"Pfizer and BioNTech thus could not actually know that their mRNA transfections would lead to such durable expression of spike protein that IgG4-mediated tolerance already emerges ..."
They were warned. So they cannot use that excuse.
Long before EUA, FDA and vaccine makers were warned about induction of inappropriate IgE and IgG4 antibodies by COVID vaccines. They ignored it. Prediction comes true, with devastating consequences.
This used mRNA to create the RBD in the cell instead of the full length spike, but it was dropped due to higher retrogenicity, ie worse side effects. The trial was a dose ranging from 1ug to 60ug, but apparently the side effects for dose 2 at 50ug (which they didn't go into 🙄) were bad enough not to give a second dose for 60ug.
So perhaps making shorter proteins with mRNA leads to greater problems, a concern if the yield is poor as for some of the commercial batches. I can't figure out if there could be a possibility the damaged mRNA could lead to shorter proteins, if free spike protein is found in post vaxx myocarditis, what other bits of random protein could there be?
Interestingly it looks like the t-cell responses for a 1ug dose were pretty good though the neutralising antibodies were weaker, though at 43 days the antibodies for 1ug were still rising though the antibodies for the higher doses were already fading.
At the time all this helped convince me they were pushing to release as soon as possible using as much mRNA as possible. It made me wonder if a younger healthy person might create more antigen in their cells than an elderly person, exactly the opposite of what's needed, leading to worse side effects in the young and inadequate immunity in the elderly.
(Of course a higher antibody read would give a better impression of protection from infection, thereby extending it's use to the whole population 'to end the pandemic') This and other things pretty well convinced me personally to give the vaxx a wide berth...
If it is true that truncated/partial RNA molecules don't get expressed, then the b1 (RBD only) construct as being far "less fragile" probably had a higher RNA integrity and thus was expressed more at any given concentration. That's a interesting link - I forget where the head-to-head Phase 1 b1 vs. b2 reactogenicity results are buried, doesn't seem to be in the Clinical Overview. Pfizer's notes are as disorganized as my own... But my impression is that basically they saw RBD could do the job at a low concentration, but picked whole spike because it doesn't do the job until high concentration. More RNA cowbell.
Bravo Brian, another pointed knock out of the park!🎩🎩👏👏👏
This is the point from the beginning- nothing, nada, zip, bupkis, zilch!! Has been done properly with these ridiculous junk shots. The signals were there and there were too many "we dont have the data, because we didnt look for that."
I read what they submitted to the TGA, back in 2020/21, and when i discussed concerns with friends that have worked on clinical trials and submitted data to TGA before- their response, "Oh, you don't understand how trials are done and data." 😐😐😑
If you passed reading and comprehension in school, then you can read a document and understand it, you just might need a dictionary while you do it, & it may take longer!
No no no, there's, like, secret regulator codes that Pfizer used to deliver their really-really-thorough safety data on that page that says there's no safety data
I thought "Due Diligence and Art" might be an actually cool contemporary media art book, which would be surprising because that whole scene was REALLY into the pandemic, as it is inherently technologically driven and has been starving for something new for over a decade.
Now I feel like that was too harsh and may be inaccurate. But you know, it points to something, and artists as a class are, you know, supposed to be a good indicator of unconscious cultural wishes and pressures, well art is supposed to be, but these days everything has to take place at the level of the human itself... there used to be a time when you'd meet someone and hit it off and maybe a few days later you'd go to a video store together and the point wasn't the content of the movie you were going to get, the point was walking around and looking at movie covers as you mutually navigated that ephemeral question, "what do I want?"... even this consumer fairytale is more sane and generous and accountable to who we are as modern humans (consumers) than I don't know, streaming spike proteins into your blood like it's Netflix or something.
I'm trying to put words to why everything is so god damn literal these days, why more than ever people have to rigidly hold to the content as the point, and over that to the most linear interpretation of such content (present context excluded of course). I think that by turning the clock back just a couple of decades to when we were consumers, we can see the whole logic, op or not, is that we are platforms. Which... could be a step in either direction actually, but in this case of course it is most certainly in the wrong one (the Gates route as opposed to Kildall if I'm kind of getting what another commenter suggested)...
The person as a platform could really go either way. Hm. We get stuck with pseudo-ecological consumerist garbage bio-chattel or whatever.
