WEBVTT 00:00:00.000 --> 00:00:02.000 I want you to picture a specific scenario for 00:00:02.000 --> 00:00:04.339 a second. It's a real medical mystery. Imagine 00:00:04.339 --> 00:00:08.580 you are in the absolute prime of your life, somewhere 00:00:08.580 --> 00:00:11.960 between 30 and 50 years old. Right. You're not 00:00:11.960 --> 00:00:15.060 a kid with a developing immune system, not elderly 00:00:15.060 --> 00:00:17.219 with a fading one. You've been healthy your whole 00:00:17.219 --> 00:00:20.300 life. No chronic issues. You're working, paying 00:00:20.300 --> 00:00:23.079 the bills. You are, for all intents and purposes, 00:00:23.399 --> 00:00:25.640 bulletproof. It's the demographic that is supposed 00:00:25.640 --> 00:00:28.370 to be... The safest from a health perspective. 00:00:28.609 --> 00:00:31.530 Exactly. And then with just no warning at all, 00:00:31.710 --> 00:00:34.649 the floor drops out. Your body just stops defending 00:00:34.649 --> 00:00:37.170 itself. Wow. And I don't mean you catch a bad 00:00:37.170 --> 00:00:39.590 flu. I mean, you start getting inflections that 00:00:39.590 --> 00:00:42.250 a healthy human body should just shrug off without 00:00:42.250 --> 00:00:45.270 a second thought. Serious disseminated infections, 00:00:45.509 --> 00:00:47.450 the kind that land you in the hospital. That 00:00:47.450 --> 00:00:49.450 is a terrifying prospect to go from a healthy 00:00:49.450 --> 00:00:53.179 adult to critically immunocompromised. With seemingly 00:00:53.179 --> 00:00:56.520 no trigger. And that is exactly what we are unpacking 00:00:56.520 --> 00:00:58.659 today. We're doing a deep dive into a condition 00:00:58.659 --> 00:01:01.600 formerly known as adult onset immunodeficiency 00:01:01.600 --> 00:01:03.979 syndrome. And you have to stop right there. You 00:01:03.979 --> 00:01:07.200 do, because I can hear the gears turning in everyone's 00:01:07.200 --> 00:01:10.739 head. You hear immunodeficiency and your brain 00:01:10.739 --> 00:01:13.040 immediately autocompletes to something else. 00:01:13.319 --> 00:01:16.180 Right. It sounds like a synonym for AIDS, which 00:01:16.180 --> 00:01:19.299 is caused by the HIV virus. And we need to be 00:01:19.299 --> 00:01:21.040 crystal clear right out of the gate. This is 00:01:21.040 --> 00:01:24.040 absolutely not HIV AIDS. It's funny because even 00:01:24.040 --> 00:01:26.280 in the research, half the literature starts with 00:01:26.280 --> 00:01:28.760 that exact disclaimer. It's the elephant in the 00:01:28.760 --> 00:01:31.640 room. It has to be. The confusion is understandable 00:01:31.640 --> 00:01:34.040 because the outcome looks similar on a chart. 00:01:34.180 --> 00:01:37.079 Both conditions lead to a patient being vulnerable 00:01:37.079 --> 00:01:40.799 to what we call opportunistic infections. Bugs 00:01:40.799 --> 00:01:42.620 that only hurt you if your shields are down. 00:01:42.859 --> 00:01:45.659 Exactly. But the mechanism how the shields go 00:01:45.659 --> 00:01:48.680 down is completely different. HIV is a viral 00:01:48.680 --> 00:01:52.420 contagion. You catch it. Adult -onset immunodeficiency 00:01:52.420 --> 00:01:54.680 syndrome. It's not contagious. You cannot catch 00:01:54.680 --> 00:01:56.980 this from anyone. Which is a huge, huge distinction. 