 Speaker 1: and we know that our immune systems attack big stuff 26 00:01:26,200 --> 00:01:28,920 Speaker 1: as well as the little stuff like bacteria and viruses. 27 00:01:29,560 --> 00:01:31,840 Speaker 1: In a past episode, we talked about how our immune 28 00:01:31,880 --> 00:01:37,000 Speaker 1: systems will attack entire organs following a transplant. So why 29 00:01:37,040 --> 00:01:39,360 Speaker 1: do our immune systems seem to do such a crummy 30 00:01:39,440 --> 00:01:43,520 Speaker 1: job of attacking parasites in our bodies, things like nematodes, 31 00:01:43,959 --> 00:01:46,240 Speaker 1: And why is it so hard to make vaccines to 32 00:01:46,280 --> 00:01:49,280 Speaker 1: give our immune system a leg up on these invaders. 33 00:01:50,000 --> 00:01:52,559 Speaker 1: We've been working on malaria vaccines for a really long time, 34 00:01:52,600 --> 00:01:56,280 Speaker 1: but only recently have two malaria vaccines become widely available 35 00:01:56,320 --> 00:01:59,880 Speaker 1: in areas in Africa where malaria is prevalent. That's good, 36 00:02:00,320 --> 00:02:02,440 Speaker 1: but why did it take so long? And why don't 37 00:02:02,480 --> 00:02:05,640 Speaker 1: we have a vaccine for hookworms yet? Remember hookworms, those 38 00:02:05,640 --> 00:02:07,600 Speaker 1: dirt worms we talked about a few months back. 39 00:02:07,840 --> 00:02:08,639 Speaker 2: Yeah, those guys. 40 00:02:09,120 --> 00:02:13,680 Speaker 1: There are many parasitic diseases that have proven stubbornly difficult 41 00:02:13,760 --> 00:02:16,359 Speaker 1: to control with vaccines, and so today we're going to 42 00:02:16,440 --> 00:02:20,440 Speaker 1: talk to doctor John Hawden, a molecular biologist and parasitologist 43 00:02:20,440 --> 00:02:23,440 Speaker 1: who's going to help us understand why it's so darn 44 00:02:23,520 --> 00:02:27,840 Speaker 1: hard to make vaccines against parasites. Welcome to Daniel and 45 00:02:27,919 --> 00:02:29,520 Speaker 1: Kelly's Extraordinary Universe. 46 00:02:42,840 --> 00:02:46,240 Speaker 3: Hi. I'm Daniel. I'm a particle physicist, and I'm excited 47 00:02:46,240 --> 00:02:48,959 Speaker 3: to be talking about all sorts of ikey invaders today. 48 00:02:49,320 --> 00:02:49,680 Speaker 2: Hello. 49 00:02:49,720 --> 00:02:52,040 Speaker 1: I'm Kelly wieder Smith, and I always love talking about 50 00:02:52,040 --> 00:02:55,160 Speaker 1: ikey invaders, although with all the required sensitivity for the 51 00:02:55,160 --> 00:02:57,639 Speaker 1: pain and suffering that these parasites cause. But anyway, I 52 00:02:57,639 --> 00:03:00,240 Speaker 1: study parasites and space, and today we're talking about my 53 00:03:00,320 --> 00:03:04,080 Speaker 1: first love, parasitology, your first love. 54 00:03:04,560 --> 00:03:08,600 Speaker 3: Something I love about science is how excited people get 55 00:03:08,639 --> 00:03:12,520 Speaker 3: about their finy, little, tiny little niche. You know, you're 56 00:03:12,560 --> 00:03:15,800 Speaker 3: going to meet somebody who's like amazed at the hairs 57 00:03:15,800 --> 00:03:19,240 Speaker 3: on spider's legs, or somebody else who like can't stop 58 00:03:19,280 --> 00:03:23,000 Speaker 3: thinking about how, you know, the mantle flows and how 59 00:03:23,080 --> 00:03:26,280 Speaker 3: rocks form, and like, these nerds get so excited about 60 00:03:26,320 --> 00:03:28,960 Speaker 3: their little niche. It's wonderful, right, that's why we know 61 00:03:29,040 --> 00:03:31,760 Speaker 3: so much about the universe and spider legs and rocks 62 00:03:31,800 --> 00:03:35,360 Speaker 3: and parasites because people get weirdly excited about stuff. 63 00:03:36,160 --> 00:03:39,440 Speaker 1: My friend Ashley Smythe refers to this as a limitless 64 00:03:39,520 --> 00:03:42,680 Speaker 1: human curiosity. Yes, because I was asking her about like, oh, 65 00:03:42,680 --> 00:03:45,800 Speaker 1: why do parasitologists sometimes infect themselves with the parasites that 66 00:03:45,840 --> 00:03:48,440 Speaker 1: they study? Isn't it weird that we do that? And 67 00:03:48,480 --> 00:03:51,960 Speaker 1: she was like, Kelly, that's our limitless human curiosity. 68 00:03:52,280 --> 00:03:55,920 Speaker 3: And I was like, Okay, I totally love that about humanity. 69 00:03:55,920 --> 00:03:59,520 Speaker 3: I mean, curiosity is something deep about being human. Actually, 70 00:03:59,520 --> 00:04:01,760 Speaker 3: I wonder if it is just about being human, or 71 00:04:01,840 --> 00:04:04,320 Speaker 3: if you know, aliens are curious about the universe also, 72 00:04:04,400 --> 00:04:08,240 Speaker 3: if that's something that really is universal. But today, unfortunately, 73 00:04:08,280 --> 00:04:11,360 Speaker 3: we're not talking about aliens. We're talking about critters so 74 00:04:11,560 --> 00:04:14,120 Speaker 3: gross that invade you that it almost feels like they 75 00:04:14,160 --> 00:04:14,960 Speaker 3: are alien. 76 00:04:15,320 --> 00:04:17,960 Speaker 1: And today we invited on the show my friend John. 77 00:04:18,160 --> 00:04:21,120 Speaker 1: He's going to be talking about three different kinds of parasites. 78 00:04:21,120 --> 00:04:23,359 Speaker 1: And specifically we invited John on the show because we 79 00:04:23,360 --> 00:04:28,080 Speaker 1: had two listener questions that felt somewhat out of my expertise, 80 00:04:28,160 --> 00:04:30,679 Speaker 1: even though I'm a parasite person and so I knew 81 00:04:30,760 --> 00:04:32,720 Speaker 1: the guy to invite on the show. So let's go 82 00:04:32,760 --> 00:04:35,880 Speaker 1: ahead and listen to the two questions from listeners before 83 00:04:35,920 --> 00:04:36,800 Speaker 1: we bring John on. 84 00:04:37,200 --> 00:04:39,240 Speaker 4: Hi, Daniel and Kelly. This is David from the San 85 00:04:39,279 --> 00:04:42,719 Speaker 4: Francisco Bay area, and this question is for Kelly. What 86 00:04:42,839 --> 00:04:46,520 Speaker 4: makes developing a vaccine for parasitic infections so difficult? It 87 00:04:46,520 --> 00:04:49,159 Speaker 4: seems like progress has been only recent and incremental with 88 00:04:49,240 --> 00:04:52,200 Speaker 4: some experimental vaccines for hookworm, and the one approved laria 89 00:04:52,279 --> 00:04:55,719 Speaker 4: vaccine is not very efficacious. So what gives? And this 90 00:04:55,800 --> 00:04:57,719 Speaker 4: topic is at least tangentially related to what I do 91 00:04:57,800 --> 00:05:00,000 Speaker 4: for a living, which is working on a new platform 92 00:05:00,000 --> 00:05:02,640 Speaker 4: produce rnaate therapeutics, So I'm especially interested in what you 93 00:05:02,720 --> 00:05:05,520 Speaker 4: have to say. Anyway, keep up the great work, both 94 00:05:05,560 --> 00:05:09,280 Speaker 4: of you and Daniel, I forgive you for your chemistry phobia. Cheers. 95 00:05:10,080 --> 00:05:12,880 Speaker 5: I got my master's degree in the late seventies. At 96 00:05:12,880 --> 00:05:16,120 Speaker 5: that time there are three theories on how sysystems evade 97 00:05:16,120 --> 00:05:20,400 Speaker 5: immune system an advisor's theory was called molecular mimicry. Although 98 00:05:20,520 --> 00:05:22,920 Speaker 5: it was over fourty years ago, I remember it well 99 00:05:23,200 --> 00:05:25,720 Speaker 5: because for the final exam we had eight hours to 100 00:05:25,760 --> 00:05:28,640 Speaker 5: answer two questions. One of which was your name, the 101 00:05:28,720 --> 00:05:31,880 Speaker 5: three current theories of how the treatment HOS evased immune 102 00:05:31,880 --> 00:05:34,000 Speaker 5: system and which one do you agree with and why? 103 00:05:34,440 --> 00:05:37,680 Speaker 5: Of course I chose my advisor's theory, but after receiving 104 00:05:37,720 --> 00:05:40,279 Speaker 5: my master's degree, I lost track of the issue. Since 105 00:05:40,279 --> 00:05:42,880 Speaker 5: I got my doctorate in different but related subjects. My 106 00:05:43,040 --> 00:05:45,880 Speaker 5: question is what advances have been made and have any 107 00:05:45,960 --> 00:05:49,000 Speaker 5: conclusions been made pertaining to their evasion of the host 108 00:05:49,040 --> 00:05:51,880 Speaker 5: immune system, and if so, will lead to a practical 109 00:05:52,240 --> 00:05:54,160 Speaker 5: subject such as tissue transplantation. 110 00:05:54,800 --> 00:05:57,520 Speaker 3: All right, these are awesome questions, and thank you to 111 00:05:57,600 --> 00:06:00,000 Speaker 3: everybody who writes to us with your questions. We really 112 00:06:00,240 --> 00:06:02,320 Speaker 3: do love to hear from you. If you have questions 113 00:06:02,560 --> 00:06:06,159 Speaker 3: about comments, or about malaria, or about parasites, or about 114 00:06:06,200 --> 00:06:10,520 Speaker 3: whatever you have limitless curiosity about, please do send them 115 00:06:10,720 --> 00:06:13,000 Speaker 3: to us. We'd love to hear from you questions at 116 00:06:13,160 --> 00:06:14,880 Speaker 3: Danielankelly dot org. 117 00:06:15,200 --> 00:06:17,520 Speaker 1: All right, and without any further ado, let's bring my 118 00:06:17,560 --> 00:06:20,280 Speaker 1: friend John on the show to answer these listener questions. 119 00:06:21,200 --> 00:06:24,560 Speaker 1: Doctor John Hawden is a parasitologist and molecular biologist at 120 00:06:24,560 --> 00:06:27,719 Speaker 1: the George Washington School of Medicine and Health Sciences. He 121 00:06:27,839 --> 00:06:30,840 Speaker 1: was previously the president of both the American Society of 122 00:06:30,880 --> 00:06:35,160 Speaker 1: Parasitologists and the Helmethological Society of Washington. He's done some 123 00:06:35,200 --> 00:06:38,160 Speaker 1: really fantastic work on hookworms, which you'll remember are one 124 00:06:38,200 --> 00:06:41,240 Speaker 1: of the dirt worms or geohelmans that we talked about 125 00:06:41,240 --> 00:06:43,599 Speaker 1: in a prior episode, and we're very lucky to have 126 00:06:43,720 --> 00:06:45,479 Speaker 1: him come on the show to talk to us about 127 00:06:45,480 --> 00:06:46,760 Speaker 1: parasites and vaccines. 128 00:06:47,000 --> 00:06:49,560 Speaker 2: Welcome to the show, John, Thank you, my pleasure. We're 129 00:06:49,560 --> 00:06:50,400 Speaker 2: excited you're here. 130 00:06:50,560 --> 00:06:51,640 Speaker 6: I'm excited to be here. 131 00:06:52,160 --> 00:06:57,360 Speaker 1: You sound really excited, John. Okay, so let's start with hookworms. 