WEBVTT 00:30.000 --> 00:32.000 You 01:00.000 --> 01:02.000 I 01:21.560 --> 01:24.520 Guess I didn't update the stream. Yes, this is part two 01:25.360 --> 01:30.040 I'll update the title later. I guess I thought I updated it here on my OBS 01:30.040 --> 01:36.440 But I guess I didn't push the button done and so that it did not date my bad. This is part two. I 01:41.160 --> 01:43.160 Shall do it 01:54.520 --> 01:59.480 I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario 01:59.480 --> 02:04.080 I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario 02:24.520 --> 02:26.520 I 02:38.680 --> 02:44.280 Think truth is good for kids. We're so busy lying. We don't even recognize the truth no more than society 02:44.800 --> 02:49.080 We want everybody to feel good. That's not that's not the way life is 02:55.520 --> 03:00.840 We should be okay here. I'm just gonna check this one. So I'm back from the gym 03:00.840 --> 03:03.080 I thought I'd get part two done before tomorrow 03:04.080 --> 03:11.200 We're eventually gonna be doing a show a day or two shows a day one at 10 10 and one at 13 13 03:12.120 --> 03:13.960 So at 10 o'clock and one o'clock 03:13.960 --> 03:19.520 But you know we got to roll slowly here and make sure that we we build this momentum 03:20.400 --> 03:25.960 Intelligently and one of the things we're trying to build momentum around is this whole pre-on biology stuff 03:26.320 --> 03:31.520 And there's a there's a lot to learn and so we were gonna finish the video that we started earlier 03:31.520 --> 03:34.720 Thank you very much for being here. See you in a second 03:37.280 --> 03:41.520 This episode is sponsored by mink that's moo plus like 03:41.520 --> 03:43.520 Mm-hmm 03:45.520 --> 03:53.080 This my point is that if if we were able to just like we're trying to get everybody to take the vaccine if we had 03:53.160 --> 03:58.480 Put that into getting everybody to take hypermectin and fluvoxamine for for a month 03:58.800 --> 04:02.720 If we and if we could accomplish that then COVID would be wiped out 04:02.720 --> 04:08.120 We could do it and actually any municipality that could regulate its borders could clear the disease 04:11.520 --> 04:15.840 But you can tell if someone's lying, you know, you can sort of feel it in people 04:17.160 --> 04:20.240 And I have lied. I'm sure I'll lie again. I don't want to lie 04:20.400 --> 04:24.080 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 04:24.080 --> 04:27.440 I think it's like really important not to be a liar 04:30.240 --> 04:33.280 I mean that stands alone as like one of the best 04:34.600 --> 04:37.240 Rapid fire statements made by anyone 04:37.240 --> 04:40.960 Ever maybe in mainstream media 05:07.240 --> 05:09.240 You 05:37.240 --> 05:39.240 I 05:43.160 --> 05:48.560 The meter this always looks like it's really soft, but it actually is always really really hard in my ears 05:57.880 --> 05:59.860 Let's do it 05:59.860 --> 06:09.620 Sweaty bombs, this is so crazy like these bumps. This is so crazy. I feel so nervous like what in the world man 06:29.860 --> 06:31.860 Oh 06:59.860 --> 07:04.500 Big-time brick 07:06.580 --> 07:13.220 I'm glad somebody noticed that that was a big-time brick. I'm not trying to represent myself as some kind of baller here 07:13.420 --> 07:18.700 That was the whole point of making it a real real clip one good shot one brick 07:19.660 --> 07:22.460 That's about what I'm good for. I don't think that's that bad though 07:22.540 --> 07:25.700 If you've been following along for a while you're here at the top of the wave 07:26.220 --> 07:31.740 Where we've been shooting three-pointers for four years now where we stay focused on the biology 07:31.740 --> 07:38.820 We don't take the bait on TV and we love our neighbors trying to rescue those skilled TV watchers in our family and on our street 07:39.420 --> 07:43.540 By sharing this biology consistently on Facebook where I am not on 07:44.300 --> 07:46.300 Twitter where I'm mostly not 07:46.820 --> 07:54.140 Shared everywhere you can and if you can maybe you can find your way to get going biological.com and find a way to support 07:54.140 --> 08:00.220 That would be also great. It's also just a great place and way to share what we do send people to get your own 08:00.420 --> 08:03.580 Biological.com. They can find everything there everything has its own link 08:04.380 --> 08:12.540 And it all just kind of centers on that all of the links to all the different places where it's stored is there and yes, this is 08:14.540 --> 08:19.900 Independent Brightwave presentation that basically means that we don't take sponsorships because we're not offered them 08:20.740 --> 08:25.420 And we are supported only only only by viewers like you 08:28.180 --> 08:31.100 Still trying to break the same illusion 08:35.380 --> 08:41.380 Sometimes it's nice for having a little live Eric Johnson Evan root fever to try and help 08:42.220 --> 08:46.260 Establish the mood that it's necessary in order to 08:47.140 --> 08:50.780 Engage in United non-compliance is what you're really doing here 08:51.300 --> 08:57.340 When you come here and try to discuss the flip side of the biology on TV the flip side of the biology on 08:58.140 --> 09:01.340 Social media and so today we're going to keep up the good work 09:02.060 --> 09:04.060 That needs to be done 09:04.060 --> 09:08.220 This is going biological the safest way to get biology in your head 09:17.020 --> 09:19.020 You 09:24.460 --> 09:30.940 Thank you very much, this is giga ohm biological a high-resistance low noise information brief brought to you by a biologist 09:30.940 --> 09:32.580 24th of April 09:32.580 --> 09:37.620 2024 we're on our second stream of the day, but that shouldn't be something we should be applauded for 09:37.900 --> 09:41.300 We need to do more and there is a lot of work to do 09:42.260 --> 09:46.260 Sometimes it's just it's handy to be ready. We were ready for this 09:46.260 --> 09:51.220 We've been preparing for this video for a long time and it's actually so far been incredibly revealing 09:51.220 --> 09:55.900 And so I want to start first by kind of reframing where we are again 09:55.900 --> 09:59.220 This is about a principle of informed consent 09:59.220 --> 10:04.100 I'm gonna escape out of here for a second just to make sure that this is going where I want it to go 10:05.780 --> 10:08.940 This is where I want it to be I'm gonna skip a couple of those slides 10:08.940 --> 10:15.940 It's always smart to make sure you are where you need to be so we've talked about these TV scenarios where there's either a lab leak or a 10:16.340 --> 10:18.420 Batcave virus, so maybe there's nothing at all 10:19.260 --> 10:22.740 And how these things have generally 10:24.220 --> 10:30.300 Hearded the vast majority of people in West Western civilization to accept a faith in 10:31.060 --> 10:35.220 What is essentially a novel biology? It's not just a novel virus 10:35.660 --> 10:41.100 But the whole story of a novel virus and how it has behaved in the last five years 10:42.020 --> 10:47.820 constitutes a novel biology because first of all the precedents of a trackable gain of function 10:48.780 --> 10:56.340 RNA because we need to be very honest with the people in our lives about what is essentially the story the story is not a virus 10:57.260 --> 11:00.860 with lots of little gears and wheels and and 11:01.740 --> 11:05.220 Enzymes and magnets and mitochondria inside 11:06.460 --> 11:10.580 It is simply an RNA molecule wrapped around a 11:11.100 --> 11:17.580 protein called the end protein and that is contained within what is essentially a cell membrane a 11:18.940 --> 11:22.060 Lipi protein coat lipo protein coat 11:22.900 --> 11:23.700 and 11:23.700 --> 11:27.620 So coronaviruses as they are presented to us are nothing more 11:28.460 --> 11:29.980 than a 11:29.980 --> 11:35.220 nanoparticle with some RNA packaged inside of it, and so by the 11:37.500 --> 11:40.900 The broad understanding of the rules of biology that 11:42.300 --> 11:44.300 that model 11:44.580 --> 11:46.180 then 11:46.180 --> 11:49.020 dictates that whatever properties are 11:49.660 --> 11:52.660 contained inside of an RNA pandemic are 11:53.100 --> 12:02.020 emergent properties that are contained within the actual sequence of that RNA and indeed that is the story that many people have 12:02.020 --> 12:06.460 been telling us from the very beginning that a fear and cleavage site that HIV inserts that 12:07.020 --> 12:13.220 homology to a staphylococcan and teratoxin B protein could be partially 12:14.180 --> 12:21.460 explanatory in terms of the severe COVID that we see in some places or the long COVID that we see in some places 12:22.660 --> 12:27.500 And this mythology is extraordinary because at the heart of it again 12:27.500 --> 12:35.260 I'm going to say it one more time is an RNA molecule that because of the actual content of its sequence the actual 12:35.380 --> 12:42.580 Order in which the bases are found it is capable of doing something that otherwise all other RNA molecules 12:43.100 --> 12:45.100 never even 12:45.980 --> 12:48.220 Never even it doesn't cut it doesn't happen 12:49.140 --> 12:54.740 Now the flu viruses is RNA molecules, but the crazy thing is is flu viruses are 12:55.420 --> 12:58.540 Supposedly packaged with some enzymes 13:00.220 --> 13:06.660 So even flu viruses have by definition even more gears and wheels and little motors in there 13:07.020 --> 13:11.380 Then a coronavirus a coronavirus is actually just an 13:12.420 --> 13:14.420 instruction module and 13:14.420 --> 13:17.020 if that instruction module is read then 13:17.860 --> 13:19.780 Apparently it makes copies of itself 13:19.780 --> 13:26.700 But the point is is that if that instruction module has a fear and cleavage site or it has HIV inserts or it has 13:28.300 --> 13:30.300 homology to to a 13:30.980 --> 13:32.580 toxin protein 13:32.580 --> 13:34.740 That now it can cause a pandemic 13:36.940 --> 13:38.940 So the second part of this is that 13:39.100 --> 13:41.740 Transfection was waiting in the wings for a very long time 13:42.420 --> 13:47.580 Just waiting for the right opportunity to come and save mankind. I mean the whole species 13:48.580 --> 13:49.740 and 13:49.740 --> 13:56.060 Since we rushed it since we tried to make a lot of money and cut corners or whatever it is that we did 13:56.620 --> 14:00.700 Or because we weren't liable. So since we weren't liable. We cut corners 14:01.300 --> 14:05.700 That some people were injured because of the contamination found in some of these 14:06.540 --> 14:09.820 And some of these countermeasures now keep in mind one of the major 14:10.780 --> 14:14.700 Lawsuits that's currently moving through the courts is a lawsuit 14:15.460 --> 14:21.820 To do with contamination of remdesivir vials so not even the use of remdesivir. Yes or no, but 14:22.900 --> 14:25.220 Contaminated remdesivir and so you see 14:25.740 --> 14:28.900 then when you realize that they've been talking since 14:29.460 --> 14:31.460 2000 14:31.460 --> 14:34.220 Wow a terrible weatherman 2020 14:35.700 --> 14:40.340 About the spike protein being the center of this whole mystery 14:40.980 --> 14:48.580 The spike proteins interaction with ACE 2 the spike proteins ability to cause multi-system inflammatory disease or whatever it's called 14:48.820 --> 14:52.780 The spike proteins targeting of the heart muscle the spike protein being 14:53.620 --> 14:59.060 amyloidogenic the spike protein being a pre-on or having pre-on-like sequences in it 15:01.220 --> 15:04.220 Has been confounded from the very beginning 15:06.460 --> 15:09.460 With the ability or the propensity for 15:09.820 --> 15:13.260 transfection or transformation technologies to 15:14.220 --> 15:16.220 result in 15:16.660 --> 15:22.260 Pre-on-like disorders or whatever these things are like crowds felt the occub in the paper of Luke Montenier 15:22.260 --> 15:26.900 The reason why the paper of Luke Montenier is so important is that it came out very early 15:27.700 --> 15:30.700 and yet those people had been actually 15:31.420 --> 15:37.140 They had been transformed with an adenovirus carrying the spike protein gene 15:39.020 --> 15:42.340 So they had been transformed they had not been infected and 15:42.980 --> 15:47.260 Of course right away the people were arguing. What were they arguing? What were they arguing? 15:47.460 --> 15:50.980 They were arguing that maybe those people had been infected before they were 15:51.860 --> 15:53.860 Before they were vaccinated 15:54.260 --> 15:59.900 And so already they needed to clean the narrative already they had to cast out already 15:59.900 --> 16:01.900 They had to speak up 16:02.020 --> 16:06.740 Because the worst-case scenario was already under threat from the very beginning the worst-case scenario 16:07.540 --> 16:12.980 Narrative centers always on the spike protein even though there are 29 or 30 other 16:13.140 --> 16:19.060 Proteins that have various isoforms that can do all kinds of things most of which we don't know and 16:20.540 --> 16:26.020 Yet we are hyper focused on the spike protein the spike protein is what's used to make the phylogenetic tree 16:26.020 --> 16:28.460 The spike protein has defined all previous 16:29.100 --> 16:34.260 Coronavirus variants in the past if you look for new SARS viruses 16:34.260 --> 16:37.900 You don't look for new N proteins you look for new spike proteins 16:38.860 --> 16:39.700 and 16:39.700 --> 16:45.700 Part of the reason you look for new spike proteins is not because the spike protein is the most variable gene 16:45.700 --> 16:47.700 It is because it's the most abundant 16:48.980 --> 16:50.980 subgenomic RNA 16:50.980 --> 16:51.860 and 16:51.860 --> 16:58.060 We've looked at the infectious cycle since early sixties through the 70s 80s 90s 16:58.460 --> 17:05.300 And now all the way up to now with nanopore sequencing and we keep finding the same weird ratio of almost no 17:06.020 --> 17:08.300 full genomic RNAs, but 17:09.100 --> 17:13.980 orders many multiple orders of magnitude more subgenomic RNAs 17:16.260 --> 17:19.340 Predominated by spike protein e gene and gene 17:20.100 --> 17:22.900 And so when you look for those subgenomic RNAs 17:23.220 --> 17:30.340 You're looking for a signal that is expected to be there and many many many many many many orders of magnitude even in their 17:31.060 --> 17:33.060 most honest appraisal of 17:33.780 --> 17:37.820 the infectious cycle of their entity called coronavirus and 17:38.980 --> 17:46.940 So so much of this biology is almost wholly based on the cartoons they draw rather than on the experimental results that they've obtained 17:47.940 --> 17:52.220 So much of this biology is based on the cartoons 17:52.220 --> 17:58.780 They draw rather than the data and the experimental results that they have actually obtained 17:58.780 --> 18:06.020 And that is the reason why this story is so complicated and needs to be obfuscated by people who say well 18:06.020 --> 18:08.020 There's just no viruses at all 18:08.220 --> 18:10.220 None of the viruses exist 18:11.220 --> 18:13.220 And 18:14.100 --> 18:20.620 So it is a very very complicated trap that we find ourselves in and prions as part of that prions and 18:21.500 --> 18:26.420 Understanding what they are and what they're what they aren't if they're anything at all is 18:28.820 --> 18:30.820 Extremely important 18:30.820 --> 18:35.260 And as with virology we would be very very 18:36.260 --> 18:45.820 It would it was we're risking a very very big error if we assume that the biology that we've been given or told or led to assume 18:45.820 --> 18:50.220 As it would be because none of us have studied this intentionally until recently 18:53.340 --> 19:01.900 That we really understand to what extent any of this stands on firm ground and so let me switch over to the the desk here 19:02.140 --> 19:09.140 One of the things that I would like to start out with with this with this second part is 19:09.340 --> 19:12.700 Just to kind of review about what he said in the first part 19:12.700 --> 19:18.100 One of the things that he said in the first part was in the beginning and I'll give you the example 19:18.100 --> 19:20.100 I think I have it up already 19:20.100 --> 19:22.100 Don't I have it up already? 