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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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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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Oh, I also forgot to change this, too, darn it.

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And all the time it was Wiggles who made that black knight come to life.

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And there was no legend.

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Positively not. Wiggles just used the story to cover up my mysterious disappearance.

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Somehow he managed to get into the armor down at the train station.

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And like on the way to the museum, he made you disappear.

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Zoints, he's alive!

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Scooby-oo!

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Good evening, ladies and gentlemen.

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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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And things are getting fun.

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We're still trying to break through this illusion.

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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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Arguing about biology that never happened, about causes that don't exist.

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And about methodologies that are unproven.

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And that's really where we are here at Gigo on Biological.

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It is a cool evening in Pittsburgh.

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A very cool brisk evening, but very, it's my kind of weather.

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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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As a tall, lanky streak of skinny man, the hot summer sun goes right through me and I love it.

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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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I kind of like that too.

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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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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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And that's unfortunate, but that is really where we are.

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I probably could make myself just a little bit bigger.

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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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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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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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That they're this kind of hyper attention shifting is actually something that is used against us.

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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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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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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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That's pretty much as drastic as it's ever been ever in the history of modern men.

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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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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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And not a biological boogie man that's almost impossible, the visualize, quantify, purify, or study in a laboratory.

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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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And lots of them probably shouldn't have been ventilated.

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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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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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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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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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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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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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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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accounted for by the biological phenomena, the mythology.

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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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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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And so we have big sharks where people had like multiple organ failure and COVID ravaged their bodies.

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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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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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And so it's really frustrating.

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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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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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And put a flag in it and claim it for giggle and biological.

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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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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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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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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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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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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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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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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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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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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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And now they've known this for very, very long time.

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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.

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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.

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And I don't think very many people are really fighting for us, but they're fighting for position in this next system.

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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.

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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.

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So let's see what we're doing here tonight.

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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.

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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.

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Might have been a lab leak. And that's why we had to close down.

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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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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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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.

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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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If we do don't do something drastic, like put everybody on a digital ID.

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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.

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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.

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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.

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And so I'm ready to pick this mantle up because I think it is a valid one.

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There may be ways of augmenting the immune system, but the formulations that have been used up until this point are really ridiculous.

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And the fact of the matter is they have not been tested.

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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.

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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.

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Because we have literally thousands and thousands of examples of this.

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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.

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Somebody sent me this blog, the second smartest guy in the world.

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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.

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That title immediately rang a bell in my head.

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That title belongs to NEPA virus vector sequences paper by Stephen Quay and Yuri Dagan.

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Stephen Quay may be a reasonably good guy. He's a businessman and a scientist.

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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.

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Adrian may be a good guy, Yuri may be a good guy, just trying to find a way to make people live longer.

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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.

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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.

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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.

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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.

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So it's, it's, it's great. Those guys are, are fantastic.

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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.

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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.

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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.

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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.

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But in this article, he's talking about a cult leader.

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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.

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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.

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Is that what he called himself in that video?

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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.

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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.

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I'm not going to play that trailer here.

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I want you to read the next paragraph.

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In 2021, I edited the Robert F Kennedy's book, the real Anthony Fauci. It was a huge undertaking.

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I was proud of my contributions, but also horrified by what that book revealed as was Jill.

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She posted a link to the book on her Facebook page, just to link mind you with a recommendation to read the book.

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In-law of ours who lives in the DC area, someone we thought of as a personal friend immediately blocked Jill permanently.

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The sin being that Jill being critical of Anthony Fauci by publicizing RFK's whoa, RFK carefully researched and footnoted book.

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This branch of our family has literally not talked to Jill or I sense.

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Literally has not talked to Jill and I sense.

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You can also just say actually or you can just say this branch of our family has not talked to Jill or I sense.

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The literally is completely incorrect there to the point where it annoys me because this is exactly how children use it all the time.

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It's awful.

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We are not invited to gatherings where they are in attendance.

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We are permanently banned from the village.

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Isn't that a Hillary Clinton takes a village to raise a child?

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For the social sin of posting a link, that was critical of Anthony Fauci.

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This is one example of cult-like behavior. I expect you are familiar with many others.

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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.

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Now, edited a book is a pretty big deal. If I edited Predator the movie, that means a certain thing.

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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?

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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.

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So then if I turned around and said, yeah, I edited that movie, it would be like, well, no, you didn't.

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You gave all the ideas or you gave some feedback on the camouflage or the shape of the mouth.

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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.

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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.

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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,

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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.

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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.

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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.

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I just, you know, I maybe I'm obsessing about him, but there's something, there's just something there.

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Oh, sorry about that.

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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.

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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.

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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.

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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.

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From Microbe TV, this is Twiv, this week in virology, episode 1045 recorded on September 15, 2023.

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I'm Vincent Drackeniello and you're listening to the podcast all about viruses.

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Joining me today from Austin, Texas, Rich Condit.

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Hi everybody.

