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4674 lines
176 KiB
4674 lines
176 KiB
12 months ago
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WEBVTT
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I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about,
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00:30.000 --> 01:00.000
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but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if it's what I'm talking about, but I'm not sure if what I'm talking about, but I'm not sure if that's how I'm not sure if it's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that's what I'm talking about, but I'm not sure if that
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01:00.000 --> 01:11.000
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Oh, I also forgot to change this, too, darn it.
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01:11.000 --> 01:14.000
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And all the time it was Wiggles who made that black knight come to life.
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01:14.000 --> 01:16.000
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And there was no legend.
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01:16.000 --> 01:22.000
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Positively not. Wiggles just used the story to cover up my mysterious disappearance.
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01:22.000 --> 01:27.000
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Somehow he managed to get into the armor down at the train station.
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01:27.000 --> 01:32.000
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And like on the way to the museum, he made you disappear.
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01:37.000 --> 01:40.000
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Zoints, he's alive!
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01:46.000 --> 01:48.000
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Scooby-oo!
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01:58.000 --> 02:00.000
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Good evening, ladies and gentlemen.
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02:00.000 --> 02:24.000
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This is Gigo on Biological, High Resistance, Low Noise Information Brief, brought to you
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by biologists at the 18th of September, 2023.
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02:29.000 --> 02:32.000
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And things are getting fun.
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02:32.000 --> 02:38.000
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We're still trying to break through this illusion.
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02:38.000 --> 02:46.000
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We're still trying to fix the problem that we're not arguing within the right spectrum of reality.
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02:46.000 --> 02:53.000
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Arguing about biology that never happened, about causes that don't exist.
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02:53.000 --> 03:00.000
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And about methodologies that are unproven.
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03:00.000 --> 03:05.000
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And that's really where we are here at Gigo on Biological.
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03:05.000 --> 03:09.000
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It is a cool evening in Pittsburgh.
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03:09.000 --> 03:16.000
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A very cool brisk evening, but very, it's my kind of weather.
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03:16.000 --> 03:21.000
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It's not that I don't enjoy the summer, don't get me wrong, I definitely enjoy the summer.
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03:21.000 --> 03:31.000
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As a tall, lanky streak of skinny man, the hot summer sun goes right through me and I love it.
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03:31.000 --> 03:43.000
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But yeah, it's this weather where I can wear a thick hoodie and pants and shoes and stuff and not be all sweaty all the time.
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03:43.000 --> 03:45.000
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I kind of like that too.
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03:45.000 --> 03:52.000
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Thanks very much for joining me on this evening or morning or afternoon or night, depending on where you are.
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03:52.000 --> 03:58.000
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Not taking the debate on not taking the bait on TV and not taking the bait on social media.
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Congratulations.
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It is very difficult because these people have tried so hard to change our minds about things.
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04:10.000 --> 04:16.000
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And that's unfortunate, but that is really where we are.
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04:16.000 --> 04:21.000
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I probably could make myself just a little bit bigger.
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04:21.000 --> 04:33.000
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And that's really how they got us to get to the stage where we could think so poorly about our own biology and our own standing in the world.
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That these kinds of bad things could be allowed to happen.
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I don't really like the way that looks, but maybe that's okay.
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04:43.000 --> 05:06.000
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It's quite a scary place where we are right now because there doesn't seem to be any real energy you want to be spent on trying to retrospectively think about what happened in 2020 and 2021 that got us to 2023.
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05:06.000 --> 05:17.000
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And I get worried sometimes that there are people out there who are so interested in the next thing coming and the so interested in the next thing coming and so interested in the next thing coming.
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05:17.000 --> 05:28.000
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That they're this kind of hyper attention shifting is actually something that is used against us.
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05:28.000 --> 05:35.000
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And we've got to be very careful that we are not encouraged to rush into the future.
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05:35.000 --> 05:45.000
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Eyes wide shut screaming and yelling, which is basically what we were encouraged to do at the beginning of the pandemic.
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05:46.000 --> 05:59.000
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Now you might look back on and think, no, that's not really true, but you know, telling people that we had to shut society down globally for 15 days or 30 days.
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05:59.000 --> 06:07.000
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That's pretty much as drastic as it's ever been ever in the history of modern men.
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06:07.000 --> 06:16.000
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Now there's been wars and all those other things where, of course, massive changes in human behavior have resulted in massive casualties.
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06:16.000 --> 06:36.000
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But with a sort of, let's say, well, a motivation based more on things that would be wars would be based on, you know, like, I don't know, people steal and people's girlfriends or lots of money or encroaching on territory.
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06:36.000 --> 06:49.000
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And not a biological boogie man that's almost impossible, the visualize, quantify, purify, or study in a laboratory.
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06:49.000 --> 07:05.000
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And so that's what I think becomes so shocking about this is that people have so willingly accepted all the tenants of the biology that has allowed us to ventilate people for a year that probably lots of them probably shouldn't have been.
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07:05.000 --> 07:08.000
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And lots of them probably shouldn't have been ventilated.
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07:08.000 --> 07:23.000
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The use of remdesivir on anybody for anything has never really been justified with any medical literature at all. I mean, let's just, let's just call a spade a spade here.
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07:23.000 --> 07:44.000
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The proxy chloroquine, Ivermectin, femotidine, any of these other drugs have at least a track record of not killing people en masse, not damaging people en masse because they've tested it on lots of people and lots of people had no damage at all.
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07:44.000 --> 07:54.000
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Remdesivir basically has a red thread through its use, and that is that if you were to give remdesivir to a healthy person, they wouldn't be healthy anymore.
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07:54.000 --> 08:03.000
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Let's just be very clear about this. This is not something you can give to a healthy person and have them go, yeah, I don't notice anything at all.
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08:03.000 --> 08:13.000
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When you give an aspirin to a person who doesn't have a lot of inflammation, it's not a lot of effects.
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08:13.000 --> 08:29.000
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And so we're not talking about apples and oranges when we talk about the things that we talk about on television, when we talk about the things that we talk about in social media, because we're not adequately assigning the gravity to the right places, the right causes.
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08:30.000 --> 08:58.000
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And we have assigned most of the gravity to this amorphous biological phenomenon called the virus, and we are, through any means necessary, forced to ignore this list over here, which is a list of harms that essentially, if we don't account for it, becomes part of the tally
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08:58.000 --> 09:03.000
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accounted for by the biological phenomena, the mythology.
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09:03.000 --> 09:25.000
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And that's again where you can take the average shark fin and make it into a megalodon if you don't adequately attribute sailboat sales to sailboats, but you start to attribute anything with the shape of a shark fin to a shark.
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09:26.000 --> 09:35.000
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And so with the PCR test, we have basically roped in anything with the shape of a shark fin and called it a shark.
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09:35.000 --> 09:43.000
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And so we have big sharks where people had like multiple organ failure and COVID ravaged their bodies.
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09:44.000 --> 09:53.000
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And we have people who got barely sick at all and had no respiratory disease, but died of a heart attack and that's also COVID.
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09:53.000 --> 10:12.000
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And then lots and lots of people with respiratory symptoms and no positive test, respiratory symptoms and a positive test and no discernible difference between them except that diagnostic test and people jumping to huge biological conclusions based on that one
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observation.
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10:17.000 --> 10:19.000
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And so it's really frustrating.
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10:19.000 --> 10:27.000
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It is really a frustrating place to be in because people are so convinced, they're so convinced that they're right.
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10:27.000 --> 10:41.000
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And that may be how people will characterize us as well, but it would be a mischaracterization, because we aren't trying to cordon off a very small possibility space and put a flag in a way that we can see.
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10:41.000 --> 10:44.000
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And put a flag in it and claim it for giggle and biological.
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10:44.000 --> 11:01.000
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What we're trying to do is illustrate the fact that almost everyone else is very hyper focused on a little pinpointed aspect of this and trying to sell you a little pinpointed aspect of this, this angle.
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11:01.000 --> 11:23.000
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And it is an angle wherein there is a possibility that a single RNA sequence can be so diabolically nasty that it can be so contagious, that it can be so infectious, that it can be so virulent
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that the entire planet should fear it.
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11:27.000 --> 11:39.000
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And that story is a lie if any of the chemistry that we understand about DNA and RNA is true, it's a lie, they have to know this.
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11:39.000 --> 12:02.000
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So the only way to achieve the illusion of an RNA that's so dangerous and so infectious and so virulent and so hyper-infective that the whole world should fear it would be to make lots of pure copies of it and put it in lots of places and let people draw that conclusion themselves.
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12:02.000 --> 12:23.000
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Even if there's no evidence for a particularly dangerous disease, just evidence of a particularly ubiquitous sequence, or even worse, a ubiquitous set of PCR amplicons that happen to show up or happen to be detectable.
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12:24.000 --> 12:45.000
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So we've got to reel it in, we've got to back the truck up and we've got to realize that we may have been set up from the very beginning with a very controlled narrative space in which many, many actors have been introduced as people representing the yin and the yang within this debate space.
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12:46.000 --> 13:09.000
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And it's little people like Tim Poole and Sam Seder, it's bigger people like, and they're not even that big, but the Weinstein's and the people under Joe Rogan, you know, I don't really know all their names, but I can see them in the pictures, you know, Shapiro, all of them that have like a million or two million followers.
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13:09.000 --> 13:32.000
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You've got all these niche sort of injection points, whereas long as those sheepdogs or whatever you want to call them magnets are there, then all of the fragments underneath, all of the shards underneath will kind of organize around those major magnetic fields.
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13:33.000 --> 13:55.000
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And some of those magnetic fields are based on their appearance and their fitness or their attractiveness like, or their, their, their beautiful set or whatever they are, but they all have this very well produced thing that I'm trying to replicate here in my garage with the same idea
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13:55.000 --> 14:12.000
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that you want to be able to sort of be as close to the people that are watching you as possible or project that idea so that you've come off as authentic as possible so that you collect the most viewers so that they listen to you the most.
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14:12.000 --> 14:17.000
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And now they've known this for very, very long time.
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14:17.000 --> 14:33.000
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And for all of us who are, you know, probably behind the times in the sense of, you know, we're not really engaged in the Internet like a lot of people are like a lot of younger people are, and we certainly haven't been engaged in it as long as them.
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14:34.000 --> 14:46.000
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This whole giggle thing for me is the, is my foray into the Internet at what was I 49 or 50 when this started, I guess 49.
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14:46.000 --> 14:58.000
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And so it's not some kind of, you know, thing that I've, I'm not that guy in the YouTube Mr. Beast who like started making videos when he was 14 just because he wanted to make videos.
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14:58.000 --> 15:15.000
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And there are people like that. For example, I did a show the other day about Z-Dog MD who we go back six or eight years and the guy was already making music videos highly produced.
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15:15.000 --> 15:35.000
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Like I really did want to be on the Internet really did want to be a media star, a thing, you know, and now he's got a very highly produced, highly, you know, algorithmically elevated YouTube thing going where I'm sure he's doing other things on the side as well.
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15:36.000 --> 15:51.000
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And good forum, right? I mean, everybody's got to make their living, but what we are suggesting at Giggle Home Biological is that they've known this and they've found these people and they've talked to them and some of them didn't need any convincing at all.
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15:52.000 --> 16:04.000
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Heck, think about it, guys. If they had come to me in 2019 when I was still struggling at the University of Pittsburgh and said, Hey, you've got this bike channel going.
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This is pretty cool. Maybe you can do a pro vaccine channel for us because there's going to be an outbreak and this is a national security thing and we'll buy you some cameras.
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We'll make sure that your channel rises and you can be a part of a movement that makes sure that America doesn't doesn't fall apart from this.
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What the hell would I have said?
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Of course, I would have said yes to the people in suits and I would have been happy to do it.
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16:36.000 --> 16:46.000
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And maybe with regular feeding of information, it would have taken me forever or never to figure out that it was all a lie.
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16:46.000 --> 16:52.000
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So I think I'm not suggesting that any of these people are necessarily bad.
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But I am suggesting that some of them have to be because at some moment, you had to figure it out.
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At some moment, some of them met me.
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And so at some moment, they figured out that somebody doesn't think it's right.
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I was never knew what was going on, but I knew these people that were certain were wrong and I couldn't understand how so many people were certain.
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And it was because of this, because the spectrum of debate has been controlled so that we get the feeling that we are struggling in this space.
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And in that struggle, we have figured out the mystery.
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We have unmasked the monster. We have solved the Scooby-Doo.
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17:35.000 --> 17:41.000
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And I think a lot of the people at the bottom of this screen have been doing it their whole lives.
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I think a lot of the people at the bottom of the screen are aware that something is being exaggerated or overextended or the fidelity of the story is being oversimplified for national security reasons.
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17:55.000 --> 18:03.000
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I mean, most of these people that watch TV are too dumb to understand anyway, so we've got to have a message for them and a message for internal.
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And that's how they tell themselves that what these emails mean.
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18:08.000 --> 18:18.000
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But none of them are probably aware that the email and the leaks and that whole thing was actually part of this bigger ploy, this bigger probably military operation.
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I don't know, some operation to make people think that a lab leak was possible and then now a lab leak happened.
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18:25.000 --> 18:40.000
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And the people that have risen inside of the narrative, I believe, at some moment, we have to think very carefully about how it happened and why it would have happened that way or not that way.
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18:41.000 --> 19:01.000
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And 2020 documented on the Internet and videos and blogs and sub stacks and 2021, the first half of it before the legendary podcast where Steve Kirsch and Robert Malone came out on the dark horse.
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Those six months are the most important months for us to document and mine for behavior.
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19:08.000 --> 19:24.000
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Because there's no reason that anyone could not have been where I was in 2020, which was natural immunity, previous exposure to any other viruses that use RNA and spike proteins.
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And the idea that transfection wasn't going to work because that's just a crazy idea.
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And I was actually too chicken to say that it might work for old people because they may be in trouble.
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And so maybe it's worthwhile giving it to them. I still wasn't there yet.
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I still didn't see that, but that rationale allows the security state to give your grandfather or grandmother anything that they want to under the pretense that old people are vulnerable.
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19:54.000 --> 20:05.000
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But I was still trying to talk myself out of the fear tree in 2020 like everybody was because there were people who ran us up the fear tree.
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|
|
||
|
20:06.000 --> 20:22.000
|
||
|
And that fear tree was this worst case scenario right that March was just the tip of the iceberg and before you knew it, everybody was going to know somebody who dropped dead in the street from COVID and had to call the police.
|
||
|
|
||
|
20:22.000 --> 20:32.000
|
||
|
They lied to us about the pandemic potential in nature and accessible and laboratories in order to invert our human rights to to a permission system.
|
||
|
|
||
|
20:32.000 --> 20:41.000
|
||
|
And I don't think very many people are really fighting for us, but they're fighting for position in this next system.
|
||
|
|
||
|
20:41.000 --> 20:51.000
|
||
|
And many of them through their experience and connections probably know that there's very, very little chance for us to turn this cruise ship around.
|
||
|
|
||
|
20:51.000 --> 21:03.000
|
||
|
But there are a few people I believe are still fighting for the possibility that we could slow the ship down first and then see if we can do something after that.
|
||
|
|
||
|
21:03.000 --> 21:07.000
|
||
|
So let's see what we're doing here tonight.
|
||
|
|
||
|
21:07.000 --> 21:20.000
|
||
|
So that's what this is all about. That's what's controlling this thing. They told us this thing happened. And, well, I don't know why I didn't mean to go through that fast. They told us this thing happened in 2020.
|
||
|
|
||
|
21:20.000 --> 21:33.000
|
||
|
And ever since they've been committed to this basic set of lies, I think, which is that a novel virus has spread from a point in Wuhan and went all around the world.
|
||
|
|
||
|
21:33.000 --> 21:38.000
|
||
|
Might have been a lab leak. And that's why we had to close down.
|
||
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|
||
|
21:38.000 --> 21:47.000
|
||
|
That's why the borders of these countries had to be closed. That's why schools had to be closed. That's why your kid loves iPads now.
|
||
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|
||
|
21:47.000 --> 22:00.000
|
||
|
And we had to use something and MRNA actually worked really well, except there was a lot of rushing. The LNP's weren't tested. There was an adequate quality control. The list goes on.
|
||
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|
||
|
22:00.000 --> 22:06.000
|
||
|
And so there's always a chance to do it better. You'll see tonight, tonight that they are going to try and do it better.
|
||
|
|
||
|
22:06.000 --> 22:14.000
|
||
|
And then finally, because it was a gain of function virus that we covered up, that we were likely involved in, it could definitely happen again.
|
||
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|
||
|
22:14.000 --> 22:22.000
|
||
|
If we do don't do something drastic, like put everybody on a digital ID.
|
||
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|
||
|
22:22.000 --> 22:34.000
|
||
|
Now it is to realize that transfection is not immunization, that intramuscular injection of any combination of substances to augment the immune system is not really a great idea.
|
||
|
|
||
|
22:34.000 --> 22:49.000
|
||
|
It's not a proven methodology. It's something that is one of the least investigated forms of therapeutic in modern western medicine, whether anybody likes to hear it or not.
|
||
|
|
||
|
22:49.000 --> 23:09.000
|
||
|
And I think it sticks my neck out in a direction that it should be sticking out simply because lots of other people have had their necks stuck out in this direction for many years while I still had my head buried in the books and in the microscope.
|
||
|
|
||
|
23:09.000 --> 23:15.000
|
||
|
And so I'm ready to pick this mantle up because I think it is a valid one.
|
||
|
|
||
|
23:15.000 --> 23:25.000
|
||
|
There may be ways of augmenting the immune system, but the formulations that have been used up until this point are really ridiculous.
|
||
|
|
||
|
23:25.000 --> 23:29.000
|
||
|
And the fact of the matter is they have not been tested.
|
||
|
|
||
|
23:30.000 --> 23:43.000
|
||
|
And there's lots of biology, if you think about it, that do not support the intramuscular injection of combination of chemicals and adjuvants and antigens to augment the immune system.
|
||
|
|
||
|
23:43.000 --> 23:56.000
|
||
|
You might get away with it, but it's not a very good way to do it, and it's certainly not a good way to avoid all kinds of other possibilities, which are most certainly possibilities.
|
||
|
|
||
|
23:56.000 --> 24:04.000
|
||
|
Because we have literally thousands and thousands of examples of this.
|
||
|
|
||
|
24:04.000 --> 24:20.000
|
||
|
So I just wanted to call attention first to a couple things that are on my radar so that you know that I hate to use that term because I think there's a lot of internet people right now that are doing news shows where they say, let's check my radar or something like that.
|
||
|
|
||
|
24:20.000 --> 24:24.000
|
||
|
Somebody sent me this blog, the second smartest guy in the world.
|
||
|
|
||
|
24:24.000 --> 24:38.000
|
||
|
And I stopped reading after the article cited this right here, which is NEPA virus vector sequences and COVID-19 patients sample sequined by the Wuhan Institute of Virology.
|
||
|
|
||
|
24:38.000 --> 24:42.000
|
||
|
That title immediately rang a bell in my head.
|
||
|
|
||
|
24:42.000 --> 24:51.000
|
||
|
That title belongs to NEPA virus vector sequences paper by Stephen Quay and Yuri Dagan.
|
||
|
|
||
|
24:51.000 --> 24:59.000
|
||
|
Stephen Quay may be a reasonably good guy. He's a businessman and a scientist.
|
||
|
|
||
|
24:59.000 --> 25:08.000
|
||
|
This, this fellow here, he may, whoops, sorry, this fellow here, he may be a good guy, Dave, Dave, or I don't know how to say those names.
|
||
|
|
||
|
25:08.000 --> 25:17.000
|
||
|
Adrian may be a good guy, Yuri may be a good guy, just trying to find a way to make people live longer.
|
||
|
|
||
|
25:17.000 --> 25:27.000
|
||
|
But I have my doubts. And more importantly, I have my doubts about NEPA virus and it's spreading without just being cloned and sprayed.
|
||
|
|
||
|
25:27.000 --> 25:38.000
|
||
|
And so this paper is actually talking about infectious clones. You can read this paper. It's not a, it's not a paper that I'm saying you have to.
|
||
|
|
||
|
25:38.000 --> 25:46.000
|
||
|
It's not a must read. But if you, if you want to know what I'm talking about in the sense of what I'm referencing, you can take a look at this paper.
|
||
|
|
||
|
25:46.000 --> 26:01.000
|
||
|
They're looking at sequences and they, they say that they're finding evidence of a, of a NEPA virus infectious clone that is listed in the, in the, in the virology database or whatever.
|
||
|
|
||
|
26:01.000 --> 26:08.000
|
||
|
So it's, it's, it's great. Those guys are, are fantastic.
|
||
|
|
||
|
26:08.000 --> 26:18.000
|
||
|
This, this article, though, also cites the fact that we're in India with it. It also cites the fact that Bill Gates has talked about.
|
||
|
|
||
|
26:18.000 --> 26:28.000
|
||
|
Oh, sorry, it's right there. It's talked about that there's going to be a next virus. And so there's, he makes the argument that maybe NEPA virus is going to be the next virus.
|
||
|
|
||
|
26:29.000 --> 26:38.000
|
||
|
I think Twiv thinks it's going to be the Lhasa virus. And so that's why I thought we would look at Twiv. Oh yeah. And I wanted to show this.
|
||
|
|
||
|
26:38.000 --> 26:51.000
|
||
|
Robert Malone did a sub stack. This is September 18. I guess that's today. You know, he puts out like four articles a day. So it's like hard to tell what day each comes out in.
|
||
|
|
||
|
26:51.000 --> 26:56.000
|
||
|
But in this article, he's talking about a cult leader.
|
||
|
|
||
|
26:56.000 --> 27:06.000
|
||
|
And I'm not really sure who he's referring to. A lot of times he talks about things that you could easily see him as being. I don't think he's a cult leader per se.
|
||
|
|
||
|
27:07.000 --> 27:23.000
|
||
|
But I kind of hypothesize that it would be better for his motivations if he became a sort of cult leader or a sort of, you know, default disambiguation wizard.
|
||
|
|
||
|
27:23.000 --> 27:27.000
|
||
|
Is that what he called himself in that video?
|
||
|
|
||
|
27:27.000 --> 27:43.000
|
||
|
I noticed in this article that that transition was rough that he says in cult over the past two years, I've come to realize how easily groups of people can be manipulated and controlled by those in power.
|
||
|
|
||
|
27:44.000 --> 27:58.000
|
||
|
The process is used for such manipulation reflect the same process is used by coal leaders and the official trailer from the documentary describes why people join cults but it also offers insights into exactly how people can be manipulated.
|
||
|
|
||
|
27:58.000 --> 28:00.000
|
||
|
I'm not going to play that trailer here.
|
||
|
|
||
|
28:00.000 --> 28:05.000
|
||
|
I want you to read the next paragraph.
|
||
|
|
||
|
28:05.000 --> 28:16.000
|
||
|
In 2021, I edited the Robert F Kennedy's book, the real Anthony Fauci. It was a huge undertaking.
|
||
|
|
||
|
28:16.000 --> 28:23.000
|
||
|
I was proud of my contributions, but also horrified by what that book revealed as was Jill.
|
||
|
|
||
|
28:23.000 --> 28:30.000
|
||
|
She posted a link to the book on her Facebook page, just to link mind you with a recommendation to read the book.
|
||
|
|
||
|
28:30.000 --> 28:37.000
|
||
|
In-law of ours who lives in the DC area, someone we thought of as a personal friend immediately blocked Jill permanently.
|
||
|
|
||
|
28:37.000 --> 28:49.000
|
||
|
The sin being that Jill being critical of Anthony Fauci by publicizing RFK's whoa, RFK carefully researched and footnoted book.
|
||
|
|
||
|
28:49.000 --> 28:53.000
|
||
|
This branch of our family has literally not talked to Jill or I sense.
|
||
|
|
||
|
28:53.000 --> 28:57.000
|
||
|
Literally has not talked to Jill and I sense.
|
||
|
|
||
|
28:57.000 --> 29:04.000
|
||
|
You can also just say actually or you can just say this branch of our family has not talked to Jill or I sense.
|
||
|
|
||
|
29:04.000 --> 29:14.000
|
||
|
The literally is completely incorrect there to the point where it annoys me because this is exactly how children use it all the time.
|
||
|
|
||
|
29:14.000 --> 29:16.000
|
||
|
It's awful.
|
||
|
|
||
|
29:16.000 --> 29:20.000
|
||
|
We are not invited to gatherings where they are in attendance.
|
||
|
|
||
|
29:20.000 --> 29:24.000
|
||
|
We are permanently banned from the village.
|
||
|
|
||
|
29:24.000 --> 29:29.000
|
||
|
Isn't that a Hillary Clinton takes a village to raise a child?
|
||
|
|
||
|
29:29.000 --> 29:36.000
|
||
|
For the social sin of posting a link, that was critical of Anthony Fauci.
|
||
|
|
||
|
29:36.000 --> 29:41.000
|
||
|
This is one example of cult-like behavior. I expect you are familiar with many others.
|
||
|
|
||
|
29:41.000 --> 30:01.000
|
||
|
The reason why I buzzed there was because I edited Robert F. Kennedy's book is a very interesting statement to publish on sub-stack to millions of followers for potentially thousands of dollars a month.
|
||
|
|
||
|
30:02.000 --> 30:12.000
|
||
|
Now, edited a book is a pretty big deal. If I edited Predator the movie, that means a certain thing.
|
||
|
|
||
|
30:12.000 --> 30:28.000
|
||
|
It doesn't mean that I was given a storyboard and said what do you think or I was given a script and said what do you think or said what do you think about this person playing that character?
|
||
|
|
||
|
30:28.000 --> 30:41.000
|
||
|
Hey, can you give me some insight into the kind of biological technology that an alien might have in this movie and I need some ideas for the script, the movie is called Predator.
|
||
|
|
||
|
30:41.000 --> 30:46.000
|
||
|
So then if I turned around and said, yeah, I edited that movie, it would be like, well, no, you didn't.
|
||
|
|
||
|
30:46.000 --> 30:57.000
|
||
|
You gave all the ideas or you gave some feedback on the camouflage or the shape of the mouth.
|
||
|
|
||
|
30:57.000 --> 31:09.000
|
||
|
So when you say I edited Robert F. Kennedy's book, you're kind of saying you sat in a certain chair that as far as I can tell Robert Malone didn't sit in.
|
||
|
|
||
|
31:09.000 --> 31:20.000
|
||
|
Now, I'm not accusing him of anything. I'm not saying anything. I don't. I'm just throwing out there that it's an interesting sentence.
|
||
|
|
||
|
31:20.000 --> 31:30.000
|
||
|
It's an interesting statement. Just walk in the line because he probably was consulted. Maybe he had an early copy.
|
||
|
|
||
|
31:30.000 --> 31:49.000
|
||
|
I don't know exactly the story because it's not my job there. So I'm not going to call anybody and ask, but I put all my chips on the fact that he didn't edit the book because I know from working on the Wuhan book, what that means and who sits in those chairs.
|
||
|
|
||
|
31:49.000 --> 32:10.000
|
||
|
And I know, I just know. And so it's not an inaccuracy that I'm very happy about because then he goes on to, you know, make it seem like, you know, in addition to all the other sacrifices he's made, you know,
|
||
|
|
||
|
32:10.000 --> 32:20.000
|
||
|
like hours that he could have been with his emus or hours where he could have been with his baby horses. He's been, you know, fighting for our freedom or on our behalf.
|
||
|
|
||
|
32:20.000 --> 32:33.000
|
||
|
He's also, you know, got his neck out on the line for the real Anthony Fauci book and even lost people in his family because they talked about the book.
|
||
|
|
||
|
32:33.000 --> 32:43.000
|
||
|
So he lost people in his family because he talked about the book, but not because of the, of the mRNA or because of coming out for the shot.
|
||
|
|
||
|
32:43.000 --> 33:00.000
|
||
|
And so it's a strange thing, like which, which part of your dissident, you know, lifestyle of the intro most interesting man in the world is the one that cost you your friends. Was it really the Anthony Fauci book and a post on Facebook.
|
||
|
|
||
|
33:00.000 --> 33:10.000
|
||
|
And then what, and then you lost all your family. So then you thought, well, heck, I'll, I'll just speak out more or what. I don't know. It's weird to me.
|
||
|
|
||
|
33:10.000 --> 33:24.000
|
||
|
I just, you know, I maybe I'm obsessing about him, but there's something, there's just something there.
|
||
|
|
||
|
33:25.000 --> 33:29.000
|
||
|
Oh, sorry about that.
|
||
|
|
||
|
33:29.000 --> 33:34.000
|
||
|
So let's do this. I think you're really going to enjoy this. I really do.
