Stream.Transcripts/twitch/2128684961 (2024-04-24) - Stanley Prusiner and Prions 2002 (PARTII) STUDY HALL -- (24 Apr 2024)/2128684961 (2024-04-24) - Stanley Prusiner and Prions 2002 (PARTII) STUDY HALL -- (24 Apr 2024).vtt

WEBVTT

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You

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I

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Guess I didn't update the stream. Yes, this is part two

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I'll update the title later. I guess I thought I updated it here on my OBS

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But I guess I didn't push the button done and so that it did not date my bad. This is part two. I

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Shall do it

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I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario

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I'm afraid that the latest data tells us that we're dealing with essentially a worst case scenario

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I

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Think truth is good for kids. We're so busy lying. We don't even recognize the truth no more than society

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We want everybody to feel good. That's not that's not the way life is

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We should be okay here. I'm just gonna check this one. So I'm back from the gym

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I thought I'd get part two done before tomorrow

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We're eventually gonna be doing a show a day or two shows a day one at 10 10 and one at 13 13

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So at 10 o'clock and one o'clock

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But you know we got to roll slowly here and make sure that we we build this momentum

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Intelligently and one of the things we're trying to build momentum around is this whole pre-on biology stuff

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And there's a there's a lot to learn and so we were gonna finish the video that we started earlier

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Thank you very much for being here. See you in a second

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This episode is sponsored by mink that's moo plus like

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Mm-hmm

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This my point is that if if we were able to just like we're trying to get everybody to take the vaccine if we had

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Put that into getting everybody to take hypermectin and fluvoxamine for for a month

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If we and if we could accomplish that then COVID would be wiped out

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We could do it and actually any municipality that could regulate its borders could clear the disease

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But you can tell if someone's lying, you know, you can sort of feel it in people

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And I have lied. I'm sure I'll lie again. I don't want to lie

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You know, I don't think I'm a liar. I try not to be a liar. I don't want to be a liar

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I think it's like really important not to be a liar

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I mean that stands alone as like one of the best

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Rapid fire statements made by anyone

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Ever maybe in mainstream media

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You

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I

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The meter this always looks like it's really soft, but it actually is always really really hard in my ears

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Let's do it

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Sweaty bombs, this is so crazy like these bumps. This is so crazy. I feel so nervous like what in the world man

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Oh

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Big-time brick

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I'm glad somebody noticed that that was a big-time brick. I'm not trying to represent myself as some kind of baller here

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That was the whole point of making it a real real clip one good shot one brick

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That's about what I'm good for. I don't think that's that bad though

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If you've been following along for a while you're here at the top of the wave

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Where we've been shooting three-pointers for four years now where we stay focused on the biology

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We don't take the bait on TV and we love our neighbors trying to rescue those skilled TV watchers in our family and on our street

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By sharing this biology consistently on Facebook where I am not on

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Twitter where I'm mostly not

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Shared everywhere you can and if you can maybe you can find your way to get going biological.com and find a way to support

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That would be also great. It's also just a great place and way to share what we do send people to get your own

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Biological.com. They can find everything there everything has its own link

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And it all just kind of centers on that all of the links to all the different places where it's stored is there and yes, this is

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Independent Brightwave presentation that basically means that we don't take sponsorships because we're not offered them

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And we are supported only only only by viewers like you

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Still trying to break the same illusion

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Sometimes it's nice for having a little live Eric Johnson Evan root fever to try and help

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Establish the mood that it's necessary in order to

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Engage in United non-compliance is what you're really doing here

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When you come here and try to discuss the flip side of the biology on TV the flip side of the biology on

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Social media and so today we're going to keep up the good work

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That needs to be done

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This is going biological the safest way to get biology in your head

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You

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Thank you very much, this is giga ohm biological a high-resistance low noise information brief brought to you by a biologist

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24th of April

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2024 we're on our second stream of the day, but that shouldn't be something we should be applauded for

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We need to do more and there is a lot of work to do

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Sometimes it's just it's handy to be ready. We were ready for this

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We've been preparing for this video for a long time and it's actually so far been incredibly revealing

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And so I want to start first by kind of reframing where we are again

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This is about a principle of informed consent

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I'm gonna escape out of here for a second just to make sure that this is going where I want it to go

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This is where I want it to be I'm gonna skip a couple of those slides

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It's always smart to make sure you are where you need to be so we've talked about these TV scenarios where there's either a lab leak or a

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Batcave virus, so maybe there's nothing at all

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And how these things have generally

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Hearded the vast majority of people in West Western civilization to accept a faith in

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What is essentially a novel biology? It's not just a novel virus

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But the whole story of a novel virus and how it has behaved in the last five years

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constitutes a novel biology because first of all the precedents of a trackable gain of function

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RNA because we need to be very honest with the people in our lives about what is essentially the story the story is not a virus

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with lots of little gears and wheels and and

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Enzymes and magnets and mitochondria inside

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It is simply an RNA molecule wrapped around a

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protein called the end protein and that is contained within what is essentially a cell membrane a

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Lipi protein coat lipo protein coat

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and

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So coronaviruses as they are presented to us are nothing more

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than a

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nanoparticle with some RNA packaged inside of it, and so by the

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The broad understanding of the rules of biology that

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that model

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then

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dictates that whatever properties are

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contained inside of an RNA pandemic are

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emergent properties that are contained within the actual sequence of that RNA and indeed that is the story that many people have

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been telling us from the very beginning that a fear and cleavage site that HIV inserts that

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homology to a staphylococcan and teratoxin B protein could be partially

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explanatory in terms of the severe COVID that we see in some places or the long COVID that we see in some places

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And this mythology is extraordinary because at the heart of it again

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I'm going to say it one more time is an RNA molecule that because of the actual content of its sequence the actual

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Order in which the bases are found it is capable of doing something that otherwise all other RNA molecules

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never even

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Never even it doesn't cut it doesn't happen

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Now the flu viruses is RNA molecules, but the crazy thing is is flu viruses are

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Supposedly packaged with some enzymes

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So even flu viruses have by definition even more gears and wheels and little motors in there

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Then a coronavirus a coronavirus is actually just an

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instruction module and

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if that instruction module is read then

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Apparently it makes copies of itself

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But the point is is that if that instruction module has a fear and cleavage site or it has HIV inserts or it has

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homology to to a

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toxin protein

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That now it can cause a pandemic

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So the second part of this is that

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Transfection was waiting in the wings for a very long time

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Just waiting for the right opportunity to come and save mankind. I mean the whole species

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and

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Since we rushed it since we tried to make a lot of money and cut corners or whatever it is that we did

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Or because we weren't liable. So since we weren't liable. We cut corners

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That some people were injured because of the contamination found in some of these

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And some of these countermeasures now keep in mind one of the major

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Lawsuits that's currently moving through the courts is a lawsuit

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To do with contamination of remdesivir vials so not even the use of remdesivir. Yes or no, but

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Contaminated remdesivir and so you see

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then when you realize that they've been talking since

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2000

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Wow a terrible weatherman 2020

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About the spike protein being the center of this whole mystery

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The spike proteins interaction with ACE 2 the spike proteins ability to cause multi-system inflammatory disease or whatever it's called

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The spike proteins targeting of the heart muscle the spike protein being

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amyloidogenic the spike protein being a pre-on or having pre-on-like sequences in it

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Has been confounded from the very beginning

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With the ability or the propensity for

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transfection or transformation technologies to

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result in

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Pre-on-like disorders or whatever these things are like crowds felt the occub in the paper of Luke Montenier

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The reason why the paper of Luke Montenier is so important is that it came out very early

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and yet those people had been actually

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They had been transformed with an adenovirus carrying the spike protein gene

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So they had been transformed they had not been infected and

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Of course right away the people were arguing. What were they arguing? What were they arguing?

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They were arguing that maybe those people had been infected before they were

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Before they were vaccinated

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And so already they needed to clean the narrative already they had to cast out already

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They had to speak up

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Because the worst-case scenario was already under threat from the very beginning the worst-case scenario

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Narrative centers always on the spike protein even though there are 29 or 30 other

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Proteins that have various isoforms that can do all kinds of things most of which we don't know and

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Yet we are hyper focused on the spike protein the spike protein is what's used to make the phylogenetic tree

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The spike protein has defined all previous

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Coronavirus variants in the past if you look for new SARS viruses

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You don't look for new N proteins you look for new spike proteins

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and

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Part of the reason you look for new spike proteins is not because the spike protein is the most variable gene

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It is because it's the most abundant

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subgenomic RNA

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and

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We've looked at the infectious cycle since early sixties through the 70s 80s 90s

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And now all the way up to now with nanopore sequencing and we keep finding the same weird ratio of almost no

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full genomic RNAs, but

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orders many multiple orders of magnitude more subgenomic RNAs

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Predominated by spike protein e gene and gene

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And so when you look for those subgenomic RNAs

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You're looking for a signal that is expected to be there and many many many many many many orders of magnitude even in their

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most honest appraisal of

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the infectious cycle of their entity called coronavirus and

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So so much of this biology is almost wholly based on the cartoons they draw rather than on the experimental results that they've obtained

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So much of this biology is based on the cartoons

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They draw rather than the data and the experimental results that they have actually obtained

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And that is the reason why this story is so complicated and needs to be obfuscated by people who say well

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There's just no viruses at all

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None of the viruses exist

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And

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So it is a very very complicated trap that we find ourselves in and prions as part of that prions and

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Understanding what they are and what they're what they aren't if they're anything at all is

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Extremely important

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And as with virology we would be very very

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It would it was we're risking a very very big error if we assume that the biology that we've been given or told or led to assume

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As it would be because none of us have studied this intentionally until recently

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That we really understand to what extent any of this stands on firm ground and so let me switch over to the the desk here

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One of the things that I would like to start out with with this with this second part is

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Just to kind of review about what he said in the first part

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One of the things that he said in the first part was in the beginning and I'll give you the example

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I think I have it up already

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Don't I have it up already?

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If we go back to the beginning of this you can find that one of the

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One of the things that they were doing first was trying to optimize the production of the disease

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So first they couldn't find it

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Right it was very hard to achieve some kind of enrichment of the disease

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Agent and so he used two different graphs here to show you where the sucrose agent

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He said well darn it

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He said what you would expect to see is some kind of peak right some kind of peak over a certain place in

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The sucrose gradient, but you instead you see all kinds of a smear now

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Here's one of the things that I find already very interesting. Let's go back

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to the other the other

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Let's go back here

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This is the the nature pre-on paper that we've we've referenced a couple times now and lead up to this discussion

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And this is perhaps a little bit better drawing. It's a little more up to date

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This is the pre-on protein, right?

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Can you see oh sorry?

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This is the pre-on protein the protein that is on the outside of the cell that we don't know very much about what it does

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but it's for sure on the outside of the cell or on the inside of lysosomes and in the basal state

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It does something but in the in the pre-onogenic

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State or the prey I guess in this case it's PRPC

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And then this is a pre-on. Sorry. I had that wrong. This is the regular

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Pre-on protein and you see three alpha helis is there and then here you see the pre-on protein

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And it's many of them all layered on top of each other. That's what you see there

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And the implication is is that it's some kind of little fibro right there all layered on top of each other

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So this is already several pre-on proteins that have folded incorrectly and then induced it on one another

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And then this one can look induce the blue one to join them you see that

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And so this concept implies a couple things if we believe that the sequence of a protein is very much

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related to how it folds and

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So the potential for it to fold

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is related to its sequence means that it was should at least in this model and it appears also to imply that it's not able to

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Able to make any other proteins fold like this

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But it can make

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proteins with the right sequence the the protein pre-on the pre-on protein

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sequence

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so what I find interesting about the

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What I find interesting about this figure in the in the video that we watched earlier today is that this

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Is still seeming to imply that there is one protein now if there's one protein that makes

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Aggregates, what can we predict? What's the model right? That's what science is all about you have a model

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And then it makes predictions about measurements in the future and those predictions if

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If done cleverly or or or tested cleverly

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can provide fruitful

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Guidance to the experiments that should be done

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So let me just take you over here and let's talk first about the the concept of pre-ons making more pre-ons

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By

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Coming together right pre-ons press pre-ons equals a fibrel

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And that was also what he was talking about with regard to amyloidosis and

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Amyloid I guess be in the same thing really just different sides of the same coin or something which I called out before as being nonsense

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But I don't so I don't want to imply that I'm I'm saying it here

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But let's just talk specifically now about this model and the idea that the actual profile that they measure in this sucrose gradient

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is smeared across densities which means

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Apparently not one thing and the argument that they might make is one where they would say

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Sorry, they would say that that the

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That the pre-on

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protein is is

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making

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Fibrels in those fibrels because they're multiples of the the pre-on protein

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Then they're going to be all across that sucrose gradient, but that's not entirely

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accurate because if the pre-on protein weighs

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X

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then two pre-on proteins will weigh two X and the and the in a gel like that you're going to get

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Lines or in a sucrose gradient you could get lines where okay

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Well, then this is you know two and then this would be five and this would be eight or whatever right?