132 00:06:57,880 --> 00:07:01,600 Speaker 1: So we did have a whole episode on the soil geohelmets, 133 00:07:01,839 --> 00:07:04,640 Speaker 1: which we call dirt worms, but just to remind everybody, 134 00:07:04,680 --> 00:07:06,839 Speaker 1: can you talk about the life cycle of hookworms? 135 00:07:07,279 --> 00:07:10,920 Speaker 6: Sure? So hookworms live as male and female worms in 136 00:07:11,000 --> 00:07:16,720 Speaker 6: the intestinal track of various mammalan hosts, and they get 137 00:07:16,760 --> 00:07:19,480 Speaker 6: together and have their little party and the female legs 138 00:07:19,520 --> 00:07:22,640 Speaker 6: that are been fertilized and they pass out in the pieces. 139 00:07:22,960 --> 00:07:25,360 Speaker 6: They spend a period in the ground where they hatch 140 00:07:25,400 --> 00:07:29,240 Speaker 6: and they develop through two molts to a third stage 141 00:07:29,320 --> 00:07:32,480 Speaker 6: larvae or L three that's infective for the next toast 142 00:07:33,000 --> 00:07:37,000 Speaker 6: and then the next host gets infected by either coming 143 00:07:37,040 --> 00:07:41,680 Speaker 6: into skin contact with the infective larvae or, in some cases, 144 00:07:42,120 --> 00:07:46,000 Speaker 6: like in dolog hookworms, for instance, by ingestion of the larvae. 145 00:07:46,440 --> 00:07:47,679 Speaker 3: We're talking about eating poop. 146 00:07:47,880 --> 00:07:51,160 Speaker 6: Well, yeah, as I tell my students, you know, when 147 00:07:51,200 --> 00:07:54,280 Speaker 6: you get one of these fecal oral diseases, it means 148 00:07:54,320 --> 00:07:55,800 Speaker 6: you ate a tiny little bit of. 149 00:07:55,720 --> 00:07:56,920 Speaker 2: Poop, yeah, poop to mouth. 150 00:07:57,160 --> 00:08:01,480 Speaker 6: So once they get into this into your the host body, 151 00:08:01,960 --> 00:08:04,520 Speaker 6: if they go through the skin, they undergo a migration 152 00:08:04,720 --> 00:08:08,480 Speaker 6: that takes them into the circulatory system to the lungs 153 00:08:08,520 --> 00:08:12,480 Speaker 6: where they break out in the bronchioles and they crawl 154 00:08:12,600 --> 00:08:16,080 Speaker 6: up your bronchile tree to the trachea to your mouth 155 00:08:16,160 --> 00:08:19,160 Speaker 6: where they're swallowed and they are carried to the small 156 00:08:19,200 --> 00:08:22,960 Speaker 6: intestine where they will resume the development and to the 157 00:08:22,960 --> 00:08:26,560 Speaker 6: adult stage. If they enter orally, they don't need to 158 00:08:26,680 --> 00:08:30,000 Speaker 6: leave the intestine and they can develop directly to the 159 00:08:30,040 --> 00:08:30,840 Speaker 6: adult stage. 160 00:08:31,120 --> 00:08:34,800 Speaker 3: And they're called hookworms because they bite onto the wall 161 00:08:34,840 --> 00:08:36,080 Speaker 3: of your intestine and hook in. 162 00:08:36,440 --> 00:08:41,560 Speaker 6: That's a common misconception, all right, it's actually it's actually 163 00:08:41,679 --> 00:08:45,800 Speaker 6: because of the way the worms appear. They can't see me. 164 00:08:45,880 --> 00:08:48,240 Speaker 6: I'm doing this for the camera, but do a little bend. 165 00:08:48,240 --> 00:08:51,880 Speaker 6: But yeah, so there's a little bend in them that 166 00:08:52,200 --> 00:08:54,480 Speaker 6: makes it look like a hook Like if you have 167 00:08:54,760 --> 00:08:57,400 Speaker 6: gotten some from inside an animal and you put them 168 00:08:57,400 --> 00:09:00,800 Speaker 6: in a dish, or even if you're looking at the 169 00:09:00,880 --> 00:09:03,400 Speaker 6: surface of an infected small intestine, they will be appear 170 00:09:03,480 --> 00:09:03,760 Speaker 6: to be. 171 00:09:03,760 --> 00:09:07,040 Speaker 3: Bent, you said, if you're looking at a dish of them, 172 00:09:07,559 --> 00:09:09,920 Speaker 3: like you mean, you at a restaurant and somebody serves 173 00:09:09,960 --> 00:09:12,520 Speaker 3: you like a hookworm salad or something. 174 00:09:16,960 --> 00:09:22,280 Speaker 1: Sorry, we love body humor us parasitologists, all right. I 175 00:09:22,280 --> 00:09:23,840 Speaker 1: don't want to get us too far off track, but 176 00:09:23,920 --> 00:09:26,480 Speaker 1: I have to ask, when the worms crawl up your 177 00:09:26,520 --> 00:09:28,960 Speaker 1: trachea into your mouth, do people feel that? 178 00:09:29,080 --> 00:09:29,280 Speaker 2: I think? 179 00:09:29,320 --> 00:09:31,640 Speaker 1: I asked our mutual friend Jimmy, who got infected with 180 00:09:31,679 --> 00:09:33,680 Speaker 1: hookworms as part of an experiment, and he said he 181 00:09:33,800 --> 00:09:36,840 Speaker 1: did not at any point feel the hookworms crawling in 182 00:09:36,880 --> 00:09:37,280 Speaker 1: his mouth. 183 00:09:37,600 --> 00:09:39,920 Speaker 6: What's the deal there, John, Well, he's the expert on that. 184 00:09:40,040 --> 00:09:42,560 Speaker 6: I have never been infected, but my understanding is you 185 00:09:42,559 --> 00:09:45,760 Speaker 6: don't notice it, okay, right, So you'll swallow them with 186 00:09:45,800 --> 00:09:47,520 Speaker 6: food or with slave or whatever. 187 00:09:47,800 --> 00:09:49,120 Speaker 2: Gross and amazing, Oh. 188 00:09:49,000 --> 00:09:52,920 Speaker 6: My god, Well, they're clean by the time they run 189 00:09:53,000 --> 00:09:57,040 Speaker 6: through your body. So sure, all right. 190 00:09:57,160 --> 00:10:00,040 Speaker 1: So with a lot of infections like chicken pox, you 191 00:10:00,120 --> 00:10:02,680 Speaker 1: get it once and then you have lifelong immunity. So 192 00:10:03,520 --> 00:10:06,040 Speaker 1: why doesn't that happen with hookworms? Like, why can't you 193 00:10:06,080 --> 00:10:08,719 Speaker 1: give everybody one hookworm and then for the rest of 194 00:10:08,760 --> 00:10:10,720 Speaker 1: their life they never have to worry about getting hookworm. 195 00:10:10,800 --> 00:10:12,520 Speaker 6: Boy, life would be a lot easier if you could 196 00:10:12,559 --> 00:10:12,719 Speaker 6: do that. 197 00:10:13,000 --> 00:10:13,400 Speaker 2: Yeah. 198 00:10:13,440 --> 00:10:18,240 Speaker 6: Hookworms are, like most parasites, are very good at evading 199 00:10:18,280 --> 00:10:21,600 Speaker 6: the immune system, and they can do this actively or passively. 200 00:10:21,679 --> 00:10:25,760 Speaker 6: Primarily actively, they release molecules, most of which are unknown, 201 00:10:25,880 --> 00:10:30,800 Speaker 6: that alter the immune response to be a favorable environment 202 00:10:30,800 --> 00:10:35,280 Speaker 6: for them to survive. The human hookworms, notably, you never 203 00:10:35,320 --> 00:10:37,480 Speaker 6: really get a sterile immunity to them. You can be 204 00:10:37,559 --> 00:10:42,920 Speaker 6: reinfected over your entire lifetime. Dog hookworm, for instance, the 205 00:10:43,000 --> 00:10:45,960 Speaker 6: second infection never takes as well as the first, and 206 00:10:46,080 --> 00:10:48,600 Speaker 6: the older the dog gets, the less likely it is 207 00:10:48,640 --> 00:10:50,800 Speaker 6: to get a heavy infection of worms. 208 00:10:50,880 --> 00:10:54,240 Speaker 1: So okay, So wait, dogs mountain immune response better than humans. 209 00:10:54,240 --> 00:10:55,880 Speaker 2: What do we understand why that's different? 210 00:10:56,280 --> 00:10:56,480 Speaker 3: Uh? 211 00:10:56,600 --> 00:11:00,800 Speaker 6: No, okay, but there's a independently there's an age associated 212 00:11:01,000 --> 00:11:04,000 Speaker 6: resistance in dog hookworm, so that the older the dog 213 00:11:04,120 --> 00:11:07,200 Speaker 6: gets the less likely it is to get a heavy infection. 214 00:11:08,480 --> 00:11:11,040 Speaker 6: You don't see this in any of the human species. 215 00:11:11,320 --> 00:11:14,280 Speaker 6: It's our knowledge. I mean, you can get infected as 216 00:11:14,280 --> 00:11:16,240 Speaker 6: a kid, and you can infect it as an elderly 217 00:11:16,320 --> 00:11:21,440 Speaker 6: person with Nicator americanas, for instance, and you're gonna you'll 218 00:11:21,480 --> 00:11:22,240 Speaker 6: still be infected. 219 00:11:22,440 --> 00:11:24,400 Speaker 1: Got it, And just a quick reminder for folks that 220 00:11:24,520 --> 00:11:27,599 Speaker 1: Nicator americanas is a species of hookworm. 221 00:11:27,640 --> 00:11:30,839 Speaker 3: But microscopically, like, what's the issue? The hookworm has got 222 00:11:30,880 --> 00:11:34,040 Speaker 3: to be a foreign body. Doesn't the immune system identify 223 00:11:34,080 --> 00:11:36,080 Speaker 3: it as foreign and attack it the way it does 224 00:11:36,120 --> 00:11:39,320 Speaker 3: if you like get a splinter or get an organ donation. 225 00:11:39,600 --> 00:11:42,359 Speaker 3: What's the obstacle for the immune system? Have these hookworms 226 00:11:42,360 --> 00:11:44,400 Speaker 3: evolved to like look like human flesh. 227 00:11:44,440 --> 00:11:48,000 Speaker 6: There's a couple problems. First of all, there's no good 228 00:11:48,080 --> 00:11:53,839 Speaker 6: way to get rid of a large organism like a hookworm. 229 00:11:53,920 --> 00:11:57,040 Speaker 6: It's also in the gut, which is a little bit 230 00:11:57,080 --> 00:11:59,440 Speaker 6: harder to deal with too, So you get what's called 231 00:11:59,480 --> 00:12:03,080 Speaker 6: a weep sweep reaction where you get a lot of 232 00:12:03,200 --> 00:12:07,400 Speaker 6: secretion of liquid of water and things into the gut 233 00:12:07,600 --> 00:12:11,040 Speaker 6: that cause it to be flushed out. And you don't 234 00:12:11,080 --> 00:12:14,480 Speaker 6: see that in hookworm, then it's probably due to them 235 00:12:14,800 --> 00:12:19,280 Speaker 6: suppressing that and turning the immune reaction into one that 236 00:12:19,600 --> 00:12:22,760 Speaker 6: they can tolerate. And it basically it becomes a trade 237 00:12:22,800 --> 00:12:27,320 Speaker 6: off because if the host puts enough evolutionary effort into 238 00:12:27,400 --> 00:12:29,600 Speaker 6: getting rid of worms, they could do it, but it 239 00:12:29,640 --> 00:12:32,640 Speaker 6: would be costly for them to do it. So in 240 00:12:32,800 --> 00:12:35,840 Speaker 6: general you come to this equilibrium where the number of 241 00:12:35,840 --> 00:12:40,520 Speaker 6: worms is not really a big has a large effect 242 00:12:40,679 --> 00:12:43,920 Speaker 6: on the host. Now there's exceptions to that. Some people 243 00:12:44,000 --> 00:12:48,320 Speaker 6: get really high level infections that are dangerous, but for 244 00:12:48,360 --> 00:12:51,200 Speaker 6: the most part, the host and the worm seem to 245 00:12:51,240 --> 00:12:55,280 Speaker 6: come to an agreement where they kind of limit the damage, right, 246 00:12:55,360 --> 00:12:58,560 Speaker 6: And it's just negotiation down on a molecular level really 247 00:12:58,960 --> 00:13:02,280 Speaker 6: between immunes them and the molecules that the worm produces. 