Stream.Transcripts/twitch/2129351324 (2024-04-25) - Susan Lindquist 2016 (Prions) STUDY HALL -- (22 Apr 2024)/2129351324 (2024-04-25) - Susan Lindquist 2016 (Prions) STUDY HALL -- (22 Apr 2024).vtt

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or CHD, and I believe he has a PhD in some sort

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of scientific discipline from what I understand.

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That probably sounds a little too good to be true,

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but I'm interested.

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I have something going with Adobe, but it's still quite a lot

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of work to clean up all the timestamps and stuff,

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and I've been trying to meaning to play around in the settings.

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And I just haven't gotten there yet.

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I have so much other.

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Anyway, I'm not whining.

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I've just got a lot of plates spinning right now

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and just trying to maintain this daily habit here.

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Oh, missed it.

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Yeah, we are here back again trying to rescue a few sheep,

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wake them up.

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It's pretty disturbing.

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Actually, I think you'll be very surprised

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to note there who's a common 434 that Kevin McCarran actually

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just had Stephanie Sinef on in the last 24 hours, which is kind

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of I'm not really sure if I should say anything about it

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other than to say that the enchantment and the faith

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is still very much intact.

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But yes, Stephanie Sinef was on Kevin McCarran's stream

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as little as 24 hours ago.

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That is a lot to unpack, indeed.

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It's a lot to unpack.

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So here we are anyway.

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And we are still in those interesting times

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where our consciousness, our actual attention

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is prime real estate, and it's not really

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about TikTok or anything else.

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I mean, all these things are being used to manipulate us.

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What we think about, what we pay attention to to make sure

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that whatever is perceived to be true is perceived to be true.

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It's just that sound, right, that it's just a magic spell

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that they cast every time they look at you.

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And yeah, we're not really arguing about anything.

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We can believe whatever we want, because we're not

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using logic anymore.

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And our money is out of our control.

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If our money is out of our control, I mean, I don't know.

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I don't know in the city of the age.

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Yeah.

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What sites do you see?

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Think you're a bear and a tummy bum.

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Good.

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You don't understand, Mr. Brown.

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You don't understand, Mr. Brown is a holy weapon.

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Please.

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Man, I still can't believe it's been so long

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since some of these people were on our screens.

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What I would challenge you to do, at some point

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when you're a little bored, is go look for Liana Wen

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and go look for some 2015 and 2014 TED Talk videos.

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Boy, you'll love those.

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Those are just great.

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Those are great.

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Ladies and gentlemen, welcome to Giga Home Biological.

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If you have been here for a while, you are here at the top

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of the wave.

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We are staying focused on the biology, not taking the bait

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and loving our neighbors.

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Thank you very much for sharing my work.

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That's how this works.

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There are people who also financially support my work,

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my family, but actually the best way you can help us

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is to spread the word because the people that can help us

05:58.720 --> 06:01.720
will click the extra times in order to get there.

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The people that really have the means to help

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and the heart to help are going to be called to help.

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And the rest of you, I just need you to share.

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If you think this is worth your while, if this is worth your time,

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the Giga Home Biological is something you need other people to see,

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then please, please share this word.

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I had to clear my throat here for a second.

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We are in the midst of a paradigm shift,

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and I think the reason why we're in the midst of a paradigm shift

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is because we've actually jumped ahead a couple of dominoes,

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which is something that somebody suggested a long time ago.

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If we want to stop this, we're going to need to jump ahead

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a few moves in the game.

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And I don't think that we're that far off right now

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from having jumped ahead a few moves.

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And that is because we've had our hands down from our eyes

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for long enough to kind of pull ourselves out of this a little bit.

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And this is Giga Home Biological, a high-resistance,

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low-noise information brief brought to you by a biologist.

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The illusion is sustained only through our active participation.

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And so we are here trying to advocate for one another

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to drop out.

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Some of that dropping out might actually be not sending our kids

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to university necessarily with any plan on what to do.

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That might be one good idea.

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So Giga Home Biological is something that started really

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from a bike riding YouTube channel in my commute

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to the University of Pittsburgh School of Medicine.

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And I was really doing just Journal Club on my bike.

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And then here we are nearly five years later.

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And we are now good afternoon.

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It is 2.14.

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I apologize.

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I started late today by one hour.

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It is the 25th of April and it's 2024.

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We've had lots of eclipses and survived.

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We are about to approach an active elective season.

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And other years, it would already be quite a bit more of an issue

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of a thing than it is now.

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And it's actually kind of surprising that we are where we are.

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But again, we are trapped underneath that hand in that,

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in that, I don't know how to point to that thing in that picture

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over here, Captain.

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Think of it like it's, it's just above the table.

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So anyway, this hand in this picture here is

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essentially representing the near total control over what we think.

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And that near total control over what we think combined with the fact

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that what we think is not related to what we need to understand.

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We're not really able to exercise informed consent.

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And specifically in the context of the pandemic,

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because we've been led to believe by the conscious,

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an intelligent manipulation of our organized habits and opinions,

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that there was at some point a bad cave virus or a lab leak that was

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responsible for the numbers that are in this graph right here.