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I'm just booting up the weather here. Yes, Austin, Texas, get this 84 degrees, man.

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That's like 20 degrees less than when I last spoke to you. And there's been rain the past couple of days.

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And so we're all really happy about that. It's kind of, I guess it's clearing up now.

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Oh, it's some sunny ish, but I think we're out of the worst of it.

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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.

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Hi, it's great to be here. And here it is 72 Fahrenheit and beautifully sunny.

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We've had a lovely last couple of days.

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From Western Massachusetts, Alan Dove.

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Good to be here. It is 67 Fahrenheit, 19C overcast.

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And we have somewhere far out off the Cape, somewhere to our east is some remnants of tropical storm Lee,

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which is supposed to bring storm surge to the Cape and islands.

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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.

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And from Montreal, Canada, Angela Mingarelli.

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Hey everyone. So for the first time, maybe the first time, it's not the coldest in Montreal.

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So it's 70 Fahrenheit and 21.

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So the first paper, they're going to look at a paper where Moderna makes an RNA virus.

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Sorry, an RNA mRNA vaccine for loss of virus.

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And they look at it in guinea pigs.

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And it's extraordinary what they find because what they find is that neutralizing antibodies don't matter.

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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.

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If you like our work, we'd love your support.

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It doesn't have to be huge, but it needs to be has to exist.

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And you can go to micro doesn't have to be.

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All right, we have a couple of announcements. First of all, if you like our work, we'd love your support.

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Your financial support. It doesn't have to be huge, but it needs to be has to exist.

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And you can go to micro.tv slash contribute to do that.

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You know, as the pandemic recedes, people forget about viruses, but we'd like to keep on communicating micro TV does more than viruses.

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There's many other cool things. And please help us do that, micro.tv slash contribute.

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I want to wish Fiona a happy 40th birthday.

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Happy birthday, Fiona. Happy birthday, Fiona.

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Well, it's September 7th.

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And I hope you had a good time. Fiona is a PhD in psychology and a massive Twiv fan.

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Cool.

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Her husband anniversary of your 39th birthday is always a good time.

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I think you could probably do a PhD in psychology shrinking the Twiv hosts.

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Oh boy.

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Indeed.

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You don't want to go into our heads.

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I don't think it's a good thing.

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No, no.

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Her husband who wrote in saying, would you please do this said she probably should be a virologist.

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She loves Twiv.

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So thanks for listening.

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Keep it up, Fiona.

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Many more.

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Don't forget there is a second position in Amy Rosenfeld's lab at the FDA.

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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.

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We'll have a link in the show notes and you can find an email to find out more.

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And sadly, I want to tell everyone that Robert Lam, or Bob Lam as we used to call him, passed away on September 2nd.

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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.

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So we will miss him.

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Sorry to lose him so early.

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Yeah.

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He was a post-doc with Purnell Schopen at Rockefeller University, which is where I first met him.

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He was on my qualifying exam committee.

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He had a wonderful British accent and he was quick and funny and a lot of fun.

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I always sought him out at meetings.

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It was fun to talk to him.

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And then for most of his career, he was at Northwestern University.

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So sorry to see you go, Bob.

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Nice picture of Bob here on the obituary.

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I hope you find some good plaque assays wherever he goes.

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Black assay heaven.

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Black assay heaven.

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Yeah, that's a good one.

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All right.

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We have two very cool papers for you today.

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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.

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And that's why I want you to know about this paper.

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You don't need antibody, apparently.

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We'll go through it, but very I want you to know about this paper.

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You don't need antibody, apparently.

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We'll go through it, but very interesting.

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Well, you don't need neutralizing antibody.

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Yes, that's a title, neutralizing antibody.

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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.

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He just was talking about this paper and I said, we're doing it on Twiv right now.

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This is from University of Texas, Galveston, Harvard, Scripps, La Jolla Institute for Immunology, and the Academic Medical Center in the Netherlands and Moderna.

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So there are a couple of vaccines in development for lassivirus.

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This is one of them, but the neutralizing antibody angle is very interesting.

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Lassivirus is the virus that got me interested in virology.

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Honestly, it really is.

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I read this book, Fever, after I graduated from college, and I said, oh, my gosh, viruses can go from animals to humans.

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And I said, that's a cool thing.

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I'm trying to rearrange my monitor here.

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That's why I'm looking funny.

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There we go.

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That's a cool thing.

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And this book, John Fuller, which is very cool.

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You should read it.

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I looked into getting into virology.

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So lassivirus, it's an envelope RNA virus, negative stranded.

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It causes up between 100 and 300,000 cases every year, primarily in Africa, first found in lassa, Nigeria, about 5,000 deaths.

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And this is an important, this is a medical need for sure, 5,000 deaths, 300,000 cases.

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They often go to other countries.

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And that's 5,000 deaths a year, right?

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Not in general, that's a year.

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Exactly.

