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4034 lines
126 KiB
4034 lines
126 KiB
WEBVTT
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00:30.000 --> 00:32.000
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You
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01:00.000 --> 01:02.000
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I
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01:21.560 --> 01:24.520
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Guess I didn't update the stream. Yes, this is part two
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01:25.360 --> 01:30.040
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I'll update the title later. I guess I thought I updated it here on my OBS
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01:30.040 --> 01:36.440
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But I guess I didn't push the button done and so that it did not date my bad. This is part two. I
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01:41.160 --> 01:43.160
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Shall do it
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01:54.520 --> 01:59.480
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I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario
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01:59.480 --> 02:04.080
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I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario
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02:24.520 --> 02:26.520
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I
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02:38.680 --> 02:44.280
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Think truth is good for kids. We're so busy lying. We don't even recognize the truth no more than society
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We want everybody to feel good. That's not that's not the way life is
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02:55.520 --> 03:00.840
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We should be okay here. I'm just gonna check this one. So I'm back from the gym
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03:00.840 --> 03:03.080
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I thought I'd get part two done before tomorrow
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03:04.080 --> 03:11.200
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We're eventually gonna be doing a show a day or two shows a day one at 10 10 and one at 13 13
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03:12.120 --> 03:13.960
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So at 10 o'clock and one o'clock
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But you know we got to roll slowly here and make sure that we we build this momentum
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03:20.400 --> 03:25.960
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Intelligently and one of the things we're trying to build momentum around is this whole pre-on biology stuff
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03:26.320 --> 03:31.520
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And there's a there's a lot to learn and so we were gonna finish the video that we started earlier
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03:31.520 --> 03:34.720
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Thank you very much for being here. See you in a second
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This episode is sponsored by mink that's moo plus like
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03:41.520 --> 03:43.520
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Mm-hmm
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03:45.520 --> 03:53.080
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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
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03:53.160 --> 03:58.480
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Put that into getting everybody to take hypermectin and fluvoxamine for for a month
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03:58.800 --> 04:02.720
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If we and if we could accomplish that then COVID would be wiped out
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04:02.720 --> 04:08.120
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We could do it and actually any municipality that could regulate its borders could clear the disease
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04:11.520 --> 04:15.840
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But you can tell if someone's lying, you know, you can sort of feel it in people
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04:17.160 --> 04:20.240
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And I have lied. I'm sure I'll lie again. I don't want to lie
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04:20.400 --> 04:24.080
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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
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04:24.080 --> 04:27.440
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I think it's like really important not to be a liar
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I mean that stands alone as like one of the best
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04:34.600 --> 04:37.240
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Rapid fire statements made by anyone
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Ever maybe in mainstream media
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You
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05:37.240 --> 05:39.240
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I
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05:43.160 --> 05:48.560
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The meter this always looks like it's really soft, but it actually is always really really hard in my ears
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05:57.880 --> 05:59.860
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Let's do it
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Sweaty bombs, this is so crazy like these bumps. This is so crazy. I feel so nervous like what in the world man
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Oh
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Big-time brick
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07:06.580 --> 07:13.220
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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
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That was the whole point of making it a real real clip one good shot one brick
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That's about what I'm good for. I don't think that's that bad though
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If you've been following along for a while you're here at the top of the wave
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07:26.220 --> 07:31.740
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Where we've been shooting three-pointers for four years now where we stay focused on the biology
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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
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07:39.420 --> 07:43.540
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By sharing this biology consistently on Facebook where I am not on
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Twitter where I'm mostly not
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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
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07:54.140 --> 08:00.220
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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
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08:00.420 --> 08:03.580
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Biological.com. They can find everything there everything has its own link
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08:04.380 --> 08:12.540
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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
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08:14.540 --> 08:19.900
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Independent Brightwave presentation that basically means that we don't take sponsorships because we're not offered them
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08:20.740 --> 08:25.420
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And we are supported only only only by viewers like you
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08:28.180 --> 08:31.100
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Still trying to break the same illusion
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08:35.380 --> 08:41.380
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Sometimes it's nice for having a little live Eric Johnson Evan root fever to try and help
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08:42.220 --> 08:46.260
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Establish the mood that it's necessary in order to
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Engage in United non-compliance is what you're really doing here
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08:51.300 --> 08:57.340
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When you come here and try to discuss the flip side of the biology on TV the flip side of the biology on
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08:58.140 --> 09:01.340
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Social media and so today we're going to keep up the good work
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That needs to be done
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This is going biological the safest way to get biology in your head
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09:17.020 --> 09:19.020
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You
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Thank you very much, this is giga ohm biological a high-resistance low noise information brief brought to you by a biologist
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09:30.940 --> 09:32.580
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24th of April
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2024 we're on our second stream of the day, but that shouldn't be something we should be applauded for
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09:37.900 --> 09:41.300
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We need to do more and there is a lot of work to do
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09:42.260 --> 09:46.260
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Sometimes it's just it's handy to be ready. We were ready for this
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09:46.260 --> 09:51.220
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We've been preparing for this video for a long time and it's actually so far been incredibly revealing
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09:51.220 --> 09:55.900
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And so I want to start first by kind of reframing where we are again
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09:55.900 --> 09:59.220
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This is about a principle of informed consent
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09:59.220 --> 10:04.100
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I'm gonna escape out of here for a second just to make sure that this is going where I want it to go
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10:05.780 --> 10:08.940
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This is where I want it to be I'm gonna skip a couple of those slides
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10:08.940 --> 10:15.940
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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
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10:16.340 --> 10:18.420
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Batcave virus, so maybe there's nothing at all
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10:19.260 --> 10:22.740
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And how these things have generally
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Hearded the vast majority of people in West Western civilization to accept a faith in
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10:31.060 --> 10:35.220
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What is essentially a novel biology? It's not just a novel virus
