It figures. Just when I didn’t have time to get a post out for tomorrow something big happened, starting off 2024 in a bad way. I’m referring to Wednesday’s press release from the Florida Department of Health, courtesy of its director, Florida Surgeon General Joseph Ladapo. In it, Dr. Ladapo calls for a halt in the use of mRNA-based COVID-19 vaccines based on, well…let me just quote the press release, because I have never in my life seen a government agency as important as the department of health for a large state issue a press release like this:
On December 6, 2023, State Surgeon General Dr. Joseph A. Ladapo sent a letter to the United States Food and Drug Administration (FDA) Commissioner Dr. Robert M. Califf and Center for Disease Control and Prevention (CDC) Director Dr. Mandy Cohen regarding questions pertaining to the safety assessments and the discovery of billions of DNA fragments per dose of the Pfizer and Moderna COVID-19 mRNA vaccines.
The Surgeon General outlined concerns regarding nucleic acid contaminants in the approved Pfizer and Moderna COVID-19 mRNA vaccines, particularly in the presence of lipid nanoparticle complexes, and Simian Virus 40 (SV40) promoter/enhancer DNA. Lipid nanoparticles are an efficient vehicle for delivery of the mRNA in the COVID-19 vaccines into human cells and may therefore be an equally efficient vehicle for delivering contaminant DNA into human cells. The presence of SV40 promoter/enhancer DNA may also pose a unique and heightened risk of DNA integration into human cells.
Let me just note that Dr. Ladapo’s letter from last month is a masterpiece of JAQing off, and basically says what is summarized above in that it lays heavily into a theoretical concern about DNA in a vaccine, specifically the “risk of tumorigenesis if insertion reduces the activity of a tumor suppressor or increases the activity of an oncogene” or if DNA integration results in “chromosomal instability through the induction of chromosomal breaks or rearrangements.” Molecular biologists (like me—remember, I’m not just a surgeon but have a PhD in cellular physiology and my research has long involved molecular biology, sometimes even hardcore old school promoter bashing and gene regulation by microRNAs) will immediately recognize that, yes, theoretically this could happen, but also that, no, the likelihood of its happening with small fragments of DNA from a plasmid that might or might not contain parts of the SV40 promoter is infinitesimally small. Also, as “Debunk the Funk” Dr. Dan Wilson notes, it is standard quality control to test biologics to determine how much residual DNA is left in the final product. It is, of course, impractical, probably impossible even, to reduce the amount of residual DNA to zero; so small amounts of short fragments of DNA are always present in any biological that uses a plasmid to produce its mRNA and, in the case of the use of these techniques to produce something like vaccine proteins or insulin, protein.
If you click on the link in the passage above claiming the “discovery of billions of DNA fragments per dose of the Pfizer and Moderna COVID-19 mRNA vaccines,” you might recognize a certain preprint by antivaxxers including Jessica Rose and Kevin McKernan that I deconstructed in detail after it was released last fall. (I also pointed out that “billions” of fragments is actually a very tiny amount, on the order of 10 femtomoles, and the use of “billions” is designed to frighten those without a background in basic chemistry.) In brief, the study claimed to have found huge amounts of “DNA contamination” in the Moderna and Pfizer COVID-19 vaccines left over from the plasmids used in the manufacturing process to generate the mRNA used in the vaccines. The long version is in the link; the CliffsNotes version can be summarized in two main points:
- McKernan and his fellow cranks, quacks, and pseudoscientists actually found DNA contamination well under the FDA-recommended limits when they used the most reliable test, namely a PCR-based assay. Basically, by the authors’ own measurements, the amount of DNA/vial was well below the FDA guidance of 10 ng DNA/dose. The authors even used a rather obvious trick to make even that small amount of DNA per vial seem like more DNA than it was compared to the FDA limit, namely graphing their results on a log scale.
- Even using the method above, the authors appear to have assumed that the numbers they got above for copy number of DNA fragments corresponded to full length plasmid copy, when clearly it was all fragments averaging ~100 base-pairs (bp) in length, compared to a multi-thousand bp plasmid
- In order to come up with the frightening estimates that they did, McKernan and his fellow disinformation agents used a fluorescence-based assay, the Qubit assay. Depending on the particular fluorescent molecular marker chosen, this assay can distinguish between double-stranded DNA (like plasmid DNA), single-stranded DNA, and RNA. (mRNA is single-stranded.) However, even a highly selective test for dsDNA, when that DNA is mixed with orders of magnitude more RNA, will detect some of that RNA, thus producing a much higher reading than what is there.
