Let me see if I understand your “anti-vax logic”. Because Offit says something in public, which repeats a calculation he and 7 co-authors made and published in a peer-reviewed journal (available for free download) with citations and backup including citations of multiple clinical trials, and in that public statement doesn’t repeat the entire list of references to clinical trials that he and his co-authors cited, then it is a legitimate “anti-vax conclusion” for a fellow doctor, a medical professional to state that Offit’s opinion that multiple vaccines are safe is unsupported by clinical trials?

Is this how “anti-vax logic” works? Is this representative of how you anti-vaxers think? Does this represent the highest levels of scholarship and analysis that the most scientific and medically knowledgeable anti-vaxers use?

You say “We know smaller specific combinations have caused problems.” You wouldn’t happen to have a citation of that to an actual clinical trial that demonstrated that do you? Or is that merely an opinion unsupported by clinical trials? An opinion that you think is legitimate because it is an “anti-vax opinion”?

“You seem to be saying that the only thing that Offit is relying on for his opinion that multiple vaccines are safe is his theoretical calculation that there are at least 3 orders of magnitude factor of safety before the immune system could possibly be “overwhelmed” (and no suggestion of what the failure mode or what the adverse consequence is if the immune system was “overwhelmed”).”

In his public statements on the 10,000 vaccine theory, that’s usually all he says on the topic—we are talking about his public statements on the 10,000 vaccine theory that are often quoted—He rarely notes the caveats in his public interviews. I’ve certainly never read them, despite the fact he notes they exist on at least one occasion. The point is that in public he applies it as evidence for safety. Since the number is not “practical” and only considers one single aspect of the immune system, it’s pretty silly to use it as an argument in public statements. As for the lack study of susceptible subsets, that’s completely unaddressed by Dr. Offit.

“Poling is saying that Offit’s opinion is unsupported by clinical trials. That is clearly false.”

To be exact (if you read your own quote again) he’s saying Dr. Offit’s “Plausible biological” theory is unsupported by clinical trials which even you note is impossible to test. Even in his paper, Offit doesn’t cite any studies in that section that are designed to test the safety aspects of concurrent vaccine application let alone any practical safety limits. Any of the studies you talk about are always based on looking first at Immunogenicity (efficacy) in different combinations.

We do have hard evidence from clinical trials that even small combinations of concomitant vaccine applications do result in higher safety risks. Why do you suppose MMRV was removed from the recommended list?

“Suppose you do a clinical trial,”
Conjecture is exactly what Dr. Poling is talking about.

“From basic research on the immune system, it is known that 10 vaccines are not stressing the immune system to close to the point of failure.”
Supported by clinical trials? Dr. Poling’s point again. We know smaller specific combinations have caused problems.

“A sophistication that anti-vaxers such as you and Poling obviously do not have.”

Very interesting that you are able to make such a qualitative assessment of someone’s qualifications without ever having spoken to him or worked with him.

“Fortunately people such as Offit can look at the totality of what is known about vaccines and the immune system;”

But Dr. Offit’s “practical” theory is exactly the opposite of looking at the totality of the system because it considers only a single aspect devoid of practicality, yet he has used the theory in absense of caveats in public statements.

Since you seem incapable of going more than one post in a row without resorting to broad generalisations, name calling, and insults—all of which are unscientific, and indicate false logic—I wish you good day, and good luck with your interactions with others.

Let me repeat again for the nth time what Poling actually wrote:

“Offit is frequently cited regarding the “biologically plausible” theory that simultaneous administration of multiple vaccines is safe. His opinion is unsupported by clinical trials, much less investigations in potentially susceptible subpopulations.”

Poling is saying that Offit’s opinion is unsupported by clinical trials. That is clearly false.

You seem to be saying that the only thing that Offit is relying on for his opinion that multiple vaccines are safe is his theoretical calculation that there are at least 3 orders of magnitude factor of safety before the immune system could possibly be “overwhelmed” (and no suggestion of what the failure mode or what the adverse consequence is if the immune system was “overwhelmed”). That is clearly false because Offit et. al. showed multiple lines of reasoning and cited multiple clinical trials to conclude that multiple vaccines are safe.

Suppose you do a clinical trial, and look at the distribution of the magnitudes of immune system reactions and find that X out of X are self-limiting and well below the limit that would be injurious. From the distribution of the magnitudes of immune reactions, you can estimate that the immune system reactions in a larger population would follow a similar distribution.

From basic research on the immune system, it is known that 10 vaccines are not stressing the immune system to close to the point of failure. That is the 3 orders of magnitude factor of safety that Offit et. al. calculated. That suggests to a high degree of reliability that modest extrapolation of the distribution of immune system activations is not going to move the results into a totally unusual regime. One can then use the results of small clinical trials to infer the distribution of magnitudes of immune system activation in larger populations.

