WEBVTT 00:00:00.000 --> 00:00:03.379 Right now, you can basically spin into a plastic 00:00:03.379 --> 00:00:06.480 tube, drop it in the mail, and for like 50 bucks, 00:00:06.719 --> 00:00:08.580 a lab will sequence your DNA. Yeah, and tell 00:00:08.580 --> 00:00:10.400 you exactly what percentage neanderthal you want. 00:00:10.539 --> 00:00:14.240 Right, exactly. We are living in this era of, 00:00:14.240 --> 00:00:18.219 I guess, biological omniscience. We sequence 00:00:18.219 --> 00:00:20.640 the microbiome of deep sea hydrothermal vents. 00:00:21.260 --> 00:00:26.059 We pull trace DNA off ancient artifacts. It really 00:00:26.059 --> 00:00:29.260 feels like modern medicine has just mapped every 00:00:29.260 --> 00:00:31.579 single inch of the microbial world. You know, 00:00:31.640 --> 00:00:34.079 like we've categorized every pathogen and just 00:00:34.079 --> 00:00:35.780 pinned it to a digital cork board. Definitely 00:00:35.780 --> 00:00:38.439 creates that illusion. Yeah. But today, for you 00:00:38.439 --> 00:00:41.340 listening, we are opening up a medical cold case 00:00:41.340 --> 00:00:43.840 that Well, it completely shatters that illusion. 00:00:44.479 --> 00:00:46.759 We're doing a deep dive into a surprisingly short 00:00:46.759 --> 00:00:49.299 but deeply mysterious Wikipedia article about 00:00:49.299 --> 00:00:53.240 an organism called Spirulum Minus. And the mission 00:00:53.240 --> 00:00:55.960 for this deep dive is to figure out how a disease 00:00:55.960 --> 00:00:58.140 -causing agent, which was discovered while Queen 00:00:58.140 --> 00:01:00.560 Victoria was literally still on the throne, has 00:01:00.560 --> 00:01:03.320 managed to almost entirely evade modern scientific 00:01:03.320 --> 00:01:05.819 understanding. Yeah, and this single organism... 00:01:05.900 --> 00:01:09.099 It serves as a perfect stress test for our modern 00:01:09.099 --> 00:01:11.739 taxonomic systems. Oh, totally. It exposes these 00:01:11.739 --> 00:01:14.640 massive unexamined assumptions that are still 00:01:14.640 --> 00:01:17.159 just lurking in our medical databases. Because 00:01:17.159 --> 00:01:19.260 when we peel back the layers on this one brief 00:01:19.260 --> 00:01:22.359 entry, we find this glaring reminder that a lot 00:01:22.359 --> 00:01:25.540 of what we accept as established medical fact, 00:01:25.540 --> 00:01:28.439 it's really just a historical placeholder. just 00:01:28.439 --> 00:01:30.439 waiting for someone to actually verify the data. 00:01:30.680 --> 00:01:32.719 OK, let's unpack this, because we have to start 00:01:32.719 --> 00:01:35.780 with the 19th century crime scene, basically. 00:01:35.840 --> 00:01:38.260 The scene of the crime, right. Yeah. So spirulum 00:01:38.260 --> 00:01:40.799 minus is the pathogen associated with rat bite 00:01:40.799 --> 00:01:43.640 fever, specifically a form of the disease called 00:01:43.640 --> 00:01:47.379 suloku. And the Wikipedia article notes it was 00:01:47.379 --> 00:01:49.519 first assigned to the genus spirulum way back 00:01:49.519 --> 00:01:54.340 in 1887 by this scientist named Carter. 1887, 00:01:54.439 --> 00:01:56.840 just think about that. Right. And based on those 00:01:56.840 --> 00:01:59.980 1887 observations, it's, well, it's presumed 00:01:59.980 --> 00:02:02.359 to be a bacterium. It stains gram -negative, 00:02:02.420 --> 00:02:05.319 and it has this very distinct, quote, coiled 00:02:05.319 --> 00:02:09.039 rod shape. Yep, the curly shape. And to me, looking 00:02:09.039 --> 00:02:11.560 at how this was classified back then, it feels 00:02:11.560 --> 00:02:15.680 exactly like a 19th century police mugshot. Oh, 00:02:15.740 --> 00:02:17.960 that's a great way to put it. Like early scientists 00:02:17.960 --> 00:02:20.740 were basically profiling a microbial suspect 00:02:20.740 --> 00:02:23.319 purely based on its blurry visual appearance. 