248 00:13:02,760 --> 00:13:05,800 Speaker 1: If the hookworms and our immune system have essentially like 249 00:13:05,840 --> 00:13:09,200 Speaker 1: come to a stand still, a standoff, why do we 250 00:13:09,840 --> 00:13:13,000 Speaker 1: need a vaccine for hookworms? If our immune system has 251 00:13:13,040 --> 00:13:14,559 Speaker 1: decided this isn't worth fighting off? 252 00:13:15,040 --> 00:13:16,240 Speaker 6: Did I say we needed one? 253 00:13:16,440 --> 00:13:21,120 Speaker 1: Okay, okay, all right, So put yourself in the shoes 254 00:13:21,160 --> 00:13:22,880 Speaker 1: of one of the people who are working on a 255 00:13:22,960 --> 00:13:24,120 Speaker 1: vaccine for hookworms. 256 00:13:24,480 --> 00:13:27,239 Speaker 2: What would they say for why we need a hookworm vaccine. 257 00:13:27,360 --> 00:13:28,959 Speaker 3: I mean, I want a vaccine. I don't want to 258 00:13:28,960 --> 00:13:32,640 Speaker 3: get hookworm. This sounds gross. Please give me a vaccine. 259 00:13:32,800 --> 00:13:34,720 Speaker 6: You know, there used to be hookworm in the United States, 260 00:13:34,760 --> 00:13:39,440 Speaker 6: and the reason you don't get hookworm here is because toilets. Right. 261 00:13:40,120 --> 00:13:43,360 Speaker 6: Once you separated people from their waist, you break the 262 00:13:43,400 --> 00:13:47,439 Speaker 6: life cycle and you don't have transmission anymore. In places 263 00:13:47,440 --> 00:13:51,480 Speaker 6: where it's too poor to have sewers and sanitation like this, 264 00:13:51,920 --> 00:13:57,760 Speaker 6: there's some need or desire to vaccinate, especially kids, so 265 00:13:57,800 --> 00:14:01,920 Speaker 6: that they can minimize the effects of the infection. So 266 00:14:02,320 --> 00:14:06,840 Speaker 6: it's thought that if you periodically deworm, or if you vaccinated, 267 00:14:07,200 --> 00:14:12,360 Speaker 6: you would improve growth and development, you would improve school 268 00:14:12,520 --> 00:14:17,280 Speaker 6: performance and all these other economic indicators later in life, 269 00:14:17,320 --> 00:14:19,560 Speaker 6: that people would make more money in this sort of thing, 270 00:14:19,600 --> 00:14:21,840 Speaker 6: And there are some evidence for that, but there's also 271 00:14:21,920 --> 00:14:25,880 Speaker 6: contradictory evidence that that would really happen. Again. In the 272 00:14:26,000 --> 00:14:32,720 Speaker 6: most cases, even children aren't infected with dangerous levels of hookworm, right. 273 00:14:33,160 --> 00:14:36,240 Speaker 6: But there is a small population, a group of the 274 00:14:36,280 --> 00:14:42,320 Speaker 6: population that is highly susceptible to worms, called wormy people basically, 275 00:14:42,360 --> 00:14:47,000 Speaker 6: and for it's either genetics or sometimes it exposure. You know, 276 00:14:47,040 --> 00:14:49,800 Speaker 6: behavioral things like that that increase exposure. 277 00:14:49,920 --> 00:14:52,920 Speaker 3: I can't tell because of your deadpan delivery if you're joking, 278 00:14:53,240 --> 00:14:55,280 Speaker 3: or if scientists really call them warmy people. 279 00:14:55,440 --> 00:14:58,160 Speaker 6: Oh, no, they do. They do. There's an article about this, 280 00:14:58,520 --> 00:15:01,200 Speaker 6: a famous article by a and named Stole. I believe 281 00:15:01,240 --> 00:15:05,280 Speaker 6: is said, this wormy world. So and if people are 282 00:15:05,280 --> 00:15:08,160 Speaker 6: called wormy because they tend to get more worms, and 283 00:15:08,240 --> 00:15:10,400 Speaker 6: it's that small that group there that's going to have 284 00:15:10,440 --> 00:15:13,640 Speaker 6: the pathology and everything. And I guess the question of 285 00:15:13,680 --> 00:15:17,360 Speaker 6: skeptics of vaccines is is it worth the investment to 286 00:15:17,480 --> 00:15:21,600 Speaker 6: get to this small population with a vaccine, to target 287 00:15:21,640 --> 00:15:24,600 Speaker 6: that small population with a vaccine, or would the money 288 00:15:24,600 --> 00:15:27,960 Speaker 6: be better spent either targeted treatment of this group of people, 289 00:15:28,280 --> 00:15:31,600 Speaker 6: identifying them and then treating them, which is also expensive 290 00:15:31,760 --> 00:15:35,920 Speaker 6: but probably not as expensive as a vaccine, or just 291 00:15:36,000 --> 00:15:41,400 Speaker 6: improving sanitation in general in these places and essentially the 292 00:15:41,480 --> 00:15:44,560 Speaker 6: only places that ever really controlled these dirt worms were 293 00:15:44,600 --> 00:15:48,520 Speaker 6: places that economically grew out of it. For instance, Japan, 294 00:15:49,280 --> 00:15:54,119 Speaker 6: South Korea, the United States, Europe. All these places basically 295 00:15:54,640 --> 00:15:58,680 Speaker 6: built toilets and economically developed their way out of these 296 00:15:58,800 --> 00:16:00,000 Speaker 6: parasites these infections. 297 00:16:00,200 --> 00:16:02,040 Speaker 3: Can I ask a question about that I have a 298 00:16:02,040 --> 00:16:06,720 Speaker 3: toilet related question. Sure, you're saying that the presence of 299 00:16:06,760 --> 00:16:10,880 Speaker 3: toilets basically separates people from their waist and that breaks 300 00:16:10,880 --> 00:16:12,560 Speaker 3: the cycle. And that makes sense to me, except that 301 00:16:12,800 --> 00:16:15,480 Speaker 3: I live with a microbiologist and she refers to toilets 302 00:16:15,480 --> 00:16:19,200 Speaker 3: as fecal tornadoes because when you flush, there's like a 303 00:16:19,280 --> 00:16:22,560 Speaker 3: spray of microscopic poop basically, And she does all these 304 00:16:22,600 --> 00:16:24,640 Speaker 3: studies that show that if you live with people long enough, 305 00:16:25,000 --> 00:16:28,080 Speaker 3: your microbiomes all sync because you're basically breathing and eating 306 00:16:28,080 --> 00:16:30,880 Speaker 3: each other's poop particles in the air. It's very romantic. 307 00:16:30,960 --> 00:16:33,080 Speaker 3: Let me tell you to be married to a microbiologist. 308 00:16:33,480 --> 00:16:36,560 Speaker 3: And so how do I understand that at the same 309 00:16:36,600 --> 00:16:39,880 Speaker 3: time as understanding that we've broken the hookworm life cycle? 310 00:16:39,920 --> 00:16:42,960 Speaker 3: Are these hookworm larva too small to take a ride 311 00:16:42,960 --> 00:16:46,480 Speaker 3: on the fecal tornadoes? Is that the issue? 312 00:16:46,680 --> 00:16:49,680 Speaker 6: I don't know, But your fecal tornado is only going 313 00:16:49,760 --> 00:16:54,160 Speaker 6: to have the eggs, which are non infectious. It takes 314 00:16:54,240 --> 00:16:57,960 Speaker 6: three or four days at a tropical temperature in order 315 00:16:58,000 --> 00:17:01,040 Speaker 6: to develop to that effective stage. So unless you're leaving 316 00:17:01,080 --> 00:17:03,880 Speaker 6: your poost it in the toilet for a few days 317 00:17:03,920 --> 00:17:06,400 Speaker 6: and then I'm not even sure they would develop in 318 00:17:06,640 --> 00:17:09,560 Speaker 6: and then you did your fecal tornado. But you know, 319 00:17:09,640 --> 00:17:11,320 Speaker 6: I mean, why do we have an immune system for 320 00:17:11,440 --> 00:17:14,600 Speaker 6: things like fecal tornadoes? Right, It's probably good for you 321 00:17:14,640 --> 00:17:17,080 Speaker 6: to stimulate your immune system. 322 00:17:17,240 --> 00:17:18,880 Speaker 3: A lot of life lessons here too. 323 00:17:19,720 --> 00:17:22,479 Speaker 6: I try to hilt the humans. Yeah, worm me or not? 324 00:17:22,680 --> 00:17:22,960 Speaker 2: Yeah? 325 00:17:23,119 --> 00:17:26,040 Speaker 1: All right, So you said that hook worms release chemicals 326 00:17:26,040 --> 00:17:28,320 Speaker 1: that sort of trick the immune system into not responding 327 00:17:28,359 --> 00:17:31,480 Speaker 1: to it. So how do we have any hope of 328 00:17:31,560 --> 00:17:34,440 Speaker 1: creating a vaccine against it? What have people tried so far? 329 00:17:34,720 --> 00:17:34,960 Speaker 2: Well? 330 00:17:35,000 --> 00:17:38,359 Speaker 6: No, I don't know how much of this I should say, 331 00:17:38,400 --> 00:17:42,440 Speaker 6: but there is some promising results with vaccines now, and 332 00:17:42,480 --> 00:17:46,160 Speaker 6: they seem to target anigens that aren't normally seen by 333 00:17:46,200 --> 00:17:49,560 Speaker 6: the body and are involved in feeding, for instance, like 334 00:17:50,000 --> 00:17:54,240 Speaker 6: gut proteins in the worm that will block feeding. Whether 335 00:17:54,320 --> 00:17:57,760 Speaker 6: these pan out eventually to be vaccines is not clear, 336 00:17:57,840 --> 00:18:01,800 Speaker 6: but in some early studies they to be promising. 337 00:18:02,440 --> 00:18:06,960 Speaker 3: Is an antigen something your immune system produces? No, that's 338 00:18:06,960 --> 00:18:09,040 Speaker 3: an antibody. So then what's an antigen? 339 00:18:09,440 --> 00:18:13,439 Speaker 6: Well, it's what your immune system recognizes to react to 340 00:18:13,480 --> 00:18:15,000 Speaker 6: produce an antibody or to. 341 00:18:15,280 --> 00:18:18,200 Speaker 3: It's a thing that triggers the immune response exactly. Okay, 342 00:18:18,760 --> 00:18:21,120 Speaker 3: to be honest, I thought, Man, this isn't gonna work. 343 00:18:21,720 --> 00:18:24,000 Speaker 3: And sometimes I think it even surprised the people who 344 00:18:24,080 --> 00:18:27,280 Speaker 3: do the experiments that work, because you know, these are 345 00:18:27,320 --> 00:18:29,919 Speaker 3: hard organisms to kill, they're big, and they have all 346 00:18:29,920 --> 00:18:33,679 Speaker 3: these chemical defenses. The more we learn about them, the 347 00:18:33,680 --> 00:18:38,960 Speaker 3: more there are there are multiple overlying mechanisms to subvert 348 00:18:39,000 --> 00:18:44,000 Speaker 3: the immune system. So yeah, it is a daunting prospect. 