No, the mRNA in the Pfizer and Moderna COVID-19 vaccines does not cause cancer by targeting tumor suppressor genes

The topic of this post might be a bit niche, but, given my background in molecular biology research, particularly earlier in my career, every so often I like to take on a topic that’s a bit “niche,” particularly if it is relevant to medical misinformation being promoted online, and even more so if it’s relevant to medical misinformation about COVID-19 and COVID-19 vaccines being promoted online. Many have been the times that I’ve mentioned how, with respect to the new COVID-19 vaccines, everything old is new again. At the risk of being repetitive (but also providing the benefit of your not having to click on a link to see what I’m talking about; that is, unless you want to), antivaxxers have falsely spread misinformation and conspiracy theories claiming that COVID-19 vaccines kill; render women infertile; cause autoimmune disease; “reprogram your DNA“; aren’t needed because COVID-19 is not only not a serious disease but is a “casedemic” based on overly sensitive tests; can cause Alzheimer’s disease; can cause prion disease; and/or are loaded with “toxins” (in this case, the lipid nanoparticles that contain the mRNA used in the vaccines). To these old antivax tropes was added the claim that the mRNA-based COVID-19 vaccines are not really vaccines at all but rather “experimental gene therapy”. (No, they’re vaccines.) Just about the only claim that antivaxxers haven’t made yet about COVID-19 vaccines is that they cause autism, and that’s only because there are as yet no COVID-19 vaccines approved for use in children and babies and no mass vaccination program of children. Just wait until there are, and you’ll see that claim too. I’ll give you a brief preview: Cancer and tumor suppressor genes.

And here it comes, the claim that COVID-19 vaccines cause cancer

I did forget one common antivaccine claim, though. It’s one that I hadn’t yet seen about the COVID-19 vaccine, even though it’s a claim that dates back decades about early versions of the polio vaccine used in the late 1950s and early 1960s, namely that vaccines cause cancer. (It’s a claim that’s morphed and metastasized to invoke “chronic inflammation”—which can contribute to cancer—from vaccines in general as a cause of cancer.) You remember that hoary old claim, don’t you, that because early versions of the polio vaccine were contaminated with a virus (SV40), those polio vaccines given to children over 60 years ago are responsible for a wave of cancer over the last two decades. I discussed in my inimitable detail how that claim was investigated and found to have no scientific basis way back in 2013. Now that claim has been repurposed for the COVID-19 vaccine. No, antivaxxers are not claiming that the COVID-19 vaccines by Moderna, Pfizer/BioNTech, or Johnson & Johnson are contaminated with SV40. Rather, they are focusing their false claim that COVID-19 vaccines will cause a wave of cancer in decades to come on the mRNA-based design of these vaccines and a cherry picked study from Memorial Sloan-Kettering Cancer Center from 2018 (to give their misinformation the patina of scientific respectability). I haven’t seen this claim widely disseminated (yet), but as a trained molecular biologist I thought I’d try to nip it in the bud before it grows too much.

Let’s start with this Tweet:

1.) What is the mortality rate of the COVID -19 vaccine?
2.) Has it been tested for pathogenic priming?
3.) Does this vaccine cause cancer in the long run since " New research suggests that mRNA itself may carry cancer-causing changes"? (source https://t.co/polCaNV7jo)

— Mo (@Mo_Forestt) March 6, 2021

To answer the first question, so far, based on observations after tens of millions of vaccines administered in the US alone, we do not yet have a single case of death that can be definitely attributed to the vaccine and the number of deaths soon after vaccination with the Pfizer and Moderna vaccines is actually less than would be expected by random chance alone if the vaccines have nothing to do with the deaths. To answer the second question, “pathogenic priming” is scare term invented by an antivaxxer named James Lyons-Weiler to describe antibody-dependent enhancement (ADE), which has been a problem in the development of vaccines against Dengue Virus, Ebola Virus, HIV, RSV, and the family of coronaviruses. In brief, ADE is a condition when insufficient antibody titers due to the vaccine trigger enhancement of disease with subsequent infection. Vaccine-induced non-neutralizing or weakly neutralizing antibodies bind to newly infecting virus to promote enhanced virus uptake into host cells. ADE was indeed a concern early on during the development of COVID-19 vaccines but fortunately appears not to be an issue. If it were, we would have seen it after the nearly 90 million doses of COVID-19 vaccines (and counting) that have been administered so far in the US (as of Sunday).