19:22.100 --> 19:32.780 If we go back to the beginning of this you can find that one of the 19:36.420 --> 19:42.260 One of the things that they were doing first was trying to optimize the production of the disease 19:42.620 --> 19:44.620 So first they couldn't find it 19:45.020 --> 19:50.820 Right it was very hard to achieve some kind of enrichment of the disease 19:51.580 --> 19:57.220 Agent and so he used two different graphs here to show you where the sucrose agent 19:57.900 --> 20:00.740 He said well darn it 20:01.980 --> 20:09.100 He said what you would expect to see is some kind of peak right some kind of peak over a certain place in 20:09.580 --> 20:14.780 The sucrose gradient, but you instead you see all kinds of a smear now 20:14.780 --> 20:18.780 Here's one of the things that I find already very interesting. Let's go back 20:19.580 --> 20:21.580 to the other the other 20:25.020 --> 20:26.620 Let's go back here 20:26.620 --> 20:34.260 This is the the nature pre-on paper that we've we've referenced a couple times now and lead up to this discussion 20:34.260 --> 20:38.580 And this is perhaps a little bit better drawing. It's a little more up to date 20:38.700 --> 20:40.900 This is the pre-on protein, right? 20:40.900 --> 20:41.860 Can you see oh sorry? 20:41.860 --> 20:48.340 This is the pre-on protein the protein that is on the outside of the cell that we don't know very much about what it does 20:48.780 --> 20:54.540 but it's for sure on the outside of the cell or on the inside of lysosomes and in the basal state 20:54.540 --> 20:57.300 It does something but in the in the pre-onogenic 20:58.260 --> 21:02.740 State or the prey I guess in this case it's PRPC 21:03.940 --> 21:07.900 And then this is a pre-on. Sorry. I had that wrong. This is the regular 21:08.660 --> 21:13.780 Pre-on protein and you see three alpha helis is there and then here you see the pre-on protein 21:13.780 --> 21:17.620 And it's many of them all layered on top of each other. That's what you see there 21:17.700 --> 21:23.540 And the implication is is that it's some kind of little fibro right there all layered on top of each other 21:23.540 --> 21:28.860 So this is already several pre-on proteins that have folded incorrectly and then induced it on one another 21:28.860 --> 21:33.060 And then this one can look induce the blue one to join them you see that 21:34.020 --> 21:41.260 And so this concept implies a couple things if we believe that the sequence of a protein is very much 21:41.740 --> 21:43.740 related to how it folds and 21:44.020 --> 21:46.020 So the potential for it to fold 21:46.340 --> 21:54.780 is related to its sequence means that it was should at least in this model and it appears also to imply that it's not able to 21:55.620 --> 21:58.820 Able to make any other proteins fold like this 21:58.820 --> 22:00.220 But it can make 22:00.220 --> 22:05.980 proteins with the right sequence the the protein pre-on the pre-on protein 22:06.580 --> 22:08.060 sequence 22:08.060 --> 22:10.580 so what I find interesting about the 22:14.100 --> 22:21.500 What I find interesting about this figure in the in the video that we watched earlier today is that this 22:22.740 --> 22:28.740 Is still seeming to imply that there is one protein now if there's one protein that makes 22:29.300 --> 22:35.900 Aggregates, what can we predict? What's the model right? That's what science is all about you have a model 22:35.900 --> 22:40.620 And then it makes predictions about measurements in the future and those predictions if 22:41.180 --> 22:46.260 If done cleverly or or or tested cleverly 22:46.980 --> 22:48.980 can provide fruitful 22:50.060 --> 22:52.900 Guidance to the experiments that should be done 22:52.900 --> 23:00.660 So let me just take you over here and let's talk first about the the concept of pre-ons making more pre-ons 23:02.500 --> 23:04.500 By 23:05.220 --> 23:09.300 Coming together right pre-ons press pre-ons equals a fibrel 23:10.860 --> 23:15.420 And that was also what he was talking about with regard to amyloidosis and 23:16.140 --> 23:23.500 Amyloid I guess be in the same thing really just different sides of the same coin or something which I called out before as being nonsense 23:23.860 --> 23:27.340 But I don't so I don't want to imply that I'm I'm saying it here 23:27.700 --> 23:36.340 But let's just talk specifically now about this model and the idea that the actual profile that they measure in this sucrose gradient 23:36.340 --> 23:38.740 is smeared across densities which means 23:39.700 --> 23:45.580 Apparently not one thing and the argument that they might make is one where they would say 23:46.220 --> 23:49.460 Sorry, they would say that that the 23:50.260 --> 23:52.260 That the pre-on 23:52.380 --> 23:54.380 protein is is 23:54.540 --> 23:56.540 making 23:57.180 --> 24:02.620 Fibrels in those fibrels because they're multiples of the the pre-on protein 24:02.620 --> 24:07.100 Then they're going to be all across that sucrose gradient, but that's not entirely 24:08.020 --> 24:11.980 accurate because if the pre-on protein weighs 24:12.700 --> 24:13.860 X 24:13.860 --> 24:21.100 then two pre-on proteins will weigh two X and the and the in a gel like that you're going to get 24:21.820 --> 24:26.180 Lines or in a sucrose gradient you could get lines where okay 24:26.180 --> 24:32.060 Well, then this is you know two and then this would be five and this would be eight or whatever right? 24:32.060 --> 24:36.700 I mean you can actually count it because it would move up in increments by weight 24:37.180 --> 24:41.340 because they move through these things by weight or by density and 24:45.340 --> 24:51.780 So in a sucrose gradient if they don't separate by density there might be a way to do it by charge in a 24:52.140 --> 24:55.620 In a gel, but there must be some way to show me 24:56.260 --> 25:03.380 That these preons are working together because if they're if they're they're coming together in multiples 25:03.380 --> 25:10.260 Then the multiples after digestion should become visible. They should be small fractions of the things that aren't digested 25:10.260 --> 25:17.620 And yet somehow or another this part of the model which I can show you again is very clearly visible 25:18.620 --> 25:20.620 Here 25:21.700 --> 25:26.620 That's exactly what's implied by this nature paper from not too long ago 25:27.620 --> 25:33.260 and in fact, I think a lot of what Stanley Prusner implies in his 25:33.940 --> 25:38.980 Oops, sorry about that. I'm just losing my buttons here implies in his 25:40.300 --> 25:43.100 In his slides and so that's what I'm a little 25:43.780 --> 25:49.500 Frustrated with in regard to that, but we're gonna keep going because there's more we're gonna we're still reviewing this 25:52.060 --> 26:00.140 So then he said that one of the best things that happened if I recall correctly is that they were able to get yet there it is 26:00.780 --> 26:06.540 The mouse model took a really long time. It took like a year and 60 animals before you could I guess 26:07.340 --> 26:15.660 Decide whether there was was scraping protein to analyze for but anyway, they got something to work much faster in hamsters 26:15.660 --> 26:22.180 And I'm still I it's still homework for me to figure out exactly this what the story is on this slide 26:22.500 --> 26:32.700 But the point would be that after this they now managed somehow this next slide suggests that they got the incubation time bio assay down low enough 26:33.420 --> 26:38.660 So that you didn't have to waste a lifetime as he said made jokes and people laughed about 26:39.300 --> 26:45.940 Waste a lifetime trying to wait for this stuff to happen so that you had something that you could use I guess to put in other animals heads 26:46.500 --> 26:49.420 And try to make the disease move from animal to animal 26:49.660 --> 26:54.140 So then he tries to purify using detergent extraction nuclei 26:55.620 --> 27:02.260 Digestion and protonase K digestion and after all of that stuff there's still some 27:02.740 --> 27:06.740 Pre-on protein present right because it's it's resistant to all of this stuff 27:06.740 --> 27:14.300 And so then that helped develop this concept that even after they get rid of the the nucleic acids even after they use detergent 27:14.300 --> 27:18.500 There's still something there that apparently causes this this 27:20.660 --> 27:24.860 Well, this disease stayed at some point when they injected into the brains of animals 27:24.860 --> 27:29.040 But already this this started to fall apart a little bit. It seemed already like 27:29.960 --> 27:31.960 Hand-waving and so then he moves on farther 27:32.880 --> 27:37.820 And he gets to this crucial point here where they're using knockout mice 27:39.720 --> 27:41.720 and 27:41.720 --> 27:45.280 In the well, they're using knockout mice and regular mice 27:45.280 --> 27:49.120 But anyway, the point in this picture was supposedly we could let him say it I guess 27:49.880 --> 27:57.040 Is that here you have the pre-on protein and then here is where you take that protein fraction and you digest it with 27:57.680 --> 28:02.000 Protonasis enzymes to cut the protein up and then essentially everything's gone 28:03.240 --> 28:05.240 but in the 28:05.320 --> 28:08.120 Pre-anagenic state or in the in the scraping state 28:08.520 --> 28:14.560 Then when you digest these proteins which are different proteins apparently then are in lane one even though 28:14.560 --> 28:18.080 This is supposed to be the control and this is supposed to be the experimental group 28:18.080 --> 28:23.120 And then you digest that fraction what you are left with is still a 28:24.080 --> 28:29.480 Fraction, I guess it kind of a similar weight as this one and so then the argument is 28:30.760 --> 28:32.760 that this represents the 28:33.120 --> 28:35.520 Pre-anscrapey form that is 28:36.240 --> 28:42.920 Undigestable by these protonasis that it's gone here because it wasn't present in this fraction in the healthy animal or in the 28:43.200 --> 28:48.440 The un-un manipulated animal we could listen to see what he says there again if you want 28:49.120 --> 28:55.000 Just to see exactly what anybody talks about destroy the protein we destroy the infectivity or every time we destroy the infectivity 28:55.000 --> 28:57.000 the protein was removed or 28:57.320 --> 28:58.840 destroyed and 28:58.840 --> 29:00.360 when we 29:00.360 --> 29:04.240 Eventually figured out what was going on we found that there was a normal form of the protein in all of us now 29:04.240 --> 29:09.520 This is a gel and the proteins migrate and the smaller they are the faster they migrate through this gel this porous material 29:09.520 --> 29:11.280 sort of like jello and 29:11.280 --> 29:12.760 Then we can stain them with antibodies 29:12.760 --> 29:16.200 And so what we found was that the protein was a protein in all of us 29:16.240 --> 29:22.200 Which is a normal form of the pre-an protein and when we treat with enzymes that destroy proteins the protein was completely destroyed 29:22.200 --> 29:24.800 But in the brains of these hamsters that became ill with Scrapey 29:25.000 --> 29:30.320 What we found was that there was both a normal form of the protein and another form of the protein that when we treated with 29:30.320 --> 29:34.160 The enzymes that destroy proteins there was a residual piece and here now this is funny 29:34.160 --> 29:37.440 I didn't catch this the first time but he was using antibodies here 29:37.440 --> 29:44.640 He gee he shows us later in the talk that there are antibodies that bind one and not the other so why do we know that the antibody 29:44.640 --> 29:47.920 He's using here doesn't bind the fraction that's left here 29:49.160 --> 29:54.080 Maybe there is a fraction here, but the antibody doesn't bind it whereas it does bind it in this form 29:56.440 --> 30:00.200 There's lots of weird things happening here because we use antibodies so 30:01.560 --> 30:07.280 The best word I guess I have is laxidazically at this time in science in 2002 30:07.480 --> 30:10.960 we were still holy clueless to the bouquet of 30:11.600 --> 30:19.960 Molecular variation that's found even in some of the best what were presumed monoclonal antibody preparations. It's a really interesting 30:21.120 --> 30:24.440 Signal here too because you know if the resolution is 30:24.960 --> 30:28.880 Like this with all this noise that he doesn't feel like he needs to explain 30:29.520 --> 30:33.800 Then you can already see that something interesting is happening here. So then they say 30:35.480 --> 30:40.320 Something about the structure of the pre-an protein and that then the normal form 30:40.960 --> 30:44.280 it has these three alpha helices and then in the 30:45.240 --> 30:52.560 Infectious not so good form. It has more beta pleated sheets or more beta helices in this region 30:54.000 --> 30:57.600 And then they go on to say that when they digested these guys 30:58.560 --> 31:01.800 They found these pre-an like rods or pre-an rods 31:02.760 --> 31:07.160 According to the guy that he was working with after they cut the N-terminal off of 31:07.880 --> 31:13.200 the pre-an protein in vitro and later this structure was apparently 31:14.440 --> 31:18.640 Compared and considered homologous to amyloid protein 31:20.600 --> 31:27.880 Plaques or or fibros that were found in the brain of amyloid disease or the hundreds many many many diseases 31:28.600 --> 31:32.720 Apparently according to to Stanley that do the amyloid thing 31:32.720 --> 31:40.840 Then he told us about this crystallization that happens when you make enough of it and how they used 31:41.360 --> 31:43.080 x-ray crystallography 31:43.080 --> 31:49.440 To start to study the formation that they make and what formations they can make with one another as subunits 31:50.240 --> 31:57.200 Inside of that crystal and then that allowed them to kind of understand indeed that there was there were these three alpha helices 31:57.600 --> 31:59.680 and confirm that and so 32:00.160 --> 32:07.160 Then he showed us this picture which isn't very unlike the infectious cycle to tell us exactly how this happens 32:07.440 --> 32:10.120 The pre-an protein gene is expressed 32:10.120 --> 32:17.640 The protein is manufactured inside of the Golgi and expressed on the chant on the outside of the membrane and then it can also be 32:18.560 --> 