The Truth about Pseudouridine

Research Paper : N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting | Nature

On Dec 6 another important paper regarding the controversial use of mRNA vaccines was published in Nature, a candidate for the most prestigious journal in the life sciences. The research paper pioneers new laboratory techniques and provides new information on the dangers of mRNA vaccines. I want to summarize for a general audience what this paper says and what it means for the debate regarding use of mRNA vaccines. The paper is linked to above, but I have to warn you that this is an especially challenging science paper to read.

I have mixed feelings towards writing about science, which I have expressed in this blog post: Confessions of an Amateur Virologist. It's not my job to write about science and I have only an amateur interest in the subject. It’s somebody else’s job, but for Covid, that person is not doing his job. The science behind Covid has been corrupted by money and politics and it is difficult for the general public to get access to the information they need. I try to fill the gap because I do have a facility for these subjects and I don’t like seeing the general public bullied by the credentialed elite. I know several people such as Alex Berenson are studying this paper and will give their own explanation for the general public, but as no one else has given an explanation aimed at the public yet I have decided to give my own.

Let me start by saying the paper is very credible. It is published in Nature, one of the most prestigious science journals in the world, and so it has been thoroughly vetted. Once submitted to the editors they will have found someone with the expertise to judge the paper, but unconnected to the authors, to refer the paper to, this referee will examine the paper for credibility and must recommend its publication for the the editors at Nature to even consider it. The chances that this paper is fraudulent or incompetently done are very small. If the paper turns out to be flawed it will be exposed very quickly, but I doubt that will happen. The paper laboriously explains its research methods in mind numbing detail.

The issue at hand is errors in protein synthesis caused by the replacement of Uridine with Pseudouridine in the mRNA formula for creating Covid Spike Proteins. The original recipe for making the Spike Protein found in the Covid virus was modified in several ways for the vaccine, one of those ways was replacing Uridine with Pseudouridine. This had never been done at a large scale and the results of this substitution were not fully known at the time of the vaccine rollout. I distinctly remember many top scientists warning that injecting people with the vaccine before we knew the consequences of using Pseudouridine was a grave error in judgment, but little attention was paid at the time. It is an obscure subject and there was no experimental data at the time to go on. Now there is.

This paper explores the consequences for the human body of this substitution of Pseudouridine for Uridine in the recipe for making Covid Spike Proteins found in the mRNA vaccines. But first, let me explain why this substitution was made. Twenty years ago when research into mRNA vaccines first began they quickly realized that the virus mRNA they were using was so quickly recognized by the body as foreign and destroyed by the immune system that there was no time to produce enough antibodies to count as a vaccine. 

Let me remind the reader that the idea here is to take part of the original recipe for making the virus and inject only a harmless(hopefully) portion of the recipe so only an incomplete and harmless(hopefully) portion of the virus is made by the human body, which then learns to make antibodies against it, and these antibodies will then work against the whole and complete virus to provide immunity to infection. This original conception of mRNA vaccines did not work and was abandoned early on. The problem is the human body recognizes these incomplete recipes for making parts of the virus as foreign too quickly and destroys them before they can cause adequate antibody production.

Very early on it was decided to modify the partial recipes for making the virus that were being injected as a vaccine to appear more like human mRNA. There are patterns in how human and virus DNA and mRNA look and scientists modified the mRNA vaccines to look more like human genetic material. In scientific terms, the immunogenicity of the mRNA vaccines was reduced through modifications to the mRNA. This made it harder for the human body to recognize it as foreign and so the mRNA vaccines would last longer in the body, ultimately producing more parts of the virus and thus more antibodies.

This wasn’t the only change made to the genetic code of the virus being used in the mRNA vaccines. The genetic code, or recipe for making proteins, from the virus, was altered in another way, it was made more durable and long-lasting. mRNA are fragile strings with a short lifetime. When they wear out the cell makes a new copy of the mRNA needed from the DNA, which is a durable repository of information on how to make mRNA strings. The DNA is a cookbook filled with recipes for specific dishes(proteins), and the mRNA strings are the recipes, each making one specific dish(protein). The mRNA wears out quickly and then the cell makes a new one from the DNA cookbook.

The faster the mRNA wears out the fewer copies of the virus part, in this case, the Spike Protein, it will make. So to make enough copies of the virus part to produce enough antibodies to be considered a useful vaccine you have to take into account the durability of the mRNA being used. If the mRNA only lasts half as long you have to use twice as many to make enough virus parts to produce enough antibodies to provide immunity, the goal of a vaccine. If the mRNA lasts twice as long you can use half the dose.

This matters because the mRNA vaccine has to transfect a cell to work and that cell will then get attacked by the immune system. Transfecting is what scientists call it when their mRNA creations infect a cell. I would prefer to just call this infecting, but I will use transfecting to remain consistent with the scientific literature and avoid confusing the reader. Making the mRNA vaccine more durable reduces the number of human cells that need to be transfected to produce enough antibodies to qualify as a useful vaccine.