Which brings us to the third question based on this study touted by MSKCC by press release two and a half years ago. The source of this “interpretation” of the MSKCC study to weaponize it as evidence that the mRNA in the Pfizer and Moderna vaccines will cause cancer appears to come from one of our favorite conspiracy quack sites, Natural News.

Quoth antivaxxers, “Oh, no, RNA targets tumor suppressor genes and causes cancer!”

The article that appears to have been the origin of the claim that somehow the RNA in COVID-19 vaccines causes cancer, based on a mechanism first described by scientists at MSKCC more than two years before the first cases of COVID-19 puzzled Chinese health authorities in Wuhan, was published last week on NaturalNews.com under the title “MEDICAL SHOCKER: Scientists at Sloan Kettering discover mRNA inactivates tumor-suppressing proteins, meaning it can promote cancer“. The article is by S.D. Wells, one of Mike Adams’ minions at Natural News, a veritable workhorse who spreads conspiracy theories and misinformation under Mike Adams’ banner.

The first paragraph is…something:

There’s a secret layer of information in your cells called messenger RNA, that’s located between DNA and proteins, that serves as a critical link. Now, in a medical shocker to the whole world of vaccine philosophy, scientists at Sloan Kettering found that mRNA itself carries cancer CAUSING changes – changes that genetic tests don’t even analyze, flying completely under the radar of oncologists across the globe.

So now, it’s time for independent laboratories that are not vaccine manufacturers (or hired by them) to run diagnostic testing on the Covid vaccine series and find out if these are cancer-driving inoculations that, once the series is complete, will cause cancer tumors in the vaccinated masses who have all rushed out to get the jab out of fear and propaganda influence. Welcome to the world of experimental and dirty vaccines known as mRNA “technology.”

That “secret layer” of information is only “secret” if you don’t know simple molecular biology, but I’ll let that pass for the moment. Instead, observe how this observation is framed as a conspiracy theory. There’s a “secret” aspect to mRNA vaccines that “they” don’t want you to know about, an aspect that will harm you because…well, you’ll learn that soon enough. I can’t help but note that the PR department at MSKCC must be aware of the conspiracy theories being spun based on this science, because someone added this disclaimer to the press release being used as justification for Wells’ claim:

Researchers at the Sloan Kettering Institute have found that changes in an information-carrying molecule called messenger RNA can inactivate tumor-suppressing proteins and thereby promote cancer. The findings pinpoint previously unknown drivers of the disease. It’s important to note that mRNAs are a normal component of all cells and the specific ones discussed here are not involved in mRNA-based vaccines, like the one developed against SARS-CoV-2.

Because, of course they’re not. Wells is interested in making it seem to those who don’t know enough molecular biology to assess the claim (the vast majority of the population) that any old “RNA” or “mRNA” can shut off tumor suppressor genes and thereby cause cancer. Still, being a molecular biologist, I was interested in the specifics. Before I do that, let’s delve deeper into the claims:

The information carrying molecule, messenger RNA, can instruct human cells ultimately in the same way as cancer drivers, playing a major role in causing cancer to thrive while inactivating natural tumor-suppressing proteins the human body creates to save you from cancer. This is the complete opposite of what the CDC and the vaccine manufactures are telling everyone right now about the Covid vaccines, and this is based on clinical research by molecular biologists at the Sloan Kettering Institute.

Even sequencing the DNA in cancer cells doesn’t reveal these changes, that’s how sneaky the vaccines are. It’s like a Trojan horse that tells your cells to allow these changes to be made, as if they were safe, but they’re not. All assumptions being made about mRNA being ‘safe’ right now have been completely turned 180 degrees with this research. Consider this very carefully if you have not yet been vaccinated with mRNA technology, and you may want to ‘lawyer-up’ if you already got the jabs.