349 00:18:44,359 --> 00:18:48,720 Speaker 3: And one argument I've always had is that we jumped 350 00:18:48,760 --> 00:18:52,679 Speaker 3: into making vaccines before we knew enough about the worm 351 00:18:52,720 --> 00:18:55,040 Speaker 3: that a lot of the money that went into early 352 00:18:55,119 --> 00:18:58,040 Speaker 3: investment into the vaccines would have been much better learning 353 00:18:58,080 --> 00:19:00,600 Speaker 3: some basic biology about the worms. And we're starting to 354 00:19:00,640 --> 00:19:03,720 Speaker 3: know more about what they release, but we still don't 355 00:19:03,760 --> 00:19:07,560 Speaker 3: know how they affect the immune system. So maybe had 356 00:19:07,600 --> 00:19:09,960 Speaker 3: we waited a little longer, we would have had better 357 00:19:10,320 --> 00:19:14,400 Speaker 3: antigens to use for the vaccine. But again, that money 358 00:19:14,440 --> 00:19:18,960 Speaker 3: could also been spent to build sustainable toilets in developing countries, 359 00:19:19,440 --> 00:19:22,679 Speaker 3: which is something I had advocated for in earlier in 360 00:19:22,680 --> 00:19:26,080 Speaker 3: my career. Well, it sounds like you have fundamental criticisms 361 00:19:26,320 --> 00:19:30,280 Speaker 3: of this whole program, and yet you're the president of 362 00:19:30,280 --> 00:19:33,800 Speaker 3: the American Society of Parasitologists. Why don't you have more influence? 363 00:19:33,800 --> 00:19:39,600 Speaker 3: Why aren't they listening to you? John former President? Because well, 364 00:19:40,520 --> 00:19:43,920 Speaker 3: there are people with bigger voices than me involved in this, 365 00:19:45,280 --> 00:19:48,320 Speaker 3: the Who and various people there. There's a lot of 366 00:19:48,480 --> 00:19:52,240 Speaker 3: money in trying to develop this. I don't want to 367 00:19:52,240 --> 00:19:54,440 Speaker 3: be a cynic and say, well, this is how they 368 00:19:54,440 --> 00:19:57,000 Speaker 3: make their money or whatever. This is what they truly believe, 369 00:19:57,080 --> 00:19:59,560 Speaker 3: and they're advocates for it, right, and they have a 370 00:19:59,640 --> 00:20:03,280 Speaker 3: larger voice, and I doing this. I don't think it's 371 00:20:03,480 --> 00:20:06,439 Speaker 3: you know, the money spent on the vaccine. You know, 372 00:20:06,480 --> 00:20:08,760 Speaker 3: we did learn some things from that, so it's not 373 00:20:08,920 --> 00:20:12,280 Speaker 3: money wasted in that case. And if they get a vaccine, 374 00:20:12,640 --> 00:20:15,919 Speaker 3: I think it made it useful in certain situations. But 375 00:20:15,960 --> 00:20:17,800 Speaker 3: then you get into the question, you know, do you 376 00:20:17,840 --> 00:20:19,000 Speaker 3: want to kill all the worms? 377 00:20:19,560 --> 00:20:22,520 Speaker 6: Right? I mean, there's a whole group of people in 378 00:20:22,560 --> 00:20:25,280 Speaker 6: this in this country and around the world who think 379 00:20:25,960 --> 00:20:30,040 Speaker 6: having a few worms is actually beneficial for your immune system. 380 00:20:30,240 --> 00:20:34,040 Speaker 6: And there's a lot of there's an absence, let's say, 381 00:20:34,119 --> 00:20:39,520 Speaker 6: or a dearth of information about how parasites and their 382 00:20:39,560 --> 00:20:43,439 Speaker 6: hosts have co evolved, and you know, does this effect 383 00:20:43,480 --> 00:20:46,360 Speaker 6: on the immune system that allows the hookworm to live, 384 00:20:46,440 --> 00:20:50,280 Speaker 6: how does that affect other parasites and other diseases. And 385 00:20:50,320 --> 00:20:53,119 Speaker 6: if you take that component away, what are you going 386 00:20:53,160 --> 00:20:55,639 Speaker 6: to do to these other diseases. Some people think that 387 00:20:55,640 --> 00:20:59,600 Speaker 6: that's why the West has this large number of autoimmune diseases, 388 00:21:00,160 --> 00:21:03,760 Speaker 6: like you know, loopus and MS and all kinds of things, 389 00:21:03,800 --> 00:21:08,399 Speaker 6: because they've taken away some of the regulatory we're getting 390 00:21:08,400 --> 00:21:11,159 Speaker 6: out into the hygiene hypothesis, but you know, they've taken 391 00:21:11,200 --> 00:21:15,600 Speaker 6: away the early exposure to things our old friends, like parasites, 392 00:21:15,960 --> 00:21:18,560 Speaker 6: that have trained our immune system to not react to 393 00:21:18,600 --> 00:21:21,120 Speaker 6: the little things and to only react to the big 394 00:21:21,160 --> 00:21:24,280 Speaker 6: things that are dangerous. And you take that away, and 395 00:21:24,320 --> 00:21:26,720 Speaker 6: now you've got an entire arm of your immune system, 396 00:21:26,760 --> 00:21:30,159 Speaker 6: which is designed to fight worms, is now looking for 397 00:21:30,200 --> 00:21:32,840 Speaker 6: something to do, and it picks on you know, it 398 00:21:32,840 --> 00:21:36,080 Speaker 6: starts going after self enagines and things like that. So 399 00:21:36,720 --> 00:21:40,160 Speaker 6: these are all questions that we don't really know enough about. 400 00:21:40,359 --> 00:21:44,600 Speaker 6: So jumping into deworming and vaccinating the entire world may 401 00:21:44,720 --> 00:21:47,639 Speaker 6: lead us to places we don't necessarily want to go. 402 00:21:47,840 --> 00:21:49,919 Speaker 3: We could end up nostalgic for the time when we 403 00:21:49,960 --> 00:21:50,600 Speaker 3: had worms. 404 00:21:50,960 --> 00:21:52,399 Speaker 6: They could some of us are. 405 00:21:54,720 --> 00:21:55,040 Speaker 4: All right. 406 00:21:55,080 --> 00:21:57,280 Speaker 1: Well, in a future episode, I think we'll do a 407 00:21:57,320 --> 00:22:00,960 Speaker 1: whole hour on the hygiene hypothesis because I find this 408 00:22:01,000 --> 00:22:04,959 Speaker 1: topic absolutely fascinating. So wait for that in the future, folks. 409 00:22:05,119 --> 00:22:06,880 Speaker 1: And in the meantime, let's take a break, and when 410 00:22:06,880 --> 00:22:16,240 Speaker 1: we get back, we'll talk about parasite number two, the schistosomes. 411 00:22:30,560 --> 00:22:33,000 Speaker 1: All right, and we're back, and now we are talking. 412 00:22:32,760 --> 00:22:34,280 Speaker 2: About the schistosomes. 413 00:22:34,359 --> 00:22:38,680 Speaker 1: They cause a disease called schistosomiasis, and they're quite nasty parasites. 414 00:22:38,680 --> 00:22:40,639 Speaker 2: And Daniel's laughing at me. Why are you laughing? 415 00:22:41,080 --> 00:22:44,439 Speaker 3: I'm laughing because we just went from the ones you 416 00:22:44,480 --> 00:22:47,600 Speaker 3: get if you eat poop to ones called shisto which 417 00:22:47,640 --> 00:22:51,320 Speaker 3: you know has some sort of resonance with other words 418 00:22:51,359 --> 00:22:53,359 Speaker 3: we shouldn't say on the podcast. So tell me, is 419 00:22:53,400 --> 00:22:55,480 Speaker 3: this another poop related parasite? 420 00:22:55,960 --> 00:22:56,240 Speaker 2: John? 421 00:22:56,720 --> 00:23:01,040 Speaker 6: Indirectly? Indirectly, it's life cycle is a little bit different 422 00:23:01,720 --> 00:23:04,840 Speaker 6: for a couple of reasons. The adults live in the 423 00:23:04,840 --> 00:23:10,080 Speaker 6: bloodstream and the eggs come out in the feces. But 424 00:23:10,200 --> 00:23:12,960 Speaker 6: let's just start with the feces. And the eggs come out, 425 00:23:13,119 --> 00:23:15,720 Speaker 6: they have to get into water, and when they get 426 00:23:15,720 --> 00:23:18,760 Speaker 6: into water, they hatch and they get a small larval 427 00:23:18,840 --> 00:23:21,120 Speaker 6: stage that now is on the hunt for a snail. 428 00:23:21,960 --> 00:23:25,960 Speaker 6: And in the case of justtosomes, the snail is very particular. 429 00:23:26,000 --> 00:23:28,760 Speaker 6: It has to be a particular species. They find it, 430 00:23:28,800 --> 00:23:32,960 Speaker 6: they penetrate into it, and then they do several generations 431 00:23:32,960 --> 00:23:36,560 Speaker 6: of asexual reproduction. And what this does is it builds 432 00:23:36,640 --> 00:23:40,560 Speaker 6: up the number of the next stage, which is called 433 00:23:40,560 --> 00:23:43,000 Speaker 6: a circarrea, and this is the stage it's going to 434 00:23:43,080 --> 00:23:46,600 Speaker 6: infect people. So in order to get schistosome, you have 435 00:23:46,640 --> 00:23:50,000 Speaker 6: to have contact with water that has had both feces 436 00:23:50,359 --> 00:23:53,199 Speaker 6: and the right species of snail. And if you do 437 00:23:53,880 --> 00:23:57,560 Speaker 6: Thisstosomali swim and it will penetrate into your skin and 438 00:23:57,600 --> 00:24:00,399 Speaker 6: then it will undergo a migration that goes up much 439 00:24:00,440 --> 00:24:02,480 Speaker 6: hits all the highlights in the body. It goes to 440 00:24:02,520 --> 00:24:06,160 Speaker 6: the liver, it goes to the lungs, and eventually they 441 00:24:06,320 --> 00:24:08,800 Speaker 6: come back to the liver and they pair up as 442 00:24:08,800 --> 00:24:11,720 Speaker 6: a male and a female and they move up into 443 00:24:11,760 --> 00:24:14,520 Speaker 6: the vessels. And depending on a species, it's either the 444 00:24:14,600 --> 00:24:18,720 Speaker 6: vessels of the large intestine, small intestine, or the bladder, 445 00:24:19,640 --> 00:24:23,119 Speaker 6: and here the male and the female live in what's 446 00:24:23,200 --> 00:24:28,520 Speaker 6: called incopulo forever. The male has a body that's split, 447 00:24:28,920 --> 00:24:33,520 Speaker 6: hence the name shisto soma split body, and the female 448 00:24:33,600 --> 00:24:37,000 Speaker 6: nestles in there and is mating essentially all the time 449 00:24:37,400 --> 00:24:40,320 Speaker 6: with the male, and then they release their eggs into 450 00:24:40,320 --> 00:24:44,960 Speaker 6: the bloodstream that then undergo a remarkable journey to get 451 00:24:45,000 --> 00:24:46,240 Speaker 6: out of the bloodstream. 452 00:24:46,400 --> 00:24:49,600 Speaker 3: This is ridiculous, I mean, it just seems so implausible, 453 00:24:49,800 --> 00:24:52,359 Speaker 3: like step after step after step, and then you got 454 00:24:52,359 --> 00:24:54,280 Speaker 3: a snail and it's got to do this and you've 455 00:24:54,280 --> 00:24:57,040 Speaker 3: got to go swimming. But my specific question is when 456 00:24:57,040 --> 00:25:00,720 Speaker 3: you're swimming and the thing crawls through your skin, how 457 00:25:00,760 --> 00:25:02,560 Speaker 3: big is this thing? Is this something you notice or 458 00:25:02,760 --> 00:25:04,840 Speaker 3: just like are you in twimming? You have no idea 459 00:25:04,880 --> 00:25:05,920 Speaker 3: and now it's inside you? 460 00:25:06,200 --> 00:25:09,000 Speaker 6: Yeah, I don't think you notice it. It's pretty tiny. 461 00:25:09,160 --> 00:25:11,840 Speaker 3: And why do they have to be snailo sexuals, Like, 462 00:25:11,840 --> 00:25:13,800 Speaker 3: why do they have to do this thing inside the snail? 