|
||
|
|
||
|
33:34.000 --> 33:50.000
|
||
|
The reason why you're going to enjoy it is because they talk about a lot of stuff that we can follow along with the paper, maybe, and you're going to see there's a couple huge biological concepts that come up in the first paper
|
||
|
|
||
|
33:51.000 --> 33:58.000
|
||
|
that are just spectacular. And then how all five of them are four of them. I don't know if there's four or five today.
|
||
|
|
||
|
33:58.000 --> 34:03.000
|
||
|
All four or five of them are kind of there. They kind of get it.
|
||
|
|
||
|
34:03.000 --> 34:15.000
|
||
|
But I'll take you all the way over the finish line to show you why these, these are these concepts and therefore biological concepts revelations they could be are completely missed.
|
||
|
|
||
|
34:16.000 --> 34:25.000
|
||
|
So, how in depth they could go, but they just don't go because the idea is to bamboozle. The idea is not to inform.
|
||
|
|
||
|
34:25.000 --> 34:37.000
|
||
|
And so let's just watch and see what, what kind of, you know, fumbles I can pick up and run in for touchdowns repeatedly as they talk about these two papers.
|
||
|
|
||
|
34:38.000 --> 34:45.000
|
||
|
This week in virology, the podcast about viruses, the kind that made it all sick.
|
||
|
|
||
|
34:49.000 --> 34:57.000
|
||
|
From Microbe TV, this is Twiv, this week in virology, episode 1045 recorded on September 15, 2023.
|
||
|
|
||
|
34:57.000 --> 35:01.000
|
||
|
I'm Vincent Drackeniello and you're listening to the podcast all about viruses.
|
||
|
|
||
|
35:01.000 --> 35:04.000
|
||
|
Joining me today from Austin, Texas, Rich Condit.
|
||
|
|
||
|
35:04.000 --> 35:05.000
|
||
|
Hi everybody.
|
||
|
|
||
|
35:05.000 --> 35:10.000
|
||
|
I'm just booting up the weather here. Yes, Austin, Texas, get this 84 degrees, man.
|
||
|
|
||
|
35:10.000 --> 35:16.000
|
||
|
That's like 20 degrees less than when I last spoke to you. And there's been rain the past couple of days.
|
||
|
|
||
|
35:16.000 --> 35:20.000
|
||
|
And so we're all really happy about that. It's kind of, I guess it's clearing up now.
|
||
|
|
||
|
35:20.000 --> 35:23.000
|
||
|
Oh, it's some sunny ish, but I think we're out of the worst of it.
|
||
|
|
||
|
35:23.000 --> 35:28.000
|
||
|
That's gotten much cooler here. I can't find the temper. I'll let Breanne do it also joining us from Madison, New Jersey, Breanne Barker.
|
||
|
|
||
|
35:28.000 --> 35:31.000
|
||
|
Hi, it's great to be here. And here it is 72 Fahrenheit and beautifully sunny.
|
||
|
|
||
|
35:31.000 --> 35:33.000
|
||
|
We've had a lovely last couple of days.
|
||
|
|
||
|
35:33.000 --> 35:35.000
|
||
|
From Western Massachusetts, Alan Dove.
|
||
|
|
||
|
35:35.000 --> 35:39.000
|
||
|
Good to be here. It is 67 Fahrenheit, 19C overcast.
|
||
|
|
||
|
35:39.000 --> 35:45.000
|
||
|
And we have somewhere far out off the Cape, somewhere to our east is some remnants of tropical storm Lee,
|
||
|
|
||
|
35:45.000 --> 35:48.000
|
||
|
which is supposed to bring storm surge to the Cape and islands.
|
||
|
|
||
|
35:48.000 --> 35:54.000
|
||
|
And we're getting no rain out of it, which is a nice relief because we have been deluged with rain for the past couple of weeks.
|
||
|
|
||
|
35:54.000 --> 35:57.000
|
||
|
And from Montreal, Canada, Angela Mingarelli.
|
||
|
|
||
|
35:57.000 --> 36:01.000
|
||
|
Hey everyone. So for the first time, maybe the first time, it's not the coldest in Montreal.
|
||
|
|
||
|
36:01.000 --> 36:03.000
|
||
|
So it's 70 Fahrenheit and 21.
|
||
|
|
||
|
36:03.000 --> 36:10.000
|
||
|
So the first paper, they're going to look at a paper where Moderna makes an RNA virus.
|
||
|
|
||
|
36:10.000 --> 36:15.000
|
||
|
Sorry, an RNA mRNA vaccine for loss of virus.
|
||
|
|
||
|
36:15.000 --> 36:18.000
|
||
|
And they look at it in guinea pigs.
|
||
|
|
||
|
36:18.000 --> 36:26.000
|
||
|
And it's extraordinary what they find because what they find is that neutralizing antibodies don't matter.
|
||
|
|
||
|
36:27.000 --> 36:49.000
|
||
|
And this twib will kind of stumble through that revelation and mention some other mechanisms in immunology that they don't think about from the perspective of, let's say, coronavirus infection or any other infection and what that might mean from the perspective of how the immune system works.
|
||
|
|
||
|
36:50.000 --> 36:52.000
|
||
|
If you like our work, we'd love your support.
|
||
|
|
||
|
36:52.000 --> 36:55.000
|
||
|
It doesn't have to be huge, but it needs to be has to exist.
|
||
|
|
||
|
36:55.000 --> 36:58.000
|
||
|
And you can go to micro doesn't have to be.
|
||
|
|
||
|
36:58.000 --> 37:02.000
|
||
|
All right, we have a couple of announcements. First of all, if you like our work, we'd love your support.
|
||
|
|
||
|
37:02.000 --> 37:06.000
|
||
|
Your financial support. It doesn't have to be huge, but it needs to be has to exist.
|
||
|
|
||
|
37:06.000 --> 37:09.000
|
||
|
And you can go to micro.tv slash contribute to do that.
|
||
|
|
||
|
37:09.000 --> 37:15.000
|
||
|
You know, as the pandemic recedes, people forget about viruses, but we'd like to keep on communicating micro TV does more than viruses.
|
||
|
|
||
|
37:15.000 --> 37:19.000
|
||
|
There's many other cool things. And please help us do that, micro.tv slash contribute.
|
||
|
|
||
|
37:19.000 --> 37:22.000
|
||
|
I want to wish Fiona a happy 40th birthday.
|
||
|
|
||
|
37:22.000 --> 37:24.000
|
||
|
Happy birthday, Fiona. Happy birthday, Fiona.
|
||
|
|
||
|
37:24.000 --> 37:26.000
|
||
|
Well, it's September 7th.
|
||
|
|
||
|
37:26.000 --> 37:32.000
|
||
|
And I hope you had a good time. Fiona is a PhD in psychology and a massive Twiv fan.
|
||
|
|
||
|
37:32.000 --> 37:33.000
|
||
|
Cool.
|
||
|
|
||
|
37:33.000 --> 37:36.000
|
||
|
Her husband anniversary of your 39th birthday is always a good time.
|
||
|
|
||
|
37:36.000 --> 37:39.000
|
||
|
I think you could probably do a PhD in psychology shrinking the Twiv hosts.
|
||
|
|
||
|
37:39.000 --> 37:40.000
|
||
|
Oh boy.
|
||
|
|
||
|
37:40.000 --> 37:41.000
|
||
|
Indeed.
|
||
|
|
||
|
37:41.000 --> 37:42.000
|
||
|
You don't want to go into our heads.
|
||
|
|
||
|
37:42.000 --> 37:43.000
|
||
|
I don't think it's a good thing.
|
||
|
|
||
|
37:43.000 --> 37:44.000
|
||
|
No, no.
|
||
|
|
||
|
37:44.000 --> 37:50.000
|
||
|
Her husband who wrote in saying, would you please do this said she probably should be a virologist.
|
||
|
|
||
|
37:50.000 --> 37:51.000
|
||
|
She loves Twiv.
|
||
|
|
||
|
37:51.000 --> 37:52.000
|
||
|
So thanks for listening.
|
||
|
|
||
|
37:52.000 --> 37:53.000
|
||
|
Keep it up, Fiona.
|
||
|
|
||
|
37:53.000 --> 37:54.000
|
||
|
Many more.
|
||
|
|
||
|
37:54.000 --> 37:59.000
|
||
|
Don't forget there is a second position in Amy Rosenfeld's lab at the FDA.
|
||
|
|
||
|
37:59.000 --> 38:10.000
|
||
|
This is a research assistant to work on enteroviruses, making animal models, understanding the consequence of cross-reactive antibody responses, doing cell culture, all BSL to work.
|
||
|
|
||
|
38:10.000 --> 38:13.000
|
||
|
We'll have a link in the show notes and you can find an email to find out more.
|
||
|
|
||
|
38:13.000 --> 38:19.000
|
||
|
And sadly, I want to tell everyone that Robert Lam, or Bob Lam as we used to call him, passed away on September 2nd.
|
||
|
|
||
|
38:19.000 --> 38:29.000
|
||
|
He was a very important influenza virologist who was on Twiv a couple of times and who was always very, very good science, but also very enjoyable person.
|
||
|
|
||
|
38:29.000 --> 38:31.000
|
||
|
So we will miss him.
|
||
|
|
||
|
38:31.000 --> 38:33.000
|
||
|
Sorry to lose him so early.
|
||
|
|
||
|
38:33.000 --> 38:34.000
|
||
|
Yeah.
|
||
|
|
||
|
38:34.000 --> 38:42.000
|
||
|
He was a post-doc with Purnell Schopen at Rockefeller University, which is where I first met him.
|
||
|
|
||
|
38:42.000 --> 38:45.000
|
||
|
He was on my qualifying exam committee.
|
||
|
|
||
|
38:45.000 --> 38:49.000
|
||
|
He had a wonderful British accent and he was quick and funny and a lot of fun.
|
||
|
|
||
|
38:49.000 --> 38:51.000
|
||
|
I always sought him out at meetings.
|
||
|
|
||
|
38:51.000 --> 38:53.000
|
||
|
It was fun to talk to him.
|
||
|
|
||
|
38:53.000 --> 38:57.000
|
||
|
And then for most of his career, he was at Northwestern University.
|
||
|
|
||
|
38:57.000 --> 38:59.000
|
||
|
So sorry to see you go, Bob.
|
||
|
|
||
|
38:59.000 --> 39:01.000
|
||
|
Nice picture of Bob here on the obituary.
|
||
|
|
||
|
39:02.000 --> 39:05.000
|
||
|
I hope you find some good plaque assays wherever he goes.
|
||
|
|
||
|
39:05.000 --> 39:07.000
|
||
|
Black assay heaven.
|
||
|
|
||
|
39:07.000 --> 39:08.000
|
||
|
Black assay heaven.
|
||
|
|
||
|
39:08.000 --> 39:09.000
|
||
|
Yeah, that's a good one.
|
||
|
|
||
|
39:09.000 --> 39:10.000
|
||
|
All right.
|
||
|
|
||
|
39:10.000 --> 39:12.000
|
||
|
We have two very cool papers for you today.
|
||
|
|
||
|
39:12.000 --> 39:20.000
|
||
|
The first, our snippet, is in Nature Communications, a lassivirus mRNA vaccine confers protection, but does not require neutralizing antibody in a guinea pig model of infection.
|
||
|
|
||
|
39:20.000 --> 39:22.000
|
||
|
And that's why I want you to know about this paper.
|
||
|
|
||
|
39:22.000 --> 39:25.000
|
||
|
You don't need antibody, apparently.
|
||
|
|
||
|
39:25.000 --> 39:28.000
|
||
|
We'll go through it, but very I want you to know about this paper.
|
||
|
|
||
|
39:28.000 --> 39:30.000
|
||
|
You don't need antibody, apparently.
|
||
|
|
||
|
39:30.000 --> 39:32.000
|
||
|
We'll go through it, but very interesting.
|
||
|
|
||
|
39:32.000 --> 39:34.000
|
||
|
Well, you don't need neutralizing antibody.
|
||
|
|
||
|
39:34.000 --> 39:36.000
|
||
|
Yes, that's a title, neutralizing antibody.
|
||
|
|
||
|
39:36.000 --> 39:44.000
|
||
|
And so this is two first authors, Adam Rankin, Nico Lloyd, and two last authors, Andrea Carphy, and Alexander Bookraev, who I noticed on LinkedIn.
|
||
|
|
||
|
39:44.000 --> 39:48.000
|
||
|
He just was talking about this paper and I said, we're doing it on Twiv right now.
|
||
|
|
||
|
39:48.000 --> 39:57.000
|
||
|
This is from University of Texas, Galveston, Harvard, Scripps, La Jolla Institute for Immunology, and the Academic Medical Center in the Netherlands and Moderna.
|
||
|
|
||
|
39:58.000 --> 40:01.000
|
||
|
So there are a couple of vaccines in development for lassivirus.
|
||
|
|
||
|
40:01.000 --> 40:05.000
|
||
|
This is one of them, but the neutralizing antibody angle is very interesting.
|
||
|
|
||
|
40:05.000 --> 40:09.000
|
||
|
Lassivirus is the virus that got me interested in virology.
|
||
|
|
||
|
40:09.000 --> 40:10.000
|
||
|
Honestly, it really is.
|
||
|
|
||
|
40:10.000 --> 40:18.000
|
||
|
I read this book, Fever, after I graduated from college, and I said, oh, my gosh, viruses can go from animals to humans.
|
||
|
|
||
|
40:18.000 --> 40:20.000
|
||
|
And I said, that's a cool thing.
|
||
|
|
||
|
40:20.000 --> 40:21.000
|
||
|
I'm trying to rearrange my monitor here.
|
||
|
|
||
|
40:21.000 --> 40:22.000
|
||
|
That's why I'm looking funny.
|
||
|
|
||
|
40:22.000 --> 40:23.000
|
||
|
There we go.
|
||
|
|
||
|
40:23.000 --> 40:24.000
|
||
|
That's a cool thing.
|
||
|
|
||
|
40:24.000 --> 40:26.000
|
||
|
And this book, John Fuller, which is very cool.
|
||
|
|
||
|
40:26.000 --> 40:27.000
|
||
|
You should read it.
|
||
|
|
||
|
40:27.000 --> 40:28.000
|
||
|
I looked into getting into virology.
|
||
|
|
||
|
40:28.000 --> 40:32.000
|
||
|
So lassivirus, it's an envelope RNA virus, negative stranded.
|
||
|
|
||
|
40:32.000 --> 40:41.000
|
||
|
It causes up between 100 and 300,000 cases every year, primarily in Africa, first found in lassa, Nigeria, about 5,000 deaths.
|
||
|
|
||
|
40:41.000 --> 40:46.000
|
||
|
And this is an important, this is a medical need for sure, 5,000 deaths, 300,000 cases.
|
||
|
|
||
|
40:46.000 --> 40:48.000
|
||
|
They often go to other countries.
|
||
|
|
||
|
40:48.000 --> 40:50.000
|
||
|
And that's 5,000 deaths a year, right?
|
||
|
|
||
|
40:50.000 --> 40:51.000
|
||
|
Not in general, that's a year.
|
||
|
|
||
|
40:51.000 --> 40:52.000
|
||
|
Exactly.
|
||
|
|
||
|
40:52.000 --> 40:55.000
|
||
|
That we know about, that we know that we're diagnosed with this virus.
|
||
|
|
||
|
40:55.000 --> 40:57.000
|
||
|
No, I mean, just for the listeners, because it's a year.
|
||
|
|
||
|
40:57.000 --> 40:58.000
|
||
|
That's 5,000 a year.
|
||
|
|
||
|
40:58.000 --> 40:59.000
|
||
|
Yes, not since.
|
||
|
|
||
|
40:59.000 --> 41:00.000
|
||
|
Not since the beginning of the month.
|
||
|
|
||
|
41:00.000 --> 41:01.000
|
||
|
A year.
|
||
|
|
||
|
41:01.000 --> 41:07.000
|
||
|
And this is, this is a virus that is, it is from animals, it comes from rodents into humans through rodent waste.
|
||
|
|
||
|
41:07.000 --> 41:12.000
|
||
|
So it's in conditions where people are around peri-domestic rodents and there are a couple of species that are especially good at carrying it.
|
||
|
|
||
|
41:12.000 --> 41:16.000
|
||
|
And they get the, they basically inhale the fumes and get the virus.
|
||
|
|
||
|
41:16.000 --> 41:18.000
|
||
|
I was impressed here.
|
||
|
|
||
|
41:18.000 --> 41:20.000
|
||
|
It mentioned something about how long.
|
||
|
|
||
|
41:21.000 --> 41:23.000
|
||
|
So again, did you hear what he said?
|
||
|
|
||
|
41:23.000 --> 41:24.000
|
||
|
Maybe you should hear that again.
|
||
|
|
||
|
41:24.000 --> 41:25.000
|
||
|
Some of that.
|
||
|
|
||
|
41:25.000 --> 41:31.000
|
||
|
A virus that is, it is from animals, it comes from rodents into humans through rodent waste.
|
||
|
|
||
|
41:31.000 --> 41:36.000
|
||
|
So it's in conditions where people are around peri-domestic rodents and there are a couple of species that are especially good at carrying it.
|
||
|
|
||
|
41:36.000 --> 41:39.000
|
||
|
And they get the, they basically inhale the fumes.
|
||
|
|
||
|
41:39.000 --> 41:48.000
|
||
|
So if you're living around rats and you have enough of a rat infestation that you have the dust from their excrement,
|
||
|
|
||
|
41:49.000 --> 41:52.000
|
||
|
you can get this virus or this pathogen.
|
||
|
|
||
|
41:53.000 --> 42:13.000
|
||
|
So again, here we are again talking about a scenario where just imagine now if at the same time people started getting houses and stopped being homeless and stopped living on the street and started eating better and started eating separately from where they,
|
||
|
|
||
|
42:14.000 --> 42:16.000
|
||
|
where they go number one and two,
|
||
|
|
||
|
42:17.000 --> 42:19.000
|
||
|
then diseases plummet.
|
||
|
|
||
|
42:20.000 --> 42:23.000
|
||
|
And so yeah, 5,000 people die every year from this.
|
||
|
|
||
|
42:23.000 --> 42:28.000
|
||
|
But do we need to vaccinate those people or should we just give them sanitary places to live?
|
||
|
|
||
|
42:31.000 --> 42:32.000
|
||
|
And let me turn that around again.
|
||
|
|
||
|
42:32.000 --> 42:35.000
|
||
|
Do we need to vaccinate those people or should we give them?
|
||
|
|
||
|
42:36.000 --> 42:38.000
|
||
|
See, that's not what they want.
|
||
|
|
||
|
42:38.000 --> 42:42.000
|
||
|
They don't want to give those places healthy, people healthy places to live.
|
||
|
|
||
|
42:42.000 --> 42:45.000
|
||
|
They don't want to improve their living conditions.
|
||
|
|
||
|
42:45.000 --> 42:52.000
|
||
|
They want to test their, their, their augmentation of the immune system.
|
||
|
|
||
|
42:53.000 --> 42:58.000
|
||
|
And this is what this is, for me, this has become obvious that this whole,
|
||
|
|
||
|
43:00.000 --> 43:02.000
|
||
|
this is, this is something else.
|
||
|
|
||
|
43:02.000 --> 43:05.000
|
||
|
They're doing something else here other than virology.
|
||
|
|
||
|
43:06.000 --> 43:13.000
|
||
|
This is, this is a mad rush to try and use this opening to,
|
||
|
|
||
|
43:14.000 --> 43:26.000
|
||
|
to blow open as many possibilities as possible in terms of methodology and new application of gene technology to every aspect of public health.
|
||
|
|
||
|
43:27.000 --> 43:32.000
|
||
|
And so any new model they can find where RNA works the better,
|
||
|
|
||
|
43:32.000 --> 43:44.000
|
||
|
because then they're going to frame it in this false frame of, well, we know that RNA works really well in people because we gave billions of doses and only a few thousand people were injured.
|
||
|
|
||
|
43:45.000 --> 43:47.000
|
||
|
Nobody died. I mean, come on.
|
||
|
|
||
|
43:48.000 --> 43:51.000
|
||
|
That's what everybody on this screen would likely say.
|
||
|
|
||
|
43:52.000 --> 43:56.000
|
||
|
We probably don't know if anybody really has died from the vaccine.
|
||
|
|
||
|
43:56.000 --> 44:03.000
|
||
|
I guess a few people had some clots, but it's an insignificant number against the billions of people who didn't.
|
||
|
|
||
|
44:06.000 --> 44:08.000
|
||
|
And so be aware that that's where we are now.
|
||
|
|
||
|
44:08.000 --> 44:17.000
|
||
|
Now we're talking about a nature paper where we're immunizing guinea pigs against a virus that comes from very bad unsanitary conditions that include rats.
|
||
|
|
||
|
44:17.000 --> 44:26.000
|
||
|
And we're talking about using an mRNA vaccine to protect from that.
|
||
|
|
||
|
44:27.000 --> 44:37.000
|
||
|
And now we're just going to stumble through the immunology and they're going to admit that, well, you know, tertiary target or quaternary targeted antibodies are important.
|
||
|
|
||
|
44:38.000 --> 44:42.000
|
||
|
And not really explain what quaternary antibodies are.
|
||
|
|
||
|
44:43.000 --> 44:45.000
|
||
|
A perfect teaching moment. Here we go.
|
||
|
|
||
|
44:46.000 --> 44:47.000
|
||
|
Get the virus.
|
||
|
|
||
|
44:47.000 --> 44:56.000
|
||
|
I was impressed here. It mentioned something about how long some of the virus could be seen in post exposure, at least in human urine and semen.
|
||
|
|
||
|
44:56.000 --> 45:01.000
|
||
|
And I was like, whoa, there's a lot of potential reservoir for this beyond what I realized.
|
||
|
|
||
|
45:01.000 --> 45:06.000
|
||
|
So I've done a couple of last episodes with experts and they say most of the transmission is actually spillover from rodents.
|
||
|
|
||
|
45:06.000 --> 45:09.000
|
||
|
There's some human human, but not a lot. Most of it is a rodent spillover.
|
||
|
|
||
|
45:09.000 --> 45:12.000
|
||
|
You live in a house where there are rodents under the floor and that's how you get it, which is amazing.
|
||
|
|
||
|
45:12.000 --> 45:17.000
|
||
|
Is the geographical distribution constrained primarily by the distribution of the host?
|
||
|
|
||
|
45:17.000 --> 45:19.000
|
||
|
The rodent host, yeah. I suspect.
|
||
|
|
||
|
45:19.000 --> 45:28.000
|
||
|
And the other thing that I was unaware of, or if I knew and forgotten, is that it says that upwards of 80% of the cases are asymptomatic.
|
||
|
|
||
|
45:28.000 --> 45:29.000
|
||
|
Yeah.
|
||
|
|
||
|
45:29.000 --> 45:30.000
|
||
|
Yeah.
|
||
|
|
||
|
45:30.000 --> 45:31.000
|
||
|
Maybe underreported, right?
|
||
|
|
||
|
45:31.000 --> 45:34.000
|
||
|
Yeah. So they've got to figure that a hundred thousand to three hundred thousand human cases.
|
||
|
|
||
|
45:34.000 --> 45:36.000
|
||
|
That's known human cases.
|
||
|
|
||
|
45:36.000 --> 45:40.000
|
||
|
You know, probably a lot more people are infected because it turns out you can get this and not even know.
|
||
|
|
||
|
45:40.000 --> 45:41.000
|
||
|
Yeah.
|
||
|
|
||
|
45:41.000 --> 45:44.000
|
||
|
It's a virus you need to work with under BSL4 conditions.
|
||
|
|
||
|
45:44.000 --> 45:45.000
|
||
|
Yes.
|
||
|
|
||
|
45:45.000 --> 45:46.000
|
||
|
And it's the Galveston contribution here.
|
||
|
|
||
|
45:46.000 --> 45:50.000
|
||
|
And that's an important thing to remember going through this paper because as I was reading, I would occasionally say,
|
||
|
|
||
|
45:50.000 --> 45:53.000
|
||
|
oh, well, why didn't they? And then, oh, right. Yeah. They're in bubble suits. That's why they didn't.
|
||
|
|
||
|
45:53.000 --> 45:56.000
|
||
|
You can't. You can't just blast through your experiments like this.
|
||
|
|
||
|
45:56.000 --> 45:57.000
|
||
|
Yes. Very expensive.
|
||
|
|
||
|
45:57.000 --> 45:59.000
|
||
|
This is all done at the SL4.
|
||
|
|
||
|
45:59.000 --> 46:00.000
|
||
|
Yeah.
|
||
|
|
||
|
46:00.000 --> 46:04.000
|
||
|
And very time consuming is everything you do. You got to suit up and go in.
|
||
|
|
||
|
46:04.000 --> 46:05.000
|
||
|
Yeah.
|
||
|
|
||
|
46:05.000 --> 46:10.000
|
||
|
This is one of the viruses on the WHO blueprint for diseases that need accelerated research.
|
||
|
|
||
|
46:10.000 --> 46:15.000
|
||
|
And so this one is definitely one where we need a vaccine. There will be a vaccine at some point used, maybe multiple,
|
||
|
|
||
|
46:15.000 --> 46:22.000
|
||
|
but this is just one of them. And it's, of course, this mRNA vaccine is it was done because of the success with the SARS-CoV-2 vaccines.
|
||
|
|
||
|
46:22.000 --> 46:27.000
|
||
|
And so they have taken the mRNA encoding the spike like a person.
|
||
|
|
||
|
46:27.000 --> 46:30.000
|
||
|
They have made two versions, one, a pre-fusion version.
|
||
|
|
||
|
46:30.000 --> 46:31.000
|
||
|
Told you.
|
||
|
|
||
|
46:31.000 --> 46:33.000
|
||
|
I told you he even said it.
|
||
|
|
||
|
46:34.000 --> 46:35.000
|
||
|
That's listening to it again.
|
||
|
|
||
|
46:35.000 --> 46:40.000
|
||
|
This one is definitely one where we need a vaccine. There will be a vaccine at some point used, maybe multiple, but this is just one of them.
|
||
|
|
||
|
46:40.000 --> 46:46.000
|
||
|
And it's, of course, this mRNA vaccine is it was done because of the success with the SARS-CoV-2 vaccines.
|
||
|
|
||
|
46:46.000 --> 46:51.000
|
||
|
And so they have taken the mRNA encoding the spike like a protein of the virus.
|
||
|
|
||
|
46:51.000 --> 46:55.000
|
||
|
They have made two versions, one, a pre-fusion version, very much like the spike pre-fusion,
|
||
|
|
||
|
46:55.000 --> 46:59.000
|
||
|
the locket in a version that displays the relevant antigenic sites.
|
||
|
|
||
|
46:59.000 --> 47:02.000
|
||
|
And then they also use one without the pre-fusion locking to compare it.
|
||
|
|
||
|
47:02.000 --> 47:09.000
|
||
|
They put it in lipid nanoparticles and they deliver it to guinea pigs, which are the model for lassa disease.
|
||
|
|
||
|
47:09.000 --> 47:10.000
|
||
|
These are outbred animals.
|
||
|
|
||
|
47:10.000 --> 47:14.000
|
||
|
So remember that there's not a lot of immunological agents available and so forth.
|
||
|
|
||
|
47:14.000 --> 47:19.000
|
||
|
I'm assuming somebody's tried this in mice and it just doesn't work because it's...
|
||
|
|
||
|
47:19.000 --> 47:20.000
|
||
|
So when I...
|
||
|
|
||
|
47:20.000 --> 47:21.000
|
||
|
Good question.
|
||
|
|
||
|
47:21.000 --> 47:23.000
|
||
|
There are mouse species that are normally infected with this going around.
|
||
|
|
||
|
47:23.000 --> 47:30.000
|
||
|
So when I was at Rocky Mountain Labs, they were trying to establish a colony of mastomas natalantis, which is the natural reservoir.
|
||
|
|
||
|
47:30.000 --> 47:31.000
|
||
|
So that's not easy.
|
||
|
|
||
|
47:31.000 --> 47:33.000
|
||
|
You have to catch them and then you bring them and you get them to breed.
|
||
|
|
||
|
47:33.000 --> 47:35.000
|
||
|
And he said it's hard to breed them in captivity.
|
||
|
|
||
|
47:35.000 --> 47:38.000
|
||
|
So this was a couple of years ago, but I think that's the need.
|
||
|
|
||
|
47:38.000 --> 47:39.000
|
||
|
You know, musculous just doesn't work.
|
||
|
|
||
|
47:39.000 --> 47:40.000
|
||
|
Right.