As for the fans of Dr. Ladapo who might be upset by my referring to the “scientists” who did this study as cranks, quacks, antivaxxers, pseudoscientists, and disinformation agents, I don’t care. That’s what they are, as I (and others, such as YouTubers “Debunk the Funk” Dan Wilson and Susan Oliver) have abundantly documented, and the “science” (such as it is) in this preprint—which, unsurprisingly, has not yet been published in the peer-reviewed literature and likely never will be, except maybe in a bottom-feeding pay-to-publish predatory open access journal—is execrable in the extreme, designed to mislead. So, naturally, a quack like Dr. Ladapo likes it.
Also, don’t even get me started on the part about SV40, which is a longstanding antivax trope dating back over a decade and based on a real incident involving the polio vaccine in the late 1950s/early 1960s. At that time, it was discovered that some of the oral polio vaccine (OPV), which is a live attenuated virus vaccine, was contaminated with SV40, as simian virus whose large T-antigen could transform cells (turn them cancerous). Again, the long version is in the link; the CliffsNotes version is that, although the SV40 large T-antigen is oncogenic, there is no epidemiological evidence of an increased risk of cancer in people who as children received the OPV contaminated with SV40 in the late 1950s and early 1960s.
Unsurprisingly, antivaxxers being antivaxxers and there never being anything truly new under the sun in antivax misinformation, COVID-19 antivaxxers glommed onto the presence of the SV40 promoter sequence, a short DNA sequence frequently used in plasmids because it is a strong promoter that drives the production of a lot of mRNA, in the plasmid used by Pfizer—but not, I note, Moderna—to drive the expression of an antibiotic resistance marker—but not, I note, the actual spike protein mRNA—to resurrect this particular fear mongering about SV40 in COVID-19 vaccines. Antivaxxers have even gone beyond old misinformation about SV40 whole virus contamination in polio vaccines causing cancer to SV40 promoter sequence in COVID-19 vaccines somehow causing “turbo cancer,” because that’s so much scarier than just cancer, no matter how ridiculous it is, so much so that COVID-19 quacks Dr. Peter McCullough and Dr. William Makis have been spreading this message. Sadly, reinforcing my point about how not knowing common antivax narratives can lead even seemingly reasonable scientists astray, even the director of a large cancer center fell for the trap of finding these claims plausible, thus totally embarrassing himself by agreeing to be interviewed by a rabid antivax conspiracy theorist.
As an aside, I can’t help but ask antivaxxers like Dr. Ladapo: Why are you calling for the cessation of use of both the Pfizer and Moderna vaccines? Only plasmid used to produce the Pfizer vaccine contains an SV40 promoter; the plasmid used to produce the Moderna vaccine does not. Look it up if you don’t believe me. If SV40 is what you’re worried about, then you should be fine with the Moderna vaccine. Dr. Ladapo, just like every other antivaxxer promoting the SV40 fear mongering narrative, fails to mention this difference between the Pfizer and Moderna vaccines because it’s not about science. it’s about fear mongering about vaccines. Moreover, the SV40 promoter, particularly fragments of it, is not oncogenic by itself. Moreover, we have good evidence, both in vitro and in vivo, that whole plasmids with just SV40 promoter elements are not by themselves oncogenic, even when used in huge amounts. If there is no actual DNA for an actual oncogene present, the whole plasmid is not oncogenic, much less fragments of it.
In any event, let’s continue, if only to see just how much Dr. Ladapo parrots antivax disinformation in his press release:
In 2007, the FDA published guidance on regulatory limits for DNA vaccines in the Guidance for Industry: Considerations for Plasmid DNA Vaccines for Infectious Disease Indication(Guidance for Industry). In this Guidance for Industry, the FDA outlines important considerations for vaccines that use novel methods of delivery regarding DNA integration, specifically:
On December 14, 2023, the FDA provided a written response providing no evidence that DNA integration assessments have been conducted to address risks outlined by the FDA themselves in 2007. Based on the FDA’s recognition of unique risks posed by DNA integration, the efficacy of the COVID-19 mRNA vaccine’s lipid nanoparticle delivery system, and the presence of DNA fragments in these vaccines, it is essential to human health to assess the risks of contaminant DNA integration into human DNA. The FDA has provided no evidence that these risks have been assessed to ensure safety.
- DNA integration could theoretically impact a human’s oncogenes – the genes which can transform a healthy cell into a cancerous cell.
- DNA integration may result in chromosomal instability.
