WEBVTT 00:00.000 --> 00:02.000 ... 00:02.000 --> 00:04.000 ... 00:30.000 --> 00:32.000 ... 00:32.000 --> 00:34.000 ... 00:34.000 --> 00:38.000 ... 00:38.000 --> 00:40.000 ... 00:40.000 --> 00:42.000 ... 00:42.000 --> 00:44.000 ... 00:44.000 --> 00:46.000 ... 00:46.000 --> 00:48.000 ... 00:48.000 --> 00:50.000 ... 00:50.000 --> 00:52.000 ... 00:52.000 --> 00:54.000 ... 00:54.000 --> 00:56.000 ... 00:56.000 --> 00:58.000 ... 00:58.000 --> 01:00.000 ... 01:00.000 --> 01:02.000 ... 01:02.000 --> 01:04.000 ... 01:04.000 --> 01:06.000 ... 01:06.000 --> 01:08.000 ... 01:08.000 --> 01:10.000 ... 01:10.000 --> 01:12.000 ... 01:12.000 --> 01:14.000 ... 01:14.000 --> 01:16.000 ... 01:16.000 --> 01:18.000 ... 01:18.000 --> 01:20.000 ... 01:20.000 --> 01:22.000 ... 01:22.000 --> 01:24.000 ... 01:24.000 --> 01:26.000 ... 01:26.000 --> 01:27.000 ... 01:27.000 --> 01:32.560 or CHD, and I believe he has a PhD in some sort 01:32.560 --> 01:35.840 of scientific discipline from what I understand. 01:38.840 --> 01:47.480 That probably sounds a little too good to be true, 01:47.480 --> 01:50.120 but I'm interested. 01:50.120 --> 01:55.320 I have something going with Adobe, but it's still quite a lot 01:55.320 --> 01:57.600 of work to clean up all the timestamps and stuff, 01:57.600 --> 02:02.120 and I've been trying to meaning to play around in the settings. 02:02.120 --> 02:03.520 And I just haven't gotten there yet. 02:03.520 --> 02:06.360 I have so much other. 02:06.360 --> 02:08.800 Anyway, I'm not whining. 02:08.800 --> 02:12.480 I've just got a lot of plates spinning right now 02:12.480 --> 02:18.440 and just trying to maintain this daily habit here. 02:18.440 --> 02:19.640 Oh, missed it. 02:25.320 --> 02:44.120 Yeah, we are here back again trying to rescue a few sheep, 02:44.120 --> 02:46.280 wake them up. 02:46.280 --> 02:51.800 It's pretty disturbing. 02:51.800 --> 02:55.200 Actually, I think you'll be very surprised 02:55.200 --> 03:01.960 to note there who's a common 434 that Kevin McCarran actually 03:01.960 --> 03:07.560 just had Stephanie Sinef on in the last 24 hours, which is kind 03:07.560 --> 03:13.600 of I'm not really sure if I should say anything about it 03:13.600 --> 03:17.640 other than to say that the enchantment and the faith 03:17.640 --> 03:19.600 is still very much intact. 03:19.600 --> 03:25.160 But yes, Stephanie Sinef was on Kevin McCarran's stream 03:25.160 --> 03:27.400 as little as 24 hours ago. 03:27.400 --> 03:29.320 That is a lot to unpack, indeed. 03:29.320 --> 03:32.600 It's a lot to unpack. 03:32.600 --> 03:35.840 So here we are anyway. 03:35.840 --> 03:38.160 And we are still in those interesting times 03:38.160 --> 03:41.320 where our consciousness, our actual attention 03:41.320 --> 03:46.840 is prime real estate, and it's not really 03:46.840 --> 03:48.640 about TikTok or anything else. 03:48.640 --> 03:51.440 I mean, all these things are being used to manipulate us. 03:51.440 --> 03:54.880 What we think about, what we pay attention to to make sure 03:54.880 --> 04:01.760 that whatever is perceived to be true is perceived to be true. 04:01.760 --> 04:06.160 It's just that sound, right, that it's just a magic spell 04:06.160 --> 04:08.640 that they cast every time they look at you. 04:12.640 --> 04:16.320 And yeah, we're not really arguing about anything. 04:16.320 --> 04:18.480 We can believe whatever we want, because we're not 04:18.480 --> 04:20.960 using logic anymore. 04:20.960 --> 04:22.880 And our money is out of our control. 04:22.880 --> 04:26.720 If our money is out of our control, I mean, I don't know. 04:26.720 --> 04:28.720 I don't know in the city of the age. 04:28.720 --> 04:29.720 Yeah. 04:29.720 --> 04:31.720 What sites do you see? 04:46.720 --> 04:50.720 Think you're a bear and a tummy bum. 04:50.720 --> 04:51.720 Good. 04:51.720 --> 04:53.720 You don't understand, Mr. Brown. 04:53.720 --> 04:55.720 You don't understand, Mr. Brown is a holy weapon. 04:55.720 --> 04:56.720 Please. 05:04.720 --> 05:07.720 Man, I still can't believe it's been so long 05:07.720 --> 05:13.720 since some of these people were on our screens. 05:13.720 --> 05:15.720 What I would challenge you to do, at some point 05:15.720 --> 05:18.720 when you're a little bored, is go look for Liana Wen 05:18.720 --> 05:23.720 and go look for some 2015 and 2014 TED Talk videos. 05:23.720 --> 05:25.720 Boy, you'll love those. 05:25.720 --> 05:26.720 Those are just great. 05:26.720 --> 05:27.720 Those are great. 05:30.720 --> 05:33.720 Ladies and gentlemen, welcome to Giga Home Biological. 05:33.720 --> 05:36.720 If you have been here for a while, you are here at the top 05:36.720 --> 05:37.720 of the wave. 05:37.720 --> 05:40.720 We are staying focused on the biology, not taking the bait 05:40.720 --> 05:43.720 and loving our neighbors. 05:43.720 --> 05:45.720 Thank you very much for sharing my work. 05:45.720 --> 05:46.720 That's how this works. 05:46.720 --> 05:49.720 There are people who also financially support my work, 05:49.720 --> 05:53.720 my family, but actually the best way you can help us 05:53.720 --> 05:58.720 is to spread the word because the people that can help us 05:58.720 --> 06:01.720 will click the extra times in order to get there. 06:01.720 --> 06:05.720 The people that really have the means to help 06:05.720 --> 06:09.720 and the heart to help are going to be called to help. 06:09.720 --> 06:13.720 And the rest of you, I just need you to share. 06:13.720 --> 06:17.720 If you think this is worth your while, if this is worth your time, 06:17.720 --> 06:20.720 the Giga Home Biological is something you need other people to see, 06:20.720 --> 06:23.720 then please, please share this word. 06:43.720 --> 06:46.720 I had to clear my throat here for a second. 06:49.720 --> 06:53.720 We are in the midst of a paradigm shift, 06:53.720 --> 06:56.720 and I think the reason why we're in the midst of a paradigm shift 06:56.720 --> 06:59.720 is because we've actually jumped ahead a couple of dominoes, 06:59.720 --> 07:02.720 which is something that somebody suggested a long time ago. 07:02.720 --> 07:05.720 If we want to stop this, we're going to need to jump ahead 07:05.720 --> 07:07.720 a few moves in the game. 07:07.720 --> 07:10.720 And I don't think that we're that far off right now 07:10.720 --> 07:13.720 from having jumped ahead a few moves. 07:13.720 --> 07:18.720 And that is because we've had our hands down from our eyes 07:18.720 --> 07:23.720 for long enough to kind of pull ourselves out of this a little bit. 07:25.720 --> 07:28.720 And this is Giga Home Biological, a high-resistance, 07:28.720 --> 07:30.720 low-noise information brief brought to you by a biologist. 07:30.720 --> 07:34.720 The illusion is sustained only through our active participation. 07:34.720 --> 07:39.720 And so we are here trying to advocate for one another 07:39.720 --> 07:40.720 to drop out. 07:40.720 --> 07:45.720 Some of that dropping out might actually be not sending our kids 07:45.720 --> 07:50.720 to university necessarily with any plan on what to do. 07:50.720 --> 07:53.720 That might be one good idea. 07:53.720 --> 07:57.720 So Giga Home Biological is something that started really 07:57.720 --> 08:02.720 from a bike riding YouTube channel in my commute 08:02.720 --> 08:05.720 to the University of Pittsburgh School of Medicine. 08:05.720 --> 08:08.720 And I was really doing just Journal Club on my bike. 08:08.720 --> 08:12.720 And then here we are nearly five years later. 08:12.720 --> 08:17.720 And we are now good afternoon. 08:17.720 --> 08:19.720 It is 2.14. 08:19.720 --> 08:20.720 I apologize. 08:20.720 --> 08:23.720 I started late today by one hour. 08:23.720 --> 08:27.720 It is the 25th of April and it's 2024. 08:27.720 --> 08:30.720 We've had lots of eclipses and survived. 