|
||
|
|
||
|
47:40.000 --> 47:45.000
|
||
|
And I imagine there would be containment concerns with bringing another wild mouse into the country and breeding up a bunch of it
|
||
|
|
||
|
47:45.000 --> 47:49.000
|
||
|
when that mouse is endemic to many parts of Africa and is a reservoir for this.
|
||
|
|
||
|
47:49.000 --> 47:50.000
|
||
|
Definitely.
|
||
|
|
||
|
47:50.000 --> 47:51.000
|
||
|
Yeah, I mean, that would be a problem.
|
||
|
|
||
|
47:51.000 --> 47:54.000
|
||
|
And then if you wanted your model to have disease particularly...
|
||
|
|
||
|
47:54.000 --> 47:55.000
|
||
|
Seems like I was wrong.
|
||
|
|
||
|
47:55.000 --> 47:59.000
|
||
|
It looks like it's mice infestations that can do it.
|
||
|
|
||
|
47:59.000 --> 48:05.000
|
||
|
And unless you're going to ask them about going to the opera, you are not going to be able to have a lot of data on protection
|
||
|
|
||
|
48:05.000 --> 48:06.000
|
||
|
and your challenge model.
|
||
|
|
||
|
48:06.000 --> 48:07.000
|
||
|
Yeah.
|
||
|
|
||
|
48:07.000 --> 48:13.000
|
||
|
So we use guinea pigs and they are vaccinated intramuscularly with these lipid nanoparticles containing the spike mRNA,
|
||
|
|
||
|
48:13.000 --> 48:15.000
|
||
|
which has been pseudo urid-related.
|
||
|
|
||
|
48:15.000 --> 48:17.000
|
||
|
So it chemically modified.
|
||
|
|
||
|
48:17.000 --> 48:20.000
|
||
|
So it doesn't induce responses that would interfere with it.
|
||
|
|
||
|
48:20.000 --> 48:23.000
|
||
|
The controls are phosphate, buffered saline, infected guinea pigs.
|
||
|
|
||
|
48:23.000 --> 48:26.000
|
||
|
And then they look for first binding antibodies.
|
||
|
|
||
|
48:26.000 --> 48:29.000
|
||
|
So antibodies that will just bind the spike and they do find those.
|
||
|
|
||
|
48:29.000 --> 48:32.000
|
||
|
And in fact, both constructs induce binding antibodies.
|
||
|
|
||
|
48:32.000 --> 48:34.000
|
||
|
And then they look for neutralizing antibodies.
|
||
|
|
||
|
48:34.000 --> 48:36.000
|
||
|
So they do a neutralization assay.
|
||
|
|
||
|
48:36.000 --> 48:38.000
|
||
|
And some of the sera...
|
||
|
|
||
|
48:38.000 --> 48:43.000
|
||
|
Well, with the wild type mRNA, encoding the wild type spike without pre-fusion stabilization.
|
||
|
|
||
|
48:43.000 --> 48:47.000
|
||
|
None of the sera demonstrate neutralizing activity over the background found in the pre-immune serum.
|
||
|
|
||
|
48:47.000 --> 48:49.000
|
||
|
So basically no neutralization.
|
||
|
|
||
|
48:49.000 --> 48:54.000
|
||
|
And in the pre-fusion stabilized vaccinated group, two out of five animals have neutralizing activity.
|
||
|
|
||
|
48:54.000 --> 48:56.000
|
||
|
So two out of five animals.
|
||
|
|
||
|
48:56.000 --> 48:59.000
|
||
|
And even then it's not particularly impressively high.
|
||
|
|
||
|
48:59.000 --> 49:00.000
|
||
|
Yeah.
|
||
|
|
||
|
49:00.000 --> 49:04.000
|
||
|
And they say this variation from animal to animal is not surprising because they're outbred animals.
|
||
|
|
||
|
49:04.000 --> 49:06.000
|
||
|
And so they're genetically diverse.
|
||
|
|
||
|
49:06.000 --> 49:08.000
|
||
|
And that's assay neutralization.
|
||
|
|
||
|
49:08.000 --> 49:12.000
|
||
|
Maybe you said this, assay neutralization on virus.
|
||
|
|
||
|
49:12.000 --> 49:13.000
|
||
|
Virus.
|
||
|
|
||
|
49:13.000 --> 49:14.000
|
||
|
Yeah.
|
||
|
|
||
|
49:14.000 --> 49:16.000
|
||
|
And they have a plaque assay.
|
||
|
|
||
|
49:16.000 --> 49:17.000
|
||
|
Let's see.
|
||
|
|
||
|
49:17.000 --> 49:18.000
|
||
|
Let's go to the methods here.
|
||
|
|
||
|
49:18.000 --> 49:19.000
|
||
|
I didn't look closely enough for that.
|
||
|
|
||
|
49:19.000 --> 49:22.000
|
||
|
I'm going to do a thing which is plaque.
|
||
|
|
||
|
49:22.000 --> 49:25.000
|
||
|
Let's search for plaque and see if...
|
||
|
|
||
|
49:25.000 --> 49:26.000
|
||
|
That's what I was doing.
|
||
|
|
||
|
49:26.000 --> 49:27.000
|
||
|
That's what I was doing.
|
||
|
|
||
|
49:27.000 --> 49:28.000
|
||
|
Yeah.
|
||
|
|
||
|
49:28.000 --> 49:29.000
|
||
|
They did a plaque assay.
|
||
|
|
||
|
49:29.000 --> 49:30.000
|
||
|
Good for them.
|
||
|
|
||
|
49:30.000 --> 49:31.000
|
||
|
Yeah, good for them.
|
||
|
|
||
|
49:31.000 --> 49:32.000
|
||
|
So that's all BSL-4 work.
|
||
|
|
||
|
49:32.000 --> 49:33.000
|
||
|
Yeah.
|
||
|
|
||
|
49:33.000 --> 49:35.000
|
||
|
So the guinea pigs can be immunized outside the BSL-4.
|
||
|
|
||
|
49:35.000 --> 49:40.000
|
||
|
And then when you want to challenge them, which we haven't done yet, we bring them inside the BSL-4, obviously.
|
||
|
|
||
|
49:40.000 --> 49:51.000
|
||
|
So it's relevant to point out that one of the things that they point out is that the neutralizing antibodies that they know of that have been identified in the past are all to quaternary epitopes.
|
||
|
|
||
|
49:52.000 --> 49:57.000
|
||
|
Meaning they're conformational epitopes that are not apparent unless you have the whole trimer assembled.
|
||
|
|
||
|
49:57.000 --> 49:58.000
|
||
|
Correct.
|
||
|
|
||
|
49:58.000 --> 50:00.000
|
||
|
So that means that they're pretty complex.
|
||
|
|
||
|
50:00.000 --> 50:03.000
|
||
|
They're bridged like two subunits of a trimer, right?
|
||
|
|
||
|
50:03.000 --> 50:04.000
|
||
|
So maybe it's not...
|
||
|
|
||
|
50:04.000 --> 50:12.000
|
||
|
Although I expect with an mRNA vaccine that this protein will assemble in a membrane in a fashion that mimics its assembly on the virus.
|
||
|
|
||
|
50:12.000 --> 50:20.000
|
||
|
Maybe it's not quite like that or maybe something about the presentation fails to present the appropriate quaternary epitope or maybe there's something...
|
||
|
|
||
|
50:20.000 --> 50:25.000
|
||
|
Okay, so let's talk about that because that's the key revelation in this twist.
|
||
|
|
||
|
50:25.000 --> 50:26.000
|
||
|
Let me go get a chord.
|
||
|
|
||
|
50:26.000 --> 50:52.000
|
||
|
So we've talked about this before with regard to antibodies and what the epitope is or what an epitope is.
|
||
|
|
||
|
50:53.000 --> 51:03.000
|
||
|
And we've struggled, like everybody does, to explain what it is, but the best way to explain it in words is to say that it's an electrostatic shape.
|
||
|
|
||
|
51:03.000 --> 51:06.000
|
||
|
A three-dimensional electrostatic shape.
|
||
|
|
||
|
51:06.000 --> 51:20.000
|
||
|
You can think of it as a three-dimensional electrostatic surface like the shape that my hand makes, but then now with positives and negatives distributed across it so that if you want to match it,
|
||
|
|
||
|
51:20.000 --> 51:29.000
|
||
|
you kind of got to match it in a shape sort of way and also to a certain extent an electrostatic negative sort of way.
|
||
|
|
||
|
51:29.000 --> 51:38.000
|
||
|
So like a mirror image, some positives should be negative, that kind of thing so that your antibody will bind to it, recognize it.
|
||
|
|
||
|
51:38.000 --> 51:41.000
|
||
|
And that's the best way to understand this.
|
||
|
|
||
|
51:41.000 --> 51:47.000
|
||
|
Now, what these guys are describing is, let's listen again.
|
||
|
|
||
|
51:48.000 --> 51:50.000
|
||
|
A parent, unless you have the whole...
|
||
|
|
||
|
51:50.000 --> 51:52.000
|
||
|
Challenge them, which we haven't done yet.
|
||
|
|
||
|
51:52.000 --> 51:55.000
|
||
|
We bring them inside the BSL4, obviously.
|
||
|
|
||
|
51:55.000 --> 52:11.000
|
||
|
So it's relevant to point out that one of the things that they point out is that the neutralizing antibodies that they know of that have been identified in the past are all two quaternary epitopes, meaning they're conformational epitopes that are not a parent unless you have the whole trimer assembled.
|
||
|
|
||
|
52:11.000 --> 52:12.000
|
||
|
Correct.
|
||
|
|
||
|
52:12.000 --> 52:14.000
|
||
|
So that means that they're pretty complex.
|
||
|
|
||
|
52:15.000 --> 52:17.000
|
||
|
They're bridged like two subunits of a trimer, right?
|
||
|
|
||
|
52:17.000 --> 52:18.000
|
||
|
Yeah.
|
||
|
|
||
|
52:18.000 --> 52:27.000
|
||
|
So maybe it's not, although I expect with an mRNA vaccine that this protein will assemble in a membrane in a fashion that mimics its assembly on the virus.
|
||
|
|
||
|
52:27.000 --> 52:36.000
|
||
|
Maybe it's not quite like that, or maybe something about the presentation fails to present the appropriate quaternary epitope, or maybe there's something else about an infection that induces those antibodies.
|
||
|
|
||
|
52:36.000 --> 52:38.000
|
||
|
Do you have any thoughts about that, Rian?
|
||
|
|
||
|
52:38.000 --> 52:48.000
|
||
|
So now here's my best, you know, back of the envelope explanation, if I was at a dinner table with you or something like that, how I would explain this.
|
||
|
|
||
|
52:48.000 --> 52:51.000
|
||
|
Here's the protein.
|
||
|
|
||
|
52:51.000 --> 52:53.000
|
||
|
It's a cord, right?
|
||
|
|
||
|
52:53.000 --> 53:02.000
|
||
|
Because it's a chain of amino acids, and it's a chain of amino acids that was encoded by triplets of nucleic acids in the RNA.
|
||
|
|
||
|
53:03.000 --> 53:10.000
|
||
|
And so then the RNA goes through the ribosome machinery, a miracle happens, and then this protein is coming out.
|
||
|
|
||
|
53:10.000 --> 53:20.000
|
||
|
As it's coming out of the ribosome, it supposedly is folding up into the shape that it needs to be in when it goes into the membrane.
|
||
|
|
||
|
53:21.000 --> 53:35.000
|
||
|
And that tertiary shape here, quaternary structure, tertiary structure, I think this is called a tertiary structure, so I'm not sure if quaternary antibodies might be the right term.
|
||
|
|
||
|
53:35.000 --> 53:37.000
|
||
|
I don't know, I need to look it up.
|
||
|
|
||
|
53:37.000 --> 53:43.000
|
||
|
It's the first time I've heard it in here, but I know of the concept, and the concept is this.
|
||
|
|
||
|
53:43.000 --> 54:00.000
|
||
|
If you're going to make an antibody to a folded, functionally relevant shape, think of like pressing a piece of clay onto this pile of cord right here in the middle where it's all together here.
|
||
|
|
||
|
54:00.000 --> 54:06.000
|
||
|
And the shape that you get from it is the epitope.
|
||
|
|
||
|
54:06.000 --> 54:10.000
|
||
|
And so they are always talking about, well what epitope is it?
|
||
|
|
||
|
54:10.000 --> 54:20.000
|
||
|
Maybe it's this epitope, or maybe it's this epitope, or maybe it's this epitope, or it could be this epitope, maybe we should make it this epitope, or this epitope.
|
||
|
|
||
|
54:20.000 --> 54:42.000
|
||
|
And in reality, the folded protein produces three-dimensional epitopes that are sometimes almost incredibly unrelated to the sequence of the protein because the folded structure creates three-dimensional electrostatic shapes that the immune system recognizes
|
||
|
|
||
|
54:42.000 --> 54:52.000
|
||
|
as functional targets and builds immunity to them, that are not so easy to predict from the sequence of the protein.
|
||
|
|
||
|
54:52.000 --> 55:07.000
|
||
|
Certainly not so easy to predict if you take the sequence of the protein that's encoded in the virus and codon optimize it, and then pseudo uradate it so that it doesn't get eliminated by the cellular machinery too quickly.
|
||
|
|
||
|
55:07.000 --> 55:15.000
|
||
|
And so you're not sure if that tertiary structure is exactly what the virus sequence would have made, of course it's not.
|
||
|
|
||
|
55:15.000 --> 55:28.000
|
||
|
And so therefore your quaternary epitopes, the ones that actually matter, won't be adequately represented by your mRNA generated protein.
|
||
|
|
||
|
55:28.000 --> 55:31.000
|
||
|
Now isn't that curious?
|
||
|
|
||
|
55:31.000 --> 55:43.000
|
||
|
Now we're still going to have to figure out what happens in this paper because somehow or another they still seem to impart immunity on the guinea pigs and the ones that are vaccinated live and the ones that aren't vaccinated die.
|
||
|
|
||
|
55:43.000 --> 55:48.000
|
||
|
Or they sacrifice them because they're suffering or something like that, we'll hear it in a minute.
|
||
|
|
||
|
55:49.000 --> 55:59.000
|
||
|
So I don't have the whole story yet, but I do have this biological concept correct and it is something that you can put in your bookshelf and never let it go.
|
||
|
|
||
|
55:59.000 --> 56:03.000
|
||
|
That antibodies are not as simple as well, here's a protein.
|
||
|
|
||
|
56:03.000 --> 56:18.000
|
||
|
And so we look at different sequences and some of those sequences your immune system remembers, you know, like the receptor binding domain or the, or the G one G protein GP 120 loop.
|
||
|
|
||
|
56:18.000 --> 56:27.000
|
||
|
Because when the protein is folded and in confirmation, yes, there are epitopes that stick out.
|
||
|
|
||
|
56:28.000 --> 56:34.000
|
||
|
And so those epitopes stick out, but it's up to your immune system, what epitopes it chooses.
|
||
|
|
||
|
56:34.000 --> 56:51.000
|
||
|
And it can choose epitopes which describe three dimensional electrostatic spaces that are formed by the tertiary or quaternary, I don't know which word it is, I think it's tertiary, but by the three dimensional structure of the protein.
|
||
|
|
||
|
56:52.000 --> 57:01.000
|
||
|
And how that sequence is folded and what kinds of three dimensional electrostatic shapes are created there.
|
||
|
|
||
|
57:01.000 --> 57:13.000
|
||
|
And this is huge, because again, as we've talked about at the beginning of the pandemic, you know, antibodies are what you make immunity and that's how it works and so all you need are antibodies.
|
||
|
|
||
|
57:14.000 --> 57:22.000
|
||
|
And these made it real simple, you know, it's just an antibody and it just sticks to things and things that sticks to like the red ball or the green ball.
|
||
|
|
||
|
57:22.000 --> 57:36.000
|
||
|
And it's not that simple. It's so not that simple. And if you knew how simple it wasn't, then you wouldn't take their word that they know that they can put a bunch of chemicals inside of your muscle and augment that system.
|
||
|
|
||
|
57:37.000 --> 57:41.000
|
||
|
You wouldn't believe that sales pitch if you knew how complicated this was.
|
||
|
|
||
|
57:41.000 --> 57:52.000
|
||
|
And this is a great example of three and a half years in, we're finally talking about kind of close to how anybody's really work and what an epitope really is.
|
||
|
|
||
|
57:52.000 --> 57:55.000
|
||
|
Are you kidding me?
|
||
|
|
||
|
57:55.000 --> 58:05.000
|
||
|
I don't know enough about lots of viral particles to really say much about that to know if say there are other proteins that may assist in that quaternary structure, perhaps, or something like that.
|
||
|
|
||
|
58:05.000 --> 58:08.000
|
||
|
This is the only membrane protein in the virus. There's nothing else as far as we know.
|
||
|
|
||
|
58:08.000 --> 58:12.000
|
||
|
I suppose there could be there must. I assume there's a matrix protein of some sort. Yeah, there is.
|
||
|
|
||
|
58:12.000 --> 58:15.000
|
||
|
Play a role at least in organizing the like a protein on the surface.
|
||
|
|
||
|
58:15.000 --> 58:22.000
|
||
|
Yeah, I just don't know enough about that to really tell you, but I agree with everything that you're saying about what that quaternary epitope means.
|
||
|
|
||
|
58:22.000 --> 58:28.000
|
||
|
They do some experiments to map the epitopes recognized by these antibodies, but I'm going to skip those because I don't think they part of what I'm interested in here.
|
||
|
|
||
|
58:28.000 --> 58:30.000
|
||
|
If that's okay with everyone, does everyone.
|
||
|
|
||
|
58:30.000 --> 58:31.000
|
||
|
That is totally fine.
|
||
|
|
||
|
58:31.000 --> 58:42.000
|
||
|
Good. Now, this is very interesting. The next section in the paper, they say, despite excellent protection observed in each vaccinated animal, we decided to look at the mechanisms of protection, but they haven't presented.
|
||
|
|
||
|
58:42.000 --> 58:44.000
|
||
|
They haven't checked for protection yet.
|
||
|
|
||
|
58:44.000 --> 58:48.000
|
||
|
Why did they think it was a mistake or it's weird that they would present this before the protection experiment?
|
||
|
|
||
|
58:49.000 --> 59:02.000
|
||
|
Yeah, I think that's just an issue with drafting the paper that they phrased that poorly, because at this point in the paper, if you are following in sequence, and as we mentioned a number of times on Twiv, when you read a paper, the sequence in which the experiments are presented is seldom the sequence in which the experiments were done.
|
||
|
|
||
|
59:02.000 --> 59:10.000
|
||
|
So, you know, they obviously knew when they were writing the paper what the outcome was, but at that point, if you're reading it, it's like, I would have next gone to the protection.
|
||
|
|
||
|
59:11.000 --> 59:14.000
|
||
|
But the next one, so I'm going to go right now to the protection because I think it makes sense.
|
||
|
|
||
|
59:14.000 --> 59:15.000
|
||
|
Okay.
|
||
|
|
||
|
59:15.000 --> 59:16.000
|
||
|
Pre-style.
|
||
|
|
||
|
59:16.000 --> 59:17.000
|
||
|
56.
|
||
|
|
||
|
59:17.000 --> 59:18.000
|
||
|
Yeah, we can.
|
||
|
|
||
|
59:18.000 --> 59:20.000
|
||
|
You know, in the old days, you could cut up the paper and paste.
|
||
|
|
||
|
59:20.000 --> 59:21.000
|
||
|
We paste.
|
||
|
|
||
|
59:21.000 --> 59:25.000
|
||
|
Day 56 after immunization, they infect the animals.
|
||
|
|
||
|
59:25.000 --> 59:29.000
|
||
|
Interpreterately with 30,000 p.f.u. of a guinea pig adapted lassavirus.
|
||
|
|
||
|
59:29.000 --> 59:30.000
|
||
|
Hozaya strain.
|
||
|
|
||
|
59:30.000 --> 59:31.000
|
||
|
I like the name Hozaya.
|
||
|
|
||
|
59:31.000 --> 59:32.000
|
||
|
Yeah.
|
||
|
|
||
|
59:32.000 --> 59:34.000
|
||
|
And they record weight temperature disease scores every day.
|
||
|
|
||
|
59:34.000 --> 59:35.000
|
||
|
Oh, yeah.
|
||
|
|
||
|
59:35.000 --> 59:36.000
|
||
|
That's right.
|
||
|
|
||
|
59:36.000 --> 59:38.000
|
||
|
No lethargy ruffled for weight loss or others.
|
||
|
|
||
|
59:39.000 --> 59:44.000
|
||
|
The best that I could find, that's what I forgot to cut that out.
|
||
|
|
||
|
59:44.000 --> 59:54.000
|
||
|
So, in the methods, they say that the strain of the virus is Josiah.
|
||
|
|
||
|
59:54.000 --> 59:55.000
|
||
|
Where is it?
|
||
|
|
||
|
59:55.000 --> 59:58.000
|
||
|
He just mentioned it right now.
|
||
|
|
||
|
59:58.000 --> 01:00:01.000
|
||
|
And as far as I can tell, that's got to be a clone.
|
||
|
|
||
|
01:00:01.000 --> 01:00:04.000
|
||
|
Like, I don't know what else it is because...
|
||
|
|
||
|
01:00:05.000 --> 01:00:06.000
|
||
|
Sorry.
|
||
|
|
||
|
01:00:06.000 --> 01:00:08.000
|
||
|
Where did I miss it?
|
||
|
|
||
|
01:00:08.000 --> 01:00:15.000
|
||
|
Anybody at the C, immunostaining analysis and animal work?
|
||
|
|
||
|
01:00:15.000 --> 01:00:17.000
|
||
|
Where is it?
|
||
|
|
||
|
01:00:23.000 --> 01:00:24.000
|
||
|
Right there.
|
||
|
|
||
|
01:00:24.000 --> 01:00:31.000
|
||
|
Passage 7 of the LASV strain Josiah.
|
||
|
|
||
|
01:00:32.000 --> 01:00:36.000
|
||
|
Now, I don't know how else to interpret that.
|
||
|
|
||
|
01:00:36.000 --> 01:00:41.000
|
||
|
Passage 7 means that they're passionate seven times in cells.
|
||
|
|
||
|
01:00:41.000 --> 01:00:44.000
|
||
|
But what did they start with?
|
||
|
|
||
|
01:00:44.000 --> 01:00:49.000
|
||
|
They can't be starting with the same patient sample forever.
|
||
|
|
||
|
01:00:49.000 --> 01:00:52.000
|
||
|
Like, that's not how this works.
|
||
|
|
||
|
01:00:52.000 --> 01:01:00.000
|
||
|
So, my guess is, is that they generate this from a clone and then passage that clone seven
|
||
|
|
||
|
01:01:00.000 --> 01:01:08.000
|
||
|
times in cell culture to generate an infectious swarm.
|
||
|
|
||
|
01:01:08.000 --> 01:01:14.000
|
||
|
That's the only way that I can interpret any of these methodologies at this point because
|
||
|
|
||
|
01:01:14.000 --> 01:01:17.000
|
||
|
they all seem to go back to a recombinant clone,
|
||
|
|
||
|
01:01:17.000 --> 01:01:23.000
|
||
|
grow in a few passages in a cell culture, and then distribute it as a product.
|
||
|
|
||
|
01:01:23.000 --> 01:01:30.000
|
||
|
That's what I think they're talking about when they say passage 7, LASV strain Josiah.
|
||
|
|
||
|
01:01:30.000 --> 01:01:37.000
|
||
|
Signs until seven to nine days after a channel animal is interprepared to nearly with 30,000
|
||
|
|
||
|
01:01:37.000 --> 01:01:40.000
|
||
|
p.f.u. of a guinea pig adapted LASV virus.
|
||
|
|
||
|
01:01:40.000 --> 01:01:42.000
|
||
|
Josiah strain, I like the name Josiah.
|
||
|
|
||
|
01:01:42.000 --> 01:01:43.000
|
||
|
Yeah.
|
||
|
|
||
|
01:01:43.000 --> 01:01:46.000
|
||
|
And they record weight, temperature, disease scores, everyday, control animals.
|
||
|
|
||
|
01:01:46.000 --> 01:01:47.000
|
||
|
That is, BBS.
|
||
|
|
||
|
01:01:47.000 --> 01:01:50.000
|
||
|
No lethargy, ruffled for weight loss or other signs until seven to nine days after a challenge,
|
||
|
|
||
|
01:01:50.000 --> 01:01:52.000
|
||
|
and then they became febrile.
|
||
|
|
||
|
01:01:52.000 --> 01:01:53.000
|
||
|
They began to lose weight.
|
||
|
|
||
|
01:01:53.000 --> 01:01:58.000
|
||
|
They got lethargic ruffled for orbital tightening their earth around the sun.
|
||
|
|
||
|
01:01:58.000 --> 01:02:00.000
|
||
|
When they're smaller and smaller, they're coming down into the atmosphere.
|
||
|
|
||
|
01:02:00.000 --> 01:02:01.000
|
||
|
That's part of like the grimace, right?
|
||
|
|
||
|
01:02:01.000 --> 01:02:03.000
|
||
|
So if they're in pain, then yeah, they'll for the listeners.
|
||
|
|
||
|
01:02:03.000 --> 01:02:04.000
|
||
|
Oh, yeah.
|
||
|
|
||
|
01:02:04.000 --> 01:02:05.000
|
||
|
Yeah.
|
||
|
|
||
|
01:02:05.000 --> 01:02:06.000
|
||
|
It's a part of that.
|
||
|
|
||
|
01:02:06.000 --> 01:02:07.000
|
||
|
Cool, but thank you for the explanation.
|
||
|
|
||
|
01:02:07.000 --> 01:02:08.000
|
||
|
Yeah.
|
||
|
|
||
|
01:02:08.000 --> 01:02:11.000
|
||
|
They became viremic by day nine, and they met the criteria for euthanasia.
|
||
|
|
||
|
01:02:11.000 --> 01:02:13.000
|
||
|
So they were euthanized on days 11 to 15.
|
||
|
|
||
|
01:02:13.000 --> 01:02:17.000
|
||
|
Vaccinated animals, both the wild type, like a protein mRNA and the pre-fusion stabilized,
|
||
|
|
||
|
01:02:17.000 --> 01:02:18.000
|
||
|
no outward signs of disease.
|
||
|
|
||
|
01:02:18.000 --> 01:02:21.000
|
||
|
They all survived challenge to day 28 when they were euthanized to take a look at the tissues.
|
||
|
|
||
|
01:02:21.000 --> 01:02:27.000
|
||
|
So none of these signs, no ruffled for, no orbital tightening, none of that.
|
||
|
|
||
|
01:02:27.000 --> 01:02:32.000
|
||
|
They had an increase in like a protein antibodies, a little increase in nuclear protein antibodies,
|
||
|
|
||
|
01:02:32.000 --> 01:02:35.000
|
||
|
and they said they never find virus in serum after challenge.
|
||
|
|
||
|
01:02:35.000 --> 01:02:38.000
|
||
|
Which is very interesting, but they say it must have been a little replication because
|
||
|
|
||
|
01:02:38.000 --> 01:02:40.000
|
||
|
there's antibodies to nuclear protein.
|
||
|
|
||
|
01:02:40.000 --> 01:02:42.000
|
||
|
But it's surprising that the clinical score is the exact same.
|
||
|
|
||
|
01:02:42.000 --> 01:02:44.000
|
||
|
Like there's no none of the animals that were vaccinated.
|
||
|
|
||
|
01:02:44.000 --> 01:02:47.000
|
||
|
Like there's no variation whatsoever, or even like you were saying, the viremia is under
|
||
|
|
||
|
01:02:47.000 --> 01:02:48.000
|
||
|
the limit of detection.
|
||
|
|
||
|
01:02:48.000 --> 01:02:49.000
|
||
|
Yeah.
|
||
|
|
||
|
01:02:49.000 --> 01:02:52.000
|
||
|
It looks like the only thing that maybe changes a little bit is like they get a teensy bit
|
||
|
|
||
|
01:02:52.000 --> 01:02:53.000
|
||
|
of temperature.
|
||
|
|
||
|
01:02:53.000 --> 01:02:56.000
|
||
|
Which is interesting actually, the only, like the, it's more than you would just expect
|
||
|
|
||
|
01:02:56.000 --> 01:03:01.000
|
||
|
in the wild type GPC vaccine, like in the, sorry I'm looking at the figure, but definitely
|
||
|
|
||
|
01:03:01.000 --> 01:03:07.000
|
||
|
almost, not almost the same as the control, but similar to, yeah.
|
||
|
|
||
|
01:03:07.000 --> 01:03:10.000
|
||
|
They do histology and the main sites of disease in the control.
