Ever since the COVID-19 pandemic began and antivaxxers made common cause with COVID-19 cranks, deniers, and conspiracy theorists, I’ve been repeating a simple message: Everything old is new again. The pandemic has resulted in a lot of scientists and other people paying attention to the antivaccine movement in a way that they never have before. Many of these newbies have been amazed at some of the antivaccine misinformation and disinformation that have been spread about the new COVID-19 vaccines. False antivax claims about these vaccines include a veritable antivax “greatest hits” of pseudoscience, conspiracy theories, and distortions, a veritable playbook of claims that COVID-19 vaccines kill, cause miscarriages and/or infertility, cause autoimmune disease, “permanently alter your DNA“, are unnecessary because COVID-19 is not dangerous, that the number of cases are exaggerated, and that the vaccines are filled with “toxins” (in the case of the mRNA vaccines, the lipid nanoparticles used to encapsulate the mRNA coding for COVID-19 spike protein). Now two more famous antivax claims from the past are popping up in my social media feeds, and they are related. I’m referring to the false claim that the COVID-19 vaccines cause prion disease and that they cause Alzheimer’s disease. We have “immunologist” Dr. J. Bart Classen to thank for this disinformation and antivaxxers like Robert F. Kennedy, Jr. for spreading it.
First, let’s show how his claim is yet another example of my adage regarding disinformation about the COVID-19 vaccine that “everything old is new again”.
Vaccines and Alzheimer’s disease: A brief history
One of the earliest antivaccine claims that I ever dealt with was a rather specific claim about the influenza vaccine. I first encountered it when Bill Maher parroted it in an interview with Larry King on Larry King Live, way back in December 2005. (Yes, you read that correctly, 2005.) I think it’s useful to recount what Maher said in this exchange:
MAHER: I’m not into western medicine. That to me is a complete scare tactic. It just shows you, you can…
KING: You mean you don’t get a — you don’t get a flu shot?
MAHER: A flu shot is the worst thing you can do.
MAHER: Because it’s got — it’s got mercury.
KING: It prevents flu.
MAHER: It doesn’t prevent. First of all, that’s…
KING: I haven’t had the flu in 25 years since I’ve been taking a flu shot.
MAHER: Well, I hate to tell you, Larry, but if you have a flu shot for more than five years in a row, there’s ten times the likelihood that you’ll get Alzheimer’s disease. I would stop getting your…
KING: What did you say?
MAHER: That went better in rehearsal but it was still good. Absolutely, no the defense against disease is to have a strong immune system. A flu shot just compromises your immune system.
Where did the claim that getting a flu shot more than five years in a row increases your risk of someday developing Alzheimer’s disease originate? While I’m not sure where the claim that the flu shot predisposes to Alzheimer’s disease truly originated, I’m pretty sure I know where the specific claim about five years’ worth of flu shots increasing the risk of Alzheimer’s disease by ten-fold came from. At the time, a search on that hoary old crank and conspiracy theory website Whale.to quickly revealed this gem from a conference held by the antivaccine group National Vaccine Information Center (NVIC) in 1997:
According to Hugh Fudenberg, MD (http://members.aol.com/nitrf), the world’s leading immunogeneticist and 13th most quoted biologist of our times (nearly 850 papers in peer review journals), if an individual has had five consecutive flu shots between 1970 and 1980 (the years studied) his/her chances of getting Alzheimer’s Disease is ten times higher than if they had one, two or no shots. I asked Dr. Fudenberg why this was so and he said it was due to the mercury and aluminum that is in every flu shot (and most childhood shots). The gradual mercury and aluminum buildup in the brain causes cognitive dysfunction. Is that why Alzheimer’s is expected to quadruple? Notes: Recorded from Dr. Fudenberg’s speech at the NVIC International Vaccine Conference, Arlington, VA September, 1997. Quoted with permission. Alzheimer’s to quadruple statement is from John’s Hopkins Newsletter Nov 1998. —-Ted Koren, D. C. http://www.odyssee.net/~expodome/autism.htm#Top Koren Publications (800-537-3001).