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That we know about, that we know that we're diagnosed with this virus.

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No, I mean, just for the listeners, because it's a year.

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That's 5,000 a year.

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Yes, not since.

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Not since the beginning of the month.

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A year.

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And this is, this is a virus that is, it is from animals, it comes from rodents into humans through rodent waste.

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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.

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And they get the, they basically inhale the fumes and get the virus.

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I was impressed here.

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It mentioned something about how long.

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So again, did you hear what he said?

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Maybe you should hear that again.

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Some of that.

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A virus that is, it is from animals, it comes from rodents into humans through rodent waste.

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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.

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And they get the, they basically inhale the fumes.

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So if you're living around rats and you have enough of a rat infestation that you have the dust from their excrement,

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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,

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where they go number one and two,

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then diseases plummet.

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And so yeah, 5,000 people die every year from this.

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But do we need to vaccinate those people or should we just give them sanitary places to live?

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And let me turn that around again.

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Do we need to vaccinate those people or should we give them?

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See, that's not what they want.

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They don't want to give those places healthy, people healthy places to live.

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They don't want to improve their living conditions.

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They want to test their, their, their augmentation of the immune system.

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And this is what this is, for me, this has become obvious that this whole,

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this is, this is something else.

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They're doing something else here other than virology.

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This is, this is a mad rush to try and use this opening to,

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to blow open as many possibilities as possible in terms of methodology and new application of gene technology to every aspect of public health.

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And so any new model they can find where RNA works the better,

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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.

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Nobody died. I mean, come on.

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That's what everybody on this screen would likely say.

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We probably don't know if anybody really has died from the vaccine.

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I guess a few people had some clots, but it's an insignificant number against the billions of people who didn't.

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And so be aware that that's where we are now.

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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.

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And we're talking about using an mRNA vaccine to protect from that.

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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.

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And not really explain what quaternary antibodies are.

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A perfect teaching moment. Here we go.

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Get the virus.

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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.

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And I was like, whoa, there's a lot of potential reservoir for this beyond what I realized.

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So I've done a couple of last episodes with experts and they say most of the transmission is actually spillover from rodents.

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There's some human human, but not a lot. Most of it is a rodent spillover.

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You live in a house where there are rodents under the floor and that's how you get it, which is amazing.

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Is the geographical distribution constrained primarily by the distribution of the host?

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The rodent host, yeah. I suspect.

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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.

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Yeah.

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Yeah.

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Maybe underreported, right?

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Yeah. So they've got to figure that a hundred thousand to three hundred thousand human cases.

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That's known human cases.

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You know, probably a lot more people are infected because it turns out you can get this and not even know.

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Yeah.

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It's a virus you need to work with under BSL4 conditions.

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Yes.

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And it's the Galveston contribution here.

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And that's an important thing to remember going through this paper because as I was reading, I would occasionally say,

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oh, well, why didn't they? And then, oh, right. Yeah. They're in bubble suits. That's why they didn't.

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You can't. You can't just blast through your experiments like this.

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Yes. Very expensive.

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This is all done at the SL4.

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Yeah.

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And very time consuming is everything you do. You got to suit up and go in.

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Yeah.

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This is one of the viruses on the WHO blueprint for diseases that need accelerated research.

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And so this one is definitely one where we need a vaccine. There will be a vaccine at some point used, maybe multiple,

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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.

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And so they have taken the mRNA encoding the spike like a person.

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They have made two versions, one, a pre-fusion version.

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Told you.

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I told you he even said it.

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That's listening to it again.

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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.

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And it's, of course, this mRNA vaccine is it was done because of the success with the SARS-CoV-2 vaccines.

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And so they have taken the mRNA encoding the spike like a protein of the virus.

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They have made two versions, one, a pre-fusion version, very much like the spike pre-fusion,

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the locket in a version that displays the relevant antigenic sites.

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And then they also use one without the pre-fusion locking to compare it.

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They put it in lipid nanoparticles and they deliver it to guinea pigs, which are the model for lassa disease.

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These are outbred animals.

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So remember that there's not a lot of immunological agents available and so forth.

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I'm assuming somebody's tried this in mice and it just doesn't work because it's...

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So when I...

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Good question.

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There are mouse species that are normally infected with this going around.

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So when I was at Rocky Mountain Labs, they were trying to establish a colony of mastomas natalantis, which is the natural reservoir.

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So that's not easy.

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You have to catch them and then you bring them and you get them to breed.

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And he said it's hard to breed them in captivity.

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So this was a couple of years ago, but I think that's the need.

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You know, musculous just doesn't work.

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Right.

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And I imagine there would be containment concerns with bringing another wild mouse into the country and breeding up a bunch of it

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when that mouse is endemic to many parts of Africa and is a reservoir for this.

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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...

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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.

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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.

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And then they look for first binding antibodies.

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So antibodies that will just bind the spike and they do find those.

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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
Because they're trying to eliminate the control group by any means necessary.