Of course it takes a sophisticated understanding of the immune system and how it reacts to be able to do this. A sophistication that anti-vaxers such as you and Poling obviously do not have. Fortunately people who actually work with vaccines such as Offit do have that degree of sophistication.

Fortunately people such as Offit can look at the totality of what is known about vaccines and the immune system; including basic research, theoretical considerations and clinical trials and use that information to design and implement safer and better vaccines.

If Poling had said that he didn’t understand how clinical trial information could be used to estimate multiple vaccine safety that would have been a true statement. His statement that Offit didn’t use any data from clinical trials to inform his opinion was clearly false.

Before you delve into the minutia of wanting to rip apart my suggestion of how safety from a clinical trial might be used, there are many different ways that clinical trial data can be looked at to assess safety of multiple vaccines. We know that such data exists, we know that Offit has looked at it, we know that Offit thinks that such data is important because he cited it when laying out his reasoning. For Poling to say there is no such data, or that Offit didn’t rely on it is clearly either a bold faced lie or a delusional rant.

This is not a close call. Offit isn’t the only person in vaccine research that is looking into this. He had 7 co-authors on that paper. I suspect that the reason the Offit is the focal point of the anti-vaxers is because he is willing to stand up to the death threats and the heat that the anti-vaxers are dishing out. How many death threats has Poling gotten from pro-vaccine activists? My guess would be zero.

Yes, he reference clinical trials but if you read Dr. Poling he’s talking about studies that are designed to study safety. Those studies, were primarily designed to study efficacy and they monitored safety. None of them were designed to test the safe limit of concomitant vaccines which is what I believe is the point he’s making.

I know that the theoretical antibody capacity is not a close call, but he’s using that single aspect of the immune system as evidence of safety. That’s the core problem.

“If Poling was referring to public statements, why didn’t he say so?”
That is a good question. It’s curious, because it seemed quite obvious to me what Dr. Poling was referring to, but clearly there are different ways of interpreting the statement and not everyone will read it that way. It’s a good lesson on language and perception.

“A point that Poling doesn’t seem to have refuted, he just lied and said there are no clinical trials that Offit could have looked at and then developed that opinion.

He certainly didn’t address every point in Dr. Offit’s initial letter. His purpose was to correct several misleading statements in his article. He selectively addressed points that were blatently incorrect, and IMO he addressed the 10K vaccines theory directly. The number of inaccuracies and misleading statements in Dr. Offit’s original letter certainly are problematic from my perspective.

The point that there is excess capacity in the immune system is not a close call. Is that excess 2,000x times greater, 500 times greater, or “only” 100 times greater? Does it matter if some children have a 579 times excess and some have a 578 excess? If the excess is large compared to our ability to measure it, what does the precision of the measurement matter?

If Poling was referring to public statements, why didn’t he say so? If he is so hung up on the 10,000 number why didn’t he refute it? Why didn’t he refer to a specific number and not just to “multiple vaccines”?

The point of the article was that there is no theoretical basis for a few vaccines to overload or overwhelm the immune system. There are multiple methods for appreciating that there is no basis for the assertion that the immune system is overwhelmed by the current vaccine schedule. A point that Poling doesn’t seem to have refuted, he just lied and said there are no clinical trials that Offit could have looked at and then developed that opinion.

Offit used several lines of reasoning to show that multiple vaccines don’t overwhelm the immune system. He cited clinical trials, he used a thought experiment of 10,000 vaccines, he gave a tutorial on the infant immune system, he explained how more immune cells are generated each day, he cited data on children with immunodeficiencies, he cited data on children with other diseases. Poling didn’t refute any of the data or any of the citations. Poling latched onto one small aspect of Offit’s reasoning (the 10,000 vaccine number) and because there obviously couldn’t be a clinical trial with 10,000 vaccines, declared that no clinical trials informed Offit’s opinion at all. That is complete nonsense.

“The only number of multiple vaccinations that is at all relevant to actual medical practice is the number of multiple vaccinations that are actually given.”

Yes, and in terms of catchups, I have not seen a clinical trial that mimics some of the hefty combinations that are given to children when they have missed previous shots. If you read the FDA and HC publications, they even note this quite clearly.

Most commonly, the studies are designed to determine if the immune response is as effective in combination A vs B while monitoring adverse events (which is the safety monitoring). From what I’ve seen, these studies usually look at less than 500 children.

“What does a number a thousand times higher than what is conceivably possible have to do with actual safety?”

Indeed, so why would Dr. Offit even bring it up? There are a lot more aspects involved in vaccination than the narrow immune response considered in this calculation. Why use it as proof of safety? Even worse, why call it a “practical approach” when it is anything but?