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I mean you can actually count it because it would move up in increments by weight

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because they move through these things by weight or by density and

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So in a sucrose gradient if they don't separate by density there might be a way to do it by charge in a

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In a gel, but there must be some way to show me

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That these preons are working together because if they're if they're they're coming together in multiples

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Then the multiples after digestion should become visible. They should be small fractions of the things that aren't digested

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And yet somehow or another this part of the model which I can show you again is very clearly visible

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Here

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That's exactly what's implied by this nature paper from not too long ago

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and in fact, I think a lot of what Stanley Prusner implies in his

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Oops, sorry about that. I'm just losing my buttons here implies in his

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In his slides and so that's what I'm a little

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Frustrated with in regard to that, but we're gonna keep going because there's more we're gonna we're still reviewing this

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So then he said that one of the best things that happened if I recall correctly is that they were able to get yet there it is

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The mouse model took a really long time. It took like a year and 60 animals before you could I guess

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Decide whether there was was scraping protein to analyze for but anyway, they got something to work much faster in hamsters

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And I'm still I it's still homework for me to figure out exactly this what the story is on this slide

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But the point would be that after this they now managed somehow this next slide suggests that they got the incubation time bio assay down low enough

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So that you didn't have to waste a lifetime as he said made jokes and people laughed about

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Waste a lifetime trying to wait for this stuff to happen so that you had something that you could use I guess to put in other animals heads

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And try to make the disease move from animal to animal

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So then he tries to purify using detergent extraction nuclei

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Digestion and protonase K digestion and after all of that stuff there's still some

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Pre-on protein present right because it's it's resistant to all of this stuff

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And so then that helped develop this concept that even after they get rid of the the nucleic acids even after they use detergent

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There's still something there that apparently causes this this

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Well, this disease stayed at some point when they injected into the brains of animals

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But already this this started to fall apart a little bit. It seemed already like

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Hand-waving and so then he moves on farther

27:32.880 --> 27:37.820
And he gets to this crucial point here where they're using knockout mice

27:39.720 --> 27:41.720
and

27:41.720 --> 27:45.280
In the well, they're using knockout mice and regular mice

27:45.280 --> 27:49.120
But anyway, the point in this picture was supposedly we could let him say it I guess

27:49.880 --> 27:57.040
Is that here you have the pre-on protein and then here is where you take that protein fraction and you digest it with

27:57.680 --> 28:02.000
Protonasis enzymes to cut the protein up and then essentially everything's gone

28:03.240 --> 28:05.240
but in the

28:05.320 --> 28:08.120
Pre-anagenic state or in the in the scraping state

28:08.520 --> 28:14.560
Then when you digest these proteins which are different proteins apparently then are in lane one even though

28:14.560 --> 28:18.080
This is supposed to be the control and this is supposed to be the experimental group

28:18.080 --> 28:23.120
And then you digest that fraction what you are left with is still a

28:24.080 --> 28:29.480
Fraction, I guess it kind of a similar weight as this one and so then the argument is

28:30.760 --> 28:32.760
that this represents the

28:33.120 --> 28:35.520
Pre-anscrapey form that is

28:36.240 --> 28:42.920
Undigestable by these protonasis that it's gone here because it wasn't present in this fraction in the healthy animal or in the

28:43.200 --> 28:48.440
The un-un manipulated animal we could listen to see what he says there again if you want

28:49.120 --> 28:55.000
Just to see exactly what anybody talks about destroy the protein we destroy the infectivity or every time we destroy the infectivity

28:55.000 --> 28:57.000
the protein was removed or

28:57.320 --> 28:58.840
destroyed and

28:58.840 --> 29:00.360
when we

29:00.360 --> 29:04.240
Eventually figured out what was going on we found that there was a normal form of the protein in all of us now

29:04.240 --> 29:09.520
This is a gel and the proteins migrate and the smaller they are the faster they migrate through this gel this porous material

29:09.520 --> 29:11.280
sort of like jello and

29:11.280 --> 29:12.760
Then we can stain them with antibodies

29:12.760 --> 29:16.200
And so what we found was that the protein was a protein in all of us

29:16.240 --> 29:22.200
Which is a normal form of the pre-an protein and when we treat with enzymes that destroy proteins the protein was completely destroyed

29:22.200 --> 29:24.800
But in the brains of these hamsters that became ill with Scrapey

29:25.000 --> 29:30.320
What we found was that there was both a normal form of the protein and another form of the protein that when we treated with

29:30.320 --> 29:34.160
The enzymes that destroy proteins there was a residual piece and here now this is funny

29:34.160 --> 29:37.440
I didn't catch this the first time but he was using antibodies here

29:37.440 --> 29:44.640
He gee he shows us later in the talk that there are antibodies that bind one and not the other so why do we know that the antibody

29:44.640 --> 29:47.920
He's using here doesn't bind the fraction that's left here

29:49.160 --> 29:54.080
Maybe there is a fraction here, but the antibody doesn't bind it whereas it does bind it in this form

29:56.440 --> 30:00.200
There's lots of weird things happening here because we use antibodies so

30:01.560 --> 30:07.280
The best word I guess I have is laxidazically at this time in science in 2002

30:07.480 --> 30:10.960
we were still holy clueless to the bouquet of

30:11.600 --> 30:19.960
Molecular variation that's found even in some of the best what were presumed monoclonal antibody preparations. It's a really interesting

30:21.120 --> 30:24.440
Signal here too because you know if the resolution is

30:24.960 --> 30:28.880
Like this with all this noise that he doesn't feel like he needs to explain

30:29.520 --> 30:33.800
Then you can already see that something interesting is happening here. So then they say

30:35.480 --> 30:40.320
Something about the structure of the pre-an protein and that then the normal form

30:40.960 --> 30:44.280
it has these three alpha helices and then in the

30:45.240 --> 30:52.560
Infectious not so good form. It has more beta pleated sheets or more beta helices in this region

30:54.000 --> 30:57.600
And then they go on to say that when they digested these guys

30:58.560 --> 31:01.800
They found these pre-an like rods or pre-an rods

31:02.760 --> 31:07.160
According to the guy that he was working with after they cut the N-terminal off of

31:07.880 --> 31:13.200
the pre-an protein in vitro and later this structure was apparently

31:14.440 --> 31:18.640
Compared and considered homologous to amyloid protein

31:20.600 --> 31:27.880
Plaques or or fibros that were found in the brain of amyloid disease or the hundreds many many many diseases

31:28.600 --> 31:32.720
Apparently according to to Stanley that do the amyloid thing

31:32.720 --> 31:40.840
Then he told us about this crystallization that happens when you make enough of it and how they used

31:41.360 --> 31:43.080
x-ray crystallography

31:43.080 --> 31:49.440
To start to study the formation that they make and what formations they can make with one another as subunits

31:50.240 --> 31:57.200
Inside of that crystal and then that allowed them to kind of understand indeed that there was there were these three alpha helices

31:57.600 --> 31:59.680
and confirm that and so

32:00.160 --> 32:07.160
Then he showed us this picture which isn't very unlike the infectious cycle to tell us exactly how this happens

32:07.440 --> 32:10.120
The pre-an protein gene is expressed

32:10.120 --> 32:17.640
The protein is manufactured inside of the Golgi and expressed on the chant on the outside of the membrane and then it can also be

32:18.560 --> 32:20.720
Taken in in some of these

32:21.160 --> 32:26.000
Evaginations and then I don't know at some point. I guess it's something bad can happen

32:26.000 --> 32:28.000
We don't know what it does

32:28.000 --> 32:30.000
Which is really interesting

32:31.520 --> 32:33.520
So then

32:33.560 --> 32:37.200
He told us about this other gene that's in the family

32:37.560 --> 32:42.440
He said that it was very much related to it and that it had the same three alpha helices

32:42.440 --> 32:47.960
But these same three alpha helices only have about a 25% amino acid homology

32:48.360 --> 32:55.440
With the pre-an protein alpha helices, so I met made the point that that doesn't seem very homologous to me

32:55.440 --> 32:56.640
but

32:56.640 --> 33:02.680
because again alpha helices beta pleated sheets and beta

33:04.800 --> 33:12.000
Heloces are all general structures that can be made with chains of amino acids and one is

33:13.120 --> 33:18.040
many different combinations of amino acids can form these these forms and so

33:18.960 --> 33:21.880
the particular shape and form and

33:22.720 --> 33:29.680
Hydrophobicity of each of these alpha helices might be very different depending on the combination, but the the general shape is not so

33:30.920 --> 33:36.360
Decimilar and so it's it's that's the reason why you can go through a sequence and identify that this is an alpha

33:36.360 --> 33:40.760
He was even though it's only 25% the same as this one

33:40.760 --> 33:43.160
It's more of the what repeats when and that kind of thing

33:43.960 --> 33:45.640
and

33:45.640 --> 33:50.760
So that's another gene that they're that he's now kind of saying might be related to this stuff

33:52.200 --> 33:56.200
then he starts talking about crowdsfeld yachob in in families and

33:57.080 --> 33:58.840
sometimes it's

33:58.840 --> 34:00.200
evidence of

34:00.200 --> 34:04.160
preons getting into humans is 20 years or 40 years later

34:04.160 --> 34:10.520
So we could still see the effects of eating preon infected meat 20 or 40 years later

34:10.720 --> 34:16.800
which is very convenient in 2002 because that could actually be right now and and

34:17.440 --> 34:19.080
timed perfectly with

34:19.080 --> 34:21.960
Transfection to cover it up and we could just turn around and say well

34:22.160 --> 34:26.720
We shouldn't have been eating meat for the last 20 years at least that's what he definitely implied

34:27.440 --> 34:30.040
There was also in here some stuff where they were

34:30.720 --> 34:38.320
Bovinizing mice, but it was a little bit of hand waving and nonsense and I still think it was probably over expression of protein rather than

34:39.240 --> 34:44.800
Replacement thereof then he talked about that was where this there it is the bovine the bovine

34:45.600 --> 34:47.600
the bovinized mice

34:48.160 --> 34:50.600
So they over express a bovine

34:52.400 --> 35:00.120
Probably under some kind of conditional promoter they over express the bovine preon protein and then they show that that

35:00.920 --> 35:02.360
makes the mouse

35:02.360 --> 35:08.520
susceptible to the bovine sponge of form encephalopathy, but not the other ones and so

35:09.400 --> 35:12.760
Kinda demonstrates that there's some specificity

35:12.760 --> 35:18.720
to the different agents, but the different agents are all basically coming from the same

35:19.680 --> 35:24.780
Protein, so I'm not really sure, you know, we'd have to go through all these papers to see how

35:26.480 --> 35:32.000
Biologically useful this model is or whether it's really just you know injecting junk in animals heads twice

35:33.000 --> 35:35.000
and

35:35.000 --> 35:39.360
Then we got to the yes

35:39.360 --> 35:46.760
these are some more antibodies and whether they bind or not and this is just showing you that they they use antibodies as a way of

35:47.640 --> 35:51.840
probing whether certain parts of a protein are present or not or whether they're

35:52.560 --> 35:58.120
Available for antibody binding or not and to a certain extent. I think this makes some

35:58.680 --> 36:04.520
Sense, but it would really requires very clever controls and very astute

36:05.320 --> 36:14.320
Alternative experiments to support and so I feel like a lot of times in this talk. It has been used as kind of a hand-waving thing

36:15.240 --> 36:18.640
Here I'm gonna prove to you that these things fold differently

36:19.480 --> 36:24.720
And the way I'm gonna do that is use antibodies that bind and don't bind and I think that's a little bit of

36:25.240 --> 36:31.560
Yeah, anyway, I think that's a little bit sketch then we might be right where we were wanting to be I

36:31.840 --> 36:33.840
Think

36:33.840 --> 36:37.320
Think we might be right where we wanted to be we stopped here because

36:38.600 --> 36:44.400
we were looking at the regular prion protein of the protein in this great escapee form and

36:44.640 --> 36:52.200
How degradation took longer in these neuroblastoma cells and I was kind of angry because I didn't understand how they were

36:52.920 --> 36:56.880
Expressing the same protein that folds in two different ways in these

36:57.760 --> 37:03.640
Separately in these cell lines it seemed to imply that they knew a sequence that was different or something and I didn't understand that

37:04.000 --> 37:06.960
So I said this is a PRPC and defined what is called the house

37:06.960 --> 37:09.160
So I said that we had I had to look into that

37:09.160 --> 37:11.160
So I think that's where we are right now

37:11.160 --> 37:13.960
So there's a few things that just don't really line up

37:13.960 --> 37:19.440
But now we're gonna go into more of the chemistry and messing around and I think we're gonna see more of the same kind of

37:20.160 --> 37:23.200
weird bridges being made that aren't really

37:24.040 --> 37:30.960
supported by very much evidence just conjecture and cartoons, so let's see half life for formation very rapid and

37:31.560 --> 37:33.560
David Borchardt working here in San Francisco

37:34.040 --> 37:39.840
Confirmed that and then showed that the half-life time for degradation is about six hours and that PRP scrapie was made even more

37:39.840 --> 37:42.560
Slowly with a half-time of formation of about three to ten hours now

37:42.560 --> 37:47.360
I had thought that PRP scrapie was complete granite and that it was never degraded

37:47.520 --> 37:52.080
But in the last slide that I showed you this is really represents the degradation of PRP scrapie

37:52.080 --> 37:54.080
the loss of prions from the culture

37:55.160 --> 38:01.100
And so we were able to calculate a number as I mentioned before where 50% of the PRP scrapie disappears of about 30 hours

38:01.960 --> 38:04.560
This has important implications for thinking about all the general

38:04.560 --> 38:07.040
You know it could be that they just stain with these different

38:07.120 --> 38:12.640
Anybodies that they claim are selective for the proteins and when the stain goes away then they say the proteins are gone

38:12.640 --> 38:16.440
If there's some indirect measurement we would have to look into it diseases

38:17.320 --> 38:21.040
It tells us that cells are capable of degrading both PRPC and PRP scrapie

38:21.040 --> 38:26.880
And it raises the question whether PRP scrapie is normally found at very low levels in normal cells and has a physiological function

38:26.880 --> 38:33.040
And that is a very appealing way of thinking about all of this because it makes much more sense than thinking that PRP scrapie is something totally apparent

38:33.560 --> 38:35.960
It raises the question of whether or not we really have an issue

38:35.960 --> 38:42.640
It's a kinetic race between the formation of PRP scrapie and the cells ability to clear PRP scrapie and that when the cell can keep up with the

38:42.680 --> 38:48.720
formation and clear it like it does with other protein all other proteins in fact that when that happens everything is functioning fine

38:48.840 --> 38:53.160
But when the cell gets out of balance see you almost felt like you had to make that point

38:53.680 --> 38:57.200
That all other proteins fold incorrectly and we have to do it

38:57.200 --> 39:01.720
We have to get rid of we have to degrade all other proteins and we do I'm not saying we don't

39:01.720 --> 39:12.880
I'll let I'll go back just so you can hear it again. I didn't interrupt

39:12.880 --> 39:17.240
It's a kinetic race between the formation of PRP scrapie and the cells ability to clear PRP scrapie