Anyway any fixation is covering for a lack. Just a good, clean psychoanalytic insight that is good to hold in mind... oh yes, the artists show us, that if this whole situation were operationalized for some yet to be understood reason, I imagine the people who were responsible for it would be like "damn these people REALLY wanted a pandemic!". To which another old grizzled operator might reply, "Yeah I've been here a long time but this one did go off hotter than expected... must be 'volatile tinder'"...
So whence this "volatile tinder"... I think part of it is the destruction of all forms (which is fun but generationally has become institutional which produces existential predicaments one would think would be obvious), the abysmal all-encompassing metaphysical cynicism of a materialist project that is not riding high, you know stuff like that... more (lacanian) psychoanalysis, last night I was like, wow, the vaccine is very obviously the phallus (formally and as language's effective agent in reality) and the virus is structurally the object cause of desire (the properties of language create a structural impossibility, that is an "object" we are always seeking and cannot ever get and somehow this impossibility becomes culturally shared, not unlike the nested inferences that gives us virus and transmission).
Thanks for letting me ramble; I managed to push a couple of thoughts I was having a little further.
Jan 16, 2023·edited Jan 16, 2023Liked by Brian Mowrey
Those perfect Western blots are suggestive of a high school science fair project. You know, the kind where they hypothesize a mechanism for training an immune response to a virus in humans and then test it on several hundred million people.
I have a lot of experience with all sorts of western blots. The Pfizer western blots look HIGHLY suspicious, there is no way to generate such even and orderly blots. Occasionally, a blot from commercial gels such as Invitrogen Nupage or BOLT type gels can look very even and synthetic but not such a large experiment with multiple lanes. You always get some noise and some deformed, irregular bands. In addition there is no loading control, such as actin, GAPDH or tubulin, which is also very unusual.
Also, I find it very hard to believe that overexpressed, full length spike protein would be such a clearly defined, crystal clear band with zero degradation and/or truncation products on the blot. HEK293 cells usually generate loads of protein but also loads of degradation/truncation products.
Right. So rather than fraud I think the situation was that the blots were perfunctory. In collaboration with the regulators, they used a computer to "snap" to only certain intensities and exclude smears as below an LOD under a rationale that those were irrelevant breakdown products, not truncated protein. Which means the test was pointless to begin with - just something to make the regulators feel like they had tried.
A blast from the past: Robert Malone explained in the Corona Investigative Committee that "the Moderna vaccine is the NIH vaccine."
Was he wrong?
NIH? Isn't that part of the USFG? Curioser and curioser.
Question: Who funds the NIH? Now, who really funds the NIH? Or, rather, who funds those who fund the NIH?
How are we so sure that "evil and greedy multinational corporations have captured regulatory agencies to maximize their profits at the expense of the blood of everyone"? Am I the only one who thinks that it seems likely that those evil corporations are captured by someone else, because the prejudices of most people against capitalism make these corporations the perfect decoy to do things that are not possible under "normal" circumstances?
Extremely effective kabuki: There are many people terrorized by the myriad of myths about spike protein and the legions of variants from hell, a situation I find so sad.
I was actually going to comment about the Alzheimer's debacle, but unfortunately Western Blot manipulation is not uncommon. It even happens with slides where someone may just take one slide and turn it 180. Apparently many Chinese labs were doing that in their reported studies.
The slides are so selective that it's extremely likely labs choose the best ones to pick from, or they can just take a photo and slide (no pun intended) over a bit and get another photo.
When writing my post on the bacteremia study I was going to have a big tirade on how I have no idea whether the crypt-ileum slides were representative of other images seen or if they just selected for one with many goblet cells to be an infected mouse while the one with fewer were ones with very few goblet cells.
As technology becomes even more advanced it's very likely that many of these issues will get even worse.
Also, this discussion made me look this up again but apparently pseudouridylation may be a common phenomenon with certain human mRNA as post-transcription modification. However, due to its selectivity it's quite possible that it may be the indiscriminate use of pseudouridine that may be the problem, and not necessarily the pseudouridine itself?
Robert Malone had a post a while back that explained this in a way I could understand. The nutshell was that intracellular immune processes are pattern matching to find certain sequences in mRNA that are commonly present in viruses and other pathogens, and destroy those strands. But sometimes those patterns are present legitimately in the genome.
Pseudouridine is used naturally and sparingly to shut off these checks when needed. Who knows what happens when you saturate yourself with this stuff.. probably cancer among other things.