Notice the conspiracy theory again. Not only did “they” not tell you about this, but “they” hid this ability of mRNA from you in a manner making it unlikely to be found, even by oncologists! (Damn, those scientists at Moderna and Pfizer/BioNTech are clever and evil, aren’t they?) I mean, seriously, Wells even brings Bill Gates into the mix, because of course Bill Gates is part of the conspiracy. He’s part of every vaccine conspiracy:

Bill Gates and the Vaccine Industrial Complex are very sinister, as we all know, but to create vaccines that truncate (disable by cutting short) cancer tumor suppressors, and destroy the human body’s ability to protect against cancer, well, that’s just complete insanity. Truncated tumor-suppressor proteins are similar to the DNA mutations that cause cancer cells to mutate and multiply uncontrollably. Will America see cancer cases skyrocket over the next few years due to Covid vaccines? Only time will tell, but right now, science is revealing that it’s likely. Pay close attention.

Therefore, anyone who is scared to death of the Covid vaccines is pro-science rather than anti-science, because the science shows the mRNA technology is very dangerous, especially concerning proteins that fuel cancer tumors. Let’s say that again: Science shows mRNA technology can fuel cancer tumor growth.

No, not exactly. Let’s look at the actual paper to see why.

Lying with science

So let’s take a look at the press release and the scientific paper the press release was promoting. The press release is entitled “In a Twist, Scientists Find Cancer Drivers Hiding in RNA, Not DNA“, and the paper was published in Nature by Christine Mayr, a molecular and cellular biologist at MSKCC who studies mRNA. The study is entitled “Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia“, which is, of course, not the sort of title that most people would understand. Don’t worry. I’ll explain.

But first, I need to explain some background. When discussing the mRNA-based COVID-19 vaccines and how they don’t “reprogram your DNA” and are not “gene therapy“, I discussed how DNA encodes RNA that ultimately encodes protein. Before I discuss what the paper actually shows and why Wells is misapplying its findings, I think it helpful to review the basics of this aspect of molecular biology again. Here is a very basic diagram of the process:

Basically, DNA replicates from a DNA template and results in a double-stranded molecule that is very stable, as it has complementary sequences that tightly bind to each other in a sequence-specific fashion. This DNA template is unwound by enzymes that use the template to make RNA strands, which are single-stranded, which is then used by a ribosome to make protein out of amino acids. Again, to put it simply, each nucleotide equals one letter of the code; each three-nucleotide sequence (codon) equals one “word” that translates to an amino acid. Given that there are four nucleotides, there are 64 possible codons. Since there are only 20 amino acids, that means that most amino acids are encoded by more than one combination of nucleotides or more than one codon; i.e., the genetic code is redundant. Of course, it’s more complicated than that, as this diagram shows:

After the genetic code was cracked 60 years ago, it soon became apparent that the RNAs encoding for proteins are often not fully formed right after they’re transcribed. Often RNA starts out as a longer precursor RNA (a pre-mRNA) that is spliced to the final mRNA sequence before being transported out of the nucleus into the cytoplasm to be used to drive the production of protein in the cytoplasm. In brief, the precursor RNA that is initially transcribed contains sequences known as “exons” and “introns”. In genes, exons contain the nucleotide sequences that encode actual protein, while introns contain nucleotide sequences that do not code for anything but can have important sequences that regulate gene production and activity. Here’s an illustration of the splicing process from Wikipedia:

This diagram is actually fairly simple, with two exons and one intron. Some genes have many exons and introns, requiring multiple splices, as in this diagram:

Did I forget to mention that mRNAs are also processed to have a “cap” at one end and a stretch of As (a poly-A tail) at the other end? The poly-A tail is very important in regulating mRNA stability and therefore its half-life in the cytoplasm. In any event, as with any biological process, things can go wrong with these splicing events. Splice site mutations, for instance, can result in mis-spliced mRNAs and proteins lacking exons:

I could go on and on and on. There are normal genes can produce more than one protein through alternative splicing:

Sometimes when splicing goes awry, it can result in a truncated protein lacking one end. For instance, if an intron is left attached to two exons, chances are that the ribosome (the enzyme complex that translates mRNA into protein) will hit a “stop” codon (three nucleotide code that tells transcription to stop) long before it reaches the other end of the intron, at which point transcription will just stop. All of this is not even counting the other molecular modifications that the RNA can undergo on its journey from transcription to pre-mRNA through splicing to the final “mature” mRNA.