39:17.240 --> 39:22.720
And that when the cell can keep up with the formation and clear it like it does with other protein all other proteins

39:22.720 --> 39:25.760
In fact that when that happens everything is functioning fine

39:25.840 --> 39:32.240
See so that's that's the place where we stopped where really the model is and let's let's let's be clear

39:32.560 --> 39:36.080
We want to do the model the model is that

39:37.840 --> 39:40.440
the pre on protein and

39:42.280 --> 39:46.560
Pre on protein folded incorrectly with the SC superscript

39:47.720 --> 39:52.360
The scrapie protein are produced by the same process

39:53.200 --> 39:59.880
But one is takes longer to degrade and so even though maybe smaller

40:01.280 --> 40:02.960
numbers of

40:02.960 --> 40:09.640
This confirmation come out of the ribosome. They take longer to degrade and so the kinetics of degradation

40:10.520 --> 40:13.680
Play into this and that's what can also make the

40:14.480 --> 40:17.400
onset anywhere from 60 days to

40:17.920 --> 40:21.120
to 40 years as he says

40:22.360 --> 40:24.600
And in theory that kind of makes sense

40:24.600 --> 40:32.440
It sounds like a fuse that could have any length of time depending on the exact parameters of by which it burns

40:35.240 --> 40:40.560
It's also a very convenient story that makes a lot of predictions that should have sort of

40:41.160 --> 40:47.040
Easily testable experiments that can grasp or can get can get at those ideas

40:47.480 --> 40:52.840
So let's listen as he develops this idea where again remember pre on protein in its good form and

40:53.520 --> 41:00.680
Pre on protein in its pre on a genic form are present at all times in all healthy animals

41:01.440 --> 41:02.520
and

41:02.520 --> 41:07.880
That it is only the kinetics of degradation and production that over time

41:08.560 --> 41:16.440
Can result in a preponderance of the scrapie form which can then of course cause this fibro formation, etc

41:18.040 --> 41:23.480
So the whole mechanism isn't quite understood yet, but the ticking time bomb part the one

41:24.480 --> 41:32.480
Molecule part doesn't really make sense anymore because according to this story. It's not just one molecule and now the ticking time bomb starts

41:34.080 --> 41:40.040
You see that's a this is a very different model if you're just gonna flip flop between those two models or

41:40.400 --> 41:45.560
If you're gonna say that Stanley Proustner in 2002 did know what he was talking about and

41:46.560 --> 41:49.720
Just one molecule is enough to cause this disease

41:50.520 --> 41:52.520
hmm interesting

41:52.960 --> 41:59.040
But when the cell gets out of balance it can no longer clear PRP scrapie at the rate that it's formed

41:59.040 --> 42:02.040
I'm talking about very very low levels that we can't detect even buying these animal assays

42:02.640 --> 42:08.840
Then something goes awry and we began to accumulate more and more PRP scrapie and eventually the animal gets sick and goes on to die or the human being

42:09.920 --> 42:11.920
Now I promise you a little chemistry at the end

42:12.760 --> 42:15.280
And if you just look down here at chlorpromisine this is Thorazine

42:15.280 --> 42:21.680
This is one of the first anti-psychotic drugs, and this is the structure of it has these three rings and when Carson Korth added one micromolar

42:21.680 --> 42:28.880
This amount he still saw these protease resistant bands this so the different the three bands are the ones with no sugars one sugar chain and two sugar chains

42:28.880 --> 42:31.240
They're showing a little better here. So what is this?

42:33.160 --> 42:38.240
Is that dr. Drew reason a lot of what I've talked about today

42:38.600 --> 42:45.960
Hilarie seems like cyber is only mode right I mean remember in 20 in 2019. I was fully a believer in vaccines

42:45.960 --> 42:52.600
I didn't know about any of this. I thought it was a godly goop. So so this is fabulous because here's what you got here, right?

42:52.600 --> 42:54.600
Here's what you got here

42:54.600 --> 42:56.200
You got a guy

42:56.200 --> 43:04.600
who basically is one of these many people who now who's an old man who's using testosterone and pushing

43:05.600 --> 43:07.280
pharma products

43:07.280 --> 43:14.160
Here you have a guy that from every other lawyer I can tell they don't take him seriously

43:15.000 --> 43:21.040
They don't think his pedigree is any good. They don't think his arguments that he makes are any good and they're pretty sure

43:21.400 --> 43:23.400
There's something up

43:24.600 --> 43:32.040
Like lawyers not me other lawyers people that I trust and people that I don't trust they're all unanimous that this this can't

43:32.360 --> 43:34.360
be someone to take seriously

43:34.560 --> 43:41.840
And this person is a person whose whose daughter was on Alex Jones at least twice

43:42.400 --> 43:46.520
In the run-up the year before the pandemic

43:47.400 --> 43:55.700
Had a million subscribers on YouTube before I guess jokingly threatened to go to the house of the YouTube CEO and kill her or him

43:55.700 --> 44:07.940
And we're supposed to believe that a retired pharma exec who sold her company to Pfizer by the way and was helping them

44:07.940 --> 44:09.940
I guess testing

44:10.140 --> 44:16.660
People before they tested them so that they if they had cardiac problems that they wouldn't be in the trial and you know

44:16.660 --> 44:18.140
I don't know

44:18.140 --> 44:24.900
maybe better ways to read the QP wave or whatever it's called and and and and the whole point is

44:25.220 --> 44:32.180
Is that it just seems like all the people that are managing to get anywhere with regard to getting their message out

44:32.180 --> 44:37.100
I've always been stepping in front of other people. She has stepped in front of Catherine Watt

44:39.020 --> 44:41.780
She has stepped in front of Craig Particopper

44:43.260 --> 44:46.860
She's been on stage with Robert Malone in Sweden

44:48.060 --> 44:50.300
When the pandemic was still hot and heavy

44:51.260 --> 44:53.460
This guy has been the lawyer of

44:54.260 --> 44:55.540
Andrew Huff

44:55.540 --> 45:03.420
The guy who says that he shot over a hundred and fifty rounds into the woods of of the upper Michigan forest surrounding his house

45:03.660 --> 45:05.660
While he was combating the state police

45:11.140 --> 45:17.980
And now we're supposed to believe that this is this is the these are the people on the white horses that are coming to our rescue

45:21.300 --> 45:25.580
Please we can't possibly take this seriously

45:26.620 --> 45:29.540
This isn't even Fox News level serious

45:31.220 --> 45:36.100
And and to give it airtime or to think that oh we got to get their attention

45:36.900 --> 45:45.420
That's playing right into the game even if even if this man in the middle isn't sophisticated enough to know he's being played

45:45.420 --> 45:47.420
I assure you that

45:47.540 --> 45:49.540
This is a play

45:50.300 --> 45:53.140
And it is a play that that was

45:53.660 --> 45:58.340
Either put in place very early ready to go or already

45:58.860 --> 46:04.260
Ready to go and then some like they were this was always where we were gonna be but I don't think that's the case

46:04.580 --> 46:11.420
But these are always the people these were always the people that were gonna be on the stage that there's no question about it

46:12.060 --> 46:15.340
Brett Weinstein was always gonna be on the stage. I

46:15.900 --> 46:17.900
I

46:17.900 --> 46:21.980
Think Robert Malone was likely always gonna be on the stage. I think

46:22.620 --> 46:24.620
Steve Kirsch maybe was

46:25.660 --> 46:27.500
Very early on

46:27.500 --> 46:32.740
Not gonna be but wanted to be and got on the stage. I think there's a lot of people that

46:33.940 --> 46:38.940
Were kind of reluctant at first didn't think that we would be where we are at this stage

46:39.220 --> 46:41.220
Who are on the stage reluctantly?

46:41.460 --> 46:44.700
Once you sign the page, you can't get off. It's a national security

46:45.620 --> 46:47.060
operation and

46:47.060 --> 46:54.420
So now remember if this is the controlled demolition of America that it makes perfect sense that many of these people would be involved

46:54.420 --> 46:56.420
most of them being privately

46:56.940 --> 47:05.100
rich privately okay with the collapse of America privately okay with the gross over inflation of the dollar and

47:08.020 --> 47:10.020
That's the point here is

47:10.260 --> 47:18.180
That the people who are rising over the last four years the people who get censored and then get on tucker and complain about it are all

47:18.660 --> 47:20.500
independently wealthy

47:20.500 --> 47:26.380
Already intimately connected to the very machine that none of us have ever gotten anything from

47:27.740 --> 47:34.300
None of us have ever sold the company none of us have had multiple consulting companies that worked with the DoD Ditra

47:34.540 --> 47:37.580
none of us have ever sat on on on

47:37.980 --> 47:42.380
DARPA grant committees to evaluate DARPA proposals

47:43.180 --> 47:46.060
none of us have ever gotten the benefit of

47:47.540 --> 47:49.540
taxpayer-funded data

47:49.580 --> 47:52.780
From your university to start a company and then sell it

47:56.060 --> 47:58.060
But all of these people have

48:00.260 --> 48:02.260
All of these people have a book

48:08.340 --> 48:14.780
What we're dealing with here is a controlled operation to make sure that you stay focused on

48:16.140 --> 48:22.660
Something that will not prevent the controlled demolition of America will not prevent us from coming together

48:22.660 --> 48:31.140
But we'll instead keep us fighting about things like where the virus came from or what killed people or whether viruses exist at all

48:38.300 --> 48:40.900
There is no way that it is random

48:42.660 --> 48:46.940
That soaf was on Alex Jones three times in

48:47.500 --> 48:52.220
2019 and now we are listening to her mom for three years as

48:52.980 --> 48:54.780
part of the

48:54.780 --> 48:56.140
alternative

48:56.140 --> 49:03.100
COVID narrative that involves a novel virus that killed millions of people that millions more were saved from

49:04.100 --> 49:07.940
That was definitely gained a function or a toxin that was

49:08.500 --> 49:12.460
sprayed on the world by the United States Department of Defense

49:14.140 --> 49:16.140
Which was a great way to

49:16.740 --> 49:18.740
implode America in a way that

49:19.780 --> 49:24.900
Turns everybody on everybody else. It doesn't realize that the military is a victim of this too

49:25.580 --> 49:27.300
the average

49:27.300 --> 49:32.340
Serving soldier is a victim of this too. They have to follow orders

49:32.340 --> 49:34.340
It's the people above

49:34.660 --> 49:41.260
Lieutenant Colonel now those are the people we need to be holding to account. Those are the people who put the mandate out

49:41.940 --> 49:43.940
Who gave the orders down the chain?

49:44.940 --> 49:50.140
The people at the bottom of the chain cannot be blamed for taking the orders or following them

49:50.460 --> 49:55.980
They are victims of this as well and yet. Who does she want us to blame the Department of Defense?

49:55.980 --> 50:06.780
Without any more specificity than that without any more chain of command to the Department of Human Health and Human Services for the

50:07.740 --> 50:10.940
Department of Homeland Security for DITRA

50:11.860 --> 50:13.860
Nothing's State Department. What's that?

50:17.340 --> 50:24.420
And this guy as I said is not a legal scholar is not some kind of courtroom killer

50:26.900 --> 50:33.380
This is a guy who is a very very very below average lawyer

50:35.020 --> 50:37.020
and

50:37.020 --> 50:40.900
He's probably in way over his head. He's probably not even a bad guy

50:44.260 --> 50:46.100
But people

50:46.100 --> 50:47.460
smarter than me

50:47.460 --> 50:53.780
Do not take him seriously and so the idea that either of these two take him seriously that either

50:54.300 --> 50:57.860
Dr. Drew or Sasha take him seriously it begs

50:59.460 --> 51:04.420
I'm I find it dubious. I find it dubious and and I don't think that

51:07.300 --> 51:09.300
Hey, I just don't

51:11.620 --> 51:14.500
I don't buy him. I don't buy him. I think that we are

51:15.300 --> 51:20.740
You need to be very pessimistic about the number of people. I mean look at how much fun she's having

51:20.740 --> 51:25.660
Americans were murdered ladies and gentlemen and

51:27.300 --> 51:34.900
Children are having needles forced upon them and adults over 50 are having needles coerced into them

51:37.300 --> 51:39.780
As we speak by this system

51:41.860 --> 51:47.860
And it is based on this mythology of a novel virus that is not being questioned here at all

51:47.860 --> 51:50.740
I can guarantee it. I mean they're looking how much fun

51:51.540 --> 51:54.820
it's so much fun to be on dr. Drew's show and

51:56.500 --> 51:59.140
Dr. Drew's weed is so good and

52:00.060 --> 52:04.700
Tom Ren's is doing the right thing. He wants to do the right thing. That's all possible. I guess

52:08.060 --> 52:13.940
But I just don't see it I do not see it if he is used he is used he is not

52:18.340 --> 52:23.380
I'm sorry, but I just I don't see it. I don't see it at all. It's unfortunate, but I just don't see it

52:25.620 --> 52:27.620
And i'm not going to subscribe to

52:29.780 --> 52:33.940
To dr. Drew. I don't think it'll get me in anyway. It's too late

52:35.300 --> 52:38.740
Uh, let's finish this. This is our work. This is our work

52:38.740 --> 52:48.260
We're up even up in here

52:49.140 --> 52:51.140
Rugs and this is the structure of it. It has these three rings

52:51.860 --> 52:56.660
And when karstin corth added one micromolar this amount he still saw these protease resistant bands

52:57.140 --> 53:01.460
This so the different the three bands are the ones with no sugars one sugar chain and two sugar chains

53:01.460 --> 53:04.020
They're showing a little better here. So two sugar chains one and none

53:04.660 --> 53:06.500
Or even up in here

53:06.500 --> 53:11.460
When he added five times as much chloropromacy and he couldn't see any and ten times as much he still couldn't see any as you would expect

53:13.380 --> 53:15.940
And when he had done the first experiments and showed them to me

53:15.940 --> 53:20.500
I said go back and look at some of these other psychoactive drugs like how apparel which doesn't do anything in similar concentrations

53:21.060 --> 53:28.180
And he did that now keep in mind what he's talking about here now. He's talking about chemicals that have anti-psychotic

53:29.780 --> 53:33.380
Properties that are used to treat dementia

53:33.380 --> 53:37.300
Demented people

53:38.580 --> 53:43.780
Which is the joke he made at the beginning of the talk that you can go back and see in the previous episode

53:45.540 --> 53:53.620
Think about that for a minute because now he's testing whether or not these compounds have any effect on the presence of or the degradation of

53:54.180 --> 53:57.940
The prion protein which is a really weird thing to test

54:00.260 --> 54:02.260
And he looked at many of them as you see on this chart

54:03.460 --> 54:07.620
And then I said to him karsten why in the world did you come with me to show me the first experiments?