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But the whole story of a novel virus and how it has behaved in the last five years
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constitutes a novel biology because first of all the precedents of a trackable gain of function
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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
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with lots of little gears and wheels and and
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Enzymes and magnets and mitochondria inside
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It is simply an RNA molecule wrapped around a
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protein called the end protein and that is contained within what is essentially a cell membrane a
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Lipi protein coat lipo protein coat
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and
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11:23.700 --> 11:27.620
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So coronaviruses as they are presented to us are nothing more
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than a
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nanoparticle with some RNA packaged inside of it, and so by the
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The broad understanding of the rules of biology that
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that model
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then
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dictates that whatever properties are
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contained inside of an RNA pandemic are
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emergent properties that are contained within the actual sequence of that RNA and indeed that is the story that many people have
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been telling us from the very beginning that a fear and cleavage site that HIV inserts that
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homology to a staphylococcan and teratoxin B protein could be partially
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explanatory in terms of the severe COVID that we see in some places or the long COVID that we see in some places
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And this mythology is extraordinary because at the heart of it again
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I'm going to say it one more time is an RNA molecule that because of the actual content of its sequence the actual
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Order in which the bases are found it is capable of doing something that otherwise all other RNA molecules
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never even
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Never even it doesn't cut it doesn't happen
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Now the flu viruses is RNA molecules, but the crazy thing is is flu viruses are
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Supposedly packaged with some enzymes
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So even flu viruses have by definition even more gears and wheels and little motors in there
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Then a coronavirus a coronavirus is actually just an
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instruction module and
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if that instruction module is read then
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Apparently it makes copies of itself
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But the point is is that if that instruction module has a fear and cleavage site or it has HIV inserts or it has
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homology to to a
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toxin protein
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That now it can cause a pandemic
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So the second part of this is that
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Transfection was waiting in the wings for a very long time
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Just waiting for the right opportunity to come and save mankind. I mean the whole species
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and
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Since we rushed it since we tried to make a lot of money and cut corners or whatever it is that we did
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Or because we weren't liable. So since we weren't liable. We cut corners
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That some people were injured because of the contamination found in some of these
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And some of these countermeasures now keep in mind one of the major
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Lawsuits that's currently moving through the courts is a lawsuit
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To do with contamination of remdesivir vials so not even the use of remdesivir. Yes or no, but
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Contaminated remdesivir and so you see
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then when you realize that they've been talking since
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2000
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Wow a terrible weatherman 2020
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About the spike protein being the center of this whole mystery
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The spike proteins interaction with ACE 2 the spike proteins ability to cause multi-system inflammatory disease or whatever it's called
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The spike proteins targeting of the heart muscle the spike protein being
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amyloidogenic the spike protein being a pre-on or having pre-on-like sequences in it
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Has been confounded from the very beginning
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With the ability or the propensity for
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transfection or transformation technologies to
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result in
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Pre-on-like disorders or whatever these things are like crowds felt the occub in the paper of Luke Montenier
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The reason why the paper of Luke Montenier is so important is that it came out very early
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and yet those people had been actually
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They had been transformed with an adenovirus carrying the spike protein gene
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So they had been transformed they had not been infected and
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Of course right away the people were arguing. What were they arguing? What were they arguing?
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They were arguing that maybe those people had been infected before they were
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Before they were vaccinated
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And so already they needed to clean the narrative already they had to cast out already
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They had to speak up
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Because the worst-case scenario was already under threat from the very beginning the worst-case scenario
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Narrative centers always on the spike protein even though there are 29 or 30 other
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Proteins that have various isoforms that can do all kinds of things most of which we don't know and
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Yet we are hyper focused on the spike protein the spike protein is what's used to make the phylogenetic tree
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The spike protein has defined all previous
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Coronavirus variants in the past if you look for new SARS viruses
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You don't look for new N proteins you look for new spike proteins
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and
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Part of the reason you look for new spike proteins is not because the spike protein is the most variable gene
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It is because it's the most abundant
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subgenomic RNA
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and
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We've looked at the infectious cycle since early sixties through the 70s 80s 90s
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And now all the way up to now with nanopore sequencing and we keep finding the same weird ratio of almost no
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full genomic RNAs, but
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orders many multiple orders of magnitude more subgenomic RNAs
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Predominated by spike protein e gene and gene
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And so when you look for those subgenomic RNAs
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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
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most honest appraisal of
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the infectious cycle of their entity called coronavirus and
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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
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So much of this biology is based on the cartoons
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They draw rather than the data and the experimental results that they have actually obtained
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And that is the reason why this story is so complicated and needs to be obfuscated by people who say well
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There's just no viruses at all
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None of the viruses exist
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And
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So it is a very very complicated trap that we find ourselves in and prions as part of that prions and
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18:21.500 --> 18:26.420
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Understanding what they are and what they're what they aren't if they're anything at all is
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18:28.820 --> 18:30.820
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Extremely important
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18:30.820 --> 18:35.260
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And as with virology we would be very very
|
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18:36.260 --> 18:45.820
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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
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18:45.820 --> 18:50.220
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As it would be because none of us have studied this intentionally until recently
|
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18:53.340 --> 19:01.900
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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
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19:02.140 --> 19:09.140
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One of the things that I would like to start out with with this with this second part is
|
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19:09.340 --> 19:12.700
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Just to kind of review about what he said in the first part
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19:12.700 --> 19:18.100
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One of the things that he said in the first part was in the beginning and I'll give you the example
|
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19:18.100 --> 19:20.100
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I think I have it up already
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19:20.100 --> 19:22.100
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Don't I have it up already?
