WEBVTT 00:00.000 --> 00:02.000 . 00:30.000 --> 00:32.000 . 01:00.000 --> 01:02.000 . 01:02.000 --> 01:04.000 . 01:04.000 --> 01:05.000 Does that look alright? 01:05.000 --> 01:06.000 Mm-hmm. 01:06.000 --> 01:08.000 That's my friend Nathan. 01:08.000 --> 01:10.000 He's dead. 01:10.000 --> 01:14.000 . 01:14.000 --> 01:18.000 . 01:18.000 --> 01:20.560 . 01:20.560 --> 01:23.060 . 01:23.060 --> 01:25.060 . 01:25.060 --> 01:28.040 . 01:58.040 --> 02:08.040 I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario. 02:08.040 --> 02:13.040 I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario. 02:13.040 --> 02:18.040 I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario. 02:28.040 --> 02:57.040 I think the truth is good for kids. We're so busy lying we don't even recognize the truth no more than society. 02:57.040 --> 03:05.040 We want everybody to feel good. That's not the way life is. 03:05.040 --> 03:13.040 This episode is sponsored by Moink. That's Mo plus Moink. 03:13.040 --> 03:18.040 But you can tell if someone's lying you know you can sort of feel it in people. 03:18.040 --> 03:22.040 And I have lied. I'm sure I'll lie again. I don't want to lie. 03:22.040 --> 03:26.040 You know I don't think I'm a liar. I try not to be a liar. I don't want to be a liar. 03:26.040 --> 03:30.040 I think it's like really important not to be a liar. 03:52.040 --> 04:22.040 I'm afraid that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data 04:22.040 --> 04:52.040 tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us that the latest data tells us 04:52.040 --> 05:22.040 that the latest data tells us that the 05:22.040 --> 05:52.040 latest data tells us that the latest data tells us that 05:52.940 --> 06:08.080 And that interview is going to entail meeting a EMT and another vaccine injured person from Canada I think it's going to be a really interesting discussion where we're going to try to stay focused on the biology. 06:08.080 --> 06:10.160 Of course, we're not going to be taking their bait. 06:10.160 --> 06:21.860 And of course we're going to be loving our neighbors even up in Canada so I'm looking forward to that, unfortunately because this is like a one man show with the help of my best friend as much a she can do and she keep us back, 06:21.860 --> 06:23.620 keeps the whole household running. 06:24.620 --> 06:26.780 It's new people sharing my work, 06:26.780 --> 06:29.940 so keep doing it, it's really working well. 06:29.940 --> 06:32.820 I mean, we're way below the number of subscribers 06:32.820 --> 06:35.900 that we need, but that doesn't necessarily mean 06:35.900 --> 06:37.420 that I'm pessimistic. 06:37.420 --> 06:40.700 I think actually we're doing pretty well. 06:40.700 --> 06:43.980 We're doing pretty well because I see the views, 06:43.980 --> 06:48.420 I see people sharing, I get feedback by email 06:48.420 --> 06:50.700 from people who are excited about the information 06:50.700 --> 06:53.140 that they're getting, not everybody can support. 06:53.140 --> 06:56.060 I get that, but the more we get this around, 06:56.060 --> 06:59.060 we're not looking for tens of thousands of subscribers. 06:59.060 --> 07:01.580 We don't need to have a sub-stack 07:01.580 --> 07:02.980 the size of Jessica Rose, 07:02.980 --> 07:06.380 we don't need to have a sub-stack the size of Robert Malone. 07:06.380 --> 07:09.700 I don't need 50,000 paid subscribers. 07:09.700 --> 07:11.140 We really just need a thousand. 07:11.140 --> 07:14.260 If we had a thousand, this family of five would be fine. 07:14.260 --> 07:16.900 I would be able to do this full-time. 07:16.900 --> 07:21.100 I think my wife would be able to do yoga 07:21.100 --> 07:24.740 and take care of our family as well 07:24.740 --> 07:26.700 as she's doing right now and better. 07:26.700 --> 07:28.460 And more importantly, this information 07:28.460 --> 07:31.140 would be sustainable forever. 07:31.140 --> 07:32.140 It would never stop. 07:32.140 --> 07:35.140 And so these people who courageously put their flag on mine 07:35.140 --> 07:37.700 or put their name on my flag, 07:37.700 --> 07:40.260 I can't thank you enough on behalf of me 07:40.260 --> 07:44.020 and my two sons and daughter and my best friend and wife. 07:44.020 --> 07:46.540 I mean, the independent Bright Web 07:46.540 --> 07:47.780 has got to start somewhere. 07:47.780 --> 07:50.900 And I think with people like Hugh Satanic Live 07:50.900 --> 07:52.740 with Mark Koolack doing his work 07:52.740 --> 07:54.940 with Jessica Hockett tearing up Twitter 07:56.260 --> 07:58.660 with Giga Home Biological now streaming 07:58.660 --> 08:00.700 at least two or three places all the time. 08:00.700 --> 08:02.820 I'm not streaming from YouTube today 08:02.820 --> 08:05.180 because I'm going to try to pull all of my stuff 08:05.180 --> 08:07.060 from YouTube Live. 08:07.060 --> 08:08.380 I didn't want to download it all 08:08.380 --> 08:10.300 and I hate to screen capture from YouTube 08:10.300 --> 08:11.460 because I'm lazy. 08:11.460 --> 08:13.340 So I'm going to use YouTube 08:13.340 --> 08:15.100 and so we're going to be streaming and pulling 08:15.100 --> 08:17.340 and so I wanted to keep that band move open. 08:18.340 --> 08:20.340 I don't know if that's going to be a trick that works 08:20.340 --> 08:21.660 but we'll see what happens. 08:23.460 --> 08:25.940 Never more than now. 08:25.940 --> 08:28.780 Is it true that this illusion is sustained 08:28.780 --> 08:31.860 only through our active participation? 08:31.860 --> 08:36.340 And every time they try to send up another signal flare 08:36.340 --> 08:38.540 like, oh my goodness, there's an eclipse coming 08:38.540 --> 08:41.860 and all the states are declaring a state of an emergency 08:41.860 --> 08:44.220 because they're going to shut down the internet 08:44.220 --> 08:45.060 or something like that. 08:45.060 --> 08:47.060 I mean, I guess that's possible. 08:47.060 --> 08:50.940 I think it's a lot more likely that the eclipse 08:50.940 --> 08:53.460 is going to cause a lot of people to want to go see it 08:53.460 --> 08:56.020 because they've got a chance to see something 08:56.020 --> 08:57.460 and they never may see again. 08:57.460 --> 09:02.460 And you know, the reality of Earth astronomy, 09:03.940 --> 09:05.420 I mean, if you want the real truth 09:05.420 --> 09:08.660 is I understand it unless you're a flat Earth Earth. 09:08.660 --> 09:10.900 Eclipse has happened quite often. 09:10.900 --> 09:13.220 It's just a question of are you there to see it 09:13.220 --> 09:14.980 and who's there to see it? 09:14.980 --> 09:16.500 And there's an awful lot of ocean 09:16.500 --> 09:18.340 over which eclipses can occur. 09:19.300 --> 09:22.980 And there's a lot of, you know, it's just all a, 09:22.980 --> 09:23.820 I don't know. 09:24.620 --> 09:28.580 I think if we stay focused and don't take the bait 09:28.580 --> 09:32.420 and assume that most of what's on that social media 09:32.420 --> 09:35.740 is bait, we're going to be all right. 09:35.740 --> 09:36.580 We're going to be all right. 09:36.580 --> 09:39.060 We stick together, everything is going to be fine. 09:40.900 --> 09:42.780 I have a real feeling that what we got to do 09:42.780 --> 09:44.140 is get biology in our head. 09:44.140 --> 09:46.420 Once we understand it better than they do, 09:46.420 --> 09:48.660 then we're immune, right? 09:48.660 --> 09:52.740 As long as we are vulnerable to bamboozlement 09:52.740 --> 09:56.700 because we lack the understanding then yes. 09:56.700 --> 10:00.580 But if we get the biology into our head as Jeff has, 10:00.580 --> 10:02.380 Jeff has really crammed it in there. 10:02.380 --> 10:04.980 I mean, he's taken it to a little extreme. 10:04.980 --> 10:09.820 I'll give you that, but, you know, God bless him. 10:09.820 --> 10:12.180 And in all seriousness, 10:12.180 --> 10:15.060 everybody should send some energy up to Canada 10:15.060 --> 10:19.180 because Jeff did that scar was made for a reason. 10:19.180 --> 10:24.180 And so we're, we're very happy that his recovery 10:24.500 --> 10:28.460 has been so relatively bump-free, 10:28.460 --> 10:31.300 but let's hope that it continues that way. 10:31.300 --> 10:32.740 Let's hope he stays in good health 10:32.740 --> 10:34.820 and the worst thing he has to pay attention to 10:34.820 --> 10:37.900 is his successful business being attacked 10:37.940 --> 10:40.780 by all the latest DEI and other crap 10:40.780 --> 10:42.980 that's going on in our world. 10:42.980 --> 10:43.820 Thank you very much. 10:43.820 --> 10:46.380 Jeff is a very good supporter of the stream. 10:46.380 --> 10:48.500 A crazy good supporter of the stream. 10:48.500 --> 10:50.260 Him and his wife, Cara, do a lot of stuff 10:50.260 --> 10:52.900 behind the scenes to organize a schedule 10:52.900 --> 10:54.060 that I don't pay attention to. 10:54.060 --> 10:55.540 So one of the reasons for example, 10:55.540 --> 10:58.820 that I'm gonna be on with Jason Levine this evening. 10:58.820 --> 10:59.660 Where the hell am I? 10:59.660 --> 11:00.980 What, what, what the? 11:03.460 --> 11:05.420 Shoot, hello, ladies and gentlemen. 11:05.420 --> 11:06.780 This is GIGO and biological, 11:06.780 --> 11:08.380 high-resistance low noise information 11:08.380 --> 11:09.740 brought to you by a biologist. 11:09.740 --> 11:11.460 It's April 4th, 2024. 11:11.460 --> 11:12.300 I apologize. 11:12.300 --> 11:15.260 I wasn't even looking at the screen at that time. 11:15.260 --> 11:18.180 We are in a situation where, you know, 11:18.180 --> 11:20.980 it's only a few of us, but it's people like Jeff and Cara 11:20.980 --> 11:25.300 in Canada that support, whoops, that's the wrong button, 11:25.300 --> 11:28.020 that support what I'm doing here 11:28.020 --> 11:30.460 and what, what, what me and my family 11:30.460 --> 11:32.180 are trying to accomplish more and more. 11:32.180 --> 11:34.820 It's becoming very obvious that this is a family affair 11:34.820 --> 11:38.340 because number one, I've always been aware 11:38.340 --> 11:41.260 that as I've been slowly losing my mind 11:41.260 --> 11:43.260 as a recovering academic biologist, 11:43.260 --> 11:45.140 that one of the reasons why I've been able 11:45.140 --> 11:46.540 to keep the train on the rails 11:46.540 --> 11:48.780 is because of my best friend and wife. 11:48.780 --> 11:51.740 Never once doubting me, even though clearly 11:51.740 --> 11:55.260 I was claiming that this guy was falling for several years. 11:55.260 --> 11:58.460 And so, yeah, thanks to her 11:58.460 --> 12:02.820 and thanks to my kids for also believing in their dad. 12:02.900 --> 12:05.620 And so, yeah, this is really an effort 12:05.620 --> 12:08.260 of just a family that rents their house in Pittsburgh 12:08.260 --> 12:10.260 coming to you live from a garage 12:10.260 --> 12:11.700 that looks a little better than a garage, 12:11.700 --> 12:14.180 but it's really not, we got kind of lucky 12:14.180 --> 12:16.140 when we had to move from our house 12:16.140 --> 12:17.980 that we hoped to own forever. 12:18.940 --> 12:20.300 In the north side of Pittsburgh, 12:20.300 --> 12:23.060 we got lucky enough to be able to move into a house 12:23.060 --> 12:25.820 that had a little kind of studio behind the garage. 12:25.820 --> 12:28.540 And we did choose it because as a family, 12:28.540 --> 12:31.380 already two years ago, we were already all in. 12:31.380 --> 12:33.060 And when we saw this house, it was like, 12:33.060 --> 12:35.460 well, we don't have enough bedrooms for the boys 12:35.460 --> 12:38.100 and the basement is small, but the garage is pretty big. 12:38.100 --> 12:40.500 It's big enough for your stupid motorcycle. 