54:08.180 --> 54:10.580
And what the background of karsten corth was that he

54:11.300 --> 54:16.580
In his late 30s had done a psychiatry residency and decided he wanted to go into molecular biology and began to work with a former postdoctoral fellow of mine

54:16.580 --> 54:23.860
Bruno ersh in Zurich and when Bruno left the university of Zurich to start a biotech company karsten wanted to stay in academic medicine and came here

54:24.500 --> 54:29.940
And I had been telling karsten for about a year and a half that he should solve one of the major problems of psychiatry like schizophrenia or bipolar disorders or autism

54:30.820 --> 54:33.620
And he looked at me and he said to answer my question

54:33.620 --> 54:34.660
Why did you do these experiments?

54:34.660 --> 54:37.940
And he said well you've been telling me to connect my work on prions with psychiatry for two years now

54:37.940 --> 54:40.580
And so I threw in chlorpromazine or thorazine into the culture

54:40.980 --> 54:47.380
Well the karsten's credit he went back and began to look at the literature in detail and all of this really begins with the German dye industry in

54:47.380 --> 54:53.220
Paul Erlich in 1891 who was using methylene blue as a weak anti-malarial substance and then through this pathway eventually these

54:53.620 --> 54:56.780
These more potent anti-malarials were synthesized and chlorpromazine

54:56.860 --> 55:02.540
Which really had marked anti-psychotic effects and chlorpromazine was the first drug to begin to empty out the insane asylums throughout the world

55:04.460 --> 55:06.940
In the 1930s the Germans synthesized

55:07.460 --> 55:10.620
Quinecrin and this turned out to be a potent anti-malarial drug

55:10.620 --> 55:12.380
But it had many more side effects than quinine

55:12.380 --> 55:16.660
But there wasn't enough quinine for use in World War two because it's extracted from the bark of the jacona tree

55:16.660 --> 55:20.660
And there wasn't a chemist in the world who was smart enough to figure out the structure and then how to synthesize it

55:20.900 --> 55:24.380
Until Robert Woodward did this at Harvard in the late 1940s

55:25.300 --> 55:30.900
So quininecrin was given to thousand I should say three million young Americans in World War two

55:30.900 --> 55:32.900
So we know a lot about quininecrin pharmacology

55:32.900 --> 55:37.660
And what karsten corth found was that quininecrin was ten times more potent than chlorpromazine

55:38.660 --> 55:41.660
So each so instead of this being a ten not being a five

55:41.660 --> 55:44.900
That's a one and point five and point one and the structure is very similar

55:46.340 --> 55:51.300
And when karsten corth treated these cultures for six days if he added enough chlorpromazine

55:51.380 --> 55:57.220
He found that there was no return of these protease resistant bands. This is this is the band as I said before that has two sugar chains one and none

56:00.460 --> 56:05.900
And because quininecrin has a 70-year history of the treatment of parasitic diseases the toxicities are well documented

56:05.980 --> 56:10.780
Bruce Miller and Michael Geshwin and I and a number of other people have been involved in this in the School of Pharmacy here

56:12.500 --> 56:15.300
We applied for an IND a new drug

56:16.100 --> 56:21.860
Investigation license from the FDA and we were able to skip what are called phases one and two of these typical clinical trials which amount to

56:22.780 --> 56:28.260
Tens of millions of dollars normally and we began to load patients with one gram followed by 300 milligrams daily

56:28.260 --> 56:32.260
And in a minority of patients what we've seen we believe and it's not just us

56:32.260 --> 56:34.700
It's many neurologists who are in contact with us throughout the world

56:34.700 --> 56:40.420
But we've not seen all these patients because we're hoping that we will get an NIH study funded over the next four or five months

56:40.420 --> 56:44.980
And that this study will provide us the funding we need to really look at all the patients throughout the world who are on quininecrin

56:45.340 --> 56:50.580
But it's our impression in that of a number of other neurologists that in a minority of CJD patients the disease is slowed by quininecrin

56:50.580 --> 56:54.140
And in a few CJD patients with quininecrin who have died later

56:54.140 --> 56:59.780
Steve Diarmidus found that there are lower levels of PRP scraping they seem to be reduced to almost zero

57:00.580 --> 57:03.980
Compared to what is generally found now the problem is that we have so few patients in this group

57:04.300 --> 57:09.300
We've been able to obtain these autopsies that we just don't know at this point the second issue is that

57:10.180 --> 57:12.100
In addition to not knowing

57:12.140 --> 57:17.140
There are some patients where we even have more doubts. These are the patients who get dramatically better on quininecrin and those patients

57:17.140 --> 57:19.420
I think it's good scientists. We're not even sure that they have CJD

57:21.260 --> 57:24.500
So we need a much more controlled study we don't want to fool ourselves

57:25.020 --> 57:29.180
Because you can't know that they have CJD until after they die, right?

57:29.180 --> 57:32.540
So that's a really actually very nice admission

57:32.540 --> 57:35.580
So what I've been telling you tonight is that sporadic and infectious forms of these diseases

57:35.580 --> 57:38.980
It's the wild type or normal form of PRPC that's converted into PRP scraping

57:39.020 --> 57:44.580
So this is an infectious form of the disease that's transmission from an animal to a man or from man-to-man or animal to animal

57:44.580 --> 57:48.300
In the sporadic form of the disease accounts for 90 85 to 90 percent of all cases

57:48.300 --> 57:51.940
We think it's a spontaneous conversion of PRPC into PRP scraping or as I told you before

57:51.940 --> 57:56.420
This is a kinetic race and that there are small amounts of PRP scraping all of us that are normally cleared

57:56.420 --> 57:58.260
So he has two models

57:58.260 --> 58:05.660
One is that it just misfolds and then you're screwed and the other one is is that it's always misfolding and it's a race to get rid of the degradation

58:06.100 --> 58:08.100
And are they gonna test it?

58:08.220 --> 58:13.780
Are they gonna use that to make any predictions either one of those models make any predictions that are testable?

58:13.780 --> 58:19.660
Are you just gonna leave it sit right there? Those are two very very mutually exclusive

58:22.980 --> 58:29.060
Powerful models they make very powerful predictions about how this should or should not work

58:29.900 --> 58:31.900
It's very bizarre

58:31.980 --> 58:36.060
In the inherited forms of these diseases, it's a germline mutation passed from parental offspring

58:37.820 --> 58:42.940
There are a whole series of new ideas that have come out of this the fact that that prions are infectious proteins is totally new

58:42.940 --> 58:49.340
This is unlike all other infectious agents prions cause brain degeneration. They cause sporadic genetic and infectious forms of these diseases

58:49.340 --> 58:52.980
There's no other disease paradigm in which you have both genetic and infectious diseases

58:53.500 --> 58:58.740
And prions are the most well understood among all the neurodegenerative diseases which include of course Alzheimer's disease and Parkinson's disease

58:58.900 --> 59:06.580
So he's saying that they actually understand prion diseases better than the others understand Alzheimer's and Parkinson's. Wow

59:06.580 --> 59:08.580
I mean wow

59:09.140 --> 59:13.340
That's impressive because I don't think I'm convinced not from this talk

59:14.020 --> 59:20.980
I'm not convinced that prions are infectious proteins yet. I'm not convinced that they cause brain degeneration

59:20.980 --> 59:25.420
I think they they can trigger it, but they don't do it

59:26.300 --> 59:31.980
Prions cause sporadic genetic and infectious diseases and humans and animals we think

59:32.300 --> 59:36.620
It's a hypothesis that has definitely not been proven as far as I can tell

59:36.940 --> 59:43.820
Not if you have to inject it into the brain of the animal and they don't do it by ingestion because all of the things that we see

59:44.380 --> 59:50.580
With kuru is ingestion with with the cattle was feeding cattle other cattle even said it

59:51.460 --> 59:53.460
Shh

59:54.340 --> 59:57.100
There are many thousands of times more common than the prion diseases

59:57.700 --> 01:00:01.100
Now it's the discovery of prions in many other new findings which allows us now

01:00:01.100 --> 01:00:04.700
I think to define neurodegenerative diseases in terms of their cause not the effect

01:00:05.060 --> 01:00:10.860
So we can I think we all most people would agree now that degenerative diseases of the nervous system are disorders of a parent protein processing

01:00:10.860 --> 01:00:16.740
Wow, so I think most people would agree that is that an illusion of consensus to you or is am I what?

01:00:16.740 --> 01:00:23.180
Wow, that is spectacular the proteins are being processed abnormally

01:00:24.260 --> 01:00:26.820
They give you a little idea of the numbers of cases in the United

01:00:26.820 --> 01:00:29.020
So we have 400 cases of prion disease annually in the US

01:00:29.020 --> 01:00:35.300
But there are four million people without Alzheimer's disease about a million with Parkinson's disease and about 20,000 with ALS or Lou Gehrig's disease

01:00:36.100 --> 01:00:38.100
So these are huge numbers

01:00:38.740 --> 01:00:44.380
Good night, Jeff. No, there are many many similarities between these diseases what we see are these abnormal protein deposits

01:00:44.380 --> 01:00:47.260
I showed you PRP scraping in the brain and I showed you these PRP amyloid plaques

01:00:47.380 --> 01:00:51.980
Well, the brains look very similar if we're not using if we use antibodies, but with these are different proteins now

01:00:51.980 --> 01:00:53.900
But the structures look very similar in Alzheimer's disease

01:00:54.260 --> 01:00:56.580
There's slightly different in Parkinson's disease and ALS

01:00:56.780 --> 01:00:58.780
But what's so interesting about all of these is that?

01:00:59.260 --> 01:01:06.220
The mutations in the genes that we find in familial forms of the disease encode the proteins that are found in these protein deposits

01:01:06.220 --> 01:01:08.220
Except here. This is less clear with ALS

01:01:09.220 --> 01:01:15.020
So the accumulation of misprocessed proteins causes the nervous system malfunction resulting in problems such as dementia

01:01:15.020 --> 01:01:18.100
We're back to this word Alan difficulty moving and weakness and

01:01:19.140 --> 01:01:25.340
Preventing the accumulation of you know, I'm in theory all down with that because one of the reasons why he says is because

01:01:25.940 --> 01:01:31.980
The protein plaques form and then also a lot of times that same protein has some mutation

01:01:32.540 --> 01:01:37.700
Which seems to sort with these familial disorders and to the extent to which that's true

01:01:38.140 --> 01:01:44.620
That could be useful. But again, remember that's not true with amyloid anymore. They don't think that's the case anymore

01:01:45.020 --> 01:01:50.180
They went crazy on it, but then they found out one of these papers wasn't right

01:01:51.180 --> 01:01:57.020
And so that just recently happened, right? Maybe we should all look into that a little bit so we understand exactly

01:01:57.900 --> 01:02:05.420
How much of this, you know, amyloid disease amyloid beta is is amyl is Alzheimer's disease is true or not a

01:02:07.020 --> 01:02:15.460
Lot of these are also just their observations of correlation. Yes, they're there, but are they present? Are they responsible? Are they?

01:02:16.540 --> 01:02:19.020
Downstream consequences of whatever's going on here

01:02:19.020 --> 01:02:22.980
I don't think we understand these as well as he's in these protein deposits, but I agree

01:02:22.980 --> 01:02:28.860
I still agree that it has to do with these proteins perhaps misfolding. That's okay with me, but again

01:02:30.500 --> 01:02:36.180
Pre-on proteins are we're supposed to be told that well, you know, you can engineer a spike protein it can have

01:02:37.060 --> 01:02:39.220
pre-onogenic sequences and that

01:02:39.740 --> 01:02:47.820
This kind of thing can happen now. That's not the same as this. These are very specific proteins that again, we have not

01:02:47.820 --> 01:02:56.780
Just because that sequence is different have we demonstrated that those are the so that's all all this work needs to be done

01:02:56.780 --> 01:02:58.780
It's less clear with ALS

01:03:00.140 --> 01:03:05.180
So the accumulation of misprocessed proteins causes the nervous system malfunction resulting in problems such as dementia

01:03:05.180 --> 01:03:08.180
We're back to this word on difficulty moving and weakness and

01:03:09.300 --> 01:03:15.620
Preventing the accumulation of these misprocessing protein provide proteins provides I think for the first time a rational approach to treating degenerative diseases

01:03:15.620 --> 01:03:24.100
Yes, so and and so we've done lots of things to get rid of the amyloid beta to get rid of these plaques and it doesn't help these people

01:03:25.980 --> 01:03:27.820
It oftentimes makes it worse

01:03:27.820 --> 01:03:33.700
It's not clear that this is the way to go and the only way to do that is with an immune response of course, which is again

01:03:34.500 --> 01:03:37.220
Something we're not prepared to augment nervous system

01:03:38.780 --> 01:03:40.780
There's a little summary of CJD

01:03:41.660 --> 01:03:46.300
And what went on as I told you I my introduction to this was a patient in 1972 here at UCSF

01:03:46.300 --> 01:03:52.780
And that it was 1921 when six patients were described and this disease was thrown into a waste basket a degenerative disorders of a nervous system

01:03:52.980 --> 01:03:58.380
But it came out of the waste basket in 1968 when Carlton Gajasek and Joe Gibbs working at the NIH along with a number of collaborators

01:03:58.580 --> 01:04:01.020
Transmitted the disease into apes and later into monkeys

01:04:03.180 --> 01:04:06.380
Preons and how did they do that they injected it directly in the brain?