32:20.720 Taken in in some of these 32:21.160 --> 32:26.000 Evaginations and then I don't know at some point. I guess it's something bad can happen 32:26.000 --> 32:28.000 We don't know what it does 32:28.000 --> 32:30.000 Which is really interesting 32:31.520 --> 32:33.520 So then 32:33.560 --> 32:37.200 He told us about this other gene that's in the family 32:37.560 --> 32:42.440 He said that it was very much related to it and that it had the same three alpha helices 32:42.440 --> 32:47.960 But these same three alpha helices only have about a 25% amino acid homology 32:48.360 --> 32:55.440 With the pre-an protein alpha helices, so I met made the point that that doesn't seem very homologous to me 32:55.440 --> 32:56.640 but 32:56.640 --> 33:02.680 because again alpha helices beta pleated sheets and beta 33:04.800 --> 33:12.000 Heloces are all general structures that can be made with chains of amino acids and one is 33:13.120 --> 33:18.040 many different combinations of amino acids can form these these forms and so 33:18.960 --> 33:21.880 the particular shape and form and 33:22.720 --> 33:29.680 Hydrophobicity of each of these alpha helices might be very different depending on the combination, but the the general shape is not so 33:30.920 --> 33:36.360 Decimilar and so it's it's that's the reason why you can go through a sequence and identify that this is an alpha 33:36.360 --> 33:40.760 He was even though it's only 25% the same as this one 33:40.760 --> 33:43.160 It's more of the what repeats when and that kind of thing 33:43.960 --> 33:45.640 and 33:45.640 --> 33:50.760 So that's another gene that they're that he's now kind of saying might be related to this stuff 33:52.200 --> 33:56.200 then he starts talking about crowdsfeld yachob in in families and 33:57.080 --> 33:58.840 sometimes it's 33:58.840 --> 34:00.200 evidence of 34:00.200 --> 34:04.160 preons getting into humans is 20 years or 40 years later 34:04.160 --> 34:10.520 So we could still see the effects of eating preon infected meat 20 or 40 years later 34:10.720 --> 34:16.800 which is very convenient in 2002 because that could actually be right now and and 34:17.440 --> 34:19.080 timed perfectly with 34:19.080 --> 34:21.960 Transfection to cover it up and we could just turn around and say well 34:22.160 --> 34:26.720 We shouldn't have been eating meat for the last 20 years at least that's what he definitely implied 34:27.440 --> 34:30.040 There was also in here some stuff where they were 34:30.720 --> 34:38.320 Bovinizing mice, but it was a little bit of hand waving and nonsense and I still think it was probably over expression of protein rather than 34:39.240 --> 34:44.800 Replacement thereof then he talked about that was where this there it is the bovine the bovine 34:45.600 --> 34:47.600 the bovinized mice 34:48.160 --> 34:50.600 So they over express a bovine 34:52.400 --> 35:00.120 Probably under some kind of conditional promoter they over express the bovine preon protein and then they show that that 35:00.920 --> 35:02.360 makes the mouse 35:02.360 --> 35:08.520 susceptible to the bovine sponge of form encephalopathy, but not the other ones and so 35:09.400 --> 35:12.760 Kinda demonstrates that there's some specificity 35:12.760 --> 35:18.720 to the different agents, but the different agents are all basically coming from the same 35:19.680 --> 35:24.780 Protein, so I'm not really sure, you know, we'd have to go through all these papers to see how 35:26.480 --> 35:32.000 Biologically useful this model is or whether it's really just you know injecting junk in animals heads twice 35:33.000 --> 35:35.000 and 35:35.000 --> 35:39.360 Then we got to the yes 35:39.360 --> 35:46.760 these are some more antibodies and whether they bind or not and this is just showing you that they they use antibodies as a way of 35:47.640 --> 35:51.840 probing whether certain parts of a protein are present or not or whether they're 35:52.560 --> 35:58.120 Available for antibody binding or not and to a certain extent. I think this makes some 35:58.680 --> 36:04.520 Sense, but it would really requires very clever controls and very astute 36:05.320 --> 36:14.320 Alternative experiments to support and so I feel like a lot of times in this talk. It has been used as kind of a hand-waving thing 36:15.240 --> 36:18.640 Here I'm gonna prove to you that these things fold differently 36:19.480 --> 36:24.720 And the way I'm gonna do that is use antibodies that bind and don't bind and I think that's a little bit of 36:25.240 --> 36:31.560 Yeah, anyway, I think that's a little bit sketch then we might be right where we were wanting to be I 36:31.840 --> 36:33.840 Think 36:33.840 --> 36:37.320 Think we might be right where we wanted to be we stopped here because 36:38.600 --> 36:44.400 we were looking at the regular prion protein of the protein in this great escapee form and 36:44.640 --> 36:52.200 How degradation took longer in these neuroblastoma cells and I was kind of angry because I didn't understand how they were 36:52.920 --> 36:56.880 Expressing the same protein that folds in two different ways in these 36:57.760 --> 37:03.640 Separately in these cell lines it seemed to imply that they knew a sequence that was different or something and I didn't understand that 37:04.000 --> 37:06.960 So I said this is a PRPC and defined what is called the house 37:06.960 --> 37:09.160 So I said that we had I had to look into that 37:09.160 --> 37:11.160 So I think that's where we are right now 37:11.160 --> 37:13.960 So there's a few things that just don't really line up 37:13.960 --> 37:19.440 But now we're gonna go into more of the chemistry and messing around and I think we're gonna see more of the same kind of 37:20.160 --> 37:23.200 weird bridges being made that aren't really 37:24.040 --> 37:30.960 supported by very much evidence just conjecture and cartoons, so let's see half life for formation very rapid and 37:31.560 --> 37:33.560 David Borchardt working here in San Francisco 37:34.040 --> 37:39.840 Confirmed that and then showed that the half-life time for degradation is about six hours and that PRP scrapie was made even more 37:39.840 --> 37:42.560 Slowly with a half-time of formation of about three to ten hours now 37:42.560 --> 37:47.360 I had thought that PRP scrapie was complete granite and that it was never degraded 37:47.520 --> 37:52.080 But in the last slide that I showed you this is really represents the degradation of PRP scrapie 37:52.080 --> 37:54.080 the loss of prions from the culture 37:55.160 --> 38:01.100 And so we were able to calculate a number as I mentioned before where 50% of the PRP scrapie disappears of about 30 hours 38:01.960 --> 38:04.560 This has important implications for thinking about all the general 38:04.560 --> 38:07.040 You know it could be that they just stain with these different 38:07.120 --> 38:12.640 Anybodies that they claim are selective for the proteins and when the stain goes away then they say the proteins are gone 38:12.640 --> 38:16.440 If there's some indirect measurement we would have to look into it diseases 38:17.320 --> 38:21.040 It tells us that cells are capable of degrading both PRPC and PRP scrapie 38:21.040 --> 38:26.880 And it raises the question whether PRP scrapie is normally found at very low levels in normal cells and has a physiological function 38:26.880 --> 38:33.040 And that is a very appealing way of thinking about all of this because it makes much more sense than thinking that PRP scrapie is something totally apparent 38:33.560 --> 38:35.960 It raises the question of whether or not we really have an issue 38:35.960 --> 38:42.640 It's a kinetic race between the formation of PRP scrapie and the cells ability to clear PRP scrapie and that when the cell can keep up with the 38:42.680 --> 38:48.720 formation and clear it like it does with other protein all other proteins in fact that when that happens everything is functioning fine 38:48.840 --> 38:53.160 But when the cell gets out of balance see you almost felt like you had to make that point 38:53.680 --> 38:57.200 That all other proteins fold incorrectly and we have to do it 38:57.200 --> 39:01.720 We have to get rid of we have to degrade all other proteins and we do I'm not saying we don't 39:01.720 --> 39:12.880 I'll let I'll go back just so you can hear it again. I didn't interrupt 39:12.880 --> 39:17.240 It's a kinetic race between the formation of PRP scrapie and the cells ability to clear PRP scrapie 39:17.240 --> 39:22.720 And that when the cell can keep up with the formation and clear it like it does with other protein all other proteins 39:22.720 --> 39:25.760 In fact that when that happens everything is functioning fine 39:25.840 --> 39:32.240 See so that's that's the place where we stopped where really the model is and let's let's let's be clear 39:32.560 --> 39:36.080 We want to do the model the model is that 39:37.840 --> 39:40.440 the pre on protein and 39:42.280 --> 39:46.560 Pre on protein folded incorrectly with the SC superscript 39:47.720 --> 39:52.360 The scrapie protein are produced by the same process 39:53.200 --> 39:59.880 But one is takes longer to degrade and so even though maybe smaller 40:01.280 --> 40:02.960 numbers of 40:02.960 --> 40:09.640 This confirmation come out of the ribosome. They take longer to degrade and so the kinetics of degradation 40:10.520 --> 40:13.680 Play into this and that's what can also make the 40:14.480 --> 40:17.400 onset anywhere from 60 days to 40:17.920 --> 40:21.120 to 40 years as he says 40:22.360 --> 40:24.600 And in theory that kind of makes sense 40:24.600 --> 40:32.440 It sounds like a fuse that could have any length of time depending on the exact parameters of by which it burns 40:35.240 --> 40:40.560 It's also a very convenient story that makes a lot of predictions that should have sort of 40:41.160 --> 40:47.040 Easily testable experiments that can grasp or can get can get at those ideas 40:47.480 --> 40:52.840 So let's listen as he develops this idea where again remember pre on protein in its good form and 40:53.520 --> 41:00.680 Pre on protein in its pre on a genic form are present at all times in all healthy animals 41:01.440 --> 41:02.520 and 41:02.520 --> 41:07.880 That it is only the kinetics of degradation and production that over time 41:08.560 --> 41:16.440 Can result in a preponderance of the scrapie form which can then of course cause this fibro formation, etc 41:18.040 --> 41:23.480 So the whole mechanism isn't quite understood yet, but the ticking time bomb part the one 41:24.480 --> 41:32.480 Molecule part doesn't really make sense anymore because according to this story. It's not just one molecule and now the ticking time bomb starts 41:34.080 --> 41:40.040 You see that's a this is a very different model if you're just gonna flip flop between those two models or 41:40.400 --> 41:45.560 If you're gonna say that Stanley Proustner in 2002 did know what he was talking about and 41:46.560 --> 41:49.720 Just one molecule is enough to cause this disease 41:50.520 --> 41:52.520 hmm interesting 41:52.960 --> 41:59.040 But when the cell gets out of balance it can no longer clear PRP scrapie at the rate that it's formed 41:59.040 --> 42:02.040 I'm talking about very very low levels that we can't detect even buying these animal assays 42:02.640 --> 42:08.840 Then something goes awry and we began to accumulate more and more PRP scrapie and eventually the animal gets sick and goes on to die or the human being 42:09.920 --> 42:11.920 Now I promise you a little chemistry at the end 42:12.760 --> 42:15.280 And if you just look down here at chlorpromisine this is Thorazine 42:15.280 --> 42:21.680 This is one of the first anti-psychotic drugs, and this is the structure of it has these three rings and when Carson Korth added one micromolar 42:21.680 --> 42:28.880 This amount he still saw these protease resistant bands this so the different the three bands are the ones with no sugars one sugar chain and two sugar chains 42:28.880 --> 42:31.240 They're showing a little better here. So what is this? 42:33.160 --> 42:38.240 Is that dr. Drew reason a lot of what I've talked about today 42:38.600 --> 42:45.960 Hilarie seems like cyber is only mode right I mean remember in 20 in 2019. I was fully a believer in vaccines 42:45.960 --> 42:52.600 I didn't know about any of this. I thought it was a godly goop. So so this is fabulous because here's what you got here, right? 42:52.600 --> 42:54.600 Here's what you got here 42:54.600 --> 42:56.200 You got a guy 42:56.200 --> 43:04.600 who basically is one of these many people who now who's an old man who's using testosterone and pushing 43:05.600 --> 43:07.280 pharma products 43:07.280 --> 43:14.160 Here you have a guy that from every other lawyer I can tell they don't take him seriously 43:15.000 --> 43:21.040 They don't think his pedigree is any good. They don't think his arguments that he makes are any good and they're pretty sure 43:21.400 --> 43:23.400 There's something up 43:24.600 --> 43:32.040 Like lawyers not me other lawyers people that I trust and people that I don't trust they're all unanimous that this this can't 43:32.360 --> 43:34.360 be someone to take seriously 43:34.560 --> 43:41.840 And this person is a person whose whose daughter was on Alex Jones at least twice 43:42.400 --> 43:46.520 In the run-up the year before the pandemic 43:47.400 --> 43:55.700 Had a million subscribers on YouTube before I guess jokingly threatened to go to the house of the YouTube CEO and kill her or him 43:55.700 --> 44:07.940 And we're supposed to believe that a retired pharma exec who sold her company to Pfizer by the way and was helping them 44:07.940 --> 44:09.940 I guess testing 44:10.140 --> 44:16.660 People before they tested them so that they if they had cardiac problems that they wouldn't be in the trial and you know 44:16.660 --> 44:18.140 I don't know 44:18.140 --> 44:24.900 maybe better ways to read the QP wave or whatever it's called and and and and the whole point is 44:25.220 --> 44:32.180 Is that it just seems like all the people that are managing to get anywhere with regard to getting their message out 44:32.180 --> 44:37.100 I've always been stepping in front of other people. She has stepped in front of Catherine Watt 44:39.020 --> 44:41.780 She has stepped in front of Craig Particopper 44:43.260 --> 44:46.860 She's been on stage with Robert Malone in Sweden 44:48.060 --> 44:50.300 When the pandemic was still hot and heavy 44:51.260 --> 44:53.460 This guy has been the lawyer of 44:54.260 --> 44:55.540 Andrew Huff 44:55.540 --> 45:03.420 The guy who says that he shot over a hundred and fifty rounds into the woods of of the upper Michigan forest surrounding his house 45:03.660 --> 45:05.660 While he was combating the state police 45:11.140 --> 45:17.980 And now we're supposed to believe that this is this is the these are the people on the white horses that are coming to our rescue 45:21.300 --> 45:25.580 Please we can't possibly take this seriously 45:26.620 --> 45:29.540 This isn't even Fox News level serious 45:31.220 --> 45:36.100 And and to give it airtime or to think that oh we got to get their attention 45:36.900 --> 45:45.420 That's playing right into the game even if even if this man in the middle isn't sophisticated enough to know he's being played 45:45.420 --> 45:47.420 I assure you that 45:47.540 --> 45:49.540 This is a play 45:50.300 --> 45:53.140 And it is a play that that was 45:53.660 --> 45:58.340 Either put in place very early ready to go or already 45:58.860 --> 46:04.260 Ready to go and then some like they were this was always where we were gonna be but I don't think that's the case 46:04.580 --> 46:11.420 But these are always the people these were always the people that were gonna be on the stage that there's no question about it 46:12.060 --> 46:15.340 Brett Weinstein was always gonna be on the stage. I 46:15.900 --> 46:17.900 I 46:17.900 --> 46:21.980 Think Robert Malone was likely always gonna be on the stage. I think 46:22.620 --> 46:24.620 Steve Kirsch maybe was 46:25.660 --> 46:27.500 Very early on 46:27.500 --> 46:32.740 Not gonna be but wanted to be and got on the stage. I think there's a lot of people that 46:33.940 --> 46:38.940 Were kind of reluctant at first didn't think that we would be where we are at this stage 46:39.220 --> 46:41.220 Who are on the stage reluctantly? 