08:30.720 --> 08:35.720 We are about to approach an active elective season. 08:35.720 --> 08:40.720 And other years, it would already be quite a bit more of an issue 08:40.720 --> 08:43.720 of a thing than it is now. 08:43.720 --> 08:46.720 And it's actually kind of surprising that we are where we are. 08:46.720 --> 08:50.720 But again, we are trapped underneath that hand in that, 08:50.720 --> 08:53.720 in that, I don't know how to point to that thing in that picture 08:53.720 --> 08:54.720 over here, Captain. 08:54.720 --> 08:57.720 Think of it like it's, it's just above the table. 08:57.720 --> 09:03.720 So anyway, this hand in this picture here is 09:04.720 --> 09:08.720 essentially representing the near total control over what we think. 09:08.720 --> 09:13.720 And that near total control over what we think combined with the fact 09:13.720 --> 09:16.720 that what we think is not related to what we need to understand. 09:16.720 --> 09:19.720 We're not really able to exercise informed consent. 09:19.720 --> 09:22.720 And specifically in the context of the pandemic, 09:22.720 --> 09:26.720 because we've been led to believe by the conscious, 09:27.720 --> 09:31.720 an intelligent manipulation of our organized habits and opinions, 09:31.720 --> 09:36.720 that there was at some point a bad cave virus or a lab leak that was 09:36.720 --> 09:41.720 responsible for the numbers that are in this graph right here. 09:41.720 --> 09:46.720 And that the novel virus equals the excess deaths. 09:46.720 --> 09:49.720 I guess you can't see that very well, but it's there. 09:50.720 --> 09:54.720 And of course, I've been arguing that this is how they did it. 09:54.720 --> 09:58.720 Exactly where and how this novel coronavirus spread to humans. 09:58.720 --> 10:02.720 Did it emerge naturally from the animal world and get transmitted 10:02.720 --> 10:04.720 to people in Wuhan, China? 10:04.720 --> 10:09.720 Or from a security breach at a research lab, also in Wuhan? 10:09.720 --> 10:12.720 That has been the subject of an ongoing research lab. 10:12.720 --> 10:16.720 William Brangham is back with details about new studies published... 10:16.720 --> 10:18.720 Does the sound occasion I start over? 10:18.720 --> 10:21.720 The point is a live animal market. 10:21.720 --> 10:23.720 Judy, trying to understand... 10:23.720 --> 10:25.720 There's any sink problem, let me know. 10:25.720 --> 10:28.720 You can also just try to refresh their SUSFIDER. 10:28.720 --> 10:32.720 So I've been making this analogy that actually the PBS NewsHour 10:32.720 --> 10:34.720 and other news agencies, 10:34.720 --> 10:37.720 and I'm going to talk a little bit about this. 10:37.720 --> 10:41.720 I've been making this analogy that actually the PBS NewsHour 10:41.720 --> 10:46.720 and other news agencies and even operators and podcasts 10:46.720 --> 10:50.720 and academics that have appeared on podcasts 10:50.720 --> 10:55.720 have systematically misled us to believe that through this illusion of consensus, 10:55.720 --> 10:59.720 that the right question to ask is where the hell did this thing come from? 10:59.720 --> 11:03.720 Not whether there is a thing or whether that thing is significant 11:03.720 --> 11:07.720 or whether that thing is part of a larger family of things, 11:07.720 --> 11:10.720 but just that where did this thing come from? 11:10.720 --> 11:15.720 And by being forced to ask that question and to debate that question, 11:15.720 --> 11:21.720 we were unable to see that the novel virus did not equal the excess deaths. 11:21.720 --> 11:25.720 We were unable to see because Judy Woodruff agreed with Tony Fauci, 11:25.720 --> 11:30.720 who actually also agreed with Brett Weinstein and a lot of other people on this, 11:30.720 --> 11:34.720 let's say, heterodox version of the Internet that also said, 11:34.720 --> 11:37.720 well, I mean, worst case scenario is it's a lab leak, 11:37.720 --> 11:40.720 and so then they're covering up something that could even be worse 11:40.720 --> 11:44.720 than a really bad, bad cave flu. 11:44.720 --> 11:48.720 And confounding this was the illusion of consensus 11:48.720 --> 11:52.720 that it didn't matter how afraid or confused everyone was. 11:52.720 --> 11:57.720 It didn't matter if they changed the way that people were rescued or not rescued at home 11:57.720 --> 12:00.720 or whether they resuscitated or didn't resuscitate people 12:00.720 --> 12:05.720 when cardiac arrest at home. 12:05.720 --> 12:08.720 There was an illusion of consensus that it didn't matter or wasn't dangerous 12:08.720 --> 12:13.720 to use pulse oximeters and the number that they read out 12:13.720 --> 12:19.720 as a meaningful indication of the presence or absence of this novel pathogen. 12:19.720 --> 12:23.720 Nobody, everybody, there was an illusion of consensus that this couldn't possibly 12:23.720 --> 12:28.720 hurt anybody. And in fact, the illusion of consensus was that it was a pretty useful tool 12:28.720 --> 12:33.720 and that F L C C C and Pierre Corey and others all said that, 12:33.720 --> 12:39.720 hey, you should use this as an indicator of whether or not to go to the hospital. 12:39.720 --> 12:44.720 There was an illusion of consensus on TV and also on social media that ventilators 12:44.720 --> 12:50.720 were definitely needed that antibiotics don't work for viruses that poor use of steroids 12:50.720 --> 12:54.720 could result in even more death that remdesivir could be very useful, 12:54.720 --> 13:00.720 especially during the hospital stay and medazolam wasn't a ridiculous thing to use in a nursing home. 13:00.720 --> 13:03.720 Opioid deaths. I don't even know what those are. 13:03.720 --> 13:05.720 We certainly shouldn't count them as anything. 13:05.720 --> 13:12.720 And since we need more numbers for COVID, why not just classify those as $35,000 dead bodies as well? 13:12.720 --> 13:16.720 We can use death certificate fraud to do it. 13:16.720 --> 13:19.720 I mean, these financial incentives are too hard to pass up. 13:19.720 --> 13:22.720 And maybe all we have to do is track and trace a few people. 13:22.720 --> 13:27.720 And now we have suspected cases of COVID. All we have to do is tell people to wear masks 13:27.720 --> 13:31.720 and close schools and get everybody all riled up about the mandates. 13:31.720 --> 13:35.720 And no one will ever question whether or not the novel virus really killed anybody. 13:35.720 --> 13:40.720 Never mind if we can detect it. 13:40.720 --> 13:45.720 We haven't even gotten to the fact that PCR is probably just one big fraud on a hot background. 13:45.720 --> 13:49.720 We haven't even gotten to the fact that lateral flow test fraud is based on antibodies. 13:49.720 --> 13:56.720 And in fact, usually three or four antibodies in the Android and at least two in each of these tests. 13:56.720 --> 14:02.720 I mean, it's just all commercial antibodies. 14:02.720 --> 14:05.720 And then the sequencing fraud. 14:05.720 --> 14:09.720 Primers and primers and primers were just supposed to take their word for it. 14:09.720 --> 14:14.720 And amplicons missing here and there was just supposed to take their word for it. 14:14.720 --> 14:18.720 Because the illusion of consensus says that all of this is right. 14:18.720 --> 14:21.720 Yes, ma'am. 14:21.720 --> 14:28.720 I don't. I'm streaming. 14:28.720 --> 14:35.720 Okay. If you want to come back later, you can remember your home for a reason. 14:35.720 --> 14:39.720 And so I find it very disturbing. 14:39.720 --> 14:44.720 What's the problem, Ruby? 14:44.720 --> 14:58.720 I find it very disturbing that in November of 2023 that these people were present with Denny Rancor in his, as far as I know his first international presentation about this stuff. 14:58.720 --> 15:01.720 He was very excited to go to Romania. 