A chiropractor. Of course, the presentation at NVIC had to be recorded by a chiropractor:
And here’s a more recent addition since 2005, dated 2006:
Vancouver neuroscientist Chris Shaw shows a link between the aluminum hydroxide used in vaccines, and symptoms associated with Parkinson’s, amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), and Alzheimer’s…..”This is suspicious,” he told the Georgia Straight in a phone interview from his lab near Heather Street and West 12th Avenue. “Either this [link] is known by industry and it was never made public, or industry was never made to do these studies by Health Canada. I’m not sure which is scarier.” Similar adjuvants are used in the following vaccines, according to Shaw’s paper: hepatitis A and B, and the Pentacel cocktail, which vaccinates against diphtheria, pertussis, tetanus, polio, and a type of meningitis….”No one in my lab wants to get vaccinated,” he said. “This totally creeped us out. We weren’t out there to poke holes in vaccines. But all of a sudden, oh my God—we’ve got neuron death!” —[Media 3/2006 Aluminium adjuvant] Vaccines show sinister side.
Over the years, I frequently saw the claim that the flu vaccine or aluminum adjuvants in flu vaccines cause Alzheimer’s disease popping up on antivaccine websites and social media. It has basically become an article of faith among antivaxxers that flu vaccine, if not aluminum adjuvants in vaccines in general, predispose to or even cause Alzheimer’s disease. As for Fudenberg, he was a real quack back in the day.
Here’s what I mean. Hugh Fudenberg was a collaborator and co-inventor with the disgraced antivaccine physician Andrew Wakefield, who committed research fraud in his “study” published in The Lancet in 1998 linking the MMR vaccine to autism and ultimately had his medical license revoked in the UK over his misconduct.
Dr. Fudenberg also happens to have been involved in some very dubious “treatments” for autism that led to some problems with his medical license. In November 1995, the South Carolina Medical Board concluded that Fudenberg was “guilty of engaging in dishonorable, unethical, or unprofessional conduct”, and he was fined $10,000 and ordered to surrender his license to prescribe controlled substances (narcotic drugs). His medical license was also placed on suspension. In March 1996, he was permitted to resume practice under terms of probation that did not permit him to prescribe any drugs. His medical license expired in January 2004; and in March 2004, he applied to have it reinstated. However, after a hearing in which the Board considered a neuropsychiatric report issued in 2003, Fudenberg agreed to remain in a “retired” status and withdrew his application for reactivation of his license.
Later, Dr. Fudenberg ran a nonprofit “research” organization called Neuro Immunotherapeutics Research Foundation that sold dubious remedies for autism. He also charged $750 per hour for “review of past medical records”, $750 per hour for “determining what new tests need to be ordered; ordering of new tests; evaluation of new tests”, and $750 per hour for “determining which therapy will work and which will not; discussing this with patient along with an in-depth study of past medical history to determine what makes a patient better or worse”. The specific dubious autism treatment with which Dr. Fudenberg was involved is the use of something called “transfer factor” to make a combined measles vaccine and autism “cure”. The method of making these so-called “transfer factors” is bizarre in the extreme and involves injecting mice with measles, extracting and processing white blood cells, injecting the result into pregnant goats, milking the goats after kid-birth and turning the product into capsules for autistic children. In a patent application (based in part on the infamous Lancet paper) obtained by Brian Deer, Wakefield represented a vaccine/therapy for “MMR-based” autism using transfer factor as potentially a “complete cure” for autism or for “alleviation of symptoms”.
And, to repeat, Fudenberg liked to claim that the flu vaccine causes Alzheimer’s disease, even though there is no evidence to support the hypothesis that the flu vaccine predisposes to autism; indeed, there is evidence for the opposite. (There’s even evidence in a mouse model that repeated vaccination against influenza is neuroprotective.)
But what about prion disease? And what are prion diseases, anyway?
Vaccines and prion disease
Before I discuss all these claims, I have to answer the question: What are prions? Prion diseases are more properly referred to as transmissible spongiform encephalopathies (TSEs) and represent a rare form of progressive neurodegenerative disorders that can affect both humans and animals. The most famous prion diseases in animals are bovine spongiform encephalopathy (BSE, also known as “Mad Cow Disease”), scrapie, and chronic wasting disease; in humans, Creutzfeldt-Jakob Disease (CJD) and kuru. These diseases have a long incubation period and produce in the brain characteristic spongiform changes associated with loss of neurons with no inflammatory response. The causative agents for these diseases are prions. According to the CDC:
The term “prions” refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. The functions of these normal prion proteins are still not completely understood. The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Prion diseases are usually rapidly progressive and always fatal.