12:40.500 --> 12:42.540 And it's got this little wood shop in the back 12:42.540 --> 12:44.660 that you could make into a studio. 12:45.580 --> 12:47.140 And so for two years now, 12:47.140 --> 12:49.100 my kids have been sharing bedrooms 12:49.100 --> 12:54.100 and we're not suffering in some terrible way, 12:54.660 --> 12:57.300 but I just want you to see how it is really a family 12:57.300 --> 13:00.580 that's all in and I got a lot of credit needs 13:00.580 --> 13:03.300 to be given to my wife who doesn't get any, 13:03.300 --> 13:07.420 there's no memorial or star here for her. 13:07.420 --> 13:10.180 And she permits me to do all this stuff 13:10.180 --> 13:15.180 and basically facilitates it by never once 13:15.540 --> 13:18.060 having an even shadow of a doubt in me. 13:18.060 --> 13:22.460 So yeah, I can't say enough about that. 13:22.460 --> 13:23.380 So thank you very much. 13:23.380 --> 13:25.100 I don't know why I'm saying it on April 4th 13:25.100 --> 13:28.100 because this is not a special date for us. 13:28.100 --> 13:30.460 Anyway, where was I going to go with this? 13:30.460 --> 13:31.300 Oh yeah. 13:31.300 --> 13:32.140 So basically, of course, 13:32.140 --> 13:33.860 we're always breaking down the same thing. 13:33.860 --> 13:35.140 You just have to understand 13:35.140 --> 13:37.100 that they've been telling us stories for a long time. 13:37.100 --> 13:38.460 We've been governed by stories. 13:38.460 --> 13:43.020 You're a revolve, whatever that skinny golem looking guy. 13:43.020 --> 13:45.300 We'll tell you that we've always been governed by stories, 13:45.300 --> 13:47.980 but the question is just what kind of truth 13:47.980 --> 13:48.980 are you willing to tell? 13:48.980 --> 13:51.820 And we're never going to have informed consent 13:51.820 --> 13:55.820 as sovereign citizens of any republic 13:55.820 --> 14:00.140 unless we exercise that informed consent with action. 14:00.140 --> 14:02.500 That means basically educating yourself. 14:02.500 --> 14:05.940 You're going to have to learn what fractional reserve banking 14:05.940 --> 14:07.420 is, you're going to have to learn 14:08.580 --> 14:11.900 how the legislative process in the United States 14:11.900 --> 14:14.260 has been used against us for decades. 14:14.260 --> 14:15.500 You're going to have to understand 14:15.500 --> 14:18.420 how secret budgets have been used against us for decades. 14:18.420 --> 14:20.100 You're going to have to understand 14:20.100 --> 14:25.100 how the forward facing sort of people of government 14:25.740 --> 14:28.420 have been used against us by telling us stories 14:28.420 --> 14:30.020 that aren't directly related 14:30.020 --> 14:32.260 to what's really going on behind the scenes. 14:32.260 --> 14:36.220 We've always known that with foreign policy 14:36.220 --> 14:38.740 and with certain stories about marriage 14:38.740 --> 14:41.340 or what's happening in their personal life, 14:41.340 --> 14:42.580 but it never dawned on us 14:42.580 --> 14:45.580 that we would be governed by a complete, 14:45.580 --> 14:49.820 encyclopedic mythological state of reality 14:49.820 --> 14:52.780 where we don't really know the cutting edge of anything. 14:52.780 --> 14:57.660 And we've been told sort of cartoon versions of it 14:57.660 --> 14:59.820 so that we could be enslaved. 14:59.820 --> 15:02.620 And it's a kind of a dark narrative, 15:02.620 --> 15:04.340 but it's also a very hopeful one 15:04.340 --> 15:06.780 because if that's where we are right now 15:06.780 --> 15:09.860 when we still have houses and we still have running water 15:09.860 --> 15:12.340 and we still have roads that we can prepare, 15:12.340 --> 15:13.980 we still have bridges we can repair, 15:13.980 --> 15:17.300 we still have banks that we can close and audit. 15:17.300 --> 15:20.500 We still have an IRS that we can close and audit. 15:20.500 --> 15:23.220 We still have a federal reserve that we could close 15:23.220 --> 15:26.580 and audit we still have people that are alive, 15:26.580 --> 15:28.100 that know what's going on, 15:28.100 --> 15:30.460 that we could water board, for example. 15:30.460 --> 15:32.460 I mean, that's kind of a joke, of course. 15:32.460 --> 15:35.460 But there is still hope and I still feel hope. 15:35.460 --> 15:38.820 I don't think that they've come anywhere near 15:38.820 --> 15:41.260 to the kind of total control that they want us to believe. 15:41.260 --> 15:44.780 I still think it's very important to have a firm grip 15:44.780 --> 15:46.700 on the standing hypothesis 15:46.700 --> 15:49.260 of what recently happened over the last four years. 15:49.260 --> 15:51.700 I think that the who declared a pandemic 15:51.700 --> 15:54.220 of a dangerous novel virus that was detectable 15:54.220 --> 15:57.580 by a nonspecific PCR test that was likely rolled out 15:57.580 --> 16:02.580 in a background and its exposure was carefully curated 16:02.980 --> 16:06.900 to be misconstrued as spread using this test 16:06.900 --> 16:10.780 and a combination of media, bullets and financial incentives, 16:10.780 --> 16:13.700 which caused a mass casualty events. 16:13.700 --> 16:16.460 Those mass casualty events may have been coordinated 16:16.460 --> 16:19.580 by the US government, the Department of Homeland Security, 16:19.580 --> 16:22.340 the Department of Defense, I don't know. 16:22.340 --> 16:24.380 It's also possible that they could have seeded 16:24.380 --> 16:29.380 the molecular evidence for the virus being in Wuhan 16:30.020 --> 16:32.900 or in Iran or in Italy or in Washington 16:32.900 --> 16:34.540 in the Shohomish County man 16:34.540 --> 16:36.780 by using what is called an infectious clone 16:36.780 --> 16:41.460 because RNA virology is essentially based on this methodology. 16:41.460 --> 16:44.820 And after carefully thinking and reading 16:44.820 --> 16:47.740 and listening to other people talk about this stuff 16:47.740 --> 16:50.540 from decades past and currently, 16:50.540 --> 16:52.820 I have come to the very humble conclusion 16:52.820 --> 16:56.700 that people like Mark Bailey are correct about SARS-CoV-2. 16:56.700 --> 16:59.980 And in particular, I think we can summarize it best 16:59.980 --> 17:03.580 and most safely by saying that an RNA molecule 17:03.580 --> 17:05.300 cannot sustain a pandemic. 17:05.300 --> 17:07.740 And yet that's what we have been told has happened. 17:07.740 --> 17:10.060 And I believe that the reason why we are being told 17:10.060 --> 17:12.700 this mythology is so that we will teach it to our children. 17:12.700 --> 17:15.980 And the direct effect of that will be that they will submit, 17:15.980 --> 17:18.500 their sovereignty will be inverted into permissions 17:18.540 --> 17:21.220 because they believe a mythology that isn't real 17:21.220 --> 17:23.780 and therefore they will behave according to the edicts 17:23.780 --> 17:24.860 of that mythology. 17:24.860 --> 17:28.100 And as they turn up the heat and the coming years 17:28.100 --> 17:29.780 or even maybe a decade, 17:29.780 --> 17:32.260 then they can easily invert those rights 17:32.260 --> 17:35.020 to permissions in our kids, no problem. 17:35.980 --> 17:37.300 And of course, you've got to remember 17:37.300 --> 17:38.860 that social media is going to be working 17:38.860 --> 17:41.340 for those whole five years or those 10 years. 17:41.340 --> 17:43.420 Social media is going to be working very hard. 17:43.420 --> 17:47.420 Government is going to continue to govern us with mythologies. 17:47.420 --> 17:49.700 And so even if it doesn't happen now, 17:49.700 --> 17:52.820 it doesn't happen in a snap, it can happen over time. 17:52.820 --> 17:54.940 And that's exactly how this game has been played. 17:54.940 --> 17:57.860 COVID was like an abrupt thing 17:57.860 --> 17:59.340 to put everybody on their heels. 17:59.340 --> 18:01.140 But now that we're on our heels, 18:01.140 --> 18:03.500 there's not as much pressure needed. 18:03.500 --> 18:06.340 I don't know if you're a person who does Udo 18:06.340 --> 18:08.100 or any kind of martial arts, 18:08.100 --> 18:10.300 but once a person is off-balanced, 18:10.300 --> 18:13.220 then there's an incredible amount of force 18:13.220 --> 18:15.380 is no longer necessary. 18:15.860 --> 18:19.420 And so I think that we're currently in that state 18:19.420 --> 18:21.580 and being sort of taken advantage of in that way. 18:21.580 --> 18:23.260 And so we got to get our feet underneath this 18:23.260 --> 18:25.340 and the way we do that is with biology. 18:25.340 --> 18:28.580 And so I have broke down a couple of days ago, 18:28.580 --> 18:31.020 the basic thing that I think where we are now, 18:31.020 --> 18:32.460 it might have taken a while to get there. 18:32.460 --> 18:33.700 And so some of you people that thought 18:33.700 --> 18:35.900 I was going to repeat everything may have missed it. 18:35.900 --> 18:37.220 But I think it was two days ago, 18:37.220 --> 18:40.980 I did a stream where this is one of the slides in that talk 18:40.980 --> 18:43.540 and I'm basically addressing one, two and three 18:43.580 --> 18:48.580 in that discussion and in addressing the third one, 18:48.980 --> 18:51.700 we are trying to sort of get ahead of the dominoes. 18:53.660 --> 18:57.660 We identified the narrative of amyloidosis 18:57.660 --> 19:00.780 and pre-on generation by the spike protein already 19:00.780 --> 19:04.780 as kind of a red herring in 2020 and 2021 19:04.780 --> 19:06.660 when a number of people were very convinced 19:06.660 --> 19:08.380 that this was the story. 19:08.380 --> 19:10.580 I don't wanna call out any particular names, 19:10.580 --> 19:12.220 but there's more than one. 19:12.260 --> 19:14.980 And some of them I even had on my stream multiple times 19:14.980 --> 19:18.020 to talk about the various aspects 19:18.020 --> 19:21.700 of this spike specific toxicity 19:21.700 --> 19:23.980 and what aspects of it we could understand 19:23.980 --> 19:25.260 and not understand. 19:25.260 --> 19:27.660 And so one of the narratives that was running 19:27.660 --> 19:30.340 in the background as a worst case scenario 19:30.340 --> 19:33.100 with regard to the spike protein in particular 19:33.100 --> 19:35.860 was the idea that it was a pre-on generating 19:35.860 --> 19:38.700 or there was a pre-on motif in it 19:38.780 --> 19:42.260 or that it could cause crowdsfeld yachab disease. 19:42.260 --> 19:44.980 And one of the little hints of that 19:44.980 --> 19:46.260 is this letter B down here. 19:46.260 --> 19:48.300 I guess you can't see that because it's too small. 19:48.300 --> 19:49.660 I have to switch over here. 19:50.660 --> 19:52.060 Is this letter B? 19:52.060 --> 19:53.700 And then I'll get rid of this 19:53.700 --> 19:56.220 because that's supposed to be like this. 19:56.220 --> 19:59.380 This letter B down here is a Luke Montenier paper 19:59.380 --> 20:02.660 where I think it was 25 people who were injected 20:02.660 --> 20:07.500 with the original J&J or the original AstraZeneca 20:07.500 --> 20:12.500 developed acute crowdsfeld yachab disease. 