|
||
|
|
||
|
01:03:10.000 --> 01:03:13.000
|
||
|
I'm going to go back there a minute because I want to see the figure they're talking
|
||
|
|
||
|
01:03:13.000 --> 01:03:14.000
|
||
|
about.
|
||
|
|
||
|
01:03:14.000 --> 01:03:15.000
|
||
|
I don't think they got it wrong.
|
||
|
|
||
|
01:03:15.000 --> 01:03:18.000
|
||
|
I just want to see what they're talking about.
|
||
|
|
||
|
01:03:18.000 --> 01:03:20.000
|
||
|
No, none of the animals that were vaccinated.
|
||
|
|
||
|
01:03:20.000 --> 01:03:23.000
|
||
|
Like there's no variation whatsoever, or even like you were saying, the viremia is under
|
||
|
|
||
|
01:03:23.000 --> 01:03:24.000
|
||
|
the limit of detection.
|
||
|
|
||
|
01:03:24.000 --> 01:03:25.000
|
||
|
Yeah.
|
||
|
|
||
|
01:03:25.000 --> 01:03:28.000
|
||
|
It looks like the only thing that maybe changes a little bit is like they get a teensy bit
|
||
|
|
||
|
01:03:28.000 --> 01:03:29.000
|
||
|
of temperature.
|
||
|
|
||
|
01:03:29.000 --> 01:03:32.000
|
||
|
Which is interesting actually, the only, like the, it's more than you would just expect
|
||
|
|
||
|
01:03:32.000 --> 01:03:37.000
|
||
|
in the wild type GPC vaccine, like in the, sorry I'm looking at the figure, but definitely
|
||
|
|
||
|
01:03:37.000 --> 01:03:43.000
|
||
|
almost, not almost the same as the control, but similar to, yeah.
|
||
|
|
||
|
01:03:43.000 --> 01:03:48.000
|
||
|
They do histology and the main sites of disease in the control group are the lungs and the
|
||
|
|
||
|
01:03:48.000 --> 01:03:49.000
|
||
|
liver.
|
||
|
|
||
|
01:03:49.000 --> 01:03:52.000
|
||
|
You see typical viral, interstitial pneumonia in sections of liver showing pathology typical
|
||
|
|
||
|
01:03:52.000 --> 01:03:53.000
|
||
|
of lasso virus infection.
|
||
|
|
||
|
01:03:53.000 --> 01:03:57.000
|
||
|
And the vaccinated animals with either vaccine, normal lung, normal liver.
|
||
|
|
||
|
01:03:57.000 --> 01:04:01.000
|
||
|
So both of these mRNA vaccines protect against the death and severe disease clearly.
|
||
|
|
||
|
01:04:01.000 --> 01:04:02.000
|
||
|
All right.
|
||
|
|
||
|
01:04:02.000 --> 01:04:06.000
|
||
|
And so now we can go back one section and say, what is protecting these animals?
|
||
|
|
||
|
01:04:06.000 --> 01:04:10.000
|
||
|
They say, despite excellent protection, there's, there's not neutralizing antibody in every
|
||
|
|
||
|
01:04:10.000 --> 01:04:11.000
|
||
|
hamster.
|
||
|
|
||
|
01:04:11.000 --> 01:04:13.000
|
||
|
And even in the ones that do have it, it's not great.
|
||
|
|
||
|
01:04:13.000 --> 01:04:14.000
|
||
|
So what are they thinking?
|
||
|
|
||
|
01:04:14.000 --> 01:04:17.640
|
||
|
Well, they're thinking about other mechanisms involving antibodies and particularly the
|
||
|
|
||
|
01:04:17.640 --> 01:04:20.000
|
||
|
FC portion and Brian has a, has a show and tell for us.
|
||
|
|
||
|
01:04:20.000 --> 01:04:21.000
|
||
|
I have, I do.
|
||
|
|
||
|
01:04:21.000 --> 01:04:24.000
|
||
|
I've talked about this exact, these exact functions today in class.
|
||
|
|
||
|
01:04:24.000 --> 01:04:27.000
|
||
|
And so I already had this out on my desk so that we can see an FC portion on an antibody.
|
||
|
|
||
|
01:04:27.000 --> 01:04:28.000
|
||
|
So that's below the eyes.
|
||
|
|
||
|
01:04:28.000 --> 01:04:29.000
|
||
|
We were listening.
|
||
|
|
||
|
01:04:29.000 --> 01:04:30.000
|
||
|
It looks like a very cute stuffed lobster.
|
||
|
|
||
|
01:04:30.000 --> 01:04:31.000
|
||
|
I was going to say the same thing.
|
||
|
|
||
|
01:04:31.000 --> 01:04:33.000
|
||
|
I was going to teach us more.
|
||
|
|
||
|
01:04:33.000 --> 01:04:36.000
|
||
|
So the FC portion combined receptors and a variety of love.
|
||
|
|
||
|
01:04:36.000 --> 01:04:37.000
|
||
|
I do.
|
||
|
|
||
|
01:04:38.000 --> 01:04:43.000
|
||
|
So the idea is that an antibody binds its epitope here or its antigen target here.
|
||
|
|
||
|
01:04:43.000 --> 01:04:50.000
|
||
|
And this is the variable region that can be remodeled to an electrostatic shape that matches the
|
||
|
|
||
|
01:04:50.000 --> 01:04:51.000
|
||
|
epitope.
|
||
|
|
||
|
01:04:51.000 --> 01:04:57.000
|
||
|
And so this can be any shape, but it's a short sequence of amino acid.
|
||
|
|
||
|
01:04:57.000 --> 01:05:06.000
|
||
|
So although it's an unlimited variety that can be created there in theory, it is a limited,
|
||
|
|
||
|
01:05:06.000 --> 01:05:10.000
|
||
|
a limited spectrum of things that can be created.
|
||
|
|
||
|
01:05:10.000 --> 01:05:15.000
|
||
|
And then down here at the bottom is this FC portion, which is the functional portion in
|
||
|
|
||
|
01:05:15.000 --> 01:05:22.400
|
||
|
the sense of whatever flag is on the end there, if that flag calls in red neutrophils or red
|
||
|
|
||
|
01:05:22.400 --> 01:05:28.000
|
||
|
team neutrophils, then the FC portion would be the red team neutrophil FC portion.
|
||
|
|
||
|
01:05:28.000 --> 01:05:33.000
|
||
|
And that would bring in neutrophils to anywhere where that antibody bound.
|
||
|
|
||
|
01:05:33.000 --> 01:05:38.000
|
||
|
So what antibodies are there are important because they do different things.
|
||
|
|
||
|
01:05:38.000 --> 01:05:44.000
|
||
|
That's what that story was about six months ago where they found IG4, I believe.
|
||
|
|
||
|
01:05:44.000 --> 01:05:54.000
|
||
|
And so these are IGG4 antibodies are antibodies with a very shortened or non receptor type
|
||
|
|
||
|
01:05:54.000 --> 01:05:55.000
|
||
|
FC portion.
|
||
|
|
||
|
01:05:55.000 --> 01:06:01.000
|
||
|
So it wasn't clear what those antibodies do other than block things or stick things together.
|
||
|
|
||
|
01:06:02.000 --> 01:06:08.000
|
||
|
And so that was sort of considered my more side of tolerance because then those antibodies
|
||
|
|
||
|
01:06:08.000 --> 01:06:13.000
|
||
|
aren't calling in other immune cells and potentially triggering cytokine cascades, et cetera.
|
||
|
|
||
|
01:06:13.000 --> 01:06:16.000
|
||
|
Anyway, it's too bad you didn't say more about it.
|
||
|
|
||
|
01:06:16.000 --> 01:06:19.000
|
||
|
Talked about this exact, these exact functions today in class.
|
||
|
|
||
|
01:06:19.000 --> 01:06:22.000
|
||
|
And so I already had this out on my desk so that we can see an FC portion on an antibody.
|
||
|
|
||
|
01:06:22.000 --> 01:06:23.000
|
||
|
That's below the eyes we were listening.
|
||
|
|
||
|
01:06:23.000 --> 01:06:25.000
|
||
|
It looks like a very cute stuffed lobster.
|
||
|
|
||
|
01:06:25.000 --> 01:06:26.000
|
||
|
I was going to say the same thing.
|
||
|
|
||
|
01:06:26.000 --> 01:06:27.000
|
||
|
It looks like a lot.
|
||
|
|
||
|
01:06:28.000 --> 01:06:33.000
|
||
|
So the FC portion combined receptors on a variety of cells and those cells can then
|
||
|
|
||
|
01:06:33.000 --> 01:06:39.000
|
||
|
mediate clearance of virus by the antibody recognizing that the antigen say on a cell surface.
|
||
|
|
||
|
01:06:39.000 --> 01:06:44.000
|
||
|
And so they tested antibody dependent neutrophil phagocytosis, antibody dependent cellular
|
||
|
|
||
|
01:06:44.000 --> 01:06:48.000
|
||
|
phagocytosis mediated by monocytes, antibody dependent NK cell activation,
|
||
|
|
||
|
01:06:48.000 --> 01:06:50.000
|
||
|
and antibody dependent complement deposition.
|
||
|
|
||
|
01:06:50.000 --> 01:06:53.000
|
||
|
So the antibody can also activate the complement system.
|
||
|
|
||
|
01:06:54.000 --> 01:07:01.000
|
||
|
So it's important to realize that those are all things that antibodies not necessarily
|
||
|
|
||
|
01:07:01.000 --> 01:07:04.000
|
||
|
specific for the virus can do.
|
||
|
|
||
|
01:07:04.000 --> 01:07:09.000
|
||
|
So understand this very, very clearly because I think this is what's going on here.
|
||
|
|
||
|
01:07:09.000 --> 01:07:16.000
|
||
|
And this is the part that makes it very disappointing from the perspective of these humans
|
||
|
|
||
|
01:07:16.000 --> 01:07:24.000
|
||
|
because they don't seem to understand immunology well enough to be able to pull back from this.
|
||
|
|
||
|
01:07:24.000 --> 01:07:33.000
|
||
|
Because the immunization of those animals has activated the immune system in response to
|
||
|
|
||
|
01:07:33.000 --> 01:07:38.000
|
||
|
an antigen.
|
||
|
|
||
|
01:07:38.000 --> 01:07:43.000
|
||
|
Now, whether or not it activates it perfectly or not doesn't change the fact that activation
|
||
|
|
||
|
01:07:43.000 --> 01:07:52.000
|
||
|
of it will allow B cells, which code for IgM antibodies, which are aimed at
|
||
|
|
||
|
01:07:52.000 --> 01:08:00.000
|
||
|
at manose binding lectins, which would bind glycoproteins, and they're more generally
|
||
|
|
||
|
01:08:00.000 --> 01:08:07.000
|
||
|
targeted antibodies so that there is an immediate antibody response that is less specific
|
||
|
|
||
|
01:08:07.000 --> 01:08:15.000
|
||
|
but still targeted for circulating things like RNA viruses that are coded in glycoproteins,
|
||
|
|
||
|
01:08:15.000 --> 01:08:22.000
|
||
|
foreign manose binding lectins, this kind of thing, are all targeting the same set of
|
||
|
|
||
|
01:08:22.000 --> 01:08:26.000
|
||
|
proteins on the outside of RNA type viruses.
|
||
|
|
||
|
01:08:26.000 --> 01:08:31.000
|
||
|
So when you vaccinate an animal, when you vaccinate a kid and activate their immune
|
||
|
|
||
|
01:08:31.000 --> 01:08:39.000
|
||
|
system with an antigen, you are activating this system and potentially increasing the
|
||
|
|
||
|
01:08:39.000 --> 01:08:47.000
|
||
|
circulatory levels of all of these nonspecific antibodies and nonspecific cells like natural
|
||
|
|
||
|
01:08:47.000 --> 01:08:50.000
|
||
|
killer cells, which they're also looking at activation of.
|
||
|
|
||
|
01:08:50.000 --> 01:08:56.000
|
||
|
So again, if natural killer cells get activated, then you're going to have an increased
|
||
|
|
||
|
01:08:56.000 --> 01:09:03.000
|
||
|
general defense against RNA viral infection, not specific for LASA.
|
||
|
|
||
|
01:09:03.000 --> 01:09:11.000
|
||
|
But if you challenge them with an RNA virus called LASA and no other virus, it might appear
|
||
|
|
||
|
01:09:11.000 --> 01:09:18.000
|
||
|
as though, wow, these are more resistant than these animals that were not injected.
|
||
|
|
||
|
01:09:18.000 --> 01:09:23.000
|
||
|
And it could make it look like in an animal model, if you kill all the animals on the same
|
||
|
|
||
|
01:09:23.000 --> 01:09:27.000
|
||
|
body and they don't let them recover, then wow, this was going to be a deadly virus.
|
||
|
|
||
|
01:09:27.000 --> 01:09:29.000
|
||
|
These animals all had symptoms.
|
||
|
|
||
|
01:09:29.000 --> 01:09:31.000
|
||
|
These animals did not.
|
||
|
|
||
|
01:09:31.000 --> 01:09:38.000
|
||
|
And worse yet, you have misrepresented the immune status of the animals that were vaccinated
|
||
|
|
||
|
01:09:38.000 --> 01:09:45.000
|
||
|
by pretending that the presence of those antibodies is somehow the only difference in those animals,
|
||
|
|
||
|
01:09:45.000 --> 01:09:50.000
|
||
|
which is relevant to their survival upon challenge.
|
||
|
|
||
|
01:09:50.000 --> 01:09:55.000
|
||
|
Without measuring the nonspecific IgMs that are produced by the B cells, which steal
|
||
|
|
||
|
01:09:55.000 --> 01:10:03.000
|
||
|
antigens from antigen-presenting cells, which are coming in to the outer layers of lymph nodes,
|
||
|
|
||
|
01:10:03.000 --> 01:10:08.000
|
||
|
that they did three different twin episodes about a year and a half ago.
|
||
|
|
||
|
01:10:08.000 --> 01:10:15.000
|
||
|
There are actually B cells which hang out at the doorways at different compartments
|
||
|
|
||
|
01:10:15.000 --> 01:10:21.000
|
||
|
with inside of lymph nodes and wait for antigen-presenting cells to come past,
|
||
|
|
||
|
01:10:21.000 --> 01:10:30.000
|
||
|
and they actually tear the MHC2 molecule and its presented antigen off of it
|
||
|
|
||
|
01:10:30.000 --> 01:10:37.000
|
||
|
so that when T cells are activated by those cells, those T cells can also turn on and boost
|
||
|
|
||
|
01:10:37.000 --> 01:10:40.000
|
||
|
these B cells to colonnally expand.
|
||
|
|
||
|
01:10:40.000 --> 01:10:47.000
|
||
|
So the nonspecific signal is boosted by any incoming antigen-presenting cell activity,
|
||
|
|
||
|
01:10:47.000 --> 01:10:55.000
|
||
|
while the specific T cell activity then allows the amplification of the nonspecific
|
||
|
|
||
|
01:10:55.000 --> 01:11:02.000
|
||
|
and any potential specific B cells which get activated by circulating antigen.
|
||
|
|
||
|
01:11:02.000 --> 01:11:08.000
|
||
|
And if you could follow that with no graphics, then you might actually understand a little
|
||
|
|
||
|
01:11:08.000 --> 01:11:12.000
|
||
|
bit about the immune system. You might actually get it.
|
||
|
|
||
|
01:11:12.000 --> 01:11:18.000
|
||
|
And these people should definitely be talking about that, but they're not.
|
||
|
|
||
|
01:11:18.000 --> 01:11:25.000
|
||
|
And instead, they're really just following the faith that's presented in this article,
|
||
|
|
||
|
01:11:25.000 --> 01:11:33.000
|
||
|
that the antibodies in Figure 1 have any bearing on what happens in Figure 6
|
||
|
|
||
|
01:11:33.000 --> 01:11:39.000
|
||
|
without talking about all the other potential changes that they're almost sure were happening
|
||
|
|
||
|
01:11:39.000 --> 01:11:43.000
|
||
|
inside of this guinea pig after they were transfected.
|
||
|
|
||
|
01:11:47.000 --> 01:11:51.000
|
||
|
So, I guess, Rian, these are all acting on infected cells,
|
||
|
|
||
|
01:11:51.000 --> 01:11:53.000
|
||
|
or some would also part virus particles, maybe?
|
||
|
|
||
|
01:11:53.000 --> 01:11:55.000
|
||
|
So it can be virus particles or infected cells.
|
||
|
|
||
|
01:11:55.000 --> 01:11:58.000
|
||
|
The NK activation is definitely acting on infected cells.
|
||
|
|
||
|
01:11:58.000 --> 01:12:03.000
|
||
|
I usually think of the phagocytosis and the complement deposition as acting more on viral particles,
|
||
|
|
||
|
01:12:03.000 --> 01:12:06.000
|
||
|
but you could perhaps come up with it.
|
||
|
|
||
|
01:12:06.000 --> 01:12:15.000
|
||
|
Complement deposition is also something that we've watched a video right before the pandemic.
|
||
|
|
||
|
01:12:15.000 --> 01:12:22.000
|
||
|
The book, so this guy.
|
||
|
|
||
|
01:12:22.000 --> 01:12:26.000
|
||
|
I don't know how to say it in German, but it's Kyrgyzath, this in a nutshell guy
|
||
|
|
||
|
01:12:26.000 --> 01:12:35.000
|
||
|
whose book I really like and whose immune system videos that were made before the pandemic are actually pretty brilliant.
|
||
|
|
||
|
01:12:35.000 --> 01:12:42.000
|
||
|
One of those immune system videos made before the pandemic talks about how viruses,
|
||
|
|
||
|
01:12:42.000 --> 01:12:49.000
|
||
|
when they float around in your plasma, have almost no chance because of the complement system.
|
||
|
|
||
|
01:12:49.000 --> 01:12:59.000
|
||
|
And so, complement deposition is something that happens spontaneously as well as antibody-directed complement deposition.
|
||
|
|
||
|
01:12:59.000 --> 01:13:05.000
|
||
|
Do not underestimate that the complement system is always trying to initiate,
|
||
|
|
||
|
01:13:05.000 --> 01:13:13.000
|
||
|
and you have in your cell membranes the lock and keys that sort of complement,
|
||
|
|
||
|
01:13:13.000 --> 01:13:19.000
|
||
|
that's the wrong word when talking about the complement system, but that's kind of by design
|
||
|
|
||
|
01:13:19.000 --> 01:13:27.000
|
||
|
that work together to neutralize that from actually building the cascade that would perforate a membrane.
|
||
|
|
||
|
01:13:27.000 --> 01:13:33.000
|
||
|
But viruses don't have that, and especially foreign ones that weren't manufactured in your own cells.
|
||
|
|
||
|
01:13:33.000 --> 01:13:37.000
|
||
|
And so, it's a brilliant statement that she's making here,
|
||
|
|
||
|
01:13:37.000 --> 01:13:42.000
|
||
|
but how come they didn't talk about how vulnerable viruses were to the complement system before this?
|
||
|
|
||
|
01:13:42.000 --> 01:13:52.000
|
||
|
How come she still hasn't realized that antibody-dependent enhancement is almost certainly antibodies binding to the outside of a virus
|
||
|
|
||
|
01:13:52.000 --> 01:13:57.000
|
||
|
and preventing complement deposition?
|
||
|
|
||
|
01:13:57.000 --> 01:14:02.000
|
||
|
And so then the viruses are more long-lived in the plasma,
|
||
|
|
||
|
01:14:02.000 --> 01:14:07.000
|
||
|
more likely to be taken up by antigen-presenting cells as opposed to just destroyed.
|
||
|
|
||
|
01:14:08.000 --> 01:14:16.000
|
||
|
And releasing their RNA, releasing the end protein, which is the most common antibody target in a viral infection,
|
||
|
|
||
|
01:14:16.000 --> 01:14:20.000
|
||
|
because of that mechanism right there. I mean, we're really on this.
|
||
|
|
||
|
01:14:20.000 --> 01:14:30.000
|
||
|
We've been on it for three years now, and it's cool to see how the immunomythology is so well-preserved on this,
|
||
|
|
||
|
01:14:31.000 --> 01:14:38.000
|
||
|
even when they skirt around these very interesting topics like quaternary target at antibodies,
|
||
|
|
||
|
01:14:38.000 --> 01:14:49.000
|
||
|
and they just still can't quite grasp how the simplification has sort of taken all the sacredness out of this.
|
||
|
|
||
|
01:14:49.000 --> 01:14:54.000
|
||
|
So wait a minute, let me make sure I got this straight.
|
||
|
|
||
|
01:14:54.000 --> 01:15:00.000
|
||
|
If you say acting, first of all, this has to do with the claw part of the lobster antibody, binding to antigen.
|
||
|
|
||
|
01:15:00.000 --> 01:15:01.000
|
||
|
Yes.
|
||
|
|
||
|
01:15:01.000 --> 01:15:03.000
|
||
|
Okay. And then the tail part of the antibody-
|
||
|
|
||
|
01:15:03.000 --> 01:15:04.000
|
||
|
Oh, there's an antigen too.
|
||
|
|
||
|
01:15:04.000 --> 01:15:10.000
|
||
|
Which is the FC portion binding to something else and affecting the fate of that antibody antigen complex, right?
|
||
|
|
||
|
01:15:10.000 --> 01:15:11.000
|
||
|
Correct.
|
||
|
|
||
|
01:15:11.000 --> 01:15:18.000
|
||
|
So when you say acting on infected cells, do you mean the antibody is binding to protein on the surface of infected cells?
|
||
|
|
||
|
01:15:18.000 --> 01:15:22.000
|
||
|
Yes, and so with an envelope to virus, you would see some amount of protein in the plasma membrane,
|
||
|
|
||
|
01:15:22.000 --> 01:15:24.000
|
||
|
and antibodies could bind to that protein.
|
||
|
|
||
|
01:15:24.000 --> 01:15:29.000
|
||
|
So let's go through again what you said some would be cell acting on cells other antibodies.
|
||
|
|
||
|
01:15:29.000 --> 01:15:32.000
|
||
|
So that would be an antibody-dependent NK activation.
|
||
|
|
||
|
01:15:32.000 --> 01:15:38.000
|
||
|
So you would have some protein on the surface of the infected cell, antibodies would bind, and then NK cells would kill the infected cell.
|
||
|
|
||
|
01:15:38.000 --> 01:15:43.000
|
||
|
Okay. And then there are a couple of phagocytosis assays. That's where there's some sort.
|
||
|
|
||
|
01:15:43.000 --> 01:15:48.000
|
||
|
And so of course, that's what happens on subsequent shots, which I've been saying over and over again.
|
||
|
|
||
|
01:15:48.000 --> 01:15:58.000
|
||
|
If on the first shot you transfect endothelial cells and endothelial cells express the transfected protein, in this case the spike protein,
|
||
|
|
||
|
01:15:58.000 --> 01:16:02.000
|
||
|
your body makes antibodies to the spike protein.
|
||
|
|
||
|
01:16:02.000 --> 01:16:04.000
|
||
|
Now those are in circulation.
|
||
|
|
||
|
01:16:04.000 --> 01:16:10.000
|
||
|
And a few months later, you take another transfection and endothelial cells are again expressing the spike protein.
|
||
|
|
||
|
01:16:11.000 --> 01:16:20.000
|
||
|
But any cells that express the spike protein now will have the potential to have antibodies bind that spike protein.
|
||
|
|
||
|
01:16:20.000 --> 01:16:32.000
|
||
|
And some of those antibodies will cause NK cell activation and NK cells, if they're activated by an antibody, will destroy the cell to which that antibody is bound.
|
||
|
|
||
|
01:16:33.000 --> 01:16:43.000
|
||
|
If that is an endothelial cell in a capillary of your lungs, you're going to have a problem because once the NK cell has done that, then you might get neutrophils coming in.
|
||
|
|
||
|
01:16:43.000 --> 01:16:46.000
|
||
|
You might have cytokine release.
|
||
|
|
||
|
01:16:46.000 --> 01:16:51.000
|
||
|
You might have previously instructed T cells from the first shot coming in.
|
||
|
|
||
|
01:16:51.000 --> 01:16:55.000
|
||
|
And now you have a real problem.
|
||
|
|
||
|
01:16:56.000 --> 01:17:06.000
|
||
|
And my guess is that if we did the math, we would find that people's propensity for damage increases with the numbers of shots that they take.
|
||
|
|
||
|
01:17:06.000 --> 01:17:08.000
|
||
|
And the safest shot is the first one.
|
||
|
|
||
|
01:17:08.000 --> 01:17:10.000
|
||
|
And this would be why?
|
||
|
|
||
|
01:17:10.000 --> 01:17:12.000
|
||
|
Because the immune system is learning.
|
||
|
|
||
|
01:17:12.000 --> 01:17:15.000
|
||
|
And then the immune system is responding.
|
||
|
|
||
|
01:17:15.000 --> 01:17:24.000
|
||
|
And in the first shot, maybe you don't have so much of the cytotoxic response because you don't have so much of these antibodies
|
||
|
|
||
|
01:17:24.000 --> 01:17:27.000
|
||
|
that would potentially cause it.
|
||
|
|
||
|
01:17:27.000 --> 01:17:29.000
|
||
|
Sort of FC receptor on the cell.
|
||
|
|
||
|
01:17:29.000 --> 01:17:30.000
|
||
|
On the phagocyte.
|
||
|
|
||
|
01:17:30.000 --> 01:17:33.000
|
||
|
On the phagocyte that just sucks up the whole antibody antigen complex and gets rid of it.
|
||
|
|
||
|
01:17:33.000 --> 01:17:35.000
|
||
|
In case it's bound to virus, right?
|
||
|
|
||
|
01:17:35.000 --> 01:17:39.000
|
||
|
Yeah, so it's probably virus and it's probably enhancing that virus's phagocytosis.
|
||
|
|
||
|
01:17:39.000 --> 01:17:42.000
|
||
|
And the compliment is that the compliment going to be acting on the virus?
|
||
|
|
||
|
01:17:42.000 --> 01:17:46.000
|
||
|
That's tougher, but I think the compliment would probably be acting on the virus.
|
||
|
|
||
|
01:17:46.000 --> 01:17:50.000
|
||
|
I don't know if the poor, it would be membrane attack and making a poor.
|
||
|
|
||
|
01:17:50.000 --> 01:17:56.000
|
||
|
You can also think about compliments helping phagocytosis or compliment inducing some inflammatory response.
|
||
|
|
||
|
01:17:56.000 --> 01:18:00.000
|
||
|
I don't know enough about their ADCD assay that they use to know exactly how it's being measured.
|
||
|
|
||
|
01:18:00.000 --> 01:18:02.000
|
||
|
I think they're just looking for a compliment being deposited.
|
||
|
|
||
|
01:18:02.000 --> 01:18:04.000
|
||
|
They don't actually look at what the deposited compliment does.
|
||
|
|
||
|
01:18:04.000 --> 01:18:09.000
|
||
|
But importantly, these are all ways to get rid of either virus in fact itself or virus that don't involve neutralization.
|
||
|
|
||
|
01:18:09.000 --> 01:18:10.000
|
||
|
Absolutely.
|
||
|
|
||
|
01:18:10.000 --> 01:18:13.000
|
||
|
And they all require the FC portion, which neutralization might not.
|
||
|
|
||
|
01:18:13.000 --> 01:18:15.000
|
||
|
And they find evidence for all of them in their assays.
|
||
|
|
||
|
01:18:15.000 --> 01:18:16.000
|
||
|
They have a variety of assays to measure these.
|
||
|
|
||
|
01:18:16.000 --> 01:18:20.000
|
||
|
And they say vaccination with either construct induce each of these FC mediated mean mechanisms.
|
||
|
|
||
|
01:18:20.000 --> 01:18:26.000
|
||
|
So if you wanted to take this further, Brianne, what would you do to show that these are working in the animals say?
|
||
|
|
||
|
01:18:26.000 --> 01:18:28.000
|
||
|
You could do an NK null guinea pig if you could do that, right?
|
||
|
|
||
|
01:18:28.000 --> 01:18:30.000
|
||
|
You could do an NK null guinea pig.
|
||
|
|
||
|
01:18:30.000 --> 01:18:36.000
|
||
|
You could, I would be interested in knowing exactly which types of antibodies they are because different antibodies,
|
||
|
|
||
|
01:18:36.000 --> 01:18:41.000
|
||
|
say I2G versus IgM, tend to do some of these functions more or less than others.
|
||
|
|
||
|
01:18:41.000 --> 01:18:44.000
|
||
|
So IgM, for example, is very good at fixing compliment.
|
||
|
|
||
|
01:18:44.000 --> 01:18:49.000
|
||
|
And so if I saw that the animals were largely making M, then I could start to look at what's going on with compliment a little more.