00:01:57.340 --> 00:01:59.480 So if it's not a virus attacking the immune system, 00:01:59.719 --> 00:02:02.319 what is it? It's an inside job. It's an autoimmune 00:02:02.319 --> 00:02:04.459 condition. Okay, so the call is coming from inside 00:02:04.459 --> 00:02:07.579 the house. Precisely. And our mission today is 00:02:07.579 --> 00:02:10.419 to figure out why the House is suddenly attacking 00:02:10.419 --> 00:02:13.199 its own security system. We've combed through 00:02:13.199 --> 00:02:15.580 the medical literature, the case studies. And 00:02:15.580 --> 00:02:17.800 we want to separate the media sensationalism, 00:02:17.800 --> 00:02:19.939 and believe me, there was a lot of it, from the 00:02:19.939 --> 00:02:22.259 biological reality. And honestly, the biological 00:02:22.259 --> 00:02:24.680 reality is fascinating enough without the hype. 00:02:24.780 --> 00:02:29.020 It forces us to ask some really... uncomfortable 00:02:29.020 --> 00:02:31.300 questions about how our immune system actually 00:02:31.300 --> 00:02:33.900 works. It does. When you look at a rare edge 00:02:33.900 --> 00:02:36.099 case like this, you aren't just studying a disease, 00:02:36.259 --> 00:02:38.259 you're studying a loophole in human biology. 00:02:38.439 --> 00:02:40.580 Right. So let's get into the mechanics of this 00:02:40.580 --> 00:02:43.860 loophole. In a standard autoimmune disease like 00:02:43.860 --> 00:02:47.759 lupus, the body attacks joints or organs. But 00:02:47.759 --> 00:02:49.659 here you're saying the body is attacking its 00:02:49.659 --> 00:02:52.020 own immune system. How does that even work? It 00:02:52.020 --> 00:02:54.080 all comes down to signaling. In this syndrome, 00:02:54.240 --> 00:02:56.759 the patient's body starts producing massive amounts 00:02:56.759 --> 00:03:00.719 of anti -interferon gamma autoantibodies. That 00:03:00.719 --> 00:03:02.979 is a mouthful. Let's break that down. Autoantibodies. 00:03:03.060 --> 00:03:05.879 Auto means self. Normal antibodies are the good 00:03:05.879 --> 00:03:07.879 guys. They're the homing missiles your body makes 00:03:07.879 --> 00:03:10.840 to lock onto viruses. Autoantibodies are defective 00:03:10.840 --> 00:03:13.939 missiles. They lock onto your own proteins. In 00:03:13.939 --> 00:03:15.500 this case, they're targeting a protein called 00:03:15.500 --> 00:03:18.240 interferon gamma. Interferon, it always sounds 00:03:18.240 --> 00:03:20.259 like some kind of sci -fi shield generator to 00:03:20.259 --> 00:03:22.819 me, but in the body, it's more like a communication 00:03:22.819 --> 00:03:24.960 line, right? That's a great way to put it. Let's 00:03:24.960 --> 00:03:28.080 use a military analogy. Your immune system is 00:03:28.080 --> 00:03:31.639 a fortress. You have foot soldiers, the macrophages, 00:03:31.780 --> 00:03:34.319 and their job is to go out and eat the enemy 00:03:34.319 --> 00:03:36.680 bacteria. Okay, the Pac -Man cells. The Pac -Man 00:03:36.680 --> 00:03:39.060 cells. Yeah. But they need orders. They need 00:03:39.060 --> 00:03:41.919 a general to tell them, hey, we're under attack. 00:03:42.139 --> 00:03:44.379 Turn on your weapons. And Interferon Gamma is 00:03:44.379 --> 00:03:47.680 the general. Exactly. When a cell spots an intruder, 00:03:47.780 --> 00:03:51.159 it releases Interferon Gamma. That signal screams, 00:03:51.360 --> 00:03:54.479 wake up, attack. It activates the macrophages 00:03:54.479 --> 00:03:56.500 to kill whatever they've swallowed. So in these 00:03:56.500 --> 00:03:58.860 patients, the body produces these autoantibodies. 00:03:58.979 --> 00:04:01.039 And those autoantibodies are like mutineers. 