20:12.740 --> 20:15.220 So that was cool, that's interesting 20:15.220 --> 20:18.340 but it had kind of in the beginning 20:18.340 --> 20:21.300 of the pandemic already was being taken out of context 20:22.300 --> 20:25.300 because those people were all convinced 20:25.300 --> 20:28.540 and uniquely, not uniquely, 20:28.540 --> 20:33.540 all united in their being convinced 20:34.420 --> 20:37.060 that the paper of Luke Montenier 20:37.060 --> 20:39.500 suggested that the spike protein did it. 20:39.500 --> 20:42.460 And so we had to be afraid of the virus 20:42.460 --> 20:45.540 and they didn't acknowledge the possibility, 20:45.540 --> 20:47.500 they didn't even spit out the possibility 20:47.500 --> 20:50.140 that it could be the transformation itself 20:50.140 --> 20:55.140 that was causing this acute protein misfolding disorder. 20:56.540 --> 20:59.500 Now, we're still in the gray area here. 20:59.500 --> 21:01.820 I'm not saying there are definitely pre-ons 21:01.820 --> 21:03.180 or definitely not pre-ons. 21:03.180 --> 21:05.900 What I'm trying to do is take a very objective approach 21:05.900 --> 21:09.420 to trying to look at the science that supports the idea. 21:09.420 --> 21:10.980 I don't wanna take a side on it 21:10.980 --> 21:13.660 especially with regard to the spike protein. 21:13.660 --> 21:15.020 I think it would be much more important 21:15.020 --> 21:18.620 to understand it as the biology as a phenomenon in general 21:18.620 --> 21:20.580 and then see if the spike protein fits it 21:20.580 --> 21:22.300 as a particular example. 21:22.300 --> 21:24.900 And I think that that's following the same sort of rubric 21:24.900 --> 21:27.740 that we did with COVID-19 because with COVID 21:27.740 --> 21:29.580 and SARS-CoV-2 we first started out 21:29.580 --> 21:32.580 with well, let's understand the immunology 21:32.580 --> 21:35.460 and the virology of coronaviruses in general 21:35.460 --> 21:37.860 before we start to try and understand the specifics 21:37.860 --> 21:40.260 of this particular story. 21:40.260 --> 21:42.420 And that got us very far, very quick. 21:42.420 --> 21:45.060 And I think that's why we were very successful 21:45.060 --> 21:46.900 in not getting too sucked in. 21:46.900 --> 21:50.660 And by 2021 we were already really pushing out. 21:50.660 --> 21:54.260 And I'm excited about this because I think 21:54.260 --> 21:59.260 this is kind of the same sort of, it's the right approach. 22:00.180 --> 22:03.940 So in doing it this way, my idea was to, again, 22:03.940 --> 22:07.780 as I said, use YouTube to do it. 22:07.780 --> 22:11.340 And so what I've found is this person named Susan, 22:11.340 --> 22:13.060 I'm gonna move my head for a second to see 22:13.060 --> 22:14.980 if I can see her name, Susan Linquist 22:14.980 --> 22:17.540 of the Whitehead Institute, MIT 22:17.540 --> 22:20.340 and the Howard Hughes, you know, Thingy Bobby. 22:20.340 --> 22:22.820 Now, of course that's already interesting, right? 22:22.820 --> 22:24.660 Because we know about the Whitehead Institute, 22:24.660 --> 22:26.380 we know about MIT. 22:26.380 --> 22:29.220 And if you go on YouTube, you will find an extraordinary 22:30.020 --> 22:35.020 number of videos about six, seven years old of this woman 22:36.100 --> 22:41.100 presenting lots of different takes on protein folding 22:41.260 --> 22:43.580 and how protein folding can go wrong. 22:43.580 --> 22:46.380 Now I'm choosing this one because I think it's a 22:46.380 --> 22:49.260 more general video that will help me introduce 22:49.260 --> 22:52.940 what I think is going to become essentially the main theme. 22:52.940 --> 22:54.820 And I'm just gonna say it right here out loud 22:54.820 --> 22:57.020 and then we'll see if that's what happens, right? 22:57.020 --> 22:58.740 We're gonna work through this together. 22:58.740 --> 23:02.100 But my feeling is, is that most of the biology 23:02.100 --> 23:07.100 in prions that is purported to be understood 23:08.780 --> 23:12.340 is actually understood in yeast. 23:12.340 --> 23:17.340 And so they have a yeast model of prionogenesis 23:17.700 --> 23:22.300 and how proteins can be a sort of genetic code 23:22.300 --> 23:27.300 all by themselves and how protein folding can be inherited. 23:28.900 --> 23:32.620 And they use this as a biological proxy 23:32.620 --> 23:36.580 and evidence for prionogenesis and prion disease 23:36.580 --> 23:41.580 and the mechanisms by which it occurs in other eukaryotes. 23:43.060 --> 23:44.500 And that's the really interesting thing. 23:44.500 --> 23:48.220 Yeast a single cellular cell organism has a eukaryote 23:48.220 --> 23:52.820 because it has a nucleus inside of a membrane 23:52.820 --> 23:55.060 and it's got some other membrane bound organelles. 23:55.060 --> 23:57.540 And so because the cells have some of the same 23:57.540 --> 24:00.500 or much of the same machinery that our cells do, 24:00.500 --> 24:04.500 we are considered part of the same large kingdom of life. 24:04.500 --> 24:07.940 And so molecular biologists studying prions 24:07.940 --> 24:12.660 have used yeast as a proxy for prionogenesis 24:12.660 --> 24:13.740 in our own cells. 24:13.740 --> 24:16.500 Now, that I'm not saying it's good or bad. 24:16.500 --> 24:19.220 I'm just wanting to understand the state of the art 24:19.220 --> 24:22.860 is that prions that we don't understand in nature, 24:22.860 --> 24:25.700 we don't understand on an island somewhere 24:25.780 --> 24:28.540 or we don't understand in a sheep field somewhere 24:28.540 --> 24:31.780 are often just assumed to work like the stuff 24:31.780 --> 24:33.900 that we have observed in yeast. 24:35.260 --> 24:37.740 And now we need to really focus together 24:37.740 --> 24:39.460 and you can do this work on your own too 24:39.460 --> 24:41.940 with PubMed and your own Google searches. 24:41.940 --> 24:44.180 We need to focus to what extent? 24:45.140 --> 24:49.820 The biology of these prions in yeast 24:49.820 --> 24:54.060 has been misconstrued as mechanistic evidence 24:54.060 --> 24:57.500 supporting the idea of how prionogenesis 24:57.500 --> 25:02.500 and these neurodegenerative diseases work in mammals. 25:05.420 --> 25:07.700 And now we're gonna have to work through this along, 25:07.700 --> 25:08.940 it's gonna take a long time. 25:08.940 --> 25:10.380 That's why maybe you thought 25:10.380 --> 25:12.380 I was just gonna throw papers up there. 25:12.380 --> 25:14.820 I did think that that's the way we would go about it, 25:14.820 --> 25:17.980 but it's become very clear to me after postponing 25:17.980 --> 25:21.300 for more than two weeks and trying to read more 25:22.300 --> 25:26.020 that in order to make my point as safely 25:26.020 --> 25:27.980 and as solid as possible, 25:27.980 --> 25:31.180 I'm gonna need to walk a little slower toward the exit 25:32.260 --> 25:35.820 because I don't wanna inadvertently somehow, 25:38.180 --> 25:41.420 yeah, not that I don't mind making mistakes, 25:41.420 --> 25:44.420 but I don't wanna make it easy 25:44.420 --> 25:46.340 for the people that are working against us 25:46.340 --> 25:49.140 to undermine what we're gonna do here. 25:49.140 --> 25:53.700 So I think the more we can let other experts speak for us 25:53.700 --> 25:57.500 and start to list the questions that we have 25:57.500 --> 26:00.980 and identify the potential incongruencies 26:00.980 --> 26:05.740 in their model, then we can more efficiently 26:05.740 --> 26:08.460 and more effectively move through the literature 26:08.460 --> 26:12.460 as we try to do journal clubs about prions 26:12.460 --> 26:14.500 because it's really important to understand 26:14.500 --> 26:17.740 what people like her see as the sort of big picture 26:17.780 --> 26:20.980 of what prions are and aren't and what they mean. 26:20.980 --> 26:23.820 And so I think this will be really interesting. 26:23.820 --> 26:26.180 I hope you will find it that way too. 26:26.180 --> 26:27.460 And we'll go from there. 26:31.740 --> 26:32.900 Let's see if this works. 26:34.620 --> 26:36.260 I just have an irregular speech. 26:36.260 --> 26:37.700 I'm Susan Lindquist. 26:37.700 --> 26:38.940 I'm at the Whitehead Institute 26:38.940 --> 26:41.500 in the Department of Biology at MIT 26:41.500 --> 26:44.180 and I'm here to tell you about protein folding. 26:45.180 --> 26:50.300 Protein folding is a universal problem of biological systems 26:50.300 --> 26:54.180 and it winds up influencing every aspect of biology 26:54.180 --> 26:55.340 that you can imagine. 26:57.260 --> 27:00.380 So these are very simple organisms 27:00.380 --> 27:02.420 called the yeast saccharomyces cerevisiae. 27:02.420 --> 27:03.660 It's a microorganism. 27:03.660 --> 27:06.300 This is obviously a very, very large magnification 27:06.300 --> 27:07.460 of these organisms. 27:08.460 --> 27:12.420 That organism is responsible for beer, bread, wine, 27:12.500 --> 27:15.500 all kinds of things that make life worth living. 27:15.500 --> 27:20.220 Anyway, that organism is also a wonderful experimental system 27:20.220 --> 27:23.540 that has the same types of problems with protein folding 27:23.540 --> 27:26.380 that those organisms over there have. 27:26.380 --> 27:30.020 This is a universal aspect of life. 27:30.020 --> 27:31.860 And we're used to thinking about life 27:31.860 --> 27:34.500 in terms of all the very different things 27:34.500 --> 27:36.900 that make up different individuals, 27:36.900 --> 27:39.780 but there's a unifying principle of life 27:39.780 --> 27:42.020 that relates to protein folding 27:42.020 --> 27:45.740 and that plays out from this organism to that organism 27:45.740 --> 27:48.700 in ways that allow us to deeply understand 27:48.700 --> 27:51.460 some of the worst problems in human biology 27:51.460 --> 27:56.060 and try to find clever solutions at to fix them. 27:56.060 --> 27:58.140 So you understand already where she's at, 27:58.140 --> 28:00.940 she's suggesting to you that the cellular machinery 28:00.940 --> 28:02.860 of yeast is so similar to ours 28:02.860 --> 28:05.780 and what they do is so similar to what we do, 28:05.780 --> 28:10.220 they have the exact same problem, protein misfolding. 28:11.220 --> 28:14.700 And so it's a very interesting place to start. 28:16.100 --> 28:18.460 And you're starting at the stage where ribosomes 28:18.460 --> 28:19.860 don't work that well, I guess, 28:19.860 --> 28:22.460 or that proteins are unpredictable 28:22.460 --> 28:24.660 or something or something. 28:24.660 --> 28:26.780 And so it's gonna be very, 28:26.780 --> 28:28.580 just feel it going forward. 28:28.580 --> 28:31.300 She starts already with saying, I'm gonna warn you, 28:31.300 --> 28:34.420 we're using yeast, yeast is a great model. 28:34.420 --> 28:35.660 They're fantastic. 28:35.660 --> 28:38.380 The first point she makes is yeast equals humans. 28:40.260 --> 28:44.540 So I think that already should shed light on where we are. 28:44.540 --> 28:48.020 And it's a very gentle presentation, 28:48.020 --> 28:49.540 but it's a very, you know, 28:49.540 --> 28:52.780 that's a forceful assumption right there. 28:52.780 --> 28:55.100 We're gonna use yeast as a model 28:55.100 --> 28:57.180 for what our own systems have to deal 28:57.180 --> 28:58.780 with what our own systems do. 29:01.500 --> 29:05.820 So proteins are us, many people think. 29:05.820 --> 29:08.060 I'm gonna stop it again because that name right there, 29:08.060 --> 29:10.660 Venki Rama Krishnan, 29:10.660 --> 29:13.020 that's the guy who studies ribosomes. 