46:41.460 --> 46:44.700 Once you sign the page, you can't get off. It's a national security 46:45.620 --> 46:47.060 operation and 46:47.060 --> 46:54.420 So now remember if this is the controlled demolition of America that it makes perfect sense that many of these people would be involved 46:54.420 --> 46:56.420 most of them being privately 46:56.940 --> 47:05.100 rich privately okay with the collapse of America privately okay with the gross over inflation of the dollar and 47:08.020 --> 47:10.020 That's the point here is 47:10.260 --> 47:18.180 That the people who are rising over the last four years the people who get censored and then get on tucker and complain about it are all 47:18.660 --> 47:20.500 independently wealthy 47:20.500 --> 47:26.380 Already intimately connected to the very machine that none of us have ever gotten anything from 47:27.740 --> 47:34.300 None of us have ever sold the company none of us have had multiple consulting companies that worked with the DoD Ditra 47:34.540 --> 47:37.580 none of us have ever sat on on on 47:37.980 --> 47:42.380 DARPA grant committees to evaluate DARPA proposals 47:43.180 --> 47:46.060 none of us have ever gotten the benefit of 47:47.540 --> 47:49.540 taxpayer-funded data 47:49.580 --> 47:52.780 From your university to start a company and then sell it 47:56.060 --> 47:58.060 But all of these people have 48:00.260 --> 48:02.260 All of these people have a book 48:08.340 --> 48:14.780 What we're dealing with here is a controlled operation to make sure that you stay focused on 48:16.140 --> 48:22.660 Something that will not prevent the controlled demolition of America will not prevent us from coming together 48:22.660 --> 48:31.140 But we'll instead keep us fighting about things like where the virus came from or what killed people or whether viruses exist at all 48:38.300 --> 48:40.900 There is no way that it is random 48:42.660 --> 48:46.940 That soaf was on Alex Jones three times in 48:47.500 --> 48:52.220 2019 and now we are listening to her mom for three years as 48:52.980 --> 48:54.780 part of the 48:54.780 --> 48:56.140 alternative 48:56.140 --> 49:03.100 COVID narrative that involves a novel virus that killed millions of people that millions more were saved from 49:04.100 --> 49:07.940 That was definitely gained a function or a toxin that was 49:08.500 --> 49:12.460 sprayed on the world by the United States Department of Defense 49:14.140 --> 49:16.140 Which was a great way to 49:16.740 --> 49:18.740 implode America in a way that 49:19.780 --> 49:24.900 Turns everybody on everybody else. It doesn't realize that the military is a victim of this too 49:25.580 --> 49:27.300 the average 49:27.300 --> 49:32.340 Serving soldier is a victim of this too. They have to follow orders 49:32.340 --> 49:34.340 It's the people above 49:34.660 --> 49:41.260 Lieutenant Colonel now those are the people we need to be holding to account. Those are the people who put the mandate out 49:41.940 --> 49:43.940 Who gave the orders down the chain? 49:44.940 --> 49:50.140 The people at the bottom of the chain cannot be blamed for taking the orders or following them 49:50.460 --> 49:55.980 They are victims of this as well and yet. Who does she want us to blame the Department of Defense? 49:55.980 --> 50:06.780 Without any more specificity than that without any more chain of command to the Department of Human Health and Human Services for the 50:07.740 --> 50:10.940 Department of Homeland Security for DITRA 50:11.860 --> 50:13.860 Nothing's State Department. What's that? 50:17.340 --> 50:24.420 And this guy as I said is not a legal scholar is not some kind of courtroom killer 50:26.900 --> 50:33.380 This is a guy who is a very very very below average lawyer 50:35.020 --> 50:37.020 and 50:37.020 --> 50:40.900 He's probably in way over his head. He's probably not even a bad guy 50:44.260 --> 50:46.100 But people 50:46.100 --> 50:47.460 smarter than me 50:47.460 --> 50:53.780 Do not take him seriously and so the idea that either of these two take him seriously that either 50:54.300 --> 50:57.860 Dr. Drew or Sasha take him seriously it begs 50:59.460 --> 51:04.420 I'm I find it dubious. I find it dubious and and I don't think that 51:07.300 --> 51:09.300 Hey, I just don't 51:11.620 --> 51:14.500 I don't buy him. I don't buy him. I think that we are 51:15.300 --> 51:20.740 You need to be very pessimistic about the number of people. I mean look at how much fun she's having 51:20.740 --> 51:25.660 Americans were murdered ladies and gentlemen and 51:27.300 --> 51:34.900 Children are having needles forced upon them and adults over 50 are having needles coerced into them 51:37.300 --> 51:39.780 As we speak by this system 51:41.860 --> 51:47.860 And it is based on this mythology of a novel virus that is not being questioned here at all 51:47.860 --> 51:50.740 I can guarantee it. I mean they're looking how much fun 51:51.540 --> 51:54.820 it's so much fun to be on dr. Drew's show and 51:56.500 --> 51:59.140 Dr. Drew's weed is so good and 52:00.060 --> 52:04.700 Tom Ren's is doing the right thing. He wants to do the right thing. That's all possible. I guess 52:08.060 --> 52:13.940 But I just don't see it I do not see it if he is used he is used he is not 52:18.340 --> 52:23.380 I'm sorry, but I just I don't see it. I don't see it at all. It's unfortunate, but I just don't see it 52:25.620 --> 52:27.620 And i'm not going to subscribe to 52:29.780 --> 52:33.940 To dr. Drew. I don't think it'll get me in anyway. It's too late 52:35.300 --> 52:38.740 Uh, let's finish this. This is our work. This is our work 52:38.740 --> 52:48.260 We're up even up in here 52:49.140 --> 52:51.140 Rugs and this is the structure of it. It has these three rings 52:51.860 --> 52:56.660 And when karstin corth added one micromolar this amount he still saw these protease resistant bands 52:57.140 --> 53:01.460 This so the different the three bands are the ones with no sugars one sugar chain and two sugar chains 53:01.460 --> 53:04.020 They're showing a little better here. So two sugar chains one and none 53:04.660 --> 53:06.500 Or even up in here 53:06.500 --> 53:11.460 When he added five times as much chloropromacy and he couldn't see any and ten times as much he still couldn't see any as you would expect 53:13.380 --> 53:15.940 And when he had done the first experiments and showed them to me 53:15.940 --> 53:20.500 I said go back and look at some of these other psychoactive drugs like how apparel which doesn't do anything in similar concentrations 53:21.060 --> 53:28.180 And he did that now keep in mind what he's talking about here now. He's talking about chemicals that have anti-psychotic 53:29.780 --> 53:33.380 Properties that are used to treat dementia 53:33.380 --> 53:37.300 Demented people 53:38.580 --> 53:43.780 Which is the joke he made at the beginning of the talk that you can go back and see in the previous episode 53:45.540 --> 53:53.620 Think about that for a minute because now he's testing whether or not these compounds have any effect on the presence of or the degradation of 53:54.180 --> 53:57.940 The prion protein which is a really weird thing to test 54:00.260 --> 54:02.260 And he looked at many of them as you see on this chart 54:03.460 --> 54:07.620 And then I said to him karsten why in the world did you come with me to show me the first experiments? 54:08.180 --> 54:10.580 And what the background of karsten corth was that he 54:11.300 --> 54:16.580 In his late 30s had done a psychiatry residency and decided he wanted to go into molecular biology and began to work with a former postdoctoral fellow of mine 54:16.580 --> 54:23.860 Bruno ersh in Zurich and when Bruno left the university of Zurich to start a biotech company karsten wanted to stay in academic medicine and came here 54:24.500 --> 54:29.940 And I had been telling karsten for about a year and a half that he should solve one of the major problems of psychiatry like schizophrenia or bipolar disorders or autism 54:30.820 --> 54:33.620 And he looked at me and he said to answer my question 54:33.620 --> 54:34.660 Why did you do these experiments? 54:34.660 --> 54:37.940 And he said well you've been telling me to connect my work on prions with psychiatry for two years now 54:37.940 --> 54:40.580 And so I threw in chlorpromazine or thorazine into the culture 54:40.980 --> 54:47.380 Well the karsten's credit he went back and began to look at the literature in detail and all of this really begins with the German dye industry in 54:47.380 --> 54:53.220 Paul Erlich in 1891 who was using methylene blue as a weak anti-malarial substance and then through this pathway eventually these 54:53.620 --> 54:56.780 These more potent anti-malarials were synthesized and chlorpromazine 54:56.860 --> 55:02.540 Which really had marked anti-psychotic effects and chlorpromazine was the first drug to begin to empty out the insane asylums throughout the world 55:04.460 --> 55:06.940 In the 1930s the Germans synthesized 55:07.460 --> 55:10.620 Quinecrin and this turned out to be a potent anti-malarial drug 55:10.620 --> 55:12.380 But it had many more side effects than quinine 55:12.380 --> 55:16.660 But there wasn't enough quinine for use in World War two because it's extracted from the bark of the jacona tree 55:16.660 --> 55:20.660 And there wasn't a chemist in the world who was smart enough to figure out the structure and then how to synthesize it 55:20.900 --> 55:24.380 Until Robert Woodward did this at Harvard in the late 1940s 55:25.300 --> 55:30.900 So quininecrin was given to thousand I should say three million young Americans in World War two 55:30.900 --> 55:32.900 So we know a lot about quininecrin pharmacology 55:32.900 --> 55:37.660 And what karsten corth found was that quininecrin was ten times more potent than chlorpromazine 55:38.660 --> 55:41.660 So each so instead of this being a ten not being a five 55:41.660 --> 55:44.900 That's a one and point five and point one and the structure is very similar 55:46.340 --> 55:51.300 And when karsten corth treated these cultures for six days if he added enough chlorpromazine 55:51.380 --> 55:57.220 He found that there was no return of these protease resistant bands. This is this is the band as I said before that has two sugar chains one and none 56:00.460 --> 56:05.900 And because quininecrin has a 70-year history of the treatment of parasitic diseases the toxicities are well documented 56:05.980 --> 56:10.780 Bruce Miller and Michael Geshwin and I and a number of other people have been involved in this in the School of Pharmacy here 56:12.500 --> 56:15.300 We applied for an IND a new drug 56:16.100 --> 56:21.860 Investigation license from the FDA and we were able to skip what are called phases one and two of these typical clinical trials which amount to 56:22.780 --> 56:28.260 Tens of millions of dollars normally and we began to load patients with one gram followed by 300 milligrams daily 56:28.260 --> 56:32.260 And in a minority of patients what we've seen we believe and it's not just us 56:32.260 --> 56:34.700 It's many neurologists who are in contact with us throughout the world 56:34.700 --> 56:40.420 But we've not seen all these patients because we're hoping that we will get an NIH study funded over the next four or five months 56:40.420 --> 56:44.980 And that this study will provide us the funding we need to really look at all the patients throughout the world who are on quininecrin 56:45.340 --> 56:50.580 But it's our impression in that of a number of other neurologists that in a minority of CJD patients the disease is slowed by quininecrin 56:50.580 --> 56:54.140 And in a few CJD patients with quininecrin who have died later 56:54.140 --> 56:59.780 Steve Diarmidus found that there are lower levels of PRP scraping they seem to be reduced to almost zero 57:00.580 --> 57:03.980 Compared to what is generally found now the problem is that we have so few patients in this group 57:04.300 --> 57:09.300 We've been able to obtain these autopsies that we just don't know at this point the second issue is that 57:10.180 --> 57:12.100 In addition to not knowing 57:12.140 --> 57:17.140 There are some patients where we even have more doubts. These are the patients who get dramatically better on quininecrin and those patients 57:17.140 --> 57:19.420 I think it's good scientists. We're not even sure that they have CJD 57:21.260 --> 57:24.500 So we need a much more controlled study we don't want to fool ourselves 57:25.020 --> 57:29.180 Because you can't know that they have CJD until after they die, right? 57:29.180 --> 57:32.540 So that's a really actually very nice admission 57:32.540 --> 57:35.580 So what I've been telling you tonight is that sporadic and infectious forms of these diseases 57:35.580 --> 57:38.980 It's the wild type or normal form of PRPC that's converted into PRP scraping 57:39.020 --> 57:44.580 So this is an infectious form of the disease that's transmission from an animal to a man or from man-to-man or animal to animal 57:44.580 --> 57:48.300 In the sporadic form of the disease accounts for 90 85 to 90 percent of all cases 57:48.300 --> 57:51.940 We think it's a spontaneous conversion of PRPC into PRP scraping or as I told you before 57:51.940 --> 57:56.420 This is a kinetic race and that there are small amounts of PRP scraping all of us that are normally cleared 57:56.420 --> 57:58.260 So he has two models 57:58.260 --> 58:05.660 One is that it just misfolds and then you're screwed and the other one is is that it's always misfolding and it's a race to get rid of the degradation 58:06.100 --> 58:08.100 And are they gonna test it? 58:08.220 --> 58:13.780 Are they gonna use that to make any predictions either one of those models make any predictions that are testable? 