|
||
|
|
||
|
01:18:49.000 --> 01:18:54.000
|
||
|
So does this mean that you would get similar results in humans?
|
||
|
|
||
|
01:18:54.000 --> 01:18:57.000
|
||
|
I think we'd have to check and see.
|
||
|
|
||
|
01:18:57.000 --> 01:18:58.000
|
||
|
Yes.
|
||
|
|
||
|
01:18:58.000 --> 01:19:01.000
|
||
|
They say they're going to do non-human primates next because this doesn't mean anything about people.
|
||
|
|
||
|
01:19:01.000 --> 01:19:05.000
|
||
|
I will also say that non-human primates are not going to definitely tell you, but it's the best you can do.
|
||
|
|
||
|
01:19:05.000 --> 01:19:07.000
|
||
|
And then you go into, you do a phase one and phase two and phase three.
|
||
|
|
||
|
01:19:07.000 --> 01:19:09.000
|
||
|
You certainly have enough cases to do phase two and three, right?
|
||
|
|
||
|
01:19:09.000 --> 01:19:10.000
|
||
|
Right.
|
||
|
|
||
|
01:19:10.000 --> 01:19:11.000
|
||
|
My slide on monkeys exaggerate it.
|
||
|
|
||
|
01:19:11.000 --> 01:19:13.000
|
||
|
I'm not sure about guinea pigs.
|
||
|
|
||
|
01:19:13.000 --> 01:19:15.000
|
||
|
Guinea pigs laugh.
|
||
|
|
||
|
01:19:15.000 --> 01:19:17.000
|
||
|
So that's the interesting part of this.
|
||
|
|
||
|
01:19:17.000 --> 01:19:20.000
|
||
|
I think it's quite interesting that this vaccine is protective.
|
||
|
|
||
|
01:19:20.000 --> 01:19:24.000
|
||
|
It looks like infection because they don't see viremia without neutralizing antibody.
|
||
|
|
||
|
01:19:24.000 --> 01:19:28.000
|
||
|
And you know, the conventional wisdom is you need neutralizing antibodies to prevent infection.
|
||
|
|
||
|
01:19:28.000 --> 01:19:29.000
|
||
|
But here's an example.
|
||
|
|
||
|
01:19:29.000 --> 01:19:35.000
|
||
|
And it may be that the replication cycle is sufficiently long of this virus that it gives time for FC-dependent mechanisms to kick in.
|
||
|
|
||
|
01:19:35.000 --> 01:19:36.000
|
||
|
I don't know.
|
||
|
|
||
|
01:19:36.000 --> 01:19:37.000
|
||
|
But I thought that was really interesting.
|
||
|
|
||
|
01:19:37.000 --> 01:19:38.000
|
||
|
It is.
|
||
|
|
||
|
01:19:38.000 --> 01:19:42.000
|
||
|
They also do mention that they have not looked at cell-mediated immune responses here, so we don't know if T cells are doing anything.
|
||
|
|
||
|
01:19:42.000 --> 01:19:49.000
|
||
|
We don't know if T cells are doing anything because they haven't done any cell-mediated responses at all.
|
||
|
|
||
|
01:19:49.000 --> 01:19:55.000
|
||
|
But how do they get B cell responses if they're not getting T cell response?
|
||
|
|
||
|
01:19:55.000 --> 01:19:59.000
|
||
|
You see that it's just crazy.
|
||
|
|
||
|
01:19:59.000 --> 01:20:01.000
|
||
|
These people know how the immune system works.
|
||
|
|
||
|
01:20:01.000 --> 01:20:06.000
|
||
|
So they know that antigen-presenting cells had to go to work.
|
||
|
|
||
|
01:20:07.000 --> 01:20:13.000
|
||
|
And if antigen-presenting cells went to work, then nonspecific B cells were activated by their passage into the lymph node,
|
||
|
|
||
|
01:20:13.000 --> 01:20:18.000
|
||
|
which means, and nonspecific IgM went up.
|
||
|
|
||
|
01:20:18.000 --> 01:20:28.000
|
||
|
It means that cells that recognize these epitopes from other viruses or similar ones could potentially be woken up,
|
||
|
|
||
|
01:20:28.000 --> 01:20:34.000
|
||
|
depending on what aspects of this protein are being presented.
|
||
|
|
||
|
01:20:35.000 --> 01:20:46.000
|
||
|
It's an incredible simplification of things going on while purporting to discuss a very interesting observation,
|
||
|
|
||
|
01:20:46.000 --> 01:20:53.000
|
||
|
which should have allowed them to bring people closer to understanding the complexity at hand.
|
||
|
|
||
|
01:20:53.000 --> 01:21:01.000
|
||
|
And instead, they're being very careful to make sure that nobody sees the complexity that's available in this paper.
|
||
|
|
||
|
01:21:01.000 --> 01:21:03.000
|
||
|
So that could perhaps be another study as well.
|
||
|
|
||
|
01:21:03.000 --> 01:21:07.000
|
||
|
Yeah, which that's something that's limited, apparently, by the available tools for guinea pigs.
|
||
|
|
||
|
01:21:07.000 --> 01:21:10.000
|
||
|
So they just don't have assays that they can use that.
|
||
|
|
||
|
01:21:10.000 --> 01:21:11.000
|
||
|
Yes.
|
||
|
|
||
|
01:21:11.000 --> 01:21:18.000
|
||
|
If you vaccinate with this mRNA vaccine, how many days later will you get effective T cells at the sites of injection?
|
||
|
|
||
|
01:21:18.000 --> 01:21:19.000
|
||
|
What are they challenging with them?
|
||
|
|
||
|
01:21:19.000 --> 01:21:21.000
|
||
|
Intraperitoneally is the challenge.
|
||
|
|
||
|
01:21:21.000 --> 01:21:26.000
|
||
|
So how long would it take to get T cells there?
|
||
|
|
||
|
01:21:26.000 --> 01:21:32.000
|
||
|
Intraperitoneally means, like, in the body cavity, they're injecting the virus.
|
||
|
|
||
|
01:21:32.000 --> 01:21:47.000
|
||
|
And the virus is generated by a few passages of something on cells and then putting that in the peritoneum.
|
||
|
|
||
|
01:21:47.000 --> 01:21:58.000
|
||
|
So you just lift the skin of the animal and poke the needle under the skin and then inject.
|
||
|
|
||
|
01:21:58.000 --> 01:22:06.000
|
||
|
It's not really how viruses tend to enter the immune system, right?
|
||
|
|
||
|
01:22:06.000 --> 01:22:24.000
|
||
|
So maybe serum antibodies are more useful in a scenario where somebody lifts your skin and injects 30 platforming units of something into your peritoneum,
|
||
|
|
||
|
01:22:24.000 --> 01:22:29.000
|
||
|
as opposed to, you know, like, breathe on you or something like that.
|
||
|
|
||
|
01:22:29.000 --> 01:22:45.000
|
||
|
But again, not wanting to sound like the Bailey's or not sounding like there's no virus, but these kinds of experiments that are done in with these methodologies have to be scrutinized for what they are.
|
||
|
|
||
|
01:22:46.000 --> 01:22:51.000
|
||
|
They're not really bona fide examples of how viruses work.
|
||
|
|
||
|
01:22:51.000 --> 01:23:01.000
|
||
|
They're not really, you know, they're not sick animals in a little animal hospital and they're, you know, getting treatment monitoring and they didn't come in sick.
|
||
|
|
||
|
01:23:01.000 --> 01:23:11.000
|
||
|
And they didn't make a little air, air, you know, connected little bubbles where they infected them all, like real animals getting infected.
|
||
|
|
||
|
01:23:11.000 --> 01:23:21.000
|
||
|
That's not what they did. They lifted the skin and they injected the contents of a cell culture into their peritoneal cavity.
|
||
|
|
||
|
01:23:21.000 --> 01:23:23.000
|
||
|
And that was infection.
|
||
|
|
||
|
01:23:23.000 --> 01:23:40.000
|
||
|
And the treated animals apparently didn't get sick from that, which is amazing, but I'm not really sure that that's the same as giving protection from whatever this virus would be and however a guinea pig would get it in the wild.
|
||
|
|
||
|
01:23:41.000 --> 01:23:48.000
|
||
|
It's super bizarre a world this. It's like they can't see this between a week and two weeks.
|
||
|
|
||
|
01:23:48.000 --> 01:23:51.000
|
||
|
So they're challenging till 56 days. Yeah. Yeah.
|
||
|
|
||
|
01:23:51.000 --> 01:23:57.000
|
||
|
Because it depends on the virus, right? Because certain viruses, it's very well defined. Like LCMB, you know that, like, by day age, you'll have, like, peak T cell response and then you'll be able to.
|
||
|
|
||
|
01:23:57.000 --> 01:23:58.000
|
||
|
Right. With Alaska.
|
||
|
|
||
|
01:23:58.000 --> 01:24:00.000
|
||
|
Has it even been studied? I don't know.
|
||
|
|
||
|
01:24:00.000 --> 01:24:06.000
|
||
|
It's a good point. But, you know, the member in the control animals, they have no signs of disease until seven to nine days. So presumably the virus is reproducing.
|
||
|
|
||
|
01:24:06.000 --> 01:24:15.000
|
||
|
But maybe that's when the T cells would be coming up, depending on the kinetics, right? Absolutely. And we talk about that with, you know, day eight or whatever as being kind of the peak response.
|
||
|
|
||
|
01:24:15.000 --> 01:24:19.000
|
||
|
Earlier, you'd see some response, just not the best possible response.
|
||
|
|
||
|
01:24:19.000 --> 01:24:30.000
|
||
|
Anyway, so when a new variant of SARS-CoV-2 shows up and they look to see whether that variant Daniel has posted a really nice thing in the chat.
|
||
|
|
||
|
01:24:30.000 --> 01:24:49.000
|
||
|
And I think that's the next immunology lecture that's coming will be one that really talks about how the tolerant side of T cells and the intolerant side of T cells is a sort of yin and yang that with a natural infection is stimulated in the correct way.
|
||
|
|
||
|
01:24:49.000 --> 01:24:55.000
|
||
|
And with an intramuscular injection is not stimulated at all.
|
||
|
|
||
|
01:24:56.000 --> 01:25:05.000
|
||
|
And so this augmentation and what we're trying to augment requires understanding the system that you're trying to change.
|
||
|
|
||
|
01:25:05.000 --> 01:25:17.000
|
||
|
And I would suggest, and I'm going to keep suggesting that intramuscular injection of a combination of chemicals and proteins suggests that people don't understand how the immune system works.
|
||
|
|
||
|
01:25:18.000 --> 01:25:30.000
|
||
|
And since I know that we understand how the immune system works better than what is belied by that methodology, we need to speak out and we need to speak out now.
|
||
|
|
||
|
01:25:30.000 --> 01:25:41.000
|
||
|
Because the vaccine act and the prep act basically allow them to call anything they want, a countermeasure, and that includes injectables.
|
||
|
|
||
|
01:25:42.000 --> 01:25:51.000
|
||
|
And there's very few good reasons for intramuscular injection of any combination of anything to augment the immune system.
|
||
|
|
||
|
01:25:51.000 --> 01:25:56.000
|
||
|
I assure you, we are going to be, we are going to be proven right on that.
|
||
|
|
||
|
01:25:56.000 --> 01:26:01.000
|
||
|
We are.
|
||
|
|
||
|
01:26:02.000 --> 01:26:09.000
|
||
|
And what we're going to be doing is how it reacts with serum from previous infections.
|
||
|
|
||
|
01:26:09.000 --> 01:26:14.000
|
||
|
The gold standard, as it were, they're usually reporting on a neutralization assay.
|
||
|
|
||
|
01:26:14.000 --> 01:26:24.000
|
||
|
And if they say the serum that was from previous infections does not neutralize or poorly neutralizes this new variant, you don't necessarily have to freak out.
|
||
|
|
||
|
01:26:25.000 --> 01:26:27.000
|
||
|
Because there, you might want to freak out.
|
||
|
|
||
|
01:26:27.000 --> 01:26:34.000
|
||
|
But yeah, a lot of people who have only the three original SARS-CoV-2 vaccines who then get infected with Omicron's, they stay out of the hospital, right?
|
||
|
|
||
|
01:26:34.000 --> 01:26:37.000
|
||
|
They're alive because of probably some of these effector functions and T cells and others.
|
||
|
|
||
|
01:26:37.000 --> 01:26:38.000
|
||
|
Yeah, I guess.
|
||
|
|
||
|
01:26:38.000 --> 01:26:40.000
|
||
|
But still, of course, with all the caveats involved.
|
||
|
|
||
|
01:26:40.000 --> 01:26:42.000
|
||
|
The skinny patients, laughing at SARS, blah, blah, blah.
|
||
|
|
||
|
01:26:42.000 --> 01:26:48.000
|
||
|
I mean, I think most people will say that antibodies are really important for preventing infection by SARS-CoV-2.
|
||
|
|
||
|
01:26:49.000 --> 01:26:53.000
|
||
|
But if you don't, if they don't neutralize, you can, you might want to speak out.
|
||
|
|
||
|
01:26:53.000 --> 01:27:01.000
|
||
|
Yeah, a lot of people who have only the three original SARS-CoV-2 vaccines who then get infected with Omicron's, they stay out of the hospital, right?
|
||
|
|
||
|
01:27:01.000 --> 01:27:03.000
|
||
|
But no more abilities you have, right?
|
||
|
|
||
|
01:27:03.000 --> 01:27:04.000
|
||
|
Right.
|
||
|
|
||
|
01:27:04.000 --> 01:27:07.000
|
||
|
Because there, you might want to freak out.
|
||
|
|
||
|
01:27:07.000 --> 01:27:17.000
|
||
|
But yeah, a lot of people who have only the three original SARS-CoV-2 vaccines who then get infected with Omicron's, they stay out of the hospital, right?
|
||
|
|
||
|
01:27:17.000 --> 01:27:22.000
|
||
|
They're alive because of probably some of these effector functions and T cells and others.
|
||
|
|
||
|
01:27:22.000 --> 01:27:24.000
|
||
|
Yeah, I guess.
|
||
|
|
||
|
01:27:24.000 --> 01:27:25.000
|
||
|
Yeah, I guess.
|
||
|
|
||
|
01:27:25.000 --> 01:27:32.000
|
||
|
I guess maybe that's why some people are still alive because of these other functions besides antibodies or not.
|
||
|
|
||
|
01:27:32.000 --> 01:27:33.000
|
||
|
But still.
|
||
|
|
||
|
01:27:33.000 --> 01:27:35.000
|
||
|
Of course, with all the caveats involved.
|
||
|
|
||
|
01:27:35.000 --> 01:27:38.000
|
||
|
The skinny pigs, the slothsets, not SARS, blah, blah, blah.
|
||
|
|
||
|
01:27:38.000 --> 01:27:46.000
|
||
|
No, I mean, I think most people will say that antibodies are really important for preventing infection by SARS-CoV-2.
|
||
|
|
||
|
01:27:47.000 --> 01:27:48.000
|
||
|
Yeah.
|
||
|
|
||
|
01:27:48.000 --> 01:27:59.000
|
||
|
But if they don't neutralize, you can still live, and some studies have shown, and we've done them, that FC-mediated mechanisms are involved in protection.
|
||
|
|
||
|
01:27:59.000 --> 01:28:05.000
|
||
|
So neutralizing antibodies is a very interesting term they keep coming bouncing back to.
|
||
|
|
||
|
01:28:05.000 --> 01:28:16.000
|
||
|
And really neutralizing antibodies comes down to a test in a laboratory where they use virus or clone or something,
|
||
|
|
||
|
01:28:16.000 --> 01:28:25.000
|
||
|
viral particles, pseudovirus particles in some cases, with the protein in question on the outside.
|
||
|
|
||
|
01:28:26.000 --> 01:28:39.000
|
||
|
And the antibodies have to prevent those proteins from causing cytotoxicity in the or psychopathic effects in the cell culture that they would otherwise infect.
|
||
|
|
||
|
01:28:39.000 --> 01:28:45.000
|
||
|
So neutralizing antibodies have to change the infectivity of the virus in a negative way.
|
||
|
|
||
|
01:28:46.000 --> 01:29:04.000
|
||
|
And so antibodies that don't do that are non neutralizing antibodies, but they can still bind quaternary epitopes that are related to the spike protein in a way that bring about the effective clearance of the virus.
|
||
|
|
||
|
01:29:05.000 --> 01:29:21.000
|
||
|
So, and again, remember they're looking for antibodies, but they have no proof that the antibodies are saving the animals because in fact half of the animals or more don't even have the antibodies that they're looking for.
|
||
|
|
||
|
01:29:22.000 --> 01:29:42.000
|
||
|
And so this whole paper is a giant incongruency that points to the fact that as we model this immunology, we are using immunomethology because we're vaccinating these animals and we're using as a proxy of immunity,
|
||
|
|
||
|
01:29:42.000 --> 01:29:56.000
|
||
|
the presence of neutralizing or non neutralizing antibodies, but even both of those categories neutralizing or non neutralizing only half of the animals have any antibodies that are detectable.
|
||
|
|
||
|
01:29:56.000 --> 01:30:09.000
|
||
|
So what's saving them the same thing that saved everybody else at the beginning of the pandemic, the same thing that saves us for all of our existence for millennia.
|
||
|
|
||
|
01:30:09.000 --> 01:30:26.000
|
||
|
This beautiful symphony of over 30 or 40 different subtypes of cells, which independently coordinate a specific and non specific wing of attack that prevents aberrant genetic signals in our body.
|
||
|
|
||
|
01:30:27.000 --> 01:30:38.000
|
||
|
That's what this is about, and they're trying to say that you can usefully augment that beautiful symphony by injecting a bunch of crap in your muscle.
|
||
|
|
||
|
01:30:38.000 --> 01:30:55.000
|
||
|
And they're also agreeing with the idea that if you take some RNA and you passage it on cells four times and then you take the contents of that of that supernatant or lysate and then you inject it interperitoneally
|
||
|
|
||
|
01:30:55.000 --> 01:31:10.000
|
||
|
under the skin of an animal, and some get sick and some don't, that the presence of those antibodies that you tested for in figures one through three is the reason why some died and some didn't.
|
||
|
|
||
|
01:31:10.000 --> 01:31:16.000
|
||
|
But you know you're augmenting an immune system that has 100 moving parts.
|
||
|
|
||
|
01:31:16.000 --> 01:31:20.000
|
||
|
Yeah, it might be that too, might be some of those other parts too.
|
||
|
|
||
|
01:31:20.000 --> 01:31:28.000
|
||
|
Because some of those animals didn't even have anybody so maybe it's those other things I don't know, it could be, it could be, sorry this isn't SARS though.
|
||
|
|
||
|
01:31:28.000 --> 01:31:32.000
|
||
|
Animal model, we did that, I think that was a Michael Diamond paper.
|
||
|
|
||
|
01:31:32.000 --> 01:31:40.000
|
||
|
Yeah, for some reason I was thinking we talked about it or somehow referenced Paul B. Nash and Theodora, maybe during that discussion.
|
||
|
|
||
|
01:31:40.000 --> 01:31:44.000
|
||
|
So, I think, yeah.
|
||
|
|
||
|
01:31:44.000 --> 01:31:49.000
|
||
|
Anyway, there are a number of other vaccines in development, I just want you to know that.
|
||
|
|
||
|
01:31:49.000 --> 01:32:00.000
|
||
|
And they're two VSV, Viscular Stomatitis Vectored Vaccines, and they're actually DNA vaccines as well.
|
||
|
|
||
|
01:32:00.000 --> 01:32:09.000
|
||
|
So there are a bunch of others which is good because we want to have a vaccine and we don't need to have 5000 deaths a year from this infection.
|
||
|
|
||
|
01:32:09.000 --> 01:32:20.000
|
||
|
Yeah, I was actually, I was impressed, they summarized in the paper the different candidates that are out there and I didn't realize there were that many for this virus.
|
||
|
|
||
|
01:32:20.000 --> 01:32:28.000
|
||
|
It is a very serious ongoing development effort and it seems likely that something's going to work.
|
||
|
|
||
|
01:32:28.000 --> 01:32:38.000
|
||
|
They also pointed out that there were differences in the immune response to those different vaccines.
|
||
|
|
||
|
01:32:39.000 --> 01:32:41.000
|
||
|
Was that, I forget.
|
||
|
|
||
|
01:32:41.000 --> 01:32:42.000
|
||
|
I'm going to speed it up again.
|
||
|
|
||
|
01:32:42.000 --> 01:32:43.000
|
||
|
Yeah, there were some.
|
||
|
|
||
|
01:32:43.000 --> 01:32:44.000
|
||
|
Whether or not they.
|
||
|
|
||
|
01:32:44.000 --> 01:32:46.000
|
||
|
Almost those things.
|
||
|
|
||
|
01:32:46.000 --> 01:32:47.000
|
||
|
Yeah.
|
||
|
|
||
|
01:32:47.000 --> 01:32:48.000
|
||
|
Yeah.
|
||
|
|
||
|
01:32:48.000 --> 01:32:49.000
|
||
|
Quaternary epitope.
|
||
|
|
||
|
01:32:49.000 --> 01:32:50.000
|
||
|
No, there we go.
|
||
|
|
||
|
01:32:50.000 --> 01:32:51.000
|
||
|
Yes.
|
||
|
|
||
|
01:32:51.000 --> 01:32:53.000
|
||
|
Yeah, there were some that seemed to work.
|
||
|
|
||
|
01:32:53.000 --> 01:32:58.000
|
||
|
There were some others, I think, that seemed to work, even though they don't always induce neutralizing antibody or moderate neutralizing antibody.
|
||
|
|
||
|
01:32:58.000 --> 01:32:59.000
|
||
|
So this may be a theme.
|
||
|
|
||
|
01:32:59.000 --> 01:33:04.000
|
||
|
So there is a looking looking at, you know, the sort of the composition of those different vaccines.
|
||
|
|
||
|
01:33:04.000 --> 01:33:09.000
|
||
|
I don't see any way you could predict that they would give different sorts of immunizations.
|
||
|
|
||
|
01:33:09.000 --> 01:33:12.000
|
||
|
A lot of them are making protein in during the immunization.
|
||
|
|
||
|
01:33:12.000 --> 01:33:13.000
|
||
|
Okay.
|
||
|
|
||
|
01:33:13.000 --> 01:33:14.000
|
||
|
Yeah.
|
||
|
|
||
|
01:33:14.000 --> 01:33:15.000
|
||
|
One's an attenuated virus.
|
||
|
|
||
|
01:33:15.000 --> 01:33:17.000
|
||
|
A couple of them, I think, are vectored.
|
||
|
|
||
|
01:33:17.000 --> 01:33:18.000
|
||
|
Yeah.
|
||
|
|
||
|
01:33:18.000 --> 01:33:27.000
|
||
|
So there are a couple of measles virus vectored constructs that don't induce neutralizing antibodies and they still give near sterilizing protection, they say, in non-human primates.
|
||
|
|
||
|
01:33:27.000 --> 01:33:31.000
|
||
|
So this is something that we're seeing with lassa virus, I suppose.
|
||
|
|
||
|
01:33:31.000 --> 01:33:32.000
|
||
|
So anyway, that's that.
|
||
|
|
||
|
01:33:32.000 --> 01:33:33.000
|
||
|
I thought that was cool.
|
||
|
|
||
|
01:33:33.000 --> 01:33:34.000
|
||
|
Very cool.
|
||
|
|
||
|
01:33:34.000 --> 01:33:35.000
|
||
|
I like that.
|
||
|
|
||
|
01:33:35.000 --> 01:33:36.000
|
||
|
Thank you.
|
||
|
|
||
|
01:33:36.000 --> 01:33:37.000
|
||
|
Yeah.
|
||
|
|
||
|
01:33:37.000 --> 01:33:39.000
|
||
|
Next paper is, well, this paper makes me obsolete.
|
||
|
|
||
|
01:33:39.000 --> 01:33:40.000
|
||
|
Okay.
|
||
|
|
||
|
01:33:40.000 --> 01:33:41.000
|
||
|
This is.
|
||
|
|
||
|
01:33:41.000 --> 01:33:42.000
|
||
|
Yeah, but they cited you.
|
||
|
|
||
|
01:33:42.000 --> 01:33:45.000
|
||
|
This is a very nice discussion that comes up next.
|
||
|
|
||
|
01:33:45.000 --> 01:33:54.000
|
||
|
So I want you to pay very close attention to how Vincent Ranson yellow introduces it without saying infectious clones.
|
||
|
|
||
|
01:33:54.000 --> 01:34:01.000
|
||
|
So he's going to try and complain that they're not really talking like they should be talking.
|
||
|
|
||
|
01:34:01.000 --> 01:34:06.000
|
||
|
Because they're not really telling you that the way that they do this is using clones.
|
||
|
|
||
|
01:34:06.000 --> 01:34:14.000
|
||
|
And I made the first clone, but he is going to say it, but it's just interesting how we go through it because there's going to be several almost.
|
||
|
|
||
|
01:34:14.000 --> 01:34:23.000
|
||
|
You would think like, wait, wow, are they actually saying that we can't work on RNA viruses without this technology called cloning.
|
||
|
|
||
|
01:34:23.000 --> 01:34:24.000
|
||
|
Really?
|
||
|
|
||
|
01:34:24.000 --> 01:34:26.000
|
||
|
Because they're about to say it right now.
|
||
|
|
||
|
01:34:26.000 --> 01:34:29.000
|
||
|
You're not going to believe it.
|
||
|
|
||
|
01:34:30.000 --> 01:34:31.000
|
||
|
Okay.
|
||
|
|
||
|
01:34:31.000 --> 01:34:32.000
|
||
|
I'm very impressed.
|
||
|
|
||
|
01:34:32.000 --> 01:34:33.000
|
||
|
They said it to me and Charlie Weissman.
|
||
|
|
||
|
01:34:33.000 --> 01:34:36.000
|
||
|
And, you know, most people forget what happens more than five years ago.
|
||
|
|
||
|
01:34:36.000 --> 01:34:37.000
|
||
|
That's right.
|
||
|
|
||
|
01:34:37.000 --> 01:34:38.000
|
||
|
Science.
|
||
|
|
||
|
01:34:38.000 --> 01:34:39.000
|
||
|
I missed that.
|
||
|
|
||
|
01:34:39.000 --> 01:34:40.000
|
||
|
What did they say you for?
|
||
|
|
||
|
01:34:40.000 --> 01:34:41.000
|
||
|
Oh, for a row.
|
||
|
|
||
|
01:34:41.000 --> 01:34:42.000
|
||
|
Okay.
|
||
|
|
||
|
01:34:42.000 --> 01:34:43.000
|
||
|
So in the discussion, this is a good way to start this actually.
|
||
|
|
||
|
01:34:43.000 --> 01:34:49.000
|
||
|
Several years after the Asilomar conference on recombinant DNA in 1975, the first complementary DNA clones of RNA viruses were created.
|
||
|
|
||
|
01:34:49.000 --> 01:34:52.000
|
||
|
References 25 and 26 Charles Weissman and Baltimore and Raccoon yellow.
|
||
|
|
||
|
01:34:52.000 --> 01:34:58.000
|
||
|
So when I went to David's lab in 1979, he said, Vinny, Asilomar said, we could clone the whole polio genome.
|
||
|
|
||
|
01:34:58.000 --> 01:35:00.000
|
||
|
I want you to do that and see if it's infectious.
|
||
|
|
||
|
01:35:00.000 --> 01:35:03.000
|
||
|
And I did it and it was infectious and that's where this came from, right?
|
||
|
|
||
|
01:35:03.000 --> 01:35:05.000
|
||
|
You can make a DNA copy of polio virus RNA genome.
|
||
|
|
||
|
01:35:05.000 --> 01:35:09.000
|
||
|
So now you could manipulate the genome because you couldn't manipulate RNA.
|
||
|
|
||
|
01:35:09.000 --> 01:35:10.000
|
||
|
Yeah.
|
||
|
|
||
|
01:35:10.000 --> 01:35:11.000
|
||
|
And now this paper is going to change that.
|
||
|
|
||
|
01:35:11.000 --> 01:35:12.000
|
||
|
It's going to.
|
||
|
|
||
|
01:35:12.000 --> 01:35:15.000
|
||
|
And that has been, we've talked about this off and on in various episodes.
|
||
|
|
||
|
01:35:15.000 --> 01:35:19.000
|
||
|
That's been a huge roadblock to studying RNA viruses in general because, I mean, Vincent did this with polio virus.
|
||
|
|
||
|
01:35:19.000 --> 01:35:23.000
|
||
|
It turns out you can't just do the same thing with every other RNA virus.
