James Lyons-Weiler and Paul Thomas: Incompetently demonizing aluminum vaccine adjuvants

I’ve frequently discussed how, to the antivaccine movement, aluminum is the new mercury? What do I mean by that? Regulars who’ve been following the misinformation, pseudoscience, and misdirections promoted by the antivaccine movement know that, way back when I first started blogging in 2004 and for several years before, one major faction of the antivaccine movement was something we dubbed the “mercury militia.” The mercury militia was more of an American phenomenon, as opposed to the Andrew Wakefield wing of the antivaccine movement that demonized the MMR vaccine for causing autism based on Wakefield’s fraudulent case series published in The Lancet in 1998. True to its name, the mercury militia demonized vaccines based on the mercury-containing preservative thimerosal, which was used in multidose vials of some childhood vaccines until around 2002, after the CDC had, in a misuse of the precautionary principal and as a result of the strong personality of one man, recommended its removal. This, of course, only fueled the mercury militia’s fear mongering about mercury. Later, as study after study after study were published showing no link between thimerosal-containing vaccines and autism, even the mercury militia had difficulty defending its key hypothesis, to the point that the mercury militia group Generation Rescue dropped mercury as The One True Cause of Autism in favor of a hypothesis positing multifactorial causes (vaccines, toxins, heavy metals, pollution) that was, conveniently, much more difficult to falsify. (More recently, Generation Rescue has rebranded itself into more general autism quackery and grift.) Enter aluminum, which became the new mercury.

Aluminum, of course, is used as an adjuvant, which increases the immune response to a vaccine, allowing less antigen to be used in the vaccine. It’s generally present in the form of aluminum hydroxide and/or aluminum phosphate salts. They’re injected intramuscularly and sit in the muscle with the antigens, provoking the desired immune response through mechanisms that aren’t well understood.

Now, also enter Paul Thomas and James Lyons-Weller, whom we’ve met before and who have apparently teamed up to do a dubious “vaxxed/unvaxxed” study. They’ve also published a paper demonizing aluminum, which Del Bigtree is touting:

Informed Consent Action Network Founder Del Bigtree today touted a new study that will be published in the March 2020 Journal of Trace Elements in Medicine and Biology, showing the U.S. Centers for Disease Control and Prevention’s (CDC) vaccine schedule is 15.9 times the recommended safety level for aluminum when adjusted for body weight.

“The researchers concluded that in the first 149 days of life, from birth to seven months, a child is in a state of ‘chronic toxicity’ for aluminum about 70% of the time,” Bigtree, an Emmy-award winning television producer and host of the weekly online science and health program The HighWire, says.

The researchers chose the time range ‘birth to seven months’ due to the significant neurodevelopmental changes that occur during that period. Aluminum has been found in the brains of patients with Parkinson’s Disease, Alzheimer’s disease, epilepsy, and autism.

How quaint. How old-fashioned. The paper is already online in an Epub Ahead of Print format, and Bigtree is acting as though print journals still matter when it comes to publication dates. Why is he waiting until early 2020 to have Lyons-Weiler and Thomas on his show? Maybe he’s not so old-fashioned after all and realizes that the impeachment drama and the impending holidays mean that a lot of people won’t be paying attention. Whatever the reason, let’s look at the paper.

Two of the authors, as I’ve mentioned before, are known to me. James Lyons-Weiler was actually a legitimate scientist before he turned to antivaccine pseudoscience, having trained in computational molecular biology and served as the director of the Bioinformatics Analysis Core at the University of Pittsburgh for several years until around five years ago, when, for whatever reason, he left and founded the Institute for Pure and Applied Knowledge (IPAK), which took to carrying out and funding pseudoscientific antivaccine projects. Basically, he’s gone full antivax. Paul Thomas, of course, is a pediatrician in Portland, OR who’s become a rising star in the antivaccine movement by coming up with a “delayed” vaccine plan that resembles Dr. Bob Sears’ plan, agitating against vaccines in his “holistic” practice with “misinformed consent” while claiming to be “pro-safe vaccine,” and claiming that, like the late Dr. Mayer Eisenstein did without ever actually showing the evidence, that the prevalence of autism in his unvaccinated patients is much lower than in the vaccinated.