It does appear that the use of pseudouridine tags mRNA to provide a "self vs nonself" presentation, so viruses not tagged would be considered foreign and therefore destroyed.
So in that regard the lack of being targeted is because the body recognizes it as self. The saturation is one of the things that seems interesting because the indiscriminate use may mean that we run into key breakdown pathways that are now obfuscated.
One thing about using pseudouridine in this way is it subverts a mechanism that is normally extremely secure against attack, so likely that we are very poorly adapted to combat this misuse of pseudouridine. I think it would be virtually impossible for a virus to evolve to incorporate pseudouridine in its RNA. One of many extremely novel facets of these shots, which would then be expected to yield unintended consequences.
Probably no life-form could get away with writing its own genome in "comic sans" because then it can't replicate with fidelity. Viruses do influence how host cells process RNAs (at least in the sense of throwing wrenches in the gears) so maybe they could promote RNA mods that increase tRNA availability of who-knows-what, but essentially everything those mods are good for is in cell machinery molecules that the host donates anyway.
The viruses likely can't utilize pseudouridine because it's a post-transcriptional modification and done so selectively. Apparently only a few number of mRNAs have been discovered to contain pseudouridine, and the process isn't the insertion of pseudouridine during transcription but the conversion of uridine into pseudouridine by pseudouridine synthase.
It's likely that viral mRNA may elude this process for rampant protein production as Brian alluded to in one of his prior posts. So it's more like conducting a hit and run being a more critical feature than being the sly virus that sticks around but evades recognition.
I agree that during high replication rates many would slip through. I was more meaning that subverting this mechanism in this way is extremely novel and therefore more likely to have intended consequences..
I went back to read it. It's interesting, as "exhaustion" may be the issue happening here. That's one of the points raised in my post on ER stress as well. It's likely that the body is being held hostage to producing spike and it's the process of producing the spike rather than the spike alone that is detrimental.
With respect to the pseudouridine it just raises the idea that everyone will respond differently in how to produce the spike, and there's no way that the vaccine manufacturers would be able to capture why people construct the spike differently, or respond to the LNPs or mRNAs differently.
It reminds me of the comment I made in my ER stress posts where the traditional vaccines (which at least used attenuated viruses or antigens) was sort of like ordering takeout, while the new vaccines are like ordering from those meal kit companies and expecting the person to cook it themselves. How many people would be able to perfectly recreate the meal, or how many would completely screw up, messy up the kitchen and use up all the pots and pans, or just burn everything and engulf the house in a plume of smoke?
We all ideally believe we would make the spike according to the recipe, but just because we are given the blueprint doesn't mean we can still make it.
Well, I guess this was a ramble meant for my own post. I'll just raise this video as the most concise way of describing all of this:
Not sure if you've seen this, but the Midwestern Doctor has shown these western blot bands, allegedly representing different proteins from different batches at different conditions, to be related by copy-pasting: https://twitter.com/MidwesternDoc/status/1613216030876176390
It’s more like someone made an app that generates images from numeric values. The question is whether the numeric values were first originally derived from different, authentic images, or just made up and typed in.
It’s not difficult or unheard-of to slice and dice authentic blots. Especially here where the goal was to show “no protein,” BioNTech could have just used blank lanes. But instead we have full-on CGI.
What would other pharmacology tests be? (besides biodistribution of lipid nanoparticles and biodistribution of cells that it took in the nanoparticles?). I recall the shot was authorized with only a handful of the normal tests done; no oncology, pregnant women, interaction with other medications.
"...showing that the product they were claiming “causes cells to produce the SARS-CoV-2 spike protein"". It's hard for me to find a source stating the difference between the vaccine spike and viral spike. Does anyone know offhand, or have a good resource? Was it about the charge...
Regarding the difference in "what was coded for," the main things are
1) Two proline substitutions that prevent the spike from entering the fusion conformation. basically it acts like a locked harpoon. But the cap of the harpoon (S1) can still fly off and give you blood clots etc., because they didn't remove the furin cleavage site.
2) The fact that, aside from the 2P, it used original Wuhan recipe spike as opposed to the circulating mutants that most people encountered.