29:13.020 --> 29:15.740 He's like got the Nobel Prize for it. 29:15.740 --> 29:17.500 Mark Coolack did a couple of videos, 29:17.500 --> 29:19.620 I think at least one video on him. 29:19.620 --> 29:22.100 And I find him a very interesting piece in the puzzle 29:22.100 --> 29:24.780 who I'm very curious what he thinks about prions 29:24.780 --> 29:27.260 and the role of ribosomes in them, et cetera. 29:27.260 --> 29:29.420 Anyway, I'll try to let it run. 29:29.420 --> 29:31.620 About proteins as being food. 29:31.620 --> 29:33.580 The reason why we think of them as being food 29:33.580 --> 29:36.740 is because we need to take some of those elements 29:36.740 --> 29:38.980 of proteins into ourselves, 29:38.980 --> 29:40.500 chop them up into little pieces, 29:40.500 --> 29:42.860 reassemble them into our own proteins 29:42.860 --> 29:45.500 because proteins do just about everything 29:45.500 --> 29:48.060 that you can think of in our bodies. 29:48.060 --> 29:52.820 Proteins are the muscle that powers our arms and legs. 29:52.820 --> 29:56.820 Proteins are carrying pigments in our eyes 29:56.820 --> 29:59.380 and it's when light strikes those pigments, 29:59.380 --> 30:01.700 it causes the protein to change shape, 30:01.700 --> 30:04.860 that sends a signal to our brain and that's how we see. 30:04.860 --> 30:07.060 Proteins are parked in our stomachs 30:07.060 --> 30:09.580 and ready to receive the food we eat 30:09.580 --> 30:13.220 and tear it apart into little component parts 30:13.220 --> 30:16.420 that we can use to build up new proteins 30:16.420 --> 30:19.940 that, as I mentioned, do just about everything 30:19.940 --> 30:24.020 in our biology that we think about as a living system. 30:25.420 --> 30:27.540 Now, the problem with protein folding 30:27.540 --> 30:31.220 is that these things look kinda complicated, right? 30:31.220 --> 30:32.900 And they are very complicated, 30:32.900 --> 30:35.900 but they start out very simply. 30:35.900 --> 30:40.420 So the code of life is often called the double helix 30:40.420 --> 30:44.900 and it's a very long linear string of information. 30:44.900 --> 30:48.020 It itself doesn't look too interesting, 30:48.020 --> 30:51.020 but along different parts of this, 30:51.020 --> 30:54.540 it codes for the essential elements of proteins 30:54.540 --> 30:56.540 that make up living systems. 30:56.540 --> 31:00.620 And a good analogy for the way in which this information 31:00.620 --> 31:04.540 is encoded in this long linear molecule 31:04.540 --> 31:07.500 is to think about cassette tapes. 31:07.500 --> 31:09.820 Now, cassette tapes were something 31:09.820 --> 31:12.060 I played all the time when I was young. 31:12.060 --> 31:15.380 I know that you're mostly playing CDs 31:15.380 --> 31:17.380 and other digital forms of music. 31:17.380 --> 31:20.380 But the cassette tape provides a really great analogy 31:20.380 --> 31:24.500 for the way in which very complex information 31:24.500 --> 31:26.420 can be encoded by a simple... 31:26.420 --> 31:29.420 Now, as a member of the Broken Science Initiative, 31:29.420 --> 31:32.540 I'd like to point out that she called this an analogy. 31:32.540 --> 31:34.700 And I think that's a very... 31:34.700 --> 31:37.540 It's appropriate for her to use that word 31:37.540 --> 31:40.660 because if she said this is a great model of DNA, 31:40.660 --> 31:43.380 then this model would make all kinds of predictions 31:43.380 --> 31:45.100 that don't work for DNA. 31:45.100 --> 31:46.660 And so she says it's an analogy 31:46.660 --> 31:50.300 because it actually weakens your potential understanding 31:50.300 --> 31:55.300 of DNA because unless the analogy is extremely on target, 31:55.420 --> 31:56.540 which it's not, 31:57.540 --> 31:58.820 if it was a good analogy, 31:58.820 --> 32:01.900 it would work as a pretty good model as well. 32:01.900 --> 32:05.860 And so keep that in mind as these people teach you biology, 32:05.860 --> 32:09.380 are they giving you an analogy which can serve then 32:09.380 --> 32:13.220 to make you understand their model better? 32:13.220 --> 32:16.340 Or is it an analogy that almost disarms you 32:16.340 --> 32:18.460 from even questioning their model? 32:18.460 --> 32:22.100 Because if you start to understand DNA as a cassette tape, 32:22.100 --> 32:23.500 then you've already been... 32:23.500 --> 32:25.180 You're already kind of limited 32:25.220 --> 32:26.820 in terms of how you're gonna understand 32:26.820 --> 32:30.020 how protein production results from that, right? 32:30.020 --> 32:35.020 It's a very subtle but spectacularly effective way 32:35.020 --> 32:40.140 to assume or pretend like you're really giving good information. 32:40.140 --> 32:44.620 When in reality, she's already undermined anybody 32:44.620 --> 32:49.620 without previous experience in her first two minutes. 32:50.940 --> 32:52.820 So it's only a 20 minute video, 32:52.820 --> 32:54.300 but it will take a while to get through it 32:54.300 --> 32:56.860 because it's very important for us 32:56.860 --> 33:00.820 to be able to efficiently do this, 33:00.820 --> 33:03.180 to be able to hear what people are saying 33:03.180 --> 33:04.500 and very quickly say, 33:04.500 --> 33:07.180 well, I understand biology like this. 33:07.180 --> 33:10.380 And so we know that DNA is more complicated than a cassette tape. 33:10.380 --> 33:12.380 We know it's not just a linear molecule. 33:12.380 --> 33:15.420 We know that there are all kinds of ways 33:15.420 --> 33:19.580 that that code can be intermixed, blocked, altered, 33:19.620 --> 33:21.060 methylated, whatever. 33:21.060 --> 33:24.220 We know that what we know is very little. 33:26.060 --> 33:28.500 And so it's frustrating that she says, 33:28.500 --> 33:30.140 this is a great analogy for it. 33:30.140 --> 33:32.940 It's a great analogy if you don't really want to understand 33:32.940 --> 33:36.180 where the irreducible complexity is 33:36.180 --> 33:37.660 and what we know about it, then yeah, 33:37.660 --> 33:39.060 this is a great analogy. 33:40.340 --> 33:42.140 Long thread. 33:42.140 --> 33:43.260 So here we go. 33:44.700 --> 33:46.420 Here's a cassette tape. 33:46.420 --> 33:49.540 You look at the tape that's wound around those two spools 33:49.700 --> 33:52.180 and it doesn't look the least but interesting. 33:52.180 --> 33:54.660 But when you put it into this machine 33:54.660 --> 33:56.620 that decodes the information, 33:56.620 --> 34:01.140 just like DNA is decoded in the machinery of the cell, 34:01.140 --> 34:05.140 outcomes the most amazing and complex and beautiful sounds. 34:06.980 --> 34:09.540 Oh, and those are proteins. 34:09.540 --> 34:13.220 She really thinks she's a good presenter. 34:13.220 --> 34:14.060 It's nice. 34:14.060 --> 34:15.340 You get completely different sounds. 34:15.340 --> 34:16.540 I'll probably turn that on. 34:16.540 --> 34:18.540 And another piece of the tape. 34:18.540 --> 34:19.540 Wow. 34:19.540 --> 34:21.540 And another piece of the tape. 34:21.540 --> 34:22.540 Wow. 34:22.540 --> 34:23.540 Wow. 34:23.540 --> 34:24.540 Wow. 34:24.540 --> 34:25.540 Wow. 34:25.540 --> 34:26.540 Wow. 34:26.540 --> 34:27.540 Wow. 34:27.540 --> 34:28.540 Wow. 34:28.540 --> 34:29.540 Wow. 34:29.540 --> 34:30.540 Wow. 34:30.540 --> 34:31.540 Wow. 34:31.540 --> 34:32.540 Wow. 34:32.540 --> 34:33.540 Wow. 34:33.540 --> 34:34.540 Wow. 34:34.540 --> 34:35.540 Wow. 34:35.540 --> 34:36.540 Wow. 34:36.540 --> 34:37.540 Wow. 34:37.540 --> 34:38.540 Wow. 34:39.540 --> 34:40.540 Wow. 34:40.540 --> 34:41.540 Wow. 34:41.540 --> 34:42.540 Wow. 34:42.540 --> 34:43.540 Wow. 34:43.540 --> 34:44.540 Wow. 34:44.540 --> 34:45.540 Wow. 34:45.540 --> 34:46.540 Wow. 34:46.540 --> 34:47.540 Wow. 34:47.540 --> 34:48.540 Wow. 34:48.540 --> 34:49.540 Wow. 34:49.540 --> 34:50.540 Wow. 34:50.540 --> 34:51.540 Wow. 34:51.540 --> 34:52.540 Wow. 34:52.540 --> 34:53.540 Wow. 34:53.540 --> 34:54.540 Wow. 34:54.540 --> 34:57.540 So how does that complexity get encoded in that simple linear molecule? 34:57.540 --> 35:06.540 Well, that's a problem biologists 35:06.540 --> 35:12.540 to fold up into very precise shapes in order to do anything interesting in the cell. 35:12.540 --> 35:18.780 I find it intriguing that there is no mention of RNA at all. Now mention of RNA editing, 35:18.780 --> 35:27.100 no mention of RNA three-dimensional shapes, no mention of RNA regulation, no mention of RNA 35:27.100 --> 35:35.100 interaction with the, wow, I mean we just went from DNA to protein, which of course even occurs 35:35.180 --> 35:41.660 in different compartments of our eukaryotic cell. Like, whoa, so now you see why that 35:41.660 --> 35:47.660 cassette tape analogy is incredible. If you combine it with this, now how much biology have you 35:47.660 --> 35:54.220 learned from the MIT lady? Are you ready to argue with somebody like Kevin McCurnan? I mean, 35:54.220 --> 36:00.140 that's, that's the frustrating thing here. And people can watch hours and, and they will be. 36:00.460 --> 36:07.980 And those shapes are incredibly complicated. So let's look at some real protein structures. 36:10.780 --> 36:16.140 You can see each of these different parts of the code has been decoded into long linear string, 36:16.860 --> 36:22.380 but that folds up and folds up and moves back and forth and back and forth on top of itself. 36:22.380 --> 36:27.100 And it's the complexity of this fold that can actually do something powerful. 36:27.980 --> 36:34.380 Now, the difficulty in terms of how this plays out into living systems is we don't really understand 36:34.380 --> 36:40.620 the forces that allow the protein to fold so precisely into exactly the right shape. What we 36:40.620 --> 36:44.860 are understanding, however, is that when they don't fold into exactly that right shape, 36:45.900 --> 36:53.900 disaster occurs. And a way of thinking about this, again, to kind of, to illustrate this, 36:53.980 --> 36:59.500 this process is to think again about that music, that long linear piece of information and a 36:59.500 --> 37:05.580 cassette tape that encodes extraordinary music. Well, it's played by instruments, right? And 37:05.580 --> 37:11.260 instruments are together playing together and they make great music. Just like the proteins 37:11.260 --> 37:16.220 are together in a cell and they make wonderful, wonderful biology and you have different proteins 37:16.220 --> 37:21.500 making different types of biology in your digestive system, in your brain, in your heart. 37:22.380 --> 37:30.700 The problem is that making these complex folds is very much like taking a lot, long sheet or 37:30.700 --> 37:35.980 square sheet of metal and moving it into forming a musical instrument. 37:40.620 --> 37:46.220 So if you get the fold exactly right, it can play some beautiful music. 