00:02:24.240 --> 00:02:27.120 They looked through a primitive lens, saw a coiled 00:02:27.120 --> 00:02:29.259 rod, and just decided they knew everything they 00:02:29.259 --> 00:02:31.719 needed to know about its identity. What's fascinating 00:02:31.719 --> 00:02:35.039 here is the absolute reliance on morphology. 00:02:35.280 --> 00:02:37.659 Meaning just the shape of it. Exactly. The physical 00:02:37.659 --> 00:02:39.919 shape and structure of the organism. Yeah. Because 00:02:39.919 --> 00:02:43.009 in 1887, I mean, Carter didn't have genome sequencing. 00:02:43.129 --> 00:02:46.189 He didn't have polymerase chain reactions or 00:02:46.189 --> 00:02:48.629 molecular phylogenetics. No, of course not. He 00:02:48.629 --> 00:02:50.550 had a light microscope and some chemical stains. 00:02:51.069 --> 00:02:54.110 That's it. And the issue with categorizing microbes 00:02:54.110 --> 00:02:56.110 purely by their shape is that the microscopic 00:02:56.110 --> 00:02:58.569 world is heavily governed by the physics of fluid 00:02:58.569 --> 00:03:00.750 dynamics. Wait, fluid dynamics? How does that? 00:03:00.870 --> 00:03:03.270 Well, for a bacterium to move efficiently through 00:03:03.270 --> 00:03:05.810 really viscous environments like mucus or blood, 00:03:05.830 --> 00:03:09.110 for instance, a coiled corkscrew shape, is just 00:03:09.110 --> 00:03:12.080 aerodynamically optimal. Oh, wow. So evolutionary 00:03:12.080 --> 00:03:14.639 pressure actually forces completely unrelated 00:03:14.639 --> 00:03:18.080 organisms to adopt the exact same spiral shape. 00:03:18.520 --> 00:03:22.120 It's convergent evolution just at the microscopic 00:03:22.120 --> 00:03:26.389 scale. Like a dolphin and a shark. Yes. The perfect 00:03:26.389 --> 00:03:28.469 example. Right. They both have dorsal fins and 00:03:28.469 --> 00:03:30.669 these torpedo -shaped bodies because they both 00:03:30.669 --> 00:03:32.930 have to swim really fast in the ocean. But, you 00:03:32.930 --> 00:03:35.210 know, one is a mammal and one is a fish. Exactly. 00:03:35.610 --> 00:03:37.610 Their genetics couldn't be more different, but 00:03:37.610 --> 00:03:39.569 their environments forced them into the exact 00:03:39.569 --> 00:03:42.610 same silhouette. So Carter sees this spiral shape 00:03:42.610 --> 00:03:45.270 through his microscope, assumes it belongs with 00:03:45.270 --> 00:03:48.250 the other spirals, and just slaps the name Spiral 00:03:48.250 --> 00:03:51.180 Minus on it. Yep, and the name just sticks. But, 00:03:51.560 --> 00:03:53.180 and this is where the source material highlights 00:03:53.180 --> 00:03:55.900 something truly wild, spirulaminus is not even 00:03:55.900 --> 00:03:59.139 like a validly published name by modern taxonomic 00:03:59.139 --> 00:04:01.939 standards. No, it's not. It causes a known human 00:04:01.939 --> 00:04:05.699 condition, sinoku, and its own name isn't officially 00:04:05.699 --> 00:04:07.960 validated by the international committees that 00:04:07.960 --> 00:04:10.520 govern bacterial nomenclature. That is insane 00:04:10.520 --> 00:04:13.280 to me. It really is. And that administrative 00:04:13.280 --> 00:04:15.400 limbo tells you a lot about the institutional 00:04:15.400 --> 00:04:18.519 inertia in microbiology. Because to get a bacterial 00:04:18.519 --> 00:04:21.459 name validly published today, you have to meet 00:04:21.459 --> 00:04:24.300 incredibly strict criteria. Like what? What do 00:04:24.300 --> 00:04:27.129 you need? Well, you need a designated type strain 00:04:27.129 --> 00:04:29.269 that's available in established culture collections. 