Who are the other two “researchers”? Both Grant McFarland and Elaine La Joie are listed as being affiliated with IPAK. McFarland’s bio lists him as having a BS in electrical engineering from Duke University, and a PhD in electrical engineering from Stanford University, whose expertise is in microprocessor design. His utter lack of expertise in epidemiology, immunology, infectious disease, and epidemiology notwithstanding, he’s listed as an investigator for a study of aluminum accumulation under alternative schedules and, of course, IPAK and Thomas’ vaccinated vs. unvaccinated study. La Joie is only slightly more qualified. Her bio lists her as having a BS in Physics from San Jose State University and a Masters in Applied Physics from Oregon Graduate Institute, but she did do a fellowship at the NIH and “worked in biomedical research at the Oregon Medical Laser Center in Portland and later in neuroscience at the University of Texas.”

Also:

Elaine also is a certified life coach, and has a shamanic work practice mainly working with clients who have experience trauma. She has written a series of books based on her client work called The Empath as Archetype. She is excited to return to science and contribute to IPAK in any way she can.

Given the nature of IPAK, I’m not sure I’d call this “returning” to science.

So what we have here are:

• An antivax pediatrician with no experience in epidemiology, basic science studies, epidemiology, advanced pharmacology research, or clinical trial design.
• An antivax computational biologist with minimal experience in epidemiology or the design of epidemiological studies, and little experience in pharmacology or pharmacokinetics.
• An electrical engineer whose expertise is microprocessor design.
• A physicist with a smattering of research experience in biomedical science.

OK, then. This lineup of qualifications hardly fills me with confidence. To do an analysis of this type, you need people with expertise in pharmacokinetics and pharmacodynamics and in modeling. None of the investigators show any evidence of having the necessary expertise, and Lyons-Weiler’s expertise in computational biology does not translate to PK/PD. That issue having been taken care of, let’s move on to the paper, Acute exposure and chronic retention of aluminum in three vaccine schedules and effects of genetic and environmental variation, published in—where else?—the latest go-to journal for antivaccine papers seeking to demonize aluminum, the Journal of Trace Elements in Medicine and Biology.

The abstract is a word salad of misapplied concepts that immediately tells me that no original research is being done. It’s all modeling, and it’s basically propaganda for Thomas’s “Vaccine-Friendly Plan” more than science. Its assumptions are so utterly simplistic that I was actually embarrassed for the investigators reading it. First of all, Lyons-Weiler harps on a 1995 paper by Priest et al, which studied the metabolism of aluminum-26 and gallium-67 by injecting them intravenously into a single healthy male subject and then measuring the retention by measuring the remaining radioactivity. Levels in blood, urine, and feces were determined by y-ray spectrometry and/or accelerator mass spectrometry. This was the basis of the modeling done by Lyons-Weiler. The problem with Lyons-Weiler assuming this to be a valid set of data to base his modeling on this study will rapidly become apparent. Maybe you have already recognized the flaw.

First, though, Lyons-Weiler’s whole bugaboo is that the FDA’s safe level for aluminum dosing is for adults and that it’s not normalized to a child’s weight:

Minimum safe levels (MSLs) for aluminum (in the form of aluminum oxyhydroxide, aluminum phosphate, or aluminum potassium sulfate) are equivalent to the Pediatric Dose Limit estimated by Lyons-Weiler and Ricketson (29,773,196), based on the FDA’s limit of 850 μg of aluminum per dose for adults. Assuming an average adult weight of 60 kg and using Clark’s rule (cited in Lyons-Weiler and Ricketson) leads to a target “safe” limit of 14.2 μg of aluminum per kg of body weight as a way of calculating a body weight-adjusted Pediatric Dose Limit (PDL: Lyons-Weiler and Ricketson, 29,773,196); Fig. 1. This curve, derived by Lyons-Weiler and Ricketson, is the only available dose limit for human infants that considers body weight. As a limit, it attends to the cumulative dosage and body burden from any source if the values are known. This target limit per body weight was used along with weight distributions across the population to estimate a minimum safe level (MSL) of aluminum exposure as a function of a child’s age and weight percentile.