37:46.220 --> 37:55.980 Music. But if there's some very small element of the fold that you get almost right, you don't 37:55.980 --> 38:08.380 get it quite right. It can be a disaster. And now the principle of prions, and I hope she's going 38:08.380 --> 38:14.860 to say that, is that there is a particular kind of fold where this horn can then sit next to other 38:14.860 --> 38:21.420 horns and ruin those horns as well. And so again, all of a sudden the analogy falls to pieces because 38:21.420 --> 38:29.820 their own model, well, that doesn't work with horns. And so you see what the issue is, when I make 38:29.820 --> 38:35.980 an analogy like this, the analogy is essentially the model and the model that I'm trying to use 38:35.980 --> 38:42.380 to make predictions that are validated in the future. And so unfortunately, this is not really a 38:42.380 --> 38:49.500 very good model, because remember, it's not a sheet of metal. It's three dimensional electrostatic 38:51.100 --> 38:59.260 shapes that are interacting with one another in a chain that are surrounded by a polar solvent 38:59.260 --> 39:09.900 called water, which we know has extraordinary attributes at a molecular scale. And so if these 39:09.900 --> 39:16.460 proteins are hydrophobic and hydrophilic, it's because they are electromagnetically hydrophobic 39:16.460 --> 39:23.100 or electromagnetically hydrophilic. And that changes their propensity to fold inside of that 39:23.660 --> 39:31.660 polar solvent. And so it's nowhere near the analogy of sheet metal. And it's nowhere near, 39:31.660 --> 39:37.740 this is not a misfolded protein. So unless she says that and prions are horns that cause other 39:37.820 --> 39:44.540 horns to crumple up, then she's not adequately taking this analogy to its logical conclusion, 39:44.540 --> 39:48.460 and therefore really not using it effectively, actually misleading people with it. 39:49.740 --> 39:52.300 Here's another example. Oh, she didn't even say anything. 39:53.020 --> 39:58.140 Piece of metal folding up into a different shape, making and doing different things. 39:58.140 --> 40:02.780 I love the French horn. It's the most beautiful sound. 40:02.780 --> 40:10.700 Right. A fold isn't quite right. It's a disaster. So now you've got this orchestra of proteins 40:10.700 --> 40:15.340 that make up the living system, and they need to play together exactly right. They need to 40:15.340 --> 40:20.380 fold properly, and then they need to play together exactly right. If you want the living system 40:20.380 --> 40:26.460 to be disease free. Wow, what an interesting, that's a whole protein instrument. That's a whole 40:26.460 --> 40:32.700 summary of biology and the broadest terms. You got to have rightfully folded proteins if you 40:32.700 --> 40:39.980 want the body to be free of disease. And it's not totally wrong. But it's interesting because this 40:39.980 --> 40:47.980 whole so far, this whole lecture has been to try and convince you of the primacy of protein folding 40:47.980 --> 40:55.020 and almost like we're always, I guess, having to deal with this problem. It's a big problem. 40:55.100 --> 40:58.060 Misfolded protein is a huge problem apparently. 40:59.580 --> 41:04.620 Are actually functioning together inside of a living cell. You're going to see pictures of 41:04.620 --> 41:11.420 proteins serving as architecture and the structural integrity of the cell. You see proteins talking 41:11.420 --> 41:17.900 to each other between cells. You'll see proteins cutting proteins, assembling into various structures, 41:18.940 --> 41:24.460 disassembling. And all of these are part of the orchestration of life inside the living cell. 41:25.180 --> 41:33.180 What is, oh no, we're going to use a cartoon to show us what it looks like so we're bamboozled 41:33.180 --> 41:40.380 into believing we know. That's what this is. It would be hard to imagine that any of this stuff 41:40.380 --> 41:46.700 is just exaggeration, right? Obviously they must know all this stuff. This must be backed by 41:47.180 --> 41:52.700 thousands of papers. Otherwise they wouldn't make such a video, right? 41:52.700 --> 42:18.860 Wow, look how that works. Gee, it just all does it. They just all assemble. That's so cool. 42:23.500 --> 42:34.060 I mean, if they can make a cartoon like this, that must be how microtubules assemble. 42:34.700 --> 42:41.580 This must be how dyin' in halls, vesicles around, must be moving along the information 42:41.580 --> 42:46.780 highway of the cell and bringing pets of goodies from one end of the cell to the other end of the 42:46.780 --> 42:51.740 cell. Anyway, you can see I think. I'm not saying it doesn't happen that way. 42:53.100 --> 43:00.220 I'm suggesting to you that there are aspects of this video which are assumed because one or two 43:00.220 --> 43:06.140 of aspects of this video are actually fairly well understood. And since we understand one or two of 43:06.140 --> 43:10.460 these things, why can't we make assumptions about all this stuff? And one of the things that is 43:10.460 --> 43:15.580 assumed is that somehow or another, these subunits of all these proteins just come together, 43:17.580 --> 43:21.580 and now in a little while, she's going to show you another video, but she's not going to point 43:21.580 --> 43:26.940 out that this video, if the other video is correct, then this video is totally wrong. 43:27.660 --> 43:32.220 And she's not going to point that out, but she's going to, at some point, make an argument that 43:32.220 --> 43:36.940 it's really crowded in a cell, but this is not a crowded cell. There aren't proteins everywhere 43:36.940 --> 43:42.700 here. And so it's a very interesting, you know, we're going to flip flop back and forth over here, 43:42.700 --> 43:45.820 and that's because she thinks you're asleep or something, I think. 43:47.180 --> 43:51.660 The extraordinary complexity of living system and the proteins that are operating in it 43:51.660 --> 43:56.300 to keep us biologically active and do all the amazing things that we can do. 43:57.740 --> 44:04.220 I urge you, by the way, to get on the web and plug in that reference and take a longer look at 44:04.220 --> 44:08.620 the movie. And there's also an animation that will tell you exactly what you're looking at all 44:08.700 --> 44:11.660 in various parts of it. I've just shown you a very small snippet. 44:12.620 --> 44:20.620 But this incredibly complicated biology that's represented by this beautiful movie 44:21.580 --> 44:27.500 is misrepresented in just one particular way. And that is that in order to illustrate how 44:27.500 --> 44:31.420 these proteins are moving about and doing their things and interacting with other proteins in 44:31.420 --> 44:36.700 the cell, they've taken most of the proteins out of that system so that you can see them. 44:37.660 --> 44:42.380 In reality, the cell is much, much, much more crowded. 44:43.580 --> 44:44.540 Okay. 44:44.540 --> 44:50.060 So you think about this complicated protein fold and the fact that different proteins have 44:50.060 --> 44:55.420 different folds, they have to go from a long linear string of amino acids into those complicated 44:55.420 --> 45:02.140 folds so that they can interact with themselves properly. And they have to do that in a really 45:02.220 --> 45:08.940 crazy environment. They have to do this in an environment that's this packed with proteins. 45:08.940 --> 45:15.420 So each one of these colors actually represents a different protein in its complex, beautiful 45:15.420 --> 45:22.780 shape that can change and move around and do various things. But this image, although it 45:22.780 --> 45:27.980 represents the crowding of the cell, is missing one other piece. By the way, this is a beautiful 45:27.980 --> 45:32.860 movie by Adrian Elcock. And again, you can find it on the web. 45:34.380 --> 45:41.420 The thing that this particular image does not convey is how energetic the system is. 45:41.420 --> 45:45.580 Proteins are actually moving about like crazy all the time. And it's this aspect of proteins 45:45.580 --> 45:50.060 being able to move and signal from one end of the cell to the other end of the cell, 45:50.860 --> 45:56.540 help us to interpret what we see one moment and I'm looking here at you or looking over here at 45:56.620 --> 46:00.460 the screen. I completely change everything I understand about what I'm looking at because 46:00.460 --> 46:06.860 the proteins are changing shape so fast. So living systems have proteins that work at incredible 46:06.860 --> 46:11.900 speed. And here's an example of the way they move about and how the crowding is 46:12.940 --> 46:17.820 jostling and banging to each other all the time. So what's missing in her explanation here, 46:17.820 --> 46:24.220 what's crucial to understand is that this is not happening in free space, right? It's happening 46:24.220 --> 46:29.980 in the polar solvent of water at the molecular scale. So there is a potential for there to be a 46:29.980 --> 46:37.660 lattice here. There are potential for there to be much more space between proteins, which is occupied 46:37.660 --> 46:45.420 by less than, I mean, water is not water at the molecular scale. Water at the molecular scale is 46:45.420 --> 46:51.820 like puzzle pieces that can kind of get locked into place, right? And so they can form kind of a 46:51.820 --> 46:57.180 crystal lattice at that, at that size scale. So do they move around like this? Probably, but 46:57.180 --> 47:03.020 they're moving around like this in the context of a polar solvent. And so other things can happen 47:03.020 --> 47:08.860 besides this. And I think that for the moment, I'm just going to say that I think this is 47:09.740 --> 47:17.980 terribly insufficient to describe what's happening. And so she's sort of hand waving over what is one 47:17.980 --> 47:24.780 of the most beautiful places that you can bring someone to understand the irreducible complexity 47:24.780 --> 47:31.740 of a cell. Because if you were to, you know, adequately explain how water plays a role in this, 47:31.740 --> 47:39.740 and that sort of bring them down to understand what water is, and how that molecular three-dimensional 47:39.740 --> 47:49.420 charged shape, polar shape, can have real physical phenomenon at that scale, and how that would then 47:49.420 --> 47:56.220 interact with these highly polarized giant molecules, it becomes a far more compelling 47:57.100 --> 48:02.940 place for your imagination to go as a biologist looking for the, you know, the edge where the 48:03.020 --> 48:09.420 irreducible complexity starts. And it feels as though this is hand waving over that instead of 48:09.420 --> 48:14.380 pointing out this is where it is. This is the irreducible complexity that we're having a lot 48:14.380 --> 48:21.260 of fun exploring, but we have no real hope of cracking in the sense of all knowing. 48:22.940 --> 48:29.580 And that's frustrating, but okay, let's go. The one way in which this animation doesn't quite convey 48:29.580 --> 48:36.860 what's happening in the cell is that it too, for the purposes of clarity, has been modified 48:36.860 --> 48:44.700 in a certain way, and that is it's been slowed down. So just as the other movie I showed you, 48:44.700 --> 48:50.620 this was not very crowded, and things are moving around rather slowly, in this movie which shows 48:50.620 --> 48:58.140 the crowding, things are actually not moving at real speed. So you can illustrate and understand 48:58.220 --> 49:01.740 and look at how these proteins are interacting with each other and moving around. 49:03.020 --> 49:07.020 In order to get a realistic idea of how fast these proteins are moving around in the cell, 49:07.660 --> 49:13.980 you'd have to speed that movie up not ten times, not a hundred times, not a thousand times, 49:13.980 --> 49:21.740 not a hundred thousand times, but one million times. So that movie is real slow motion compared 49:21.740 --> 49:27.420 to what's happening in the biology and living system. And there you have the heart of the protein 49:27.420 --> 49:33.340 folding problem, because if these long linear strings of amino acids have to fold up into these 49:33.340 --> 49:39.260 very, very precise shapes without getting into trouble with other proteins while they're doing it, 49:39.900 --> 49:45.980 under such incredibly kinetic energetic conditions, you can imagine that sometimes they get that 49:46.060 --> 49:51.580 fold wrong, just like those musical instruments, if you don't, but don't fold the metal exactly. 