15:02.720 --> 15:24.720 And several of these people came home and wrote blog posts about the impressive presentation, the data set that they had seen, but never mentioned the part about that data set, which said that there was no evidence of spread of a risk additive pathogen. 15:24.720 --> 15:34.720 I'm happy to say that Denny Rancor estimated that 17 million people around the world were killed by the shot, and they were happy to call it a vaccine. 15:34.720 --> 15:50.720 Now, the strange thing about this is, is that those people know that Denny has been saying this since 2020 because he told them that in in Bucharest or Budapest. 15:50.720 --> 16:05.720 And I don't know which one it is. I'm sorry, I'm dumb. I think it's Budapest, Budapest, Romania. Yes. Is it Bucharest or Budapest? Wow, Maya, that much of a dick. Bucharest. Oh my gosh, I'm an idiot. 16:05.720 --> 16:20.720 There you go. I'm not definitely not geography. So they all saw him in Romania. They all know because he toots his own horn all the time that he's been saying this earlier than anybody. 16:20.720 --> 16:32.720 That excess mortality is never correlated with some kind of respiratory disease. It's always correlated with poverty, household income, and whether or not you went to the hospital or not, right? 16:32.720 --> 16:44.720 And so obviously they would have heard that and seen that and said, wow, that's pretty striking. Not only were 17 million people killed by the shot, but not a whole hell of a lot of people seem to have been killed by a virus, but they leave that out. 16:44.720 --> 16:54.720 And they leave it out for many months until they were in front of the US Senate. Some kind of meeting organized by Ron Johnson and they still left it out. 16:54.720 --> 17:07.720 They even invited more people that were present at that Romanian thing that are actually Romanian. Some of these guys are one of these are not that guy. That's Randy somebody or other from Canada, but this guy maybe or that guy. 17:07.720 --> 17:16.720 There are a couple other people there that are from Romania that were at the same talk and none of them said it. 17:17.720 --> 17:27.720 None of them would question the dangerous novel virus. None of them would question the death count associated with it. Do I need to open the door. 17:27.720 --> 17:34.720 Are you just going to sit there and hop and puff until I open the door. 17:34.720 --> 17:50.720 I'm going to go to the garage. 17:50.720 --> 17:52.720 Sorry about that. 17:53.720 --> 17:56.720 Sometimes I have to unplug. 17:56.720 --> 18:13.720 And so I'm frustrated because we're not really talking about that. We're not talking about the fact that everybody has an explanation for this and the explanation is all an illusion of consensus about the fact that transfection and healthy humans was rushed, but it did work. 18:14.720 --> 18:22.720 People have also been hurt by it, though, because there was an adulteration because it was rushed because they use process to whatever the story is. 18:22.720 --> 18:27.720 Maybe because it went into the vein sometimes like Marc Girodo says. 18:27.720 --> 18:36.720 There's always some excuse, but if it would have gone exactly the way it should have, then transfection is still pretty good. 18:37.720 --> 18:58.720 And an RNA can cause a pandemic. Everybody agrees that that's something that started in a point can can travel the world long to long and faithfully reproduce itself into a reconstructable phylogenetic tree of genetic information into a reconstructable phylogenetic tree of genetic 18:58.720 --> 19:10.720 information that is a level of unprecedented detail of molecular evolution of a single RNA molecule than we've ever obtained in the history of the world. 19:10.720 --> 19:16.720 We tried to track SARS, but we only got about 60 sequences. 19:16.720 --> 19:36.720 We tried to track Mark von Rundst from Belgium tried to track NL67, the coronavirus that was discovered in 2007. He was able to track it for about 28 cases in kids and got 28 sequences or something like that, or maybe he didn't get sequences. 19:36.720 --> 19:44.720 Maybe he just tracked the PCR amplicons through symptomatic. I don't know, but it was like, you know, not very many people. 19:44.720 --> 19:56.720 Now we're tracking the same virus since, I guess a little before 2020 like in October, if you're really a conspiracy theorist. 19:56.720 --> 20:02.720 And we have more than 16 million sequences now. 20:02.720 --> 20:11.720 They all agree this entire table agreed about that. 20:11.720 --> 20:19.720 The entire table agrees that whatever the question, the answer to that question mark is, this is basically true. 20:19.720 --> 20:28.720 Transfection worked, but hurt people because we rushed it because it had double stranded DNA in it or something like that. 20:29.720 --> 20:49.720 Process one, instead of process two, an RNA can definitely pandemic and not RNA plus enzymes like the flu is, but just an RNA wrapped in an envelope can get inside you and make copies of itself and then get inside another person and make copies of itself 20:49.720 --> 20:57.720 and do that millions and millions of times, even in different species and white tail deer and zoo animals. 20:57.720 --> 21:01.720 And they all agree. 21:01.720 --> 21:11.720 Even though almost all of them have known my message since at least 2021, some of them since 2020, the transfection in healthy humans is criminally negligent. 21:12.720 --> 21:20.720 We shouldn't do it because it will provoke an autoimmune response or at least challenge the body not to make one. 21:20.720 --> 21:37.720 And more recently that RNA doesn't really have the biology behind it to sustain a pandemic in the, in the definition of the word, which is it's not nowhere and then it's everywhere. 21:37.720 --> 21:48.720 And the idea that something all that was already there is being misconstrued as something that spread everywhere. 21:48.720 --> 22:04.720 And the fact that they're ignoring that idea, all of these people ignore that idea, all these people have ignored that idea since I put it forth in 2020 and all the way up until since I came up with an even better biological explanation for how that could be. 22:04.720 --> 22:08.720 With respect to infectious clones. 22:08.720 --> 22:10.720 Nothing. 22:10.720 --> 22:15.720 Zippo zero zilch, if anything, everyone's lost their minds more. 22:15.720 --> 22:30.720 The farther along we've come to be able to most succinctly describe that this question mark has not adequately described by any of their narratives and any of their combinations of explanations. 22:31.720 --> 22:39.720 And it all goes back to Jessica Hockett's observation about New York City being a pretty unreal event. 22:39.720 --> 22:48.720 Very, very unlikely to be natural at all. 22:48.720 --> 22:58.720 And in fact we know it's not natural at all we know we've got all kinds of explanations for why it happened and it's very, very obvious once you tally up all those explanations. 22:58.720 --> 23:07.720 And look at the temporal data of deaths that has claimed to have happened and just compare it to what normal is. 23:07.720 --> 23:11.720 Most people don't know that 3 million people in America die every year. 23:11.720 --> 23:27.720 Most people don't understand this curve right here between 60,000 and 50,000 people die every week in America. They don't get that. 23:28.720 --> 23:43.720 And so we have books that have come out over the last 5 years that are part of this slow role to try and coerce us out of our sovereignty to convince us that Mother Nature is so out to get us. 23:43.720 --> 23:57.720 And that transhumanism is so inevitable that we might as well just subscribe to Netflix and order in. 23:57.720 --> 24:01.720 Ladies and gentlemen, it's not just these 5 books, right? 