00:04:29.930 --> 00:04:32.310 You need comprehensive biochemical profiling. 00:04:33.029 --> 00:04:36.050 And, increasingly, you need full genomic data 00:04:36.050 --> 00:04:38.990 to prove its exact phylogenetic position. Right. 00:04:39.230 --> 00:04:41.269 The fact that spirulaminus hasn't crossed that 00:04:41.269 --> 00:04:44.110 threshold in over a century means literally nobody 00:04:44.110 --> 00:04:46.829 has been able to produce the modern data required 00:04:46.829 --> 00:04:49.709 to formalize its identity. Which... I mean, that 00:04:49.709 --> 00:04:51.750 brings up a glaring question. If it causes rat 00:04:51.750 --> 00:04:54.170 bite fever, and we've known about it since 1887, 00:04:54.870 --> 00:04:57.449 why hasn't modern science simply dragged this 00:04:57.449 --> 00:04:59.569 mugshot into the 21st century? You'd think it 00:04:59.569 --> 00:05:02.529 would be easy, right? Yeah. Why hasn't some enterprising 00:05:02.529 --> 00:05:05.209 grad student just, you know, run the standard 00:05:05.209 --> 00:05:07.829 tests to update the paperwork? Well, the organism 00:05:07.829 --> 00:05:10.410 itself absolutely refuses to cooperate with the 00:05:10.410 --> 00:05:12.149 standard protocols of modern science. It's a 00:05:12.149 --> 00:05:15.379 diva. Total diva. The article points out a fundamental 00:05:15.379 --> 00:05:18.439 biological bottleneck here. Spirulum minus does 00:05:18.439 --> 00:05:21.899 not grow in vitro. Okay, meaning? Meaning, it 00:05:21.899 --> 00:05:24.980 cannot be cultivated on the standard agar plates 00:05:24.980 --> 00:05:28.079 or in the liquid broths that form the entire 00:05:28.079 --> 00:05:31.560 backbone of modern microbiology labs. It is entirely 00:05:31.560 --> 00:05:35.100 fastidious. It requires inoculation in live animals 00:05:35.100 --> 00:05:37.660 to achieve any sort of growth or multiplication. 00:05:38.279 --> 00:05:40.540 Wait, so if a scientist wants to study this today... 00:05:40.589 --> 00:05:42.790 They can't just swab it onto a gel plate like 00:05:42.790 --> 00:05:45.110 we learned in high school biology. Nope. Won't 00:05:45.110 --> 00:05:47.189 grow. Let me push back on this though. Yeah? 00:05:47.410 --> 00:05:49.769 Because we constantly hear about breakthroughs 00:05:49.769 --> 00:05:53.189 in metagenomics, right? We sequence uncultivable 00:05:53.189 --> 00:05:55.910 bacteria all the time now. True, we do. Like 00:05:55.910 --> 00:05:58.610 we take samples from ocean water or dirt environments 00:05:58.610 --> 00:06:00.829 where we can't grow the bacteria in a lab and 00:06:00.829 --> 00:06:02.970 we just extract all the DNA directly from the 00:06:02.970 --> 00:06:04.850 sample to figure out what's in there. So why 00:06:04.850 --> 00:06:06.790 couldn't a researcher just take a blood sample 00:06:06.790 --> 00:06:09.310 from an infected animal or a human patient with 00:06:09.310 --> 00:06:11.879 Sudoku and sequence the pathogen directly, just 00:06:11.879 --> 00:06:14.540 bypassing the petri dish entirely. That is the 00:06:14.540 --> 00:06:16.899 logical modern workaround. It really is. But 00:06:16.899 --> 00:06:19.279 it runs into a massive signal -to -noise problem. 