01:04:06.380 --> 01:04:13.020
I imagine like, you know some preparation unlike all other infectious pathogens viruses, viroids, bacteria, fungi, parasites

01:04:13.020 --> 01:04:17.220
All of which multiply by having an RNA or DNA genome direct the synthesis

01:04:17.420 --> 01:04:23.960
Interesting that they don't say anything about phage here even though that's one of the most common forms of viruses not one

01:04:24.820 --> 01:04:31.220
No mention of bacteriophage here at all. That is a gigantic red flag

01:04:32.220 --> 01:04:39.220
No mention of bacteriophage here at all. Why would I care about bacteriophage? Well, let's see. Let's get out of this

01:04:40.220 --> 01:04:42.220
And let's go back to the beginning

01:04:43.220 --> 01:04:45.220
Let's take a look at this

01:04:46.220 --> 01:04:48.220
And current slide just to give you

01:04:50.220 --> 01:04:52.220
An example of what's going on here

01:04:52.220 --> 01:04:59.220
There's a bacteriophage right there on the third live podcast at the beginning of the pandemic of the Dark Horse podcast

01:04:59.220 --> 01:05:04.220
with Brett Bandana and glasses himself

01:05:05.220 --> 01:05:07.220
And right there

01:05:07.220 --> 01:05:13.220
Conspicuously at the front of the podcast is a coffee cup with a bacteriophage on it

01:05:13.220 --> 01:05:20.220
Isn't that weird because it doesn't seem like he really doesn't think that bacteriophages are actually a thing

01:05:20.220 --> 01:05:26.220
Phages are maybe he goofs it in with the viruses, but that would be very disingenuous because

01:05:26.220 --> 01:05:28.220
Phages are everywhere

01:05:30.220 --> 01:05:37.220
Even the no virus people even the no virus people acknowledge that bacteriophages exist isn't that cool

01:05:37.220 --> 01:05:41.220
Isn't that funny and he doesn't exogenous at all

01:05:41.220 --> 01:05:46.220
Strange the progeny pathogens. It's only prions which contain only a protein

01:05:46.220 --> 01:05:50.220
And they co-opt a normal form of that protein to produce more of the misfolded form

01:05:50.220 --> 01:05:52.220
PRP scraping

01:05:52.220 --> 01:05:55.220
Now all of this like what I'm telling you seem like science fiction to a lot of people

01:05:56.220 --> 01:05:58.220
And about seven or eight years ago

01:05:58.220 --> 01:06:02.220
I was a meeting in New Mexico and I was hearing everything that I was been saying

01:06:02.220 --> 01:06:04.220
But it was being said by somebody else

01:06:04.220 --> 01:06:08.220
And I looked at a good friend of mine, Hilary Keprowski, and I said Hilary this is really unbelievable

01:06:08.220 --> 01:06:11.220
This guy even thinks he'd found all of this and Hilary said

01:06:11.220 --> 01:06:15.220
I'm sorry, what did you just what excuse me what? Holy shit, what?

01:06:15.220 --> 01:06:18.220
Did you hear that Mark?

01:06:18.220 --> 01:06:20.220
Mark?

01:06:20.220 --> 01:06:23.220
Did you hear what he just said?

01:06:23.220 --> 01:06:25.220
Holy shit balls

01:06:25.220 --> 01:06:28.220
I mean this is red alert time

01:06:28.220 --> 01:06:31.220
And Hilary Keprowski and I said Hilary this is really unbelievable

01:06:31.220 --> 01:06:32.220
What?

01:06:32.220 --> 01:06:34.220
Seriously what?

01:06:34.220 --> 01:06:35.220
Here we go

01:06:35.220 --> 01:06:37.220
And I was hearing everything that I had been saying

01:06:37.220 --> 01:06:39.220
But it was being said by somebody else

01:06:39.220 --> 01:06:42.220
And I looked at a good friend of mine, Hilary Keprowski, and I said

01:06:42.220 --> 01:06:44.220
Hilary this is really unbelievable

01:06:44.220 --> 01:06:45.220
What?

01:06:45.220 --> 01:06:47.220
Seriously what?

01:06:47.220 --> 01:06:48.220
Here we go

01:06:48.220 --> 01:06:50.220
And I was hearing everything that I had been saying

01:06:50.220 --> 01:06:52.220
But it was being said by somebody else

01:06:52.220 --> 01:06:54.220
Hilary

01:06:54.220 --> 01:06:57.220
My good friend Hilary Keprowski

01:06:59.220 --> 01:07:03.220
Mark Coolax got some information and stories and connections

01:07:03.220 --> 01:07:05.220
Hilary Keprowski

01:07:05.220 --> 01:07:07.220
Stanley Plotkin

01:07:09.220 --> 01:07:12.220
This goes back right to the

01:07:12.220 --> 01:07:17.220
I mean all these people, Gallo, they're all in the same little group of white haired men or whatever

01:07:17.220 --> 01:07:19.220
It's absolutely incredible

01:07:19.220 --> 01:07:21.220
And all of this

01:07:21.220 --> 01:07:23.220
And Hilary said I've got a slide for you, I'll send it to you

01:07:23.220 --> 01:07:26.220
So he sent me this slide about the four stages of adopting a new idea

01:07:26.220 --> 01:07:27.220
The reaction at first is it's impossible

01:07:27.220 --> 01:07:30.220
Second, maybe it's possible but it's weak and uninteresting

01:07:30.220 --> 01:07:31.220
Third, it's true and I told you so

01:07:31.220 --> 01:07:33.220
And the fourth one you can read

01:07:33.220 --> 01:07:35.220
Now there's another way of thinking about this

01:07:35.220 --> 01:07:39.220
And Lou Thomas, who was the director at Sloan Kettering in New York for many years

01:07:39.220 --> 01:07:40.220
was also

01:07:40.220 --> 01:07:44.220
Now he's quoting a director from Sloan Kettering

01:07:44.220 --> 01:07:47.220
Are you giving me, is this a joke?

01:07:48.220 --> 01:07:52.220
I mean what is happening here is this some kind of Christmas gift

01:07:52.220 --> 01:07:55.220
I never thought I would get to open what's going on

01:07:55.220 --> 01:07:57.220
There's another way of thinking about this

01:07:57.220 --> 01:08:00.220
And Lou Thomas, who was the director at Sloan Kettering in New York for many years

01:08:00.220 --> 01:08:02.220
was also a brilliant writer

01:08:02.220 --> 01:08:06.220
And in a book called Lives of the Cell in 1974 he wrote an essay about research

01:08:06.220 --> 01:08:08.220
And these are a couple paragraphs

01:08:08.220 --> 01:08:11.220
Somehow the atmosphere has to be set so that a disquieting sense of being wrong

01:08:11.220 --> 01:08:13.220
is the normal attitude of the investigators

01:08:13.220 --> 01:08:15.220
It has to be taken for granted that the only way in is by writing the

01:08:15.220 --> 01:08:17.220
unencumbered human imagination

01:08:17.220 --> 01:08:20.220
With a special rigor required for recognizing that something can be highly improbable

01:08:20.220 --> 01:08:23.220
May be almost impossible and at the same time true

01:08:23.220 --> 01:08:26.220
Locally, a good way to tell how the work is going is to listen in the corridors

01:08:26.220 --> 01:08:29.220
If you hear the word impossible, spoken with an expletive, followed by laughter

01:08:29.220 --> 01:08:32.220
You will know somebody's orderly research plan is coming along nicely

01:08:32.220 --> 01:08:34.220
Now that's a lot of words

01:08:34.220 --> 01:08:37.220
And if you're Winston Churchill you can describe all this in many fewer words

01:08:37.220 --> 01:08:39.220
This is 1936 in the House of Parliament

01:08:39.220 --> 01:08:42.220
He's talking about Hitler and evaluating the Rhineland

01:08:42.220 --> 01:08:44.220
And he says to Stanley Baldwin in the House of Commons

01:08:44.220 --> 01:08:46.220
Men occasionally stumble across the truth

01:08:46.220 --> 01:08:48.220
But most pick themselves up and hurry off as if nothing had happened

01:08:48.220 --> 01:08:50.220
And with that I'll end, thank you

01:08:50.220 --> 01:08:54.220
So the question is do prions trigger the immune system?

01:08:54.220 --> 01:08:55.220
And the answer is no

01:08:55.220 --> 01:08:59.220
And the reason that we think that they don't is that PRPC is present in all of us

01:08:59.220 --> 01:09:05.220
And we are tolerant to antibodies and also to immune cells that specifically recognize PRPC

01:09:05.220 --> 01:09:07.220
And there are very few regions on PRPC

01:09:07.220 --> 01:09:10.220
In fact we've not been able to identify any looking for more than ten years now

01:09:10.220 --> 01:09:13.220
That are present on PRPC to which antibodies are formed

01:09:13.220 --> 01:09:15.220
That are not present on PRPC

01:09:15.220 --> 01:09:18.220
We found others, as I told you about before, where a region is exposed on PRPC

01:09:18.220 --> 01:09:20.220
But now becomes buried in PRPC

01:09:20.220 --> 01:09:22.220
But that doesn't generate a new antigenic region

01:09:22.220 --> 01:09:25.220
Wow, think about how much of a claim that is

01:09:25.220 --> 01:09:28.220
That goes against everything that we know about the immune system

01:09:28.220 --> 01:09:34.220
That it can't make antibodies specific for prion protein scrappy

01:09:34.220 --> 01:09:37.220
It can only make antibodies that recognize both

01:09:37.220 --> 01:09:41.220
It can make antibodies that don't recognize prion scrappy

01:09:41.220 --> 01:09:42.220
But they don't

01:09:42.220 --> 01:09:45.220
That's an incredible claim, that is an abs

01:09:45.220 --> 01:09:48.220
And you heard me ask that question earlier in the talk

01:09:48.220 --> 01:09:51.220
Like why don't they make antibodies that I think I asked that in the first half

01:09:51.220 --> 01:09:53.220
Holy cow

01:09:53.220 --> 01:09:54.220
There can be an immune response

01:09:54.220 --> 01:09:57.220
And in fact a tremendous step forward in making all of these antibodies

01:09:57.220 --> 01:10:01.220
Was created when a collaborative study that we were involved in

01:10:01.220 --> 01:10:03.220
With Charles Weissman and Zurich produced knockout mice

01:10:03.220 --> 01:10:06.220
In which the prion protein gene of a mouse could be knocked out

01:10:06.220 --> 01:10:08.220
These mice are totally resistant to prion disease

01:10:08.220 --> 01:10:10.220
And when we immunize these mice

01:10:10.220 --> 01:10:16.220
So what does the prion protein do if you can knock the protein out and the mouse is fine?

01:10:16.220 --> 01:10:19.220
Because that's not true for very many proteins

01:10:19.220 --> 01:10:22.220
Strange, huh?

01:10:22.220 --> 01:10:25.220
With the prion protein they form huge numbers of antibodies

01:10:25.220 --> 01:10:29.220
In contrast to normal mice which form very few or no antibodies

01:10:29.220 --> 01:10:32.220
And if I'm no antibodies, if it's a mouse prion protein

01:10:32.220 --> 01:10:34.220
Are you hearing this shit?

01:10:34.220 --> 01:10:38.220
He's telling you that when that animal doesn't have that gene

01:10:38.220 --> 01:10:41.220
That they produce more antibodies to the prion protein

01:10:41.220 --> 01:10:46.220
Which makes them un-susceptible to the prion protein

01:10:49.220 --> 01:10:53.220
He's telling you that antibodies play a role in

01:10:58.220 --> 01:11:01.220
But they've been unable to generate antibodies to the prion protein

01:11:01.220 --> 01:11:03.220
That's specific for the prion protein

01:11:03.220 --> 01:11:08.220
They're just generating antibodies to the endogenous epitopes

01:11:08.220 --> 01:11:11.220
That are exposed in the endogenous form

01:11:11.220 --> 01:11:14.220
Do you see the hand waving is extraordinary?

01:11:14.220 --> 01:11:19.220
I do not believe the papers support these as being firm conclusions

01:11:19.220 --> 01:11:25.220
But it's extraordinary the kind of exceptional biology

01:11:25.220 --> 01:11:28.220
The number of exceptions that we need to make

01:11:28.220 --> 01:11:31.220
In order for this to be true

01:11:35.220 --> 01:11:37.220
Now is these mice with the prion protein

01:11:37.220 --> 01:11:39.220
They form huge numbers of antibodies

01:11:39.220 --> 01:11:42.220
In contrast to normal mice which form very few or no antibodies

01:11:42.220 --> 01:11:46.220
That is a absolute

01:11:46.220 --> 01:11:48.220
It's a mouse model of the disease

01:11:48.220 --> 01:11:51.220
That he's saying that if you don't have the prion protein

01:11:51.220 --> 01:11:54.220
Then you can make antibodies to the scraping protein

01:11:54.220 --> 01:11:56.220
And then you won't get it

01:11:56.220 --> 01:12:00.220
And so one of the reasons and the way to understand

01:12:00.220 --> 01:12:04.220
That this works is that we could respond to you here

01:12:04.220 --> 01:12:06.220
Wait, it's coming, you see

01:12:06.220 --> 01:12:10.220
They're going to treat prion disease with antibodies

01:12:10.220 --> 01:12:12.220
That's what he's proposing here

01:12:12.220 --> 01:12:15.220
And that we should use money and grant proposals

01:12:15.220 --> 01:12:19.220
To find the antibodies which we could use to fight prion disease

01:12:19.220 --> 01:12:21.220
Antibodies, you know antibodies

01:12:21.220 --> 01:12:24.220
The things that they fight all these other diseases with

01:12:24.220 --> 01:12:28.220
That they want to produce as the perfect

01:12:28.220 --> 01:12:32.220
Inject it in your soldiers and your immune for 30 days

01:12:32.220 --> 01:12:35.220
Kind of thing, it's a little cludgy but it works

01:12:35.220 --> 01:12:38.220
And if I'm no antibodies if it's a mouse prion protein

01:12:38.220 --> 01:12:40.220
If it's a human they might form one

01:12:40.220 --> 01:12:41.220
So the immune system

01:12:41.220 --> 01:12:45.220
So they could easily use an mRNA to generate the prion antibodies

01:12:45.220 --> 01:12:48.220
That they say are found in this mouse

01:12:48.220 --> 01:12:51.220
But aren't found in any animals that have the prion protein

01:12:51.220 --> 01:12:53.220
Then it would be a cell protein

01:12:53.220 --> 01:12:55.220
So, wow!