As for difference in what actually would get produced, we don't know. Patterson et al. found mutant S1 https://joomi.substack.com/p/what-proteins-are-we-actually-getting. There's probably differences in how the spike gets processed in the cell as well, vs. what happens in viral infection. What transfected cells do in vitro and in the body as far as adding sugar molecules to spike probably aren't the same.
Radiolabeled RNA as MD said. Animal histology. Verify what proteins animals actually make. As Latypova's post mentions, these are pro-drugs, you have to verify that they are processed in the body into the expected "real drug," in this case spike.
It's very hard for me to believe that a commercial RNA vaccine would actually get to market without the developer thinking, "Hey what if we looked at where the RNA goes? What if we looked at what these mice actually made?" But supposedly that is what happened here. So the question is if it was indifference/incompetence or someone had already done the real development before the product was given to BioNTech and Pfizer.
That is just stunning, that it was never confirmed in the body that it actually makes what it's coded for. Thanks for these answers, it feels good to be clear on the difference between the vaccine and viral spikes because a lot of people write as if they're the same (although they may know that there's a difference but it may be cumbersome to state it every time).
Likely interactions with organ systems, radiolabeled mRNA and not just the radiolabeled LNPs and then the use of luciferase for proxy spike production.
Possibly isolation of spike products, but that may seem far too difficult. I think the biggest one would be to have radiolabeled the mRNA and see how long it took to release from the body. I think that would at least assuage some concerns, or tell us that the mRNA actually remain for quite some time.
Thank you for those explanations. This is much appreciated as I am unfamiliar with much of molecular biology. Most importantly to me, we don't have the sequence of the spike protein made by the vax, that I can find. I have been suspicious for 2 yrs that other cryptic proteins are being made, the spike is cleaved in more than one place....etc etc.
Yes, my big issue is there is no pharmacology!. None. A big black hole from injection to antibodies. Have pieced some of the kinetics of this product and I have a pretty good idea of how transfection occurs, but after that it's another blank (from transfection to antibodies).
And how does that modified mRNA get degraded in the cytosol? New paper says it gets repolyadenylated in vivo (but not in vitro) and continue to make protein, so could those fragments get polyadenylated in vivo too?
And those LNPs get hydrolyzed with the modRNA and form adducts. They had no idea that would happen.
My thinking is Pfizer/BioNTech must have been given the sequence (like Moderna was?) and was told to go make it. I think the goal of these products was to get mRNA into arms, and not necessarily to get antibodies.
Either way, the (fake) Western Blots don't touch on the question of whether cells read "full-length" modRNA with fidelity, or pump out mutant spikes en masse due to codon optimization and pseudo-U'n.
What is the protein quality control you are referring to above? Jessica Rose explains a mechanism on her substack where the translated proteins are lysed inside the ER if a large enough fraction of the translation products do not fold. I guess you are referring to something else?
Right, cells have garbage disposals for misfolded proteins. So like with cancer it's not just a question of causing a mutation but of a failure of the correction process. So the vax RNA could be throwing out lots of mutants but only the S1 mutants get past the garbage disposal. The virus also mutates S1 a lot and S2 hardly at all so this could be due to the S2 having a confined landscape as far as mutations that don't mess up structure.
The only paper I have found to address this, is this stealth paper by a tiny Christian pharmacy school which likely has no pharma funding. And they were told the spike protein is proprietary. REALLY?
So that looks like they found loads of truncated spike despite the protease inhibitor cocktail. But it would be nice if they used a time-point between 6 and 24hr. Given that 6 looks so clean, the other smears *could* just be intracellular proteases since spike has multiple cathepsin motifs.
What are the best data sources for trying to analyze the question of whether or not there have been excess deaths since late 2021?
How much can we believe Arkmedic's new post on "Don't be an arse (ass)"?
It certainly seems worse that I thought.
https://arkmedic.substack.com/p/dont-be-arrsey
"Pfizer and BioNTech thus could not actually know that their mRNA transfections would lead to such durable expression of spike protein that IgG4-mediated tolerance already emerges ..."
They were warned. So they cannot use that excuse.
Long before EUA, FDA and vaccine makers were warned about induction of inappropriate IgE and IgG4 antibodies by COVID vaccines. They ignored it. Prediction comes true, with devastating consequences.
https://vinuarumugham.substack.com/p/long-before-eua-fda-and-vaccine-makers
Late to this, but it reminded me of a paper I read in mid 21 when considering the vaxx, written about the other Biontech candidate BNT162b1
https://www.nature.com/articles/s41586-020-2814-7
This used mRNA to create the RBD in the cell instead of the full length spike, but it was dropped due to higher retrogenicity, ie worse side effects. The trial was a dose ranging from 1ug to 60ug, but apparently the side effects for dose 2 at 50ug (which they didn't go into 🙄) were bad enough not to give a second dose for 60ug.