Basically, prions are believed to be misfolded proteins that can transmit their misfolded shape onto normal variants of the same protein. I don’t need to go into the details for you to understand the very basics of prion disease, other than to note that the protein that makes up prions (PrP) is found in many places in the body in healthy people and animals, and its normal function in biology and physiology is poorly understood.
The claim by antivaxxers that vaccines can result in prion disease is one that I’ve seen far less frequently than the claim that they cause Alzheimer’s disease, so much so that a review of SBM found that we’ve only touched on it briefly in John Snyder’s review of Dr. Bob Sears’ book touting his “alternative” vaccine schedule. The origin of the claim appears to derive from the observation that the media used to support the growth of some of the cell lines used to grow virus stock from which vaccines are made contains fetal bovine serum (FBS), a common ingredient in cell culture media. Antivaxxers use that observation to claim a risk of “prion contamination” of vaccines. Never mind that such contamination of a vaccine has never been demonstrated.
Like many antivaccine myths, the myth that vaccines might become contaminated with prions originates from a grain of truth. Decades ago, during the height of the mad cow disease outbreak in the UK, there was indeed concern about using FBS from British herds of cattle to manufacture vaccines. A news article in Nature from 2000 reported on the findings of an inquiry into Britain’s BSE epidemic and even specifically asked the question: “Were some CJD victims infected by vaccines?” The report basically concluded that the answer to that question was unknown, but:
The BSE inquiry’s report (see above) calls for vaccines to be investigated as a possible route of transmission. But it concedes that this will be hampered by the fact that “systematic records of the action taken in response to BSE in respect of individual medical products are lacking”.
Alarmingly, vaccines produced after the point at which the BSE epidemic had been identified — possibly using British bovine material — were still in use as recently as November 1993. According to the inquiry’s report, the chief medical officer of the day, Donald Acheson, decided to phase out the existing stocks because new batches of vaccines take time to grow, and medical experts considered that the benefit of maintaining a continuous national immunization programme outweighed the risk of interrupting it.
An article in MPR from 2010 by pediatrician Dr. Gary S. Marshall, author of The Vaccine Handbook: A Practical Guide for Clinicians (The Purple Book), is more reassuring. Noting that the FDA convened a meeting in 2000 to discuss the very question of whether vaccines could transmit BSE, Dr. Marshall characterizes the conclusions of the FDA thusly:
Although the risk of transmission of vCJD to humans from such vaccines was considered theoretic and remote, the recommendation was made that vaccines use bovine materials originating from countries without endogenous MCD. Mathematical models suggest that the agent of MCD first entered cattle feed in the United Kingdom around 1980; since the vast majority of initial cases of vCJD were born well before then, childhood vaccines were not likely to be the cause.
Maternal-fetal transmission of prions has never been documented in animals and fetal blood is not known to contain prions. Moreover, the fetal bovine serum used in vaccine manufacture is highly diluted and eventually removed from cells during purification of vaccine viruses. It should be pointed out as well that prions propagate in mammalian brain but not in cell culture.
Final reassurance comes from the fact that transmission of prions occurs from eating the brains of infected animals or from directly inoculating preparations of brains of infected animals into the brains of experimental animals. Transmission of prions has not been documented after inoculation into the muscles or under the skin, which are the routes used for vaccination. Taken together, the chances that currently licensed vaccines contain prions and represent a risk to humans is essentially zero.
So, basically, although the claim that vaccines could transmit prions entered the antivaccine lexicon of disinformation in the 1990s, after billions upon billions of doses of vaccines for which the viral stock was grown in FBS-containing media, there remains no good evidence that vaccines have ever been contaminated with prions or ever caused a single case of prion disease in humans or animals.