01:12:55.220 --> 01:12:57.220
Quiet in these diseases

01:12:57.220 --> 01:13:00.220
Well, alright, so the question is very technical

01:13:00.220 --> 01:13:03.220
Is the normal form of the prion protein the kinetic product

01:13:03.220 --> 01:13:05.220
Or a kinetically trapped molecule and that

01:13:05.220 --> 01:13:09.220
This scraping form is a thermodynamically more stable protein

01:13:09.220 --> 01:13:12.220
And the answer is probably yes, but we're not sure

01:13:12.220 --> 01:13:16.220
So the normal form of the prion protein is on the surface

01:13:16.220 --> 01:13:19.220
And that's where it's converted into PRP scraping

01:13:19.220 --> 01:13:21.220
And how much of it remains there we don't know

01:13:21.220 --> 01:13:24.220
In some experiments by Stevie Arman where he fractionates these cells

01:13:24.220 --> 01:13:27.220
So he grinds them up and looks for the membrane fraction that's found on the surface

01:13:27.220 --> 01:13:30.220
He finds as much as 60% of the scraping form

01:13:30.220 --> 01:13:33.220
The abnormal form is in the plasma membrane fraction

01:13:33.220 --> 01:13:36.220
Others suggest that it's much less than that, so I don't really know

01:13:36.220 --> 01:13:38.220
But he's probably right

01:13:38.220 --> 01:13:40.220
So the question is what is the mechanism of action of quinocrine?

01:13:40.220 --> 01:13:43.220
And how does it work on patients with CJD and new variants CJD?

01:13:43.220 --> 01:13:44.220
And the answer is we don't know

01:13:44.220 --> 01:13:46.220
Initially I thought what we should do is spend a lot of time

01:13:46.220 --> 01:13:48.220
Several years probably to track that down and understand it

01:13:48.220 --> 01:13:50.220
Before we would do anything further

01:13:50.220 --> 01:13:52.220
But when I realized that the concentrations were close

01:13:52.220 --> 01:13:54.220
Probably only off by a factor of 10 to 50

01:13:54.220 --> 01:13:56.220
From what an ideal drug would be

01:13:56.220 --> 01:13:59.220
We decided to spend a lot of effort starting giving this to people

01:13:59.220 --> 01:14:03.220
But we're also now slowly starting to investigate the mechanism of action

01:14:03.220 --> 01:14:05.220
I'm sure many other people are doing that too

01:14:05.220 --> 01:14:10.220
Alright, so TSE is a term called transmissible spongiform encephalopathy

01:14:10.220 --> 01:14:13.220
It's a term I don't particularly like, but maybe that's because other people use it all the time

01:14:13.220 --> 01:14:16.220
And the reason I don't like it is that many of these diseases

01:14:16.220 --> 01:14:18.220
There's very little spongiform change

01:14:18.220 --> 01:14:22.220
But this is a term that really refers to the diseases caused by prions specifically

01:14:22.220 --> 01:14:26.220
And the other neurodegenerative diseases are not classified as prion diseases

01:14:26.220 --> 01:14:29.220
Or as TSE diseases

01:14:29.220 --> 01:14:31.220
They're classified as neurodegenerative diseases

01:14:31.220 --> 01:14:33.220
For instance Alzheimer's disease is distinguished

01:14:33.220 --> 01:14:36.220
From the prion diseases by the fact that there's a different set of proteins that are involved

01:14:36.220 --> 01:14:39.220
And all attempts to really transmit the disease have failed so far

01:14:39.220 --> 01:14:42.220
That doesn't mean it won't be transmissible in the proper animal model

01:14:42.220 --> 01:14:44.220
But it's not transmissible in a natural setting

01:14:45.220 --> 01:14:47.220
See, they're trying to transmit it though

01:14:47.220 --> 01:14:49.220
Think about that for a second

01:14:53.220 --> 01:14:56.220
And why would they be doing that? Because they're testing this model

01:14:56.220 --> 01:15:00.220
Or they're trying to find examples that seem to indicate that this model would work

01:15:00.220 --> 01:15:02.220
How do they test it? They probably inject the shit

01:15:02.220 --> 01:15:04.220
It's crazy

01:15:04.220 --> 01:15:08.220
I don't know how the spongiform change comes about

01:15:08.220 --> 01:15:11.220
What we find is that the vacuals

01:15:12.220 --> 01:15:14.220
That the more prp scraper there is, the more vaculation there is

01:15:14.220 --> 01:15:16.220
So this is correlation between prp scrapers

01:15:16.220 --> 01:15:18.220
They want nothing to do with the immune system

01:15:18.220 --> 01:15:20.220
If they had anything to do with the immune system

01:15:20.220 --> 01:15:23.220
It's immediately a black box that they can't penetrate

01:15:23.220 --> 01:15:25.220
So they have to stay away from it

01:15:25.220 --> 01:15:29.220
How is the spongiform tissue phenotype formed?

01:15:29.220 --> 01:15:31.220
They don't know, of course it's the immune system

01:15:31.220 --> 01:15:34.220
Excuse me, prp scraped deposition and the vacuals that are formed

01:15:34.220 --> 01:15:37.220
But the mechanism by which the vacuals are formed, I don't understand

01:15:37.220 --> 01:15:40.220
Something happens to the signaling mechanisms in the cells

01:15:40.220 --> 01:15:43.220
And whether that happens because prp scrapes on the surface

01:15:43.220 --> 01:15:48.220
Or whether it's deep in the cell and it mucks up the signaling mechanisms

01:15:48.220 --> 01:15:50.220
I don't know, that's a very simplistic answer

01:15:50.220 --> 01:15:52.220
Who a very complicated question, but I can't answer it

01:15:52.220 --> 01:15:55.220
So the question is, what is the function of prp?

01:15:55.220 --> 01:15:58.220
We all have a gene for prp, we all make the protein, prpc

01:15:58.220 --> 01:16:01.220
And what is its function and the answer is we don't know its function

01:16:01.220 --> 01:16:03.220
And we don't know the function of its brother or sister, papal

01:16:03.220 --> 01:16:05.220
We just don't know

01:16:06.220 --> 01:16:13.220
No, so the question is, why is it that in Britain

01:16:13.220 --> 01:16:16.220
People with new variants CJD are in their teens and early 20s

01:16:16.220 --> 01:16:18.220
For the most part, and the answer is we don't have any idea

01:16:18.220 --> 01:16:22.220
For a long time I thought that this was really a clue to the fact that

01:16:22.220 --> 01:16:25.220
Disease was unconnected to the cows and that there was some other mechanism

01:16:25.220 --> 01:16:29.220
But I threw that idea away once we had all this transgenic mouse data

01:16:29.220 --> 01:16:32.220
And the answer is I don't have any idea why they're so young

01:16:32.220 --> 01:16:33.220
I just don't know

01:16:33.220 --> 01:16:35.220
One patient who's 70, another who's 50

01:16:35.220 --> 01:16:37.220
But the vast majority of these people are under 40

01:16:39.220 --> 01:16:43.220
So the first part of this question is, how did this all start in cows?

01:16:43.220 --> 01:16:47.220
And the second question is, how do prions make it through your brain from your gut?

01:16:47.220 --> 01:16:50.220
So how did prion disease start?

01:16:50.220 --> 01:16:54.220
And I think most people were reasonably well convinced that it began with sheep

01:16:54.220 --> 01:16:57.220
Because scrapes and stomach in Britain, it's been there for hundreds of years

01:16:57.220 --> 01:17:00.220
And it came from the sheep, but nobody knows the exact statistics

01:17:00.220 --> 01:17:03.220
People who are farmers tend to get rid of their animals when they're not doing well

01:17:03.220 --> 01:17:06.220
And the easiest way to get rid of them is to get them into the human food chain

01:17:06.220 --> 01:17:09.220
Not to burn them up, because they don't get any money for that

01:17:09.220 --> 01:17:13.220
So we don't know how many scrapes sheep enter the human food chain every year in Britain

01:17:13.220 --> 01:17:15.220
We have scrapes in the United States, too

01:17:15.220 --> 01:17:18.220
Then there was a huge inquiry which you can look up on the Internet

01:17:18.220 --> 01:17:22.220
If you have nothing better to do, there are 3,500 pages on this question of how to BSE start

01:17:22.220 --> 01:17:28.220
And what happened afterwards was an official inquiry that was created by Tony Blair

01:17:28.220 --> 01:17:31.220
And they only allowed the inquiry to go up to the day of his election

01:17:31.220 --> 01:17:35.220
So they could look at John Majors with severe eyes, but not at Tony Blair

01:17:35.220 --> 01:17:39.220
And that's what this does, it goes up to 1996, and it begins in the late 1970s

01:17:39.220 --> 01:17:41.220
In terms of questioning what happened

01:17:41.220 --> 01:17:46.220
And in that inquiry, you'll see that they think it began with a spontaneous or sporadic case of mad cow disease somewhere in southern England

01:17:46.220 --> 01:17:49.220
I don't think there's a lot of evidence for that, but that's what they hypothesized

01:17:49.220 --> 01:17:52.220
So prions are resisted to proteases, as I showed you, or enzyme digestion

01:17:52.220 --> 01:17:54.220
Which is what happens to proteins when they enter your gut

01:17:54.220 --> 01:17:59.220
If we take animals and we do a study, we find that we need about a billion times more prions

01:17:59.220 --> 01:18:03.220
When they're ingested, then if you put a needle in the head of the animal and inject them directly into the brain

01:18:03.220 --> 01:18:06.220
I thought it was one protein is all you needed, that's weird

01:18:06.220 --> 01:18:12.220
But nevertheless, if we give the animals enough, we give them a billion times more, orally, and they all get sick

01:18:12.220 --> 01:18:14.220
And so we presume the prions now cross the gut

01:18:14.220 --> 01:18:17.220
If we give them a billion times more, he said, that's hilarious

01:18:17.220 --> 01:18:19.220
Probably in the small intestine

01:18:19.220 --> 01:18:24.220
And that they multiply in lymphoid cells, and then they go through the brain

01:18:24.220 --> 01:18:25.220
Through the blood

01:18:25.220 --> 01:18:28.220
The other way we think they can make it to the brain is that they travel backwards

01:18:28.220 --> 01:18:32.220
Up the nerves of the gut, called the spinaic nerve bed, into the spinal cord

01:18:32.220 --> 01:18:36.220
And then up the spinal cord to the brain

01:18:36.220 --> 01:18:40.220
Question is, how do you disinfect scalpels and other medical instruments

01:18:40.220 --> 01:18:44.220
Because there have been cases where CJD has been transmitted from one patient to another

01:18:44.220 --> 01:18:46.220
By this route

01:18:46.220 --> 01:18:52.220
And what I was about to say was that it's very difficult to properly disinfect instruments

01:18:52.220 --> 01:18:54.220
And we're working on this now very hard

01:18:54.220 --> 01:18:56.220
I guess we have some new approaches that seem to be very useful

01:18:56.220 --> 01:18:57.220
And I'm very...

01:18:57.220 --> 01:18:58.220
Sure, they'll be patentable

01:18:58.220 --> 01:19:01.220
I'm very encouraged that soon we'll be able to do this in a much better way

01:19:01.220 --> 01:19:02.220
And it's commonly done

01:19:02.220 --> 01:19:04.220
Fortunately, the number of examples of that is still small

01:19:04.220 --> 01:19:09.220
But as the number of surgical procedures keeps increasing every year, this may become a bigger and bigger problem

01:19:09.220 --> 01:19:10.220
Hopefully we can stop it

01:19:10.220 --> 01:19:14.220
The question was, how do these poor cannibals in New Guinea keep on perpetuating their society

01:19:14.220 --> 01:19:18.220
Because if they keep eating each other and they keep getting sick with Peru, aren't they all going to die out?

01:19:18.220 --> 01:19:22.220
And the answer is that in the late 1950s, as this was starting to...