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And that the novel virus equals the excess deaths.

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I guess you can't see that very well, but it's there.

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And of course, I've been arguing that this is how they did it.

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Exactly where and how this novel coronavirus spread to humans.

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Did it emerge naturally from the animal world and get transmitted

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to people in Wuhan, China?

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Or from a security breach at a research lab, also in Wuhan?

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That has been the subject of an ongoing research lab.

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William Brangham is back with details about new studies published...

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Does the sound occasion I start over?

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The point is a live animal market.

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Judy, trying to understand...

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There's any sink problem, let me know.

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You can also just try to refresh their SUSFIDER.

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So I've been making this analogy that actually the PBS NewsHour

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and other news agencies,

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and I'm going to talk a little bit about this.

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I've been making this analogy that actually the PBS NewsHour

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and other news agencies and even operators and podcasts

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and academics that have appeared on podcasts

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have systematically misled us to believe that through this illusion of consensus,

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that the right question to ask is where the hell did this thing come from?

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Not whether there is a thing or whether that thing is significant

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or whether that thing is part of a larger family of things,

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but just that where did this thing come from?

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And by being forced to ask that question and to debate that question,

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we were unable to see that the novel virus did not equal the excess deaths.

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We were unable to see because Judy Woodruff agreed with Tony Fauci,

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who actually also agreed with Brett Weinstein and a lot of other people on this,

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let's say, heterodox version of the Internet that also said,

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well, I mean, worst case scenario is it's a lab leak,

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and so then they're covering up something that could even be worse

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than a really bad, bad cave flu.

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And confounding this was the illusion of consensus

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that it didn't matter how afraid or confused everyone was.

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It didn't matter if they changed the way that people were rescued or not rescued at home

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or whether they resuscitated or didn't resuscitate people

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when cardiac arrest at home.

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There was an illusion of consensus that it didn't matter or wasn't dangerous

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to use pulse oximeters and the number that they read out

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as a meaningful indication of the presence or absence of this novel pathogen.

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Nobody, everybody, there was an illusion of consensus that this couldn't possibly

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hurt anybody. And in fact, the illusion of consensus was that it was a pretty useful tool

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and that F L C C C and Pierre Corey and others all said that,

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hey, you should use this as an indicator of whether or not to go to the hospital.

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There was an illusion of consensus on TV and also on social media that ventilators

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were definitely needed that antibiotics don't work for viruses that poor use of steroids

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could result in even more death that remdesivir could be very useful,

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especially during the hospital stay and medazolam wasn't a ridiculous thing to use in a nursing home.

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Opioid deaths. I don't even know what those are.

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We certainly shouldn't count them as anything.

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And since we need more numbers for COVID, why not just classify those as $35,000 dead bodies as well?

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We can use death certificate fraud to do it.

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I mean, these financial incentives are too hard to pass up.

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And maybe all we have to do is track and trace a few people.

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And now we have suspected cases of COVID. All we have to do is tell people to wear masks

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and close schools and get everybody all riled up about the mandates.

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And no one will ever question whether or not the novel virus really killed anybody.

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Never mind if we can detect it.

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We haven't even gotten to the fact that PCR is probably just one big fraud on a hot background.

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We haven't even gotten to the fact that lateral flow test fraud is based on antibodies.

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And in fact, usually three or four antibodies in the Android and at least two in each of these tests.

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I mean, it's just all commercial antibodies.

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And then the sequencing fraud.

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Primers and primers and primers were just supposed to take their word for it.

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And amplicons missing here and there was just supposed to take their word for it.

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Because the illusion of consensus says that all of this is right.

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Yes, ma'am.

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I don't. I'm streaming.

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Okay. If you want to come back later, you can remember your home for a reason.

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And so I find it very disturbing.

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What's the problem, Ruby?

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I find it very disturbing that in November of 2023 that these people were present with Denny Rancor in his, as far as I know his first international presentation about this stuff.

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He was very excited to go to Romania.

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And several of these people came home and wrote blog posts about the impressive presentation, the data set that they had seen, but never mentioned the part about that data set, which said that there was no evidence of spread of a risk additive pathogen.

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I'm happy to say that Denny Rancor estimated that 17 million people around the world were killed by the shot, and they were happy to call it a vaccine.

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Now, the strange thing about this is, is that those people know that Denny has been saying this since 2020 because he told them that in in Bucharest or Budapest.

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And I don't know which one it is. I'm sorry, I'm dumb. I think it's Budapest, Budapest, Romania. Yes. Is it Bucharest or Budapest? Wow, Maya, that much of a dick. Bucharest. Oh my gosh, I'm an idiot.

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There you go. I'm not definitely not geography. So they all saw him in Romania. They all know because he toots his own horn all the time that he's been saying this earlier than anybody.

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That excess mortality is never correlated with some kind of respiratory disease. It's always correlated with poverty, household income, and whether or not you went to the hospital or not, right?