49:51.580 --> 49:56.300 I really feel something's wrong with this. I don't know how to say it any other way that I 49:56.300 --> 50:01.260 don't think that that is a good portrayal of what goes on inside of a cell given what we've seen 50:01.260 --> 50:07.340 under a microscope, given what I've seen under a microscope. I don't believe it anymore. So 50:10.460 --> 50:15.660 I'm doing some reading on the side over here, and I'm just not buying this. I think that this 50:15.660 --> 50:19.980 is one of those things where if you can make a computational biology paper, look at that. 50:20.940 --> 50:26.780 It's right there. If you can make a model of something like this, that's great. That's perfect, 50:26.780 --> 50:32.780 because that's exactly what we have with that model of the end protein and the RNA getting 50:32.780 --> 50:38.780 packaged into a endosome with spike protein on the outside of it. We made a beautiful model 50:38.780 --> 50:44.300 of how this works, and we have all kinds of variables in our model, and it just works out great. 50:46.140 --> 50:51.420 And that's what I think this is. It's designed to confuse you. It's designed to make it again, 50:51.420 --> 50:57.660 seem like everything that happens in a cell is just a random, it's just a random nonsense. 50:57.660 --> 51:04.380 It is not a clock. Don't think of a cell like a clock. Think of it as a sack of assorted beans 51:04.380 --> 51:10.380 that you just get, gets lucky all the time. Think about that. She's trying to convince you 51:10.460 --> 51:17.020 that our cells work like this, and just the right enzymes come together, the right 51:18.620 --> 51:26.780 tRNA shows up at the right ribosome at the right time through all of this mess. I mean, come on, come on. 51:29.980 --> 51:34.540 Right. It could ruin an orchestra. The same thing can happen in living systems. 51:35.500 --> 51:39.900 And when you say what I see on a microscope is on a fixed slide, it's actually not. I've 51:39.980 --> 51:47.980 looked at live neurons. I've looked at live cell cultures of all kinds of cells in my career, 51:47.980 --> 51:53.100 and they're all alive. And when you use fluorescence or you use other kinds of 51:54.140 --> 52:03.020 means of labeling different parts, then you can see them. I've watched a frog embryo divide to 52:03.020 --> 52:08.700 48 cells once by staying in a laboratory for almost 48 hours straight. 52:10.860 --> 52:16.620 So I've definitely taken the time to look under real microscopes at real living cells. 52:17.500 --> 52:24.700 In fact, I had a couple friends at Pitt that I just spent time with in the confocal microscope 52:24.700 --> 52:29.020 room just because of what they were doing. And at least one of them was working on hippocampal 52:29.020 --> 52:34.060 cell cultures. So again, that's live cells with with several different fluorescent labels. And so 52:34.060 --> 52:40.060 you can see the space inside of the cells can't possibly look like what she just showed you. Otherwise, 52:40.060 --> 52:44.700 you wouldn't be able to watch the trafficking of proteins and stuff like that, right? I mean, 52:44.700 --> 52:50.940 that's just weird. It's strange. I don't know. And now this this if she's going to say this 52:50.940 --> 52:54.540 has something to do with prions, I'm going to be very sad. 52:55.420 --> 53:02.220 So I want to give you one more illustration, one more analogy. What happens when proteins start 53:02.220 --> 53:07.340 to misfold and bang into each other in inappropriate ways and stick to each other and 53:08.700 --> 53:15.900 something a process we call protein aggregation? And you know exactly what protein aggregation is 53:15.900 --> 53:24.060 like. I know that you've seen it many times. The egg white in this little photograph is actually 53:24.140 --> 53:28.380 a solution. I think we should just go back because before she ruins this idea, 53:29.180 --> 53:33.660 I want to put something else on the screen. Think about this for a second. 53:41.100 --> 53:45.500 Yeah, I really want to say, okay, I'm going to let her I'm sorry, I'm going to let her speak. 53:45.500 --> 53:51.020 I don't want to ruin too much. I don't want to say too much. I just I want to let it go. 53:51.020 --> 53:57.020 So I want to give you one more illustration, one more analogy. What happens when proteins 53:57.020 --> 54:02.460 start to misfold and bang into each other in inappropriate ways and stick to each other and 54:03.820 --> 54:11.020 something a process we call protein aggregation? And you know exactly what protein aggregation is 54:11.020 --> 54:19.260 like. I know that you've seen it many times. The egg white in this little photograph is actually 54:19.260 --> 54:25.660 a solution of protein. The proteins are all folded properly and so they're clear and beautiful 54:25.660 --> 54:32.380 and not in any trouble. But when you apply heat to that system, the proteins start to move around 54:32.380 --> 54:37.580 a little faster. They start banging into each other. They start unfolding a little bit. And what 54:37.580 --> 54:44.540 happens is the properties of the biological system change completely. And that is in fact what you 54:44.620 --> 54:50.460 get. So those and so this is actually a combination of the boiling of water, right? 54:51.900 --> 54:58.060 And the denaturing of protein. So they go to a linear form. Now the reason why this is annoying 54:58.060 --> 55:03.020 is because supposedly prions are you can't you can't you can't destroy them with heat. 55:04.460 --> 55:10.300 So then prions don't are not related to that. Because if prions are a kind of protein 55:10.300 --> 55:17.340 configuration that is immune to heat, immune to auto-claving, then this is not a good analogy 55:17.340 --> 55:23.660 because they are proteins that can't be denatured, I guess. Why don't we use the word denatured here 55:23.660 --> 55:29.900 because then when we come to proteins, she could say that proteins like prions can't be denatured. 55:31.500 --> 55:36.460 In all of the reading that I've done in preparation for taking you through this part of the cave, 55:37.420 --> 55:44.380 I have never heard anyone say that proteins can be denatured, but prion proteins cannot be denatured. 55:44.380 --> 55:51.500 Even though as a biologist, since I was at least in high school, this is denatured protein. 55:52.140 --> 56:00.300 Protein that is linearized linear, I can't even say it, is made linear by the application of 56:00.300 --> 56:05.900 heat because you break all the hydrogen bonds because you of course increase the kinetic energy 56:05.980 --> 56:18.860 of the water. I'm just very curious as to where this is going. And I know that I think you're going 56:18.860 --> 56:24.620 to enjoy this journey that we go on. And I think at the end of this, we're going to have a very, 56:24.620 --> 56:29.980 very succinct message about what's going on here. And we're going to be able to say, look, 56:30.060 --> 56:35.660 anybody that's pushing this and is not saying very specifically that 56:35.660 --> 56:41.500 transfection and healthy humans is criminally negligent because one of the worst case scenarios 56:41.500 --> 56:50.860 is a protein misfolding disorder, then they're being extremely disingenuous. They are not playing 56:50.860 --> 56:55.100 for our grandchildren. They were playing for team worst case scenario from the very beginning. 56:55.100 --> 57:00.780 Anybody that sold this as a as a part of the spike protein on the virus, I'm going to put 57:00.780 --> 57:05.900 all my chips on the fact that they have to be working against us, at least in America. 57:07.660 --> 57:14.780 Most of the people that are anybody that's fighting for the American Republic and whatever's left of it 57:16.940 --> 57:24.460 cannot by definition have been pushing the pre on hypothesis in 2020 or 2021 because they had to be 57:25.340 --> 57:30.620 either wittingly or unwittingly involved in ceding that narrative because there was, 57:30.620 --> 57:36.620 it had nothing to do with that. It had only to do with transfection and the potential for it. 57:37.900 --> 57:45.100 And this complete whiff. This is a whiff. If you're not a baseball fan, it's when you swing and you 57:45.100 --> 57:48.940 miss, you have a perfect pitch. It's right down in the middle. You could hit a home run with it. 57:49.020 --> 57:56.380 You got a great big giant bat and you missed because she could just say this is denatured 57:56.380 --> 58:01.900 protein. And so she could make two points with one. You've seen proteins that go into aggregate 58:01.900 --> 58:06.460 aggregate proteins are often denatured ones. The examples that you know of are scrambled eggs. 58:07.820 --> 58:12.860 But interestingly, prions are really cool because they can't be denatured. So when you apply heat 58:12.860 --> 58:18.220 to them, they don't go away. And now she's made an adequate analogy. But instead, 58:18.940 --> 58:24.220 this MIT professor says that this is aggregate protein. It's not denatured protein. It's 58:24.220 --> 58:30.860 aggregated protein, which is really weird because she has to know that's wrong. 58:30.860 --> 58:43.820 These are aggregated proteins. And it's just a nice visual illustration of the problem that 58:43.820 --> 58:50.780 can occur when proteins don't fall properly in our living systems. So we want to understand 58:50.780 --> 58:57.100 how we can keep the proteins looking more like this and how if they start to go off. 58:57.100 --> 59:04.620 I just said it right there. I think that using modified RNA to transfect healthy humans is a 59:04.620 --> 59:09.660 I don't see any reason why that couldn't result in protein misfolding. They're using a chemically 59:09.660 --> 59:16.380 modified codon optimized viral RNA or that an RNA that they claim came from a virus. And they're 59:16.380 --> 59:21.020 transfecting healthy humans with it. So do I know what's going to happen? Absolutely not. 59:21.020 --> 59:25.900 As far as I'm concerned, we should leave room on that list no matter how many things we add to it 59:25.900 --> 59:31.580 because there's always possibly another one. And one of them, unfortunately, I think is possible 59:31.580 --> 59:36.380 is a protein misfolding disorder. Why not? I don't know if we understand these things yet, 59:36.380 --> 59:43.020 but I'm going to show you that I think we understand a lot less about the protein misfolding disorders 59:43.020 --> 59:49.340 that we seem to find in mammals versus what we purport to understand in yeast. And that's the 59:49.900 --> 59:55.660 disconnect and maybe contradiction or incongruency that is being weaponized against us. 59:58.060 --> 01:00:01.980 Pathway and start to form little bitty aggregates. We can bring them back to life. 01:00:03.180 --> 01:00:09.340 Because just a little bit of that aggregation state causes disaster for a living system. 01:00:11.260 --> 01:00:14.380 So what are the solutions that life I don't I don't like this analogy at all. 01:00:14.380 --> 01:00:19.420 The first way we started to discover and learn something about the solutions to that problem 01:00:19.420 --> 01:00:27.180 actually involved heat. So here we have a very simple experiment that was done with yeast cells. 