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19:22.100 --> 19:32.780
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If we go back to the beginning of this you can find that one of the
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19:36.420 --> 19:42.260
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One of the things that they were doing first was trying to optimize the production of the disease
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19:42.620 --> 19:44.620
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So first they couldn't find it
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19:45.020 --> 19:50.820
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Right it was very hard to achieve some kind of enrichment of the disease
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19:51.580 --> 19:57.220
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Agent and so he used two different graphs here to show you where the sucrose agent
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19:57.900 --> 20:00.740
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He said well darn it
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20:01.980 --> 20:09.100
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He said what you would expect to see is some kind of peak right some kind of peak over a certain place in
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20:09.580 --> 20:14.780
|
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The sucrose gradient, but you instead you see all kinds of a smear now
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20:14.780 --> 20:18.780
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Here's one of the things that I find already very interesting. Let's go back
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20:19.580 --> 20:21.580
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to the other the other
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20:25.020 --> 20:26.620
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Let's go back here
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20:26.620 --> 20:34.260
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This is the the nature pre-on paper that we've we've referenced a couple times now and lead up to this discussion
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20:34.260 --> 20:38.580
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And this is perhaps a little bit better drawing. It's a little more up to date
|
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20:38.700 --> 20:40.900
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This is the pre-on protein, right?
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20:40.900 --> 20:41.860
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Can you see oh sorry?
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20:41.860 --> 20:48.340
|
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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
|
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20:48.780 --> 20:54.540
|
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but it's for sure on the outside of the cell or on the inside of lysosomes and in the basal state
|
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20:54.540 --> 20:57.300
|
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It does something but in the in the pre-onogenic
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20:58.260 --> 21:02.740
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State or the prey I guess in this case it's PRPC
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21:03.940 --> 21:07.900
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And then this is a pre-on. Sorry. I had that wrong. This is the regular
|
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21:08.660 --> 21:13.780
|
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Pre-on protein and you see three alpha helis is there and then here you see the pre-on protein
|
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21:13.780 --> 21:17.620
|
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And it's many of them all layered on top of each other. That's what you see there
|
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21:17.700 --> 21:23.540
|
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And the implication is is that it's some kind of little fibro right there all layered on top of each other
|
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21:23.540 --> 21:28.860
|
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So this is already several pre-on proteins that have folded incorrectly and then induced it on one another
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21:28.860 --> 21:33.060
|
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And then this one can look induce the blue one to join them you see that
|
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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
|
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21:41.740 --> 21:43.740
|
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related to how it folds and
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21:44.020 --> 21:46.020
|
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So the potential for it to fold
|
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21:46.340 --> 21:54.780
|
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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
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21:55.620 --> 21:58.820
|
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Able to make any other proteins fold like this
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21:58.820 --> 22:00.220
|
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But it can make
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22:00.220 --> 22:05.980
|
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proteins with the right sequence the the protein pre-on the pre-on protein
|
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22:06.580 --> 22:08.060
|
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sequence
|
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22:08.060 --> 22:10.580
|
|
so what I find interesting about the
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22:14.100 --> 22:21.500
|
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What I find interesting about this figure in the in the video that we watched earlier today is that this
|
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22:22.740 --> 22:28.740
|
|
Is still seeming to imply that there is one protein now if there's one protein that makes
|
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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
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22:35.900 --> 22:40.620
|
|
And then it makes predictions about measurements in the future and those predictions if
|
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22:41.180 --> 22:46.260
|
|
If done cleverly or or or tested cleverly
|
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22:46.980 --> 22:48.980
|
|
can provide fruitful
|
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22:50.060 --> 22:52.900
|
|
Guidance to the experiments that should be done
|
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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
|
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23:02.500 --> 23:04.500
|
|
By
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23:05.220 --> 23:09.300
|
|
Coming together right pre-ons press pre-ons equals a fibrel
|
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23:10.860 --> 23:15.420
|
|
And that was also what he was talking about with regard to amyloidosis and
|
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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
|
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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
|
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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
|
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23:36.340 --> 23:38.740
|
|
is smeared across densities which means
|
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23:39.700 --> 23:45.580
|
|
Apparently not one thing and the argument that they might make is one where they would say
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23:46.220 --> 23:49.460
|
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Sorry, they would say that that the
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23:50.260 --> 23:52.260
|
|
That the pre-on
|
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|
23:52.380 --> 23:54.380
|
|
protein is is
|
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23:54.540 --> 23:56.540
|
|
making
|
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23:57.180 --> 24:02.620
|
|
Fibrels in those fibrels because they're multiples of the the pre-on protein
|
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|
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24:02.620 --> 24:07.100
|
|
Then they're going to be all across that sucrose gradient, but that's not entirely
|
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|
|
24:08.020 --> 24:11.980
|
|
accurate because if the pre-on protein weighs
|
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|
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24:12.700 --> 24:13.860
|
|
X
|
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|
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
|
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|
|
24:21.820 --> 24:26.180
|
|
Lines or in a sucrose gradient you could get lines where okay
|
|
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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?