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And so obviously they would have heard that and seen that and said, wow, that's pretty striking. Not only were 17 million people killed by the shot, but not a whole hell of a lot of people seem to have been killed by a virus, but they leave that out.

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And they leave it out for many months until they were in front of the US Senate. Some kind of meeting organized by Ron Johnson and they still left it out.

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They even invited more people that were present at that Romanian thing that are actually Romanian. Some of these guys are one of these are not that guy. That's Randy somebody or other from Canada, but this guy maybe or that guy.

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There are a couple other people there that are from Romania that were at the same talk and none of them said it.

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None of them would question the dangerous novel virus. None of them would question the death count associated with it. Do I need to open the door.

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Are you just going to sit there and hop and puff until I open the door.

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I'm going to go to the garage.

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Sorry about that.

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Sometimes I have to unplug.

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And so I'm frustrated because we're not really talking about that. We're not talking about the fact that everybody has an explanation for this and the explanation is all an illusion of consensus about the fact that transfection and healthy humans was rushed, but it did work.

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People have also been hurt by it, though, because there was an adulteration because it was rushed because they use process to whatever the story is.

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Maybe because it went into the vein sometimes like Marc Girodo says.

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There's always some excuse, but if it would have gone exactly the way it should have, then transfection is still pretty good.

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And an RNA can cause a pandemic. Everybody agrees that that's something that started in a point can can travel the world long to long and faithfully reproduce itself into a reconstructable phylogenetic tree of genetic information into a reconstructable phylogenetic tree of genetic

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information that is a level of unprecedented detail of molecular evolution of a single RNA molecule than we've ever obtained in the history of the world.

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We tried to track SARS, but we only got about 60 sequences.

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We tried to track Mark von Rundst from Belgium tried to track NL67, the coronavirus that was discovered in 2007. He was able to track it for about 28 cases in kids and got 28 sequences or something like that, or maybe he didn't get sequences.

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Maybe he just tracked the PCR amplicons through symptomatic. I don't know, but it was like, you know, not very many people.

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Now we're tracking the same virus since, I guess a little before 2020 like in October, if you're really a conspiracy theorist.

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And we have more than 16 million sequences now.

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They all agree this entire table agreed about that.

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The entire table agrees that whatever the question, the answer to that question mark is, this is basically true.

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Transfection worked, but hurt people because we rushed it because it had double stranded DNA in it or something like that.

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Process one, instead of process two, an RNA can definitely pandemic and not RNA plus enzymes like the flu is, but just an RNA wrapped in an envelope can get inside you and make copies of itself and then get inside another person and make copies of itself

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and do that millions and millions of times, even in different species and white tail deer and zoo animals.

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And they all agree.

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Even though almost all of them have known my message since at least 2021, some of them since 2020, the transfection in healthy humans is criminally negligent.

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We shouldn't do it because it will provoke an autoimmune response or at least challenge the body not to make one.

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And more recently that RNA doesn't really have the biology behind it to sustain a pandemic in the, in the definition of the word, which is it's not nowhere and then it's everywhere.

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And the idea that something all that was already there is being misconstrued as something that spread everywhere.

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And the fact that they're ignoring that idea, all of these people ignore that idea, all these people have ignored that idea since I put it forth in 2020 and all the way up until since I came up with an even better biological explanation for how that could be.

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With respect to infectious clones.

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Nothing.

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Zippo zero zilch, if anything, everyone's lost their minds more.

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The farther along we've come to be able to most succinctly describe that this question mark has not adequately described by any of their narratives and any of their combinations of explanations.

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And it all goes back to Jessica Hockett's observation about New York City being a pretty unreal event.

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Very, very unlikely to be natural at all.

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And in fact we know it's not natural at all we know we've got all kinds of explanations for why it happened and it's very, very obvious once you tally up all those explanations.

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And look at the temporal data of deaths that has claimed to have happened and just compare it to what normal is.

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Most people don't know that 3 million people in America die every year.

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Most people don't understand this curve right here between 60,000 and 50,000 people die every week in America. They don't get that.

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And so we have books that have come out over the last 5 years that are part of this slow role to try and coerce us out of our sovereignty to convince us that Mother Nature is so out to get us.

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And that transhumanism is so inevitable that we might as well just subscribe to Netflix and order in.

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Ladies and gentlemen, it's not just these 5 books, right?

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It's all these books.

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It's all these books.

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I gotta plug in again.

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It's all these books. I had so many books under that desk back there. I had to get one of our library carts, which I got out of the garbage can at the University of Pittsburgh. They throw these things away at universities.

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Let me see if I can make the camera focus back here.

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There, all of these books.

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A lot of these books in the middle are books that start with emerging viruses from Dr. Leonard Horowitz.

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Go right through the big shot.

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And they go right through up until dissolving illusions.

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The same year that Nathan Wolf's book came out. These are all in alphabetical and chronological order.

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And they're all books about the pandemic. Sorry.

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Gotta put this fun one in there somewhere.

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Way at the end.

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And so you see it's not, it's not just a.

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It's not just a small.

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This, this has been an ongoing operation to convince you of this stuff.