Enter J. Bart Classen
You might wonder why I spent so much time going over the history of (and lack of evidence for) the claims that vaccines can cause Alzheimer’s disease or transmit prion diseases. My answer is simple and involves repeating my mantras with respect to the antivaccine movement and COVID-19. There is nothing new under the sun (in the antivaccine movement), and everything old is new again (when it comes to COVID-19 vaccines). Now that you know that there is no evidence to support these claims and that they are totally antivaccine disinformation, you know that J. Bart Classen’s claims about the COVID-19 vaccine are likely, similarly, to be nonsense. You can reflect back on the information I’ve imparted as I discuss Classen’s claims in a paper, even as I bring in the twist that Classen adds to try to make these claims seem plausible for the COVID-19 vaccine. Predictably, the twist is the claim that the mRNA in vaccines is what causes prion disease and results in Alzheimer’s disease.
So let’s look at the paper, which was published in an online journal, Microbiology & Infectious Diseases, and entitled “COVID-19 RNA Based Vaccines and the Risk of Prion Disease“. Unsurprisingly, it’s an open access journal not indexed in PubMed that’s published by SciVision Publishers, which shows up in Beall’s list of predatory publishers. Is this a predatory publisher? I don’t know, as there is apparently not strong agreement whether it should be classified as such, but the fact that it’s not indexed in PubMed certainly suggests that, at the very least, it’s not very likely to be a quality journal.
Deceptively, Classen writes this paper as though it were a real research paper, complete with hypothesis, experimental approach, results, and conclusions, starting with this fine bit of handwaving in the introduction:
The advent of new vaccine technology creates new potential mechanisms of vaccine adverse events. For example, the first killed polio vaccine actually caused polio in recipients because the up scaled manufacturing process did not effectively kill the polio virus before it was injected into patients. RNA based vaccines offers special risks of inducing specific adverse events. One such potential adverse event is prion based diseases caused by activation of intrinsic proteins to form prions. A wealth of knowledge has been published on a class of RNA binding proteins shown to [sic] participating in causing a number of neurological diseases including Alzheimer’s disease and ALS. TDP-43 and FUS are among the best studied of these proteins .
The Pfizer RNA based COVID-19 vaccine was approved by the US FDA under an emergency use authorization without long term safety data. Because of concerns about the safety of this vaccine a study was performed to determine if the vaccine could potentially induce prion based disease.
The first rule of reading an introduction like this is simple: Always look up the reference cited, in this case, this article. In this case, the article is a review article that looks at RNA binding proteins (not mRNAs or RNAs) that have prion-like domains found in neurodegenerative diseases:
Scouring the human genome with this algorithm enriches a select group of RNA-binding proteins harboring a canonical RNA recognition motif (RRM) and a putative prion domain. Indeed, of 210 human RRM-bearing proteins, 29 have a putative prion domain, and 12 of these are in the top 60 prion candidates in the entire genome. Startlingly, these RNA-binding prion candidates are inexorably emerging, one by one, in the pathology and genetics of devastating neurodegenerative disorders, including: amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer’s disease and Huntington’s disease. For example, FUS and TDP-43, which rank 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating motor neurons of ALS patients and mutations in TDP-43 and FUS cause familial ALS.
So right off the bat, I know that Classen’s rationale for making the claim that the COVID-19 vaccine can induce prion disease is very weak. He’s pointing to RNA binding proteins, not mRNAs or RNAs, and he’s using that as a rationale to imply that a vaccine that contains only lipid nanoparticles and mRNA can cause prion disease. How, you might wonder, did he do this?
Let’s look at the methods section:
Pfizer’s RNA based vaccine against COVID-19 was evaluated for the potential to convert TDP-43 and or FUS to their prion based disease causing states. The vaccine RNA was analyzed for the presence of sequences that can activate TDP-43 and FUS. The interaction of the transcribed spike protein with its target was analyzed to determine if this action could also activate TDP-43 and FUS.