- The Guidance for Industry discusses biodistribution of DNA vaccines and how such integration could affect unintended parts of the body including blood, heart, brain, liver, kidney, bone marrow, ovaries/testes, lung, draining lymph nodes, spleen, the site of administration and subcutis at injection site.
So let’s see how much further Dr. Ladapo will go in his lies and misinformation in his press release:
As such, Florida State Surgeon General Dr. Joseph A. Ladapo has released the following statement:
“The FDA’s response does not provide data or evidence that the DNA integration assessments they recommended themselves have been performed. Instead, they pointed to genotoxicity studies – which are inadequate assessments for DNA integration risk. In addition, they obfuscated the difference between the SV40 promoter/enhancer and SV40 proteins, two elements that are distinct.
DNA integration poses a unique and elevated risk to human health and to the integrity of the human genome, including the risk that DNA integrated into sperm or egg gametes could be passed onto offspring of mRNA COVID-19 vaccine recipients. If the risks of DNA integration have not been assessed for mRNA COVID-19 vaccines, these vaccines are not appropriate for use in human beings.
Providers concerned about patient health risks associated with COVID-19 should prioritize patient access to non-mRNA COVID-19 vaccines and treatment. It is my hope that, in regard to COVID-19, the FDA will one day seriously consider its regulatory responsibility to protect human health, including the integrity of the human genome.”
In the spirit of transparency and scientific integrity, State Surgeon General Dr. Joseph A. Ladapo will continue to assess research surrounding these risks and provide updates to Floridians.
I nearly ruined another keyboard spitting up the coffee I was drinking as I wrote this. “Transparency and scientific integrity”? You mean like the transparency and scientific integrity when Dr. Ladapo altered a draft of a study he commissioned the Florida Department of Health to do in order to have the final version of the study show harm from COVID-19 vaccines that the study did not in fact support? The mind boggles. Also, I have to wonder about Dr. Ladapo’s call for prioritizing “non-mRNA COVID-19 vaccines and treatment.” Right now, the only non-mRNA options for COVID-19 vaccines in the US are either adenovirus-based vaccines like the J&J/Janssen COVID-19 vaccine (which is no longer available in the US) or the Novavax COVID-19 vaccine, which is a protein subunit vaccine. Guess what? Even though it’s a protein subunit vaccines, antivaxxers have been fear mongering about “moth DNA” in the vaccine because Novavax uses the baculovirus system, which uses moth cells, to produce the protein subunit used as the vaccine antigen. How long before antivaxxers like Dr. Ladapo start fear mongering about that? Not long, unsurprisingly:
The non-mRNA shots are not named – does he mean Novavax? Janssen? These products are also EUA Countermeasures, full of junk, saponin adjuvant, insect legs, and e.coli/endotoxin and also utilize plasmids in manufacture. Which can also be “forgotten” in them. And none of these companies tested for genetic integration, and the FDA also wasn’t interested in this question. Dr. Ladapo is “hoping that FDA will one day consider, etc.”
His statement is not a real action, it is a political performance to aid his boss DeSantis run for political office. He knows very well these shots can be legally adulterated as EUA Countermeasures and the FDA had no lawful basis to “approve” them since the clinical trials were fake – conducted for non-investigational chemical entities without the IRB approval and without informed consent. That’s why an FDA approved product was never shipped in the US. He is calling for a “halt” – can we ask by whom, and using what procedure? Not good enough, at all. Therefore, my grading of Dr. Ladapo’s performance is a C+.
Of course, antivaxxers are unhappy, because it’s all about fear mongering about vaccines and even Dr. Ladapo isn’t radical enough for them!
As for “treatments,” given that Dr. Ladapo first became famous as part of America’s Frontline Doctors pushing hydroxychloroquine as a cure for COVID-19 back during that first summer of the pandemic in 2020, you can probably guess what he means: disproven treatments like repurposed hydroxychloroquine and ivermectin.
Here’s the thing. Copious evidence exists in the scientific literature that small amounts of random fragments of DNA are not a major risk. Moreover, to believe Dr. Ladapo’s claim that the lipid nanoparticles in which the mRNA in the vaccines is contained are a novel risk because they can get the residual plasmid DNA into cells in a manner that’s never been studied before, you have to ignore about 35 years of history and experiments in molecular biology. As I sometimes like to point out, I did my PhD in the early 1990s in a laboratory where one of the graduate students was working on a project that specifically tried to introduce whole plasmid DNA into chick embryo muscle in order to measure the expression of a marker gene. It was difficult, and it was inefficient. When Dr. Ladapo fear mongers about DNA fragments in lipid nanoparticles, he is either basically ignorant himself about well-established molecular biology conclusions or he knows and is lying. Indeed, it’s not as though this hasn’t been studied; for example, injection of whole plasmid—again, that’s whole plasmid—results in nearly all of the plasmid being extrachromosomal (outside of the chromosomes in the nucleus), with one group of investigators finding that the frequency of integration of plasmid elements into chromosomal DNA of ” ≤1–8 integrations per 150,000 diploid cells, which would be at least three orders of magnitude below the spontaneous mutation rate,” leading them to conclude that the “risk of mutation due to integration of plasmid DNA vaccines following intramuscular injection is negligible.” Even using a method more efficient than lipid nanoparticles (electroporation) and way more plasmid DNA, they found that integration events were quite rare and less frequent than the rate of spontaneous mutation.