00:04:01.039 --> 00:04:03.300 They tackle the general, gag him, tie him up. 00:04:03.460 --> 00:04:05.900 The signal never goes out. Wow. So you have these 00:04:05.900 --> 00:04:08.620 foot soldiers, the macrophages, standing right 00:04:08.620 --> 00:04:11.030 next to the bacteria. They might even swallow 00:04:11.030 --> 00:04:13.030 them. But because they never get the order to 00:04:13.030 --> 00:04:15.509 kill, the bacteria just sit there inside the 00:04:15.509 --> 00:04:18.170 cell multiplying. That is incredibly unsettling. 00:04:18.209 --> 00:04:20.889 It's not that the army is dead like an untreated 00:04:20.889 --> 00:04:23.649 HIV. No, not at all. The army is there. They're 00:04:23.649 --> 00:04:26.050 just waiting for orders that never arrive. Correct. 00:04:26.089 --> 00:04:29.470 And that specific failure makes the body vulnerable 00:04:29.470 --> 00:04:33.069 to a very specific type of enemy, intracellular 00:04:33.069 --> 00:04:36.089 pathogens. These are germs that have evolved 00:04:36.089 --> 00:04:38.930 to hide inside your cells. A healthy person fights 00:04:38.930 --> 00:04:41.129 them off easily because the general spots them. 00:04:41.189 --> 00:04:43.709 Right. But without that signal, these specific 00:04:43.709 --> 00:04:46.410 bugs just run rampant. And that explains why 00:04:46.410 --> 00:04:48.670 the infection is disseminated. It's not just 00:04:48.670 --> 00:04:50.910 a localized thing. The system -wide coordination 00:04:50.910 --> 00:04:53.569 is gone. Exactly. The alarm wire's a big cut. 00:04:53.750 --> 00:04:57.189 Okay, so we understand the mechanism, this mutiny 00:04:57.189 --> 00:04:59.550 against the general, but this is where the story 00:04:59.550 --> 00:05:02.310 gets really weird for me. The WHO... is just 00:05:02.310 --> 00:05:04.790 as baffling as the how. The demographics are 00:05:04.790 --> 00:05:07.949 incredibly specific. Yeah, it's not random. This 00:05:07.949 --> 00:05:10.050 condition is overwhelmingly found in Southeast 00:05:10.050 --> 00:05:12.810 Asians. We're seeing the majority of cases in 00:05:12.810 --> 00:05:16.170 Thailand, Taiwan, Vietnam, and among immigrants 00:05:16.170 --> 00:05:18.730 from those regions. Yes, and combined with that, 00:05:18.829 --> 00:05:21.250 we have the age factor. The average age of onset 00:05:21.250 --> 00:05:24.069 is 30 to 50. See, that's the part that trips 00:05:24.069 --> 00:05:26.410 me up. Usually, if you have a genetic problem 00:05:26.410 --> 00:05:29.449 with your immune system, a primary immunodeficiency. 00:05:29.569 --> 00:05:31.699 You know about it when you're a toddler. Right. 00:05:31.779 --> 00:05:34.199 You're the kid who's always sick. Exactly. Primary 00:05:34.199 --> 00:05:36.519 immunodeficiency is almost always present in 00:05:36.519 --> 00:05:39.680 infancy. To go 40 years with a perfectly good 00:05:39.680 --> 00:05:41.839 immune system and then have it suddenly collapse, 00:05:42.160 --> 00:05:45.199 well, that implies this isn't just a simple genetic 00:05:45.199 --> 00:05:47.720 error. But there is a genetic component, right? 00:05:47.800 --> 00:05:50.459 The notes mention HLA genes. There is absolutely 00:05:50.459 --> 00:05:53.240 a genetic component. The research shows a strong 00:05:53.240 --> 00:05:56.920 link to specific HLA genes. These are the genes 00:05:56.920 --> 00:05:58.420 that help your immune system tell the difference 00:05:58.420 --> 00:06:00.699 between self and foreign. So the blueprint for 00:06:00.699 --> 00:06:03.360 this is there. It is. And there's also research 00:06:03.360 --> 00:06:05.620 pointing to a gene called Serpina1, which is 00:06:05.620 --> 00:06:08.810 involved in controlling inflammation. But here's 00:06:08.810 --> 00:06:11.149 the paradox, and this is what drives researchers 00:06:11.149 --> 00:06:14.189 nuts. Even though it's clearly linked to genetics, 00:06:14.410 --> 00:06:17.649 the disease is not heritable. Wait, run that 00:06:17.649 --> 00:06:20.430 by me again. It's genetic, but not hereditary. 