|
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24:32.060 --> 24:36.700
|
|
I mean you can actually count it because it would move up in increments by weight
|
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|
24:37.180 --> 24:41.340
|
|
because they move through these things by weight or by density and
|
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|
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
|
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|
|
24:52.140 --> 24:55.620
|
|
In a gel, but there must be some way to show me
|
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|
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
|
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|
|
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
|
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|
|
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
|
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|
|
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
|
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33:04.800 --> 33:12.000
|
|
Heloces are all general structures that can be made with chains of amino acids and one is
|
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33:13.120 --> 33:18.040
|
|
many different combinations of amino acids can form these these forms and so
|
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33:18.960 --> 33:21.880
|
|
the particular shape and form and
|
|
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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
|
|
|
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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
|
|
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|
33:36.360 --> 33:40.760
|
|
He was even though it's only 25% the same as this one
|
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33:40.760 --> 33:43.160
|
|
It's more of the what repeats when and that kind of thing
|
|
|
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33:43.960 --> 33:45.640
|
|
and
|
|
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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
|
|
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33:52.200 --> 33:56.200
|
|
then he starts talking about crowdsfeld yachob in in families and
|
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33:57.080 --> 33:58.840
|
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sometimes it's
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33:58.840 --> 34:00.200
|
|
evidence of
|
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34:00.200 --> 34:04.160
|
|
preons getting into humans is 20 years or 40 years later
|
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34:04.160 --> 34:10.520
|
|
So we could still see the effects of eating preon infected meat 20 or 40 years later
|
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34:10.720 --> 34:16.800
|
|
which is very convenient in 2002 because that could actually be right now and and
|
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34:17.440 --> 34:19.080
|
|
timed perfectly with
|
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34:19.080 --> 34:21.960
|
|
Transfection to cover it up and we could just turn around and say well
|
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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
|
|
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34:27.440 --> 34:30.040
|
|
There was also in here some stuff where they were
|
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34:30.720 --> 34:38.320
|
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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
|
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34:39.240 --> 34:44.800
|
|
Replacement thereof then he talked about that was where this there it is the bovine the bovine
|
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34:45.600 --> 34:47.600
|
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the bovinized mice
|
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34:48.160 --> 34:50.600
|
|
So they over express a bovine
|
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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
|
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35:00.920 --> 35:02.360
|
|
makes the mouse
|
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|
|
35:02.360 --> 35:08.520
|
|
susceptible to the bovine sponge of form encephalopathy, but not the other ones and so
|
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35:09.400 --> 35:12.760
|
|
Kinda demonstrates that there's some specificity
|
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|
|
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
|
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|
35:33.000 --> 35:35.000
|
|
and
|
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35:35.000 --> 35:39.360
|
|
Then we got to the yes
|
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|
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
|
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|
35:47.640 --> 35:51.840
|
|
probing whether certain parts of a protein are present or not or whether they're
|
|
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|
35:52.560 --> 35:58.120
|
|
Available for antibody binding or not and to a certain extent. I think this makes some
|
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|
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
|
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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
|
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|
36:31.840 --> 36:33.840
|
|
Think
|
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|
|
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
|
|
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47:27.740 --> 47:34.300
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None of us have ever sold the company none of us have had multiple consulting companies that worked with the DoD Ditra
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47:34.540 --> 47:37.580
|
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none of us have ever sat on on on
|
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47:37.980 --> 47:42.380
|
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DARPA grant committees to evaluate DARPA proposals
|
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47:43.180 --> 47:46.060
|
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none of us have ever gotten the benefit of
|
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47:47.540 --> 47:49.540
|
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taxpayer-funded data
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47:49.580 --> 47:52.780
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From your university to start a company and then sell it
|
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47:56.060 --> 47:58.060
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But all of these people have
|
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48:00.260 --> 48:02.260
|
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All of these people have a book
|
|
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48:08.340 --> 48:14.780
|
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What we're dealing with here is a controlled operation to make sure that you stay focused on
|
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48:16.140 --> 48:22.660
|
|
Something that will not prevent the controlled demolition of America will not prevent us from coming together
|
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48:22.660 --> 48:31.140
|
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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
|
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48:38.300 --> 48:40.900
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There is no way that it is random
|
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48:42.660 --> 48:46.940
|
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That soaf was on Alex Jones three times in
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48:47.500 --> 48:52.220
|
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2019 and now we are listening to her mom for three years as
|
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48:52.980 --> 48:54.780
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part of the
|
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48:54.780 --> 48:56.140
|
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alternative
|
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48:56.140 --> 49:03.100
|
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COVID narrative that involves a novel virus that killed millions of people that millions more were saved from
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49:04.100 --> 49:07.940
|
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That was definitely gained a function or a toxin that was
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49:08.500 --> 49:12.460
|
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sprayed on the world by the United States Department of Defense
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49:14.140 --> 49:16.140
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Which was a great way to
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49:16.740 --> 49:18.740
|
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implode America in a way that
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49:19.780 --> 49:24.900
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Turns everybody on everybody else. It doesn't realize that the military is a victim of this too
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49:25.580 --> 49:27.300
|
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the average
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49:27.300 --> 49:32.340
|
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Serving soldier is a victim of this too. They have to follow orders
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49:32.340 --> 49:34.340
|
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It's the people above
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49:34.660 --> 49:41.260
|
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Lieutenant Colonel now those are the people we need to be holding to account. Those are the people who put the mandate out
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49:41.940 --> 49:43.940
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Who gave the orders down the chain?