00:06:19.500 --> 00:06:21.720 What do you mean? Well, when you sequence an 00:06:21.720 --> 00:06:24.339 environmental sample, like ocean water, the DNA 00:06:24.339 --> 00:06:27.180 you extract is mostly microbial, right? Right, 00:06:27.319 --> 00:06:29.980 yeah. But when you extract DNA from the blood 00:06:29.980 --> 00:06:34.139 or tissue of a living infected mammal, the biological 00:06:34.139 --> 00:06:37.540 math changes drastically. A single milliliter 00:06:37.540 --> 00:06:40.560 of infected animal blood contains billions of 00:06:40.560 --> 00:06:43.620 host cells. And each one of those is packed with 00:06:43.620 --> 00:06:47.079 a massive mammalian genome. Oh, oh, I see where 00:06:47.079 --> 00:06:49.759 this is going. Yeah. Floating among those billions 00:06:49.759 --> 00:06:53.079 of host cells are perhaps a few thousand bacterial 00:06:53.079 --> 00:06:55.560 cells. So if you run that raw sample through 00:06:55.560 --> 00:06:59.899 a sequencer, 99 .9 % of your data will just be 00:06:59.899 --> 00:07:02.910 the animal's DNA. The rat's DNA. Exactly. The 00:07:02.910 --> 00:07:04.730 sequence of the pathogen gets completely drowned 00:07:04.730 --> 00:07:07.050 out by the host genome. So it's not just looking 00:07:07.050 --> 00:07:09.790 for a needle in a haystack. It's looking for 00:07:09.790 --> 00:07:12.029 a microscopic needle in a haystack where the 00:07:12.029 --> 00:07:14.370 needle is made of hay and you're blindfolded. 00:07:14.509 --> 00:07:15.870 That's a great way to visualize it. You would 00:07:15.870 --> 00:07:18.029 have to somehow filter out the mammalian DNA 00:07:18.029 --> 00:07:21.050 without destroying the tiny fragment of bacterial 00:07:21.050 --> 00:07:23.410 DNA you actually want. Which sounds impossible. 00:07:23.589 --> 00:07:26.240 It's precisely the challenge. I mean, there are 00:07:26.240 --> 00:07:28.639 host depletion techniques, but they're technically 00:07:28.639 --> 00:07:31.839 demanding, they're expensive, and they often 00:07:31.839 --> 00:07:34.779 result in losing the pathogen DNA entirely if 00:07:34.779 --> 00:07:37.279 the bacterial load is too low. Wow. Which means 00:07:37.279 --> 00:07:41.139 you're back to requiring live animal inoculation 00:07:41.139 --> 00:07:43.779 just to keep the pathogen alive to get enough 00:07:43.779 --> 00:07:47.199 of it. And that introduces immense logistical 00:07:47.199 --> 00:07:49.040 hurdles. Right, because now you're not just dealing 00:07:49.040 --> 00:07:52.079 with glass tubes. Exactly. Instead of a stack 00:07:52.079 --> 00:07:54.519 of plastic Petri ditches in a standard incubator, 00:07:54.899 --> 00:07:56.860 a researcher now needs an ethically approved 00:07:56.860 --> 00:07:59.420 animal facility, specialized veterinary care, 00:07:59.920 --> 00:08:01.959 highly controlled biocontainment environments. 00:08:02.100 --> 00:08:04.959 That sounds incredibly expensive. It is. The 00:08:04.959 --> 00:08:07.939 barrier to entry to study this single pathogen 00:08:07.939 --> 00:08:09.939 shifts from, you know, a few hundred dollars 00:08:09.939 --> 00:08:12.920 of lab supplies to hundreds of thousands of dollars 00:08:12.920 --> 00:08:15.550 in infrastructure. Man, this raises an important 00:08:15.550 --> 00:08:17.370 question for you, the listener, to consider. 00:08:17.600 --> 00:08:20.100 How much of our accepted medical knowledge is 00:08:20.100 --> 00:08:22.439 heavily skewed to the pathogens that are just 00:08:22.439 --> 00:08:24.800 convenient to study? Oh, massively skewed. Like, 00:08:25.100 --> 00:08:28.680 we have these massive, highly detailed databases 00:08:28.680 --> 00:08:31.040 on organisms that happen to thrive in a glass 00:08:31.040 --> 00:08:34.039 tube at 37 degrees Celsius. But the difficult 00:08:34.039 --> 00:08:36.740 ones, the ones that demand a live host and refuse 00:08:36.740 --> 00:08:39.980 to grow under our artificial conditions, they 00:08:39.980 --> 00:08:42.340 just get left behind in the 19th century. And 00:08:42.340 --> 00:08:44.700 that's because the scientific method relies on 00:08:44.700 --> 00:08:47.970 reproducibility. Right. makes the reproduction 00:08:47.970 --> 00:08:51.830 of experiments prohibitively expensive or just 00:08:51.830 --> 00:08:55.230 biologically