So perhaps making shorter proteins with mRNA leads to greater problems, a concern if the yield is poor as for some of the commercial batches. I can't figure out if there could be a possibility the damaged mRNA could lead to shorter proteins, if free spike protein is found in post vaxx myocarditis, what other bits of random protein could there be?
Interestingly it looks like the t-cell responses for a 1ug dose were pretty good though the neutralising antibodies were weaker, though at 43 days the antibodies for 1ug were still rising though the antibodies for the higher doses were already fading.
At the time all this helped convince me they were pushing to release as soon as possible using as much mRNA as possible. It made me wonder if a younger healthy person might create more antigen in their cells than an elderly person, exactly the opposite of what's needed, leading to worse side effects in the young and inadequate immunity in the elderly.
(Of course a higher antibody read would give a better impression of protection from infection, thereby extending it's use to the whole population 'to end the pandemic') This and other things pretty well convinced me personally to give the vaxx a wide berth...
If it is true that truncated/partial RNA molecules don't get expressed, then the b1 (RBD only) construct as being far "less fragile" probably had a higher RNA integrity and thus was expressed more at any given concentration. That's a interesting link - I forget where the head-to-head Phase 1 b1 vs. b2 reactogenicity results are buried, doesn't seem to be in the Clinical Overview. Pfizer's notes are as disorganized as my own... But my impression is that basically they saw RBD could do the job at a low concentration, but picked whole spike because it doesn't do the job until high concentration. More RNA cowbell.
Bravo Brian, another pointed knock out of the park!🎩🎩👏👏👏
This is the point from the beginning- nothing, nada, zip, bupkis, zilch!! Has been done properly with these ridiculous junk shots. The signals were there and there were too many "we dont have the data, because we didnt look for that."
I read what they submitted to the TGA, back in 2020/21, and when i discussed concerns with friends that have worked on clinical trials and submitted data to TGA before- their response, "Oh, you don't understand how trials are done and data." 😐😐😑
If you passed reading and comprehension in school, then you can read a document and understand it, you just might need a dictionary while you do it, & it may take longer!
No no no, there's, like, secret regulator codes that Pfizer used to deliver their really-really-thorough safety data on that page that says there's no safety data
🤣🤣🤣🤣🤦♀️🤦♂️ Its like all the regulatory bodies around the world are systematically filled with "Mean Girls" and "Clueless" types in the roles!
I thought "Due Diligence and Art" might be an actually cool contemporary media art book, which would be surprising because that whole scene was REALLY into the pandemic, as it is inherently technologically driven and has been starving for something new for over a decade.
Now I feel like that was too harsh and may be inaccurate. But you know, it points to something, and artists as a class are, you know, supposed to be a good indicator of unconscious cultural wishes and pressures, well art is supposed to be, but these days everything has to take place at the level of the human itself... there used to be a time when you'd meet someone and hit it off and maybe a few days later you'd go to a video store together and the point wasn't the content of the movie you were going to get, the point was walking around and looking at movie covers as you mutually navigated that ephemeral question, "what do I want?"... even this consumer fairytale is more sane and generous and accountable to who we are as modern humans (consumers) than I don't know, streaming spike proteins into your blood like it's Netflix or something.
I'm trying to put words to why everything is so god damn literal these days, why more than ever people have to rigidly hold to the content as the point, and over that to the most linear interpretation of such content (present context excluded of course). I think that by turning the clock back just a couple of decades to when we were consumers, we can see the whole logic, op or not, is that we are platforms. Which... could be a step in either direction actually, but in this case of course it is most certainly in the wrong one (the Gates route as opposed to Kildall if I'm kind of getting what another commenter suggested)...
The person as a platform could really go either way. Hm. We get stuck with pseudo-ecological consumerist garbage bio-chattel or whatever.
Anyway any fixation is covering for a lack. Just a good, clean psychoanalytic insight that is good to hold in mind... oh yes, the artists show us, that if this whole situation were operationalized for some yet to be understood reason, I imagine the people who were responsible for it would be like "damn these people REALLY wanted a pandemic!". To which another old grizzled operator might reply, "Yeah I've been here a long time but this one did go off hotter than expected... must be 'volatile tinder'"...