Clark’s rule is basically a quick and dirty formula to scale adult doses of a medicine to pediatric doses by weight. A certain feathery dinosaur has already discussed this in detail. (Actually, he hosted an article by aultDwellerSYR, a pseudonym used by a faculty member of a School of Pharmacy within a large medical school.) So I don’t see a lot of value to explaining the same thing, other than maybe to add some sarcasm that our raptory friend’s guest blogger left out. So I’ll both quote liberally and add my sarcasm. After all, Lyons-Weiler definitely deserves a fair amount of not-so-Respectful Insolence. The article to which Lyons-Weiler refers was, not surprisingly, also published in the same journal in 2018. In it, in his arrogance of ignorance, Lyons-Weiler argues that “several critical mistakes have been made in the consideration of pediatric dosing of aluminum in vaccines” and “on Day 1 of life, infants receive 17 times more aluminum than would be allowed if doses were adjusted per body weight.” The only redeeming feature of the paper is that Weiler outright admits that his “revised minimum risk level (MRL)” for aluminum dosing in infants is “based on derived speculation, not on safety data.” Well OK, then. Again.

Based on that paper, Lyons-Weiler states:

None of the individual vaccines violates the guidance of a maximum of 850 μg of aluminum for an adult (Table 1). However, because of multiple vaccines typically given together at 2, 4, and 6 months, the CDC schedule violates this limit even assuming an adult weight ([27]; 29,773,196). Adjusting the safe dose limit based on a child’s weight at these ages therefore results in doses that far exceed the estimated safe limit of acute toxicity (Lyons-Weiler and Ricketson, 29,773,196).

In any case, let’s quote what a certain pseudonymous pharmacologist has to say about the use of Clark’s formula and Lyons-Weiler’s use of it, using a hypothetical example of a boy dosed with amoxicillin:

But you cannot use this formula to determine the average plasma concentration of amoxicillin in this boy just by knowing the dose administered. It needs a completely different formula that accounts for important PK parameters such as the bioavailability (if you give the medication outside an IV route), the dosing interval (how many times a day you give that boy the antibiotics) and the clearance of the drug (how fast the antibiotic is removed from the body).

And:

It is also important to factor in the bioavailability of a drug (F) for the determination of Cave. By default, F=1 for injection via a vascular route (commonly via intravenous route), whereas F<1 for any extravascular route (including oral (PO) and intramuscular administration (IM) route). In other words, the only situation where you can assume all the substance goes into the bloodstream is when the substance is given directly into the vein – any other form of administration, including intramuscular administration (the common way vaccines are given), leads to less of the substance ending in the bloodstream (see discussion below).

And that’s where Lyons-Weiler stumbles. Nowhere in his model does he consider bioavailability. Antivaxxers somewhat correctly point out that the bioavailability of aluminum in the diet is low, making comparisons with vaccine injections problematic. I say “somewhat correctly” because it turns out that bioavailability of aluminum injected intramuscularly is also low. Our pseudonymous pharmacologist cites a paper that estimated the bioavailability of aluminum to be 0.6% for intramuscular (IM) administration and 0.3% for oral administration. So both IM and oral dosing of aluminum result in a low (and similar) bioavailability. The difference is only two-fold, not so great after all, unlike the assumption of antivaxxers that IM dosing will have a much higher bioavailability than oral dosing. Lyons-Weiler misapplies the Priest model, which was based on IV injection (100% bioavailability) and a single dose.

That being said, the FDA safe limit for aluminum dosing was based on a paper by Bishop et al, in which the authors demonstrated better neurological outcomes in premature newborns fed by total parenteral nutrition (intravenous nutrition) when an aluminum-depleted formula was used. One can’t help but note with amusement that Lyons-Weiler was apparently utterly oblivious to that fact by his emphasis of the FDA limit applying only to adults.