“in the NEJM, I presume that Poling is talking about actual…”

And I presume he is referring to the attitude and approach to safety when Dr. Offit disregards such concerns with his 10,000 vaccine theory. He directly uses the words “biologically plausible theory”. Certainly I agree that Dr. Poling doesn’t believe we would test 10,000 simultaneous vaccines, but he is pointing out that using such a theory as an assurance of safety is wrong given that the number hasn’t and can’t be tested—so why bring it up. From a practical perspective, it might as well be an arbitrary number that adds no value to the discussion. I believe he is also pointing out that most combinations are not explicitly safety tested, especially combinations that happen outside of the ideal world of the recommended schedule. Even the recommended schedule isn’t always fully tested.

I also think Dr. Poling is referring to Dr. Offit’s public statement citations of “theory”, not scientific study citation. He himself brings up the “10,000” vaccine theory on a regular basis in public statements.

I also think that you’re misreading the context. Remember, Dr. Offit wrote his original piece in the context of public messaging summarized in his conclusion:

“Otherwise, the message that the program inadvertently sends to the public will further erode confidence in vaccines and hurt those whom it is charged with protecting.”

Even more context setting occurs in the first line of Dr. Poling’s response where he notes that Dr. Offit made similar errors (or lies as you call them) in his NYTimes op ed piece. In Dr. Offit’s public messaging, the 10,000 vaccine theory is often cited.

“Taken at face value Poling’s statement is a lie.”
Only based on your interpretation. Your definition would also classify several of Dr. Offit’s statements as lies, which is not how I would classify them at all.

“Science is all about being honest with ourselves and with our colleagues. Poling and the other anti-vax activists are not being honest.”

You may feel that. I feel that he is being more honest than Dr. Offit in this case, as most of Dr. Poling’s points were dead on accurate and only a few of them are even debatable. In fact that is the point of him writing in to the NEJM to correct a number of misconceptions that Dr. Offit wrote into his original piece.

“Offit is frequently cited regarding the “biologically plausible” theory that simultaneous administration of multiple vaccines is safe. His opinion is unsupported by clinical trials, much less investigations in potentially susceptible subpopulations.”

in the NEJM, I presume that Poling is talking about actual scientific citations and not anti-vax screeds and/or anti-vax polemics where Offit’s quote is distorted and taken out of context and used to frighten people into thinking that Offit is some ogre/vaccine fiend ready to inject 10,000 vaccines into their child.

A search on Google Scholar shows up 115 citations. 115 citations is enough to be called frequent. Going through the list of them, I don’t see that any of them are obvious anti-vax screeds (from their titles only). Virtually all of them pertain to actual vaccination schedules and not some weird hypothetical thought experiment of giving 10,000 vaccines simultaneously. As I mentioned earlier, there are not 10,000 vaccines available or even 10,000 diseases that can be vaccinated against, let alone vaccinated against simultaneously. At 0.5 mL per vaccination, 10,000 vaccinations would require the injection of 5 liters of fluid. There is no fluid that can be injected at a dose of 5 liters anywhere in the body that would not be fatal. Injecting that much water or saline would be fatal just from mechanical effects. Offit’s calculation that the immunological effects of that many antigens is tolerable is reassuring to me that there is plenty of excess capacity in the immune system.

The only number of multiple vaccinations that is at all relevant to actual medical practice is the number of multiple vaccinations that are actually given. What does a number a thousand times higher than what is conceivably possible have to do with actual safety?

Are you saying that Poling expected Offit to run clinical trials where he actually injected 10,000 vaccines into children in a clinical trial before suggesting the thought experiment that he did? Such a trial could not be done for multiple reasons. There are not 10,000 vaccines available, there are not 10,000 diseases to be vaccinated for, the Declaration of Helsinki requires that human experiments be done ethically and for the benefit of the experimental subjects. With no conceivable benefit to those being injected, a clinical trial injecting 10,000 vaccines into children could not be done.

I doubt that any of those 115 papers citing Offit’s work even mention the 10,000 vaccine calculation. To infer that Poling’s statement that “Offit is frequently cited regarding the “biologically plausible” theory that simultaneous administration of multiple vaccines is safe.” refers to the 10,000 vaccine calculation there would have to be actual citations that mention it. Can you show that more than half of the citations that Offit’s paper received refer to his 10,000 vaccine calculation? If you can’t, then that is not a legitimate inference from Poling’s statement.

If Poling had referred to the 10,000 number and not “multiple vaccines”, or had referred to anti-vax polemics and not citations, his statement might be legitimate. He didn’t. Taken at face value Poling’s statement is a lie. There is no way it can be parsed into something that is not a lie.

Maybe Poling was thinking about the 10,000 vaccines but wanted the readers to think he meant multiple vaccines as in the normal vaccine schedule. That is being dishonest, and is clearly a lie in this context. That type of disinformation is unacceptable in a scientific journal. If that is what he meant, then he should retract his statement as it is clearly scientific misconduct.

Science is all about being honest with ourselves and with our colleagues. Poling and the other anti-vax activists are not being honest.