58:13.780 --> 58:19.660 Are you just gonna leave it sit right there? Those are two very very mutually exclusive 58:22.980 --> 58:29.060 Powerful models they make very powerful predictions about how this should or should not work 58:29.900 --> 58:31.900 It's very bizarre 58:31.980 --> 58:36.060 In the inherited forms of these diseases, it's a germline mutation passed from parental offspring 58:37.820 --> 58:42.940 There are a whole series of new ideas that have come out of this the fact that that prions are infectious proteins is totally new 58:42.940 --> 58:49.340 This is unlike all other infectious agents prions cause brain degeneration. They cause sporadic genetic and infectious forms of these diseases 58:49.340 --> 58:52.980 There's no other disease paradigm in which you have both genetic and infectious diseases 58:53.500 --> 58:58.740 And prions are the most well understood among all the neurodegenerative diseases which include of course Alzheimer's disease and Parkinson's disease 58:58.900 --> 59:06.580 So he's saying that they actually understand prion diseases better than the others understand Alzheimer's and Parkinson's. Wow 59:06.580 --> 59:08.580 I mean wow 59:09.140 --> 59:13.340 That's impressive because I don't think I'm convinced not from this talk 59:14.020 --> 59:20.980 I'm not convinced that prions are infectious proteins yet. I'm not convinced that they cause brain degeneration 59:20.980 --> 59:25.420 I think they they can trigger it, but they don't do it 59:26.300 --> 59:31.980 Prions cause sporadic genetic and infectious diseases and humans and animals we think 59:32.300 --> 59:36.620 It's a hypothesis that has definitely not been proven as far as I can tell 59:36.940 --> 59:43.820 Not if you have to inject it into the brain of the animal and they don't do it by ingestion because all of the things that we see 59:44.380 --> 59:50.580 With kuru is ingestion with with the cattle was feeding cattle other cattle even said it 59:51.460 --> 59:53.460 Shh 59:54.340 --> 59:57.100 There are many thousands of times more common than the prion diseases 59:57.700 --> 01:00:01.100 Now it's the discovery of prions in many other new findings which allows us now 01:00:01.100 --> 01:00:04.700 I think to define neurodegenerative diseases in terms of their cause not the effect 01:00:05.060 --> 01:00:10.860 So we can I think we all most people would agree now that degenerative diseases of the nervous system are disorders of a parent protein processing 01:00:10.860 --> 01:00:16.740 Wow, so I think most people would agree that is that an illusion of consensus to you or is am I what? 01:00:16.740 --> 01:00:23.180 Wow, that is spectacular the proteins are being processed abnormally 01:00:24.260 --> 01:00:26.820 They give you a little idea of the numbers of cases in the United 01:00:26.820 --> 01:00:29.020 So we have 400 cases of prion disease annually in the US 01:00:29.020 --> 01:00:35.300 But there are four million people without Alzheimer's disease about a million with Parkinson's disease and about 20,000 with ALS or Lou Gehrig's disease 01:00:36.100 --> 01:00:38.100 So these are huge numbers 01:00:38.740 --> 01:00:44.380 Good night, Jeff. No, there are many many similarities between these diseases what we see are these abnormal protein deposits 01:00:44.380 --> 01:00:47.260 I showed you PRP scraping in the brain and I showed you these PRP amyloid plaques 01:00:47.380 --> 01:00:51.980 Well, the brains look very similar if we're not using if we use antibodies, but with these are different proteins now 01:00:51.980 --> 01:00:53.900 But the structures look very similar in Alzheimer's disease 01:00:54.260 --> 01:00:56.580 There's slightly different in Parkinson's disease and ALS 01:00:56.780 --> 01:00:58.780 But what's so interesting about all of these is that? 01:00:59.260 --> 01:01:06.220 The mutations in the genes that we find in familial forms of the disease encode the proteins that are found in these protein deposits 01:01:06.220 --> 01:01:08.220 Except here. This is less clear with ALS 01:01:09.220 --> 01:01:15.020 So the accumulation of misprocessed proteins causes the nervous system malfunction resulting in problems such as dementia 01:01:15.020 --> 01:01:18.100 We're back to this word Alan difficulty moving and weakness and 01:01:19.140 --> 01:01:25.340 Preventing the accumulation of you know, I'm in theory all down with that because one of the reasons why he says is because 01:01:25.940 --> 01:01:31.980 The protein plaques form and then also a lot of times that same protein has some mutation 01:01:32.540 --> 01:01:37.700 Which seems to sort with these familial disorders and to the extent to which that's true 01:01:38.140 --> 01:01:44.620 That could be useful. But again, remember that's not true with amyloid anymore. They don't think that's the case anymore 01:01:45.020 --> 01:01:50.180 They went crazy on it, but then they found out one of these papers wasn't right 01:01:51.180 --> 01:01:57.020 And so that just recently happened, right? Maybe we should all look into that a little bit so we understand exactly 01:01:57.900 --> 01:02:05.420 How much of this, you know, amyloid disease amyloid beta is is amyl is Alzheimer's disease is true or not a 01:02:07.020 --> 01:02:15.460 Lot of these are also just their observations of correlation. Yes, they're there, but are they present? Are they responsible? Are they? 01:02:16.540 --> 01:02:19.020 Downstream consequences of whatever's going on here 01:02:19.020 --> 01:02:22.980 I don't think we understand these as well as he's in these protein deposits, but I agree 01:02:22.980 --> 01:02:28.860 I still agree that it has to do with these proteins perhaps misfolding. That's okay with me, but again 01:02:30.500 --> 01:02:36.180 Pre-on proteins are we're supposed to be told that well, you know, you can engineer a spike protein it can have 01:02:37.060 --> 01:02:39.220 pre-onogenic sequences and that 01:02:39.740 --> 01:02:47.820 This kind of thing can happen now. That's not the same as this. These are very specific proteins that again, we have not 01:02:47.820 --> 01:02:56.780 Just because that sequence is different have we demonstrated that those are the so that's all all this work needs to be done 01:02:56.780 --> 01:02:58.780 It's less clear with ALS 01:03:00.140 --> 01:03:05.180 So the accumulation of misprocessed proteins causes the nervous system malfunction resulting in problems such as dementia 01:03:05.180 --> 01:03:08.180 We're back to this word on difficulty moving and weakness and 01:03:09.300 --> 01:03:15.620 Preventing the accumulation of these misprocessing protein provide proteins provides I think for the first time a rational approach to treating degenerative diseases 01:03:15.620 --> 01:03:24.100 Yes, so and and so we've done lots of things to get rid of the amyloid beta to get rid of these plaques and it doesn't help these people 01:03:25.980 --> 01:03:27.820 It oftentimes makes it worse 01:03:27.820 --> 01:03:33.700 It's not clear that this is the way to go and the only way to do that is with an immune response of course, which is again 01:03:34.500 --> 01:03:37.220 Something we're not prepared to augment nervous system 01:03:38.780 --> 01:03:40.780 There's a little summary of CJD 01:03:41.660 --> 01:03:46.300 And what went on as I told you I my introduction to this was a patient in 1972 here at UCSF 01:03:46.300 --> 01:03:52.780 And that it was 1921 when six patients were described and this disease was thrown into a waste basket a degenerative disorders of a nervous system 01:03:52.980 --> 01:03:58.380 But it came out of the waste basket in 1968 when Carlton Gajasek and Joe Gibbs working at the NIH along with a number of collaborators 01:03:58.580 --> 01:04:01.020 Transmitted the disease into apes and later into monkeys 01:04:03.180 --> 01:04:06.380 Preons and how did they do that they injected it directly in the brain? 01:04:06.380 --> 01:04:13.020 I imagine like, you know some preparation unlike all other infectious pathogens viruses, viroids, bacteria, fungi, parasites 01:04:13.020 --> 01:04:17.220 All of which multiply by having an RNA or DNA genome direct the synthesis 01:04:17.420 --> 01:04:23.960 Interesting that they don't say anything about phage here even though that's one of the most common forms of viruses not one 01:04:24.820 --> 01:04:31.220 No mention of bacteriophage here at all. That is a gigantic red flag 01:04:32.220 --> 01:04:39.220 No mention of bacteriophage here at all. Why would I care about bacteriophage? Well, let's see. Let's get out of this 01:04:40.220 --> 01:04:42.220 And let's go back to the beginning 01:04:43.220 --> 01:04:45.220 Let's take a look at this 01:04:46.220 --> 01:04:48.220 And current slide just to give you 01:04:50.220 --> 01:04:52.220 An example of what's going on here 01:04:52.220 --> 01:04:59.220 There's a bacteriophage right there on the third live podcast at the beginning of the pandemic of the Dark Horse podcast 01:04:59.220 --> 01:05:04.220 with Brett Bandana and glasses himself 01:05:05.220 --> 01:05:07.220 And right there 01:05:07.220 --> 01:05:13.220 Conspicuously at the front of the podcast is a coffee cup with a bacteriophage on it 01:05:13.220 --> 01:05:20.220 Isn't that weird because it doesn't seem like he really doesn't think that bacteriophages are actually a thing 01:05:20.220 --> 01:05:26.220 Phages are maybe he goofs it in with the viruses, but that would be very disingenuous because 01:05:26.220 --> 01:05:28.220 Phages are everywhere 01:05:30.220 --> 01:05:37.220 Even the no virus people even the no virus people acknowledge that bacteriophages exist isn't that cool 01:05:37.220 --> 01:05:41.220 Isn't that funny and he doesn't exogenous at all 01:05:41.220 --> 01:05:46.220 Strange the progeny pathogens. It's only prions which contain only a protein 01:05:46.220 --> 01:05:50.220 And they co-opt a normal form of that protein to produce more of the misfolded form 01:05:50.220 --> 01:05:52.220 PRP scraping 01:05:52.220 --> 01:05:55.220 Now all of this like what I'm telling you seem like science fiction to a lot of people 01:05:56.220 --> 01:05:58.220 And about seven or eight years ago 01:05:58.220 --> 01:06:02.220 I was a meeting in New Mexico and I was hearing everything that I was been saying 01:06:02.220 --> 01:06:04.220 But it was being said by somebody else 01:06:04.220 --> 01:06:08.220 And I looked at a good friend of mine, Hilary Keprowski, and I said Hilary this is really unbelievable 01:06:08.220 --> 01:06:11.220 This guy even thinks he'd found all of this and Hilary said 01:06:11.220 --> 01:06:15.220 I'm sorry, what did you just what excuse me what? Holy shit, what? 01:06:15.220 --> 01:06:18.220 Did you hear that Mark? 01:06:18.220 --> 01:06:20.220 Mark? 01:06:20.220 --> 01:06:23.220 Did you hear what he just said? 01:06:23.220 --> 01:06:25.220 Holy shit balls 01:06:25.220 --> 01:06:28.220 I mean this is red alert time 01:06:28.220 --> 01:06:31.220 And Hilary Keprowski and I said Hilary this is really unbelievable 01:06:31.220 --> 01:06:32.220 What? 01:06:32.220 --> 01:06:34.220 Seriously what? 01:06:34.220 --> 01:06:35.220 Here we go 01:06:35.220 --> 01:06:37.220 And I was hearing everything that I had been saying 01:06:37.220 --> 01:06:39.220 But it was being said by somebody else 01:06:39.220 --> 01:06:42.220 And I looked at a good friend of mine, Hilary Keprowski, and I said 01:06:42.220 --> 01:06:44.220 Hilary this is really unbelievable 01:06:44.220 --> 01:06:45.220 What? 01:06:45.220 --> 01:06:47.220 Seriously what? 01:06:47.220 --> 01:06:48.220 Here we go 01:06:48.220 --> 01:06:50.220 And I was hearing everything that I had been saying 01:06:50.220 --> 01:06:52.220 But it was being said by somebody else 01:06:52.220 --> 01:06:54.220 Hilary 01:06:54.220 --> 01:06:57.220 My good friend Hilary Keprowski 01:06:59.220 --> 01:07:03.220 Mark Coolax got some information and stories and connections 01:07:03.220 --> 01:07:05.220 Hilary Keprowski 01:07:05.220 --> 01:07:07.220 Stanley Plotkin 01:07:09.220 --> 01:07:12.220 This goes back right to the 01:07:12.220 --> 01:07:17.220 I mean all these people, Gallo, they're all in the same little group of white haired men or whatever 01:07:17.220 --> 01:07:19.220 It's absolutely incredible 01:07:19.220 --> 01:07:21.220 And all of this 01:07:21.220 --> 01:07:23.220 And Hilary said I've got a slide for you, I'll send it to you 01:07:23.220 --> 01:07:26.220 So he sent me this slide about the four stages of adopting a new idea 01:07:26.220 --> 01:07:27.220 The reaction at first is it's impossible 01:07:27.220 --> 01:07:30.220 Second, maybe it's possible but it's weak and uninteresting 01:07:30.220 --> 01:07:31.220 Third, it's true and I told you so 01:07:31.220 --> 01:07:33.220 And the fourth one you can read 01:07:33.220 --> 01:07:35.220 Now there's another way of thinking about this 01:07:35.220 --> 01:07:39.220 And Lou Thomas, who was the director at Sloan Kettering in New York for many years 01:07:39.220 --> 01:07:40.220 was also 01:07:40.220 --> 01:07:44.220 Now he's quoting a director from Sloan Kettering 01:07:44.220 --> 01:07:47.220 Are you giving me, is this a joke? 01:07:48.220 --> 01:07:52.220 I mean what is happening here is this some kind of Christmas gift 01:07:52.220 --> 01:07:55.220 I never thought I would get to open what's going on 01:07:55.220 --> 01:07:57.220 There's another way of thinking about this 01:07:57.220 --> 01:08:00.220 And Lou Thomas, who was the director at Sloan Kettering in New York for many years 01:08:00.220 --> 01:08:02.220 was also a brilliant writer 01:08:02.220 --> 01:08:06.220 And in a book called Lives of the Cell in 1974 he wrote an essay about research 01:08:06.220 --> 01:08:08.220 And these are a couple paragraphs 01:08:08.220 --> 01:08:11.220 Somehow the atmosphere has to be set so that a disquieting sense of being wrong 01:08:11.220 --> 01:08:13.220 is the normal attitude of the investigators 01:08:13.220 --> 01:08:15.220 It has to be taken for granted that the only way in is by writing the 01:08:15.220 --> 01:08:17.220 unencumbered human imagination 01:08:17.220 --> 01:08:20.220 With a special rigor required for recognizing that something can be highly improbable 01:08:20.220 --> 01:08:23.220 May be almost impossible and at the same time true 01:08:23.220 --> 01:08:26.220 Locally, a good way to tell how the work is going is to listen in the corridors 01:08:26.220 --> 01:08:29.220 If you hear the word impossible, spoken with an expletive, followed by laughter 01:08:29.220 --> 01:08:32.220 You will know somebody's orderly research plan is coming along nicely 01:08:32.220 --> 01:08:34.220 Now that's a lot of words 01:08:34.220 --> 01:08:37.220 And if you're Winston Churchill you can describe all this in many fewer words 01:08:37.220 --> 01:08:39.220 This is 1936 in the House of Parliament 01:08:39.220 --> 01:08:42.220 He's talking about Hitler and evaluating the Rhineland 01:08:42.220 --> 01:08:44.220 And he says to Stanley Baldwin in the House of Commons 01:08:44.220 --> 01:08:46.220 Men occasionally stumble across the truth 01:08:46.220 --> 01:08:48.220 But most pick themselves up and hurry off as if nothing had happened 01:08:48.220 --> 01:08:50.220 And with that I'll end, thank you 01:08:50.220 --> 01:08:54.220 So the question is do prions trigger the immune system? 