463 00:25:13,840 --> 00:25:15,560 Speaker 3: Why can't they just do it themselves in the water. 464 00:25:16,119 --> 00:25:18,960 Speaker 6: Well, they first of all will need something to feed on, 465 00:25:19,119 --> 00:25:22,399 Speaker 6: where they basically will feed on the snail. Then it 466 00:25:22,440 --> 00:25:26,680 Speaker 6: absorbs nutrients from the snail and makes all these new 467 00:25:26,760 --> 00:25:30,679 Speaker 6: stages the circarria. The purpose of this is that this 468 00:25:30,800 --> 00:25:34,040 Speaker 6: allows them to go from a single mirror citium it's 469 00:25:34,040 --> 00:25:38,679 Speaker 6: called that infects the snail into thousands of these circarria 470 00:25:38,760 --> 00:25:41,679 Speaker 6: that's going to affect the next toast. And what that 471 00:25:41,840 --> 00:25:45,080 Speaker 6: does is it increases the odds of infection by putting 472 00:25:45,119 --> 00:25:48,119 Speaker 6: more of these infective stages into the environment. If the 473 00:25:48,160 --> 00:25:51,920 Speaker 6: mirror citium just tried to infect the host directly, even 474 00:25:51,960 --> 00:25:54,560 Speaker 6: if it developed to the effective stage, the odds of 475 00:25:54,640 --> 00:25:57,520 Speaker 6: that happening are pretty low. But the more of these 476 00:25:57,520 --> 00:26:00,000 Speaker 6: infective stages you can put into the environment, the high 477 00:26:00,119 --> 00:26:02,520 Speaker 6: or the odds are that one or more of them 478 00:26:02,600 --> 00:26:04,359 Speaker 6: is going to get into the next toast. And in 479 00:26:04,359 --> 00:26:05,920 Speaker 6: the case it's just the sums, you need a male 480 00:26:06,000 --> 00:26:08,159 Speaker 6: and a female sir carrier to get in. 481 00:26:08,600 --> 00:26:11,120 Speaker 3: So the snail is like a schisto amplifier or something. 482 00:26:11,160 --> 00:26:13,439 Speaker 6: It's just like exactly, that's exactly what it is. 483 00:26:13,520 --> 00:26:15,120 Speaker 2: Crazy, it's kind of ingenious. 484 00:26:15,160 --> 00:26:15,320 Speaker 4: You know. 485 00:26:15,320 --> 00:26:18,159 Speaker 1: The snail goes around grazing and collecting more food, and 486 00:26:18,200 --> 00:26:20,440 Speaker 1: that energy goes towards making more parasites, and so the 487 00:26:20,480 --> 00:26:23,119 Speaker 1: parasites are getting like a buffet for doing nothing. 488 00:26:23,160 --> 00:26:24,880 Speaker 2: Once they establish in the snail. 489 00:26:26,480 --> 00:26:28,879 Speaker 6: This is a pretty gruesome parasite in the host, though. 490 00:26:28,920 --> 00:26:31,359 Speaker 6: It causes a lot of problems. And it's not because 491 00:26:31,400 --> 00:26:34,000 Speaker 6: of the worm, which is relatively tiny and living in 492 00:26:34,000 --> 00:26:37,439 Speaker 6: the blood vessels. It's because of the eggs. So this 493 00:26:37,600 --> 00:26:40,439 Speaker 6: mechanism that gets the eggs out is really elegant, but 494 00:26:40,560 --> 00:26:43,720 Speaker 6: it's very inefficient, so a vast majority of the eggs 495 00:26:44,080 --> 00:26:47,160 Speaker 6: don't get out. They end up in the liver and 496 00:26:47,560 --> 00:26:50,400 Speaker 6: they form what are called granulomas when the host reacts 497 00:26:50,400 --> 00:26:53,960 Speaker 6: to them, and that's where the damage comes from. Are 498 00:26:54,000 --> 00:26:56,640 Speaker 6: these granulomas in the liver and other organs as well? 499 00:26:56,880 --> 00:26:59,159 Speaker 3: Well, that was gonna be my question. The hookworm we 500 00:26:59,160 --> 00:27:01,040 Speaker 3: were talking about was most in the gut, and there's 501 00:27:01,040 --> 00:27:03,440 Speaker 3: some sort of negotiation. You can hang out there because 502 00:27:03,440 --> 00:27:06,239 Speaker 3: it's difficult for us to attack you anyway. But these 503 00:27:06,280 --> 00:27:08,399 Speaker 3: guys are all over I hear them being in the blood, 504 00:27:08,520 --> 00:27:11,320 Speaker 3: they're in the bladder, they're in the liver. So the 505 00:27:11,320 --> 00:27:17,080 Speaker 3: immune sism does respond to them. It forms these glass ulummas, granulomas, granulomas, yes, 506 00:27:17,080 --> 00:27:20,480 Speaker 3: thank you, yes, Why doesn't it get rid of them? 507 00:27:20,760 --> 00:27:22,720 Speaker 6: Well, the worms in the blood are pretty much untouched 508 00:27:22,760 --> 00:27:25,400 Speaker 6: and they have a bunch of immunovasive mechanisms as well. 509 00:27:25,640 --> 00:27:28,440 Speaker 6: It sort of similar to the whole worm, but different mechanisms. 510 00:27:28,920 --> 00:27:32,320 Speaker 6: The eggs, on the other hand, they alter the immune 511 00:27:32,359 --> 00:27:36,120 Speaker 6: system to make what's called a THH two response, which 512 00:27:36,160 --> 00:27:38,360 Speaker 6: is when you get a whole bunch of cells will 513 00:27:38,359 --> 00:27:41,800 Speaker 6: come in and they'll surround the egg and form this granuloma, 514 00:27:41,880 --> 00:27:44,400 Speaker 6: and then it will slowly move it through the tissue 515 00:27:44,880 --> 00:27:48,639 Speaker 6: right and eventually they'll come to the bladder wall or 516 00:27:48,720 --> 00:27:52,119 Speaker 6: the intestinal wall and they will just basically dump the 517 00:27:52,160 --> 00:27:55,240 Speaker 6: egg out, but they often get stuck, so you'll have 518 00:27:55,320 --> 00:27:58,600 Speaker 6: these eggs stuck in the bladder wall. All this depends 519 00:27:58,600 --> 00:28:01,200 Speaker 6: on the species where is is it in a bladder, 520 00:28:01,359 --> 00:28:03,560 Speaker 6: is it in a large or small intestine, But in 521 00:28:03,600 --> 00:28:06,800 Speaker 6: any case, you'll get them stuck in those in the 522 00:28:06,840 --> 00:28:08,960 Speaker 6: wall of those organs, as well as in the liver, 523 00:28:09,640 --> 00:28:14,120 Speaker 6: and then they're constantly releasing anigens that are pulling more 524 00:28:14,240 --> 00:28:16,880 Speaker 6: cells in, and these gran omans can get very big 525 00:28:16,920 --> 00:28:20,000 Speaker 6: and then start impacting the function of the tissue that 526 00:28:20,000 --> 00:28:23,800 Speaker 6: they're in, and you get fibrosis in the liver and 527 00:28:24,680 --> 00:28:27,920 Speaker 6: just the surmises can be really nasty disease. It's probably 528 00:28:27,920 --> 00:28:31,720 Speaker 6: the most pathogenic of the worms that in fact humans. 529 00:28:31,680 --> 00:28:33,800 Speaker 1: I thought I heard, and remind me if I'm wrong. 530 00:28:33,840 --> 00:28:35,919 Speaker 1: I thought there were some areas where the kind of 531 00:28:36,000 --> 00:28:40,600 Speaker 1: schistosome that they have is near the bladder, and the 532 00:28:40,840 --> 00:28:43,520 Speaker 1: granulomas build up in the bladder, and every once in 533 00:28:43,600 --> 00:28:45,360 Speaker 1: a while, like the males will get it so much 534 00:28:45,440 --> 00:28:48,400 Speaker 1: that they will start to bleed along with the you know, 535 00:28:48,480 --> 00:28:50,560 Speaker 1: with the females of a certain age, and it's almost 536 00:28:50,600 --> 00:28:52,400 Speaker 1: like a rite of passage. So many kids get this. 537 00:28:52,560 --> 00:28:55,360 Speaker 1: That blood in your urine is just something you expect 538 00:28:55,400 --> 00:28:58,120 Speaker 1: for both sexes. Is that Wow? Is that still the case? 539 00:28:58,200 --> 00:28:58,440 Speaker 2: John? 540 00:28:58,720 --> 00:29:02,240 Speaker 6: Yeah, that's the called just the soma heematobium. It's found 541 00:29:02,520 --> 00:29:07,200 Speaker 6: exclusively in Africa. And yeah, it will cause it because 542 00:29:07,240 --> 00:29:10,320 Speaker 6: these granny loanans move it to the bladder wall. They 543 00:29:10,440 --> 00:29:13,000 Speaker 6: cause it to erode and then you will get blood 544 00:29:13,000 --> 00:29:16,800 Speaker 6: in the urine. And there's some evidence that I think 545 00:29:16,840 --> 00:29:20,120 Speaker 6: they're pretty convinced now that schistosome as well, some of 546 00:29:20,120 --> 00:29:24,960 Speaker 6: these other trematodes can cause cancer as well, including bladder 547 00:29:25,000 --> 00:29:28,400 Speaker 6: cancer in that case, because of over years and years 548 00:29:28,720 --> 00:29:32,440 Speaker 6: of this erosion occurring and the body responding to it 549 00:29:32,480 --> 00:29:36,720 Speaker 6: in the eggs releasing these these antigens that it could 550 00:29:36,760 --> 00:29:37,680 Speaker 6: result in cancer. 551 00:29:37,800 --> 00:29:40,040 Speaker 3: Well, that sounds like something we should vaccinate against. 552 00:29:40,360 --> 00:29:43,320 Speaker 6: Yes, I would be in favor of that. I think 553 00:29:43,360 --> 00:29:46,240 Speaker 6: I think schistosimiasis is one that we can do without. 554 00:29:47,200 --> 00:29:48,600 Speaker 6: It's going to be just as hard to go to 555 00:29:48,640 --> 00:29:52,640 Speaker 6: make a vaccine. Again, they have some promising candidates, but 556 00:29:53,160 --> 00:29:56,960 Speaker 6: we're still a long way away from the actually using 557 00:29:57,000 --> 00:30:02,160 Speaker 6: a vaccine. Again, it's a sanitar thing, right in this case, 558 00:30:02,200 --> 00:30:05,200 Speaker 6: if you keep your feces away from water, you're not 559 00:30:05,200 --> 00:30:09,280 Speaker 6: going to have a problem. Snail control is possible, but 560 00:30:09,440 --> 00:30:15,440 Speaker 6: it's difficult, it's expensive. We see some promise with introducing 561 00:30:15,520 --> 00:30:18,400 Speaker 6: predators that actually eat the snails. In some areas in 562 00:30:18,520 --> 00:30:21,800 Speaker 6: West Africa they've done this and they've seen you know, 563 00:30:21,840 --> 00:30:25,520 Speaker 6: you can combine it with chemotherapy and snail control and 564 00:30:25,520 --> 00:30:29,200 Speaker 6: you could see a huge decrease in the prevalence and 565 00:30:29,520 --> 00:30:32,360 Speaker 6: just to some infections. But step one you said was 566 00:30:32,680 --> 00:30:35,560 Speaker 6: keep your feces away from water. But in the previous 567 00:30:35,560 --> 00:30:37,520 Speaker 6: segment we were talking about toilets, and that's like the 568 00:30:37,560 --> 00:30:41,360 Speaker 6: basic operating principles like turn your poop into sewage, right, right, 569 00:30:41,440 --> 00:30:43,520 Speaker 6: how do you do both at once? Well? As long 570 00:30:43,520 --> 00:30:45,680 Speaker 6: as you don't have snails in your sewage, you're gonna 571 00:30:45,680 --> 00:30:48,520 Speaker 6: be okay. And plus people generally, I mean, if you're 572 00:30:48,520 --> 00:30:51,760 Speaker 6: talking about Western sewage systems, you've kept away from the 573 00:30:51,800 --> 00:30:55,080 Speaker 6: sewage the entire time. The water, you know, goes through 574 00:30:55,080 --> 00:30:58,080 Speaker 6: a sewage treatment plant and gets treated and converted back 575 00:30:58,120 --> 00:31:02,800 Speaker 6: into usable water. So you know you're still breaking the 576 00:31:02,920 --> 00:31:08,240 Speaker 6: transmission in that case, right, Remember you need water and snails. 