How did Classen “evaluate the potential to convert TDP-43 and or FUS to their prion based disease causing states.” No, seriously, exactly how did he do that? He doesn’t say. Sure, he claims to have “analyzed” the mRNA sequence encoding the SARS-CoV-2 spike protein that was used in the Pfizer/BioNTech COVID-19 vaccine to induce cells to encode the protein to be used as the vaccine’s antigen, but he didn’t say how he did that. Classen appears to be leading readers to believe that he did some sort of bioinformatics analysis of the nucleotide sequence of the mRNA used in Pfizer’s COVID-19 vaccine, but details matter. Nowhere is there a figure showing the alignments of the sequences that he allegedly found that can “activate” TDP-43 and FUS. Nowhere in the paper is a description of the specific algorithms used to produce these claimed “alignments”. Nowhere is there a description of the methodology used or the analysis of the “goodness of fit” for the sequences that he claims to have identified that align with prion “activating” proteins. Nowhere is there a description of the controls, such as normal RNA sequences that contain the relevant sequences, which are common, so common as to be ubiquitous.
Instead, he engages in this bit of handwaving:
Analysis of the Pfizer vaccine against COVID-19 identified two potential risk factors for inducing prion disease is [sic] humans. The RNA sequence in the vaccine  contains sequences believed to induce TDP-43 and FUS to aggregate in their prion based conformation leading to the development of common neurodegerative diseases. In particular it has been shown that RNA sequences GGUA , UG rich sequences , UG tandem repeats , and G Quadruplex sequences , have increased affinity to bind TDP-43 and or FUS and may cause TDP-43 or FUS to take their pathologic configurations in the cytoplasm. In the current analysis a total of sixteen UG tandem repeats (ΨGΨG) were identified and additional UG (ΨG) rich sequences were identified. Two GGΨA sequences were found. G Quadruplex sequences are possibly present but sophisticated computer programs are needed to verify these.
Unfortunately, some of the papers cited by Classen show that what he is claiming, namely that the mRNA in the Pfizer COVID-19 vaccine can induce TDP-43 and FUS to “go prion,” is basically impossible. For example, this paper points out that TDP-43 is an RBP that exists predominantly in the nucleus. As I pointed out the last time I took on the antivaccine claim that mRNA-based COVID-19 vaccines can “reprogram your DNA”, the mRNA from the vaccine never makes it into the nucleus. Guess what? FUS is a nuclear RBP as well!
So what we have here is a whole heck of a lot of speculation, with the finding of an obscure connection based on methodology that is not explained with anywhere near the level of rigor that a real molecular biologist or bioinformatics scientist would require to be convinced. Basically, Classen points to the mRNA sequence in the Pfizer COVID-19 vaccine and finds sequences associated with the “prionization” of these proteins, while completely ignoring the known fact that these are nuclear proteins and that the mRNA in the COVID-19 vaccine remains in the cytoplasm. In fact, the whole idea that there are mRNAs that can behave like prions and induce misfolded proteins appears, if this recent review arguing for an expansion of the definition of prion is any indication, to be largely speculative and not yet firmly demonstrated at this time.
Amusingly, Classen can’t resist adding one more layer to his speculation:
The spike protein encoded by the vaccine binds angiotensin converting enzyme 2 (ACE2), an enzyme which contains zinc molecules . The binding of spike protein to ACE2 has the potential to release the zinc molecule, an ion that causes TDP-43 to assume its pathologic prion transformation .
First, it’s a zinc ion that binds ACE2, not a “molecule”. “Dr.” Classen should really get some basic chemical terminology right if he wants to be taken seriously. Second, this is the purest speculation to claim that the spike protein will somehow result in the release of zinc from ACE2 that will then cause TDP-43 to “go prion”. Again, all you have to know to realize how much handwaving is involved here is to know that ACE2 is a cell surface receptor and TDP-43 is a nuclear protein. The two proteins aren’t even in the same compartment of the cell. Truly, Classen’s handwaving here is achieving sufficient velocity for him to lift off and fly like a bird!
Of course, in his discussion, Classen also can’t resist the JAQing off (if you don’t know what that means, click here) portion of his handwaving speculation:
Another related concern is that the Pfizer vaccine uses a unique RNA nucleoside 1-methyl-3′-pseudouridylyl (Ψ). According to FDA briefing documents, this nucleoside was chosen to reduce activation of the innate immune system . RNA molecules containing this nucleoside will undoubtedly have altered binding . Unfortunately, the effect on TDP-43, FUS and other RNA binding proteins is not published. The use of this nucleoside in a vaccine can potentially enhance the binding affinity of RNA sequences capable of causing TDP-43 and FUS to assume toxic configurations.