Another part of the passage in Dr. Ladapo’s response struck me, namely his hope that “the FDA will one day seriously consider its regulatory responsibility to protect human health, including the integrity of the human genome.” (Emphasis mine.) Remember the whole antivax “pureblood” thing, in which antivaxxers who had refused the COVID-19 vaccine bragged that they were “purebloods,” a nod to the Harry Potter novels in which wizards whose ancestry had nonmagical humans in it referred to themselves as “pureblood” and disparagingly referred to those who did have nonmagical humans (Muggles) in their ancestry as “mudbloods”? Also remember how obsession about the “purity” of one’s blood was very much a part of Nazi beliefs regarding the Aryan race, which was why being “pureblood” was associated with followers of the main villain of the Harry Potter novels, Lord Voldemort? Dr. Ladapo is clearly dog whistling to the fascist “pureblood” crowd, as he did on Bigtree’s show when he claimed that DNA from the vaccine is “hitchhiking into human cells.” After all, it’s not as though it wasn’t incredibly clear in the Harry Potter novels and movies that the magical “pureblood”/”mudblood” dichotomy was an obvious metaphor for Nazi ideas about racial “purity” and superiority, with the Muggles being viewed by Voldemort and his followers as inferiors who were “contaminating” the pure wizard race, complete with a horror on the part of Voldemort at the thought of magical people mating with Muggles and having children that was every bit as strong as the disgust that Nazis expressed at Jews mixing with “pure Aryans.” An obsession with vaccines being supposedly “contaminated” with DNA and thus prone to “permanently altering” your DNA is just one example of how the antivax purity cult manifests its beliefs.
I could go on and on and on—and have gone on and on and on—about how horribly wrong Dr. Ladapo is about COVID-19 vaccines on a scientific basis and how the minuscule amount of plasmid DNA fragments left over from the manufacturing process is nothing to be afraid of, but why bother? What is truly disturbing about this incident is not so much the form of the antivax misinformation being parroted—and, make no mistake, Dr. Ladapo is parroting antivax disinformation—but rather who is parroting it. Never before can I recall—at least not in the US—a whole state government having co-opted its health department to promote antivaccine misinformation, thus taking advantage of the credibility with which Americans have generally viewed state health departments to spread a message that will actively harm the health of the population of not just one state, but all states. Why? Well, if you think that what Florida does affects only Floridians, you have a very narrow view of politics. Of course Dr. Ladapo’s lies and disinformation affect more than just Florida, because a whole disinformation ecosystem was waiting to take up his message and promote it as government-sanctioned “validation” of their misinformation, disinformation, pseudoscience, quackery, and conspiracy mongering. That’s the idea, and he and Gov. DeSantis surely know that.
Back in the beforetime (actually, more like 10-15 years ago) I used to say—correctly, I might add—that, contrary to the stereotype then that antivax was an ideology primarily limited to granola-crunching, sandal-wearing lefties, it was actually the conspiracy theory shared by the left and the right. I also used to point out that it wasn’t all that long ago that standard public health measures, including school vaccine mandates, once shared wide bipartisan support and were fairly uncontroversial. That started to change beginning around 15 years ago, give or take, when the center of gravity of the antivax movement started drifting to the right. The pandemic accelerated the process far beyond anything I could have predicted to the point that right here, right now, in 2024, one party—the Republican Party—has adopted the most bonkers of old antivax conspiracy theories, pseudoscience, and misinformation as a major part of its core ideology. Gov. Ron DeSantis and his lackey Dr. Joseph Ladapo are just one manifestation of that and how we can’t count on civil servants to save us from this; once cranks take over the levers of government, opposition will eventually be purged. I pity any scientists and physicians still dedicated to actual public health science who might remain in the Florida Department of Health. They face an awful choice of going along with their new masters, quitting, or being eventually purged.