577 00:31:08,880 --> 00:31:11,320 Speaker 1: This sounds like a particularly tricky problem because you've got 578 00:31:11,320 --> 00:31:14,200 Speaker 1: like the adults that hide from the immune system, and 579 00:31:14,240 --> 00:31:16,400 Speaker 1: then you've got the eggs that as they pass through 580 00:31:16,480 --> 00:31:19,040 Speaker 1: the body definitely do not seem to be good at 581 00:31:19,080 --> 00:31:21,520 Speaker 1: hiding from the immune system, and the immune system responds 582 00:31:21,560 --> 00:31:24,120 Speaker 1: and that's what causes the problem for people. So it 583 00:31:24,160 --> 00:31:27,000 Speaker 1: seems to me that if you made a vaccine, you'd 584 00:31:27,040 --> 00:31:29,680 Speaker 1: need to be careful to not make the problem with 585 00:31:29,720 --> 00:31:33,080 Speaker 1: the eggs worse because now your immune system is over responding. 586 00:31:33,800 --> 00:31:36,320 Speaker 6: Yeah, I think you would have to stop it before 587 00:31:36,320 --> 00:31:38,560 Speaker 6: they got to the egg producing adults, and you would 588 00:31:38,560 --> 00:31:41,440 Speaker 6: have to make your vaccine against the stages that are 589 00:31:41,480 --> 00:31:43,560 Speaker 6: penetrating into the host. 590 00:31:43,760 --> 00:31:45,920 Speaker 2: Do we understand how the adults are hiding from the 591 00:31:45,920 --> 00:31:47,000 Speaker 2: immune system. 592 00:31:46,960 --> 00:31:50,040 Speaker 6: Right, so they do several things. First of all, they 593 00:31:50,040 --> 00:31:54,360 Speaker 6: will actually take host molecules and bind them to their 594 00:31:54,360 --> 00:31:58,520 Speaker 6: cuticle so that then the host immune system doesn't see 595 00:31:58,520 --> 00:32:01,440 Speaker 6: it as foreign. I mean, yes, we can. 596 00:32:01,480 --> 00:32:02,960 Speaker 1: We just sit on that for a second. That's like 597 00:32:03,080 --> 00:32:05,680 Speaker 1: taking like you know, taking the skin off of a 598 00:32:05,800 --> 00:32:07,840 Speaker 1: human and putting it on themselves or something like that. 599 00:32:07,840 --> 00:32:11,400 Speaker 1: That's amazing. They hide with our own material to. 600 00:32:11,440 --> 00:32:12,520 Speaker 3: Wolf in sheep's clothing. 601 00:32:12,720 --> 00:32:16,240 Speaker 6: Yeah, but that's not all go on. They also make 602 00:32:16,800 --> 00:32:20,400 Speaker 6: what's molecular mimicry. They will make molecules that are very 603 00:32:20,400 --> 00:32:24,240 Speaker 6: similar to molecules in the host, like a hormone for instance. 604 00:32:24,280 --> 00:32:27,280 Speaker 6: They will then get processed by the host enzymes and 605 00:32:27,400 --> 00:32:30,240 Speaker 6: act as a suppressor of the immune response. 606 00:32:30,480 --> 00:32:33,000 Speaker 3: Do we know how all of this elaborate machinery evolved? 607 00:32:33,080 --> 00:32:34,920 Speaker 3: We have any idea of the history here? Is that, like, 608 00:32:35,320 --> 00:32:38,360 Speaker 3: do you need all these pieces together to survive? Can 609 00:32:38,440 --> 00:32:40,000 Speaker 3: you like do it one step at a time and 610 00:32:40,040 --> 00:32:43,080 Speaker 3: refine it? How does it work? How does it evolve incrementally? 611 00:32:43,360 --> 00:32:46,280 Speaker 3: And ones that add more and more mechanisms probably are 612 00:32:46,280 --> 00:32:49,840 Speaker 3: better at survival. So it might have one of these 613 00:32:49,880 --> 00:32:53,040 Speaker 3: things initially and at lets more of them survive, and 614 00:32:53,040 --> 00:32:55,440 Speaker 3: then you will get the mutations for the other things 615 00:32:55,440 --> 00:32:59,040 Speaker 3: that occur, and they get just pile up to have 616 00:32:59,080 --> 00:33:01,760 Speaker 3: a whole suite of thing that is really efficient at 617 00:33:02,160 --> 00:33:05,280 Speaker 3: inhimbiting the immune system. So each of these tricks is helpful. 618 00:33:05,360 --> 00:33:08,240 Speaker 3: None of them are absolutely necessary, and so as you evolve, 619 00:33:08,360 --> 00:33:11,520 Speaker 3: you developed more and more tricks to sort of optimize 620 00:33:11,640 --> 00:33:12,600 Speaker 3: survival in the host. 621 00:33:12,760 --> 00:33:12,920 Speaker 6: Right. 622 00:33:13,000 --> 00:33:13,920 Speaker 3: Wow, impressive. 623 00:33:14,080 --> 00:33:16,280 Speaker 1: I know this episode isn't about the history of Kelly, 624 00:33:16,320 --> 00:33:19,480 Speaker 1: but when I read about this in Curl Zimmer's book 625 00:33:19,520 --> 00:33:22,520 Speaker 1: Parasite Rex, this was like literally a turning point in 626 00:33:22,560 --> 00:33:24,959 Speaker 1: my life. I had gone from being like parasites, Oh, 627 00:33:25,000 --> 00:33:27,520 Speaker 1: they're just kind of gross, to being like, holy cow, 628 00:33:27,680 --> 00:33:30,280 Speaker 1: it's like amazing the way they've managed to hide inside 629 00:33:30,280 --> 00:33:33,240 Speaker 1: of our bodies, and like it totally changed the way 630 00:33:33,240 --> 00:33:36,480 Speaker 1: I looked at parasites and like literally altered the course 631 00:33:36,520 --> 00:33:38,760 Speaker 1: of my life. So anyway it infected your mind, it 632 00:33:38,760 --> 00:33:41,320 Speaker 1: infected my mind, and now we got to share it 633 00:33:41,400 --> 00:33:43,800 Speaker 1: with everybody, and so I'm very excited. 634 00:33:44,000 --> 00:33:46,479 Speaker 3: Wait, no, this is the like intellectual version of the 635 00:33:46,520 --> 00:33:50,480 Speaker 3: snail amplification that goes into Kelly's brain just states for 636 00:33:50,480 --> 00:33:52,880 Speaker 3: a while, she gets a podcast and then she spreads 637 00:33:52,880 --> 00:33:55,240 Speaker 3: it to the whole community through John. 638 00:33:55,400 --> 00:33:57,960 Speaker 1: John is my snail and I am the parasite and 639 00:33:58,040 --> 00:34:03,520 Speaker 1: this is gone. This has gone too okay, So let's well, 640 00:34:03,720 --> 00:34:05,960 Speaker 1: I can I play on the word shisto, like take 641 00:34:05,960 --> 00:34:06,440 Speaker 1: a break? 642 00:34:06,800 --> 00:34:10,399 Speaker 2: Can we split for a second? Nope? Not clever enough. 643 00:34:11,560 --> 00:34:13,839 Speaker 2: All right, Daniel, do you have something in. 644 00:34:13,719 --> 00:34:16,320 Speaker 3: Case anybody needs to take a break and have a shift. 645 00:34:16,800 --> 00:34:19,279 Speaker 3: Go ahead and we'll be back in a minute to 646 00:34:19,320 --> 00:34:22,360 Speaker 3: talk about another parasite poop related jokes. 647 00:34:22,400 --> 00:34:44,359 Speaker 1: Love it, and we're back, and we are going to 648 00:34:44,680 --> 00:34:47,560 Speaker 1: start with John's snail related joke that he queued up 649 00:34:47,680 --> 00:34:48,640 Speaker 1: during the break for us. 650 00:34:49,280 --> 00:34:50,640 Speaker 2: Oh wait, did you just say that this might not 651 00:34:50,640 --> 00:34:51,680 Speaker 2: be appropriate for the show? 652 00:34:52,000 --> 00:34:54,879 Speaker 6: This one's fine. Okay, this one's fine. So I tell 653 00:34:54,920 --> 00:34:59,040 Speaker 6: this in my class. So this guy goes to a 654 00:34:59,280 --> 00:35:03,040 Speaker 6: Halloween park a costume party and he's got this girl 655 00:35:03,520 --> 00:35:06,600 Speaker 6: draped over his shoulders and he goes in and the 656 00:35:06,640 --> 00:35:09,440 Speaker 6: host says, hey, how you doing great, and everything says 657 00:35:10,480 --> 00:35:12,960 Speaker 6: are you a costume? He goes, yeah, this is my costume. 658 00:35:13,640 --> 00:35:16,640 Speaker 6: Well what's with the girl? And I said, well that's Michelle, 659 00:35:18,239 --> 00:35:20,120 Speaker 6: Oh my Shelle. 660 00:35:20,160 --> 00:35:20,840 Speaker 2: He's a snail. 661 00:35:22,600 --> 00:35:24,480 Speaker 6: I think I left out the snail part. 662 00:35:28,160 --> 00:35:32,000 Speaker 2: We got there though as a team, as a team, so. 663 00:35:33,719 --> 00:35:35,120 Speaker 6: Yeah, sorry, I blew the d. 664 00:35:36,800 --> 00:35:40,760 Speaker 1: So malaria has some tricky ways of evading the immune system. 665 00:35:40,960 --> 00:35:43,040 Speaker 1: But we're going to start with the malarial life cycle 666 00:35:43,040 --> 00:35:44,760 Speaker 1: and get to the immune system stuff in a second. 667 00:35:45,120 --> 00:35:48,279 Speaker 1: And I've always found the malarial life cycle to be 668 00:35:48,719 --> 00:35:51,799 Speaker 1: super confusing. It has a bunch of stages. All the 669 00:35:51,840 --> 00:35:54,520 Speaker 1: stages have similar and kind of heart to remember names. 670 00:35:54,800 --> 00:35:57,319 Speaker 1: So I'm going to give a super simplified version of 671 00:35:57,320 --> 00:35:59,799 Speaker 1: the life cycle that I think will be sufficient for 672 00:35:59,840 --> 00:36:02,399 Speaker 1: the discussion we're about to have. All right, So, when 673 00:36:02,400 --> 00:36:06,160 Speaker 1: a mosquito bites a person who's already infected by malaria, 674 00:36:06,680 --> 00:36:10,200 Speaker 1: the parasite goes to the mosquito's gut and it starts 675 00:36:10,200 --> 00:36:13,239 Speaker 1: to replicate. So after that it moves to the mosquito's 676 00:36:13,480 --> 00:36:17,640 Speaker 1: salivary glands. And that's right, mosquitoes have salivary glands. I 677 00:36:17,640 --> 00:36:19,480 Speaker 1: don't know why that's surprising to me, but anyway, when 678 00:36:19,480 --> 00:36:23,759 Speaker 1: a mosquito bites a person, the parasites are injected by 679 00:36:23,800 --> 00:36:27,040 Speaker 1: the mosquito into the human body. The stage of the 680 00:36:27,080 --> 00:36:31,800 Speaker 1: parasite that gets released into a person is called a sporozoite. 