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To persuade you of these things. And I don't think it is, it is by happenstance. I think this is the evidence of a long standing plan.

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To make the vaccine schedule kind of crash to be inevitably blamed for stuff to be saying, Oh, that's pretty bad.

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But we're going to replace it with gene therapy and personalized medicine,

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and it's a lot of satisfaction and transformation.

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Things that just happen to work during a pandemic or get worked out during a pandemic or get worked out during an anthrax terrorist attack.

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I don't think these people have ever known for sure where the finish line is what the goal is what would be the next plan because their understanding of this biology started out as a complete bluff.

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And the reason is they were still bluffing about where they were going and how far they would get.

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In the nineties, they were still bluffing.

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They didn't know how far they were going to get in the 2000s with coronaviruses. They're still bluffing. They don't know how far they're going to get there hopeful that things are going to work that they're going to find all this biotechnology.

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But we have been misled over decades about the potential for RNA viruses to pandemic. We have been misled over decades about the what the worst case scenario is in the context of RNA virology with Ebola and Zika and all of these stories which have been

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exaggerated just as Peter Thiel said they would.

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And these worst case scenarios are the frame in which the pandemic occurred that frame is false and we're trapped within it.

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And that frame was put there so that when transfection and transformation were rolled out in the old and some of these expected bad outcomes started to become more mainstream and younger people.

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And that we would just dismiss them as part of the natural course of history and unhealth and that public health needs to fix these problems.

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And so I really think that this hypothesis is a pretty good one that they declared a pandemic of a dangerous novel virus on a hot background.

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The PCR test that could be varied in terms of sensitivity and positivity and all other things they had complete control.

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And all the while this was specifically designed to create more respiratory disease to increase the all cause mortality associated with respiratory disease and get more people in the hospital early on.

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That could be classified as this new thing that isn't pneumonia and influenza as a general category but it's now pneumonia influenza and COVID as a general category, which is quite extraordinary from the official perspective that all these people just kind of ignore that confounding.

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One thing that everybody hates is that I think giga ohm biological has really led the way in understanding that RNA virology is to a large extent an exaggeration of fidelity and certainly an exaggeration of biological revela relevance simply because in order for RNA virology to exist as it does.

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And the RNA sequences that are assumed to underlie these phenomenon in nature are always almost without exception recreated in a DNA form.

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And then those DNA molecules are mass produced using recombinant DNA technology and bacteria.

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And then those DNA can be converted to RNA which can be then transfected into a cell culture and whatever happens in that cell culture can be misconstrued has viral replication that can then be sent around used to seed experiments, etc.

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Sequenced, whatever needs to be done.

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That whole phenomenon can't be done with the natural form of the RNA.

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It has to first be amplified using a DNA synthetic construct.

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And that weak link is something that none of these people that were in front of the Senate will talk about even though they've all heard it from me.

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We even have a video where Jessica Rose says, wow, it's such a great idea, JJ, can you tell the, can you use the mixed tape analogy because that just made so much sense to me.

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I couldn't go to sleep. I was dreaming about the implications of this idea last night and it's just so cool.

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And then she got in front of the Senate and the most important thing she could say was that bears seems to be a lie or they're distorting bears or they're not counting the numbers right in bears.

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Even though she was the only one on that whole panel with like six degrees in all of the relevant fields where she could say, well, I'm a virologist and an immunologist and, you know, Jonathan Cooley isn't.

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But man, oh man, is he right about infectious clones and the fact that RNA can't pandemic.

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And so the only way this could happen and be real is if they actually put these sequences there with the intention of telling us.

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But it even a simpler explanation which just blew my mind when Jay said it was that what if there was this background that they've been characterizing for the last five or 10 years with the intention of rolling it out as a phylogeny that's already there that they know is there that they

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don't need to worry about being there because it is there and they're already very familiar with it.

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But of course, none of that was said, even though Robert Malone is shaking my hand and Ben on Robert F Kennedy juniors podcast and heard this theory first hand.

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Even though Meryl Nasse was on that same podcast, even though Jessica Rose was on that same podcast, even though I've worked for Brian Hooker.

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Though I've been on a podcast with Harvey Reich where I argued with him about man if you say that you're on hydroxychloroquine and you've had the shots and you got COVID for the third time and it was worse the third time that it sounds like to me you don't know a lot about

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prophylaxis and you don't know a lot about how vaccines work.

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Nothing you know about COVID is right. Otherwise, if you knew it, then none of these things would have happened to you.

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All those people know who I am and that's not to say anything other than to say. And let's just go back there to make sure we show the picture who I'm talking about here.

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Jessica Rose knows who's who I am. She's known who I am for at least at least three years. If not four. Kevin McCurnan knows who I am he's been on my stream twice.

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He knows who I am because I was at a signal chat with him for almost a year where I taught him almost everything that he claims to have known before the pandemic started.

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And that's evident by the number of times him and his wife have mentioned be in passing on his stream about very serious ideas like transfection and what transfection might do is terms of an autoimmune response.