01:00:27.900 --> 01:00:35.260 We're growing yeast cells in a culture, in a shaking roman mire flask. And we took some of those 01:00:35.260 --> 01:00:41.100 cells out. We took two identical alichlots of cells out. What I mean by an alichlot is just a 01:00:41.100 --> 01:00:48.060 little portion of the culture. Two identical portions of the culture out. And that one on the 01:00:48.060 --> 01:00:54.620 top there was exposed directly to a high temperature. And the proteins denatured and killed the cell. 01:00:55.660 --> 01:01:01.100 This one on the bottom was first exposed to an intermediate temperature to allow it to 01:01:01.100 --> 01:01:07.420 kind of condition. Basically it was exposed for half an hour to 39 degrees instead of being 01:01:07.420 --> 01:01:12.940 shifted directly to 50 degrees. And as you can see that short half hour pre-treatment 01:01:13.580 --> 01:01:20.540 provided tremendous increased capacity of the cells to survive that second higher heat treatment. 01:01:21.500 --> 01:01:30.220 Now this is a universal property of life. And so it is not only true for yeast cells. It's true 01:01:30.220 --> 01:01:34.540 for a rabbit opposite seedlings. This is basically the same experiment. A rabbit opposite seedlings 01:01:34.540 --> 01:01:39.500 were planted in these little dishes. One treated directly at high temperatures. The other one 01:01:39.500 --> 01:01:44.140 given this intermediate treatment that allowed it to condition itself. And then to withstand 01:01:44.140 --> 01:01:51.260 the rigors of that more intense condition. And these are human cells in culture. Basically 01:01:51.260 --> 01:01:57.180 the same experiment. You can do this experiment with all living organisms on earth. Because all 01:01:57.260 --> 01:02:03.980 living organisms face the same problem of protein folding. And they all prepare for problems in 01:02:03.980 --> 01:02:10.700 protein folding the same way. By making other proteins that help proteins to stay in their 01:02:10.700 --> 01:02:17.340 normal shapes and sizes. So how do we find out what they're doing during those conditioning 01:02:17.340 --> 01:02:23.340 pre-treatments? Okay so here's where the bridge gets made. Right now they do heat treatments on those 01:02:24.140 --> 01:02:31.740 eridopsis things are on those human cells. And we need to do the the real leg work to find out if 01:02:31.740 --> 01:02:36.300 the genes that are activated have anything to do with the genes that are activated in the yeast. 01:02:36.860 --> 01:02:40.860 Because that's where we're going now. Now we're going to look at the genes and the proteins that 01:02:40.860 --> 01:02:47.660 are activated in the yeast in that heat experiment. And I think although I could be wrong a lot of the 01:02:48.300 --> 01:02:55.580 correlates in the eridopsis experiment or the correlates in a human cell experiment haven't 01:02:55.580 --> 01:03:03.180 been fully developed. And so will can we we need to go through there's a lot of literature here. 01:03:03.180 --> 01:03:08.540 So this is not a small task. Okay it's not going to be you know Saturday afternoon biology 01:03:08.540 --> 01:03:13.580 prions don't exist anymore. We need to understand it and in order to understand it it's a lot of 01:03:13.660 --> 01:03:18.940 work. And so for a while I've been thinking that I would just prepare the summary lectures 01:03:18.940 --> 01:03:23.580 and that would be fine but it's become more and more apparent to me that I need to really 01:03:24.540 --> 01:03:30.060 bring everybody along with me in order that you see why there's so much work necessary. Why we 01:03:30.060 --> 01:03:36.780 have to break it down. And why after a week or two we might decide that wow this is an incredible 01:03:36.780 --> 01:03:40.860 distraction and maybe that's the whole reason why we were throwing this in the beginning. But in 01:03:40.860 --> 01:03:46.700 so doing in doing this exercise what we're going to be able to do is definitively say okay so do 01:03:46.700 --> 01:03:52.060 we need to worry about this or not. And who doesn't need to worry about it why do they need to worry 01:03:52.060 --> 01:03:57.820 about it how can we use this story to move our ball forward and that's that's what this is about. 01:03:57.820 --> 01:04:03.580 And I think that already you're starting to see it right here I hope I chose this video correctly 01:04:03.580 --> 01:04:09.580 so that you can it's a good on ramp to see how these shells are going to be moved around where 01:04:09.660 --> 01:04:14.620 sometimes we're talking about human cells and and whatever and sometimes we're talking about yeast 01:04:14.620 --> 01:04:20.460 and so it was interesting that she went to plants and an aerodopsis but we'll see we'll see what 01:04:20.460 --> 01:04:27.020 she's got for us. What we do is we again take out a small portion of the cells and label them 01:04:27.020 --> 01:04:34.860 with radioactive amino acids so that as the shell is making its own proteins each of those proteins 01:04:34.860 --> 01:04:41.100 will get radioactive amino acids incorporated into it. That allows us then to visualize it what's 01:04:41.100 --> 01:04:47.740 happened we spread those proteins out on a gel and we put a film on top of it and wherever there's 01:04:47.740 --> 01:04:53.500 radioactivity from a newly made protein we can see the imprint will line on the gel. 01:04:55.100 --> 01:04:59.980 And so you can see that at 25 degrees the normal temperature for this organism it's making one 01:04:59.980 --> 01:05:05.420 group of proteins. At 39 degrees it started making a whole bunch of other proteins and the 01:05:05.420 --> 01:05:10.860 sole function of all of those proteins is to cope with this protein folding problem. 01:05:11.740 --> 01:05:17.020 Her assumption is the function of all those proteins is to cope with the folding problem. 01:05:17.020 --> 01:05:22.540 That's an extraordinary thing to say. I'm sure she's done a lot of experiments they're all called 01:05:22.540 --> 01:05:28.620 heat shock proteins but already we're working with high levels of certainty even though her 01:05:28.620 --> 01:05:35.740 introduction was was subpar at best. They help other proteins in the cell maintain their normal 01:05:35.740 --> 01:05:42.940 shapes or to get rid of them when they've lost their normal shapes. Now this is a very broadly 01:05:42.940 --> 01:05:48.460 used survival response we first started working with it with heat because that's an awful simple 01:05:49.420 --> 01:05:55.100 manipulation to make within the laboratory but it turns out these same proteins provide protection 01:05:55.100 --> 01:06:01.740 against all sorts of different difficult conditions changes in pH, changes in the energy balance 01:06:01.740 --> 01:06:09.180 of the cell, changes in osmotic strength, many many many different changes in the cell. In fact 01:06:09.180 --> 01:06:13.740 but then doesn't that suggest that they should always be there and that this is just a change 01:06:13.740 --> 01:06:20.300 in relative abundance? Wouldn't you always need those there then? I'm curious about that because 01:06:20.860 --> 01:06:26.780 that seems to also indicate then that there are situations where the danger of misfolding is 01:06:26.780 --> 01:06:32.940 higher or lower depending on the concentration of these proteins, right? There's a lot of things 01:06:32.940 --> 01:06:38.860 that their model makes predictions about that they just kind of talk around. That's where I 01:06:38.860 --> 01:06:45.180 used to annoy people all the time in neuroscience as well because they make these ridiculous simple 01:06:45.180 --> 01:06:50.060 models of the animal's behavior and it's like well dude if that's your model you could do a 01:06:50.060 --> 01:06:58.140 really easy experiment to test that why don't you do that first and so make sure you see what's 01:06:58.140 --> 01:07:06.300 happening here. This is how academic biology has gotten so twisted up in itself because everybody 01:07:06.300 --> 01:07:12.140 does this. Everybody gets their own little story tells it their own little way with their own 01:07:12.300 --> 01:07:20.220 little characters that are the main story. When I started in in biophysics in 2001 as a 01:07:20.220 --> 01:07:32.780 sodium, potassium channel expert wannabe that that I learned from my my supervisor that that 01:07:32.780 --> 01:07:37.820 potassium channels that are activated by calcium are orchestrating the entire brain 01:07:38.460 --> 01:07:46.780 and we made arguments in prose and discussed how important they were for the finest tuning 01:07:46.780 --> 01:07:50.060 of neurons and the finest tuning of neurons is what matters 01:07:54.220 --> 01:07:58.780 and so if you have a story about SK channels then that's the story you tell 01:07:59.900 --> 01:08:07.420 and she has a story about heat shock proteins and so her story is about how yeast is a great 01:08:07.500 --> 01:08:14.780 proxy for the protein folding challenges of all other eukaryotic life and so my work is 01:08:14.780 --> 01:08:20.540 applicable to all other eukaryotic work. It's a pretty awesome place to be working 01:08:22.060 --> 01:08:27.580 and these heat shock proteins are made exclusively to chaperone and to prevent 01:08:27.580 --> 01:08:33.900 misfolding and also to get rid of them when they do misfold so we don't need them all the time or 01:08:33.900 --> 01:08:40.780 or what strange what what does those jobs when when the heat shock proteins haven't been called 01:08:40.780 --> 01:08:46.300 into action we don't have any part of that model nothing about that model is explained. 01:08:46.300 --> 01:08:52.460 These proteins are constantly being made made in smaller amounts over and over and over again 01:08:52.460 --> 01:08:58.540 to help cope with this very broad problem in protein folding. So this very broadly used 01:08:58.540 --> 01:09:03.180 survival response as I showed you yeast cells I showed you arabidopsis ceilings 01:09:03.180 --> 01:09:08.860 arabidopsis is a small little mustard plant I showed you human cells every organism on earth 01:09:08.860 --> 01:09:13.980 is making very highly conserved very similar patterns of proteins under these stress conditions 01:09:14.700 --> 01:09:19.980 and it turns out that that plays into human biology and medicine and just an extraordinary 01:09:19.980 --> 01:09:26.860 variety of different ways. One of the major reasons why we want so deeply to understand 01:09:26.860 --> 01:09:34.700 this problem is that it drives many aspects of human disease. So one of the things that it drives 01:09:34.700 --> 01:09:41.580 is the process of infection when organisms come into our body and you can see here we've got 01:09:42.380 --> 01:09:47.980 a fungus that is growing under normal conditions not inside the body but when it starts to grow 01:09:47.980 --> 01:09:54.460 inside the body it senses this change in temperature and it and it starts to realize that it can 01:09:54.460 --> 01:10:00.780 invade the biological system and the only way it can do that is by making new proteins and by 01:10:00.780 --> 01:10:05.820 making this survival response that allows those new proteins to fold properly. 