00:06:20.569 --> 00:06:23.569 It means it doesn't pass down directly in families 00:06:23.569 --> 00:06:26.449 like, say, cystic fibrosis does. You don't see 00:06:26.449 --> 00:06:29.550 a clear family tree of grandma had it, mom had 00:06:29.550 --> 00:06:31.550 it, now I have it. That seems like a contradiction. 00:06:31.689 --> 00:06:33.769 If it's in the genes, why isn't it running in 00:06:33.769 --> 00:06:36.069 the family? It suggests that genetics are necessary, 00:06:36.209 --> 00:06:38.170 but not sufficient. Think of it like a loaded 00:06:38.170 --> 00:06:41.230 gun. The genetics, being Southeast Asian, having 00:06:41.230 --> 00:06:44.930 those HLA alleles, that loads the gun. But a 00:06:44.930 --> 00:06:47.410 loaded gun can sit on a table for 50 years and 00:06:47.410 --> 00:06:49.970 never go off. You need a trigger. Exactly. You 00:06:49.970 --> 00:06:52.329 need something to pull the trigger. The theory 00:06:52.329 --> 00:06:54.370 is that this is an interaction between nature 00:06:54.370 --> 00:06:56.850 and nurture. You have the genetic susceptibility, 00:06:56.850 --> 00:06:58.829 and then halfway through your life, you encounter 00:06:58.829 --> 00:07:01.750 an environmental factor, maybe a virus, maybe 00:07:01.750 --> 00:07:04.160 a bacterial infection. And that trigger event 00:07:04.160 --> 00:07:06.959 confuses the immune system just enough to start 00:07:06.959 --> 00:07:09.519 making those autoantibodies. Right. And once 00:07:09.519 --> 00:07:12.079 those autoantibodies start forming, they block 00:07:12.079 --> 00:07:15.079 the interferon gamma, which lets infections take 00:07:15.079 --> 00:07:17.899 hold. And the cruel irony is that the more infections 00:07:17.899 --> 00:07:20.319 you get, the more your immune system tries to 00:07:20.319 --> 00:07:23.519 activate. Which might just stimulate more autoantibody 00:07:23.519 --> 00:07:25.439 production. It becomes a vicious cycle. It's 00:07:25.439 --> 00:07:28.160 the two -hit hypothesis. Hit one is your DNA. 00:07:28.360 --> 00:07:30.910 Hit two is the environment. And you need both. 00:07:31.129 --> 00:07:33.230 And that would perfectly explain the age of onset. 00:07:33.329 --> 00:07:35.790 You need time to stumble across that environmental 00:07:35.790 --> 00:07:38.029 trigger. It might take 30 or 40 years before 00:07:38.029 --> 00:07:39.870 you encounter the specific thing that sets this 00:07:39.870 --> 00:07:43.250 all in motion. That is both fascinating and slightly 00:07:43.250 --> 00:07:46.089 terrifying. Makes you wonder what other triggers 00:07:46.089 --> 00:07:49.370 we're just waiting to walk into. But let's ground 00:07:49.370 --> 00:07:51.110 this. What does this actually look like for the 00:07:51.110 --> 00:07:53.529 person going through it? Because this list of 00:07:53.529 --> 00:07:56.569 opportunistic pathogens is, well, it's a horror 00:07:56.569 --> 00:07:59.629 show. It is a brutal clinical picture. Patients 00:07:59.629 --> 00:08:01.649 are flooded by germs that exist everywhere but 00:08:01.649 --> 00:08:04.589 usually don't hurt us. I saw salmonella on the 00:08:04.589 --> 00:08:08.110 list and I thought, OK, food poisoning. But it's 00:08:08.110 --> 00:08:10.290 not just food poisoning here, is it? No, this 00:08:10.290 --> 00:08:13.350 is non -typhoidal salmonella. But in these patients, 00:08:13.410 --> 00:08:15.670 it becomes invasive. It gets into the bloodstream. 