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He's known and his wife I have selfies with them they met me at the CHD inaugural conference in Knoxville, which was nine days after I was on the podcast of Robert F Kennedy Jr with him and Jessica Rose and Meryl Nass.

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Harvey Reich was in a private zoom meeting with me where we had an hour long discussion about my hypothesis versus his mainstream TV narrative.

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And not that I made any progress with him but boy there are a lot of contradictions that these people hold in their head very, very, very adeptly.

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So today we are going to take a look at another Susan Lindquist video and I know that might sound.

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I don't.

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It might sound like we're going to waste our time here but actually Susan Lindquist has a really good video out about prions where she tries again.

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Now I hope and this is what I'm hoping here. We've looked into Susan three times now one about prions which was a really basic video that was the first one we watched.

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Then we watched Susan Lindquist twice where she was talking about protein folding and the role of chaperone proteins that were originally called heat shock proteins but they're not just from heat shock they're from any kind of stresses she told us.

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And that these proteins are chaperone proteins that help other proteins fold and may or may not be involved in things like protein pre on misfolding or amyloid misfolding this kind of thing but she never really got there in that two part talk.

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This talk that we're going to watch today is from 2016 and she is going to address the phenomenon of prions and she is going to talk about it in the context of her cellular model which is of course yeast.

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Now it is 247 so what's most likely going to happen is we're going to get an intro to this we're going to get started on this but because of my long winded introduction we're going to take a break I'm going to go to basketball and then I'm going to come back and I'm going to do it after dinner or after six like I did yesterday

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and I'm going to talk about protein folding as a part one and a part two that's most likely the way it will be.

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Let's see if it's not like that it'll be because it's so good I can't stop and then I'll have to meet the kids at the gym after

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so let's see where we go.

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This is on one and a half speed so you know.

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Hi I'm Susan Lindquist I'm at the Whitehead Institute at MIT and remember the Howard Hughes Medical Institute.

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I'm going to talk about protein folding as a powerful driver of evolutionary novelty.

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Last time I talked to about HSP 90 and the ways in which it can influence protein folding and the manifestation of genetic variation in very powerful ways.

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So I'm going to tell you about a very different way in which protein folding can influence the manifestation of genetic variation and lead to the appearance of all kinds of nutrients.

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That's the pre-ense.

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So it's an interesting story that starts in a place in New Guinea and we'll move on to Cambridge, Massachusetts.

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The protein folding problem which drives all of this that I've been talking to you about is simply that protein started as long linear strength of amino acids and they have a folding of very complicated shapes like this.

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And they do that in a crazy environment they do that in this really crowded environment of the cell where proteins are jostling around and bumping into each other all the time.

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The story on pre-ense as I mentioned starts out in New Guinea.

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And there was a tribe that was a very large number of people were dying from a very bizarre horrible neurodegenerative disease.

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And Carlton Gaddischuk found out that it was in fact due to an infectious agent.

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And Stan Prusner and many other investigators have contributed to this I should say but these guys were very very important in the field.

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Found out that this disease was caused by protein folding.

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Now protein folding problem creating an infectious element was really quite an amazing thing.

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It meant that proteins when they change their folds can have genetic manifestations.

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These agents are usually agents that carry along DNA with them.

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So it was quite a revelation.

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But what I want to talk to you about is thinking about pre-ense like this.

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Because the story of pre-ense as disease causing agents is so extraordinary and wonderful and amazing.

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It's kind of dominated and quite naturally so the concept of pre-ense biology.

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But what I think is that we have to think about pre-ense as this creature and it's time to get rid of some of the baggage because it's my belief that pre-ense actually are amazing protein based genetic elements.

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They can do all kinds of really wonderful things in biological systems.

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And I think also that we're only at the very tip of the iceberg for revealing this.

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So here's some of the great things about pre-ense that I want to tell you about.

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Pre-ense form of mechanism for the inheritance of a protein based trait.

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We found more than 50 of them in yeast.

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We and other people have recorded on these.

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25 of them are yet unpublished but there's just a lot of them.

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They're caused.

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25 yet unpublished pre-ense in yeast.

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And she's arguing these are proteins which are inherited separate from their genetics.

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Which is a interesting thing to happen in a yeast.

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A single-celled organism.

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It's a very different thing to suggest that this is a phenomenon which goes all the way up the chain invertebrates.

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Protein based inheritance is nothing that Stanley Proustner was talking about in his talk in 2002.

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And it's extraordinary because this is in 2016.

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This is really 14 years later.

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So we could be quite a long ways.

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But she seems to like prions as much as Vincent Rackeniello likes viruses.

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It's pretty impressive.

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Dozens of new traits.

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Dozens of them are doing a variety of all sorts of new traits.

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They allow organisms, the yeast organism at least, that we've been looking at to survive in fluctuating environments.

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Oh, so it's just right now at least the yeast is using prions to survive in fluctuating environments.

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I think she's using the word prion to describe any protein that might be inherited separate from genetics.

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And that's very different than a prion which causes other proteins to fold like it.

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Which is what is implied by Stephanie Sineff and other pseudo-experts when it comes to the spike protein having prionogenic domains or prionogenic epitopes.