24:28.720 --> 24:31.720 It's all these books. 24:31.720 --> 24:36.720 It's all these books. 24:36.720 --> 24:42.720 I gotta plug in again. 24:42.720 --> 24:53.720 It's all these books. I had so many books under that desk back there. I had to get one of our library carts, which I got out of the garbage can at the University of Pittsburgh. They throw these things away at universities. 24:53.720 --> 24:58.720 Let me see if I can make the camera focus back here. 24:58.720 --> 25:02.720 There, all of these books. 25:02.720 --> 25:14.720 A lot of these books in the middle are books that start with emerging viruses from Dr. Leonard Horowitz. 25:15.720 --> 25:19.720 Go right through the big shot. 25:19.720 --> 25:27.720 And they go right through up until dissolving illusions. 25:27.720 --> 25:36.720 The same year that Nathan Wolf's book came out. These are all in alphabetical and chronological order. 25:36.720 --> 25:42.720 And they're all books about the pandemic. Sorry. 25:42.720 --> 25:45.720 Gotta put this fun one in there somewhere. 25:45.720 --> 25:47.720 Way at the end. 25:47.720 --> 25:50.720 And so you see it's not, it's not just a. 25:50.720 --> 25:53.720 It's not just a small. 25:53.720 --> 26:00.720 This, this has been an ongoing operation to convince you of this stuff. 26:00.720 --> 26:11.720 To persuade you of these things. And I don't think it is, it is by happenstance. I think this is the evidence of a long standing plan. 26:11.720 --> 26:20.720 To make the vaccine schedule kind of crash to be inevitably blamed for stuff to be saying, Oh, that's pretty bad. 26:20.720 --> 26:24.720 But we're going to replace it with gene therapy and personalized medicine, 26:24.720 --> 26:27.720 and it's a lot of satisfaction and transformation. 26:27.720 --> 26:38.720 Things that just happen to work during a pandemic or get worked out during a pandemic or get worked out during an anthrax terrorist attack. 26:38.720 --> 26:53.720 I don't think these people have ever known for sure where the finish line is what the goal is what would be the next plan because their understanding of this biology started out as a complete bluff. 26:53.720 --> 26:59.720 And the reason is they were still bluffing about where they were going and how far they would get. 26:59.720 --> 27:02.720 In the nineties, they were still bluffing. 27:02.720 --> 27:14.720 They didn't know how far they were going to get in the 2000s with coronaviruses. They're still bluffing. They don't know how far they're going to get there hopeful that things are going to work that they're going to find all this biotechnology. 27:15.720 --> 27:37.720 But we have been misled over decades about the potential for RNA viruses to pandemic. We have been misled over decades about the what the worst case scenario is in the context of RNA virology with Ebola and Zika and all of these stories which have been 27:37.720 --> 27:42.720 exaggerated just as Peter Thiel said they would. 27:42.720 --> 27:53.720 And these worst case scenarios are the frame in which the pandemic occurred that frame is false and we're trapped within it. 27:53.720 --> 28:06.720 And that frame was put there so that when transfection and transformation were rolled out in the old and some of these expected bad outcomes started to become more mainstream and younger people. 28:06.720 --> 28:20.720 And that we would just dismiss them as part of the natural course of history and unhealth and that public health needs to fix these problems. 28:20.720 --> 28:30.720 And so I really think that this hypothesis is a pretty good one that they declared a pandemic of a dangerous novel virus on a hot background. 28:30.720 --> 28:42.720 The PCR test that could be varied in terms of sensitivity and positivity and all other things they had complete control. 28:42.720 --> 28:57.720 And all the while this was specifically designed to create more respiratory disease to increase the all cause mortality associated with respiratory disease and get more people in the hospital early on. 28:57.720 --> 29:16.720 That could be classified as this new thing that isn't pneumonia and influenza as a general category but it's now pneumonia influenza and COVID as a general category, which is quite extraordinary from the official perspective that all these people just kind of ignore that confounding. 29:17.720 --> 29:38.720 One thing that everybody hates is that I think giga ohm biological has really led the way in understanding that RNA virology is to a large extent an exaggeration of fidelity and certainly an exaggeration of biological revela relevance simply because in order for RNA virology to exist as it does. 29:38.720 --> 29:50.720 And the RNA sequences that are assumed to underlie these phenomenon in nature are always almost without exception recreated in a DNA form. 29:50.720 --> 29:57.720 And then those DNA molecules are mass produced using recombinant DNA technology and bacteria. 29:57.720 --> 30:13.720 And then those DNA can be converted to RNA which can be then transfected into a cell culture and whatever happens in that cell culture can be misconstrued has viral replication that can then be sent around used to seed experiments, etc. 30:14.720 --> 30:17.720 Sequenced, whatever needs to be done. 30:17.720 --> 30:22.720 That whole phenomenon can't be done with the natural form of the RNA. 30:22.720 --> 30:27.720 It has to first be amplified using a DNA synthetic construct. 30:27.720 --> 30:35.720 And that weak link is something that none of these people that were in front of the Senate will talk about even though they've all heard it from me. 30:35.720 --> 30:46.720 We even have a video where Jessica Rose says, wow, it's such a great idea, JJ, can you tell the, can you use the mixed tape analogy because that just made so much sense to me. 30:46.720 --> 30:53.720 I couldn't go to sleep. I was dreaming about the implications of this idea last night and it's just so cool. 30:53.720 --> 31:04.720 And then she got in front of the Senate and the most important thing she could say was that bears seems to be a lie or they're distorting bears or they're not counting the numbers right in bears. 31:04.720 --> 31:16.720 Even though she was the only one on that whole panel with like six degrees in all of the relevant fields where she could say, well, I'm a virologist and an immunologist and, you know, Jonathan Cooley isn't. 31:16.720 --> 31:21.720 But man, oh man, is he right about infectious clones and the fact that RNA can't pandemic. 31:21.720 --> 31:28.720 And so the only way this could happen and be real is if they actually put these sequences there with the intention of telling us. 31:28.720 --> 31:44.720 But it even a simpler explanation which just blew my mind when Jay said it was that what if there was this background that they've been characterizing for the last five or 10 years with the intention of rolling it out as a phylogeny that's already there that they know is there that they 31:44.720 --> 31:50.720 don't need to worry about being there because it is there and they're already very familiar with it. 31:50.720 --> 32:01.720 But of course, none of that was said, even though Robert Malone is shaking my hand and Ben on Robert F Kennedy juniors podcast and heard this theory first hand. 32:01.720 --> 32:14.720 Even though Meryl Nasse was on that same podcast, even though Jessica Rose was on that same podcast, even though I've worked for Brian Hooker. 