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49:44.940 --> 49:50.140
|
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The people at the bottom of the chain cannot be blamed for taking the orders or following them
|
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49:50.460 --> 49:55.980
|
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They are victims of this as well and yet. Who does she want us to blame the Department of Defense?
|
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49:55.980 --> 50:06.780
|
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Without any more specificity than that without any more chain of command to the Department of Human Health and Human Services for the
|
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50:07.740 --> 50:10.940
|
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Department of Homeland Security for DITRA
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50:11.860 --> 50:13.860
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Nothing's State Department. What's that?
|
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50:17.340 --> 50:24.420
|
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And this guy as I said is not a legal scholar is not some kind of courtroom killer
|
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50:26.900 --> 50:33.380
|
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This is a guy who is a very very very below average lawyer
|
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50:35.020 --> 50:37.020
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and
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50:37.020 --> 50:40.900
|
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He's probably in way over his head. He's probably not even a bad guy
|
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50:44.260 --> 50:46.100
|
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But people
|
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50:46.100 --> 50:47.460
|
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smarter than me
|
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50:47.460 --> 50:53.780
|
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Do not take him seriously and so the idea that either of these two take him seriously that either
|
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50:54.300 --> 50:57.860
|
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Dr. Drew or Sasha take him seriously it begs
|
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50:59.460 --> 51:04.420
|
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I'm I find it dubious. I find it dubious and and I don't think that
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51:07.300 --> 51:09.300
|
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Hey, I just don't
|
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51:11.620 --> 51:14.500
|
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I don't buy him. I don't buy him. I think that we are
|
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51:15.300 --> 51:20.740
|
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You need to be very pessimistic about the number of people. I mean look at how much fun she's having
|
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51:20.740 --> 51:25.660
|
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Americans were murdered ladies and gentlemen and
|
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51:27.300 --> 51:34.900
|
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Children are having needles forced upon them and adults over 50 are having needles coerced into them
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51:37.300 --> 51:39.780
|
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As we speak by this system
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51:41.860 --> 51:47.860
|
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And it is based on this mythology of a novel virus that is not being questioned here at all
|
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51:47.860 --> 51:50.740
|
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I can guarantee it. I mean they're looking how much fun
|
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51:51.540 --> 51:54.820
|
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it's so much fun to be on dr. Drew's show and
|
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51:56.500 --> 51:59.140
|
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Dr. Drew's weed is so good and
|
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|
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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
|
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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
|
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|
52:18.340 --> 52:23.380
|
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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
|
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52:25.620 --> 52:27.620
|
|
And i'm not going to subscribe to
|
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|
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52:29.780 --> 52:33.940
|
|
To dr. Drew. I don't think it'll get me in anyway. It's too late
|
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52:35.300 --> 52:38.740
|
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Uh, let's finish this. This is our work. This is our work
|
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52:38.740 --> 52:48.260
|
|
We're up even up in here
|
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|
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52:49.140 --> 52:51.140
|
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Rugs and this is the structure of it. It has these three rings
|
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52:51.860 --> 52:56.660
|
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And when karstin corth added one micromolar this amount he still saw these protease resistant bands
|
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52:57.140 --> 53:01.460
|
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This so the different the three bands are the ones with no sugars one sugar chain and two sugar chains
|
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53:01.460 --> 53:04.020
|
|
They're showing a little better here. So two sugar chains one and none
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53:04.660 --> 53:06.500
|
|
Or even up in here
|
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|
53:06.500 --> 53:11.460
|
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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
|
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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
|
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|
|
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
|
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53:29.780 --> 53:33.380
|
|
Properties that are used to treat dementia
|
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|
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
|
|
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|
53:54.180 --> 53:57.940
|
|
The prion protein which is a really weird thing to test
|
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|
54:00.260 --> 54:02.260
|
|
And he looked at many of them as you see on this chart
|
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|
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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?
|
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54:08.180 --> 54:10.580
|
|
And what the background of karsten corth was that he
|
|
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|
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
|
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|
|
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
|
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54:30.820 --> 54:33.620
|
|
And he looked at me and he said to answer my question
|
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|
54:33.620 --> 54:34.660
|
|
Why did you do these experiments?