01:08:54.220 --> 01:08:55.220 And the answer is no 01:08:55.220 --> 01:08:59.220 And the reason that we think that they don't is that PRPC is present in all of us 01:08:59.220 --> 01:09:05.220 And we are tolerant to antibodies and also to immune cells that specifically recognize PRPC 01:09:05.220 --> 01:09:07.220 And there are very few regions on PRPC 01:09:07.220 --> 01:09:10.220 In fact we've not been able to identify any looking for more than ten years now 01:09:10.220 --> 01:09:13.220 That are present on PRPC to which antibodies are formed 01:09:13.220 --> 01:09:15.220 That are not present on PRPC 01:09:15.220 --> 01:09:18.220 We found others, as I told you about before, where a region is exposed on PRPC 01:09:18.220 --> 01:09:20.220 But now becomes buried in PRPC 01:09:20.220 --> 01:09:22.220 But that doesn't generate a new antigenic region 01:09:22.220 --> 01:09:25.220 Wow, think about how much of a claim that is 01:09:25.220 --> 01:09:28.220 That goes against everything that we know about the immune system 01:09:28.220 --> 01:09:34.220 That it can't make antibodies specific for prion protein scrappy 01:09:34.220 --> 01:09:37.220 It can only make antibodies that recognize both 01:09:37.220 --> 01:09:41.220 It can make antibodies that don't recognize prion scrappy 01:09:41.220 --> 01:09:42.220 But they don't 01:09:42.220 --> 01:09:45.220 That's an incredible claim, that is an abs 01:09:45.220 --> 01:09:48.220 And you heard me ask that question earlier in the talk 01:09:48.220 --> 01:09:51.220 Like why don't they make antibodies that I think I asked that in the first half 01:09:51.220 --> 01:09:53.220 Holy cow 01:09:53.220 --> 01:09:54.220 There can be an immune response 01:09:54.220 --> 01:09:57.220 And in fact a tremendous step forward in making all of these antibodies 01:09:57.220 --> 01:10:01.220 Was created when a collaborative study that we were involved in 01:10:01.220 --> 01:10:03.220 With Charles Weissman and Zurich produced knockout mice 01:10:03.220 --> 01:10:06.220 In which the prion protein gene of a mouse could be knocked out 01:10:06.220 --> 01:10:08.220 These mice are totally resistant to prion disease 01:10:08.220 --> 01:10:10.220 And when we immunize these mice 01:10:10.220 --> 01:10:16.220 So what does the prion protein do if you can knock the protein out and the mouse is fine? 01:10:16.220 --> 01:10:19.220 Because that's not true for very many proteins 01:10:19.220 --> 01:10:22.220 Strange, huh? 01:10:22.220 --> 01:10:25.220 With the prion protein they form huge numbers of antibodies 01:10:25.220 --> 01:10:29.220 In contrast to normal mice which form very few or no antibodies 01:10:29.220 --> 01:10:32.220 And if I'm no antibodies, if it's a mouse prion protein 01:10:32.220 --> 01:10:34.220 Are you hearing this shit? 01:10:34.220 --> 01:10:38.220 He's telling you that when that animal doesn't have that gene 01:10:38.220 --> 01:10:41.220 That they produce more antibodies to the prion protein 01:10:41.220 --> 01:10:46.220 Which makes them un-susceptible to the prion protein 01:10:49.220 --> 01:10:53.220 He's telling you that antibodies play a role in 01:10:58.220 --> 01:11:01.220 But they've been unable to generate antibodies to the prion protein 01:11:01.220 --> 01:11:03.220 That's specific for the prion protein 01:11:03.220 --> 01:11:08.220 They're just generating antibodies to the endogenous epitopes 01:11:08.220 --> 01:11:11.220 That are exposed in the endogenous form 01:11:11.220 --> 01:11:14.220 Do you see the hand waving is extraordinary? 01:11:14.220 --> 01:11:19.220 I do not believe the papers support these as being firm conclusions 01:11:19.220 --> 01:11:25.220 But it's extraordinary the kind of exceptional biology 01:11:25.220 --> 01:11:28.220 The number of exceptions that we need to make 01:11:28.220 --> 01:11:31.220 In order for this to be true 01:11:35.220 --> 01:11:37.220 Now is these mice with the prion protein 01:11:37.220 --> 01:11:39.220 They form huge numbers of antibodies 01:11:39.220 --> 01:11:42.220 In contrast to normal mice which form very few or no antibodies 01:11:42.220 --> 01:11:46.220 That is a absolute 01:11:46.220 --> 01:11:48.220 It's a mouse model of the disease 01:11:48.220 --> 01:11:51.220 That he's saying that if you don't have the prion protein 01:11:51.220 --> 01:11:54.220 Then you can make antibodies to the scraping protein 01:11:54.220 --> 01:11:56.220 And then you won't get it 01:11:56.220 --> 01:12:00.220 And so one of the reasons and the way to understand 01:12:00.220 --> 01:12:04.220 That this works is that we could respond to you here 01:12:04.220 --> 01:12:06.220 Wait, it's coming, you see 01:12:06.220 --> 01:12:10.220 They're going to treat prion disease with antibodies 01:12:10.220 --> 01:12:12.220 That's what he's proposing here 01:12:12.220 --> 01:12:15.220 And that we should use money and grant proposals 01:12:15.220 --> 01:12:19.220 To find the antibodies which we could use to fight prion disease 01:12:19.220 --> 01:12:21.220 Antibodies, you know antibodies 01:12:21.220 --> 01:12:24.220 The things that they fight all these other diseases with 01:12:24.220 --> 01:12:28.220 That they want to produce as the perfect 01:12:28.220 --> 01:12:32.220 Inject it in your soldiers and your immune for 30 days 01:12:32.220 --> 01:12:35.220 Kind of thing, it's a little cludgy but it works 01:12:35.220 --> 01:12:38.220 And if I'm no antibodies if it's a mouse prion protein 01:12:38.220 --> 01:12:40.220 If it's a human they might form one 01:12:40.220 --> 01:12:41.220 So the immune system 01:12:41.220 --> 01:12:45.220 So they could easily use an mRNA to generate the prion antibodies 01:12:45.220 --> 01:12:48.220 That they say are found in this mouse 01:12:48.220 --> 01:12:51.220 But aren't found in any animals that have the prion protein 01:12:51.220 --> 01:12:53.220 Then it would be a cell protein 01:12:53.220 --> 01:12:55.220 So, wow! 01:12:55.220 --> 01:12:57.220 Quiet in these diseases 01:12:57.220 --> 01:13:00.220 Well, alright, so the question is very technical 01:13:00.220 --> 01:13:03.220 Is the normal form of the prion protein the kinetic product 01:13:03.220 --> 01:13:05.220 Or a kinetically trapped molecule and that 01:13:05.220 --> 01:13:09.220 This scraping form is a thermodynamically more stable protein 01:13:09.220 --> 01:13:12.220 And the answer is probably yes, but we're not sure 01:13:12.220 --> 01:13:16.220 So the normal form of the prion protein is on the surface 01:13:16.220 --> 01:13:19.220 And that's where it's converted into PRP scraping 01:13:19.220 --> 01:13:21.220 And how much of it remains there we don't know 01:13:21.220 --> 01:13:24.220 In some experiments by Stevie Arman where he fractionates these cells 01:13:24.220 --> 01:13:27.220 So he grinds them up and looks for the membrane fraction that's found on the surface 01:13:27.220 --> 01:13:30.220 He finds as much as 60% of the scraping form 01:13:30.220 --> 01:13:33.220 The abnormal form is in the plasma membrane fraction 01:13:33.220 --> 01:13:36.220 Others suggest that it's much less than that, so I don't really know 01:13:36.220 --> 01:13:38.220 But he's probably right 01:13:38.220 --> 01:13:40.220 So the question is what is the mechanism of action of quinocrine? 01:13:40.220 --> 01:13:43.220 And how does it work on patients with CJD and new variants CJD? 01:13:43.220 --> 01:13:44.220 And the answer is we don't know 01:13:44.220 --> 01:13:46.220 Initially I thought what we should do is spend a lot of time 01:13:46.220 --> 01:13:48.220 Several years probably to track that down and understand it 01:13:48.220 --> 01:13:50.220 Before we would do anything further 01:13:50.220 --> 01:13:52.220 But when I realized that the concentrations were close 01:13:52.220 --> 01:13:54.220 Probably only off by a factor of 10 to 50 01:13:54.220 --> 01:13:56.220 From what an ideal drug would be 01:13:56.220 --> 01:13:59.220 We decided to spend a lot of effort starting giving this to people 01:13:59.220 --> 01:14:03.220 But we're also now slowly starting to investigate the mechanism of action 01:14:03.220 --> 01:14:05.220 I'm sure many other people are doing that too 01:14:05.220 --> 01:14:10.220 Alright, so TSE is a term called transmissible spongiform encephalopathy 01:14:10.220 --> 01:14:13.220 It's a term I don't particularly like, but maybe that's because other people use it all the time 01:14:13.220 --> 01:14:16.220 And the reason I don't like it is that many of these diseases 01:14:16.220 --> 01:14:18.220 There's very little spongiform change 01:14:18.220 --> 01:14:22.220 But this is a term that really refers to the diseases caused by prions specifically 01:14:22.220 --> 01:14:26.220 And the other neurodegenerative diseases are not classified as prion diseases 01:14:26.220 --> 01:14:29.220 Or as TSE diseases 01:14:29.220 --> 01:14:31.220 They're classified as neurodegenerative diseases 01:14:31.220 --> 01:14:33.220 For instance Alzheimer's disease is distinguished 01:14:33.220 --> 01:14:36.220 From the prion diseases by the fact that there's a different set of proteins that are involved 01:14:36.220 --> 01:14:39.220 And all attempts to really transmit the disease have failed so far 01:14:39.220 --> 01:14:42.220 That doesn't mean it won't be transmissible in the proper animal model 01:14:42.220 --> 01:14:44.220 But it's not transmissible in a natural setting 01:14:45.220 --> 01:14:47.220 See, they're trying to transmit it though 01:14:47.220 --> 01:14:49.220 Think about that for a second 01:14:53.220 --> 01:14:56.220 And why would they be doing that? Because they're testing this model 01:14:56.220 --> 01:15:00.220 Or they're trying to find examples that seem to indicate that this model would work 01:15:00.220 --> 01:15:02.220 How do they test it? They probably inject the shit 01:15:02.220 --> 01:15:04.220 It's crazy 01:15:04.220 --> 01:15:08.220 I don't know how the spongiform change comes about 01:15:08.220 --> 01:15:11.220 What we find is that the vacuals 01:15:12.220 --> 01:15:14.220 That the more prp scraper there is, the more vaculation there is 01:15:14.220 --> 01:15:16.220 So this is correlation between prp scrapers 01:15:16.220 --> 01:15:18.220 They want nothing to do with the immune system 01:15:18.220 --> 01:15:20.220 If they had anything to do with the immune system 01:15:20.220 --> 01:15:23.220 It's immediately a black box that they can't penetrate 01:15:23.220 --> 01:15:25.220 So they have to stay away from it 01:15:25.220 --> 01:15:29.220 How is the spongiform tissue phenotype formed? 01:15:29.220 --> 01:15:31.220 They don't know, of course it's the immune system 01:15:31.220 --> 01:15:34.220 Excuse me, prp scraped deposition and the vacuals that are formed 01:15:34.220 --> 01:15:37.220 But the mechanism by which the vacuals are formed, I don't understand 01:15:37.220 --> 01:15:40.220 Something happens to the signaling mechanisms in the cells 01:15:40.220 --> 01:15:43.220 And whether that happens because prp scrapes on the surface 01:15:43.220 --> 01:15:48.220 Or whether it's deep in the cell and it mucks up the signaling mechanisms 01:15:48.220 --> 01:15:50.220 I don't know, that's a very simplistic answer 01:15:50.220 --> 01:15:52.220 Who a very complicated question, but I can't answer it 01:15:52.220 --> 01:15:55.220 So the question is, what is the function of prp? 01:15:55.220 --> 01:15:58.220 We all have a gene for prp, we all make the protein, prpc 01:15:58.220 --> 01:16:01.220 And what is its function and the answer is we don't know its function 01:16:01.220 --> 01:16:03.220 And we don't know the function of its brother or sister, papal 01:16:03.220 --> 01:16:05.220 We just don't know 01:16:06.220 --> 01:16:13.220 No, so the question is, why is it that in Britain 01:16:13.220 --> 01:16:16.220 People with new variants CJD are in their teens and early 20s 01:16:16.220 --> 01:16:18.220 For the most part, and the answer is we don't have any idea 01:16:18.220 --> 01:16:22.220 For a long time I thought that this was really a clue to the fact that 01:16:22.220 --> 01:16:25.220 Disease was unconnected to the cows and that there was some other mechanism 01:16:25.220 --> 01:16:29.220 But I threw that idea away once we had all this transgenic mouse data 01:16:29.220 --> 01:16:32.220 And the answer is I don't have any idea why they're so young 01:16:32.220 --> 01:16:33.220 I just don't know 01:16:33.220 --> 01:16:35.220 One patient who's 70, another who's 50 01:16:35.220 --> 01:16:37.220 But the vast majority of these people are under 40 01:16:39.220 --> 01:16:43.220 So the first part of this question is, how did this all start in cows? 01:16:43.220 --> 01:16:47.220 And the second question is, how do prions make it through your brain from your gut? 01:16:47.220 --> 01:16:50.220 So how did prion disease start? 01:16:50.220 --> 01:16:54.220 And I think most people were reasonably well convinced that it began with sheep 01:16:54.220 --> 01:16:57.220 Because scrapes and stomach in Britain, it's been there for hundreds of years 01:16:57.220 --> 01:17:00.220 And it came from the sheep, but nobody knows the exact statistics 01:17:00.220 --> 01:17:03.220 People who are farmers tend to get rid of their animals when they're not doing well 01:17:03.220 --> 01:17:06.220 And the easiest way to get rid of them is to get them into the human food chain 01:17:06.220 --> 01:17:09.220 Not to burn them up, because they don't get any money for that 01:17:09.220 --> 01:17:13.220 So we don't know how many scrapes sheep enter the human food chain every year in Britain 01:17:13.220 --> 01:17:15.220 We have scrapes in the United States, too 01:17:15.220 --> 01:17:18.220 Then there was a huge inquiry which you can look up on the Internet 01:17:18.220 --> 01:17:22.220 If you have nothing better to do, there are 3,500 pages on this question of how to BSE start 01:17:22.220 --> 01:17:28.220 And what happened afterwards was an official inquiry that was created by Tony Blair 01:17:28.220 --> 01:17:31.220 And they only allowed the inquiry to go up to the day of his election 01:17:31.220 --> 01:17:35.220 So they could look at John Majors with severe eyes, but not at Tony Blair 01:17:35.220 --> 01:17:39.220 And that's what this does, it goes up to 1996, and it begins in the late 1970s 01:17:39.220 --> 01:17:41.220 In terms of questioning what happened 01:17:41.220 --> 01:17:46.220 And in that inquiry, you'll see that they think it began with a spontaneous or sporadic case of mad cow disease somewhere in southern England 01:17:46.220 --> 01:17:49.220 I don't think there's a lot of evidence for that, but that's what they hypothesized 01:17:49.220 --> 01:17:52.220 So prions are resisted to proteases, as I showed you, or enzyme digestion 01:17:52.220 --> 01:17:54.220 Which is what happens to proteins when they enter your gut 01:17:54.220 --> 01:17:59.220 If we take animals and we do a study, we find that we need about a billion times more prions 01:17:59.220 --> 01:18:03.220 When they're ingested, then if you put a needle in the head of the animal and inject them directly into the brain 01:18:03.220 --> 01:18:06.220 I thought it was one protein is all you needed, that's weird 01:18:06.220 --> 01:18:12.220 But nevertheless, if we give the animals enough, we give them a billion times more, orally, and they all get sick 01:18:12.220 --> 01:18:14.220 And so we presume the prions now cross the gut 01:18:14.220 --> 01:18:17.220 If we give them a billion times more, he said, that's hilarious 01:18:17.220 --> 01:18:19.220 Probably in the small intestine 01:18:19.220 --> 01:18:24.220 And that they multiply in lymphoid cells, and then they go through the brain 01:18:24.220 --> 01:18:25.220 Through the blood 01:18:25.220 --> 01:18:28.220 The other way we think they can make it to the brain is that they travel backwards 01:18:28.220 --> 01:18:32.220 Up the nerves of the gut, called the spinaic nerve bed, into the spinal cord 01:18:32.220 --> 01:18:36.220 And then up the spinal cord to the