|
||
|
|
||
|
01:35:23.000 --> 01:35:25.000
|
||
|
Some of them you can, some of them you can't do.
|
||
|
|
||
|
01:35:25.000 --> 01:35:28.000
|
||
|
You get the cDNA, that part is now relatively straightforward.
|
||
|
|
||
|
01:35:28.000 --> 01:35:31.000
|
||
|
But whether or not it's infectious depends a lot, virus to virus.
|
||
|
|
||
|
01:35:31.000 --> 01:35:36.000
|
||
|
So there are a lot of RNA viruses that we can't do molecular biology on very easily or at least we couldn't.
|
||
|
|
||
|
01:35:36.000 --> 01:35:38.000
|
||
|
And that's what these folks are trying to address.
|
||
|
|
||
|
01:35:38.000 --> 01:35:39.000
|
||
|
Yeah.
|
||
|
|
||
|
01:35:39.000 --> 01:35:42.000
|
||
|
And I mean, you could imagine other ways that somebody might think about wanting to edit RNA.
|
||
|
|
||
|
01:35:42.000 --> 01:35:44.000
|
||
|
And editing RNA basically wasn't a choice.
|
||
|
|
||
|
01:35:44.000 --> 01:35:45.000
|
||
|
Yeah.
|
||
|
|
||
|
01:35:45.000 --> 01:35:51.000
|
||
|
I mean, I mentioned, you know, SARS-CoV-2, you couldn't take a single 30,000 base piece of DNA and stick it in a plasmid.
|
||
|
|
||
|
01:35:51.000 --> 01:35:56.000
|
||
|
You had to make fragments and clone them in multiple plasmids and put them in cells so they recombine and so forth.
|
||
|
|
||
|
01:35:56.000 --> 01:35:57.000
|
||
|
So it was tricky.
|
||
|
|
||
|
01:35:57.000 --> 01:35:59.000
|
||
|
But in theory, this method, which is in this paper, it could get around that.
|
||
|
|
||
|
01:35:59.000 --> 01:36:10.000
|
||
|
It's called CRISPR-based engineering of RNA viruses by Artem Nemudry, Anna Nemudrya, Joseph Nichols, Andrew Schifersall, and Blake Wiedenheft.
|
||
|
|
||
|
01:36:10.000 --> 01:36:15.000
|
||
|
And they're from Post Montana State University in Bozeman, Montana.
|
||
|
|
||
|
01:36:15.000 --> 01:36:17.000
|
||
|
So I'm thinking, okay, where is this?
|
||
|
|
||
|
01:36:17.000 --> 01:36:20.000
|
||
|
UCSF, Chicago Stanford, Harvard, no, it's Bozeman.
|
||
|
|
||
|
01:36:20.000 --> 01:36:22.000
|
||
|
So good work can be done anywhere.
|
||
|
|
||
|
01:36:22.000 --> 01:36:23.000
|
||
|
You need a lot of things.
|
||
|
|
||
|
01:36:23.000 --> 01:36:25.000
|
||
|
You need money, you need interest, and so forth.
|
||
|
|
||
|
01:36:25.000 --> 01:36:27.000
|
||
|
Anyway, so there's only six authors on this paper.
|
||
|
|
||
|
01:36:27.000 --> 01:36:28.000
|
||
|
No, it's cool.
|
||
|
|
||
|
01:36:28.000 --> 01:36:29.000
|
||
|
Not an enormous group these days.
|
||
|
|
||
|
01:36:29.000 --> 01:36:31.000
|
||
|
Hey, when I did this with David, there were two authors on the page.
|
||
|
|
||
|
01:36:31.000 --> 01:36:32.000
|
||
|
Yeah, they had a different time.
|
||
|
|
||
|
01:36:32.000 --> 01:36:36.000
|
||
|
Those are the old days when we walked uphill 30 miles to get to school in the snow.
|
||
|
|
||
|
01:36:36.000 --> 01:36:37.000
|
||
|
In other ways, yeah.
|
||
|
|
||
|
01:36:37.000 --> 01:36:42.000
|
||
|
Anyway, you know, you can, they make this very interesting historical statement.
|
||
|
|
||
|
01:36:42.000 --> 01:36:45.000
|
||
|
The first was the first to make a recombinant DNA molecule in 1972.
|
||
|
|
||
|
01:36:45.000 --> 01:36:49.000
|
||
|
And then we have used recombinant DNA to study many, many things, not just viruses.
|
||
|
|
||
|
01:36:49.000 --> 01:36:55.000
|
||
|
But, and then CRISPR came along to allow editing of DNAs, but very few tools to do RNA.
|
||
|
|
||
|
01:36:55.000 --> 01:37:00.000
|
||
|
So just, just to remind you, CRISPR is a defense system from bacteria and archaea that evolved
|
||
|
|
||
|
01:37:00.000 --> 01:37:04.000
|
||
|
to protect against viruses and incoming DNAs into bacteria and archaea.
|
||
|
|
||
|
01:37:04.000 --> 01:37:09.000
|
||
|
And it involves a system where a set of nucleases in the host cell combined with a guide RNA
|
||
|
|
||
|
01:37:09.000 --> 01:37:13.000
|
||
|
and targets a specific sequence will say if a phage infects a cell, the DNA will be degraded.
|
||
|
|
||
|
01:37:13.000 --> 01:37:16.000
|
||
|
And it's been repurposed by scientists to do gene editing.
|
||
|
|
||
|
01:37:16.000 --> 01:37:21.000
|
||
|
So you can take a guide RNA and the proteins and nucleases and so forth and put them in cells
|
||
|
|
||
|
01:37:21.000 --> 01:37:24.000
|
||
|
and you can edit DNA in reasonably precise ways.
|
||
|
|
||
|
01:37:24.000 --> 01:37:26.000
|
||
|
But we haven't been able to do that with RNA.
|
||
|
|
||
|
01:37:26.000 --> 01:37:28.000
|
||
|
And that's what they're going to do in this paper.
|
||
|
|
||
|
01:37:28.000 --> 01:37:30.000
|
||
|
Yeah, I really liked how they laid this out in the introduction.
|
||
|
|
||
|
01:37:30.000 --> 01:37:31.000
|
||
|
Yeah.
|
||
|
|
||
|
01:37:31.000 --> 01:37:35.000
|
||
|
Because they kind of, they made it in a way that I'm interested to think about with students
|
||
|
|
||
|
01:37:35.000 --> 01:37:38.000
|
||
|
because they basically talk about the fact that, well, if you're going to manipulate DNA,
|
||
|
|
||
|
01:37:38.000 --> 01:37:42.000
|
||
|
you need an enzyme that cuts the DNA in a place where you want, or some way to get the DNA cut where you want to.
|
||
|
|
||
|
01:37:42.000 --> 01:37:48.000
|
||
|
And of course, the problem here is, again, what we heard Vincent Rancin yellow tell us the other night.
|
||
|
|
||
|
01:37:48.000 --> 01:37:52.000
|
||
|
Sorry, Vincent Raccoon yellow.
|
||
|
|
||
|
01:37:52.000 --> 01:37:57.000
|
||
|
Did you hear, by the way, that he referred to David Baltimore as calling him Vinnie?
|
||
|
|
||
|
01:37:57.000 --> 01:37:58.000
|
||
|
Did you catch that part?
|
||
|
|
||
|
01:37:58.000 --> 01:38:00.000
|
||
|
Hey, Vinnie, I want you to do that.
|
||
|
|
||
|
01:38:00.000 --> 01:38:04.000
|
||
|
No, I kind of forgot what I was going to say.
|
||
|
|
||
|
01:38:04.000 --> 01:38:06.000
|
||
|
Sorry, I got, oh, yeah, sorry.
|
||
|
|
||
|
01:38:06.000 --> 01:38:09.000
|
||
|
The, the idea was that thanks for that.
|
||
|
|
||
|
01:38:09.000 --> 01:38:16.000
|
||
|
Watch or be CRISPR will save us reminded me that they, they're trying to edit a genome.
|
||
|
|
||
|
01:38:16.000 --> 01:38:24.000
|
||
|
And if you're culturing a genome in, in, in cell culture, the way that they do.
|
||
|
|
||
|
01:38:24.000 --> 01:38:33.000
|
||
|
And it is a, it is a virus as we understand it, then the replication will be erroneous and, and not imperfect.
|
||
|
|
||
|
01:38:33.000 --> 01:38:37.000
|
||
|
You'll have a cloud of particles. A lot of them won't have a complete genome.
|
||
|
|
||
|
01:38:37.000 --> 01:38:41.000
|
||
|
And any of them that do will have a unique complete genome.
|
||
|
|
||
|
01:38:41.000 --> 01:38:53.000
|
||
|
And so if you want to do CRISPR editing on RNA and study the mechanisms by which it works, you got to start with a pure RNA sample.
|
||
|
|
||
|
01:38:53.000 --> 01:38:59.000
|
||
|
Not a swarm of all kinds of different genomes that would be made in a culture.
|
||
|
|
||
|
01:38:59.000 --> 01:39:02.000
|
||
|
You got to start with a, with a clone.
|
||
|
|
||
|
01:39:02.000 --> 01:39:14.000
|
||
|
A whole bunch of identical molecules. And then if you want to see the signal of the alteration that you make, those molecules have to be sufficiently homologous and homogenous.
|
||
|
|
||
|
01:39:14.000 --> 01:39:23.000
|
||
|
So that the change will be visible in the two, the differences between the original molecule and the changed one.
|
||
|
|
||
|
01:39:23.000 --> 01:39:31.000
|
||
|
If you only change a small portion of them or the changes in all different places, it won't become a signal that you can see.
|
||
|
|
||
|
01:39:31.000 --> 01:39:43.000
|
||
|
And so the whole idea of sequencing DNA and all this other stuff relies on being able to make many high fidelity copies.
|
||
|
|
||
|
01:39:43.000 --> 01:39:49.000
|
||
|
And you can't do that with RNA. You just can't. You can do it with DNA.
|
||
|
|
||
|
01:39:49.000 --> 01:40:13.000
|
||
|
And so if you start and we look at this carefully, you will see that this is an evolution of this synthetic DNA and RNA technology and editing the DNA and RNA is an evolution and another little step in our ability to make these sequences from scratch.
|
||
|
|
||
|
01:40:14.000 --> 01:40:38.000
|
||
|
But it doesn't change the fact that any one of these sequences, regardless of what they're endowed with, do not gain God-like powers where they have infinite fidelity and can circulate the globe for years and years and years through all the people that you test positive.
|
||
|
|
||
|
01:40:38.000 --> 01:40:46.000
|
||
|
That's not how this works. If that signal is real, it was there before the pandemic.
|
||
|
|
||
|
01:40:46.000 --> 01:41:00.000
|
||
|
And if that signal is semi-real and the rest is fake, it was done with clones because they're telling you right here, we couldn't work on these things until we figured out how to do this.
|
||
|
|
||
|
01:41:00.000 --> 01:41:10.000
|
||
|
And Vincent Rancin, Yellow, was asked by his then new boss, Baltimore, to do that very thing, make the RNA, make it whole, and then let's do it.
|
||
|
|
||
|
01:41:10.000 --> 01:41:14.000
|
||
|
Let's talk about it some more because they're going to keep going. They're going to keep talking.
|
||
|
|
||
|
01:41:14.000 --> 01:41:21.000
|
||
|
And you need repair. And fortunately, ourselves can do lots of DNA repair. So we just cut the DNA where we want, and then we set up repair in a useful way.
|
||
|
|
||
|
01:41:21.000 --> 01:41:29.000
|
||
|
And they talk a little bit about the fact that, well, first, we need to have some way to cut RNA and we found some of that with other crispers, but they don't always cut exactly the right place.
|
||
|
|
||
|
01:41:29.000 --> 01:41:37.000
|
||
|
And as soon as I started reading this, that approach of, well, first, you need to cut, then you need to repair, just made it very clear in my mind of like, oh, yeah, RNA repair.
|
||
|
|
||
|
01:41:37.000 --> 01:41:39.000
|
||
|
What? That's that's that's.
|
||
|
|
||
|
01:41:39.000 --> 01:41:42.000
|
||
|
Nobody repairs RNA. It's possible.
|
||
|
|
||
|
01:41:42.000 --> 01:41:48.000
|
||
|
And the crisper system evolved as a way to destroy RNA. So you're not going to find much luck there, right?
|
||
|
|
||
|
01:41:48.000 --> 01:41:56.000
|
||
|
So there are many different kinds of DNA crisper systems, and there are also some that target RNA, and it's the one they're going to use here is a type three crisper system.
|
||
|
|
||
|
01:41:56.000 --> 01:42:03.000
|
||
|
But there are other RNA crisper systems that have the problem that when they're activated, they also degrade other RNAs.
|
||
|
|
||
|
01:42:03.000 --> 01:42:09.000
|
||
|
But this particular one, this type three crisper RNA system doesn't have this other nuclease that's going to just degrade RNA.
|
||
|
|
||
|
01:42:09.000 --> 01:42:14.000
|
||
|
And so you can do precise targeting of RNAs in theory with not a lot of off target effects. Well, that remains to be seen.
|
||
|
|
||
|
01:42:14.000 --> 01:42:16.000
|
||
|
So that's what they're using in this paper.
|
||
|
|
||
|
01:42:16.000 --> 01:42:25.000
|
||
|
Is it fair to say that all of these crisper systems are basically a protein RNA complex where the RNA guides the protein to a complementary sequence and there's cleavage?
|
||
|
|
||
|
01:42:25.000 --> 01:42:30.000
|
||
|
And beyond that, there's huge variation on that theme, much greater variation than I was aware of before.
|
||
|
|
||
|
01:42:30.000 --> 01:42:36.000
|
||
|
I read this, I said, Oh, yeah, there's a lot, you know, because we look in various species of bacteria and you can get different enzymes and they have different properties.
|
||
|
|
||
|
01:42:36.000 --> 01:42:39.000
|
||
|
And furthermore, you can modify the enzymes to restrict and expand their properties as well.
|
||
|
|
||
|
01:42:39.000 --> 01:42:44.000
|
||
|
So it's a huge enterprise because people want to be able to do gene editing, right? That's what they want to do.
|
||
|
|
||
|
01:42:44.000 --> 01:42:53.000
|
||
|
So this one, this type three crisper system in this paper, very interesting, it's made up of five subunits, which assemble around a crisper RNA.
|
||
|
|
||
|
01:42:53.000 --> 01:43:00.000
|
||
|
And there's an endo ribonuclease that will bind to the target RNA and cut it at six nucleotide intervals.
|
||
|
|
||
|
01:43:00.000 --> 01:43:03.000
|
||
|
A very nice picture here showing how that works.
|
||
|
|
||
|
01:43:03.000 --> 01:43:06.000
|
||
|
So there's a series of proteins including the nucleates that will bind to the RNA.
|
||
|
|
||
|
01:43:06.000 --> 01:43:11.000
|
||
|
And you can direct it to some specific place on the RNA by using a target RNA.
|
||
|
|
||
|
01:43:11.000 --> 01:43:14.000
|
||
|
So they first establish that this works.
|
||
|
|
||
|
01:43:14.000 --> 01:43:18.000
|
||
|
They take the nucleocapsid gene of SARS-CoV-2 and they make the proteins.
|
||
|
|
||
|
01:43:18.000 --> 01:43:23.000
|
||
|
So they have to produce the proteins and cells and purify them and add the RNA that will target it to the RNA.
|
||
|
|
||
|
01:43:23.000 --> 01:43:28.000
|
||
|
They show that it will cleave it with very high efficiency and they make the fragments that are of the expected size.
|
||
|
|
||
|
01:43:28.000 --> 01:43:31.000
|
||
|
Actually, it's a very nice diagram in this supplementary.
|
||
|
|
||
|
01:43:31.000 --> 01:43:35.000
|
||
|
Don't let the chat distract you. Just block those people.
|
||
|
|
||
|
01:43:35.000 --> 01:43:40.000
|
||
|
You're missing this really good video here where they're explaining how clones are made.
|
||
|
|
||
|
01:43:40.000 --> 01:43:42.000
|
||
|
Figure is where it's expected to make the sequence.
|
||
|
|
||
|
01:43:42.000 --> 01:43:43.000
|
||
|
This checkology is.
|
||
|
|
||
|
01:43:43.000 --> 01:43:45.000
|
||
|
That's what they want to do.
|
||
|
|
||
|
01:43:45.000 --> 01:43:49.000
|
||
|
So this one, this Type 3 CRISPR system in this paper, very interesting.
|
||
|
|
||
|
01:43:49.000 --> 01:43:54.000
|
||
|
It's made up of five subunits which assemble around a CRISPR RNA.
|
||
|
|
||
|
01:43:54.000 --> 01:44:01.000
|
||
|
And there's an endo ribonuclease that will bind to the target RNA and cut it at six nucleotide intervals.
|
||
|
|
||
|
01:44:01.000 --> 01:44:04.000
|
||
|
A very nice picture here showing how that works.
|
||
|
|
||
|
01:44:04.000 --> 01:44:07.000
|
||
|
So there's a series of proteins including the nucleates that will bind to the RNA.
|
||
|
|
||
|
01:44:07.000 --> 01:44:12.000
|
||
|
And you can direct it to some specific place on the RNA by using a target RNA.
|
||
|
|
||
|
01:44:12.000 --> 01:44:14.000
|
||
|
So they first establish that this works.
|
||
|
|
||
|
01:44:14.000 --> 01:44:18.000
|
||
|
They take the nucleocapsogen of SARS-CoV-2 and they make the proteins.
|
||
|
|
||
|
01:44:18.000 --> 01:44:23.000
|
||
|
So they have to produce the proteins and cells and purify them and add the RNA that will target it to the RNA.
|
||
|
|
||
|
01:44:23.000 --> 01:44:28.000
|
||
|
They show that it will cleave it with very high efficiency and they make the fragments that are of the expected size.
|
||
|
|
||
|
01:44:28.000 --> 01:44:37.000
|
||
|
Actually, it's a very nice diagram in this supplementary figures where they show the RNA that they've made to target this protein complex to the target RNA
|
||
|
|
||
|
01:44:37.000 --> 01:44:43.000
|
||
|
and how the proteins line up one after another and cut that target RNA in every six spaces or so.
|
||
|
|
||
|
01:44:43.000 --> 01:44:44.000
|
||
|
So it works.
|
||
|
|
||
|
01:44:44.000 --> 01:44:48.000
|
||
|
Now, here's the cool part that brings me back to the old days.
|
||
|
|
||
|
01:44:48.000 --> 01:44:52.000
|
||
|
When this enzyme, it's purified from streptococcus thermophilus.
|
||
|
|
||
|
01:44:52.000 --> 01:44:56.000
|
||
|
So this particular enzyme, the type 3a CRISPR, is purified from there.
|
||
|
|
||
|
01:44:56.000 --> 01:45:02.000
|
||
|
When it cuts the RNA, it makes two prime, three prime cyclic phosphates and a five prime hydroxyl at each cut site.
|
||
|
|
||
|
01:45:02.000 --> 01:45:06.000
|
||
|
And if you remember anything about DNA, that can't be ligated.
|
||
|
|
||
|
01:45:06.000 --> 01:45:09.000
|
||
|
DNA ligases need three prime hydroxyls and five prime phosphates.
|
||
|
|
||
|
01:45:09.000 --> 01:45:13.000
|
||
|
And in fact, when we used the ligate in the old days, phage T4 ligase, right?
|
||
|
|
||
|
01:45:13.000 --> 01:45:15.000
|
||
|
We used to buy it and use that to ligase.
|
||
|
|
||
|
01:45:15.000 --> 01:45:17.000
|
||
|
But you needed to have a five prime phosphate.
|
||
|
|
||
|
01:45:17.000 --> 01:45:20.000
|
||
|
And if you had DNA without it, you had to add it with poly nucleotide kinase.
|
||
|
|
||
|
01:45:20.000 --> 01:45:26.000
|
||
|
However, there's a ligase from E. coli that can join the RNAs that are made by this CRISPR cleavage,
|
||
|
|
||
|
01:45:26.000 --> 01:45:28.000
|
||
|
the two prime, three prime cyclic and the five prime hydroxyl.
|
||
|
|
||
|
01:45:28.000 --> 01:45:30.000
|
||
|
So they try both of those.
|
||
|
|
||
|
01:45:30.000 --> 01:45:32.000
|
||
|
And to enhance the reaction, they make DNA.
|
||
|
|
||
|
01:45:32.000 --> 01:45:33.000
|
||
|
They call them DNA splints.
|
||
|
|
||
|
01:45:33.000 --> 01:45:37.000
|
||
|
The DNA is hybridized to both ends of the RNA that have been cut and kind of hold them together
|
||
|
|
||
|
01:45:37.000 --> 01:45:39.000
|
||
|
while the ligase is ligated at the ends.
|
||
|
|
||
|
01:45:39.000 --> 01:45:40.000
|
||
|
I thought this was very clever.
|
||
|
|
||
|
01:45:40.000 --> 01:45:42.000
|
||
|
So they basically came up with RNA repair?
|
||
|
|
||
|
01:45:42.000 --> 01:45:43.000
|
||
|
Yeah, they had to, right.
|
||
|
|
||
|
01:45:43.000 --> 01:45:44.000
|
||
|
This is not going to be over there.
|
||
|
|
||
|
01:45:44.000 --> 01:45:45.000
|
||
|
Well, there isn't a good RNA repair mechanism.
|
||
|
|
||
|
01:45:45.000 --> 01:45:46.000
|
||
|
Let's build one.
|
||
|
|
||
|
01:45:46.000 --> 01:45:47.000
|
||
|
Right.
|
||
|
|
||
|
01:45:47.000 --> 01:45:51.000
|
||
|
And so they found that both of these ligations worked, but the T4 was more efficient.
|
||
|
|
||
|
01:45:51.000 --> 01:45:52.000
|
||
|
So they decided to follow that.
|
||
|
|
||
|
01:45:52.000 --> 01:45:54.000
|
||
|
It's 25-fold more.
|
||
|
|
||
|
01:45:55.000 --> 01:45:57.000
|
||
|
So I think it's important to see that here.
|
||
|
|
||
|
01:45:57.000 --> 01:46:03.000
|
||
|
The only way that they can get a signal that this clean is if the product that they start
|
||
|
|
||
|
01:46:03.000 --> 01:46:09.000
|
||
|
with, the target RNA that they're manipulating is pure.
|
||
|
|
||
|
01:46:09.000 --> 01:46:15.000
|
||
|
Because then when they make the alteration, the DNA splint that they choose will be specific
|
||
|
|
||
|
01:46:15.000 --> 01:46:20.000
|
||
|
for every one of them because there's no variation or very little.
|
||
|
|
||
|
01:46:20.000 --> 01:46:30.000
|
||
|
And so the only way this really works is they get, now they get GFP signal, which is
|
||
|
|
||
|
01:46:30.000 --> 01:46:35.000
|
||
|
really, again, just whether a protein is being produced or not.
|
||
|
|
||
|
01:46:35.000 --> 01:46:42.000
|
||
|
You don't know at this stage how many of these are genuinely the same sequence because they've
|
||
|
|
||
|
01:46:42.000 --> 01:46:47.000
|
||
|
distilled it down to the presence or absence of a green signal.
|
||
|
|
||
|
01:46:47.000 --> 01:46:52.000
|
||
|
So you've got to be very careful here because, again, it's not to say that something isn't
|
||
|
|
||
|
01:46:52.000 --> 01:46:55.000
|
||
|
happening here and that molecular biology doesn't work.
|
||
|
|
||
|
01:46:55.000 --> 01:47:02.000
|
||
|
It is that when you start with a pure sample of RNA, you're not starting with something
|
||
|
|
||
|
01:47:02.000 --> 01:47:07.000
|
||
|
that represents the natural viral RNA genome.
|
||
|
|
||
|
01:47:07.000 --> 01:47:14.000
|
||
|
You're starting with a hyper-pure version that produces a hyper-pure set of viral particles
|
||
|
|
||
|
01:47:14.000 --> 01:47:17.000
|
||
|
or virions or whatever you call them.
|
||
|
|
||
|
01:47:17.000 --> 01:47:24.000
|
||
|
And you start with this, in this case, a hyper-pure RNA sample that you're then going to expose to
|
||
|
|
||
|
01:47:24.000 --> 01:47:26.000
|
||
|
an enzyme that does predictable things.
|
||
|
|
||
|
01:47:26.000 --> 01:47:30.000
|
||
|
And then in the products, you can see predictable changes.
|
||
|
|
||
|
01:47:30.000 --> 01:47:34.000
|
||
|
That's not very surprising.
|
||
|
|
||
|
01:47:34.000 --> 01:47:40.000
|
||
|
And what it does is it kind of clouds the water that you're still talking about.
|
||
|
|
||
|
01:47:40.000 --> 01:47:44.000
|
||
|
Now, you have to start with a pure RNA, which means you have to start with an infectious
|
||
|
|
||
|
01:47:44.000 --> 01:47:45.000
|
||
|
clone.
|
||
|
|
||
|
01:47:45.000 --> 01:47:50.000
|
||
|
This whole thing has to be based on an infectious clone.
|
||
|
|
||
|
01:47:50.000 --> 01:47:53.000
|
||
|
And so then we're not talking about natural viruses.
|
||
|
|
||
|
01:47:53.000 --> 01:47:58.000
|
||
|
We're talking about synthetic viruses here, which I'm making the argument is the only
|
||
|
|
||
|
01:47:58.000 --> 01:47:59.000
|
||
|
danger.
|
||
|
|
||
|
01:47:59.000 --> 01:48:08.000
|
||
|
They had to produce a lot of it in order to get it to be all over the world like it was.
|
||
|
|
||
|
01:48:08.000 --> 01:48:13.000
|
||
|
And if they didn't produce it, the easiest way would be for it to already be there, the
|
||
|
|
||
|
01:48:13.000 --> 01:48:16.000
|
||
|
signal, not the virus.
|
||
|
|
||
|
01:48:16.000 --> 01:48:20.000
|
||
|
It doesn't have to be that there's SARS virus everywhere in the background for there to
|
||
|
|
||
|
01:48:20.000 --> 01:48:25.000
|
||
|
be a signal that was said to be SARS virus.
|
||
|
|
||
|
01:48:25.000 --> 01:48:31.000
|
||
|
If the PCR could not differentiate from other N proteins, could not differentiate from other
|
||
|
|
||
|
01:48:31.000 --> 01:48:39.000
|
||
|
RNA-dependent RNA polymerases, and there is a background signal of those two, then
|
||
|
|
||
|
01:48:39.000 --> 01:48:45.000
|
||
|
sequence over PCRing with a specific primers that aren't properly nested for those two
|
||
|
|
||
|
01:48:45.000 --> 01:48:51.000
|
||
|
targets will give you false positives all the time.
|
||
|
|
||
|
01:48:51.000 --> 01:48:54.000
|
||
|
And that's what this whole mess is about.
|
||
|
|
||
|
01:48:54.000 --> 01:49:00.000
|
||
|
It's about people being so compartmentalized in their thinking and so presumptive in the
|
||
|
|
||
|
01:49:00.000 --> 01:49:05.000
|
||
|
narrative being right that all of these people would have never lied to us about the potential
|
||
|
|
||
|
01:49:05.000 --> 01:49:07.000
|
||
|
for a pandemic.
|
||
|
|
||
|
01:49:07.000 --> 01:49:13.000
|
||
|
All of these people wouldn't lie to us about the potential for worst case scenario.
|
||
|
|
||
|
01:49:13.000 --> 01:49:20.000
|
||
|
Nobody would ever go and lie about the possibility that a billion people could die from a spilled
|
||
|
|
||
|
01:49:20.000 --> 01:49:22.000
|
||
|
RNA.
|
||
|
|
||
|
01:49:22.000 --> 01:49:29.000
|
||
|
Nobody would ever go on and that knew anything about biology that a PhD in biology would
|
||
|
|
||
|
01:49:29.000 --> 01:49:36.000
|
||
|
go on on the internet and say that a billion people could get killed because RNA virus got
|
||
|
|
||
|
01:49:36.000 --> 01:49:37.000
|
||
|
out.
|
||
|
|
||
|
01:49:37.000 --> 01:49:42.000
|
||
|
No one would do that.
|
||
|
|
||
|
01:49:42.000 --> 01:49:45.000
|
||
|
Or fish and probably the smart thing to do.
|
||
|
|
||
|
01:49:45.000 --> 01:49:46.000
|
||
|
And there's the papers open access.
|
||
|
|
||
|
01:49:46.000 --> 01:49:50.000
|
||
|
And if you look at figure one, there's actually a really good, almost graphical abstract of
|
||
|
|
||
|
01:49:50.000 --> 01:49:53.000
|
||
|
what they're doing in the beginning of that figure.