|
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|
|
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
|
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|
54:37.940 --> 54:40.580
|
|
And so I threw in chlorpromazine or thorazine into the culture
|
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|
|
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
|
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|
|
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
|
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|
|
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
|
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|
55:04.460 --> 55:06.940
|
|
In the 1930s the Germans synthesized
|
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55:07.460 --> 55:10.620
|
|
Quinecrin and this turned out to be a potent anti-malarial drug
|
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|
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
|
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|
|
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
|
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|
|
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
|
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That are exposed in the endogenous form
|
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01:11:11.220 --> 01:11:14.220
|
|
Do you see the hand waving is extraordinary?
|
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01:11:14.220 --> 01:11:19.220
|
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I do not believe the papers support these as being firm conclusions
|
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01:11:19.220 --> 01:11:25.220
|
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But it's extraordinary the kind of exceptional biology
|
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01:11:25.220 --> 01:11:28.220
|
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The number of exceptions that we need to make
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01:11:28.220 --> 01:11:31.220
|
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In order for this to be true
|
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01:11:35.220 --> 01:11:37.220
|
|
Now is these mice with the prion protein
|
|
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|
01:11:37.220 --> 01:11:39.220
|
|
They form huge numbers of antibodies
|
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01:11:39.220 --> 01:11:42.220
|
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In contrast to normal mice which form very few or no antibodies
|
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01:11:42.220 --> 01:11:46.220
|
|
That is a absolute
|
|
|
|
01:11:46.220 --> 01:11:48.220
|
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It's a mouse model of the disease
|
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01:11:48.220 --> 01:11:51.220
|
|
That he's saying that if you don't have the prion protein
|
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01:11:51.220 --> 01:11:54.220
|
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Then you can make antibodies to the scraping protein
|
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01:11:54.220 --> 01:11:56.220
|
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And then you won't get it
|
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01:11:56.220 --> 01:12:00.220
|
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And so one of the reasons and the way to understand
|
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01:12:00.220 --> 01:12:04.220
|
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That this works is that we could respond to you here
|
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01:12:04.220 --> 01:12:06.220
|
|
Wait, it's coming, you see
|
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01:12:06.220 --> 01:12:10.220
|
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They're going to treat prion disease with antibodies
|
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01:12:10.220 --> 01:12:12.220
|
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That's what he's proposing here
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01:12:12.220 --> 01:12:15.220
|
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And that we should use money and grant proposals
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01:12:15.220 --> 01:12:19.220
|
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To find the antibodies which we could use to fight prion disease
|
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01:12:19.220 --> 01:12:21.220
|
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Antibodies, you know antibodies
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01:12:21.220 --> 01:12:24.220
|
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The things that they fight all these other diseases with
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01:12:24.220 --> 01:12:28.220
|
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That they want to produce as the perfect
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01:12:28.220 --> 01:12:32.220
|
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Inject it in your soldiers and your immune for 30 days
|
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01:12:32.220 --> 01:12:35.220
|
|
Kind of thing, it's a little cludgy but it works
|
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01:12:35.220 --> 01:12:38.220
|
|
And if I'm no antibodies if it's a mouse prion protein
|
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01:12:38.220 --> 01:12:40.220
|
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If it's a human they might form one
|
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01:12:40.220 --> 01:12:41.220
|
|
So the immune system
|
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|
|
01:12:41.220 --> 01:12:45.220
|
|
So they could easily use an mRNA to generate the prion antibodies
|
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|
01:12:45.220 --> 01:12:48.220
|
|
That they say are found in this mouse
|
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|
|
01:12:48.220 --> 01:12:51.220
|
|
But aren't found in any animals that have the prion protein
|
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|
01:12:51.220 --> 01:12:53.220
|
|
Then it would be a cell protein
|
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|
01:12:53.220 --> 01:12:55.220
|
|
So, wow!