So whence this "volatile tinder"... I think part of it is the destruction of all forms (which is fun but generationally has become institutional which produces existential predicaments one would think would be obvious), the abysmal all-encompassing metaphysical cynicism of a materialist project that is not riding high, you know stuff like that... more (lacanian) psychoanalysis, last night I was like, wow, the vaccine is very obviously the phallus (formally and as language's effective agent in reality) and the virus is structurally the object cause of desire (the properties of language create a structural impossibility, that is an "object" we are always seeking and cannot ever get and somehow this impossibility becomes culturally shared, not unlike the nested inferences that gives us virus and transmission).
Thanks for letting me ramble; I managed to push a couple of thoughts I was having a little further.
Those perfect Western blots are suggestive of a high school science fair project. You know, the kind where they hypothesize a mechanism for training an immune response to a virus in humans and then test it on several hundred million people.
HOW DID I NOT SEE “BLOTTER-GATE” AT FIRST
Corrected.
I have a lot of experience with all sorts of western blots. The Pfizer western blots look HIGHLY suspicious, there is no way to generate such even and orderly blots. Occasionally, a blot from commercial gels such as Invitrogen Nupage or BOLT type gels can look very even and synthetic but not such a large experiment with multiple lanes. You always get some noise and some deformed, irregular bands. In addition there is no loading control, such as actin, GAPDH or tubulin, which is also very unusual.
Also, I find it very hard to believe that overexpressed, full length spike protein would be such a clearly defined, crystal clear band with zero degradation and/or truncation products on the blot. HEK293 cells usually generate loads of protein but also loads of degradation/truncation products.
Right. So rather than fraud I think the situation was that the blots were perfunctory. In collaboration with the regulators, they used a computer to "snap" to only certain intensities and exclude smears as below an LOD under a rationale that those were irrelevant breakdown products, not truncated protein. Which means the test was pointless to begin with - just something to make the regulators feel like they had tried.
A blast from the past: Robert Malone explained in the Corona Investigative Committee that "the Moderna vaccine is the NIH vaccine."
Was he wrong?
NIH? Isn't that part of the USFG? Curioser and curioser.
Question: Who funds the NIH? Now, who really funds the NIH? Or, rather, who funds those who fund the NIH?
How are we so sure that "evil and greedy multinational corporations have captured regulatory agencies to maximize their profits at the expense of the blood of everyone"? Am I the only one who thinks that it seems likely that those evil corporations are captured by someone else, because the prejudices of most people against capitalism make these corporations the perfect decoy to do things that are not possible under "normal" circumstances?
So evil and powerful they tried out four RNAs on six mice each.
Just kabuki.
Extremely effective kabuki: There are many people terrorized by the myriad of myths about spike protein and the legions of variants from hell, a situation I find so sad.
Who crwated it? Just Connecticut the DODs.
Thanks Brian, brilliant analysis.
Do you have a Twitter handle so that I can follow on Twitter?
Thank you.
Only active here on substack
which is why I subscribe...
I was actually going to comment about the Alzheimer's debacle, but unfortunately Western Blot manipulation is not uncommon. It even happens with slides where someone may just take one slide and turn it 180. Apparently many Chinese labs were doing that in their reported studies.
The slides are so selective that it's extremely likely labs choose the best ones to pick from, or they can just take a photo and slide (no pun intended) over a bit and get another photo.
When writing my post on the bacteremia study I was going to have a big tirade on how I have no idea whether the crypt-ileum slides were representative of other images seen or if they just selected for one with many goblet cells to be an infected mouse while the one with fewer were ones with very few goblet cells.
As technology becomes even more advanced it's very likely that many of these issues will get even worse.
Also, this discussion made me look this up again but apparently pseudouridylation may be a common phenomenon with certain human mRNA as post-transcription modification. However, due to its selectivity it's quite possible that it may be the indiscriminate use of pseudouridine that may be the problem, and not necessarily the pseudouridine itself?
Robert Malone had a post a while back that explained this in a way I could understand. The nutshell was that intracellular immune processes are pattern matching to find certain sequences in mRNA that are commonly present in viruses and other pathogens, and destroy those strands. But sometimes those patterns are present legitimately in the genome.