Also, to echo our friendly neighborhood pseudomyous pharmacologist, Lyons-Weiler misunderstands pharmacology, pharmacokinetics, and pharmacodynamics. Specifically, he does not differentiate between a vascular route of administration (intravenous) and the nonvascular route used for vaccines (IM). Let me, as a physician and someone with a fair amount of training pharmacology and pharmacokinetics training (although clearly not nearly as extensive training as a real pharmacologist like the raptor’s guest blogger, who included equations and everything in his deconstruction), IV and IM routes of administration often produce very different rates of increase and decrease of plasma levels of drug. In his model, Lyons-Weiler assumed 100% bioavailability of vaccine-associated aluminum and nearly instantaneous peak plasma concentrations.

Read the deconstruction hosted by our feathery scaly friend. I’m going to quote a bit more and then add my own concluding thoughts:

What is really concerning and should have been an immediate rejection of the study was the inability of the authors to integrate that IV routes and non-IV routes have distinct features when it comes to absorption. You cannot immediately compare them unless you integrate the bioavailability for oral and injections (I refer here to IM and SC routes). You have to consider the fraction that is bioavailable (in other words, the amount that reached the whole blood circulation) and only then you can compare such fraction to values obtained from IV data.

This callousness of the author to compare IV and IM routes as is, assuming that the amount of aluminum injected from vaccines was delivered instantaneously all at once into the bloodstream is reflective of a severe deficiency in understanding basic concepts of pharmacokinetics, making them unfit to run such study.

The second mistake made by the author is that the safety limit set by the FDA was set based on the work made by Bishop and colleagues on premature infants. Therefore, the need for the Clark formula to adjust a dose from an adult population to an infant population is completely useless: the source is already in infants.

Further, the authors also omitted to cite relevant literature, both from preclinical and clinical studies, that shown no increase in aluminum plasma levels in infants and toddlers [7-10] following immunization with aluminum adjuvants-containing vaccines, or following IM injections of aluminum adjuvants in rodent models at doses reflective or significantly higher than humans.

So. Many. Screwups. Our pharmacologist friend also noted that, contrary to Lyons-Weiler’s “calculations” and “modeling,” even with repeated dosing aluminum can’t accumulate the way Lyons-Weiler claims:

If we assume a dosing interval (Tau) between two rounds of 2 months (60 days = 1440 hours), and a terminal half-life of 6 hours (according to Priest), the ratio obtained is 6/1440 = 0.004. It is impossible mathematically to achieve an accumulation of aluminum in the central compartment with the recommended CDC schedule.

Let’s just put it this way. The flaws in this paper are so bad that even I, a nonpharmacologist with some training in pharmacology, can easily spot them, although admittedly I can’t deconstruct them at the same level of exquisite detail, complete with equations and graphs, as our friendly neighborhood pseudonymous pharmacologist can. I immediately spotted the sloppy, false assumption behind Lyons-Weiler’s “model,” namely its use of data from intravenous, one dose administration of aluminum to base its model for IM doses of aluminum on and its failure to take into account the much lower bioavailability of aluminum from IM administration compared to IV. I also recognized the cherry picking of the literature used to come up with this model.

The question I’m left with here is simple. Is Lyons-Weiler incompetent and unaware of it, leading him to march bravely and foolishly into a discipline in which he is utterly unqualified and do an analysis of this type? Or does he know better and is instead dishonestly constructing a model that he knows will sound plausible to someone without training in PK/PD in order to provide propaganda material for antivaxxers like Del Bigtree, Robert F. Kennedy, Jr., and the like to trumpet as “scientific support” for their claim that aluminum adjuvants are dangerous. In my opinion, those really are the only two possibilities (incompetent or dishonest), although I suppose that it’s possible that the explanation could be a little of both. After all, incompetence and dishonesty are at the ends of the spectrum of possibilities explaining a paper like this. Lyons-Weiler could well be somewhere between the two.

Whatever the case, it’s clear that the Journal of Trace Elements in Medicine and Biology has become the go-to journal for antivaxxers who want to publish pseudoscience and execrable science about aluminum.