This is important because if everything works the way it's supposed to, every transfected cell will eventually be killed by the immune system. The key word in this sentence is “if”. It has already been shown that everything is not working as it's supposed to, but that is a different subject. The scientists want to minimize the number of transfected cells to minimize the number of human cells attacked by the immune system. They want to minimize the inevitable autoimmune reaction. Anyone following the Covid vaccine debate will be familiar with claims of the vaccine causing medical problems ending in -itis. This suffix merely means inflamed, the first part of the word is the name of the tissue being inflamed, Inflamed means targeted by the immune system in this context, it means autoimmune damage in the context of being caused by the vaccines.

So to minimize the inevitable autoimmune response the vaccine makers want the mRNA to be as durable as possible. To do this they often imitate the mRNA of red blood cells, which use unique formulations which are longer lasting than those used by the rest of the body. Red blood cells lack DNA and so cannot replace mRNA when it wears out, so they use unique mRNA formulations that are longer lasting. The vaccine makers imitate these features to make the mRNA in the vaccine more durable than normal mRNA.

Replacing Uridine with Pseudouridine accomplishes the two goals of modifying the virus mRNA I have discussed. It makes the mRNA less immunogenic, meaning the immune system is less likely to attack it. It does this by making it look more like human mRNA. The substitution of Uridine with Pseudouridine also makes the mRNA more durable, which reduces the number of human cells that must be transfected to produce immunity. The important point here is the vaccine makers have to modify the mRNA from the virus, they have no choice. There may be other ways to modify it than using Pseudouridine, but the modifications must be made. However, the consequences of using Pseudouridine were unknown at the time they decided to inject billions of people with these vaccines. Top scientists warned this would most likely not end well, but they were ignored because the subject is so obscure and they had no data to point to. Now we have data, that is what this paper represents.

This particular paper is impenetrable to the non-expert for most of its length. The researchers had to invent several new laboratory techniques to measure exactly what is happening in the cell due to the Pseudouridine. When researchers use well known laboratory techniques they merely mention these techniques by name in the paper. Since these techniques are newly invented by the researchers they make a great effort to explain these newly invented techniques to the reader. This very detailed explanation of how the new techniques they invented work constitutes the majority of the paper’s text. I have no idea what any of this means. If you don’t work in this field you will never understand what any of it means. But I rely on the good reputation of Nature and trust that they have thoroughly vetted the paper and made sure these new techniques are sound. There is nothing else a non-expert can do.

We now slowly arrive at the heart of the matter, what does substituting Uridine with Pseudouridine in the recipe for making the Covid Spike Protein do to the human body? The answer is that when the cell is using the mRNA recipe to make the Spike Protein and it gets to the Pseudouridine it often makes a mistake. It's like when a typewriter jams when certain letter combinations are used. The strange layout of the QWERTY keyboard is designed to minimize the likelihood of typewriter jams by placing the troublesome combinations far apart on the keyboard. Something analogous happens with protein synthesis using genetic material, putting certain things in a certain order can cause the replication to have a higher rate of failure. Including the Pseudouridine in the mRNA is doing this.

But it gets worse, the specific type of error being made is called a Frameshift, which makes everything that comes after it also be in error. Imagine if your job is to write numbers as they come off an assembly line and you forget your place and guess wrong, now every item you number from that point on is numbered wrong. This is what a Frameshift error does, everything that comes after it is also wrong, and wrong in a somewhat unpredictable way. This means that after the Frameshift error has occurred everything after it will be a mutant protein string that will not form the intended Covid Spike Protein. Instead this mutant protein will be recognized as foreign by the immune system and destroyed.

But yet again, it gets worse. The immune system will try to destroy any cell making these mutant proteins, but they will eventually try to destroy any transfected cell anyway. Once the mRNA vaccine has entered the cell it is transfected, and if everything goes the way it's supposed to it will eventually be killed. The key word here is “if”. But the key point here is that the main problem with this production of mutant protein strings(my terminology, this is not the scientific term) is that they could cause the body to produce antibodies to protein strings that overlap with protein strings found in the human body, causing an autoimmune reaction.

Offending foreign material, such as viruses and bacteria, are chopped up by the cells into short protein strings called peptides which are roughly between five and ten amino acids long. These short strings then become antigens, which is short for Antibody Generating. An antibody that fits that exact peptide, or short protein string, is created and it will float around the body and attach to any protein that has this sequence within it. To use an analogy, let's say the antibody attached to the letters t-h-e. Then it would attach to the words, the, there, and therefore. It would attach to anything that has the string t-h-e within it.