Pseudouridine is used naturally and sparingly to shut off these checks when needed. Who knows what happens when you saturate yourself with this stuff.. probably cancer among other things.
It does appear that the use of pseudouridine tags mRNA to provide a "self vs nonself" presentation, so viruses not tagged would be considered foreign and therefore destroyed.
So in that regard the lack of being targeted is because the body recognizes it as self. The saturation is one of the things that seems interesting because the indiscriminate use may mean that we run into key breakdown pathways that are now obfuscated.
One thing about using pseudouridine in this way is it subverts a mechanism that is normally extremely secure against attack, so likely that we are very poorly adapted to combat this misuse of pseudouridine. I think it would be virtually impossible for a virus to evolve to incorporate pseudouridine in its RNA. One of many extremely novel facets of these shots, which would then be expected to yield unintended consequences.
Probably no life-form could get away with writing its own genome in "comic sans" because then it can't replicate with fidelity. Viruses do influence how host cells process RNAs (at least in the sense of throwing wrenches in the gears) so maybe they could promote RNA mods that increase tRNA availability of who-knows-what, but essentially everything those mods are good for is in cell machinery molecules that the host donates anyway.
The viruses likely can't utilize pseudouridine because it's a post-transcriptional modification and done so selectively. Apparently only a few number of mRNAs have been discovered to contain pseudouridine, and the process isn't the insertion of pseudouridine during transcription but the conversion of uridine into pseudouridine by pseudouridine synthase.
It's likely that viral mRNA may elude this process for rampant protein production as Brian alluded to in one of his prior posts. So it's more like conducting a hit and run being a more critical feature than being the sly virus that sticks around but evades recognition.
Thanks for the explanation of how that works!
I agree that during high replication rates many would slip through. I was more meaning that subverting this mechanism in this way is extremely novel and therefore more likely to have intended consequences..
Or just the end-stream effect on expression. Essentially this is the thesis of my Liquid Cancer post. Cells turn into overworked beasts of burden
I went back to read it. It's interesting, as "exhaustion" may be the issue happening here. That's one of the points raised in my post on ER stress as well. It's likely that the body is being held hostage to producing spike and it's the process of producing the spike rather than the spike alone that is detrimental.
With respect to the pseudouridine it just raises the idea that everyone will respond differently in how to produce the spike, and there's no way that the vaccine manufacturers would be able to capture why people construct the spike differently, or respond to the LNPs or mRNAs differently.
It reminds me of the comment I made in my ER stress posts where the traditional vaccines (which at least used attenuated viruses or antigens) was sort of like ordering takeout, while the new vaccines are like ordering from those meal kit companies and expecting the person to cook it themselves. How many people would be able to perfectly recreate the meal, or how many would completely screw up, messy up the kitchen and use up all the pots and pans, or just burn everything and engulf the house in a plume of smoke?
We all ideally believe we would make the spike according to the recipe, but just because we are given the blueprint doesn't mean we can still make it.
Well, I guess this was a ramble meant for my own post. I'll just raise this video as the most concise way of describing all of this:
https://www.youtube.com/watch?v=A4FjJ9tH5HY
Not sure if you've seen this, but the Midwestern Doctor has shown these western blot bands, allegedly representing different proteins from different batches at different conditions, to be related by copy-pasting: https://twitter.com/MidwesternDoc/status/1613216030876176390
It’s more like someone made an app that generates images from numeric values. The question is whether the numeric values were first originally derived from different, authentic images, or just made up and typed in.
It’s not difficult or unheard-of to slice and dice authentic blots. Especially here where the goal was to show “no protein,” BioNTech could have just used blank lanes. But instead we have full-on CGI.
What would other pharmacology tests be? (besides biodistribution of lipid nanoparticles and biodistribution of cells that it took in the nanoparticles?). I recall the shot was authorized with only a handful of the normal tests done; no oncology, pregnant women, interaction with other medications.
"...showing that the product they were claiming “causes cells to produce the SARS-CoV-2 spike protein"". It's hard for me to find a source stating the difference between the vaccine spike and viral spike. Does anyone know offhand, or have a good resource? Was it about the charge...
Regarding the difference in "what was coded for," the main things are
1) Two proline substitutions that prevent the spike from entering the fusion conformation. basically it acts like a locked harpoon. But the cap of the harpoon (S1) can still fly off and give you blood clots etc., because they didn't remove the furin cleavage site.