frustrating, researchers are inevitably 00:08:55.230 --> 00:08:57.389 going to focus their grants and their careers 00:08:57.389 --> 00:09:00.350 on more tractable models. The literature moves 00:09:00.350 --> 00:09:03.190 on and these historical errors just sit there 00:09:03.190 --> 00:09:06.009 calcifying into accepted fact. And the evidence 00:09:06.009 --> 00:09:08.629 heavily suggests that spirulum minus is exactly 00:09:08.629 --> 00:09:10.570 one of those historical errors. We're spouted 00:09:10.570 --> 00:09:12.570 out. Because the Wikipedia article presents this 00:09:12.570 --> 00:09:14.669 massive scientific contradiction regarding its 00:09:14.669 --> 00:09:17.350 behavior and its environment. Carter named its 00:09:17.350 --> 00:09:19.370 spirulum based on its curly shape, like we said. 00:09:19.429 --> 00:09:21.730 Right. But the text states that organisms in 00:09:21.730 --> 00:09:24.110 the true spirulum genus are generally, quote, 00:09:24.649 --> 00:09:27.049 obligately microerophiles. And that metabolic 00:09:27.049 --> 00:09:29.309 classification is the smoking gun here. Okay, 00:09:29.350 --> 00:09:32.110 break that down for us. What is a microaerophile? 00:09:32.549 --> 00:09:34.769 So, an omlicate microaerophile requires a very 00:09:34.769 --> 00:09:37.809 delicate atmospheric balance to survive. It needs 00:09:37.809 --> 00:09:39.929 a small amount of oxygen to generate energy, 00:09:40.529 --> 00:09:43.610 but standard atmospheric oxygen levels are actually 00:09:43.610 --> 00:09:46.809 highly toxic to it. Wait, really? Oxygen is toxic 00:09:46.809 --> 00:09:50.659 to it? Yeah. True spirulum species lack the robust 00:09:50.659 --> 00:09:54.279 oxidative stress enzymes necessary to neutralize 00:09:54.279 --> 00:09:57.240 the reactive oxygen species that build up in 00:09:57.240 --> 00:10:00.299 high oxygen environments. So they thrive in places 00:10:00.299 --> 00:10:03.460 like stagnant water or specific soil layers where 00:10:03.460 --> 00:10:05.720 oxygen is naturally depleted. Okay, here's where 00:10:05.720 --> 00:10:08.320 it gets really interesting. The source explicitly 00:10:08.320 --> 00:10:11.019 points out that true spirulum species are not 00:10:11.019 --> 00:10:13.600 typically found in mammals, which makes sense 00:10:13.600 --> 00:10:15.940 because mammals have heavily oxygenated arterial 00:10:15.940 --> 00:10:18.120 blood rushing through their... systems. I mean, 00:10:18.379 --> 00:10:20.240 the internal environment of a rat or a human 00:10:20.240 --> 00:10:22.899 is practically bathing in oxygen. Exactly. So 00:10:22.899 --> 00:10:25.360 finding an obligately microaerophilic spirulum 00:10:25.360 --> 00:10:27.899 thriving inside a mammal causing a systemic infection 00:10:27.899 --> 00:10:30.399 like Sudoku makes absolutely no sense. None at 00:10:30.399 --> 00:10:33.000 all. To me, that is like finding a deep -sea 00:10:33.000 --> 00:10:35.500 anglerfish living comfortably in a desert oasis. 00:10:36.000 --> 00:10:38.659 It shouldn't be there. It completely defies the 00:10:38.659 --> 00:10:41.539 physiological constraints of its own genus. The 00:10:41.539 --> 00:10:44.139 environment is entirely wrong for what the nametag 00:10:44.139 --> 00:10:46.460 claims it is. And if we connect this to the bigger 00:10:46.460 --> 00:10:49.100 picture, the contradiction between its metabolic 00:10:49.100 --> 00:10:51.960 requirements and its chosen habitat strongly 00:10:51.960 --> 00:10:56.019 suggests that Carver's 1887 classification is 00:10:56.019 --> 00:10:58.080 just fundamentally wrong. He just messed up. 00:10:58.379 --> 00:11:00.700 The morphology tricked him. He saw a spiral, 00:11:00.940 --> 00:11:03.639 he signed into the spiral genus, and he either 00:11:03.639 --> 00:11:06.460 ignored or simply didn't know the metabolic realities 00:11:06.460 --> 00:11:09.460 of that genus. The behavior of spirula minus 00:11:09.460 --> 00:11:11.779 its ability to survive the highly oxygenated 00:11:11.779 --> 00:11:14.299 mammalian bloodstream screams that it belongs 00:11:14.299 --> 00:11:16.399 to a completely different biological family. 