So the antigen causes antibodies to be produced which attach to any protein that contains a sequence matching the protein sequence of the original antigen, even if this means attacking part of the human body. So every time the immune system creates an antibody for a protein sequence found on an infecting agent there is a chance this antibody will attach to the human body and cause the body to be attacked by the immune system. The issue here is that the more antibody types produced, the more likely you are to produce one which causes the human body to be attacked.

This is the problem, the Frameshift error caused by the inclusion of Pseudouridine in the mRNA vaccine causes the cell to make unpredictable mutant proteins of many types. Since a larger number of protein types are being produced, a larger number of antigens are being produced, which means there is a greater chance of an autoimmune reaction. Simply because the Frameshift error increases the variety of protein strings created by the mRNA vaccine, it is also increasing the chances of producing antibodies that attack the human body. This is the main cause for concern here.

The paper is highly technical and written for a specialized audience, but I believe the paper's authors are saying they have evidence(evidence is different from proof) that the inclusion of Pseudouridine is leading to a greater variety of antibodies being produced, and logic leads one to believe this increases the likelihood of the mRNA vaccine causing an autoimmune reaction. Let me quote statements from the paper that support this conclusion:

From the abstract: “Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination.” 

Science papers begin with the abstract, which is somewhat like a summary. This is the first sentence in the paper, it is saying that the use of Pseudouridine in the Covid mRNA vaccine is causing Frameshifting errors and thus mutant proteins(“+1 frameshifted products”) and the body is creating antibodies to these mutant proteins, this is what the part about “cellular immunity” means, and they indicate they have seen this occur in both mice and humans. This is the first sentence of the entire paper for a reason. The issue here is that using Pseudouridine is causing mutant proteins to be created and the body is making antibodies to them.

“To address this possibility, we vaccinated mice with BNT162b2 and quantified their T cell response to in-frame SARS-CoV-2 spike protein and +1 frameshifted products predicted to occur by translation of the mRNA +1 frame, as well as an unrelated control antigen (SARS-CoV-2 M protein), by interferon-γ (IFNγ) ELISpot assay. Junction peptides consisting of in-frame N-terminal residues and C-terminal +1 frameshifted residues were not included. We found that responses to +1 frameshifted spike peptides were significantly increased in vaccinated mice compared to untreated mice or those vaccinated with ChAdOx nCoV-19, which does not produce antigen from translation of N1-methylpseudouridylated mRNA22 (Fig. 2b).”

This is a complicated passage, so I will try to explain it clearly. They found that mice given the Pfizer mRNA vaccine were getting a T-cell response to the mutant proteins created by Frameshifting errors. This means the mutant proteins were being created and the body was creating antibodies to them. They compared these results to unvaccinated mice and to mice vaccinated against Covid using a vaccine that does use Pseudouridine and the differences were great enough to indicate the Pfizer vaccine was causing significant production of the mutant proteins and the body was creating antibodies against them.

“Alongside this impact on host T cell immunity, the off-target effects of ribosomal frameshifting could include increased production of new B cell antigens.”

Meaning the body will be producing antibodies to what I am here calling mutant proteins.

Last sentence in conclusion: “These findings are of particular importance to our fundamental understanding of how ribonucleotide modification affects mRNA translation, and for designing and optimizing future mRNA-based therapeutics to avoid mistranslation events that may decrease efficacy or increase toxicity.”

The first and last sentences of a writing should be the ones given the most thought. What the last sentence is politely, and diplomatically saying, is that using Pseudouridine is leading to toxicity. It's a very polite way of saying that they caught the mRNA vaccines doing something bad. The last two words of the paper are “increase toxicity”. The researchers are very politely saying that the autoimmune reaction created by the occurrence of mutant proteins is having a harmful effect on patients. They are saying using Pseudouridine is harmful, but just being polite to their colleagues in the community.

I hope the reader now understands what the research paper says, now what impact does this have on medicine? I see two consequences, one this should simply reinforce the idea that granting exemptions from safety testing and speeding up the approval process for Covid was a mistake. No one ever injected this many people with genetic material modified with Pseudouridine and no one knew in advance what would happen. This is why regulatory approval is supposed to take years, not months. Hopefully, the next time someone tries to shorten the approval period this unfortunate result will be remembered.

The more specific consequence is that this is one more nail in the coffin of mRNA vaccines. There are so many nails already in the coffin that it looks like a cybertruck. mRNA technology was already dead before this study, now it's just deader. This is just one more reason why mRNA vaccines are a bad idea. The only thing they do better is they grow faster in the vats of liquid nutrients they use for this than the normal vaccines. This is why the military funded the development of mRNA vaccines, they wanted to be able to vaccinate the soldiers fast enough to win a war against an enemy who surprised them with a new virus. Other than growing faster in the vats of liquid goop they grow in they do nothing better than normal vaccines and many things worse. This whole thing was a mistake and I hate the people who pushed this on the public. I hate them all.