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Which are the terms that these people use.

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These worst case scenario team members.

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Which since early on, if not the very beginning of the pandemic have been seeding this narrative of all kinds of worst case scenario outcomes that I think were always associated with transfection and transformation had never expected to come from an RNA pandemic.

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But they were encouraged.

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They were there already with these narratives and knew that they would get away with it.

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In fact, they knew they would get amplified if they pushed these narratives.

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And I think that it's possible.

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It is absolutely possible that academia has these people in it that are feeling very safe about pushing these ideas knowing full well they're exaggerating.

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Knowing full well that they might even be lying about certain things because it's part of the national security operation which is to protect the secret stuff.

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And so the way you protect the secret stuff is to tell some stories that mask it to make up some mythologies that can distract from it.

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And I think as we as we start to really lift the veil on this stuff there are going to be a few things a few ideas and biology that we're going to hone in on that are more likely to be ideas which were pursued and amplified with the idea of using them to obfuscate other ideas and other

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directions of investigation.

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Bright shiny objects with lots of funding that keep people from asking questions where there is no funding.

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There's something super slick about this in 2016.

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It's a protein based inheritance you know she's using these these terms which are very attractive to the the the people who want there to be new biology that we don't understand or or spooky biology that can be.

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Yeah it's very dubious to me already.

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They provide a fast route to the evolution of complexity and their reversible traits so you can acquire the organism can acquire these traits and they can lose them.

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They form a very sophisticated strategy for survival.

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And they form a system of biological memory in which a change in protein folding self perpetuates and then that self perpetuating change in protein folding changes the function of the protein.

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And that creates can both create new phenotypes it actually serves as a kind of a biological memory when you think about it.

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And there's evidence now that this is really occurring at the ends of synapses in our brain and helping to maintain long term synaptic connections.

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Also we have found in my lab evidence that prions can enable life in complex biological systems and communities creating different ways for organisms to relate to each other.

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Now the point would be right let's just say optimistically speaking because again we're probably going to we're probably going to run into a time crunch here.

43:05.720 --> 43:14.720
Let's just say optimistically speaking that this is a good woman and she's doing all of her all of her work is good and none of it is to obfuscate anything else at MIT.

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None of it is to help anybody else with any interest in or controlling interest at MIT and that MIT is just a great school with a lot of people and nobody there's any has any other conflicts of interest you know like connected to intelligence or government

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or multinationals or other other national national governments or anything like that it's just a great school with super smart people that like trains and ham radio.

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And this lady is a molecular biologist and she thinks proteins are really cool and prions are very special and that they represent a level of sort of biological complexity that not very many people are aware of because you can inherit proteins

43:56.720 --> 44:06.720
and folded proteins that can also fold other proteins and so that inheritance that genetic information is essentially encoded in a way that we never thought was possible.

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And so the more we look into this the more impressive it is and then wait a minute hold on stop.

44:14.720 --> 44:29.720
So best case scenario Susan linguist says is that biology is even frickin more complex than you thought it was when you just thought it was DNA gets translated to RNA gets translated to proteins that are oftentimes misfolded because the ribosome is so complicated

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and RNA can be edited and those knots do things and the code is different and misfolding is a thing and wait a minute holy cow and then after that there's more inheritance.

44:41.720 --> 44:44.720
There's more transmission of information.

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It's reversible.

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So the best case scenario.

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If Susan is an obfuscating anything or trying to muddy the water I've understanding and trying to make it even harder for us to appreciate the sacredness of our biology or to or to appreciate the reduce irreducible complexity that we come against as we look at the molecular basis

45:12.720 --> 45:16.720
of a cell.

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Then she's adding a dimension that just makes it absolutely impossible that we understand any of these phenomenon that we call the immune system or nutrition or genetics for that matter.

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You can't have it both ways.

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And yet somehow or another the magic spell has been cast on us that you can actually have it both ways that all of this stuff can be beautiful and people like Susan can really appreciate the magnificence of it and how wonderful it is that life is even more complex than we thought.

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You can have Stanley Prusner saying that these are diseases that could probably be cured with a combination of antipsychotics and antibodies to the pre on protein.

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So we have people telling us that again a function spike protein that was specially designed to be a pre on a genetic protein specially designed to be amyloidogenic or whatever which term they choose on a given day or what depends on really the paper that they're

46:32.720 --> 46:48.720
talking about whether it's amyloidogenic or pre on a genetic or whether it's staphylococcan and teratoxin B or whether it's the HIV inserts or maybe we'll circle back soon to the fear and cleavage site again.

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And that is the magnificence of this that they have been laying the groundwork for this massive amount of confusion for a very, very long time many people unwittingly I'm sure.