00:11:16.620 --> 00:11:19.159 Perhaps one entirely unrelated to true spirilla. 00:11:19.360 --> 00:11:21.860 So it's a century -old case of mistaken identity. 00:11:22.279 --> 00:11:24.519 Basically, yes. And in modern biology, when you 00:11:24.519 --> 00:11:26.820 have visual evidence from 1887 clashing with 00:11:26.820 --> 00:11:29.700 metabolic evidence, there's really only one definitive 00:11:29.700 --> 00:11:32.259 way to solve the puzzle. You need the genetic 00:11:32.259 --> 00:11:34.720 code. You need the DNA. Right, you need the DNA 00:11:34.720 --> 00:11:37.220 sequence to see exactly where this organism actually 00:11:37.220 --> 00:11:39.879 sits on the phylogenetic tree. Which brings us 00:11:39.879 --> 00:11:42.639 to what is honestly... The most staggering detail 00:11:42.639 --> 00:11:45.539 in this entire stack of sources. The total absence 00:11:45.539 --> 00:11:48.500 of that genetic data. Yes, the forgotten genome. 00:11:49.379 --> 00:11:52.259 According to a 2015 reference, specifically Washburn's 00:11:52.259 --> 00:11:54.419 chapter in the authoritative text on the principles 00:11:54.419 --> 00:11:57.460 and practice of infectious diseases, no attempts 00:11:57.460 --> 00:12:00.559 to sequence the organism are known. Zero. It's 00:12:00.559 --> 00:12:02.659 really hard to wrap your head around. As of that 00:12:02.659 --> 00:12:05.539 2015 publication, the global scientific community 00:12:05.539 --> 00:12:09.039 had no known record of anyone even attempting 00:12:09.039 --> 00:12:11.500 to sequence the DNA of a pathogen that causes 00:12:11.500 --> 00:12:13.740 a documented human disease. So what does this 00:12:13.740 --> 00:12:16.509 all mean? We live in an era where we are mapping 00:12:16.509 --> 00:12:19.409 the genomes of extinct species. We are engineering 00:12:19.409 --> 00:12:22.309 synthetic bacteria from scratch. But a pathogen 00:12:22.309 --> 00:12:24.909 that causes rat bite fever has literally evaded 00:12:24.909 --> 00:12:27.570 the entire genomic revolution. And it's not like 00:12:27.570 --> 00:12:29.830 rat bite fever is completely ignored by science. 00:12:30.149 --> 00:12:31.990 The sources mention that the disease is also 00:12:31.990 --> 00:12:35.450 caused by another established pathogen, streptobacillus 00:12:35.450 --> 00:12:38.110 moniliformis. Right, a completely different bacteria. 00:12:38.370 --> 00:12:41.250 So we clearly study this arena of infectious 00:12:41.250 --> 00:12:44.419 disease. We know about the condition. How does 00:12:44.419 --> 00:12:47.340 spirulum minus just fall completely off the radar? 00:12:47.580 --> 00:12:50.139 Well, it requires synthesizing the economic and 00:12:50.139 --> 00:12:52.200 biological realities we've just been discussing 00:12:52.200 --> 00:12:55.379 to understand how a blind spot this large forms. 00:12:55.600 --> 00:12:57.960 Okay. First, you have the biological barrier. 00:12:58.360 --> 00:13:01.139 The absolute reliance on live animal models and 00:13:01.139 --> 00:13:04.100 that terrible signal -to -noise ratio in extracting 00:13:04.100 --> 00:13:07.639 DNA makes sequencing it a formidable technical 00:13:07.639 --> 00:13:10.500 challenge. The hay needle problem. Exactly. But 00:13:10.500 --> 00:13:13.240 second, you have the economic barrier. Rapite 00:13:13.240 --> 00:13:16.039 fever, while it's historically significant, is 00:13:16.039 --> 00:13:18.580 a relatively rare condition in modern developed 00:13:18.580 --> 00:13:21.059 nations with strong sanitation infrastructure. 