32:15.720 --> 32:30.720 Though I've been on a podcast with Harvey Reich where I argued with him about man if you say that you're on hydroxychloroquine and you've had the shots and you got COVID for the third time and it was worse the third time that it sounds like to me you don't know a lot about 32:30.720 --> 32:35.720 prophylaxis and you don't know a lot about how vaccines work. 32:35.720 --> 32:42.720 Nothing you know about COVID is right. Otherwise, if you knew it, then none of these things would have happened to you. 32:42.720 --> 32:54.720 All those people know who I am and that's not to say anything other than to say. And let's just go back there to make sure we show the picture who I'm talking about here. 32:54.720 --> 33:06.720 Jessica Rose knows who's who I am. She's known who I am for at least at least three years. If not four. Kevin McCurnan knows who I am he's been on my stream twice. 33:07.720 --> 33:20.720 He knows who I am because I was at a signal chat with him for almost a year where I taught him almost everything that he claims to have known before the pandemic started. 33:20.720 --> 33:35.720 And that's evident by the number of times him and his wife have mentioned be in passing on his stream about very serious ideas like transfection and what transfection might do is terms of an autoimmune response. 33:35.720 --> 33:52.720 He's known and his wife I have selfies with them they met me at the CHD inaugural conference in Knoxville, which was nine days after I was on the podcast of Robert F Kennedy Jr with him and Jessica Rose and Meryl Nass. 33:52.720 --> 34:04.720 Harvey Reich was in a private zoom meeting with me where we had an hour long discussion about my hypothesis versus his mainstream TV narrative. 34:04.720 --> 34:17.720 And not that I made any progress with him but boy there are a lot of contradictions that these people hold in their head very, very, very adeptly. 34:17.720 --> 34:27.720 So today we are going to take a look at another Susan Lindquist video and I know that might sound. 34:27.720 --> 34:32.720 I don't. 34:32.720 --> 34:42.720 It might sound like we're going to waste our time here but actually Susan Lindquist has a really good video out about prions where she tries again. 34:42.720 --> 34:54.720 Now I hope and this is what I'm hoping here. We've looked into Susan three times now one about prions which was a really basic video that was the first one we watched. 34:54.720 --> 35:07.720 Then we watched Susan Lindquist twice where she was talking about protein folding and the role of chaperone proteins that were originally called heat shock proteins but they're not just from heat shock they're from any kind of stresses she told us. 35:07.720 --> 35:23.720 And that these proteins are chaperone proteins that help other proteins fold and may or may not be involved in things like protein pre on misfolding or amyloid misfolding this kind of thing but she never really got there in that two part talk. 35:24.720 --> 35:37.720 This talk that we're going to watch today is from 2016 and she is going to address the phenomenon of prions and she is going to talk about it in the context of her cellular model which is of course yeast. 35:37.720 --> 35:52.720 Now it is 247 so what's most likely going to happen is we're going to get an intro to this we're going to get started on this but because of my long winded introduction we're going to take a break I'm going to go to basketball and then I'm going to come back and I'm going to do it after dinner or after six like I did yesterday 35:52.720 --> 35:58.720 and I'm going to talk about protein folding as a part one and a part two that's most likely the way it will be. 35:58.720 --> 36:08.720 Let's see if it's not like that it'll be because it's so good I can't stop and then I'll have to meet the kids at the gym after 36:08.720 --> 36:10.720 so let's see where we go. 36:10.720 --> 36:13.720 This is on one and a half speed so you know. 36:13.720 --> 36:17.720 Hi I'm Susan Lindquist I'm at the Whitehead Institute at MIT and remember the Howard Hughes Medical Institute. 36:17.720 --> 36:20.720 I'm going to talk about protein folding as a powerful driver of evolutionary novelty. 36:20.720 --> 36:27.720 Last time I talked to about HSP 90 and the ways in which it can influence protein folding and the manifestation of genetic variation in very powerful ways. 36:27.720 --> 36:34.720 So I'm going to tell you about a very different way in which protein folding can influence the manifestation of genetic variation and lead to the appearance of all kinds of nutrients. 36:34.720 --> 36:35.720 That's the pre-ense. 36:35.720 --> 36:42.720 So it's an interesting story that starts in a place in New Guinea and we'll move on to Cambridge, Massachusetts. 36:42.720 --> 36:51.720 The protein folding problem which drives all of this that I've been talking to you about is simply that protein started as long linear strength of amino acids and they have a folding of very complicated shapes like this. 36:51.720 --> 36:57.720 And they do that in a crazy environment they do that in this really crowded environment of the cell where proteins are jostling around and bumping into each other all the time. 36:57.720 --> 37:00.720 The story on pre-ense as I mentioned starts out in New Guinea. 37:00.720 --> 37:06.720 And there was a tribe that was a very large number of people were dying from a very bizarre horrible neurodegenerative disease. 37:06.720 --> 37:10.720 And Carlton Gaddischuk found out that it was in fact due to an infectious agent. 37:10.720 --> 37:18.720 And Stan Prusner and many other investigators have contributed to this I should say but these guys were very very important in the field. 37:18.720 --> 37:22.720 Found out that this disease was caused by protein folding. 37:22.720 --> 37:26.720 Now protein folding problem creating an infectious element was really quite an amazing thing. 37:26.720 --> 37:30.720 It meant that proteins when they change their folds can have genetic manifestations. 37:31.720 --> 37:34.720 These agents are usually agents that carry along DNA with them. 37:34.720 --> 37:35.720 So it was quite a revelation. 37:35.720 --> 37:39.720 But what I want to talk to you about is thinking about pre-ense like this. 37:39.720 --> 37:44.720 Because the story of pre-ense as disease causing agents is so extraordinary and wonderful and amazing. 37:44.720 --> 37:49.720 It's kind of dominated and quite naturally so the concept of pre-ense biology. 37:49.720 --> 37:58.720 But what I think is that we have to think about pre-ense as this creature and it's time to get rid of some of the baggage because it's my belief that pre-ense actually are amazing protein based genetic elements. 37:58.720 --> 38:01.720 They can do all kinds of really wonderful things in biological systems. 38:01.720 --> 38:05.720 And I think also that we're only at the very tip of the iceberg for revealing this. 38:05.720 --> 38:08.720 So here's some of the great things about pre-ense that I want to tell you about. 38:08.720 --> 38:12.720 Pre-ense form of mechanism for the inheritance of a protein based trait. 38:12.720 --> 38:14.720 We found more than 50 of them in yeast. 38:14.720 --> 38:15.720 We and other people have recorded on these. 38:15.720 --> 38:18.720 25 of them are yet unpublished but there's just a lot of them. 38:18.720 --> 38:19.720 They're caused. 38:20.720 --> 38:24.720 25 yet unpublished pre-ense in yeast. 38:24.720 --> 38:30.720 And she's arguing these are proteins which are inherited separate from their genetics. 38:30.720 --> 38:34.720 Which is a interesting thing to happen in a yeast. 38:34.720 --> 38:36.720 A single-celled organism. 38:36.720 --> 38:41.720 It's a very different thing to suggest that this is a phenomenon which goes all the way up the chain invertebrates. 38:42.720 --> 38:49.720 Protein based inheritance is nothing that Stanley Proustner was talking about in his talk in 2002. 38:49.720 --> 38:53.720 And it's extraordinary because this is in 2016. 38:53.720 --> 38:55.720 This is really 14 years later. 