Unsurprisingly, if these sorts of errors occur in genes important to processes regulating cell growth and invasion, cancer can result, either from a mis-splicing removing a regulatory region in the protein that keeps it in check or by producing a protein that doesn’t function as it should. Examples of cancers that are caused or accelerated by a splice site mutation are accumulating. It is this latter possibility, a truncated protein that doesn’t function, that the paper being misapplied by Wells examines. The proteins compromised by the truncation are tumor suppressor proteins, whose function is to shut down growth or other processes that can result in cancer when they are overly active.

So what did the paper show? What was interesting about the paper is that it showed the existence of splicing errors in tumor suppressor genes in a specific cancer, chronic lymphocytic leukemia, without mutations in splice sites to explain how these proteins became truncated due to splicing errors, or, as the authors put it in the manuscript:

We discovered widespread upregulation of truncated mRNAs and proteins in primary CLL cells that were not generated by genetic alterations but instead occurred by intronic polyadenylation

And:

The truncated proteins generated by intronic polyadenylation often lack the tumour-suppressive functions of the corresponding full-length proteins (such as DICER and FOXN3), and several even acted in an oncogenic manner (such as CARD11, MGA and CHST11). In CLL, the inactivation of tumour-suppressor genes by aberrant mRNA processing is substantially more prevalent than the functional loss of such genes through genetic events.

So what does this all mean? First, to reiterate and simplify, the authors detected truncated mRNAs and proteins for a number of tumor suppressor genes in CLL that could not be explained by DNA mutations in the genes themselves, such as splice site mutations. They did a lot of other controls, such as making sure that the explanation for the truncated proteins was not cleavage by proteases, enzymes that cut proteins at specific amino acid sequences. After ruling out other possibilities, the authors demonstrated that these mRNAs and proteins were truncated because of a process called intronic polyadenylation. But what is that?

Polyadenylation is the process of adding a bunch of adenosines (As) to the 3′ end of an RNA molecule. It’s how the poly-A tail is added to the end of an mRNA, but it turns out that it’s a common process for polyadenylation to occur in introns. This process is very widespread and was appreciated well over a decade ago. It’s involved in diversifying the products of immune cell mRNAs, the process explained thusly:

In the splicing literature, isoforms generated through recognition of an IpA signal are often described as ‘alternative last exon’ events. Genes that generate IpA isoforms are thought to harbor competing splicing and polyadenylation signals, producing a full-length messenger RNA (mRNA) when splicing outcompetes polyadenylation and otherwise producing a truncated mRNA. As the defining event is the recognition of an IpA signal, we call these transcripts IpA isoforms. It is now possible to recognize the widespread expression of IpA isoforms through the analysis of 3ʹ-end sequencing data.

Or, to put it more simply, whether there is a truncated protein or a full-length protein depends on the balance of splicing to poly-adenylation at the site in the intron. If there’s more splicing activity, you get much more of the whole protein. If there’s more polyadenylation, you get much more of the truncated protein. What Mayr’s lab found was that too much polyadenylation can result in truncated tumor suppressor proteins in CLL, contributing to the development of the cancer, which is why, according to the MSKCC press release which explains the findings pretty well:

These findings help explain a long-standing conundrum, which is that CLL cells have relatively few known DNA mutations. Some CLL cells lack even known mutations. In effect, the mRNA changes that Dr. Mayr’s team discovered could account for the missing DNA mutations.

Because CLL is such a slow-growing cancer and people with CLL often live for many years, it’s too early to say whether these mRNA changes are associated with a poorer prognosis.

There are some important differences between the mRNA changes and a bona fide DNA mutation. Most important, the inactivation of tumor suppressors through mRNA is usually only partial; only about half of the relevant protein molecules in the tumor cells are truncated. But in many cases this is enough to completely override the function of the normal versions that are present. And because this truncation could apply to 100 different genes at once, the changes can add up.

So why does none of this have anything to do with mRNA-based vaccines causing cancer? I’m glad you asked and hope you don’t mind that I took this opportunity to geek out a bit, in a molecular biology sense. The biology being abused by Wells is actually quite complex and fascinating, and I don’t get to discuss pure molecular biology very often any more. I hope I didn’t lose too many readers with the explanation, but I also bet more than a few of you have already figured out why what Wells is peddling is utter nonsense. If not, here we go.