00:13:21.100 --> 00:13:23.460 Sure. And when it does occur, whether it's caused 00:13:23.460 --> 00:13:25.940 by streptobacillus or the posun spirula minus, 00:13:26.460 --> 00:13:28.820 it generally responds really well to standard 00:13:28.820 --> 00:13:31.259 broad -spectrum antibiotics. Yeah. Like penicillin. 00:13:31.419 --> 00:13:33.559 Oh, OK. So doctors don't actually need to know 00:13:33.559 --> 00:13:36.220 its exact taxonomic classification to cure the 00:13:36.220 --> 00:13:38.230 patient? No, they don't. If the patient comes 00:13:38.230 --> 00:13:41.350 in with a rat bite and a fever, the doctor prescribes 00:13:41.350 --> 00:13:43.889 antibiotics, the patient gets better, and the 00:13:43.889 --> 00:13:46.929 clinical mystery is solved. Even if the biological 00:13:46.929 --> 00:13:50.769 mystery remains completely untouched. That is 00:13:50.769 --> 00:13:53.470 exactly the dynamic at play. You have a pathogen 00:13:53.470 --> 00:13:56.409 that is incredibly expensive and technically 00:13:56.409 --> 00:13:59.649 grueling to cultivate. causing a rare disease 00:13:59.649 --> 00:14:02.110 that already has an effect of clinical treatment. 00:14:02.990 --> 00:14:05.889 So it doesn't represent a massive unfunded global 00:14:05.889 --> 00:14:09.169 public health emergency. It lacks the targeted 00:14:09.169 --> 00:14:11.730 grant funding necessary to overcome all those 00:14:11.730 --> 00:14:13.990 massive logistical hurdles we talked about. Right, 00:14:13.990 --> 00:14:16.450 because a researcher looking to secure a multi 00:14:16.450 --> 00:14:18.429 -million dollar grant to sequence a packaging 00:14:18.429 --> 00:14:21.409 is going to have a very hard time justifying 00:14:21.409 --> 00:14:24.289 that cost for spirulum minus when the clinical 00:14:24.289 --> 00:14:26.850 outcomes are already perfectly manageable. Exactly. 00:14:26.990 --> 00:14:29.129 an orphan pathogen. That's the perfect term for 00:14:29.129 --> 00:14:31.289 it. It's too hard to study for basic research, 00:14:31.370 --> 00:14:33.730 and it's not dangerous enough to demand emergency 00:14:33.730 --> 00:14:36.830 medical funding. And because it sits in that 00:14:36.830 --> 00:14:39.570 exact intersection of difficult and non -critical, 00:14:39.909 --> 00:14:43.250 nobody studies it. Its 1887 mugshot remains its 00:14:43.250 --> 00:14:45.710 official profile just by default. And this is 00:14:45.710 --> 00:14:47.549 a vital lesson in the philosophy of science, 00:14:48.029 --> 00:14:50.830 really. Critical thinking requires us to actively 00:14:50.830 --> 00:14:53.330 hunt for the gaps in our knowledge, not just 00:14:53.330 --> 00:14:55.649 to plot our technological achievements. Right. 00:14:55.769 --> 00:14:58.629 We celebrate the ease of modern genetic sequencing, 00:14:59.649 --> 00:15:03.029 but we must rigorously ask what is being left 00:15:03.029 --> 00:15:06.549 unsequenced? What is sitting in the dark simply 00:15:06.549 --> 00:15:09.649 because it's too biologically stubborn or economically 00:15:09.649 --> 00:15:12.070 unviable to bring into the light? That's such 00:15:12.070 --> 00:15:15.169 a good point. Spirulum minus is the perfect embodiment 00:15:15.169 --> 00:15:18.250 of that systemic blind spot. The sequencing data 00:15:18.250 --> 00:15:20.570 is the only empirical tool that could finally 00:15:20.570 --> 00:15:23.450 resolve the question of its true evolutionary 00:15:23.450 --> 00:15:26.419 lineage. But the hurdles to acquire that data 00:15:26.419 --> 00:15:29.139 have proven just a bit too high