681 00:36:32,120 --> 00:36:34,120 Speaker 1: This is the only stage we're going to name, so 682 00:36:34,200 --> 00:36:37,640 Speaker 1: just remember the sporozoite is the early stage in humans. 683 00:36:38,239 --> 00:36:41,000 Speaker 1: From there, the parasite moves onto the liver and does 684 00:36:41,000 --> 00:36:44,279 Speaker 1: some replicating. After that, it moves on to our red 685 00:36:44,440 --> 00:36:48,400 Speaker 1: blood cells. When a parasite gets into the red blood cell, 686 00:36:48,880 --> 00:36:52,440 Speaker 1: it's able to sneak proteins through the surface of the 687 00:36:52,480 --> 00:36:56,080 Speaker 1: red blood cell, and those proteins stick onto the surface 688 00:36:56,120 --> 00:36:58,960 Speaker 1: of the red blood cell. This helps the parasite hide 689 00:36:58,960 --> 00:37:00,880 Speaker 1: from the immune system. And I'm sure John's going to 690 00:37:00,920 --> 00:37:03,080 Speaker 1: tell us more about this later, all right, So, the 691 00:37:03,080 --> 00:37:06,000 Speaker 1: parasite is living in the red blood cell and it's 692 00:37:06,080 --> 00:37:08,200 Speaker 1: eating the hemoglobin. 693 00:37:07,600 --> 00:37:08,160 Speaker 2: In the cell. 694 00:37:08,480 --> 00:37:11,040 Speaker 1: And as you might remember from our past conversation about 695 00:37:11,040 --> 00:37:15,240 Speaker 1: synthetic blood, hemoglobin is the protein in your red blood 696 00:37:15,280 --> 00:37:18,719 Speaker 1: cell that helps your cells carry oxygen to different parts 697 00:37:18,719 --> 00:37:21,000 Speaker 1: of the body. So the parasite is hiding in the 698 00:37:21,000 --> 00:37:24,239 Speaker 1: red blood cell and shower down on the hemoglobin. It's 699 00:37:24,360 --> 00:37:27,520 Speaker 1: replicating while it's in the red blood cell, And every 700 00:37:27,719 --> 00:37:30,440 Speaker 1: like twenty four to forty eight hours, the red blood 701 00:37:30,440 --> 00:37:34,080 Speaker 1: cell will burst open and these newly released stages will 702 00:37:34,120 --> 00:37:36,680 Speaker 1: go off to search for new red blood cells to 703 00:37:36,719 --> 00:37:39,120 Speaker 1: infect so that like red blood cell cycle will start 704 00:37:39,160 --> 00:37:42,440 Speaker 1: again over time. A lot of the red blood cells 705 00:37:42,440 --> 00:37:46,160 Speaker 1: get infected this way, so you're regularly losing your red 706 00:37:46,160 --> 00:37:49,600 Speaker 1: blood cells, which can result in anemia. And your body 707 00:37:49,600 --> 00:37:52,920 Speaker 1: gets poisoned when these red blood cells burst open, and 708 00:37:53,000 --> 00:37:54,560 Speaker 1: all of the stuff that used to be in the 709 00:37:54,640 --> 00:37:57,759 Speaker 1: red blood cells is now like in circulation, and that's 710 00:37:57,800 --> 00:38:01,839 Speaker 1: not good. Plus when the red blood cells burst, there's 711 00:38:01,880 --> 00:38:05,120 Speaker 1: suddenly loads of new parasites in the circulation and the 712 00:38:05,120 --> 00:38:08,640 Speaker 1: immune system goes nuts. You get chills, you get fevers, 713 00:38:08,760 --> 00:38:11,120 Speaker 1: et cetera. And the parasite is bad for a lot 714 00:38:11,120 --> 00:38:13,080 Speaker 1: of other reasons, some of which I'm sure John is 715 00:38:13,080 --> 00:38:15,040 Speaker 1: going to tell us about in a few moments here. 716 00:38:15,480 --> 00:38:18,279 Speaker 1: And all of this on note is particularly dangerous for 717 00:38:18,400 --> 00:38:20,960 Speaker 1: children or for adults who have never been exposed to 718 00:38:21,000 --> 00:38:23,200 Speaker 1: malaria before, like travelers for example. 719 00:38:23,480 --> 00:38:25,560 Speaker 3: And does it use the mosquito just as a way 720 00:38:25,600 --> 00:38:27,719 Speaker 3: to get from one body to another or is this 721 00:38:27,800 --> 00:38:30,960 Speaker 3: something that happens inside the mosquito like snail amplification. 722 00:38:31,239 --> 00:38:33,880 Speaker 6: Oh yeah, very important part of life cycle happens in 723 00:38:33,920 --> 00:38:37,160 Speaker 6: the snail. So there is an amplification in number. Plus 724 00:38:37,160 --> 00:38:41,200 Speaker 6: there's also sex or recombination occurring in the mosquito. 725 00:38:40,880 --> 00:38:42,960 Speaker 3: So we can definitely blame the mosquito for part of this. 726 00:38:43,239 --> 00:38:46,840 Speaker 6: Absolutely absolutely good. And you know it, blame the female 727 00:38:46,880 --> 00:38:49,399 Speaker 6: mosquitoes because they're the only ones that take a blood male. 728 00:38:51,000 --> 00:38:52,280 Speaker 2: I don't like where this is going. 729 00:38:55,000 --> 00:38:58,440 Speaker 3: So I'm broadly into mosquito female male. I don't care. 730 00:38:58,520 --> 00:38:59,600 Speaker 3: I'm not sexist about it. 731 00:38:59,719 --> 00:39:01,759 Speaker 6: You know, it doesn't work without the male, So they're 732 00:39:01,800 --> 00:39:04,360 Speaker 6: partially involved, but they're not the ones that are lighting you. 733 00:39:04,480 --> 00:39:06,640 Speaker 3: Yeah, exactly blame them all. 734 00:39:06,840 --> 00:39:11,000 Speaker 1: I'm broadly antidipterine, so dipterines are flies and mosquitoes. 735 00:39:11,239 --> 00:39:12,680 Speaker 2: I'm not a big fan of any of them. 736 00:39:12,680 --> 00:39:17,359 Speaker 1: But anyway, so inside the body of us, we get 737 00:39:17,360 --> 00:39:19,640 Speaker 1: these cycles where they live in our red blood cells. 738 00:39:19,880 --> 00:39:21,799 Speaker 1: They replicate and then they burst out of our red 739 00:39:21,840 --> 00:39:24,000 Speaker 1: blood cells, and then they go back into red blood cells. 740 00:39:24,120 --> 00:39:26,280 Speaker 1: So it seems like when they're in red blood cells, 741 00:39:26,960 --> 00:39:28,760 Speaker 1: I can imagine it would be harder for our immune 742 00:39:28,760 --> 00:39:31,480 Speaker 1: system to find them because they're like hiding in our cells. 743 00:39:31,680 --> 00:39:35,480 Speaker 6: They have evolved ways to transport things across their membrane, 744 00:39:36,239 --> 00:39:40,640 Speaker 6: across the vacual membrane to be displayed on the red 745 00:39:40,680 --> 00:39:44,759 Speaker 6: cell membrane, and one of the things that they display 746 00:39:45,440 --> 00:39:48,880 Speaker 6: is a molecule called, in the case of plasmonium fell siperum, 747 00:39:48,880 --> 00:39:53,200 Speaker 6: which is the most dangerous one erythrocytic membrane protein one, 748 00:39:53,360 --> 00:39:57,879 Speaker 6: or as I call it, PfEMP one, and p FMP 749 00:39:58,000 --> 00:40:01,800 Speaker 6: one then is expressed on the surface of the cell, 750 00:40:02,719 --> 00:40:07,040 Speaker 6: so there is an immune reaction that develops against this 751 00:40:07,239 --> 00:40:11,239 Speaker 6: PFMP one molecular. And the PFMP is interesting because it 752 00:40:11,320 --> 00:40:16,000 Speaker 6: is able to bind to receptors in the blood vessels, 753 00:40:16,040 --> 00:40:20,040 Speaker 6: the veins of the host, and it basically takes those 754 00:40:20,120 --> 00:40:23,560 Speaker 6: out of circulation, right, so they're bound to the inner 755 00:40:23,760 --> 00:40:28,719 Speaker 6: vessels right of your larger veins in everything, and they 756 00:40:28,760 --> 00:40:31,640 Speaker 6: just sit there so they're not being circulated through the spleen, 757 00:40:32,160 --> 00:40:35,560 Speaker 6: which would recognize the red cells as being deformed and 758 00:40:35,600 --> 00:40:38,359 Speaker 6: would take them out of circulation. So that's one way 759 00:40:38,400 --> 00:40:42,680 Speaker 6: they avoid the physical destruction associated with the spleen, and 760 00:40:42,719 --> 00:40:44,480 Speaker 6: they'll sit there and they'll do their you know, their 761 00:40:44,520 --> 00:40:47,960 Speaker 6: replication bound to these vessels. And that's also a major 762 00:40:48,000 --> 00:40:50,440 Speaker 6: cause of the pathology because when they bind to the 763 00:40:50,520 --> 00:40:55,040 Speaker 6: small vessels like in the brain or in the placenta, 764 00:40:55,360 --> 00:40:58,360 Speaker 6: in the kidney. This is where you get this micro 765 00:40:58,920 --> 00:41:03,040 Speaker 6: occlusion of the the capitilarias, and you get decreased oxygenation, 766 00:41:03,360 --> 00:41:06,440 Speaker 6: and then you get the metabolic acidosis. And these are 767 00:41:06,520 --> 00:41:10,480 Speaker 6: the kind of things that cause the big problems with malarium. 768 00:41:10,480 --> 00:41:12,200 Speaker 1: Not one hundred percent sure I understand. Let me see 769 00:41:12,200 --> 00:41:14,239 Speaker 1: if I can explain it back and if if I'm right. So, 770 00:41:14,400 --> 00:41:16,960 Speaker 1: I think what you're saying is that the red blood cells, 771 00:41:17,200 --> 00:41:18,880 Speaker 1: they end up with the stuff that sticks out of 772 00:41:18,920 --> 00:41:22,920 Speaker 1: the cell. It connects them to like the veins or 773 00:41:23,080 --> 00:41:26,719 Speaker 1: arteries so that they don't go to the spleen, whose 774 00:41:26,840 --> 00:41:30,680 Speaker 1: job is to remove infected or disfigured cells and get 775 00:41:30,760 --> 00:41:33,560 Speaker 1: rid of them. So they essentially keep themselves from going 776 00:41:33,600 --> 00:41:37,000 Speaker 1: to the police station by hanging on in one spot. 777 00:41:37,120 --> 00:41:39,320 Speaker 1: And if that happens, like in your brain or in 778 00:41:39,360 --> 00:41:42,279 Speaker 1: a placenta, it causes clogs that are bad. 779 00:41:42,320 --> 00:41:45,080 Speaker 6: Right, and it seems to be particular bad, like it's 780 00:41:45,120 --> 00:41:48,319 Speaker 6: one of the major causes of the cerebral malarium, which 781 00:41:48,360 --> 00:41:49,160 Speaker 6: is the big killer. 782 00:41:49,760 --> 00:41:52,960 Speaker 3: So then what are the possibilities here for a vaccine? 783 00:41:53,080 --> 00:41:55,759 Speaker 3: Since this sounds pretty bad and we all hate mosquitoes 784 00:41:55,960 --> 00:41:57,920 Speaker 3: and nobody wants the stuff in your brain. 785 00:41:58,320 --> 00:42:01,440 Speaker 6: Yeah, that's a good question. So I think most of 786 00:42:01,480 --> 00:42:04,680 Speaker 6: the success for the vaccines has been against the sporsoa. 787 00:42:05,680 --> 00:42:07,880 Speaker 6: If you have an immune response to sporizoi when it 788 00:42:07,920 --> 00:42:12,520 Speaker 6: gets into the skin, that can stop the infection right there. 