01:19:22.220 --> 01:19:25.220
At that point, in fact, Peru was the most common cause of death in women

01:19:25.220 --> 01:19:27.220
This was a society that all men would like to have lived in

01:19:27.220 --> 01:19:29.220
Because they never had to do anything, women did absolutely everything

01:19:29.220 --> 01:19:34.220
And at that point, the most common cause of death in women was Peru

01:19:34.220 --> 01:19:37.220
And they died in their 30s

01:19:37.220 --> 01:19:39.220
They virtually never made it to age 40

01:19:39.220 --> 01:19:42.220
So we had generations of young people who were motherless

01:19:42.220 --> 01:19:45.220
And it was in the late 1950s that two things happened

01:19:45.220 --> 01:19:49.220
One of the missionaries who began to colonize that area told them that nice people don't eat their relatives

01:19:49.220 --> 01:19:50.220
Whether they're dead or alive

01:19:50.220 --> 01:19:55.220
And these people were eating their dead relatives to really immortalize them

01:19:55.220 --> 01:19:59.220
This was their way of immortalizing them through taking their soul, which they believed was in the brain, not in the heart

01:19:59.220 --> 01:20:02.220
And the second thing that happened was that the Australian authorities

01:20:02.220 --> 01:20:06.220
Who now began to occupy the Highlands of New Guinea, which up until the late 1940s

01:20:06.220 --> 01:20:09.220
Had not seen any Western people

01:20:09.220 --> 01:20:12.220
And began to occupy that area and they outlawed cannibalism

01:20:12.220 --> 01:20:14.220
So that's how these tribes have now survived

01:20:14.220 --> 01:20:19.220
And so what you basically have here is very

01:20:19.220 --> 01:20:21.220
Let's say

01:20:21.220 --> 01:20:28.220
Outland, outlier examples of where protein misfolding can go wrong

01:20:28.220 --> 01:20:37.220
And it's usually an autoimmune reaction to exposure to proteins that would normally not be exposed to your systemic

01:20:38.220 --> 01:20:40.220
systemic immune system

01:20:41.220 --> 01:20:46.220
And so I don't know exactly how to draw it out on a piece of paper

01:20:46.220 --> 01:20:50.220
But it makes sense to me that this phenomenon, however rare it was

01:20:50.220 --> 01:20:55.220
Would be something that you would want to understand from the perspective of how ribosomes function

01:20:55.220 --> 01:20:58.220
From the perspective of protein folding

01:20:58.220 --> 01:21:03.220
And from the perspective of wanting to alter the function of proteins

01:21:03.220 --> 01:21:06.220
And knowing how to stay away from this potential danger

01:21:07.220 --> 01:21:12.220
So if there's anything that's dual use, it is the research into prions

01:21:12.220 --> 01:21:20.220
Because this is the sort of worst case scenario that in the situation where women are eating their dead relatives

01:21:20.220 --> 01:21:23.220
And they're eating their brain that occasionally you get this

01:21:23.220 --> 01:21:28.220
And more often you get this generated and it could be something to do with this phenomenon

01:21:29.220 --> 01:21:34.220
Could also be something to do with an immune reaction to that consumption

01:21:34.220 --> 01:21:40.220
An immune reaction that occurs in the gut in the place where tolerance is normally built

01:21:43.220 --> 01:21:48.220
And you could have a situation where something happens where that immune response is thrown off kilter

01:21:48.220 --> 01:21:55.220
Because self-antigens are present where they shouldn't be present, i.e. in the gut

01:21:58.220 --> 01:22:02.220
And so we're throwing out, there's no role for the immune system at all

01:22:02.220 --> 01:22:08.220
There's no role at all, and in fact, there's so no role at all

01:22:08.220 --> 01:22:14.220
That the picture that we were looking at earlier had no role for the immune system either

01:22:14.220 --> 01:22:18.220
This is just something that right, it just starts occurring

01:22:18.220 --> 01:22:21.220
And it was happening

01:22:21.220 --> 01:22:23.220
No

01:22:23.220 --> 01:22:25.220
Damn it

01:22:25.220 --> 01:22:28.220
Clicked on the frickin slide, sorry

01:22:32.220 --> 01:22:34.220
That there's no immune system here, right?

01:22:39.220 --> 01:22:44.220
There's no immune system here, this is just proteins doing their protein thing

01:22:46.220 --> 01:22:49.220
Sell the cell spread by nanotunnels

01:22:50.220 --> 01:22:55.220
Person to person spread by instruments, what he was talking about here, right there it is

01:22:56.220 --> 01:22:58.220
But

01:22:59.220 --> 01:23:05.220
There's no, he said earlier in the talk that they don't think that prions activate the immune system

01:23:06.220 --> 01:23:08.220
So the immune system does nothing

01:23:09.220 --> 01:23:11.220
Think about that

01:23:12.220 --> 01:23:14.220
If the immune system

01:23:14.220 --> 01:23:22.220
Memorizes damage-associated patterns and the immune system better dang well recognize a protein that could fold other proteins wrong

01:23:22.220 --> 01:23:27.220
That can cause protein aggregation, aggregates that are non-degradable

01:23:29.220 --> 01:23:31.220
It's interesting, right?

01:23:31.220 --> 01:23:36.220
And what did he say was the immune response that was so interesting in those knockout mice? Antibodies

01:23:37.220 --> 01:23:40.220
It's absolutely positively immunomythology

01:23:46.220 --> 01:23:48.220
I eat meat

01:23:48.220 --> 01:23:50.220
The question was do I eat meat?

01:23:50.220 --> 01:23:53.220
And I said yes, and then Alan chimed in with do I eat meat in England?

01:23:53.220 --> 01:23:55.220
And the answer is not now

01:24:00.220 --> 01:24:03.220
There's been a lot of discussion about this, there are no assets

01:24:03.220 --> 01:24:06.220
So the question is, is there any screening for blood or blood products?

01:24:06.220 --> 01:24:09.220
And right now there's no reliable assay for prions in blood

01:24:10.220 --> 01:24:15.220
And so what was done by the FDA was to first, about four years ago, put it into an effect

01:24:15.220 --> 01:24:21.220
If you had lived in the UK for six months or more, you could not get blood in the United States

01:24:21.220 --> 01:24:24.220
And then last year, this was reduced to three months

01:24:24.220 --> 01:24:28.220
And then it was something on the order of three years or four years for the rest of Europe

01:24:28.220 --> 01:24:30.220
So this is a cumulative time that you've spent

01:24:30.220 --> 01:24:32.220
And you get asked these questions when you get blood

01:24:32.220 --> 01:24:36.220
And so basically what has happened is that we've seeded a narrative about this potential

01:24:36.220 --> 01:24:42.220
We've seeded a narrative where it could be 60 days or it could be 40 years before

01:24:42.220 --> 01:24:45.220
The consequences of you eating contaminated meat

01:24:45.220 --> 01:24:51.220
Or the consequences of you being exposed to some farmland or you being exposed to the wrong blood

01:24:51.220 --> 01:24:56.220
Could result in symptomatic CJD or something related to it

01:24:56.220 --> 01:24:58.220
Alzheimer's disease, this kind of thing

01:24:59.220 --> 01:25:05.220
And he's being very imprecise on purpose trying to group them all together

01:25:05.220 --> 01:25:08.220
Has they're all related to protein misfolding?

01:25:08.220 --> 01:25:12.220
Yet some stories involve induction of the protein

01:25:12.220 --> 01:25:18.220
Others involve degradation and production and the rate limiting steps

01:25:18.220 --> 01:25:25.220
Somehow outweighing the takeover and eventually the bad protein outweighs the good protein

01:25:25.220 --> 01:25:27.220
And then you get the disease state

01:25:27.220 --> 01:25:33.220
Now testing those two ideas and how they're contradicting one another or they're mutually exclusive

01:25:33.220 --> 01:25:35.220
But okay

01:25:37.220 --> 01:25:43.220
One involves an tremendous amount of sort of hand waving with regard to the structure

01:25:43.220 --> 01:25:48.220
And function relationship between the sequence of a protein and its tertiary structure

01:25:48.220 --> 01:25:52.220
And its function, which we don't know yet

01:25:55.220 --> 01:26:00.220
It's an extraordinary biology that we're listening to

01:26:00.220 --> 01:26:03.220
So a lot of interest at the level of the FDA and drug companies

01:26:03.220 --> 01:26:09.220
To carry out analyses of their methods when they produce a biological such as

01:26:09.220 --> 01:26:12.220
Let me give you an example, TPA for heart attacks

01:26:12.220 --> 01:26:16.220
Are perceptin for cancer treatment, these are biologics that are produced in cells

01:26:16.220 --> 01:26:18.220
And when these kinds of drugs are produced

01:26:18.220 --> 01:26:22.220
There's a lot of interest in analyzing whether there's any possibility that prions could be carried along with them

01:26:22.220 --> 01:26:25.220
So this is going on now

01:26:25.220 --> 01:26:28.220
Some thought about prions and schizophrenia

01:26:28.220 --> 01:26:32.220
I think that we're going to see many, many more diseases that are due to these changes in protein shape

01:26:32.220 --> 01:26:33.220
Of course!

01:26:33.220 --> 01:26:36.220
Every disease from which we have no understanding is right for such a possibility

01:26:36.220 --> 01:26:37.220
Of course!

01:26:37.220 --> 01:26:39.220
I think one can't speculate with any certainty

01:26:39.220 --> 01:26:41.220
But I love to speculate

01:26:41.220 --> 01:26:45.220
Okay, so could I talk more about how understanding prions would be used

01:26:45.220 --> 01:26:48.220
Can benefit an understanding of Alzheimer's disease?

01:26:48.220 --> 01:26:52.220
So if one understands any of these degenerative diseases in great detail

01:26:52.220 --> 01:26:54.220
The implications for understanding the others are immense

01:26:54.220 --> 01:26:58.220
They're immense in terms of new ways of thinking about the control of protein shape

01:26:58.220 --> 01:27:01.220
And the control of protein processing going from a normal form to an abnormal form

01:27:01.220 --> 01:27:02.220
Do you understand?

01:27:02.220 --> 01:27:05.220
We're talking about protein processing and protein folding

01:27:05.220 --> 01:27:07.220
We're not talking about anything else

01:27:07.220 --> 01:27:11.220
And so this is an excuse to understand aberrant forms of it

01:27:11.220 --> 01:27:15.220
It's an excuse to induce aberrant forms of it

01:27:15.220 --> 01:27:20.220
And explore the possibility of harnessing that in a biological weapon scenario

01:27:20.220 --> 01:27:23.220
Avoiding it in a gene therapy scenario

01:27:23.220 --> 01:27:28.220
Avoiding it in a transfection or transformation scenario going forward

01:27:28.220 --> 01:27:32.220
That's what this is on its surface and at its heart

01:27:32.220 --> 01:27:37.220
It's all the same operation to get you to accept a gene therapy

01:27:37.220 --> 01:27:40.220
And the consequences of it

01:27:41.220 --> 01:27:48.220
And to think that there is a reflected natural threat that has an analog

01:27:48.220 --> 01:27:52.220
So every single thing that they thought that was going to happen

01:27:52.220 --> 01:27:57.220
As a result of transforming and transfecting humans in a medical way

01:27:57.220 --> 01:28:00.220
Using CRISPR or whatever all this shit is

01:28:00.220 --> 01:28:05.220
They've got to convince you that there is a natural way for these disasters to occur

01:28:06.220 --> 01:28:09.220
A natural way for this disease cascade to exist

01:28:09.220 --> 01:28:11.220
So that when it finally came

01:28:13.220 --> 01:28:17.220
And maybe we're here right now in 2024-2025-2026

01:28:17.220 --> 01:28:19.220
They know it's coming

01:28:21.220 --> 01:28:24.220
They had to tie it to the virus to the spike

01:28:24.220 --> 01:28:29.220
So that they could absolve transfection as a methodology

01:28:29.220 --> 01:28:33.220
Even though they were seeding it this far back probably because they knew

01:28:36.220 --> 01:28:40.220
Or let's say it's very possible that they knew

01:28:40.220 --> 01:28:43.220
And that's why this guy is so confident that this

01:28:43.220 --> 01:28:47.220
Wide net that he's casting that we can understand one mechanism

01:28:47.220 --> 01:28:51.220
We understand all the mechanisms and protein folding and folding and folding

01:28:51.220 --> 01:28:56.220
Remember the lady Susan Lindquist from MIT that we've been listening to

01:28:56.220 --> 01:28:58.220
Over the last few weeks as well

01:28:58.220 --> 01:29:02.220
That lady was working in the same department as Venki

01:29:02.220 --> 01:29:04.220
Rosham-Shami

01:29:04.220 --> 01:29:08.220
Whatever the guy that Mark has done a couple programs on that has done

01:29:08.220 --> 01:29:12.220
Got the Nobel Prize for the ribosome

01:29:12.220 --> 01:29:20.220
These are all in the same small group of people trying to figure out how the machinery of a cell works

01:29:20.220 --> 01:29:22.220
How the machinery on DNA works

01:29:22.220 --> 01:29:29.220
How DNA to RNA to protein can be understood and harnessed and hijacked

01:29:32.220 --> 01:29:35.220
And so they talk a mean game about how much we understand

01:29:35.220 --> 01:29:37.220
But we don't understand this stuff like this

01:29:37.220 --> 01:29:40.220
And I'm learning a lot from this

01:29:40.220 --> 01:29:44.220
Accumulating an abnormal form, causing as we had questions before

01:29:44.220 --> 01:29:46.220
About how do these changes in protein shape

01:29:46.220 --> 01:29:49.220
And then manifest themselves in neurologic signs and symptoms

01:29:49.220 --> 01:29:52.220
Decrease thinking, decrease memory, inability to walk

01:29:52.220 --> 01:29:55.220
What is the process by which this goes on? We have no idea

01:29:55.220 --> 01:29:57.220
And so what we're seeing is

01:29:57.220 --> 01:30:01.220
We have no idea, he couldn't at least say we think it's the immune system

01:30:01.220 --> 01:30:05.220
Seriously? It's kind of sad

01:30:05.220 --> 01:30:09.220
Why is it sad? Because once you invoke the immune system

01:30:09.220 --> 01:30:11.220
Your protein

01:30:11.220 --> 01:30:16.220
Your protein is no longer the center

01:30:16.220 --> 01:30:20.220
It's no longer a target

01:30:20.220 --> 01:30:22.220
It's no longer a toy

01:30:22.220 --> 01:30:24.220
It's no longer a thing that you have

01:30:24.220 --> 01:30:28.220
That you have intellectual property rights over

01:30:28.220 --> 01:30:31.220
Instead, now you're going into the immune system

01:30:31.220 --> 01:30:33.220
Where antibodies dominate

01:30:33.220 --> 01:30:35.220
Where we can't study T cells

01:30:35.220 --> 01:30:40.220
T cells are so hard to study that Christian Anderson decided to drop out of that

01:30:40.220 --> 01:30:43.220
PhD and go into infectious diseases instead

01:30:43.220 --> 01:30:47.220
He told that story on Twiv in 2021

01:30:47.220 --> 01:30:50.220
It's hilarious these people

01:30:50.220 --> 01:30:52.220
As more and more information

01:30:52.220 --> 01:30:55.220
Anything to stay away from the sacred biology

01:30:55.220 --> 01:30:58.220
That irreducible complexity, stay far away from it

01:30:58.220 --> 01:31:01.220
And go somewhere where it's only smoke and mirrors

01:31:01.220 --> 01:31:03.220
Like infectious diseases

01:31:03.220 --> 01:31:05.220
It comes from all these neurodegenerative diseases

01:31:05.220 --> 01:31:06.220
About them and the mechanisms

01:31:06.220 --> 01:31:08.220
We're going to see more and more cross fertilization

01:31:08.220 --> 01:31:11.220
The prion diseases have the advantages that we know much more about prions

01:31:11.220 --> 01:31:13.220
Than we do about the process of Alzheimer's disease

01:31:13.220 --> 01:31:14.220
We have much better animal models

01:31:14.220 --> 01:31:16.220
These transgenic or genetically...