brain 01:18:36.220 --> 01:18:40.220 Question is, how do you disinfect scalpels and other medical instruments 01:18:40.220 --> 01:18:44.220 Because there have been cases where CJD has been transmitted from one patient to another 01:18:44.220 --> 01:18:46.220 By this route 01:18:46.220 --> 01:18:52.220 And what I was about to say was that it's very difficult to properly disinfect instruments 01:18:52.220 --> 01:18:54.220 And we're working on this now very hard 01:18:54.220 --> 01:18:56.220 I guess we have some new approaches that seem to be very useful 01:18:56.220 --> 01:18:57.220 And I'm very... 01:18:57.220 --> 01:18:58.220 Sure, they'll be patentable 01:18:58.220 --> 01:19:01.220 I'm very encouraged that soon we'll be able to do this in a much better way 01:19:01.220 --> 01:19:02.220 And it's commonly done 01:19:02.220 --> 01:19:04.220 Fortunately, the number of examples of that is still small 01:19:04.220 --> 01:19:09.220 But as the number of surgical procedures keeps increasing every year, this may become a bigger and bigger problem 01:19:09.220 --> 01:19:10.220 Hopefully we can stop it 01:19:10.220 --> 01:19:14.220 The question was, how do these poor cannibals in New Guinea keep on perpetuating their society 01:19:14.220 --> 01:19:18.220 Because if they keep eating each other and they keep getting sick with Peru, aren't they all going to die out? 01:19:18.220 --> 01:19:22.220 And the answer is that in the late 1950s, as this was starting to... 01:19:22.220 --> 01:19:25.220 At that point, in fact, Peru was the most common cause of death in women 01:19:25.220 --> 01:19:27.220 This was a society that all men would like to have lived in 01:19:27.220 --> 01:19:29.220 Because they never had to do anything, women did absolutely everything 01:19:29.220 --> 01:19:34.220 And at that point, the most common cause of death in women was Peru 01:19:34.220 --> 01:19:37.220 And they died in their 30s 01:19:37.220 --> 01:19:39.220 They virtually never made it to age 40 01:19:39.220 --> 01:19:42.220 So we had generations of young people who were motherless 01:19:42.220 --> 01:19:45.220 And it was in the late 1950s that two things happened 01:19:45.220 --> 01:19:49.220 One of the missionaries who began to colonize that area told them that nice people don't eat their relatives 01:19:49.220 --> 01:19:50.220 Whether they're dead or alive 01:19:50.220 --> 01:19:55.220 And these people were eating their dead relatives to really immortalize them 01:19:55.220 --> 01:19:59.220 This was their way of immortalizing them through taking their soul, which they believed was in the brain, not in the heart 01:19:59.220 --> 01:20:02.220 And the second thing that happened was that the Australian authorities 01:20:02.220 --> 01:20:06.220 Who now began to occupy the Highlands of New Guinea, which up until the late 1940s 01:20:06.220 --> 01:20:09.220 Had not seen any Western people 01:20:09.220 --> 01:20:12.220 And began to occupy that area and they outlawed cannibalism 01:20:12.220 --> 01:20:14.220 So that's how these tribes have now survived 01:20:14.220 --> 01:20:19.220 And so what you basically have here is very 01:20:19.220 --> 01:20:21.220 Let's say 01:20:21.220 --> 01:20:28.220 Outland, outlier examples of where protein misfolding can go wrong 01:20:28.220 --> 01:20:37.220 And it's usually an autoimmune reaction to exposure to proteins that would normally not be exposed to your systemic 01:20:38.220 --> 01:20:40.220 systemic immune system 01:20:41.220 --> 01:20:46.220 And so I don't know exactly how to draw it out on a piece of paper 01:20:46.220 --> 01:20:50.220 But it makes sense to me that this phenomenon, however rare it was 01:20:50.220 --> 01:20:55.220 Would be something that you would want to understand from the perspective of how ribosomes function 01:20:55.220 --> 01:20:58.220 From the perspective of protein folding 01:20:58.220 --> 01:21:03.220 And from the perspective of wanting to alter the function of proteins 01:21:03.220 --> 01:21:06.220 And knowing how to stay away from this potential danger 01:21:07.220 --> 01:21:12.220 So if there's anything that's dual use, it is the research into prions 01:21:12.220 --> 01:21:20.220 Because this is the sort of worst case scenario that in the situation where women are eating their dead relatives 01:21:20.220 --> 01:21:23.220 And they're eating their brain that occasionally you get this 01:21:23.220 --> 01:21:28.220 And more often you get this generated and it could be something to do with this phenomenon 01:21:29.220 --> 01:21:34.220 Could also be something to do with an immune reaction to that consumption 01:21:34.220 --> 01:21:40.220 An immune reaction that occurs in the gut in the place where tolerance is normally built 01:21:43.220 --> 01:21:48.220 And you could have a situation where something happens where that immune response is thrown off kilter 01:21:48.220 --> 01:21:55.220 Because self-antigens are present where they shouldn't be present, i.e. in the gut 01:21:58.220 --> 01:22:02.220 And so we're throwing out, there's no role for the immune system at all 01:22:02.220 --> 01:22:08.220 There's no role at all, and in fact, there's so no role at all 01:22:08.220 --> 01:22:14.220 That the picture that we were looking at earlier had no role for the immune system either 01:22:14.220 --> 01:22:18.220 This is just something that right, it just starts occurring 01:22:18.220 --> 01:22:21.220 And it was happening 01:22:21.220 --> 01:22:23.220 No 01:22:23.220 --> 01:22:25.220 Damn it 01:22:25.220 --> 01:22:28.220 Clicked on the frickin slide, sorry 01:22:32.220 --> 01:22:34.220 That there's no immune system here, right? 01:22:39.220 --> 01:22:44.220 There's no immune system here, this is just proteins doing their protein thing 01:22:46.220 --> 01:22:49.220 Sell the cell spread by nanotunnels 01:22:50.220 --> 01:22:55.220 Person to person spread by instruments, what he was talking about here, right there it is 01:22:56.220 --> 01:22:58.220 But 01:22:59.220 --> 01:23:05.220 There's no, he said earlier in the talk that they don't think that prions activate the immune system 01:23:06.220 --> 01:23:08.220 So the immune system does nothing 01:23:09.220 --> 01:23:11.220 Think about that 01:23:12.220 --> 01:23:14.220 If the immune system 01:23:14.220 --> 01:23:22.220 Memorizes damage-associated patterns and the immune system better dang well recognize a protein that could fold other proteins wrong 01:23:22.220 --> 01:23:27.220 That can cause protein aggregation, aggregates that are non-degradable 01:23:29.220 --> 01:23:31.220 It's interesting, right? 01:23:31.220 --> 01:23:36.220 And what did he say was the immune response that was so interesting in those knockout mice? Antibodies 01:23:37.220 --> 01:23:40.220 It's absolutely positively immunomythology 01:23:46.220 --> 01:23:48.220 I eat meat 01:23:48.220 --> 01:23:50.220 The question was do I eat meat? 01:23:50.220 --> 01:23:53.220 And I said yes, and then Alan chimed in with do I eat meat in England? 01:23:53.220 --> 01:23:55.220 And the answer is not now 01:24:00.220 --> 01:24:03.220 There's been a lot of discussion about this, there are no assets 01:24:03.220 --> 01:24:06.220 So the question is, is there any screening for blood or blood products? 01:24:06.220 --> 01:24:09.220 And right now there's no reliable assay for prions in blood 01:24:10.220 --> 01:24:15.220 And so what was done by the FDA was to first, about four years ago, put it into an effect 01:24:15.220 --> 01:24:21.220 If you had lived in the UK for six months or more, you could not get blood in the United States 01:24:21.220 --> 01:24:24.220 And then last year, this was reduced to three months 01:24:24.220 --> 01:24:28.220 And then it was something on the order of three years or four years for the rest of Europe 01:24:28.220 --> 01:24:30.220 So this is a cumulative time that you've spent 01:24:30.220 --> 01:24:32.220 And you get asked these questions when you get blood 01:24:32.220 --> 01:24:36.220 And so basically what has happened is that we've seeded a narrative about this potential 01:24:36.220 --> 01:24:42.220 We've seeded a narrative where it could be 60 days or it could be 40 years before 01:24:42.220 --> 01:24:45.220 The consequences of you eating contaminated meat 01:24:45.220 --> 01:24:51.220 Or the consequences of you being exposed to some farmland or you being exposed to the wrong blood 01:24:51.220 --> 01:24:56.220 Could result in symptomatic CJD or something related to it 01:24:56.220 --> 01:24:58.220 Alzheimer's disease, this kind of thing 01:24:59.220 --> 01:25:05.220 And he's being very imprecise on purpose trying to group them all together 01:25:05.220 --> 01:25:08.220 Has they're all related to protein misfolding? 01:25:08.220 --> 01:25:12.220 Yet some stories involve induction of the protein 01:25:12.220 --> 01:25:18.220 Others involve degradation and production and the rate limiting steps 01:25:18.220 --> 01:25:25.220 Somehow outweighing the takeover and eventually the bad protein outweighs the good protein 01:25:25.220 --> 01:25:27.220 And then you get the disease state 01:25:27.220 --> 01:25:33.220 Now testing those two ideas and how they're contradicting one another or they're mutually exclusive 01:25:33.220 --> 01:25:35.220 But okay 01:25:37.220 --> 01:25:43.220 One involves an tremendous amount of sort of hand waving with regard to the structure 01:25:43.220 --> 01:25:48.220 And function relationship between the sequence of a protein and its tertiary structure 01:25:48.220 --> 01:25:52.220 And its function, which we don't know yet 01:25:55.220 --> 01:26:00.220 It's an extraordinary biology that we're listening to 01:26:00.220 --> 01:26:03.220 So a lot of interest at the level of the FDA and drug companies 01:26:03.220 --> 01:26:09.220 To carry out analyses of their methods when they produce a biological such as 01:26:09.220 --> 01:26:12.220 Let me give you an example, TPA for heart attacks 01:26:12.220 --> 01:26:16.220 Are perceptin for cancer treatment, these are biologics that are produced in cells 01:26:16.220 --> 01:26:18.220 And when these kinds of drugs are produced 01:26:18.220 --> 01:26:22.220 There's a lot of interest in analyzing whether there's any possibility that prions could be carried along with them 01:26:22.220 --> 01:26:25.220 So this is going on now 01:26:25.220 --> 01:26:28.220 Some thought about prions and schizophrenia 01:26:28.220 --> 01:26:32.220 I think that we're going to see many, many more diseases that are due to these changes in protein shape 01:26:32.220 --> 01:26:33.220 Of course! 01:26:33.220 --> 01:26:36.220 Every disease from which we have no understanding is right for such a possibility 01:26:36.220 --> 01:26:37.220 Of course! 01:26:37.220 --> 01:26:39.220 I think one can't speculate with any certainty 01:26:39.220 --> 01:26:41.220 But I love to speculate 01:26:41.220 --> 01:26:45.220 Okay, so could I talk more about how understanding prions would be used 01:26:45.220 --> 01:26:48.220 Can benefit an understanding of Alzheimer's disease? 01:26:48.220 --> 01:26:52.220 So if one understands any of these degenerative diseases in great detail 01:26:52.220 --> 01:26:54.220 The implications for understanding the others are immense 01:26:54.220 --> 01:26:58.220 They're immense in terms of new ways of thinking about the control of protein shape 01:26:58.220 --> 01:27:01.220 And the control of protein processing going from a normal form to an abnormal form 01:27:01.220 --> 01:27:02.220 Do you understand? 01:27:02.220 --> 01:27:05.220 We're talking about protein processing and protein folding 01:27:05.220 --> 01:27:07.220 We're not talking about anything else 01:27:07.220 --> 01:27:11.220 And so this is an excuse to understand aberrant forms of it 01:27:11.220 --> 01:27:15.220 It's an excuse to induce aberrant forms of it 01:27:15.220 --> 01:27:20.220 And explore the possibility of harnessing that in a biological weapon scenario 01:27:20.220 --> 01:27:23.220 Avoiding it in a gene therapy scenario 01:27:23.220 --> 01:27:28.220 Avoiding it in a transfection or transformation scenario going forward 01:27:28.220 --> 01:27:32.220 That's what this is on its surface and at its heart 01:27:32.220 --> 01:27:37.220 It's all the same operation to get you to accept a gene therapy 01:27:37.220 --> 01:27:40.220 And the consequences of it 01:27:41.220 --> 01:27:48.220 And to think that there is a reflected natural threat that has an analog 01:27:48.220 --> 01:27:52.220 So every single thing that they thought that was going to happen 01:27:52.220 --> 01:27:57.220 As a result of transforming and transfecting humans in a medical way 01:27:57.220 --> 01:28:00.220 Using CRISPR or whatever all this shit is 01:28:00.220 --> 01:28:05.220 They've got to convince you that there is a natural way for these disasters to occur 01:28:06.220 --> 01:28:09.220 A natural way for this disease cascade to exist 01:28:09.220 --> 01:28:11.220 So that when it finally came 01:28:13.220 --> 01:28:17.220 And maybe we're here right now in 2024-2025-2026 01:28:17.220 --> 01:28:19.220 They know it's coming 01:28:21.220 --> 01:28:24.220 They had to tie it to the virus to the spike 01:28:24.220 --> 01:28:29.220 So that they could absolve transfection as a methodology 01:28:29.220 --> 01:28:33.220 Even though they were seeding it this far back probably because they knew 01:28:36.220 --> 01:28:40.220 Or let's say it's very possible that they knew 01:28:40.220 --> 01:28:43.220 And that's why this guy is so confident that this 01:28:43.220 --> 01:28:47.220 Wide net that he's casting that we can understand one mechanism 01:28:47.220 --> 01:28:51.220 We understand all the mechanisms and protein folding and folding and folding 01:28:51.220 --> 01:28:56.220 Remember the lady Susan Lindquist from MIT that we've been listening to 01:28:56.220 --> 01:28:58.220 Over the last few weeks as well 01:28:58.220 --> 01:29:02.220 That lady was working in the same department as Venki 01:29:02.220 --> 01:29:04.220 Rosham-Shami 01:29:04.220 --> 01:29:08.220 Whatever the guy that Mark has done a couple programs on that has done 01:29:08.220 --> 01:29:12.220 Got the Nobel Prize for the ribosome 01:29:12.220 --> 01:29:20.220 These are all in the same small group of people trying to figure out how the machinery of a cell works 01:29:20.220 --> 01:29:22.220 How the machinery on DNA works 01:29:22.220 --> 01:29:29.220 How DNA to RNA to protein can be understood and harnessed and hijacked 01:29:32.220 --> 01:29:35.220 And so they talk a mean game about how much we understand 01:29:35.220 --> 01:29:37.220 But we don't understand this stuff like this 01:29:37.220 --> 01:29:40.220 And I'm learning a lot from this 01:29:40.220 --> 01:29:44.220 Accumulating an abnormal form, causing as we had questions before 01:29:44.220 --> 01:29:46.220 About how do these changes in protein shape 01:29:46.220 --> 01:29:49.220 And then manifest themselves in neurologic signs and symptoms 01:29:49.220 --> 01:29:52.220 Decrease thinking, decrease memory, inability to walk 01:29:52.220 --> 01:29:55.220 What is the process by which this goes on? We have no idea 01:29:55.220 --> 01:29:57.220 And so what we're seeing is 01:29:57.220 --> 01:30:01.220 We have no idea, he couldn't at least say we think it's the immune system 01:30:01.220 --> 01:30:05.220 Seriously? It's kind of sad 01:30:05.220 --> 01:30:09.220 Why is it sad? Because once you invoke the immune system 01:30:09.220 --> 01:30:11.220 Your protein 01:30:11.220 --> 01:30:16.220 Your protein is no longer the center 01:30:16.220 --> 01:30:20.220 It's no longer a target 01:30:20.220 --> 01:30:22.220 It's no longer a toy 01:30:22.220 --> 01:30:24.220 It's no longer a thing that you have 01:30:24.220 --> 01:30:28.220 That you have intellectual property rights over 01:30:28.220 --> 01:30:31.220 Instead, now you're going into the immune system 01:30:31.220 --> 01:30:33.220 Where antibodies dominate 01:30:33.220 --> 01:30:35.220 Where we can't study T cells 01:30:35.220 --> 01:30:40.220 T cells are so hard to study that Christian Anderson decided to drop out of that 01:30:40.220 --> 01:30:43.220 PhD and go into infectious diseases instead 01:30:43.220 --> 01:30:47.220 He told that story on Twiv in 2021 01:30:47.220 --> 01:30:50.220 It's hilarious these people 01:30:50.220 --> 01:30:52.220 As more and more information 01:30:52.220 --> 01:30:55.220 Anything to stay away from the sacred biology 01:30:55.220 --> 01:30:58.220 That irreducible complexity, stay far away from it 01:30:58.220 --> 01:31:01.220 And go somewhere where it's only smoke and mirrors 01:31:01.220 --> 01:31:03.220 Like infectious diseases 01:31:03.220 --> 01:31:05.220 It comes from all these neurodegenerative diseases 01:31:05.220 --> 01:31:06.220 About them and the mechanisms 01:31:06.220 --> 01:31:08.220 We're going to see more and more cross fertilization 01:31:08.220 --> 01:31:11.220 The prion diseases have the advantages that we know much more about prions 01:31:11.220 --> 01:31:13.220 Than we do about the process of Alzheimer's disease 01:31:13.220 --> 01:31:14.220 We have much better animal models 01:31:14.220 --> 01:31:16.220 These transgenic or genetically... 