00:08:15.790 --> 00:08:18.410 It causes sepsis. It is life -threatening. And 00:08:18.410 --> 00:08:20.670 that's just one of them. Right. The hallmark 00:08:20.670 --> 00:08:24.389 infection is actually non -tuberculous mycobacteria. 00:08:24.490 --> 00:08:26.790 These are cousins of tuberculosis that live in 00:08:26.790 --> 00:08:29.110 soil and water. OK. If you or I breathe them 00:08:29.110 --> 00:08:31.610 in, our macrophages eat them and destroy them. 00:08:31.670 --> 00:08:34.210 Done. But for these patients, the macrophages 00:08:34.210 --> 00:08:36.370 eat them and then just sit there. The bacteria 00:08:36.370 --> 00:08:39.429 multiply inside the cells, causing massive infection. 00:08:39.690 --> 00:08:42.169 And physically, what are the symptoms? It often 00:08:42.169 --> 00:08:44.690 manifests as generalized pustular psoriasis. 00:08:44.710 --> 00:08:46.970 So we're talking about widespread painful skin 00:08:46.970 --> 00:08:49.909 lesions, fevers, wasting away. The lymph nodes 00:08:49.909 --> 00:08:51.909 swell up because they're packed with infected 00:08:51.909 --> 00:08:54.360 cells that can't clear anything. And this leads 00:08:54.360 --> 00:08:56.820 to a diagnosis problem. I read that one physician 00:08:56.820 --> 00:08:59.059 noted how often this gets confused with actual 00:08:59.059 --> 00:09:02.519 tuberculosis. It's a tragic masquerade. A patient 00:09:02.519 --> 00:09:05.820 comes in, maybe from Thailand or Vietnam, coughing, 00:09:05.960 --> 00:09:08.860 losing weight, swollen lymph nodes. The doctor 00:09:08.860 --> 00:09:11.460 does a scan and sees granulomas in the lungs. 00:09:11.620 --> 00:09:14.500 It looks exactly like TB. So they start TB treatment. 00:09:14.740 --> 00:09:18.120 They start standard anti -TB drugs. Yeah. But 00:09:18.120 --> 00:09:20.500 the patient doesn't get better. Or maybe they 00:09:20.500 --> 00:09:22.519 get better for a week. And then crash again. 00:09:22.720 --> 00:09:25.299 Why? Because it's not just the bacteria. It's 00:09:25.299 --> 00:09:27.600 the immune system failure allowing the bacteria 00:09:27.600 --> 00:09:30.720 to thrive. You can poison the bacteria, sure. 00:09:30.960 --> 00:09:33.279 But if the body can't clean up the mess, you're 00:09:33.279 --> 00:09:35.580 fighting a losing battle. That must be agonizing. 00:09:35.600 --> 00:09:37.659 To be treated for the wrong thing while your 00:09:37.659 --> 00:09:40.279 body is just failing. So once they finally realize 00:09:40.279 --> 00:09:43.559 what it is, what can they do? Is there a cure? 00:09:44.029 --> 00:09:46.110 There isn't a cure in the sense of a magic pill. 00:09:46.210 --> 00:09:48.110 You can't just give them interferon gamma injections 00:09:48.110 --> 00:09:50.570 because remember... Bodies making antibodies 00:09:50.570 --> 00:09:52.769 that will just neutralize it instantly. Exactly. 00:09:52.850 --> 00:09:54.850 It's like pouring water into a bucket with a 00:09:54.850 --> 00:09:56.789 giant hole in it. So it's all about management. 00:09:57.090 --> 00:10:00.429 It's a two -pronged war. First, you have to aggressively 00:10:00.429 --> 00:10:03.549 treat the infection itself. Long -term antibiotics, 00:10:03.730 --> 00:10:06.389 sometimes for years. But you also have to stop 00:10:06.389 --> 00:10:09.539 the mutiny. The notes mention rituximab. Now, 00:10:09.580 --> 00:10:11.759 I know that's a serious drug. It's used in chemotherapy, 00:10:12.059 --> 00:10:14.179 right? It is. It's a monoclonal antibody that 00:10:14.179 --> 00:10:16.820 targets B cells. And B cells are the factories 00:10:16.820 --> 00:10:19.240 in your body that produce antibodies. So the 00:10:19.240 --> 00:10:22.159 logic is, if the factory is making bad parts... 