47:01.720 --> 47:17.720
And so if you want to believe that Susan is unwittingly participating in this then the best case scenario is that she is adding a dimension to our biology that Stanley Prusner is not acknowledging

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that anybody that's talking about the spike protein having pre on a genetic epitopes is not acknowledging

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but is instead insulting with the simplicity of you can just add the you know add that alpha helix or this beta pleated sheet and there you go you've got a little pre on how long is the pre on

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and the pre on protein that that they're always talking about is 28 kill adult and this is not a

47:44.720 --> 47:48.720
hmm hmm

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seems like more than an epitope right

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how many different antibodies was Prusner talking about how many different epitopes was he taught

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and it's all just incongruency and nonsense and so when we listen to Susan and she's gone now when we listen to Susan

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let's just assume that this is a person who's trying to add to our understanding of the sacred biology of the irreducible complexity that is us

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not trying to define a particular kind of disease and if we listen to it that way I think what we're going to hear is another side of this

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protein based inheritance I mean that's a way to get grant money holy cow I'm going to try to give you an overview of this very complex and rich and wonderful subject

48:40.720 --> 48:55.720
and I'm going to end with pre on forming the really ultimate example of Lamarckian evolution in which organisms can acquire a heritable nutrient that they pass on from generation to generation by being exposed to a new environment

48:55.720 --> 49:06.720
so she keeps talking about organism even though she means yeast and so that's kind of frustrating and then Lamarckian inheritance is really also an interesting thing to evoke

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because generally speaking Lamarckian inheritance is not considered something that that generally happens so I'm not

49:14.720 --> 49:30.720
going to get into that at all because I'm not Brett oh the pre on story slot starts with this these two strains of yeast red versus white and remember she just said the pre on story starts with two strains of yeast the red

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and the white so we're not starting with eating brains we're not starting with feeding cows cows we're not starting with sheep scrapey keep that in mind

49:45.720 --> 49:55.720
but this these organisms have a very odd genetic behavior Brian Cox did some wonderful work on this many years ago and a lot of people thought this was really kind of a strange thing why is he working on this

49:55.720 --> 50:05.720
but he his early work really laid the foundation for for all of this everything I'm going to be talking to you about today what he found was the red stream was really very stable and you could streak it out and it would give rise to more red colonies

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every once in a while they would turn white and the white stranger could then streak out and they were very stable very heritable trait and every once in a while they would turn red and that of course was metastable inheritance

50:14.720 --> 50:32.720
what Brian also found out is that when you made it the red cells to the white cells and then you spoil it and got out genetic progeny you would normally expect if those traits were due to changes in the DNA the difference between the red and white cells changes in DNA that some half of the progeny would now be red and half of the progeny would be white as those pieces of DNA would be a sort of in subsequent generations

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they weren't all the cells all the progeny for white so odd inheritance Brian also realized that this this change in color was due to a change in translation the way in which messenger RNAs are decoded into proteins that there was a translation termination defect and the cells switched from red to white because of a change in ribosome red or stop glands

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and that was linked to this protein here in the simple cartoon it's a protein that's involved in a translation termination and it's only this portion of the protein over here that's actually required for translation termination activity

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it's a very important factor it tells ribosomes to stop when they hit a stop cutout

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attached to it as these two weird domains called the internal domain and the middle domain that just have a very unusual type of amino acid composition and it was discovered that those properties of inheritance really depended upon that but that was those odd properties of hair dependent on that region of the protein

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now your return sure enough comes into this story because he was searching for what could govern this odd pattern of genetic behavior not like the genetics that we normally think about as being driven by changes in DNA

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and he was working with Sue Liebman's laboratory and he did a screen for factors in the genome of yeast that could could alter or influence this inheritance pattern

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and what he came up with was HSP 104 what the heck did that mean? Well at that point I got a phone call from here because he knew I had been working on HSP 104 I'd shown that my laboratory had shown that it saved cells from high temperature death

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and he was wondering if I had knew any aspect of how it worked I did I knew how it worked but nobody else didn't the reason for that was because we couldn't get our paper published

52:05.720 --> 52:10.720
there's no one of four did something unusual and it was very hard for people to accept what it did

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so I'm just to want to be sure that you understand I'm confused as well because she has prion protein at the top of this slide but she's not defined this protein as the prion protein

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and as far as I know she says the protein that she's talking about is a protein which is involved in the ribosomal complex

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and dictates how the ribosomal reads stop codons someone in the chat correct me if I'm wrong that's what we're talking about here

52:42.720 --> 52:47.720
Y330

52:47.720 --> 52:56.720
okay that's fine so what does HSP 104 do by the way these are many many many people who contributed to the story of trying to figure out this different parts of this translation

52:57.720 --> 53:04.720
which one's contributed to the genetic behavior C translation termination factor but she's got prion protein written up there it's very bizarre hold on

53:04.720 --> 53:07.720
so what does HSP 104 do?

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so now we're on HSP 104 so my assumption has to be that HSP 104 is the factor that they're talking about there with the C and N domains there

53:21.720 --> 53:26.720
attributed to the genetic behavior this story of trying to figure out what is it or did some new medical from the 5th was yeast

53:26.720 --> 53:36.720
he was working with like the gene what could govern this odd pattern of of genetic behavior not like the genetics that we normally think about as being driven by chases and DNA

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and he was working with Sue Liebman's laboratory and he did a screen for factors in the genome of yeast that could could alter or influence this inheritance pattern

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what he came up with was HSP 104 what the heck does that mean?