01:31:16.220 --> 01:31:19.220 I am really upset with the disease, the use of the word disease 01:31:19.220 --> 01:31:21.220 Because it's super annoying 01:31:21.220 --> 01:31:26.220 We shouldn't have infectious disease 01:31:26.220 --> 01:31:29.220 And then genetic disease 01:31:29.220 --> 01:31:32.220 It should be genetic disorder 01:31:32.220 --> 01:31:35.220 Protein folding disorder 01:31:35.220 --> 01:31:40.220 Malaria disease 01:31:40.220 --> 01:31:41.220 Something like that 01:31:41.220 --> 01:31:43.220 I don't like this, but that's the way we do it 01:31:43.220 --> 01:31:46.220 And it's frustrating, but it's biologically confusing 01:31:46.220 --> 01:31:49.220 And biologically imprecise 01:31:49.220 --> 01:31:52.220 Near mice reproduce every aspect of a prion disease 01:31:52.220 --> 01:31:55.220 Of humans, of a cow, depending on what gene we express in the mouse 01:31:55.220 --> 01:32:00.220 And so we have tools with prion diseases that we don't have with any of the other diseases 01:32:00.220 --> 01:32:03.220 And I think if we're successful in the therapy and prion disease 01:32:03.220 --> 01:32:06.220 This will generate an enormous interest in the drug companies 01:32:06.220 --> 01:32:08.220 As well as the governments as well as foundations throughout the world 01:32:08.220 --> 01:32:12.220 But enormous amounts more money into solving a problem like Alzheimer's disease 01:32:12.220 --> 01:32:16.220 Anybody's, anybody's for amyloid beta 01:32:16.220 --> 01:32:19.220 I mean, it's hilarious how naive he sounds here 01:32:19.220 --> 01:32:22.220 Because we have, of course, the benefit of 22 years of research 01:32:22.220 --> 01:32:25.220 But it's very, very funny 01:32:25.220 --> 01:32:28.220 How naive he sounds here 01:32:28.220 --> 01:32:32.220 I'm so excited about these antibodies as therapeutics 01:32:32.220 --> 01:32:34.220 And also as bench tools 01:32:34.220 --> 01:32:37.220 And even structural dissection tools 01:32:37.220 --> 01:32:42.220 It's hilarious how naive he is to what he's using as tools 01:32:42.220 --> 01:32:47.220 Anybody's for a long time have played various roles like this 01:32:47.220 --> 01:32:54.220 That lots and lots of academic biologists are unaware of the huge, huge grey area 01:32:54.220 --> 01:32:57.220 That they've been playing with unless they've been using the proper controls 01:32:57.220 --> 01:33:02.220 Which is a growing and growing problem because of the change in demography of our populations 01:33:02.220 --> 01:33:06.220 When you're 85 years old, you have a one and three chance of having Alzheimer's disease 01:33:06.220 --> 01:33:09.220 And as we have more and more people who become octogenarians 01:33:09.220 --> 01:33:12.220 The number of people without Alzheimer's diseases that keep going up 01:33:12.220 --> 01:33:14.220 Other questions? 01:33:14.220 --> 01:33:17.220 So the question is, in late onset muscular dystrophies 01:33:17.220 --> 01:33:22.220 Where they have these mutations that expand the size of the protein 01:33:22.220 --> 01:33:25.220 Or sometimes don't expand the size of the protein but expand the gene 01:33:25.220 --> 01:33:27.220 Are there similarities? And the answer is yes 01:33:27.220 --> 01:33:30.220 One of the diseases I put up, but I didn't talk about was Huntington's disease 01:33:30.220 --> 01:33:32.220 And then I put up some of the spinal cerebellar ataxios 01:33:32.220 --> 01:33:35.220 And these diseases have these same kinds of expanded repeats 01:33:35.220 --> 01:33:39.220 And the answer is, I think we're talking about many similar phenomena 01:33:39.220 --> 01:33:41.220 Now in these cases, these are all inherited diseases 01:33:41.220 --> 01:33:43.220 So it's only the genetic form of disease 01:33:43.220 --> 01:33:48.220 But we have no understanding of why it is that these diseases have such a late onset 01:33:48.220 --> 01:33:51.220 What is clear is that the bigger the repeat, the earlier the onset 01:33:51.220 --> 01:33:54.220 But then all of that has to be qualified by many other factors 01:33:54.220 --> 01:33:57.220 That shift these curves up and down with respect to the repeats 01:33:57.220 --> 01:34:00.220 In the prion diseases, we have absolutely no understanding why it is that 01:34:00.220 --> 01:34:03.220 A single mutation, meaning one amino acid has changed 01:34:03.220 --> 01:34:07.220 Some members of the family, the same family, are 40 years old when they get the disease 01:34:07.220 --> 01:34:09.220 And others are 80 or 90 years old 01:34:11.220 --> 01:34:15.220 It's more likely to be exposure to a toxin or some other trigger than 01:34:15.220 --> 01:34:22.220 Rather than a disease process that's like a ticking clock or a degradation against production rate 01:34:22.220 --> 01:34:26.220 So again, the model makes predictions but he doesn't bother to test him 01:34:26.220 --> 01:34:29.220 He doesn't even bother to list the options that he sees 01:34:29.220 --> 01:34:31.220 It's really disingenuous 01:34:32.220 --> 01:34:35.220 The question is about these areas where PRPC is converted into PRPC scraping 01:34:35.220 --> 01:34:37.220 On the surface of the cell, these cholesterol-rich micro-domains 01:34:37.220 --> 01:34:41.220 One of the reasons we know they're cholesterol-rich is that with low estatin and other drugs 01:34:41.220 --> 01:34:44.220 We can completely abolish the formation of PRPC scraping 01:34:44.220 --> 01:34:47.220 Now we can't give that drug in high enough concentrations to humans 01:34:47.220 --> 01:34:49.220 Because we would dissolve the human 01:34:49.220 --> 01:34:53.220 The cells are not very happy in these very high concentrations of low estatin 01:34:53.220 --> 01:34:57.220 These are very important regions, these cholesterol-rich micro-domains are rafts 01:34:57.220 --> 01:34:59.220 That people have been studying only for the last few years 01:34:59.220 --> 01:35:01.220 They seem to coalesce and form caves or cabbioli 01:35:01.220 --> 01:35:03.220 And we really don't understand their function 01:35:03.220 --> 01:35:05.220 But there are more and more studies in this area 01:35:05.220 --> 01:35:08.220 And I think as time goes on we'll understand much more about them 01:35:12.220 --> 01:35:16.220 So the way the protein is multiplying is that we're seeing new PRPC being made all the time 01:35:16.220 --> 01:35:18.220 And then it's being degraded 01:35:18.220 --> 01:35:23.220 But about 5% of it in a scraping-infected cell is being bled off into the formation of new PRPC scraping 01:35:23.220 --> 01:35:28.220 And the old PRPC scraping, the existing PRPC scraping, drives the formation of new PRPC scraping 01:35:28.220 --> 01:35:30.220 See, he's saying it like he knows 01:35:30.220 --> 01:35:34.220 He's saying it like they have all these high fidelity images of it happening in a time-lapse photograph 01:35:34.220 --> 01:35:38.220 With stains that show everything and can double-dip control 01:35:38.220 --> 01:35:42.220 And it's just ridiculous, it's still just that cartoon 01:35:42.220 --> 01:35:47.220 It's still just a series of assumptions that haven't been confirmed by much other than that they can 01:35:47.220 --> 01:35:50.220 Sometimes see a fraction that's degradable and sometimes not 01:35:50.220 --> 01:35:51.220 Ting is multiplying 01:35:51.220 --> 01:36:00.220 So again, that's the same answer that I gave of question is what's the relationship of scraping to Parkinson's disease? 01:36:00.220 --> 01:36:04.220 So the same answer that I gave about the relationship of pre-owned research 01:36:04.220 --> 01:36:07.220 To Alzheimer's disease is the answer to what is the relationship to Parkinson's disease 01:36:07.220 --> 01:36:10.220 As we learn more about all of the processes that occur in 01:36:10.220 --> 01:36:14.220 So that kind of already helps you understand why it's a little ridiculous 01:36:14.220 --> 01:36:20.220 That people with regard to the spike protein will flip-flop between it being amyloidogenic 01:36:20.220 --> 01:36:22.220 And it being pre-anagenic 01:36:22.220 --> 01:36:26.220 Because as he's telling you right now, they're different proteins 01:36:26.220 --> 01:36:31.220 They're likely different mechanisms, they're likely different causes 01:36:31.220 --> 01:36:35.220 We just think that one might help us think about the other one 01:36:35.220 --> 01:36:39.220 There's no reason to believe if the protein is completely different 01:36:39.220 --> 01:36:43.220 That the mechanism is that all related and yet somehow or another 01:36:44.220 --> 01:36:48.220 These amateur hour worst case scenario 01:36:48.220 --> 01:36:54.220 Whitting or unwitting narrative pushers from 2020 01:36:54.220 --> 01:36:59.220 Have been interchangeably using the word pre-anagenic and amyloidogenic 01:36:59.220 --> 01:37:01.220 As though they're kind of just synonyms 01:37:01.220 --> 01:37:06.220 When here's the Nobel Prize winner telling you they are definitely not 01:37:07.220 --> 01:37:14.220 In scrapie, in the pre-owned diseases, those will translate into learning much more about Parkinson's disease 01:37:14.220 --> 01:37:17.220 In Parkinson's disease, there is a protein called alpha-synuclein 01:37:17.220 --> 01:37:19.220 Which is normally made in all of us 01:37:19.220 --> 01:37:23.220 And when the disease occurs, or even long before the disease occurs 01:37:23.220 --> 01:37:26.220 Alpha-synuclein is being mishandled, improperly handled 01:37:26.220 --> 01:37:29.220 It starts accumulating not outside the cell as big plaques 01:37:29.220 --> 01:37:32.220 But inside the cell as what are called lewy bodies 01:37:32.220 --> 01:37:34.220 And specifically in the cells of the substantia nigra 01:37:34.220 --> 01:37:37.220 Which are the cells that die out in Parkinson's disease 01:37:37.220 --> 01:37:40.220 So there is a PRP in birds, it's very much different than mammalian PRP 01:37:40.220 --> 01:37:44.220 And whether birds have pre-owned diseases, I don't know 01:37:44.220 --> 01:37:49.220 So the question is, are there cases of CJD where it's come from a vaccine 01:37:49.220 --> 01:37:51.220 Or it's come from a blood transfusion 01:37:51.220 --> 01:37:54.220 There are several cases where there have been blood transfusions 01:37:54.220 --> 01:37:56.220 But one can't be sure that it either came from the blood transfusion 01:37:56.220 --> 01:37:58.220 Or it was simply a sporadic case of CJD 01:37:58.220 --> 01:38:01.220 And the same thing's true of a couple of vaccine cases 01:38:01.220 --> 01:38:03.220 But the problem is everybody's vaccinated 01:38:03.220 --> 01:38:06.220 And so we can't really make any relationship there 01:38:06.220 --> 01:38:09.220 So the question is, since ALS is a relatively rare disease 01:38:09.220 --> 01:38:11.220 Is there much research being done here at UCSF? 01:38:11.220 --> 01:38:13.220 And the answer is that 01:38:13.220 --> 01:38:15.220 There's a small amount of research being done here 01:38:15.220 --> 01:38:16.220 But it's significant 01:38:16.220 --> 01:38:18.220 And we have a clinical center and in that clinical center 01:38:18.220 --> 01:38:20.220 We're trying to get much more information 01:38:20.220 --> 01:38:24.220 And our hope is to expand ALS research in the near future 01:38:24.220 --> 01:38:28.220 You stand on behalf of many men, thank you so much 01:38:28.220 --> 01:38:32.220 Thanks guys 01:38:32.220 --> 01:38:36.220 I hope you found that useful 01:38:36.220 --> 01:38:42.220 I hope you find it definitely a little bit useful 01:38:42.220 --> 01:38:45.220 Please stop transfection in humans 01:38:45.220 --> 01:38:48.220 They are trying to eliminate the control group 01:38:48.220 --> 01:38:52.220 Especially in the old people, don't let those over 50 in your life 01:38:52.220 --> 01:38:55.220 Take any vaccine advice from their doctor 01:38:55.220 --> 01:39:00.220 Intramuscular injection of any combination of substances with the intent of augmenting the healthy immune system 01:39:00.220 --> 01:39:04.220 Of your friends, your relatives, your neighbors 01:39:04.220 --> 01:39:05.220 It's dumb 01:39:05.220 --> 01:39:10.220 Transfection in healthy humans is criminally negligent in RNA camp pandemic 01:39:15.220 --> 01:39:17.220 Mark got a new Lego train 01:39:17.220 --> 01:39:19.220 But it's wheels don't turn 01:39:19.220 --> 01:39:21.220 It's kind of annoying 01:39:22.220 --> 01:39:26.220 I don't see if there's any dinner left over for me 01:39:26.220 --> 01:39:28.220 Thank you very much for joining me 01:39:28.220 --> 01:39:31.220 Ladies and gentlemen, these are the people that support giggle and biological 01:39:31.220 --> 01:39:33.220 If your name's not up here yet 01:39:33.220 --> 01:39:36.220 It might be because I haven't updated the list in a little while 01:39:36.220 --> 01:39:39.220 Or it might be because you are not yet a subscriber 01:39:39.220 --> 01:39:42.220 And if you'd like to be, you can go to giggleandbiological.com 01:39:42.220 --> 01:39:45.220 And you can find a lot of different ways to set up a one time 01:39:45.220 --> 01:39:49.220 Or even monthly donation to our work 01:39:49.220 --> 01:39:53.220 Actually, as I left this play 01:39:53.220 --> 01:39:57.220 I'm going to cut over to the desk 01:39:57.220 --> 01:40:02.220 And I got a card from New Mexico today 01:40:02.220 --> 01:40:06.220 Thanks very much Christy, it made it 01:40:06.220 --> 01:40:10.220 And thanks for the grocery money 01:40:10.220 --> 01:40:13.220 You know, like every little bit counts 01:40:13.220 --> 01:40:15.220 And this is not a little bit, so thanks a lot 01:40:15.220 --> 01:40:17.220 Christy, thanks a lot 01:40:19.220 --> 01:40:22.220 See you guys again tomorrow