00:10:22.159 --> 00:10:24.539 You shut down the factory. But wait, you're taking 00:10:24.539 --> 00:10:27.259 a patient... who is already riddled with severe 00:10:27.259 --> 00:10:29.919 infections, and you're suppressing their immune 00:10:29.919 --> 00:10:32.700 system even more. That is the paradox. It sounds 00:10:32.700 --> 00:10:35.019 completely counterintuitive, almost dangerous. 00:10:35.240 --> 00:10:37.820 You are nuking the B cells of an immunocompromised 00:10:37.820 --> 00:10:41.179 person. But? But the goal is to stop the production 00:10:41.179 --> 00:10:44.059 of that specific autoantibody that's blinding 00:10:44.059 --> 00:10:46.539 the rest of the immune system. If you can lower 00:10:46.539 --> 00:10:49.139 those levels, the captain interferon gamma can 00:10:49.139 --> 00:10:51.220 finally start shouting orders again, and the 00:10:51.220 --> 00:10:53.389 macrophages can wake up and start fighting. It's 00:10:53.389 --> 00:10:56.090 an incredibly high -stakes balancing act. Incredibly 00:10:56.090 --> 00:10:58.889 high stakes. But for many patients, it's the 00:10:58.889 --> 00:11:01.350 only thing that works. It's just wild complexity, 00:11:01.690 --> 00:11:05.190 and yet, looking at how the media handled this, 00:11:05.250 --> 00:11:07.350 you'd think it was a script for a zombie movie. 00:11:07.549 --> 00:11:10.090 Ah, yes, the AIDS 2 .0 narrative. This really 00:11:10.090 --> 00:11:12.350 got under my skin. I was looking at headlines 00:11:12.350 --> 00:11:14.990 from a few years ago. You had websites literally 00:11:14.990 --> 00:11:18.169 calling it AIDS 2 .0. The Epoch Times ran with... 00:11:18.649 --> 00:11:21.490 apparently highly contagious AIDS -like condition. 00:11:21.809 --> 00:11:24.289 It's a textbook example of irresponsible medical 00:11:24.289 --> 00:11:27.570 journalism. It's scientific illiteracy weaponized 00:11:27.570 --> 00:11:30.129 for clicks. It's fear -mongering, plain and simple. 00:11:30.289 --> 00:11:33.070 It is. And it's so dangerous because it conflates 00:11:33.070 --> 00:11:36.090 two things that scare people, AIDS and contagion. 00:11:36.269 --> 00:11:39.409 By calling it AIDS 2 .0, they imply a death sentence. 00:11:39.549 --> 00:11:42.370 And by calling it contagious, they imply a pandemic. 00:11:42.669 --> 00:11:44.730 Which isolates the patients even more. I mean, 00:11:44.730 --> 00:11:46.950 imagine having this rare autoimmune condition 00:11:46.950 --> 00:11:49.009 and suddenly your neighbors are afraid of you 00:11:49.009 --> 00:11:51.590 because of some headline. Exactly. We have to 00:11:51.590 --> 00:11:53.590 give credit to the experts who pushed back. The 00:11:53.590 --> 00:11:56.629 Daily Beast ran a piece quoting Dr. Kent Sepkovitz, 00:11:56.669 --> 00:11:59.129 who practically shouted from the rooftops. This 00:11:59.129 --> 00:12:02.330 is not AIDS 2 .0. A necessary correction. He 00:12:02.330 --> 00:12:04.149 had to explain that just because the symptom 00:12:04.149 --> 00:12:06.850 is an opportunistic infection, it doesn't mean 00:12:06.850 --> 00:12:09.909 the cause is a contagious virus. It is crucial 00:12:09.909 --> 00:12:12.149 to understand that. You are not going to catch 00:12:12.149 --> 00:12:15.169 anti -interferon autoantibodies from a handshake. 