38:55.720 --> 38:59.720 So we could be quite a long ways. 38:59.720 --> 39:05.720 But she seems to like prions as much as Vincent Rackeniello likes viruses. 39:05.720 --> 39:07.720 It's pretty impressive. 39:07.720 --> 39:09.720 Dozens of new traits. 39:10.720 --> 39:13.720 Dozens of them are doing a variety of all sorts of new traits. 39:13.720 --> 39:18.720 They allow organisms, the yeast organism at least, that we've been looking at to survive in fluctuating environments. 39:18.720 --> 39:25.720 Oh, so it's just right now at least the yeast is using prions to survive in fluctuating environments. 39:25.720 --> 39:32.720 I think she's using the word prion to describe any protein that might be inherited separate from genetics. 39:33.720 --> 39:39.720 And that's very different than a prion which causes other proteins to fold like it. 39:39.720 --> 39:54.720 Which is what is implied by Stephanie Sineff and other pseudo-experts when it comes to the spike protein having prionogenic domains or prionogenic epitopes. 39:55.720 --> 39:57.720 Which are the terms that these people use. 39:57.720 --> 40:00.720 These worst case scenario team members. 40:00.720 --> 40:17.720 Which since early on, if not the very beginning of the pandemic have been seeding this narrative of all kinds of worst case scenario outcomes that I think were always associated with transfection and transformation had never expected to come from an RNA pandemic. 40:18.720 --> 40:20.720 But they were encouraged. 40:20.720 --> 40:24.720 They were there already with these narratives and knew that they would get away with it. 40:24.720 --> 40:31.720 In fact, they knew they would get amplified if they pushed these narratives. 40:31.720 --> 40:33.720 And I think that it's possible. 40:33.720 --> 40:46.720 It is absolutely possible that academia has these people in it that are feeling very safe about pushing these ideas knowing full well they're exaggerating. 40:46.720 --> 41:00.720 Knowing full well that they might even be lying about certain things because it's part of the national security operation which is to protect the secret stuff. 41:00.720 --> 41:11.720 And so the way you protect the secret stuff is to tell some stories that mask it to make up some mythologies that can distract from it. 41:12.720 --> 41:34.720 And I think as we as we start to really lift the veil on this stuff there are going to be a few things a few ideas and biology that we're going to hone in on that are more likely to be ideas which were pursued and amplified with the idea of using them to obfuscate other ideas and other 41:34.720 --> 41:38.720 directions of investigation. 41:38.720 --> 41:46.720 Bright shiny objects with lots of funding that keep people from asking questions where there is no funding. 41:46.720 --> 41:51.720 There's something super slick about this in 2016. 41:51.720 --> 42:08.720 It's a protein based inheritance you know she's using these these terms which are very attractive to the the the people who want there to be new biology that we don't understand or or spooky biology that can be. 42:08.720 --> 42:12.720 Yeah it's very dubious to me already. 42:12.720 --> 42:21.720 They provide a fast route to the evolution of complexity and their reversible traits so you can acquire the organism can acquire these traits and they can lose them. 42:21.720 --> 42:25.720 They form a very sophisticated strategy for survival. 42:25.720 --> 42:34.720 And they form a system of biological memory in which a change in protein folding self perpetuates and then that self perpetuating change in protein folding changes the function of the protein. 42:34.720 --> 42:39.720 And that creates can both create new phenotypes it actually serves as a kind of a biological memory when you think about it. 42:39.720 --> 42:46.720 And there's evidence now that this is really occurring at the ends of synapses in our brain and helping to maintain long term synaptic connections. 42:46.720 --> 42:56.720 Also we have found in my lab evidence that prions can enable life in complex biological systems and communities creating different ways for organisms to relate to each other. 42:56.720 --> 43:05.720 Now the point would be right let's just say optimistically speaking because again we're probably going to we're probably going to run into a time crunch here. 43:05.720 --> 43:14.720 Let's just say optimistically speaking that this is a good woman and she's doing all of her all of her work is good and none of it is to obfuscate anything else at MIT. 43:14.720 --> 43:29.720 None of it is to help anybody else with any interest in or controlling interest at MIT and that MIT is just a great school with a lot of people and nobody there's any has any other conflicts of interest you know like connected to intelligence or government 43:29.720 --> 43:41.720 or multinationals or other other national national governments or anything like that it's just a great school with super smart people that like trains and ham radio. 43:41.720 --> 43:56.720 And this lady is a molecular biologist and she thinks proteins are really cool and prions are very special and that they represent a level of sort of biological complexity that not very many people are aware of because you can inherit proteins 43:56.720 --> 44:06.720 and folded proteins that can also fold other proteins and so that inheritance that genetic information is essentially encoded in a way that we never thought was possible. 44:06.720 --> 44:14.720 And so the more we look into this the more impressive it is and then wait a minute hold on stop. 44:14.720 --> 44:29.720 So best case scenario Susan linguist says is that biology is even frickin more complex than you thought it was when you just thought it was DNA gets translated to RNA gets translated to proteins that are oftentimes misfolded because the ribosome is so complicated 44:29.720 --> 44:41.720 and RNA can be edited and those knots do things and the code is different and misfolding is a thing and wait a minute holy cow and then after that there's more inheritance. 44:41.720 --> 44:44.720 There's more transmission of information. 44:44.720 --> 44:49.720 It's reversible. 44:50.720 --> 44:52.720 So the best case scenario. 44:52.720 --> 45:12.720 If Susan is an obfuscating anything or trying to muddy the water I've understanding and trying to make it even harder for us to appreciate the sacredness of our biology or to or to appreciate the reduce irreducible complexity that we come against as we look at the molecular basis 45:12.720 --> 45:16.720 of a cell. 45:16.720 --> 45:32.720 Then she's adding a dimension that just makes it absolutely impossible that we understand any of these phenomenon that we call the immune system or nutrition or genetics for that matter. 45:32.720 --> 45:37.720 You can't have it both ways. 45:37.720 --> 45:58.720 And yet somehow or another the magic spell has been cast on us that you can actually have it both ways that all of this stuff can be beautiful and people like Susan can really appreciate the magnificence of it and how wonderful it is that life is even more complex than we thought. 45:59.720 --> 46:17.720 You can have Stanley Prusner saying that these are diseases that could probably be cured with a combination of antipsychotics and antibodies to the pre on protein. 46:17.720 --> 46:32.720 So we have people telling us that again a function spike protein that was specially designed to be a pre on a genetic protein specially designed to be amyloidogenic or whatever which term they choose on a given day or what depends on really the paper that they're 46:32.720 --> 46:48.720 talking about whether it's amyloidogenic or pre on a genetic or whether it's staphylococcan and teratoxin B or whether it's the HIV inserts or maybe we'll circle back soon to the fear and cleavage site again. 