The payoff of all that beautiful science: Mayr’s paper has nothing to say about whether COVID-19 vaccines targets tumor suppressors

So why do I say that Wells is totally misapplying Mayr’s paper? Simple. There are three reasons that anyone with a knowledge of molecular biology could identify. First, both mRNA vaccines, Moderna and Pfizer, use mRNAs encoding the SARS-CoV-2 spike protein. (The Moderna version, for instance, uses a pre-fusion stabilized spike protein. This detail isn’t really important to understand why Wells is misrepresenting the science, but the molecular biology geek in me wanted to mention this.) Unlike oncogenes and tumor suppressor proteins, which are mutated versions of proteins with normal functions in normal cells, the coronavirus spike protein is not made by normal human cells and has no normal function in human biology. Its only function is for the virus. SARS-CoV-2 binds to the ACE2 receptor on human cells and thereby allows the coronavirus to enter cells to set up shop and start the COVID-19 infection process and churn out more virus. Even if a truncated spike protein were made through the mechanism that Wells apparently doesn’t understand or is lying about, there’s no known biological mechanism for these mRNAs to cause cancer.

Second, the mRNA in the Moderna and Pfizer/BioNTech vaccines does not undergo any splicing, both of which occur in the nucleus. The mRNA sequences in these vaccines is a complete mRNA sequence for the SARS-CoV-2 spike protein and needs no splicing before transcription. Indeed, it really wouldn’t make any sense at all to include in a vaccine an mRNA that requires splicing, as that’s an extra step where things could go wrong and that doesn’t provide any countervailing advantage to make it worthwhile to do. Basically, when you are trying to get eukaryotic cells (as in human cells) to produce a protein from an RNA, keeping the design of the mRNA as simple as possible is best. Use the RNA sequence encoding the protein you want to produce, tack on whatever regulatory sequences to the coding sequence in order to drive expression of the protein, and get as much of the RNA into the cytoplasm to encounter as many ribosomes and churn out as much protein as possible before the RNA, unstable molecule that it is, inevitably degrades. In other words, no splicing or truncated proteins, even if the proteins being produced were even relevant to cancer, which the coronavirus spike protein is not.

Finally, for cancer to develop there needs to be continuing production of the oncogene or continuing elimination of tumor suppressor function in the cell over the long term. The mRNA vaccines used against COVID-19 were intentionally designed to be short-lived. Even if they did produce some sort of truncated protein that could potentially cause cancer, the mRNA and the protein would be gone long before they could trigger cancer, as carcinogenesis is a process that takes months to years, not days to weeks. As I discussed before, the mRNA from these vaccines hangs around for days at most and the protein for a couple of weeks at most. The vaccine’s effects with respect to making spike protein are transient by design.

I will give S.D. Wells credit in a warped sort of way. He understands that the vast majority of people do not have a sufficient background in molecular biology to understand why the Mayr lab paper says nothing about whether COVID-19 vaccines could potentially cause cancer, why even applying it to cancer causation through splicing errors that are not caused by mutations in DNA is a risible misapplication of the paper. He knows that people will see the MSKCC press release about the Mayr lab’s finding that truncated mRNAs can contribute to the development of CLL in the context of his false claims that mRNA-based COVID-19 cause cancer and just make the connection, as scientifically baseless as it is, that the Mayr lab paper found a mechanism by which the mRNA from COVID-19 vaccines can cause cancer too. Again, to misapply a study that deceptively and effectively, I suspect that Wells must have some background in molecular biology, particularly if he was the one who found that paper to cherry pick. Either that, or he’s the luckiest antivaccine propagandist I’ve encountered in a long time.

In the meantime, I’ll finish this post the way I like to finish posts about COVID-19 vaccines and say that, in the age of COVID-19 everything old is new again when it comes to antivax disinformation. There is no good evidence that mRNA-based COVID-19 vaccines cause cancer or even have a plausible mechanism by which they could cause cancer. Mike Adams’ minion S.D. Wells is, quite simply, spreading disinformation. I’m still waiting for antivaxxers to claim that COVID-19 vaccines cause autism, and I know it’s coming sooner or later.