00:12:15.190 --> 00:12:18.330 The biological impossibility. It really highlights 00:12:18.330 --> 00:12:21.450 how careful we have to be with language, but... 00:12:21.899 --> 00:12:24.960 And this is a big but. While the media was busy 00:12:24.960 --> 00:12:27.080 getting it wrong, the scientific community was 00:12:27.080 --> 00:12:29.480 quietly finding a connection that turned out 00:12:29.480 --> 00:12:33.059 to be hugely important. And this brings us to 00:12:33.059 --> 00:12:36.220 the so what of this whole deep dive. This is 00:12:36.220 --> 00:12:38.659 where the story shifts. Up until now, we've been 00:12:38.659 --> 00:12:41.360 talking about a rare regional disease, a curiosity. 00:12:41.539 --> 00:12:44.179 But then 2020 happened. The pandemic. The COVID 00:12:44.179 --> 00:12:47.080 -19 pandemic. And suddenly, researchers noticed 00:12:47.080 --> 00:12:49.740 something strange. We all know the pattern. Most 00:12:49.740 --> 00:12:52.220 people got COVID and had a bad flu. But some 00:12:52.220 --> 00:12:54.039 healthy adults, people with no pre -existing 00:12:54.039 --> 00:12:56.139 conditions, were crashing. Ending up in the ICU. 00:12:56.399 --> 00:12:58.980 Right. With severe pneumonia and many were dying. 00:12:59.320 --> 00:13:01.440 And doctors couldn't figure out why. And I'm 00:13:01.440 --> 00:13:03.080 looking at the study here. They started looking 00:13:03.080 --> 00:13:05.100 at the blood of these severe COVID patients. 00:13:05.159 --> 00:13:07.159 And what did they find? They found the exact 00:13:07.159 --> 00:13:09.799 same mechanism we've been discussing. A significant 00:13:09.799 --> 00:13:12.320 percentage of those patients with life -threatening 00:13:12.320 --> 00:13:16.559 COVID had high levels of anti interferon autoantibodies. 00:13:16.659 --> 00:13:19.139 Their bodies were blocking their own interferon 00:13:19.139 --> 00:13:22.559 signals. So the same sabotage mechanism that 00:13:22.559 --> 00:13:24.980 drives this rare Southeast Asian syndrome was 00:13:24.980 --> 00:13:27.620 actually a huge factor in making COVID deadly 00:13:27.620 --> 00:13:29.840 for a chunk of the global population. Exactly. 00:13:30.320 --> 00:13:32.860 Interferons are the body's primary defense against 00:13:32.860 --> 00:13:36.039 viruses. If you block them, the virus replicates 00:13:36.039 --> 00:13:39.139 unchecked. It turns out that this rare mechanism, 00:13:39.480 --> 00:13:41.799 it wasn't so rare after all, it was just hiding, 00:13:41.840 --> 00:13:43.659 waiting for the right trigger. In this case, 00:13:43.700 --> 00:13:46.570 SARS -CoV -2. That is a Rosetta Stone moment. 00:13:46.710 --> 00:13:49.029 It validates the entire field of rare disease 00:13:49.029 --> 00:13:51.110 research. You might look at this syndrome and 00:13:51.110 --> 00:13:53.129 say, why spend money studying something that 00:13:53.129 --> 00:13:55.549 only affects a few thousand people? Yeah. But 00:13:55.549 --> 00:13:58.090 by studying that edge case, we learned how the 00:13:58.090 --> 00:14:01.210 immune system fails. And that knowledge gave 00:14:01.210 --> 00:14:03.710 us a massive clue to understanding a global pandemic 00:14:03.710 --> 00:14:06.330 that killed millions. It's humbling. It really 00:14:06.330 --> 00:14:08.789 changes how you look at healthy people. You might 00:14:08.789 --> 00:14:10.870 walk around feeling invincible, but you could 00:14:10.870 --> 00:14:13.259 have these. autoantibodies or the potential to 00:14:13.259 --> 00:14:16.059 make them just sitting there. It forces us to 00:14:16.059 --> 00:14:19.440 rethink the very definition of immunocompromised. 00:14:20.139 --> 00:14:23.120 We used to think it was a binary thing. You either 00:14:23.120 --> 00:14:25.519 have a disease or you don't. But this suggests 00:14:25.519 --> 00:14:28.000 there is a whole spectrum of silent vulnerability. 