for over 130 00:15:29.139 --> 00:15:31.879 years. It really forces you to re -evaluate how 00:15:31.879 --> 00:15:34.100 you look at a textbook, honestly. It really does. 00:15:34.340 --> 00:15:36.120 Okay, to bring this all together for you listening, 00:15:36.679 --> 00:15:39.539 we started this deep dive with a historical cold 00:15:39.539 --> 00:15:42.659 case, a mysterious pathogen associated with Sudoku, 00:15:43.019 --> 00:15:45.799 a form of rat bite fever, an organism named in 00:15:45.799 --> 00:15:48.899 1887 based purely on its curly shape viewed through 00:15:48.899 --> 00:15:51.730 a primitive microscope. We explored the immense 00:15:51.730 --> 00:15:54.830 biological friction it creates, stubbornly refusing 00:15:54.830 --> 00:15:57.750 to grow outside of a live animal host and making 00:15:57.750 --> 00:16:00.529 modern genetic extraction a nightmare of signal 00:16:00.529 --> 00:16:02.509 -to -noise ratios. Which is why no one wants 00:16:02.509 --> 00:16:06.909 to cut it. Exactly. We exposed a glaring physiological 00:16:06.909 --> 00:16:09.850 contradiction, realizing that a microaerophile 00:16:09.850 --> 00:16:13.090 thriving in a highly oxygenated mammalian bloodstream 00:16:13.090 --> 00:16:15.950 is the biological equivalent of a deep sea fish 00:16:15.950 --> 00:16:18.289 in a desert. This doesn't belong there. And we 00:16:18.289 --> 00:16:20.769 ended with the shocking revelation from the Washburn 00:16:20.769 --> 00:16:24.110 reference that, as of 2015, this organism had 00:16:24.110 --> 00:16:25.889 completely slipped through the cracks of the 00:16:25.889 --> 00:16:28.610 genomic era, leaving its true identity a total 00:16:28.610 --> 00:16:31.269 mystery. It forces a necessary humility upon 00:16:31.269 --> 00:16:33.450 the scientific community, I think. Oh, absolutely. 00:16:33.669 --> 00:16:36.450 The biological map is not a pristine finished 00:16:36.450 --> 00:16:39.539 document. It is heavily biased toward the organisms 00:16:39.539 --> 00:16:42.100 that are easy to observe and cheap to cultivate. 00:16:42.340 --> 00:16:45.100 The relevance here is profound. Science is an 00:16:45.100 --> 00:16:48.039 ongoing, frequently messy process. It carries 00:16:48.039 --> 00:16:50.379 historical baggage and outdated assumptions. 00:16:50.799 --> 00:16:53.159 There are literal cold cases in our medical databases 00:16:53.159 --> 00:16:55.480 just waiting for the technology or the funding 00:16:55.480 --> 00:16:57.840 to catch up with the organism. And I want to 00:16:57.840 --> 00:17:00.019 leave you with a final lingering thought to mull 00:17:00.019 --> 00:17:04.650 over. If a known disease -causing agent, one 00:17:04.650 --> 00:17:06.609 that we have a name for, that we know affects 00:17:06.609 --> 00:17:08.730 humans, and that we have been aware of since 00:17:08.730 --> 00:17:11.670 the 19th century, has remained a genetic ghost 00:17:11.670 --> 00:17:13.849 simply because it's difficult to grow in a lab. 00:17:14.529 --> 00:17:16.890 What other foundational facts about our natural 00:17:16.890 --> 00:17:20.190 world are fundamentally flawed? How many of our 00:17:20.190 --> 00:17:22.990 modern ecological or medical models are silently 00:17:22.990 --> 00:17:25.549 relying on 19th century visual descriptions, 00:17:25.950 --> 00:17:27.829 just waiting for someone to finally take a closer 00:17:27.829 --> 00:17:30.009 look at the DNA? What a brilliant question to 00:17:30.009 --> 00:17:32.430 end on. A huge thank you to you for joining us 00:17:32.430 --> 00:17:35.109 on this deep dive into the messy, fascinating 00:17:35.109 --> 00:17:37.750 fringes of medical science. Keep questioning 00:17:37.750 --> 00:17:40.150 the map, and most importantly, stay curious.