|
||
|
|
||
|
01:49:53.000 --> 01:49:59.000
|
||
|
So the basic way these experiments go, they will edit the RNA and then they convert the
|
||
|
|
||
|
01:49:59.000 --> 01:50:02.000
|
||
|
products to DNA and sequence them to deep sequencing on them so they can see all the products
|
||
|
|
||
|
01:50:02.000 --> 01:50:03.000
|
||
|
that have been made.
|
||
|
|
||
|
01:50:03.000 --> 01:50:08.000
|
||
|
And they say we can make DNA splints that will capture different kinds of editing outcomes.
|
||
|
|
||
|
01:50:08.000 --> 01:50:12.000
|
||
|
So you could say if you want only 12 bases deleted, you could design your DNA splint to
|
||
|
|
||
|
01:50:12.000 --> 01:50:14.000
|
||
|
select for that or six bases or whatever.
|
||
|
|
||
|
01:50:14.000 --> 01:50:15.000
|
||
|
So you could pick it.
|
||
|
|
||
|
01:50:15.000 --> 01:50:16.000
|
||
|
All right.
|
||
|
|
||
|
01:50:16.000 --> 01:50:17.000
|
||
|
So how do they actually show this is working?
|
||
|
|
||
|
01:50:17.000 --> 01:50:22.000
|
||
|
They picked Sinbus virus, which is a plus-stranded RNA virus, 12.5 KB single strand RNA genome.
|
||
|
|
||
|
01:50:22.000 --> 01:50:27.000
|
||
|
And it's got a green fluorescent protein gene inserted near the three prime end.
|
||
|
|
||
|
01:50:27.000 --> 01:50:29.000
|
||
|
So in fact, the cells are going to be green.
|
||
|
|
||
|
01:50:29.000 --> 01:50:30.000
|
||
|
So they designed a guide RNA.
|
||
|
|
||
|
01:50:30.000 --> 01:50:37.000
|
||
|
Remember, they're going to make an RNA, which will hybridize to a part of the GFP RNA.
|
||
|
|
||
|
01:50:37.000 --> 01:50:42.000
|
||
|
And it's going to encode an amino acid that will disrupt the fluorescence.
|
||
|
|
||
|
01:50:42.000 --> 01:50:44.000
|
||
|
So they're going to wreck the light bulb.
|
||
|
|
||
|
01:50:44.000 --> 01:50:45.000
|
||
|
They're going to wreck the light bulb.
|
||
|
|
||
|
01:50:45.000 --> 01:50:46.000
|
||
|
They're going to change one amino acid, right?
|
||
|
|
||
|
01:50:46.000 --> 01:50:47.000
|
||
|
And there's no longer going to be green.
|
||
|
|
||
|
01:50:47.000 --> 01:50:48.000
|
||
|
It's going to be dark.
|
||
|
|
||
|
01:50:49.000 --> 01:50:50.000
|
||
|
All right.
|
||
|
|
||
|
01:50:50.000 --> 01:50:54.000
|
||
|
So they show that this guide RNA works on GFP RNA by itself.
|
||
|
|
||
|
01:50:54.000 --> 01:50:57.000
|
||
|
So they can get six or 12 bases excised.
|
||
|
|
||
|
01:50:57.000 --> 01:51:00.000
|
||
|
And then they take infectious viral RNA that they've extracted from cells.
|
||
|
|
||
|
01:51:00.000 --> 01:51:06.000
|
||
|
They incubate it with their nucleates, their CRISPR proteins and the RNA treated with T4,
|
||
|
|
||
|
01:51:06.000 --> 01:51:08.000
|
||
|
poly nucleotide kinase to put phosphate at the five prime end.
|
||
|
|
||
|
01:51:08.000 --> 01:51:11.000
|
||
|
And then they put their DNA splint in and put it in T4 RNA ligase.
|
||
|
|
||
|
01:51:11.000 --> 01:51:17.000
|
||
|
I don't even know if there's viral replication here, just the production of GFP protein.
|
||
|
|
||
|
01:51:18.000 --> 01:51:24.000
|
||
|
Because see, they're saying it is producing GFP-labeled virus here.
|
||
|
|
||
|
01:51:24.000 --> 01:51:26.000
|
||
|
Can you see my arrow?
|
||
|
|
||
|
01:51:26.000 --> 01:51:35.000
|
||
|
But there's no way that they can tell the difference between GFP-labeled virus and the production of GFP, the protein.
|
||
|
|
||
|
01:51:35.000 --> 01:51:40.000
|
||
|
If you look up glee-green fluorescent protein, which is derived from a jellyfish protein,
|
||
|
|
||
|
01:51:40.000 --> 01:51:43.000
|
||
|
you will find that it's not a small protein.
|
||
|
|
||
|
01:51:43.000 --> 01:51:45.000
|
||
|
It's huge.
|
||
|
|
||
|
01:51:47.000 --> 01:51:54.000
|
||
|
Cells that produce GFP forever tend to die because they get overloaded with this huge protein.
|
||
|
|
||
|
01:51:56.000 --> 01:52:02.000
|
||
|
So it's really interesting that again, it's almost like magic tricks are possible here.
|
||
|
|
||
|
01:52:02.000 --> 01:52:12.000
|
||
|
Because if you convince people in a laboratory that that green signal that you get when you shine the blue light on the cell culture
|
||
|
|
||
|
01:52:12.000 --> 01:52:22.000
|
||
|
is evidence of viral replication as opposed to the production of a protein that glows green,
|
||
|
|
||
|
01:52:22.000 --> 01:52:25.000
|
||
|
well, that's a pretty magic spell you're casting there.
|
||
|
|
||
|
01:52:25.000 --> 01:52:34.000
|
||
|
Because there is no evidence in this figure that viruses are being made except this cartoon right here in the right corner.
|
||
|
|
||
|
01:52:34.000 --> 01:52:37.000
|
||
|
There's no evidence at all.
|
||
|
|
||
|
01:52:37.000 --> 01:52:44.000
|
||
|
The only evidence that they have is that in this unedited version, the green protein gets produced and in the edited version,
|
||
|
|
||
|
01:52:44.000 --> 01:52:53.000
|
||
|
it doesn't get produced, which would be expected if you transfected a cell culture with RNA that was edited or not edited.
|
||
|
|
||
|
01:52:53.000 --> 01:52:55.000
|
||
|
That's incredible.
|
||
|
|
||
|
01:52:55.000 --> 01:52:57.000
|
||
|
Wow.
|
||
|
|
||
|
01:52:58.000 --> 01:53:02.000
|
||
|
So they're going to cut it specifically and ligate it together.
|
||
|
|
||
|
01:53:02.000 --> 01:53:08.000
|
||
|
And then they transfect this bulk edited RNA into cells and it's viral RNA now.
|
||
|
|
||
|
01:53:08.000 --> 01:53:12.000
|
||
|
So it's going to infect the cells and it's going to produce GFP and they see a reduction in GFP.
|
||
|
|
||
|
01:53:12.000 --> 01:53:14.000
|
||
|
See there he said it's viral RNA now.
|
||
|
|
||
|
01:53:14.000 --> 01:53:17.000
|
||
|
They transfect this RNA into cells.
|
||
|
|
||
|
01:53:17.000 --> 01:53:19.000
|
||
|
It's viral RNA now.
|
||
|
|
||
|
01:53:19.000 --> 01:53:21.000
|
||
|
The hell is he talking about?
|
||
|
|
||
|
01:53:21.000 --> 01:53:23.000
|
||
|
That was a total bait and switch.
|
||
|
|
||
|
01:53:23.000 --> 01:53:25.000
|
||
|
That was a total shell game there.
|
||
|
|
||
|
01:53:26.000 --> 01:53:28.000
|
||
|
There's no viruses in this.
|
||
|
|
||
|
01:53:28.000 --> 01:53:31.000
|
||
|
Just because they call it a sin V.
|
||
|
|
||
|
01:53:31.000 --> 01:53:33.000
|
||
|
It's an RNA.
|
||
|
|
||
|
01:53:33.000 --> 01:53:35.000
|
||
|
Listen.
|
||
|
|
||
|
01:53:35.000 --> 01:53:41.000
|
||
|
And then they transfect this bulk edited RNA into cells and it's viral RNA now.
|
||
|
|
||
|
01:53:41.000 --> 01:53:46.000
|
||
|
So it's going to infect the cells and it's going to produce GFP and they see a reduction in GFP when they've done the editing,
|
||
|
|
||
|
01:53:46.000 --> 01:53:48.000
|
||
|
consistent with breaking the light bulb.
|
||
|
|
||
|
01:53:48.000 --> 01:53:51.000
|
||
|
So viral means that it can be expressed or what?
|
||
|
|
||
|
01:53:51.000 --> 01:53:53.000
|
||
|
There's no RNA dependent polymerase.
|
||
|
|
||
|
01:53:53.000 --> 01:53:54.000
|
||
|
There's no making of viruses.
|
||
|
|
||
|
01:53:54.000 --> 01:53:58.000
|
||
|
There's just the GFP.
|
||
|
|
||
|
01:53:58.000 --> 01:54:02.000
|
||
|
And whatever viral genome was there, what are we talking about?
|
||
|
|
||
|
01:54:02.000 --> 01:54:06.000
|
||
|
Did we look for viruses being produced?
|
||
|
|
||
|
01:54:06.000 --> 01:54:09.000
|
||
|
Did you see any viruses produced in that figure?
|
||
|
|
||
|
01:54:09.000 --> 01:54:10.000
|
||
|
Holy crap.
|
||
|
|
||
|
01:54:10.000 --> 01:54:11.000
|
||
|
This is amazing.
|
||
|
|
||
|
01:54:11.000 --> 01:54:13.000
|
||
|
So as Alan said, everybody got that?
|
||
|
|
||
|
01:54:13.000 --> 01:54:14.000
|
||
|
Basically they can edit.
|
||
|
|
||
|
01:54:14.000 --> 01:54:19.000
|
||
|
They can edit the RNA and change amino acid by this approach, which is pretty cool, which you can do last week.
|
||
|
|
||
|
01:54:19.000 --> 01:54:20.000
|
||
|
Yes.
|
||
|
|
||
|
01:54:20.000 --> 01:54:21.000
|
||
|
Well, actually they published this.
|
||
|
|
||
|
01:54:21.000 --> 01:54:23.000
|
||
|
Well, no, I guess that was still this week.
|
||
|
|
||
|
01:54:23.000 --> 01:54:24.000
|
||
|
So you're right.
|
||
|
|
||
|
01:54:24.000 --> 01:54:25.000
|
||
|
They could do this for the past.
|
||
|
|
||
|
01:54:25.000 --> 01:54:27.000
|
||
|
I don't know how long they've been working on it, right?
|
||
|
|
||
|
01:54:27.000 --> 01:54:28.000
|
||
|
It's pretty cool.
|
||
|
|
||
|
01:54:28.000 --> 01:54:29.000
|
||
|
Okay.
|
||
|
|
||
|
01:54:29.000 --> 01:54:30.000
|
||
|
So then they say, what about deletions?
|
||
|
|
||
|
01:54:30.000 --> 01:54:31.000
|
||
|
Can we make deletions?
|
||
|
|
||
|
01:54:31.000 --> 01:54:33.000
|
||
|
Because here they've changed the single amino acid.
|
||
|
|
||
|
01:54:33.000 --> 01:54:39.000
|
||
|
Again, they've done it by putting an RNA in there with the DNA splint so that it gets ligated in.
|
||
|
|
||
|
01:54:39.000 --> 01:54:42.000
|
||
|
So now they do this.
|
||
|
|
||
|
01:54:42.000 --> 01:54:49.000
|
||
|
They again take viral genomes and do their CRISPR and do the deletions and they then extract RNA from infected cells and they sequence them.
|
||
|
|
||
|
01:54:49.000 --> 01:54:54.000
|
||
|
And they have a DNA splint designed to make a 12 nucleotide deletion.
|
||
|
|
||
|
01:54:54.000 --> 01:54:55.000
|
||
|
And they do see that.
|
||
|
|
||
|
01:54:55.000 --> 01:55:01.000
|
||
|
34% of the RNA genomes have that deletion, but they also see 18 base deletions, 24 or 30 and 6, interestingly.
|
||
|
|
||
|
01:55:01.000 --> 01:55:02.000
|
||
|
So it's not perfect.
|
||
|
|
||
|
01:55:02.000 --> 01:55:06.000
|
||
|
These DNA splints are allowing a little bit of flexibility.
|
||
|
|
||
|
01:55:06.000 --> 01:55:16.000
|
||
|
Then they pick plaques, dear to our heart, and they get RNA from 11 wells that had CPE that virus is reproducing, but they're negative for GFPs, so they've been edited.
|
||
|
|
||
|
01:55:17.000 --> 01:55:20.000
|
||
|
For the genomes to have a 12 nucleotide deletion, which is what they selected.
|
||
|
|
||
|
01:55:20.000 --> 01:55:21.000
|
||
|
Okay, so there we heard something.
|
||
|
|
||
|
01:55:21.000 --> 01:55:31.000
|
||
|
So the way they do this is they select for viruses that show CPE, cytopathic effects, but aren't green.
|
||
|
|
||
|
01:55:31.000 --> 01:55:34.000
|
||
|
So they would have been edited because then the green is broken.
|
||
|
|
||
|
01:55:34.000 --> 01:55:41.000
|
||
|
The protein of GFP is broken, so it doesn't, it's got a deletion so that it doesn't fluoresce anymore.
|
||
|
|
||
|
01:55:42.000 --> 01:55:50.000
|
||
|
And so that's interesting because when they do that, then they find groups of viruses that seem to have multiples of that delete deletion.
|
||
|
|
||
|
01:55:50.000 --> 01:55:53.000
|
||
|
So again, it's editing the genome.
|
||
|
|
||
|
01:55:53.000 --> 01:55:57.000
|
||
|
It's not surprising that they can apply these tools to RNA.
|
||
|
|
||
|
01:55:57.000 --> 01:56:05.000
|
||
|
And it's not surprising how they do it, which is used starting with a pure stock of cloned RNA.
|
||
|
|
||
|
01:56:06.000 --> 01:56:15.000
|
||
|
If you start with a pure stock of cloned RNA, you're starting where every other infectious RNA article has ever started with an infectious clone.
|
||
|
|
||
|
01:56:15.000 --> 01:56:25.000
|
||
|
And only sufficient quantities of an infectious clone can explain what happened if what happened needs a better explanation than lying.
|
||
|
|
||
|
01:56:25.000 --> 01:56:28.000
|
||
|
And that's a huge if still.
|
||
|
|
||
|
01:56:28.000 --> 01:56:33.000
|
||
|
The reason why I believe it's still a huge if is because of how many people
|
||
|
|
||
|
01:56:33.000 --> 01:56:55.000
|
||
|
were parading around their credentials at the beginning of the pandemic that weren't necessarily related to epidemiology or epidemics or infectious disease in any way, but were convinced that this was a worst case scenario likely a bio weapon yada yada yada.
|
||
|
|
||
|
01:56:56.000 --> 01:57:03.000
|
||
|
That's the reason why I still think the window for is being one great big giant lie should be left open.
|
||
|
|
||
|
01:57:03.000 --> 01:57:12.000
|
||
|
If it was just a bunch of people scrambling to figure out what was going on and in earnest working together to solve this problem.
|
||
|
|
||
|
01:57:12.000 --> 01:57:19.000
|
||
|
And I saw no evidence of liars, cheaters, grifters, stealers, backstabbers.
|
||
|
|
||
|
01:57:19.000 --> 01:57:28.000
|
||
|
Then I would say that, wow, you might be dealing with some real biology here. There might be a real problem. They might have really put clones everywhere.
|
||
|
|
||
|
01:57:28.000 --> 01:57:45.000
|
||
|
But when I realized the extent to which the depth and the breadth of these actors and the extent to which they're willing to go in this campaign against other people as opposed to just fighting the truth.
|
||
|
|
||
|
01:57:45.000 --> 01:57:54.000
|
||
|
I realized that the only explanation for that many people to be around is that there is a lie to protect.
|
||
|
|
||
|
01:57:54.000 --> 01:57:59.000
|
||
|
There's no lie to protect. Then there's no reason to behave the way that these people behave.
|
||
|
|
||
|
01:57:59.000 --> 01:58:14.000
|
||
|
There's no reason for my chat to be filled the way it is except for there is a lie to be protected and we are very close if not having already uncovered it.
|
||
|
|
||
|
01:58:14.000 --> 01:58:17.000
|
||
|
Welcome to the real world.
|
||
|
|
||
|
01:58:17.000 --> 01:58:20.000
|
||
|
And the rest have a mixture of 1218 and 24 base deletion.
|
||
|
|
||
|
01:58:20.000 --> 01:58:27.000
|
||
|
So you have to look, you have to search for the virus that you want. If you want a 12 base deletion, it can assume that they all have 12 base deletions by this technique.
|
||
|
|
||
|
01:58:27.000 --> 01:58:31.000
|
||
|
And maybe it'll get better. I don't know, but it's got a little bit of flexibility.
|
||
|
|
||
|
01:58:31.000 --> 01:58:36.000
|
||
|
Yeah, I sort of, I think it's interesting that most of the numbers they're using here are divisible by three, so they aren't giving the frame shifts.
|
||
|
|
||
|
01:58:36.000 --> 01:58:43.000
|
||
|
And I wonder what would happen if you were trying, if they use something that was five, would they get a frame shift basically every time, whether it was five or 10, and that might be a little more complete.
|
||
|
|
||
|
01:58:43.000 --> 01:58:52.000
|
||
|
You mean if they designed a DNA splint to do that? Yeah, to give them a five or 10 deletion, even if you got half, it would still be a 10, you get five, and you're still making a frame shift that way.
|
||
|
|
||
|
01:58:52.000 --> 01:59:01.000
|
||
|
Okay, so the last experiment they do, can we insert a sequence into the genome? So far, we've changed the single amino acid, right? But that's not the only thing we'd like to be able to do.
|
||
|
|
||
|
01:59:01.000 --> 01:59:03.000
|
||
|
We'd like to delete what you can do with this.
|
||
|
|
||
|
01:59:03.000 --> 01:59:06.000
|
||
|
So you could take polyvirus and delete it an entire gene.
|
||
|
|
||
|
01:59:06.000 --> 01:59:12.000
|
||
|
Of course, it wouldn't be infectious, but you could do that in theory. But what if you wanted to put a different gene in? We do that a lot with infectious DNAs, right?
|
||
|
|
||
|
01:59:12.000 --> 01:59:21.000
|
||
|
So they take a cymbis virus with blue fluorescent protein in it, and you can make it into a green fluorescent.
|
||
|
|
||
|
01:59:21.000 --> 01:59:29.000
|
||
|
And so here again, you're starting with what? You're starting with a recombinant cymbis BFP virus.
|
||
|
|
||
|
01:59:29.000 --> 01:59:40.000
|
||
|
Recombinant means that it is a clone that was started in DNA, grown in bacteria, converted to RNA, and then sent out as a product.
|
||
|
|
||
|
01:59:40.000 --> 01:59:45.000
|
||
|
Or it means that they did the same thing in their lab.
|
||
|
|
||
|
01:59:45.000 --> 01:59:50.000
|
||
|
That's what it means. That's what it means. That's what it means. You have to see it. It's just a clone.
|
||
|
|
||
|
01:59:50.000 --> 02:00:04.000
|
||
|
They started with an infectious clone of this RNA, and then they used a CRISPR protein or enzyme combination to change it and lo and behold, it works. Big deal.
|
||
|
|
||
|
02:00:04.000 --> 02:00:19.000
|
||
|
What it does is it disguises in plain sight the fact that they don't have RNA viruses that behave like they told you on TV that just replicate and grow.
|
||
|
|
||
|
02:00:19.000 --> 02:00:23.000
|
||
|
They don't have those.
|
||
|
|
||
|
02:00:23.000 --> 02:00:31.000
|
||
|
Please understand what we're dealing with here. We've got to break free, and these people are not going to help us break free.
|
||
|
|
||
|
02:00:31.000 --> 02:00:36.000
|
||
|
They're actually keeping everybody trapped. They're keeping themselves trapped, it seems.
|
||
|
|
||
|
02:00:36.000 --> 02:00:50.000
|
||
|
It's hard for me to put these people in a bad place except for maybe this one, because it would be very easy from my own experience as a neurobiologist.
|
||
|
|
||
|
02:00:50.000 --> 02:01:03.000
|
||
|
It would be very easy from the pressure of what it takes to get to the place where this young woman is, this young woman is.
|
||
|
|
||
|
02:01:03.000 --> 02:01:08.000
|
||
|
It takes a lot of accepting what you're told.
|
||
|
|
||
|
02:01:08.000 --> 02:01:21.000
|
||
|
It's a lot of time when you've got to decide what to read, and it takes a very long time to get to the stage where you know enough and have read enough to start to be critical.
|
||
|
|
||
|
02:01:21.000 --> 02:01:44.000
|
||
|
And with regard to the immune system because of the absolute overwhelming lack of proper investigation because of the overwhelming funding thrown at these bad models of immunology, antibodies, and serial prevalence, and injectable vaccines,
|
||
|
|
||
|
02:01:45.000 --> 02:02:02.000
|
||
|
that we have come to a state where our understanding of the immune system is such that this might be the state of the art for a lot of people because there is no literature that you can dive into that will admit that they don't understand.
|
||
|
|
||
|
02:02:02.000 --> 02:02:07.000
|
||
|
They just work under the premises that they're working under like that paper we listened to in the beginning.
|
||
|
|
||
|
02:02:07.000 --> 02:02:10.000
|
||
|
This one.
|
||
|
|
||
|
02:02:10.000 --> 02:02:13.000
|
||
|
I'm going to wrap this up.
|
||
|
|
||
|
02:02:13.000 --> 02:02:15.000
|
||
|
Oops.
|
||
|
|
||
|
02:02:15.000 --> 02:02:18.000
|
||
|
This paper.
|
||
|
|
||
|
02:02:18.000 --> 02:02:26.000
|
||
|
Where really what they looked at was they look at neutralizing antibodies and they look for a few other things that they don't really see.
|
||
|
|
||
|
02:02:26.000 --> 02:02:29.000
|
||
|
They hear its peptide array mapping of linear epitopes.
|
||
|
|
||
|
02:02:29.000 --> 02:02:44.000
|
||
|
But the linear epitopes are exactly what don't matter because the quaternary epitopes, the epitopes that are aimed at the three dimensional structure that doesn't necessarily relate to the linear sequence of the protein are where the rubber hits the road.
|
||
|
|
||
|
02:02:44.000 --> 02:02:55.000
|
||
|
And this paper unintentionally revealed that and left the door open wide for a million other explanations for why these animals survived.
|
||
|
|
||
|
02:02:55.000 --> 02:03:08.000
|
||
|
That because of the nature of the immune mythology, we don't even consider because there were antibodies in figure one and the antibody and the animals in figure six survived.
|
||
|
|
||
|
02:03:08.000 --> 02:03:16.000
|
||
|
And so the animals that got sick in this figure must have died because they didn't have antibodies right.
|
||
|
|
||
|
02:03:16.000 --> 02:03:22.000
|
||
|
And when when you're going up into the field and everybody in the room agrees.
|
||
|
|
||
|
02:03:22.000 --> 02:03:29.000
|
||
|
All the old people in the back room are answering asking questions related to this and it all seems like everybody agrees.
|
||
|
|
||
|
02:03:29.000 --> 02:03:34.000
|
||
|
The illusion of consensus is strong.
|
||
|
|
||
|
02:03:34.000 --> 02:03:38.000
|
||
|
And why do you think they have five people on here for a journal club?
|
||
|
|
||
|
02:03:38.000 --> 02:03:49.000
|
||
|
It's for the illusion of consensus. There's almost no way that without us being together here and having worked as long as we have together.
|
||
|
|
||
|
02:03:49.000 --> 02:03:56.000
|
||
|
Would we have the confidence to question these five authorities on this immunology?
|
||
|
|
||
|
02:03:56.000 --> 02:04:04.000
|
||
|
But at some moment you see that even consensus doesn't make dumb smart.
|
||
|
|
||
|
02:04:04.000 --> 02:04:16.000
|
||
|
And the idea that we can distill immunology down to the presence of neutralizing antibodies or quaternary antibodies, there might be other stuff too, is ridiculous.
|
||
|
|
||
|
02:04:16.000 --> 02:04:27.000
|
||
|
But they're still doing it. Three years in. No more nuance, no more details, no more nothing.
|
||
|
|
||
|
02:04:27.000 --> 02:04:39.000
|
||
|
And I thought it was important to point out because it's really when we take things for granted, you know, and then we don't see them for what they are.
|
||
|
|
||
|
02:04:39.000 --> 02:04:46.000
|
||
|
We don't, you know, people say, well, this is nature communications. I mean, look at this set up they've got here.
|
||
|
|
||
|
02:04:46.000 --> 02:04:56.000
|
||
|
They're immunizing and then they're challenging the animals and the animals die and they have these, you know, fancy figures that make it really hard.
|
||
|
|
||
|
02:04:56.000 --> 02:05:01.000
|
||
|
You know, what's the absorbance mean here?
|
||
|
|
||
|
02:05:01.000 --> 02:05:08.000
|
||
|
I mean, how do we, how do we explain the serial dilution and what this, what these graphs mean to people at home?
|
||
|
|
||
|
02:05:08.000 --> 02:05:11.000
|
||
|
They didn't even bother.
|
||
|
|
||
|
02:05:11.000 --> 02:05:22.000
|
||
|
What about this one, the mapping of linear epitopes? Why didn't they explain then that this whole thing, that we do all the time that we've been doing for decades?
|
||
|
|
||
|
02:05:22.000 --> 02:05:26.000
|
||
|
Well, let's look at the epitopes based on the linear sequence.
|
||
|
|
||
|
02:05:26.000 --> 02:05:33.000
|
||
|
The little fragments of the linear sequence never realizing that we were probably looking at bunk.
|
||
|
|
||
|
02:05:33.000 --> 02:05:44.000
|
||
|
And then if we were going to do this scan, we would need some way of identifying all the possible three-dimensional nonlinear
|
||
|
|
||
|
02:05:44.000 --> 02:05:54.000
|
||
|
quaternary epitopes that are possible to functionally attack a spike protein or identify it to the immune system appropriately.
|
||
|
|
||
|
02:05:54.000 --> 02:06:01.000
|
||
|
Can anyone else see how this very quickly combinatorially expands into infinity?
|
||
|
|
||
|
02:06:01.000 --> 02:06:08.000
|
||
|
And so the reason why I have this backdrop right now is because this is Google Fold or Alpha Fold.
|
||
|
|
||
|
02:06:08.000 --> 02:06:16.000
|
||
|
And it's supposed to be the video that announces that they figured out how proteins fold.
|
||
|
|
||
|
02:06:16.000 --> 02:06:20.000
|
||
|
Or why would that be important? They certainly haven't figured it out yet.
|
||
|
|
||
|
02:06:20.000 --> 02:06:27.000
|
||
|
But they would like you to believe that they understand how proteins fold so that they can start to address questions like this.
|
||
|
|
||
|
02:06:27.000 --> 02:06:37.000
|
||
|
Where the linear epitopes don't actually mean anything, but before Google Fold or Alpha Fold, there was no chance for us to figure it out.
|
||
|
|
||
|
02:06:37.000 --> 02:06:46.000
|
||
|
But now that Google's cracked it, we're going to make real vaccines this time.
|
||
|
|
||
|
02:06:46.000 --> 02:06:50.000
|
||
|
And so they went through all of this stuff showing there's no difference between animals.
|
||
|
|
||
|
02:06:50.000 --> 02:07:02.000
|
||
|
There's nothing that they have to find that expresses or adequately explains why the animals survive.
|
||
|
|
||
|
02:07:02.000 --> 02:07:10.000
|
||
|
It's a pity. Then we went to CRISPR-based engineering of RNA viruses and we talked about making the PR RNA.
|
||
|
|
||
|
02:07:10.000 --> 02:07:24.000
|
||
|
And Vincent Rancin-Yello claimed the title that I've been trying to give him, which is really the guy that invented it with David Baltimore.
|
||
|
|
||
|
02:07:24.000 --> 02:07:34.000
|
||
|
If you've ever seen an interview with David Baltimore, you know that he's not a particularly hospitable man when it comes to questions about viruses anyway.
|
||
|
|
||
|
02:07:34.000 --> 02:07:39.000
|
||
|
So then we talked about RNA and changing RNA, but we're starting with a pure aversion.