00:14:28.639 --> 00:14:30.860 You might have a chink in the armor regarding 00:14:30.860 --> 00:14:34.320 interferon that never ever matters until you 00:14:34.320 --> 00:14:38.559 meet a specific mycobacteria. or a specific coronavirus. 00:14:39.059 --> 00:14:41.259 And then the drawbridge comes down. And you don't 00:14:41.259 --> 00:14:43.100 even know why. It highlights that the immune 00:14:43.100 --> 00:14:45.500 system is not just about strength. It's about 00:14:45.500 --> 00:14:47.779 regulation. It's about the general being able 00:14:47.779 --> 00:14:50.120 to shout orders. If that one signal gets crossed, 00:14:50.399 --> 00:14:52.820 the whole fortress can fall. So let's bring this 00:14:52.820 --> 00:14:54.899 all back together. We started with a mystery. 00:14:55.399 --> 00:14:58.600 Healthy adults, 30 to 50 years old, suddenly 00:14:58.600 --> 00:15:00.899 losing their immune defense. We discovered it's 00:15:00.899 --> 00:15:03.240 an autoimmune mutiny antibodies blocking the 00:15:03.240 --> 00:15:06.690 captain, interferon gamma. allowing common bacteria 00:15:06.690 --> 00:15:09.330 to become deadly. We learned it's a genetic puzzle, 00:15:09.490 --> 00:15:12.250 concentrated in Southeast Asia, linked to certain 00:15:12.250 --> 00:15:15.049 genes, but triggered by the environment later 00:15:15.049 --> 00:15:18.090 in life, not a contagious plague, despite what 00:15:18.090 --> 00:15:20.629 the headlines tried to sell us. And finally, 00:15:20.649 --> 00:15:23.629 we realized this obscure mechanism is actually 00:15:23.629 --> 00:15:27.090 a fundamental key to understanding human immunity, 00:15:27.330 --> 00:15:30.330 linking a rare syndrome directly to the mechanics 00:15:30.330 --> 00:15:33.509 of severe COVID -19. It's a perfect example of 00:15:33.509 --> 00:15:36.070 why we do these deep dives. You pull a loose 00:15:36.070 --> 00:15:38.370 thread on a rare sweater and you find out it's 00:15:38.370 --> 00:15:40.330 connected to the fabric of everyone's health. 00:15:40.549 --> 00:15:42.690 It certainly makes you appreciate the days when 00:15:42.690 --> 00:15:45.049 your signaling proteins are all doing their job 00:15:45.049 --> 00:15:47.509 correctly. Absolutely. Before we sign off, I 00:15:47.509 --> 00:15:48.950 want to leave you with a thought that's been 00:15:48.950 --> 00:15:51.330 nagging me. We talked about how this condition 00:15:51.330 --> 00:15:54.970 is genetic but not heritable. A loaded gun waiting 00:15:54.970 --> 00:15:57.289 for a trigger. The dormant instruction concept. 00:15:57.470 --> 00:16:00.419 Exactly. It makes you wonder... If the code for 00:16:00.419 --> 00:16:02.960 this immune collapse is hiding in the DNA of 00:16:02.960 --> 00:16:05.379 some people, just waiting for the right environmental 00:16:05.379 --> 00:16:08.279 key to unlock it, what else is in there? What 00:16:08.279 --> 00:16:10.240 other dormant instructions are hiding in our 00:16:10.240 --> 00:16:12.919 DNA right now? What other switches are sitting 00:16:12.919 --> 00:16:16.320 there in your code or mine just waiting for the 00:16:16.320 --> 00:16:18.919 right virus, the right chemical, or the right 00:16:18.919 --> 00:16:21.559 environment to wake them up? That is a question 00:16:21.559 --> 00:16:24.240 that biology is only just beginning to answer. 00:16:24.419 --> 00:16:26.240 And on that slightly existential note, thanks 00:16:26.240 --> 00:16:27.799 for diving deep with us. We'll see you on the 00:16:27.799 --> 00:16:28.159 next one.