2) The fact that, aside from the 2P, it used original Wuhan recipe spike as opposed to the circulating mutants that most people encountered.
As for difference in what actually would get produced, we don't know. Patterson et al. found mutant S1 https://joomi.substack.com/p/what-proteins-are-we-actually-getting. There's probably differences in how the spike gets processed in the cell as well, vs. what happens in viral infection. What transfected cells do in vitro and in the body as far as adding sugar molecules to spike probably aren't the same.
Radiolabeled RNA as MD said. Animal histology. Verify what proteins animals actually make. As Latypova's post mentions, these are pro-drugs, you have to verify that they are processed in the body into the expected "real drug," in this case spike.
It's very hard for me to believe that a commercial RNA vaccine would actually get to market without the developer thinking, "Hey what if we looked at where the RNA goes? What if we looked at what these mice actually made?" But supposedly that is what happened here. So the question is if it was indifference/incompetence or someone had already done the real development before the product was given to BioNTech and Pfizer.
That is just stunning, that it was never confirmed in the body that it actually makes what it's coded for. Thanks for these answers, it feels good to be clear on the difference between the vaccine and viral spikes because a lot of people write as if they're the same (although they may know that there's a difference but it may be cumbersome to state it every time).
Likely interactions with organ systems, radiolabeled mRNA and not just the radiolabeled LNPs and then the use of luciferase for proxy spike production.
Possibly isolation of spike products, but that may seem far too difficult. I think the biggest one would be to have radiolabeled the mRNA and see how long it took to release from the body. I think that would at least assuage some concerns, or tell us that the mRNA actually remain for quite some time.
Thank you for those explanations. This is much appreciated as I am unfamiliar with much of molecular biology. Most importantly to me, we don't have the sequence of the spike protein made by the vax, that I can find. I have been suspicious for 2 yrs that other cryptic proteins are being made, the spike is cleaved in more than one place....etc etc.
Yes, my big issue is there is no pharmacology!. None. A big black hole from injection to antibodies. Have pieced some of the kinetics of this product and I have a pretty good idea of how transfection occurs, but after that it's another blank (from transfection to antibodies).
And how does that modified mRNA get degraded in the cytosol? New paper says it gets repolyadenylated in vivo (but not in vitro) and continue to make protein, so could those fragments get polyadenylated in vivo too?
And those LNPs get hydrolyzed with the modRNA and form adducts. They had no idea that would happen.
My thinking is Pfizer/BioNTech must have been given the sequence (like Moderna was?) and was told to go make it. I think the goal of these products was to get mRNA into arms, and not necessarily to get antibodies.
Right, up to 200A https://www.biorxiv.org/content/10.1101/2022.12.01.518149v1
Patterson et al. verifies that mutant S1 (moreso than S2) can be detected in monocytes after transfection https://joomi.substack.com/i/72612566/mutant-spike-pieces-in-vaccinated-people-who-never-had-covid This might simply mean that mutant S2s are more likely to be scrapped by protein quality control, whereas mutant S1 is more promiscuous.
Either way, the (fake) Western Blots don't touch on the question of whether cells read "full-length" modRNA with fidelity, or pump out mutant spikes en masse due to codon optimization and pseudo-U'n.
What is the protein quality control you are referring to above? Jessica Rose explains a mechanism on her substack where the translated proteins are lysed inside the ER if a large enough fraction of the translation products do not fold. I guess you are referring to something else?
Right, cells have garbage disposals for misfolded proteins. So like with cancer it's not just a question of causing a mutation but of a failure of the correction process. So the vax RNA could be throwing out lots of mutants but only the S1 mutants get past the garbage disposal. The virus also mutates S1 a lot and S2 hardly at all so this could be due to the S2 having a confined landscape as far as mutations that don't mess up structure.
The only paper I have found to address this, is this stealth paper by a tiny Christian pharmacy school which likely has no pharma funding. And they were told the spike protein is proprietary. REALLY?
https://irispublishers.com/sjbls/pdf/SJBLS.MS.ID.000541.pdf
So that looks like they found loads of truncated spike despite the protease inhibitor cocktail. But it would be nice if they used a time-point between 6 and 24hr. Given that 6 looks so clean, the other smears *could* just be intracellular proteases since spike has multiple cathepsin motifs.