|
||
|
|
||
|
02:07:39.000 --> 02:07:45.000
|
||
|
And so that's, again, here it is, pictures of virus. Look at these pictures of virus.
|
||
|
|
||
|
02:07:45.000 --> 02:07:47.000
|
||
|
That must mean there's really virus in here.
|
||
|
|
||
|
02:07:47.000 --> 02:07:53.000
|
||
|
It can't just be green for less than protein being excluded as exosomes.
|
||
|
|
||
|
02:07:53.000 --> 02:07:58.000
|
||
|
It can't just be over expression of green protein leading to psychopathic effects.
|
||
|
|
||
|
02:07:58.000 --> 02:08:12.000
|
||
|
No, that couldn't be. And indeed, it doesn't seem to be the case because they have some psychopathic effects with unedited or sorry, edited virus that doesn't appear to turn green.
|
||
|
|
||
|
02:08:12.000 --> 02:08:23.000
|
||
|
So all that means is what? It means that that RNA is also toxic. That RNA is also able to cause psychopathic effects. It's not that surprising.
|
||
|
|
||
|
02:08:23.000 --> 02:08:33.000
|
||
|
You're putting pure RNA onto a cell culture, whether or not it makes green fluorescent protein doesn't really necessarily matter. It's not surprising.
|
||
|
|
||
|
02:08:34.000 --> 02:08:47.000
|
||
|
And so this paper is about editing RNA, but it actually reveals the weaknesses of this virology, especially coronavirus biology and how it's done.
|
||
|
|
||
|
02:08:47.000 --> 02:08:56.000
|
||
|
And how much effort is necessary to gloss over the immunology that they're talking about so that you don't make this connection in your head.
|
||
|
|
||
|
02:08:56.000 --> 02:09:05.000
|
||
|
That you don't actually hear what they're saying is perfectly confirming more or less what we've been talking about for the last year.
|
||
|
|
||
|
02:09:05.000 --> 02:09:10.000
|
||
|
That RNA viruses are very easy to work out in the laboratory.
|
||
|
|
||
|
02:09:10.000 --> 02:09:19.000
|
||
|
And until we realize we could make DNA copies of them to generate RNA clones, it was virtually impossible to work on them.
|
||
|
|
||
|
02:09:19.000 --> 02:09:31.000
|
||
|
And now that we have these CRISPR editing things, we can even start to more aggressively manipulate them, but it's a misnomer. It's an illusion.
|
||
|
|
||
|
02:09:31.000 --> 02:09:36.000
|
||
|
Why is it an illusion? Because we can print the DNA.
|
||
|
|
||
|
02:09:36.000 --> 02:09:44.000
|
||
|
Because we can make synthetic DNA. However we want to. We don't need this. We don't need this.
|
||
|
|
||
|
02:09:44.000 --> 02:09:53.000
|
||
|
It's like, oh, it's real cool. We don't need this for viruses. We can just make the RNA from scratch. Right Vincent?
|
||
|
|
||
|
02:09:53.000 --> 02:09:59.000
|
||
|
So isn't it weird then? Why are they talking about this like it's a big deal?
|
||
|
|
||
|
02:09:59.000 --> 02:10:10.000
|
||
|
If we can make viruses from scratch by just typing on a keyboard and then hitting synthesize.
|
||
|
|
||
|
02:10:10.000 --> 02:10:21.000
|
||
|
Because that's for sure. And if we can't do it quite with the fidelity we need now, it's going to be there in four years or five years because that's the technology that's improving.
|
||
|
|
||
|
02:10:21.000 --> 02:10:26.000
|
||
|
That's what Vincent Ransom Yellow makes the argument about how we're going to improve the RNA.
|
||
|
|
||
|
02:10:26.000 --> 02:10:36.000
|
||
|
Technology is to make synthetic RNA, manufacture it using printing kind of printing techniques rather than so you get perfect purity.
|
||
|
|
||
|
02:10:36.000 --> 02:10:46.000
|
||
|
They've already talked about that. That's how they're going to do the specialized medicine stuff.
|
||
|
|
||
|
02:10:46.000 --> 02:10:59.000
|
||
|
So anyway, they told us about a dangerous virus and then they had a bunch of people come around and tell us stories about where this virus came from and what it means for our future pandemic potential.
|
||
|
|
||
|
02:11:00.000 --> 02:11:13.000
|
||
|
I mean, this is Robert Malone on a podcast with the original with the original press secretary of Donald Trump. I mean, are you kidding? I mean, are you joking?
|
||
|
|
||
|
02:11:13.000 --> 02:11:16.000
|
||
|
Standing up your knees buckle.
|
||
|
|
||
|
02:11:16.000 --> 02:11:24.000
|
||
|
And I've been trying to make this a point that consensus is like track laughter.
|
||
|
|
||
|
02:11:25.000 --> 02:11:32.000
|
||
|
There's a soup stand. He's always raving. I finally got a chance to go there the other day and I tell you this.
|
||
|
|
||
|
02:11:32.000 --> 02:11:47.000
|
||
|
Seinfeld isn't funny without the track laughter. At least it's not nearly as funny as it would be as with the track laughter because this sense of consensus that other people think this is funny too is missing.
|
||
|
|
||
|
02:11:47.000 --> 02:11:59.000
|
||
|
And the Vincent Rancin yellow was to talk to you about viruses. The consensus would be missing, but when five people go, yeah, that's right. That makes sense. Oh, yeah, that's right. That's right, Glenn. Yep.
|
||
|
|
||
|
02:11:59.000 --> 02:12:04.000
|
||
|
The consensus bamboozles.
|
||
|
|
||
|
02:12:04.000 --> 02:12:12.000
|
||
|
And even when there's little incongruities or when it seems like it's not quite right, the consensus bamboozles.
|
||
|
|
||
|
02:12:12.000 --> 02:12:14.000
|
||
|
Listen when the consensus is removed.
|
||
|
|
||
|
02:12:14.000 --> 02:12:16.000
|
||
|
You will be stunned.
|
||
|
|
||
|
02:12:16.000 --> 02:12:17.000
|
||
|
Stunned by soup?
|
||
|
|
||
|
02:12:17.000 --> 02:12:22.000
|
||
|
You can't eat this soup standing up your knees buckle.
|
||
|
|
||
|
02:12:22.000 --> 02:12:29.000
|
||
|
There's only one caveat. The guy who runs a place with a little temperamental, especially about the ordering procedure.
|
||
|
|
||
|
02:12:29.000 --> 02:12:33.000
|
||
|
He secretly referred to as the soup Nazi.
|
||
|
|
||
|
02:12:33.000 --> 02:12:35.000
|
||
|
What happens if you don't order right?
|
||
|
|
||
|
02:12:35.000 --> 02:12:37.000
|
||
|
He yells and you don't get your soup.
|
||
|
|
||
|
02:12:37.000 --> 02:12:38.000
|
||
|
What?
|
||
|
|
||
|
02:12:38.000 --> 02:12:40.000
|
||
|
Just follow the ordering procedure and you will be fine.
|
||
|
|
||
|
02:12:41.000 --> 02:12:43.000
|
||
|
Let's go over that again.
|
||
|
|
||
|
02:12:43.000 --> 02:12:47.000
|
||
|
As you walk in the place, move immediately to your right.
|
||
|
|
||
|
02:12:47.000 --> 02:12:50.000
|
||
|
The main thing is to keep the line moving.
|
||
|
|
||
|
02:12:50.000 --> 02:12:53.000
|
||
|
Hold out your money. Speak your soup in a loud clear voice.
|
||
|
|
||
|
02:12:53.000 --> 02:12:55.000
|
||
|
Step to the left and receive the right.
|
||
|
|
||
|
02:12:55.000 --> 02:13:01.000
|
||
|
Very important. Not to embellish on your order. No extraneous comment. No question. No compliment.
|
||
|
|
||
|
02:13:01.000 --> 02:13:04.000
|
||
|
Oh, look, look, look. I'm really scared.
|
||
|
|
||
|
02:13:05.000 --> 02:13:09.000
|
||
|
Medium turkey chili.
|
||
|
|
||
|
02:13:09.000 --> 02:13:14.000
|
||
|
Medium crab bisque.
|
||
|
|
||
|
02:13:14.000 --> 02:13:23.000
|
||
|
You didn't get any bread. Just forget it. Let it go.
|
||
|
|
||
|
02:13:23.000 --> 02:13:26.000
|
||
|
Excuse me, I think we forgot my bread.
|
||
|
|
||
|
02:13:26.000 --> 02:13:28.000
|
||
|
Bread, $2 extra.
|
||
|
|
||
|
02:13:29.000 --> 02:13:31.000
|
||
|
Everyone in front of me got free bread.
|
||
|
|
||
|
02:13:31.000 --> 02:13:32.000
|
||
|
You want bread?
|
||
|
|
||
|
02:13:32.000 --> 02:13:33.000
|
||
|
Yes, please.
|
||
|
|
||
|
02:13:33.000 --> 02:13:35.000
|
||
|
$3.
|
||
|
|
||
|
02:13:35.000 --> 02:13:38.000
|
||
|
Nothing for you.
|
||
|
|
||
|
02:13:38.000 --> 02:13:45.000
|
||
|
No, it's funny, but it's not nearly as funny when there's an audience full of laughter, right?
|
||
|
|
||
|
02:13:45.000 --> 02:13:51.000
|
||
|
And the view is not nearly as convincing if there aren't four ladies all going, yeah, that's right.
|
||
|
|
||
|
02:13:51.000 --> 02:13:56.000
|
||
|
Twiv is not as convincing. Tim Poole is not as convincing.
|
||
|
|
||
|
02:13:56.000 --> 02:14:01.000
|
||
|
Even Joe Rogan is not as convincing unless he's talking to somebody else.
|
||
|
|
||
|
02:14:01.000 --> 02:14:18.000
|
||
|
That's why the PBS NewsHour is not always just talking to you, but is also talking with other people so that they can create this consensus of understanding that you feel very enticed to adopt.
|
||
|
|
||
|
02:14:18.000 --> 02:14:38.000
|
||
|
Just like when somebody tells a joke and you don't get it, you tend to laugh along because maybe you'll get it in a second or maybe somebody's going to say something that'll clue you in and then you'll get it or maybe you'll be embarrassed
|
||
|
|
||
|
02:14:38.000 --> 02:14:43.000
|
||
|
because you didn't get it so you'll laugh along.
|
||
|
|
||
|
02:14:43.000 --> 02:14:54.000
|
||
|
And that's no different than the pressure to go along with the TV when the TV says, if you don't take this shot, you're endangering, you don't even love your neighbor then.
|
||
|
|
||
|
02:14:54.000 --> 02:15:07.000
|
||
|
If you don't take this shot, you don't love your neighbor is a pretty malevolent thing to say across channels and creating a consensus.
|
||
|
|
||
|
02:15:07.000 --> 02:15:31.000
|
||
|
A consensus beyond a little talk show with three people, but a consensus across channels and a consensus across people on this device, a consensus across podcasts, a consensus among people that disagree.
|
||
|
|
||
|
02:15:31.000 --> 02:15:35.000
|
||
|
It's a magic spell, ladies and gentlemen.
|
||
|
|
||
|
02:15:35.000 --> 02:15:41.000
|
||
|
And the only way to get out of it is to learn biology.
|
||
|
|
||
|
02:15:41.000 --> 02:15:47.000
|
||
|
You can see it because the players that are playing along ignore these things.
|
||
|
|
||
|
02:15:47.000 --> 02:15:58.000
|
||
|
They don't explain the PCR and why it's so diabolical that we had 250 different products in America during 2020 and 21.
|
||
|
|
||
|
02:15:58.000 --> 02:16:15.000
|
||
|
They don't explain the masking and what it does to people and why it was so diabolical to mask children, especially the people who advocated for masks because this could be a worst case scenario that could be prevented by masks.
|
||
|
|
||
|
02:16:15.000 --> 02:16:25.000
|
||
|
They don't talk about the fact that we have new data that shows that in 2020 there was no spread in New York City. They won't talk about it.
|
||
|
|
||
|
02:16:25.000 --> 02:16:37.000
|
||
|
Because if they talk about it, they will have to admit that when they said that the New York City could be sign of a worst case scenario and a billion people could die, they might have scared people.
|
||
|
|
||
|
02:16:37.000 --> 02:16:41.000
|
||
|
They might have scared people into dividing.
|
||
|
|
||
|
02:16:41.000 --> 02:16:51.000
|
||
|
They might have scared people into ostracizing their friends. They might have scared people into believing that a transfection might be better than getting this gain a function virus.
|
||
|
|
||
|
02:16:52.000 --> 02:16:59.000
|
||
|
So they can't admit that Jessica Hockett has data. They can't admit that Denny Rancor has data.
|
||
|
|
||
|
02:16:59.000 --> 02:17:17.000
|
||
|
Because if they do, then they will start to have, you will start to see through them and you will start to realize that they were part of ceding the worst case scenario narrative which scared everyone, confused everyone and instilled doubt in everyone.
|
||
|
|
||
|
02:17:17.000 --> 02:17:21.000
|
||
|
So that the rolling out of the shot was possible.
|
||
|
|
||
|
02:17:21.000 --> 02:17:27.000
|
||
|
And so yeah, it's great that there were different doses and they confused us by having placebo lots and all this other stuff.
|
||
|
|
||
|
02:17:27.000 --> 02:17:33.000
|
||
|
But if you had spoke out on time, there would have been no shot at all.
|
||
|
|
||
|
02:17:33.000 --> 02:17:44.000
|
||
|
If you spoke out on time, there would have been no need for the shot. We would have seen through the protocols before the people in 2021 were killed.
|
||
|
|
||
|
02:17:44.000 --> 02:17:47.000
|
||
|
These people didn't speak up and they're still not speaking up now.
|
||
|
|
||
|
02:17:47.000 --> 02:17:54.000
|
||
|
And I think it's because they might not be good people. Because good people would just say, wow, I can't believe I made the mistake.
|
||
|
|
||
|
02:17:54.000 --> 02:17:56.000
|
||
|
Like I have.
|
||
|
|
||
|
02:17:56.000 --> 02:18:01.000
|
||
|
Like Mark Hewson-Tonic, Mark Koolak has said.
|
||
|
|
||
|
02:18:01.000 --> 02:18:10.000
|
||
|
Mark Koolak has videos where he's saying the same thing that everybody else did that George Webb said that some person took it to Wuhan.
|
||
|
|
||
|
02:18:11.000 --> 02:18:16.000
|
||
|
Or brought it back from Wuhan. We were all on board.
|
||
|
|
||
|
02:18:16.000 --> 02:18:19.000
|
||
|
The question is why?
|
||
|
|
||
|
02:18:19.000 --> 02:18:31.000
|
||
|
And I think that there were actors, there were people that were encouraged to get that fear of frustration, fear, uncertainty and doubt going.
|
||
|
|
||
|
02:18:32.000 --> 02:18:37.000
|
||
|
And they're making it continue by not telling this story.
|
||
|
|
||
|
02:18:37.000 --> 02:18:52.000
|
||
|
And just talking about lab leak and lab cover up and dangerous spike protein and dangerous LNP and dangerous DNA and SV 40 and variants and immune escape.
|
||
|
|
||
|
02:18:52.000 --> 02:18:57.000
|
||
|
None of which are on this list.
|
||
|
|
||
|
02:18:57.000 --> 02:19:08.000
|
||
|
And so the crime of 2020 and 2021 is going to go on unsolved because as Robert Malone said, it's 5th generation warfare and you have no chance of figuring out who did it.
|
||
|
|
||
|
02:19:08.000 --> 02:19:16.000
|
||
|
Yes, Robert Malone said that several times, most of the time while he was in Europe, Stockholm and other places, but he's always said it.
|
||
|
|
||
|
02:19:16.000 --> 02:19:22.000
|
||
|
That's what's so awful about 5th generation warfare. You can never find it.
|
||
|
|
||
|
02:19:22.000 --> 02:19:26.000
|
||
|
And so I believe that a bunch of people are committed to this lie.
|
||
|
|
||
|
02:19:26.000 --> 02:19:33.000
|
||
|
And I believe it's if there was any biology involved in the molecular signal, it had to have been an infectious clone.
|
||
|
|
||
|
02:19:33.000 --> 02:19:40.000
|
||
|
And I think Twiv and their program from this week actually lends credence to that idea.
|
||
|
|
||
|
02:19:40.000 --> 02:19:46.000
|
||
|
And I think it's much easier to lie than it is to orchestrate a biological event over three years.
|
||
|
|
||
|
02:19:46.000 --> 02:19:58.000
|
||
|
And if their goal is to invert sovereignty to permissions, then it has really nothing to do with biology except for collecting your data, which we already know is the plan.
|
||
|
|
||
|
02:19:58.000 --> 02:20:07.000
|
||
|
So they lied to you about this stuff in order to invert this permission system.
|
||
|
|
||
|
02:20:07.000 --> 02:20:22.000
|
||
|
And so, you know, laboratory, bad cave zone, no, this doesn't matter. All those, all those hypotheses are united by the idea that something wasn't here before and then showed up in 2019.
|
||
|
|
||
|
02:20:22.000 --> 02:20:27.000
|
||
|
And that's what we're tracking around the world.
|
||
|
|
||
|
02:20:27.000 --> 02:20:32.000
|
||
|
And that is impossible.
|
||
|
|
||
|
02:20:33.000 --> 02:20:44.000
|
||
|
And that's the reason why I don't believe in either of those two ideas because they all rely on a point release and worldwide spread continuously for years.
|
||
|
|
||
|
02:20:44.000 --> 02:20:49.000
|
||
|
Those are that's a false narrative. It has to be.
|
||
|
|
||
|
02:20:49.000 --> 02:20:54.000
|
||
|
And that's why I say conflated background signal because it doesn't matter if they put it there.
|
||
|
|
||
|
02:20:54.000 --> 02:21:03.000
|
||
|
If it was there, or if they put something there that they could then pretend was that other thing.
|
||
|
|
||
|
02:21:03.000 --> 02:21:05.000
|
||
|
That's what's happening here.
|
||
|
|
||
|
02:21:05.000 --> 02:21:07.000
|
||
|
I'm sure of it.
|
||
|
|
||
|
02:21:07.000 --> 02:21:11.000
|
||
|
And it doesn't matter whether it's an endemic background coronavirus.
|
||
|
|
||
|
02:21:12.000 --> 02:21:25.000
|
||
|
Protocols were murdered and transfection is not medicine. It doesn't matter if it wasn't infectious clone release because protocols were murder and transfection is not medicine. It doesn't matter if it was a transfection agent.
|
||
|
|
||
|
02:21:25.000 --> 02:21:28.000
|
||
|
Or anthrax spores.
|
||
|
|
||
|
02:21:28.000 --> 02:21:40.000
|
||
|
There was a conflated background signal that allowed the protocols to be murder and transfection is not medicine and it never will be.
|
||
|
|
||
|
02:21:41.000 --> 02:21:48.000
|
||
|
And that's why this is insufficient because it distracts you from the real molecular biology that we know they can do.
|
||
|
|
||
|
02:21:48.000 --> 02:21:54.000
|
||
|
They can definitely make pure RNA and DNA and they can definitely aerosolize that.
|
||
|
|
||
|
02:21:54.000 --> 02:21:59.000
|
||
|
And the virology or the no virus people don't want to talk about that.
|
||
|
|
||
|
02:21:59.000 --> 02:22:04.000
|
||
|
Aerosolized infectious clones distributed by the kilo kiloton.
|
||
|
|
||
|
02:22:04.000 --> 02:22:09.000
|
||
|
Even if that's what they did, these guys would say that that's a lie.
|
||
|
|
||
|
02:22:09.000 --> 02:22:13.000
|
||
|
And I'm not saying that's what they did, but that technology is all available.
|
||
|
|
||
|
02:22:13.000 --> 02:22:18.000
|
||
|
If they wanted to do it, they could do that.
|
||
|
|
||
|
02:22:18.000 --> 02:22:22.000
|
||
|
And so I just think it's best to think about it as them lying.
|
||
|
|
||
|
02:22:22.000 --> 02:22:29.000
|
||
|
And the most likely lie is that they're just conflating a background signal.
|
||
|
|
||
|
02:22:29.000 --> 02:22:35.000
|
||
|
And the idea is to inject fear, uncertainty and doubt around this background signal
|
||
|
|
||
|
02:22:35.000 --> 02:22:42.000
|
||
|
and around its interpretation as a spreading pathogen so that nobody can escape.
|
||
|
|
||
|
02:22:42.000 --> 02:22:48.000
|
||
|
And more importantly, as Robert Malone so aptly said, so that nobody knows who to blame.
|
||
|
|
||
|
02:22:48.000 --> 02:22:52.000
|
||
|
Because nobody's really acting entirely in bad faith.
|
||
|
|
||
|
02:22:52.000 --> 02:22:56.000
|
||
|
They're just omitting things. They're just ignoring things.
|
||
|
|
||
|
02:22:56.000 --> 02:23:03.000
|
||
|
They're not acknowledging things. They're confusing things.
|
||
|
|
||
|
02:23:03.000 --> 02:23:08.000
|
||
|
And in doing so, they've been able to change the way we think about how respiratory disease works
|
||
|
|
||
|
02:23:08.000 --> 02:23:14.000
|
||
|
and they've changed the way we think about how our immune system responds to that respiratory disease.
|
||
|
|
||
|
02:23:14.000 --> 02:23:19.000
|
||
|
They've changed the way we think about all cause mortality and how to talk about it,
|
||
|
|
||
|
02:23:19.000 --> 02:23:26.000
|
||
|
how we don't and attribute it to different causes, when it should have been a three-year lesson
|
||
|
|
||
|
02:23:26.000 --> 02:23:32.000
|
||
|
in all cause mortality and how to attribute it to what caused it.
|
||
|
|
||
|
02:23:32.000 --> 02:23:36.000
|
||
|
And they changed the way we think about immunization and vaccination in immunity
|
||
|
|
||
|
02:23:36.000 --> 02:23:42.000
|
||
|
because they want us to adopt this super-simplification of the immune response
|
||
|
|
||
|
02:23:42.000 --> 02:23:46.000
|
||
|
so that the nature papers like the one that they watched on Twiv
|
||
|
|
||
|
02:23:46.000 --> 02:23:52.000
|
||
|
end up seeming like, wow, everything is hunky-dory, we can use RNA to augment the immune system
|
||
|
|
||
|
02:23:52.000 --> 02:24:00.000
|
||
|
because look, guinea pigs that have antibodies don't get sick.
|
||
|
|
||
|
02:24:00.000 --> 02:24:06.000
|
||
|
And by changing the way that we think about these things, they were able to murder people.
|
||
|
|
||
|
02:24:06.000 --> 02:24:12.000
|
||
|
They were able to get doctors and nurses to effectively murder people, thinking that they were helping them
|
||
|
|
||
|
02:24:12.000 --> 02:24:15.000
|
||
|
or that they were doing what they were supposed to do.
|
||
|
|
||
|
02:24:15.000 --> 02:24:19.000
|
||
|
Because there's a novel virus, we don't know what to do.
|
||
|
|
||
|
02:24:19.000 --> 02:24:22.000
|
||
|
CDC says do this, I'm doing it.
|
||
|
|
||
|
02:24:22.000 --> 02:24:27.000
|
||
|
And doc, whatever says that if we don't do this, then we might be liable.
|
||
|
|
||
|
02:24:27.000 --> 02:24:34.000
|
||
|
But if we do what the CDC tells us, we're not any, we have no liability, so do it or you're fired.
|
||
|
|
||
|
02:24:34.000 --> 02:24:38.000
|
||
|
That's how this happened, sorry.
|
||
|
|
||
|
02:24:38.000 --> 02:24:42.000
|
||
|
It wasn't because we did this because there was an especially dangerous virus
|
||
|
|
||
|
02:24:42.000 --> 02:24:47.000
|
||
|
with an especially dangerous spike protein rolling around the earth like wildfire.
|
||
|
|
||
|
02:24:47.000 --> 02:24:51.000
|
||
|
No matter what they told us.
|
||
|
|
||
|
02:24:51.000 --> 02:24:56.000
|
||
|
That's what this slide means, I don't know why that's in there again, I apologize for that.
|
||
|
|
||
|
02:24:56.000 --> 02:25:03.000
|
||
|
We are at a time point when the population is going to plateau and inevitably decline.
|
||
|
|
||
|
02:25:04.000 --> 02:25:15.000
|
||
|
And they have this belief that artificial intelligence someday will be able to solve the mystery of our sacredness, the sacredness of life.
|
||
|
|
||
|
02:25:15.000 --> 02:25:25.000
|
||
|
How the genetic code is somehow related to the manifestation of this pattern integrity that is us.
|
||
|
|
||
|
02:25:25.000 --> 02:25:37.000
|
||
|
And they think that if they feed enough data from enough pattern integrity complete with genomes and as much medical data from their lifetime as possible,
|
||
|
|
||
|
02:25:37.000 --> 02:25:54.000
|
||
|
that eventually an artificial intelligence computer will be able to solve the mystery of how a DNA molecule is somehow translated or encodes the pattern integrity that we become as mature humans.
|
||
|
|
||
|
02:25:54.000 --> 02:26:00.000
|
||
|
The pattern integrity that forms inside of the womb of a mom.
|
||
|
|
||
|
02:26:00.000 --> 02:26:03.000
|
||
|
That's their belief.
|
||
|
|
||
|
02:26:03.000 --> 02:26:13.000
|
||
|
And in order for them to pursue this belief that we're going to become God someday by learning how to build ourselves, they need children to believe that.
|
||
|
|
||
|
02:26:13.000 --> 02:26:32.000
|
||
|
So much so that they accept that it's their duty to society to give up their data because they believe that one day that data will lead to cures and happiness and less suffering.
|
||
|
|
||
|
02:26:32.000 --> 02:26:43.000
|
||
|
It's that malevolent mythology that is the the sugar coating over the top of this poison pill.
|
||
|
|
||
|
02:26:43.000 --> 02:26:55.000
|
||
|
This poison pill that is this immunomethology that they are trapping us in that there's gain of function viruses and only vaccines will save you from them.
|
||
|
|
||
|
02:26:55.000 --> 02:27:00.000
|
||
|
It's spectacular.
|
||
|
|
||
|
02:27:00.000 --> 02:27:14.000
|
||
|
But we're on it. And we are communicating in different ways these days. I'm actually not doing as much communicating as I used to do because it's toxic in a lot of those places.
|
||
|
|
||
|
02:27:14.000 --> 02:27:18.000
|
||
|
But I am trying to get more and more on GigaOM.Bio when I have time.
|
||
|
|
||
|
02:27:18.000 --> 02:27:22.000
|
||
|
And so I would invite you to engage me there.
|
||
|
|
||
|
02:27:22.000 --> 02:27:32.000
|
||
|
But also you can find an email for me. You can find a telephone number on GigaOMbiological.com that you can leave a voicemail. Not very many people do it.
|
||
|
|
||
|
02:27:32.000 --> 02:27:35.000
|
||
|
But you can.
|
||
|
|
||
|
02:27:35.000 --> 02:27:40.000
|
||
|
And I don't know what to say other than thank you for joining me. I hope you enjoyed it. I hope it was useful.
|
||
|
|
||
|
02:27:40.000 --> 02:27:45.000
|
||
|
I'm going to be here every day because that's how we win. Steady pressure.
|
||
|
|
||
|
02:27:45.000 --> 02:27:55.000
|
||
|
We're going to work harder than them. So let's just keep working. Keep sharing the stream. If you want to support, it would be greatly appreciated.
|
||
|
|
||
|
02:27:55.000 --> 02:28:02.000
|
||
|
But it's definitely not necessary. I really would rather have you share the work more than anything else.
|
||
|
|
||
|
02:28:02.000 --> 02:28:09.000
|
||
|
But there are plans in the future to become independent. And if it's possible.
|
||
|
|
||
|
02:28:09.000 --> 02:28:21.000
|
||
|
And so that would be only you guys making that possible. So if someone wants to donate, you know, half a million dollars for me to go independent of everybody.
|
||
|
|
||
|
02:28:21.000 --> 02:28:27.000
|
||
|
And just report biology. Feel free to do so.
|
||
|
|
||
|
02:28:27.000 --> 02:28:33.000
|
||
|
Anyway, thanks very much for joining me guys. It's been really fun. I hope it was useful.
|
||
|
|
||
|
02:28:33.000 --> 02:28:40.000
|
||
|
Transfection is not immunization. Intramuscular injection is not a means of immunization. Stop all transfections in humans.
|
||
|
|
||
|
02:28:40.000 --> 02:28:45.000
|
||
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Because they're trying to eliminate the control group by any means necessary.
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