46:48.720 --> 47:01.720 And that is the magnificence of this that they have been laying the groundwork for this massive amount of confusion for a very, very long time many people unwittingly I'm sure. 47:01.720 --> 47:17.720 And so if you want to believe that Susan is unwittingly participating in this then the best case scenario is that she is adding a dimension to our biology that Stanley Prusner is not acknowledging 47:17.720 --> 47:27.720 that anybody that's talking about the spike protein having pre on a genetic epitopes is not acknowledging 47:27.720 --> 47:37.720 but is instead insulting with the simplicity of you can just add the you know add that alpha helix or this beta pleated sheet and there you go you've got a little pre on how long is the pre on 47:37.720 --> 47:44.720 and the pre on protein that that they're always talking about is 28 kill adult and this is not a 47:44.720 --> 47:48.720 hmm hmm 47:48.720 --> 47:51.720 seems like more than an epitope right 47:51.720 --> 47:56.720 how many different antibodies was Prusner talking about how many different epitopes was he taught 47:56.720 --> 48:06.720 and it's all just incongruency and nonsense and so when we listen to Susan and she's gone now when we listen to Susan 48:06.720 --> 48:18.720 let's just assume that this is a person who's trying to add to our understanding of the sacred biology of the irreducible complexity that is us 48:18.720 --> 48:30.720 not trying to define a particular kind of disease and if we listen to it that way I think what we're going to hear is another side of this 48:30.720 --> 48:40.720 protein based inheritance I mean that's a way to get grant money holy cow I'm going to try to give you an overview of this very complex and rich and wonderful subject 48:40.720 --> 48:55.720 and I'm going to end with pre on forming the really ultimate example of Lamarckian evolution in which organisms can acquire a heritable nutrient that they pass on from generation to generation by being exposed to a new environment 48:55.720 --> 49:06.720 so she keeps talking about organism even though she means yeast and so that's kind of frustrating and then Lamarckian inheritance is really also an interesting thing to evoke 49:06.720 --> 49:14.720 because generally speaking Lamarckian inheritance is not considered something that that generally happens so I'm not 49:14.720 --> 49:30.720 going to get into that at all because I'm not Brett oh the pre on story slot starts with this these two strains of yeast red versus white and remember she just said the pre on story starts with two strains of yeast the red 49:30.720 --> 49:45.720 and the white so we're not starting with eating brains we're not starting with feeding cows cows we're not starting with sheep scrapey keep that in mind 49:45.720 --> 49:55.720 but this these organisms have a very odd genetic behavior Brian Cox did some wonderful work on this many years ago and a lot of people thought this was really kind of a strange thing why is he working on this 49:55.720 --> 50:05.720 but he his early work really laid the foundation for for all of this everything I'm going to be talking to you about today what he found was the red stream was really very stable and you could streak it out and it would give rise to more red colonies 50:05.720 --> 50:14.720 every once in a while they would turn white and the white stranger could then streak out and they were very stable very heritable trait and every once in a while they would turn red and that of course was metastable inheritance 50:14.720 --> 50:32.720 what Brian also found out is that when you made it the red cells to the white cells and then you spoil it and got out genetic progeny you would normally expect if those traits were due to changes in the DNA the difference between the red and white cells changes in DNA that some half of the progeny would now be red and half of the progeny would be white as those pieces of DNA would be a sort of in subsequent generations 50:32.720 --> 50:50.720 they weren't all the cells all the progeny for white so odd inheritance Brian also realized that this this change in color was due to a change in translation the way in which messenger RNAs are decoded into proteins that there was a translation termination defect and the cells switched from red to white because of a change in ribosome red or stop glands 50:51.720 --> 51:02.720 and that was linked to this protein here in the simple cartoon it's a protein that's involved in a translation termination and it's only this portion of the protein over here that's actually required for translation termination activity 51:02.720 --> 51:06.720 it's a very important factor it tells ribosomes to stop when they hit a stop cutout 51:06.720 --> 51:19.720 attached to it as these two weird domains called the internal domain and the middle domain that just have a very unusual type of amino acid composition and it was discovered that those properties of inheritance really depended upon that but that was those odd properties of hair dependent on that region of the protein 51:20.720 --> 51:32.720 now your return sure enough comes into this story because he was searching for what could govern this odd pattern of genetic behavior not like the genetics that we normally think about as being driven by changes in DNA 51:32.720 --> 51:41.720 and he was working with Sue Liebman's laboratory and he did a screen for factors in the genome of yeast that could could alter or influence this inheritance pattern 51:41.720 --> 51:54.720 and what he came up with was HSP 104 what the heck did that mean? Well at that point I got a phone call from here because he knew I had been working on HSP 104 I'd shown that my laboratory had shown that it saved cells from high temperature death 51:54.720 --> 52:05.720 and he was wondering if I had knew any aspect of how it worked I did I knew how it worked but nobody else didn't the reason for that was because we couldn't get our paper published 52:05.720 --> 52:10.720 there's no one of four did something unusual and it was very hard for people to accept what it did 52:10.720 --> 52:21.720 so I'm just to want to be sure that you understand I'm confused as well because she has prion protein at the top of this slide but she's not defined this protein as the prion protein 52:21.720 --> 52:29.720 and as far as I know she says the protein that she's talking about is a protein which is involved in the ribosomal complex 52:30.720 --> 52:42.720 and dictates how the ribosomal reads stop codons someone in the chat correct me if I'm wrong that's what we're talking about here 52:42.720 --> 52:47.720 Y330 52:47.720 --> 52:56.720 okay that's fine so what does HSP 104 do by the way these are many many many people who contributed to the story of trying to figure out this different parts of this translation 52:57.720 --> 53:04.720 which one's contributed to the genetic behavior C translation termination factor but she's got prion protein written up there it's very bizarre hold on 53:04.720 --> 53:07.720 so what does HSP 104 do? 53:07.720 --> 53:20.720 so now we're on HSP 104 so my assumption has to be that HSP 104 is the factor that they're talking about there with the C and N domains there 53:21.720 --> 53:26.720 attributed to the genetic behavior this story of trying to figure out what is it or did some new medical from the 5th was yeast 53:26.720 --> 53:36.720 he was working with like the gene what could govern this odd pattern of of genetic behavior not like the genetics that we normally think about as being driven by chases and DNA 53:36.720 --> 53:45.720 and he was working with Sue Liebman's laboratory and he did a screen for factors in the genome of yeast that could could alter or influence this inheritance pattern 53:46.720 --> 53:50.720 what he