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well at that point I got a problem with any aspect of why it how it worked and I did I knew how it worked but nobody else didn't the reason for that was because we couldn't get our paper published

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there's no one before did something unusual and it was very hard for people to accept what it did so what does HSP 104 do?

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these are many many many people who contributed to the story of trying to figure out this these different parts of this translation termination factor and which ones contributed to the genetic behavior

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so what does HSP 104 do? HSP 104 plays a major role in something called induced thermal talent so I talked about this briefly in one of my earlier lectures

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when organisms are exposed to mild heat temperatures they make new proteins called heat shock proteins and those proteins help to save them from the death caused by protein misfolding at high temperatures

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here's an experiment in which cells have been exposed to the same heat treatments but in one case the cells have HSP 104 and in the other case the cells do not have HSP 104 makes a big difference to their ability to survive

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and the way it makes it in terms of their ability to survive is that it takes apart protein aggregates so what are protein aggregates?

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these are well-folded proteins, you've all seen the effects of heat on these well-folded proteins, it causes proteins to aggregate

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now HSP 104 I don't want to say can unfry that egg but just a little bit of that kind of aggregation occurs in cells in response to stresses and that can kill them

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this is a wonderful example of how academic biologists will get stuck in an analogy that is inadequate but because it gets to the lay person's idea

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they keep using it but it's a terrible example of what she purports to happen here

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she purports that misfolded proteins make aggregates and that these proteins like heat shock protein 104 actually prevents those aggregates from forming

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now that's a very different thing than what's happening when you fry an egg and so it's pretty annoying because anybody with a little sophistication knows that it's different

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and so to use such an inadequate explanation actually suggests that this is not intended to inform

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oops that wasn't what I meant to do that kind of aggregation occurs in cells in response to stresses and that can kill them HSP 104 saves them by disaggregating

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so that led us to think well maybe how can it be involved in inheritance of this trait, maybe inheritance of that trait depended in some way upon protein aggregation phenomenon

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so we looked at the protein that had been tied to that trait that translation termination factor and asked whether it existed in the different conformational state in the red cells or the white cells

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and sure enough in the red cells the protein was soluble and functional and in the white cells the protein was tied up in little aggregates and you can see by the way so aggregates

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they're actually being inherited being passed from the mother cell into the daughter cell

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now about the time when we were in the midst of these experiments and where we hadn't yet published anything and hadn't yet been able to publish even our story on HSP 104

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we did wind up getting a really great paper in the suggestions of the reviewers in the long run.

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While we were in the midst of this along came a paper by Reed Wickner which was a very very clever interpretation of some genetic experiments

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on another factor that was inherited in the very bizarre way inherited and had the same kind of genetic properties that the side element had that red white element had

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this was called Yuri III and he suggested that the way in which this was inherited was that it was due to some kind of a pre-unlike phenomenon

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a self-perpetuating change in protein function not knowing whether it was an aggregate or was it changing the activity of the protein or what was going on

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but he also suggested that this might apply to that this pre-unlike mechanism might apply to that inheritance of that red white trait

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so as I say it could have been anything it could have been an enzyme that catalyzed its own modification it could have been lots of different things

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but because we knew that it was controlled by HSP 104 which we knew was involved in protein aggregation this paper was really made a tremendous amount of sense

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and so we decided to look at this in even greater detail and we found that in fact the aggregation state of that protein sub-35 translation termination factor

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was not just a generalized aggregate but a very special kind of aggregate a self-templating amyloid aggregate

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so on the left there you see the protein fibers of sub-35 that we found after a great deal of effort

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aggregated proteins are a lot of work to work with but you eventually looked at the aggregates under the electron microscope

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Now remember all of this stuff is in yeast all of this stuff is yeast proteins the argument is is that yeast are eukaryotes and were eukaryotes

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so some are all of these cellular factors may have a homolog in our cells the question will be to what extent are these homologues identified

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and to what extent are these observations sort of paralleled in any system that is related to ours except for by this you know

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it's insofar as what she means that they have nuclei and they have machinery inside their cells that's analogous to ours I don't think she's wrong

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but now the question is going to become how does this bridge our way to understanding what prions and prion disease

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and whether a prion epitope can exist or not exist inside of a gain of function protein

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that's really our goal here and I'm going to go get a drink and fill up my water bottle and then head to the gym with the boys

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we're in half an hour early today please remember that intramuscular injection of any combination of substances with the intent of augmenting the immune system is dumb

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transfection in healthy humans is criminally negligent in RNA, cannot pandemic I will be back

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I'm probably going to start it right after I get back so I don't know why I wouldn't start when I get back so it'll probably be

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thirty four forty five maybe five o'clock I'll start it and I'll start it right here and we'll finish this video with Susan that we just barely started

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and try to figure out if Susan can give us a better idea of what prions are all about

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I guess I'll do that too why not

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this is our hypothesis

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and yeah I'll leave it at that I will be back don't forget I will be back

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and that will be a part two thanks

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you

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you

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you