|
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01:12:55.220 --> 01:12:57.220
|
|
Quiet in these diseases
|
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|
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01:12:57.220 --> 01:13:00.220
|
|
Well, alright, so the question is very technical
|
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|
|
01:13:00.220 --> 01:13:03.220
|
|
Is the normal form of the prion protein the kinetic product
|
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|
|
01:13:03.220 --> 01:13:05.220
|
|
Or a kinetically trapped molecule and that
|
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|
|
01:13:05.220 --> 01:13:09.220
|
|
This scraping form is a thermodynamically more stable protein
|
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|
|
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
|
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|
|
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
|
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|
|
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
|
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|
|
01:13:46.220 --> 01:13:48.220
|
|
Several years probably to track that down and understand it
|
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|
|
01:13:48.220 --> 01:13:50.220
|
|
Before we would do anything further
|
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|
|
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
|
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|
|
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
|
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|
01:19:37.220 --> 01:19:39.220
|
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They virtually never made it to age 40
|
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01:19:39.220 --> 01:19:42.220
|
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So we had generations of young people who were motherless
|
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01:19:42.220 --> 01:19:45.220
|
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And it was in the late 1950s that two things happened
|
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01:19:45.220 --> 01:19:49.220
|
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One of the missionaries who began to colonize that area told them that nice people don't eat their relatives
|
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01:19:49.220 --> 01:19:50.220
|
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Whether they're dead or alive
|
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01:19:50.220 --> 01:19:55.220
|
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And these people were eating their dead relatives to really immortalize them
|
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01:19:55.220 --> 01:19:59.220
|
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This was their way of immortalizing them through taking their soul, which they believed was in the brain, not in the heart
|
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01:19:59.220 --> 01:20:02.220
|
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And the second thing that happened was that the Australian authorities
|
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01:20:02.220 --> 01:20:06.220
|
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Who now began to occupy the Highlands of New Guinea, which up until the late 1940s
|
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01:20:06.220 --> 01:20:09.220
|
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Had not seen any Western people
|
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01:20:09.220 --> 01:20:12.220
|
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And began to occupy that area and they outlawed cannibalism
|
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01:20:12.220 --> 01:20:14.220
|
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So that's how these tribes have now survived
|
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01:20:14.220 --> 01:20:19.220
|
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And so what you basically have here is very
|
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01:20:19.220 --> 01:20:21.220
|
|
Let's say
|
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01:20:21.220 --> 01:20:28.220
|
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Outland, outlier examples of where protein misfolding can go wrong
|
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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
|
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01:20:38.220 --> 01:20:40.220
|
|
systemic immune system
|
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01:20:41.220 --> 01:20:46.220
|
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And so I don't know exactly how to draw it out on a piece of paper
|
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01:20:46.220 --> 01:20:50.220
|
|
But it makes sense to me that this phenomenon, however rare it was
|
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|
01:20:50.220 --> 01:20:55.220
|
|
Would be something that you would want to understand from the perspective of how ribosomes function
|
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01:20:55.220 --> 01:20:58.220
|
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From the perspective of protein folding
|
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|
01:20:58.220 --> 01:21:03.220
|
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And from the perspective of wanting to alter the function of proteins
|
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|
01:21:03.220 --> 01:21:06.220
|
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And knowing how to stay away from this potential danger
|
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|
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
|
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|
01:21:20.220 --> 01:21:23.220
|
|
And they're eating their brain that occasionally you get this
|
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|
|
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
|
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|
|
01:21:29.220 --> 01:21:34.220
|
|
Could also be something to do with an immune reaction to that consumption
|
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01:21:34.220 --> 01:21:40.220
|
|
An immune reaction that occurs in the gut in the place where tolerance is normally built
|
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|
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
|
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|
01:21:48.220 --> 01:21:55.220
|
|
Because self-antigens are present where they shouldn't be present, i.e. in the gut
|
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|
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
|
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|
|
01:22:21.220 --> 01:22:23.220
|
|
No
|
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|
|
01:22:23.220 --> 01:22:25.220
|
|
Damn it
|
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|
|
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
|
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|
|
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
|
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01:31:01.220 --> 01:31:03.220
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Like infectious diseases
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01:31:03.220 --> 01:31:05.220
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It comes from all these neurodegenerative diseases
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01:31:05.220 --> 01:31:06.220
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About them and the mechanisms
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01:31:06.220 --> 01:31:08.220
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We're going to see more and more cross fertilization
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01:31:08.220 --> 01:31:11.220
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The prion diseases have the advantages that we know much more about prions
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01:31:11.220 --> 01:31:13.220
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Than we do about the process of Alzheimer's disease
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01:31:13.220 --> 01:31:14.220
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We have much better animal models
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01:31:14.220 --> 01:31:16.220
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These transgenic or genetically...
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01:31:16.220 --> 01:31:19.220
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I am really upset with the disease, the use of the word disease
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01:31:19.220 --> 01:31:21.220
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Because it's super annoying
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01:31:21.220 --> 01:31:26.220
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We shouldn't have infectious disease
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01:31:26.220 --> 01:31:29.220
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And then genetic disease
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01:31:29.220 --> 01:31:32.220
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It should be genetic disorder
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01:31:32.220 --> 01:31:35.220
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Protein folding disorder
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01:31:35.220 --> 01:31:40.220
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Malaria disease
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01:31:40.220 --> 01:31:41.220
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Something like that
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01:31:41.220 --> 01:31:43.220
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I don't like this, but that's the way we do it
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01:31:43.220 --> 01:31:46.220
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And it's frustrating, but it's biologically confusing
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01:31:46.220 --> 01:31:49.220
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And biologically imprecise
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01:31:49.220 --> 01:31:52.220
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Near mice reproduce every aspect of a prion disease
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01:31:52.220 --> 01:31:55.220
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Of humans, of a cow, depending on what gene we express in the mouse
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01:31:55.220 --> 01:32:00.220
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And so we have tools with prion diseases that we don't have with any of the other diseases
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01:32:00.220 --> 01:32:03.220
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And I think if we're successful in the therapy and prion disease
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01:32:03.220 --> 01:32:06.220
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This will generate an enormous interest in the drug companies
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01:32:06.220 --> 01:32:08.220
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As well as the governments as well as foundations throughout the world
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01:32:08.220 --> 01:32:12.220
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But enormous amounts more money into solving a problem like Alzheimer's disease
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01:32:12.220 --> 01:32:16.220
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Anybody's, anybody's for amyloid beta
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01:32:16.220 --> 01:32:19.220
|
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I mean, it's hilarious how naive he sounds here
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01:32:19.220 --> 01:32:22.220
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Because we have, of course, the benefit of 22 years of research
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01:32:22.220 --> 01:32:25.220
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But it's very, very funny
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01:32:25.220 --> 01:32:28.220
|
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How naive he sounds here
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01:32:28.220 --> 01:32:32.220
|
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I'm so excited about these antibodies as therapeutics
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01:32:32.220 --> 01:32:34.220
|
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And also as bench tools
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01:32:34.220 --> 01:32:37.220
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And even structural dissection tools
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01:32:37.220 --> 01:32:42.220
|
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It's hilarious how naive he is to what he's using as tools
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01:32:42.220 --> 01:32:47.220
|
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Anybody's for a long time have played various roles like this
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01:32:47.220 --> 01:32:54.220
|
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That lots and lots of academic biologists are unaware of the huge, huge grey area
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01:32:54.220 --> 01:32:57.220
|
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That they've been playing with unless they've been using the proper controls
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01:32:57.220 --> 01:33:02.220
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Which is a growing and growing problem because of the change in demography of our populations
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01:33:02.220 --> 01:33:06.220
|
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When you're 85 years old, you have a one and three chance of having Alzheimer's disease
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01:33:06.220 --> 01:33:09.220
|
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And as we have more and more people who become octogenarians
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01:33:09.220 --> 01:33:12.220
|
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The number of people without Alzheimer's diseases that keep going up
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01:33:12.220 --> 01:33:14.220
|
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Other questions?