01:10:08.300 --> 01:10:14.620 So that's one aspect of disease biology that uses that survival response all the time. 01:10:15.340 --> 01:10:20.300 Here's another aspect of human biology that uses the survival response. So what you have 01:10:21.180 --> 01:10:29.020 in blue is normal proteins and what you have labeled in brown here is the master regulator 01:10:29.020 --> 01:10:36.060 of the survival response and that's normal tissue over there and you can see that the survival 01:10:36.060 --> 01:10:42.220 response protein is kind of tucked away in little corners of the cells because it's not being used 01:10:42.220 --> 01:10:49.900 under this normal biological system but in the cancer cells you can see that that master regulator 01:10:49.980 --> 01:10:55.340 has been amplified a great deal it's actually present now in the center of the cell and it's 01:10:55.340 --> 01:11:00.700 directing a whole new program of gene expression whole new sets of proteins are being made 01:11:01.820 --> 01:11:07.420 at the dictum of the cancer cells to help protect those cancer cells and drive the malignant state. 01:11:09.340 --> 01:11:17.020 And neurodegenerative disease these are two brain sections from a normal person and from 01:11:17.020 --> 01:11:22.540 someone with who has died from neurodegenerative disease and what you're seeing here is the 01:11:22.540 --> 01:11:31.260 devastation brought by misfolded proteins in the brain. So it turns out that in terms of human beings 01:11:31.260 --> 01:11:36.300 we are a bit between a rock and a hard place with regard to this problem in protein folding 01:11:36.300 --> 01:11:44.620 because cancer cells and infectious organisms are using their survival response this heat shock 01:11:44.620 --> 01:11:52.620 response to kill us because it strengthens them it allows them to survive the rigors of a living 01:11:52.620 --> 01:12:00.940 system and our brains conversely are not using the survival response when we would normally think 01:12:00.940 --> 01:12:06.060 they should be because when we die of neurodegenerative diseases it's because proteins have 01:12:06.060 --> 01:12:11.740 misfolded misfunction and just like those instruments that are not playing right with the orchestra 01:12:12.300 --> 01:12:18.380 they're causing devastating disease. See how that whole now see how that whole thing fell apart 01:12:19.260 --> 01:12:24.780 how the whole analogy fell apart now she went back to the protein folding in the in the horns and the 01:12:26.060 --> 01:12:31.260 orchestra not playing so what she's saying that the brain doesn't have heat shock proteins and 01:12:31.260 --> 01:12:35.660 otherwise those proteins wouldn't have misfolded that's again the same question I had before 01:12:36.540 --> 01:12:44.380 what does this stuff in normal conditions don't they need proteins to fold correctly in normal 01:12:44.380 --> 01:12:49.420 conditions isn't there still a chance that they will fold incorrectly in normal conditions you 01:12:49.420 --> 01:12:57.180 showed us this chaotic you know internal cell I mean it seems really like there we have a foot 01:12:57.180 --> 01:13:05.180 in and a foot out of this analogy and I find it very frustrating because I have the background 01:13:05.180 --> 01:13:11.500 to follow along and I don't think she's painting a coherent picture of what the the biological question 01:13:11.500 --> 01:13:18.380 is. This puts us in a difficult position but it's not a place where we can't move and we can't do 01:13:18.380 --> 01:13:24.300 something important in biological experimentation and the reason why we can do do things that will 01:13:24.940 --> 01:13:31.580 help to fix these problems is because it is such a universal problem and so we can take these very 01:13:31.580 --> 01:13:38.140 simple organisms here these cells it's really understand more about how it's really like an 01:13:38.140 --> 01:13:47.340 enchantment you can't see it any other way this is a carefully constructed set of slides that 01:13:47.340 --> 01:13:53.500 ends with the same image that it began with which is a cheap trick but it's also a very 01:13:54.940 --> 01:14:00.620 effective one and a good one that a lot of good teachers will use because you you want to run a 01:14:00.620 --> 01:14:04.540 full circle right you want to bring people back to where you were in the beginning especially 01:14:04.540 --> 01:14:11.900 if the beginning is the take-home message what's the take-home message here that yeast is a great 01:14:11.900 --> 01:14:20.140 cellular proxy model for us and so now in the next video that we watch we're going to listen to how 01:14:20.140 --> 01:14:27.420 pre-owned disease is recapitulated in yeast protein inheritance and you're going to see very easily 01:14:27.500 --> 01:14:33.260 how it is that these two things have been misconstrued our understanding of whatever goes on in a 01:14:33.260 --> 01:14:39.740 dish with yeast has been misconstrued with whatever goes on in the forest of a cannibalist 01:14:40.620 --> 01:14:48.460 place in New Guinea or or in a sheep field in the UK I really think that's a possible 01:14:49.660 --> 01:14:54.860 a possible problem in our near future and I think that they would love it they would absolutely 01:14:54.860 --> 01:15:02.860 love it if the skilled tv watchers would really take pre-ons at cartoon face value they are 01:15:02.860 --> 01:15:11.020 proteins that are unable to be you know destroyed by autoclave if you just get one protein in you 01:15:11.020 --> 01:15:17.180 you are definitely dead once you once you have it it's over and this is just the way these things work 01:15:18.140 --> 01:15:20.940 um I think we're we're gonna have a lot of fun over the next couple of weeks 01:15:20.940 --> 01:15:25.660 simple organisms here these cells I think we're gonna have a lot of fun over the next couple of weeks 01:15:25.660 --> 01:15:31.580 how that the biology of that system is driven how how to correct protein folding and how it goes 01:15:31.580 --> 01:15:37.740 wrong in order to help these people over here with all of those different protein probing problems 01:15:37.740 --> 01:15:43.180 I just mentioned to you so I'll be talking to you about that in the next lecture I'm so excited so 01:15:43.180 --> 01:15:47.420 that we've really found our thing here I think we really did we found it I think this is our new 01:15:47.420 --> 01:15:53.020 teacher um we're going to use her regularly because I do think that's the way we go forward 01:15:53.980 --> 01:15:59.420 it's not that it's not that I'm always going to use videos but I really need you to feel it 01:15:59.420 --> 01:16:06.780 I need you to feel how there has been a concerted effort to push this idea out I've also found it 01:16:06.780 --> 01:16:16.140 feels like countless countless like mid-level podcasters with very good production values 01:16:16.780 --> 01:16:25.100 relatively decent followings making very certain videos about pre-on disease and what happened 01:16:25.100 --> 01:16:30.060 before and what's gonna happen in the future and making fun of how the worst-case scenario is 01:16:30.060 --> 01:16:38.060 pretty ugly it is starting to become to me very obvious that something strange is going on 01:16:38.060 --> 01:16:44.060 and so we have the opportunity to get ahead of the dominoes and before this becomes some kind 01:16:44.060 --> 01:16:51.980 of weird narrative that they start to misconstrue what we're probably well expected developments 01:16:51.980 --> 01:16:57.820 from the multiple transfections that they've rolled out they're going to be able to cover it up 01:16:57.820 --> 01:17:03.340 and they're going to try to cover it up by misconstruing the spike as having a particular 01:17:03.340 --> 01:17:09.660 effect the transfection itself of course doesn't and that's a lie I'm sure it's a lie and I'm sure 01:17:09.660 --> 01:17:14.940 it's well I'm not sure but I got a lot of chips on the fact that that's probably coming and so if 01:17:14.940 --> 01:17:20.380 that is the case then this is the way we get ahead of it we learn this biology better than they know 01:17:20.380 --> 01:17:26.620 it and if we do that then we will be able to exercise informed consent because they won't be 01:17:26.620 --> 01:17:33.580 able to bamboozle us I think this is a good place for me to stop I hope you don't mind if I 01:17:33.580 --> 01:17:39.340 stop now I'm going to go to basketball at four and then I do have this stream with Jason Levine 01:17:39.340 --> 01:17:46.060 tonight at seven o'clock I'll talk to Jason he uses Google Google whatever you call it so I 01:17:46.060 --> 01:17:53.580 might be able to do it with sound only and then I could go live while he's recording it so I'll 01:17:53.660 --> 01:17:57.980 just see what he thinks about it I'm not going to do it without his permission or something but 01:17:57.980 --> 01:18:03.100 that would be at seven o'clock if that's going to happen and yeah I think this has been a pretty 01:18:03.100 --> 01:18:11.660 good start again I'm what I'm trying to do is break you into the idea that that pre-owned biology 01:18:11.660 --> 01:18:18.860 is for the most part based in yeast and so it we we really need to dig into what do we understand 01:18:18.860 --> 01:18:24.780 from yeast and what we understand from pre-owned disease in the wild and see if these two things 01:18:24.780 --> 01:18:31.500 can be brought together in a way that allows us to truly assess what the what you know the real 01:18:31.500 --> 01:18:36.300 biology is that's what we do here um ladies and gentlemen stop all transfections and humans 01:18:36.300 --> 01:18:43.340 because they are trying to eliminate the control group by any means necessary and this has been 01:18:43.340 --> 01:18:49.100 giga-owned biological a high-resistance low-noise information for you brought to you by a biologist 01:18:49.100 --> 01:18:53.820 where intramuscular injection of any combination of substances with the intent of augmenting the 01:18:53.820 --> 01:18:59.420 immune system is dumb. Transfection in healthy humans is criminally negligent and I'm going to 01:18:59.420 --> 01:19:05.580 be a little less complicated than here and say RNA cannot pandemic that's the way it should be 01:19:06.140 --> 01:19:13.100 um so yeah that was the show um thanks very much again for coming and uh I will see you 01:19:13.100 --> 01:19:19.180 probably tonight um but you won't be able to see Jason you won't be able to see Chet um so I don't 01:19:19.180 --> 01:19:25.020 I don't know it might be better than nothing um and then uh yeah it's giga-owned biological.com 01:19:25.020 --> 01:19:30.460 if you want to share the stream um there's all kinds of ways to do it but that might be one um 01:19:30.540 --> 01:19:38.220 also screen.gigome.vio is really the algorithm free search engine free you just find our stuff 01:19:38.220 --> 01:19:43.500 there just the recent stuff there's a little bit from mark um and then the rest of the stuff is 01:19:43.500 --> 01:19:48.780 just for me it's kind of a new archive that we're building um and so yeah thanks a lot for joining 01:19:48.780 --> 01:19:53.900 me and I will see you tonight and definitely also tomorrow I swear we are eventually gonna 01:19:53.900 --> 01:20:02.460 get to 1313 eastern time every day um it's just uh yeah it's a priority thing and sometimes 01:20:03.660 --> 01:20:09.020 I have one paying client right now and so when I get a phone call from her I do need to take it 01:20:09.020 --> 01:20:13.260 and so that sometimes it's during containing it so I have to wait till two or whatever 01:20:13.260 --> 01:20:19.580 anyway thank you very much thanks Jeff from Earth for all the clips on instagram um and uh yeah 01:20:19.580 --> 01:20:25.900 see you guys soon