came up with was HSP 104 what the heck does that mean? 53:50.720 --> 54:00.720 well at that point I got a problem with any aspect of why it how it worked and I did I knew how it worked but nobody else didn't the reason for that was because we couldn't get our paper published 54:00.720 --> 54:07.720 there's no one before did something unusual and it was very hard for people to accept what it did so what does HSP 104 do? 54:07.720 --> 54:15.720 these are many many many people who contributed to the story of trying to figure out this these different parts of this translation termination factor and which ones contributed to the genetic behavior 54:15.720 --> 54:23.720 so what does HSP 104 do? HSP 104 plays a major role in something called induced thermal talent so I talked about this briefly in one of my earlier lectures 54:23.720 --> 54:32.720 when organisms are exposed to mild heat temperatures they make new proteins called heat shock proteins and those proteins help to save them from the death caused by protein misfolding at high temperatures 54:32.720 --> 54:42.720 here's an experiment in which cells have been exposed to the same heat treatments but in one case the cells have HSP 104 and in the other case the cells do not have HSP 104 makes a big difference to their ability to survive 54:42.720 --> 54:48.720 and the way it makes it in terms of their ability to survive is that it takes apart protein aggregates so what are protein aggregates? 54:48.720 --> 54:54.720 these are well-folded proteins, you've all seen the effects of heat on these well-folded proteins, it causes proteins to aggregate 54:54.720 --> 55:04.720 now HSP 104 I don't want to say can unfry that egg but just a little bit of that kind of aggregation occurs in cells in response to stresses and that can kill them 55:04.720 --> 55:14.720 this is a wonderful example of how academic biologists will get stuck in an analogy that is inadequate but because it gets to the lay person's idea 55:14.720 --> 55:22.720 they keep using it but it's a terrible example of what she purports to happen here 55:22.720 --> 55:33.720 she purports that misfolded proteins make aggregates and that these proteins like heat shock protein 104 actually prevents those aggregates from forming 55:33.720 --> 55:43.720 now that's a very different thing than what's happening when you fry an egg and so it's pretty annoying because anybody with a little sophistication knows that it's different 55:43.720 --> 55:53.720 and so to use such an inadequate explanation actually suggests that this is not intended to inform 55:53.720 --> 56:03.720 oops that wasn't what I meant to do that kind of aggregation occurs in cells in response to stresses and that can kill them HSP 104 saves them by disaggregating 56:03.720 --> 56:11.720 so that led us to think well maybe how can it be involved in inheritance of this trait, maybe inheritance of that trait depended in some way upon protein aggregation phenomenon 56:11.720 --> 56:20.720 so we looked at the protein that had been tied to that trait that translation termination factor and asked whether it existed in the different conformational state in the red cells or the white cells 56:20.720 --> 56:30.720 and sure enough in the red cells the protein was soluble and functional and in the white cells the protein was tied up in little aggregates and you can see by the way so aggregates 56:30.720 --> 56:34.720 they're actually being inherited being passed from the mother cell into the daughter cell 56:34.720 --> 56:42.720 now about the time when we were in the midst of these experiments and where we hadn't yet published anything and hadn't yet been able to publish even our story on HSP 104 56:42.720 --> 56:46.720 we did wind up getting a really great paper in the suggestions of the reviewers in the long run. 56:46.720 --> 56:55.720 While we were in the midst of this along came a paper by Reed Wickner which was a very very clever interpretation of some genetic experiments 56:55.720 --> 57:02.720 on another factor that was inherited in the very bizarre way inherited and had the same kind of genetic properties that the side element had that red white element had 57:02.720 --> 57:10.720 this was called Yuri III and he suggested that the way in which this was inherited was that it was due to some kind of a pre-unlike phenomenon 57:10.720 --> 57:18.720 a self-perpetuating change in protein function not knowing whether it was an aggregate or was it changing the activity of the protein or what was going on 57:18.720 --> 57:25.720 but he also suggested that this might apply to that this pre-unlike mechanism might apply to that inheritance of that red white trait 57:26.720 --> 57:32.720 so as I say it could have been anything it could have been an enzyme that catalyzed its own modification it could have been lots of different things 57:32.720 --> 57:39.720 but because we knew that it was controlled by HSP 104 which we knew was involved in protein aggregation this paper was really made a tremendous amount of sense 57:39.720 --> 57:48.720 and so we decided to look at this in even greater detail and we found that in fact the aggregation state of that protein sub-35 translation termination factor 57:49.720 --> 57:56.720 was not just a generalized aggregate but a very special kind of aggregate a self-templating amyloid aggregate 57:56.720 --> 58:02.720 so on the left there you see the protein fibers of sub-35 that we found after a great deal of effort 58:02.720 --> 58:07.720 aggregated proteins are a lot of work to work with but you eventually looked at the aggregates under the electron microscope 58:07.720 --> 58:14.720 Now remember all of this stuff is in yeast all of this stuff is yeast proteins the argument is is that yeast are eukaryotes and were eukaryotes 58:14.720 --> 58:23.720 so some are all of these cellular factors may have a homolog in our cells the question will be to what extent are these homologues identified 58:23.720 --> 58:33.720 and to what extent are these observations sort of paralleled in any system that is related to ours except for by this you know 58:33.720 --> 58:41.720 it's insofar as what she means that they have nuclei and they have machinery inside their cells that's analogous to ours I don't think she's wrong 58:41.720 --> 58:49.720 but now the question is going to become how does this bridge our way to understanding what prions and prion disease 58:49.720 --> 58:55.720 and whether a prion epitope can exist or not exist inside of a gain of function protein 58:55.720 --> 59:05.720 that's really our goal here and I'm going to go get a drink and fill up my water bottle and then head to the gym with the boys 59:05.720 --> 59:13.720 we're in half an hour early today please remember that intramuscular injection of any combination of substances with the intent of augmenting the immune system is dumb 59:13.720 --> 59:19.720 transfection in healthy humans is criminally negligent in RNA, cannot pandemic I will be back 59:19.720 --> 59:29.720 I'm probably going to start it right after I get back so I don't know why I wouldn't start when I get back so it'll probably be 59:29.720 --> 59:39.720 thirty four forty five maybe five o'clock I'll start it and I'll start it right here and we'll finish this video with Susan that we just barely started 59:39.720 --> 59:45.720 and try to figure out if Susan can give us a better idea of what prions are all about 59:45.720 --> 59:48.720 I guess I'll do that too why not 59:48.720 --> 59:51.720 this is our hypothesis 59:51.720 --> 01:00:01.720 and yeah I'll leave it at that I will be back don't forget I will be back 01:00:01.720 --> 01:00:05.720 and that will be a part two thanks 01:00:21.720 --> 01:00:23.720 you 01:00:51.720 --> 01:00:53.720 you 01:01:21.720 --> 01:01:23.720 you