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01:33:14.220 --> 01:33:17.220
|
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So the question is, in late onset muscular dystrophies
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01:33:17.220 --> 01:33:22.220
|
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Where they have these mutations that expand the size of the protein
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01:33:22.220 --> 01:33:25.220
|
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Or sometimes don't expand the size of the protein but expand the gene
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01:33:25.220 --> 01:33:27.220
|
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Are there similarities? And the answer is yes
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01:33:27.220 --> 01:33:30.220
|
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One of the diseases I put up, but I didn't talk about was Huntington's disease
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01:33:30.220 --> 01:33:32.220
|
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And then I put up some of the spinal cerebellar ataxios
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01:33:32.220 --> 01:33:35.220
|
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And these diseases have these same kinds of expanded repeats
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01:33:35.220 --> 01:33:39.220
|
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And the answer is, I think we're talking about many similar phenomena
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01:33:39.220 --> 01:33:41.220
|
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Now in these cases, these are all inherited diseases
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01:33:41.220 --> 01:33:43.220
|
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So it's only the genetic form of disease
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01:33:43.220 --> 01:33:48.220
|
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But we have no understanding of why it is that these diseases have such a late onset
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01:33:48.220 --> 01:33:51.220
|
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What is clear is that the bigger the repeat, the earlier the onset
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01:33:51.220 --> 01:33:54.220
|
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But then all of that has to be qualified by many other factors
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01:33:54.220 --> 01:33:57.220
|
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That shift these curves up and down with respect to the repeats
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01:33:57.220 --> 01:34:00.220
|
|
In the prion diseases, we have absolutely no understanding why it is that
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01:34:00.220 --> 01:34:03.220
|
|
A single mutation, meaning one amino acid has changed
|
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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
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01:34:07.220 --> 01:34:09.220
|
|
And others are 80 or 90 years old
|
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|
|
01:34:11.220 --> 01:34:15.220
|
|
It's more likely to be exposure to a toxin or some other trigger than
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|
|
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
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|
|
01:34:22.220 --> 01:34:26.220
|
|
So again, the model makes predictions but he doesn't bother to test him
|
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|
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01:34:26.220 --> 01:34:29.220
|
|
He doesn't even bother to list the options that he sees
|
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|
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01:34:29.220 --> 01:34:31.220
|
|
It's really disingenuous
|
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|
|
01:34:32.220 --> 01:34:35.220
|
|
The question is about these areas where PRPC is converted into PRPC scraping
|
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|
|
01:34:35.220 --> 01:34:37.220
|
|
On the surface of the cell, these cholesterol-rich micro-domains
|
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|
|
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
|
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|
|
01:34:41.220 --> 01:34:44.220
|
|
We can completely abolish the formation of PRPC scraping
|
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|
|
01:34:44.220 --> 01:34:47.220
|
|
Now we can't give that drug in high enough concentrations to humans
|
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|
|
01:34:47.220 --> 01:34:49.220
|
|
Because we would dissolve the human
|
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|
|
01:34:49.220 --> 01:34:53.220
|
|
The cells are not very happy in these very high concentrations of low estatin
|
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|
|
01:34:53.220 --> 01:34:57.220
|
|
These are very important regions, these cholesterol-rich micro-domains are rafts
|
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|
|
01:34:57.220 --> 01:34:59.220
|
|
That people have been studying only for the last few years
|
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|
|
01:34:59.220 --> 01:35:01.220
|
|
They seem to coalesce and form caves or cabbioli
|
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|
|
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
|
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|
|
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
|
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|
|
01:40:15.220 --> 01:40:17.220
|
|
Christy, thanks a lot
|
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|
|
01:40:19.220 --> 01:40:22.220
|
|
See you guys again tomorrow
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