789 00:42:12,920 --> 00:42:16,560 Speaker 6: And I there are some promising vaccines, some that have 790 00:42:16,640 --> 00:42:21,040 Speaker 6: actually been used are in use that maybe give you 791 00:42:21,080 --> 00:42:25,360 Speaker 6: sixty percent protection or so, I'll ticket. Yeah, it's you know, 792 00:42:25,360 --> 00:42:28,480 Speaker 6: it's kind of what a flu vaccine does too, you know. Yeah, 793 00:42:28,520 --> 00:42:30,919 Speaker 6: So there are some promising ones in there, maybe more 794 00:42:30,960 --> 00:42:33,359 Speaker 6: in the future because it put a lot of a 795 00:42:33,400 --> 00:42:38,040 Speaker 6: lot of effort into this vaccine development from malaria, and 796 00:42:38,840 --> 00:42:41,200 Speaker 6: definitely would be a good thing. You just need to 797 00:42:41,200 --> 00:42:45,439 Speaker 6: prevent people from dying because as they live there, they're 798 00:42:45,440 --> 00:42:48,239 Speaker 6: going to build up this natural immunity that occurs over 799 00:42:48,320 --> 00:42:50,480 Speaker 6: time and then it won't be an issue anymore. But 800 00:42:50,520 --> 00:42:53,640 Speaker 6: it'd be important for kids and also for travelers, like 801 00:42:53,680 --> 00:42:56,480 Speaker 6: if you're going into Africa and you've never had malaria, 802 00:42:57,280 --> 00:43:00,680 Speaker 6: then that would be very useful to have a vaccine, 803 00:43:00,719 --> 00:43:04,759 Speaker 6: or for the military or something like that. So there's 804 00:43:04,760 --> 00:43:07,719 Speaker 6: definitely a need for vaccine here. We're getting closer. I 805 00:43:07,800 --> 00:43:10,920 Speaker 6: think there are, Like I said, several have been deployed, 806 00:43:11,280 --> 00:43:14,080 Speaker 6: so it's promising, I think, more so, I think than 807 00:43:14,120 --> 00:43:16,080 Speaker 6: with the worms at this point. 808 00:43:16,160 --> 00:43:17,840 Speaker 1: Oh yeah, we never said what kind of an organism 809 00:43:17,920 --> 00:43:20,080 Speaker 1: malaria is. So the first example we talked about was 810 00:43:20,120 --> 00:43:23,400 Speaker 1: a nematode, the second one was a trematode, and malaria 811 00:43:23,520 --> 00:43:25,720 Speaker 1: is a protozoan protist. 812 00:43:25,840 --> 00:43:26,320 Speaker 3: Yeah. 813 00:43:26,440 --> 00:43:28,600 Speaker 1: Why is it so much harder to make vaccines for 814 00:43:28,680 --> 00:43:32,200 Speaker 1: parasites than for bacteria and viruses? And so my first 815 00:43:32,239 --> 00:43:37,360 Speaker 1: question is that actually true? I feel like the answer 816 00:43:37,400 --> 00:43:40,440 Speaker 1: is yes. And then is there a big picture reason 817 00:43:40,480 --> 00:43:40,879 Speaker 1: for why? 818 00:43:41,360 --> 00:43:41,520 Speaker 5: Uh? 819 00:43:41,920 --> 00:43:45,720 Speaker 6: Well, okay, it's generally it's true. But think about HIV. 820 00:43:46,040 --> 00:43:48,560 Speaker 6: I haven't had a vaccine against that yet, right, Yeah, 821 00:43:48,640 --> 00:43:52,640 Speaker 6: so it's not always easy to do, but I think 822 00:43:52,680 --> 00:43:56,640 Speaker 6: it's because the immune system seems to be much better 823 00:43:56,760 --> 00:43:59,799 Speaker 6: able to handle small things. Right. You can make an 824 00:43:59,800 --> 00:44:04,120 Speaker 6: antibody response, it'll bind to the bacterium or to the 825 00:44:04,239 --> 00:44:08,360 Speaker 6: viral particle, and then you can get your complement system 826 00:44:08,400 --> 00:44:12,759 Speaker 6: involved to destroy it. But you know the pathogens have 827 00:44:12,840 --> 00:44:15,520 Speaker 6: ways to get around the immune system as well, right, 828 00:44:15,760 --> 00:44:18,520 Speaker 6: So your bacteria and your viruses could subvert the immune 829 00:44:18,520 --> 00:44:19,120 Speaker 6: system too. 830 00:44:19,800 --> 00:44:21,759 Speaker 3: Wait, I didn't understand that first thing you said, and 831 00:44:21,800 --> 00:44:24,160 Speaker 3: it reminds me of a big puzzle in physics, you know, 832 00:44:24,200 --> 00:44:27,200 Speaker 3: you said, essentially, the immune system is better at attacking 833 00:44:27,280 --> 00:44:29,440 Speaker 3: small things, but big things are all made out of 834 00:44:29,480 --> 00:44:32,000 Speaker 3: small things. So why can't you just attack all the 835 00:44:32,040 --> 00:44:34,400 Speaker 3: small things that a big thing is made out of. 836 00:44:34,680 --> 00:44:37,239 Speaker 3: It's like the puzzle of like every classical object is 837 00:44:37,239 --> 00:44:39,920 Speaker 3: made of quantum particles. Why can't we understand it? I'm 838 00:44:39,920 --> 00:44:43,200 Speaker 3: not suggesting this quantum mechanical magic happening here, but what 839 00:44:43,360 --> 00:44:47,440 Speaker 3: keeps the immune system from attacking each individual cell inside 840 00:44:47,440 --> 00:44:48,680 Speaker 3: one of these bigger objects. 841 00:44:49,040 --> 00:44:51,880 Speaker 6: In case of the worms, they all have a cuticle 842 00:44:51,960 --> 00:44:56,799 Speaker 6: that protects the inner cells from damage. Right In the 843 00:44:56,840 --> 00:44:59,319 Speaker 6: case of like the hookworms, the immune system's able to 844 00:44:59,360 --> 00:45:01,600 Speaker 6: go after the small part of the worm, which is 845 00:45:01,640 --> 00:45:05,239 Speaker 6: the gut right that is exposed. It also takes a 846 00:45:05,280 --> 00:45:08,280 Speaker 6: lot of cells to kill, you know, a bigger worm. 847 00:45:08,320 --> 00:45:12,719 Speaker 6: It's just harder to do, I think. And like I said, 848 00:45:12,760 --> 00:45:15,160 Speaker 6: a lot of the mechanisms get where the worms involve 849 00:45:15,239 --> 00:45:17,680 Speaker 6: things like, well, we're just gonna flush them out, right, 850 00:45:17,719 --> 00:45:19,080 Speaker 6: We're not going to try to kill them. We're just 851 00:45:19,200 --> 00:45:22,920 Speaker 6: to try to flush them out. Whereas we have cells 852 00:45:22,920 --> 00:45:27,360 Speaker 6: that will actually ingest viruses and opsonize viruses at least 853 00:45:27,719 --> 00:45:32,080 Speaker 6: and bacteria, right, they recognize the antibody and they bind 854 00:45:32,120 --> 00:45:35,200 Speaker 6: to it and then ingest it and destroy it. Right. 855 00:45:35,360 --> 00:45:37,879 Speaker 6: So it's a lot easier to do that than it 856 00:45:37,960 --> 00:45:40,960 Speaker 6: is to try to kill a big worm that's got 857 00:45:40,960 --> 00:45:44,600 Speaker 6: this protective armor around it and is living in the gut, 858 00:45:44,640 --> 00:45:45,120 Speaker 6: for instance. 859 00:45:45,200 --> 00:45:46,840 Speaker 1: Yeah, So as a biologist, one of the things I 860 00:45:46,840 --> 00:45:49,319 Speaker 1: think is super interesting about this conversation is not just 861 00:45:49,640 --> 00:45:52,160 Speaker 1: how do the parasites evaide the immune system, but it's 862 00:45:52,200 --> 00:45:55,160 Speaker 1: also just that they have such complicated life cycles. There's 863 00:45:55,200 --> 00:45:57,520 Speaker 1: so many different places where you could choose to try 864 00:45:57,560 --> 00:46:00,080 Speaker 1: to protect against parasites. So you know, for mosquitos, you 865 00:46:00,120 --> 00:46:02,799 Speaker 1: can pay for bed nets because the mosquitos are most 866 00:46:02,800 --> 00:46:04,800 Speaker 1: active at night, and maybe you just keep the mosquitos 867 00:46:04,800 --> 00:46:07,279 Speaker 1: from biting, and maybe that's even you know, better than 868 00:46:07,280 --> 00:46:08,879 Speaker 1: some of the medicines. Just you know, if you don't 869 00:46:08,920 --> 00:46:11,360 Speaker 1: encounter with them in the first place, that's hopeful. But 870 00:46:11,480 --> 00:46:13,640 Speaker 1: you know, all of these systems are evolving, so if you, 871 00:46:14,040 --> 00:46:18,160 Speaker 1: for example, go after the mosquitoes with pesticides, they evolve 872 00:46:18,280 --> 00:46:21,279 Speaker 1: resistance and anyway, it's a very complicated problem, and all 873 00:46:21,320 --> 00:46:23,560 Speaker 1: of those complications is sort of what got me interested 874 00:46:23,600 --> 00:46:27,360 Speaker 1: in parasitology in the first place. Anyway, back to Kelly's 875 00:46:27,360 --> 00:46:31,280 Speaker 1: origin story, but this has been a fascinating, fascinating chat. 876 00:46:31,600 --> 00:46:33,319 Speaker 1: Thanks so much, John for coming on the show to 877 00:46:33,360 --> 00:46:36,640 Speaker 1: tell us all about the parasites you study and the 878 00:46:36,640 --> 00:46:38,279 Speaker 1: parasites you don't study that I put you on the 879 00:46:38,280 --> 00:46:39,160 Speaker 1: spot to talk about. 880 00:46:39,200 --> 00:46:39,560 Speaker 2: Anyway. 881 00:46:39,800 --> 00:46:43,000 Speaker 6: Ah, well, you know, all these years of teaching, I've 882 00:46:43,080 --> 00:46:43,680 Speaker 6: learned something. 883 00:46:43,800 --> 00:46:45,000 Speaker 2: So that's excellent. 884 00:46:45,160 --> 00:46:47,640 Speaker 3: You've learned how to nail a snail joke or snail 885 00:46:47,680 --> 00:46:48,200 Speaker 3: it I guess. 886 00:46:48,360 --> 00:46:50,520 Speaker 2: Yeah, well, John, let's save those for another episode. We 887 00:46:50,520 --> 00:46:52,520 Speaker 2: don't want to overwhelm the audience. 888 00:46:52,760 --> 00:46:53,960 Speaker 6: Thank you was fun. 889 00:47:01,400 --> 00:47:04,960 Speaker 1: Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. 890 00:47:05,160 --> 00:47:07,840 Speaker 2: We would love to hear from you, We really would. 891 00:47:08,000 --> 00:47:10,719 Speaker 3: We want to know what questions you have about this 892 00:47:10,960 --> 00:47:12,600 Speaker 3: Extraordinary Universe. 893 00:47:12,719 --> 00:47:15,640 Speaker 1: We want to know your thoughts on recent shows, suggestions 894 00:47:15,640 --> 00:47:16,640 Speaker 1: for future shows. 895 00:47:16,760 --> 00:47:19,080 Speaker 2: If you contact us, we will get back to you. 896 00:47:19,360 --> 00:47:22,879 Speaker 3: We really mean it. We answer every message. Email us 897 00:47:22,920 --> 00:47:26,040 Speaker 3: at Questions at Danielandkelly. 898 00:47:25,200 --> 00:47:27,239 Speaker 1: Dot org, or you can find us on social media. 899 00:47:27,360 --> 00:47:31,200 Speaker 1: We have accounts on x Instagram, Blue Sky, and on 900 00:47:31,239 --> 00:47:32,160 Speaker 1: all of those platforms. 901 00:47:32,239 --> 00:47:35,160 Speaker 2: You can find us at D and K Universe. 902 00:47:35,400 --> 00:47:36,960 Speaker 3: Don't be shy, write to us,