Again, none of this matters because these proteins are not even in the same cellular compartment that the COVID-19 vaccine mRNA enters. That’s not all, though. Prion diseases are diseases of the central nervous system. These vaccines are injected into the muscle, and, even if Classen’s ideas were anything other than speculation pulled out of his nether regions about highly tenuous and, yes, speculative associations, COVID-19 vaccines aren’t injected into the central nervous system.
Who is J. Bart Classen?
It turns out that he’s been a subject on this particular blog before, primarily as scientist who gave antivaxxer Robert F. Kennedy, Jr. ammunition for his false claim that vaccines are responsible for the obesity epidemic. According to Wikipedia, Dr. Classen received his MD from the University of Maryland, Baltimore in 1988 and also has an MBA from Columbia University. Unsurprisingly, he’s been quoted by Sharyl Attkisson, a reporter who’s become an antivaccine activist and conspiracy theorist in her own right. Classen’s website, Vaccines.net, is pretty rudimentary but does proclaim:
The content of this site is not intended to be anti-immunization but instead to promote the concept that the goal of immunization is to promote health not eradicate infections. It is hoped that through the collection and dissemination of information about the chronic effects of vaccines, safer immunization practices will become available for those who choose to be immunized.
There it is, the “I’m not ‘antivaccine’; I’m a pro-safe vaccine” gambit, beloved of antivaxxers going back at least to Jenny McCarthy 14 years ago. Naturally, after proclaiming himself a “vaccine safety advocate”, Dr. Classen then goes on to spout antivaccine misinformation:
There is growing evidence that immunization causes a large number of other chronic diseases including autism, diabetes, obesity, metabolic syndrome, autoimmune diseases, allergies, asthma, cancers, and Gulf War Syndrome. Data linking these diseases to vaccines includes human and animal data. In many cases, the increased risk of developing these diseases following immunization exceeds the risk of infectious complications prevented by immunization.
In other words, “I’m not antivaccine, but I believe that vaccines cause every disease under the sun and are riskier than infectious disease”. (Actually, that’s the very definition of being antivaccine.) It turns out that Classen originally made his name in the 1990s claiming that vaccines cause diabetes. Ultimately, he ended up forming an antivaccine company, Classen Immunotherapies, which is the organization that appears on his paper. Unsurprisingly, of late, Classen Immunotherapeutics has been proclaiming how “concerned” it has become about the “safety of vaccines for COVID-19” and how it “believes all the risks are not known and have not been discussed with the public”.
Just for amusement, I perused the list of publications on Classen’s website. Unsurprisingly, he believes the conspiracy theory that COVID-19 is a bioweapon that was initially spread clandestinely and a new one on me, namely that the 2019 epidemic of E-vaping acute lung injury was caused in part by COVID-19, never mind that the first case of COVID-19 wasn’t identified as a new disease in China until very late in 2019 and the disease didn’t become widespread outside of China until early 2020.
And now he thinks that mRNA-based COVID-19 vaccines can cause prion disease leading to neurodegenerative diseases like Alzheimer’s disease. With zero evidence to support his idea and very close to zero biological plausibility. Of course.
Variations on a theme
I return to my mantras about the antivaccine movement in the age of COVID-19: There is nothing new under the sun (in antivaccine circles), and everything old is new again (when it comes to antivaccine conspiracy theories and disinformation). Even the most obscure antivaccine pseudoscience and conspiracy theories are being resurrected, dusted off, tweaked a bit, and repurposed to use to attack COVID-19 vaccines. There doesn’t need to be any evidence or even biological plausibility, just science-y speculation that sounds impressive to people without a background in the relevant sciences. Classen’s claim that mRNA vaccines can cause prion disease leading to neurodegenerative disorders like Alzheimer’s disease is just another example of this.
With Classen’s claim, I’m hard pressed to think of an old antivaccine trope that hasn’t yet been weaponized against COVID-19 vaccines, with one exception. No one, to my knowledge, has yet claimed that COVID-19 vaccines cause autism. The reason for that omission is simple, however. As of today, no COVID-19 vaccine has been authorized for use in children. As soon as a COVID-19 vaccine is authorized or approved for use in children, antivaxxers will claim it causes autism. It’s coming. You know it is.