01:31:16.220 --> 01:31:19.220
I am really upset with the disease, the use of the word disease

01:31:19.220 --> 01:31:21.220
Because it's super annoying

01:31:21.220 --> 01:31:26.220
We shouldn't have infectious disease

01:31:26.220 --> 01:31:29.220
And then genetic disease

01:31:29.220 --> 01:31:32.220
It should be genetic disorder

01:31:32.220 --> 01:31:35.220
Protein folding disorder

01:31:35.220 --> 01:31:40.220
Malaria disease

01:31:40.220 --> 01:31:41.220
Something like that

01:31:41.220 --> 01:31:43.220
I don't like this, but that's the way we do it

01:31:43.220 --> 01:31:46.220
And it's frustrating, but it's biologically confusing

01:31:46.220 --> 01:31:49.220
And biologically imprecise

01:31:49.220 --> 01:31:52.220
Near mice reproduce every aspect of a prion disease

01:31:52.220 --> 01:31:55.220
Of humans, of a cow, depending on what gene we express in the mouse

01:31:55.220 --> 01:32:00.220
And so we have tools with prion diseases that we don't have with any of the other diseases

01:32:00.220 --> 01:32:03.220
And I think if we're successful in the therapy and prion disease

01:32:03.220 --> 01:32:06.220
This will generate an enormous interest in the drug companies

01:32:06.220 --> 01:32:08.220
As well as the governments as well as foundations throughout the world

01:32:08.220 --> 01:32:12.220
But enormous amounts more money into solving a problem like Alzheimer's disease

01:32:12.220 --> 01:32:16.220
Anybody's, anybody's for amyloid beta

01:32:16.220 --> 01:32:19.220
I mean, it's hilarious how naive he sounds here

01:32:19.220 --> 01:32:22.220
Because we have, of course, the benefit of 22 years of research

01:32:22.220 --> 01:32:25.220
But it's very, very funny

01:32:25.220 --> 01:32:28.220
How naive he sounds here

01:32:28.220 --> 01:32:32.220
I'm so excited about these antibodies as therapeutics

01:32:32.220 --> 01:32:34.220
And also as bench tools

01:32:34.220 --> 01:32:37.220
And even structural dissection tools

01:32:37.220 --> 01:32:42.220
It's hilarious how naive he is to what he's using as tools

01:32:42.220 --> 01:32:47.220
Anybody's for a long time have played various roles like this

01:32:47.220 --> 01:32:54.220
That lots and lots of academic biologists are unaware of the huge, huge grey area

01:32:54.220 --> 01:32:57.220
That they've been playing with unless they've been using the proper controls

01:32:57.220 --> 01:33:02.220
Which is a growing and growing problem because of the change in demography of our populations

01:33:02.220 --> 01:33:06.220
When you're 85 years old, you have a one and three chance of having Alzheimer's disease

01:33:06.220 --> 01:33:09.220
And as we have more and more people who become octogenarians

01:33:09.220 --> 01:33:12.220
The number of people without Alzheimer's diseases that keep going up

01:33:12.220 --> 01:33:14.220
Other questions?

01:33:14.220 --> 01:33:17.220
So the question is, in late onset muscular dystrophies

01:33:17.220 --> 01:33:22.220
Where they have these mutations that expand the size of the protein

01:33:22.220 --> 01:33:25.220
Or sometimes don't expand the size of the protein but expand the gene

01:33:25.220 --> 01:33:27.220
Are there similarities? And the answer is yes

01:33:27.220 --> 01:33:30.220
One of the diseases I put up, but I didn't talk about was Huntington's disease

01:33:30.220 --> 01:33:32.220
And then I put up some of the spinal cerebellar ataxios

01:33:32.220 --> 01:33:35.220
And these diseases have these same kinds of expanded repeats

01:33:35.220 --> 01:33:39.220
And the answer is, I think we're talking about many similar phenomena

01:33:39.220 --> 01:33:41.220
Now in these cases, these are all inherited diseases

01:33:41.220 --> 01:33:43.220
So it's only the genetic form of disease

01:33:43.220 --> 01:33:48.220
But we have no understanding of why it is that these diseases have such a late onset

01:33:48.220 --> 01:33:51.220
What is clear is that the bigger the repeat, the earlier the onset

01:33:51.220 --> 01:33:54.220
But then all of that has to be qualified by many other factors

01:33:54.220 --> 01:33:57.220
That shift these curves up and down with respect to the repeats

01:33:57.220 --> 01:34:00.220
In the prion diseases, we have absolutely no understanding why it is that

01:34:00.220 --> 01:34:03.220
A single mutation, meaning one amino acid has changed

01:34:03.220 --> 01:34:07.220
Some members of the family, the same family, are 40 years old when they get the disease

01:34:07.220 --> 01:34:09.220
And others are 80 or 90 years old

01:34:11.220 --> 01:34:15.220
It's more likely to be exposure to a toxin or some other trigger than

01:34:15.220 --> 01:34:22.220
Rather than a disease process that's like a ticking clock or a degradation against production rate

01:34:22.220 --> 01:34:26.220
So again, the model makes predictions but he doesn't bother to test him

01:34:26.220 --> 01:34:29.220
He doesn't even bother to list the options that he sees

01:34:29.220 --> 01:34:31.220
It's really disingenuous

01:34:32.220 --> 01:34:35.220
The question is about these areas where PRPC is converted into PRPC scraping

01:34:35.220 --> 01:34:37.220
On the surface of the cell, these cholesterol-rich micro-domains

01:34:37.220 --> 01:34:41.220
One of the reasons we know they're cholesterol-rich is that with low estatin and other drugs

01:34:41.220 --> 01:34:44.220
We can completely abolish the formation of PRPC scraping

01:34:44.220 --> 01:34:47.220
Now we can't give that drug in high enough concentrations to humans

01:34:47.220 --> 01:34:49.220
Because we would dissolve the human

01:34:49.220 --> 01:34:53.220
The cells are not very happy in these very high concentrations of low estatin

01:34:53.220 --> 01:34:57.220
These are very important regions, these cholesterol-rich micro-domains are rafts

01:34:57.220 --> 01:34:59.220
That people have been studying only for the last few years

01:34:59.220 --> 01:35:01.220
They seem to coalesce and form caves or cabbioli

01:35:01.220 --> 01:35:03.220
And we really don't understand their function

01:35:03.220 --> 01:35:05.220
But there are more and more studies in this area

01:35:05.220 --> 01:35:08.220
And I think as time goes on we'll understand much more about them

01:35:12.220 --> 01:35:16.220
So the way the protein is multiplying is that we're seeing new PRPC being made all the time

01:35:16.220 --> 01:35:18.220
And then it's being degraded

01:35:18.220 --> 01:35:23.220
But about 5% of it in a scraping-infected cell is being bled off into the formation of new PRPC scraping

01:35:23.220 --> 01:35:28.220
And the old PRPC scraping, the existing PRPC scraping, drives the formation of new PRPC scraping

01:35:28.220 --> 01:35:30.220
See, he's saying it like he knows

01:35:30.220 --> 01:35:34.220
He's saying it like they have all these high fidelity images of it happening in a time-lapse photograph

01:35:34.220 --> 01:35:38.220
With stains that show everything and can double-dip control

01:35:38.220 --> 01:35:42.220
And it's just ridiculous, it's still just that cartoon

01:35:42.220 --> 01:35:47.220
It's still just a series of assumptions that haven't been confirmed by much other than that they can

01:35:47.220 --> 01:35:50.220
Sometimes see a fraction that's degradable and sometimes not

01:35:50.220 --> 01:35:51.220
Ting is multiplying

01:35:51.220 --> 01:36:00.220
So again, that's the same answer that I gave of question is what's the relationship of scraping to Parkinson's disease?

01:36:00.220 --> 01:36:04.220
So the same answer that I gave about the relationship of pre-owned research

01:36:04.220 --> 01:36:07.220
To Alzheimer's disease is the answer to what is the relationship to Parkinson's disease

01:36:07.220 --> 01:36:10.220
As we learn more about all of the processes that occur in

01:36:10.220 --> 01:36:14.220
So that kind of already helps you understand why it's a little ridiculous

01:36:14.220 --> 01:36:20.220
That people with regard to the spike protein will flip-flop between it being amyloidogenic

01:36:20.220 --> 01:36:22.220
And it being pre-anagenic

01:36:22.220 --> 01:36:26.220
Because as he's telling you right now, they're different proteins

01:36:26.220 --> 01:36:31.220
They're likely different mechanisms, they're likely different causes

01:36:31.220 --> 01:36:35.220
We just think that one might help us think about the other one

01:36:35.220 --> 01:36:39.220
There's no reason to believe if the protein is completely different

01:36:39.220 --> 01:36:43.220
That the mechanism is that all related and yet somehow or another

01:36:44.220 --> 01:36:48.220
These amateur hour worst case scenario

01:36:48.220 --> 01:36:54.220
Whitting or unwitting narrative pushers from 2020

01:36:54.220 --> 01:36:59.220
Have been interchangeably using the word pre-anagenic and amyloidogenic

01:36:59.220 --> 01:37:01.220
As though they're kind of just synonyms

01:37:01.220 --> 01:37:06.220
When here's the Nobel Prize winner telling you they are definitely not

01:37:07.220 --> 01:37:14.220
In scrapie, in the pre-owned diseases, those will translate into learning much more about Parkinson's disease

01:37:14.220 --> 01:37:17.220
In Parkinson's disease, there is a protein called alpha-synuclein

01:37:17.220 --> 01:37:19.220
Which is normally made in all of us

01:37:19.220 --> 01:37:23.220
And when the disease occurs, or even long before the disease occurs

01:37:23.220 --> 01:37:26.220
Alpha-synuclein is being mishandled, improperly handled

01:37:26.220 --> 01:37:29.220
It starts accumulating not outside the cell as big plaques

01:37:29.220 --> 01:37:32.220
But inside the cell as what are called lewy bodies

01:37:32.220 --> 01:37:34.220
And specifically in the cells of the substantia nigra

01:37:34.220 --> 01:37:37.220
Which are the cells that die out in Parkinson's disease

01:37:37.220 --> 01:37:40.220
So there is a PRP in birds, it's very much different than mammalian PRP

01:37:40.220 --> 01:37:44.220
And whether birds have pre-owned diseases, I don't know

01:37:44.220 --> 01:37:49.220
So the question is, are there cases of CJD where it's come from a vaccine

01:37:49.220 --> 01:37:51.220
Or it's come from a blood transfusion

01:37:51.220 --> 01:37:54.220
There are several cases where there have been blood transfusions

01:37:54.220 --> 01:37:56.220
But one can't be sure that it either came from the blood transfusion

01:37:56.220 --> 01:37:58.220
Or it was simply a sporadic case of CJD

01:37:58.220 --> 01:38:01.220
And the same thing's true of a couple of vaccine cases

01:38:01.220 --> 01:38:03.220
But the problem is everybody's vaccinated

01:38:03.220 --> 01:38:06.220
And so we can't really make any relationship there

01:38:06.220 --> 01:38:09.220
So the question is, since ALS is a relatively rare disease

01:38:09.220 --> 01:38:11.220
Is there much research being done here at UCSF?

01:38:11.220 --> 01:38:13.220
And the answer is that

01:38:13.220 --> 01:38:15.220
There's a small amount of research being done here

01:38:15.220 --> 01:38:16.220
But it's significant

01:38:16.220 --> 01:38:18.220
And we have a clinical center and in that clinical center

01:38:18.220 --> 01:38:20.220
We're trying to get much more information

01:38:20.220 --> 01:38:24.220
And our hope is to expand ALS research in the near future

01:38:24.220 --> 01:38:28.220
You stand on behalf of many men, thank you so much

01:38:28.220 --> 01:38:32.220
Thanks guys

01:38:32.220 --> 01:38:36.220
I hope you found that useful

01:38:36.220 --> 01:38:42.220
I hope you find it definitely a little bit useful

01:38:42.220 --> 01:38:45.220
Please stop transfection in humans

01:38:45.220 --> 01:38:48.220
They are trying to eliminate the control group

01:38:48.220 --> 01:38:52.220
Especially in the old people, don't let those over 50 in your life

01:38:52.220 --> 01:38:55.220
Take any vaccine advice from their doctor

01:38:55.220 --> 01:39:00.220
Intramuscular injection of any combination of substances with the intent of augmenting the healthy immune system

01:39:00.220 --> 01:39:04.220
Of your friends, your relatives, your neighbors

01:39:04.220 --> 01:39:05.220
It's dumb

01:39:05.220 --> 01:39:10.220
Transfection in healthy humans is criminally negligent in RNA camp pandemic

01:39:15.220 --> 01:39:17.220
Mark got a new Lego train

01:39:17.220 --> 01:39:19.220
But it's wheels don't turn

01:39:19.220 --> 01:39:21.220
It's kind of annoying

01:39:22.220 --> 01:39:26.220
I don't see if there's any dinner left over for me

01:39:26.220 --> 01:39:28.220
Thank you very much for joining me

01:39:28.220 --> 01:39:31.220
Ladies and gentlemen, these are the people that support giggle and biological

01:39:31.220 --> 01:39:33.220
If your name's not up here yet

01:39:33.220 --> 01:39:36.220
It might be because I haven't updated the list in a little while

01:39:36.220 --> 01:39:39.220
Or it might be because you are not yet a subscriber

01:39:39.220 --> 01:39:42.220
And if you'd like to be, you can go to giggleandbiological.com

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And you can find a lot of different ways to set up a one time

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Or even monthly donation to our work

01:39:49.220 --> 01:39:53.220
Actually, as I left this play

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I'm going to cut over to the desk

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And I got a card from New Mexico today

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Thanks very much Christy, it made it

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And thanks for the grocery money

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You know, like every little bit counts

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And this is not a little bit, so thanks a lot

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Christy, thanks a lot

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See you guys again tomorrow