Immune Debt Denialism

The latest trend in the "Covid is not over" cult co-opts the hygiene hypothesis backlash.

Reader warning: The following is a meandering, philosophical post.

Meanwhile, if any readers are wondering whether I have a take on the “Omicron Chimera Freakout,” Modern Discontent’s review reflects my own entirely indifferent response:

Let's Discuss the "Chimeric Omicron Gain-of-Function" Study

This is Sparta Thymus

On the first of the month, Vinay Prasad ventured the following reasonable remarks:

Second, there is the arrogance that avoiding colds and flu is good for us. Of course it is the case that getting sick is unpleasant, but our knowledge of immunology and the body is so primitive we should not conclude that avoiding it is ‘good for us.’ We have no idea if that is true in the long run.

It is natural to be infected repeatedly with respiratory viruses— if we got fewer infections what would that mean for auto-immunity for cancer?¹

Setting aside that this is essentially an unintentional² argument against all vaccines, my intuition is that Prasad’s logic is sound.

Our germ cells — sperm and egg — are forced to run a gauntlet through chemical migration signals when we are still embryos, with those that can’t make the cut being denied survival; this is a form of internal quality control of the genome.³ Immune cells face similar signaling gauntlets before (at least in the case of memory immune cells) they are allowed to take their final phenotype — their “badge and gun.” This ranges from innate immune monocytes touring the bloodstream before converting into tissue-resident dendritic cells and two opposing “genders” of macrophages, T Cells demonstrating ability to select against self-antigens, and germinal center B Cells competing to show avidity for not-self-antigens.

What happens to T and B Cells that don’t make the cut? Like a Spartan boy who can’t best the wolf, they die. The immune system, like our germ cells, is built on a “no pain, no gain” model — it is meant to be trained in the core competency of distinguishing self from not-self. How can it do this without being challenged by not-self?

(Again, an obvious argument against all vaccines except probably OPV.)

Edgar Degas: Young Spartans Exercising. “I bet you couldn’t even tell a beta cell from a rabies virus, Billy.”

“No pain, no gain” may, of course, include a cost in terms of wear and tear; this is simply a manifestation of inevitable tradeoffs. Viruses and other immune challenges may drive much of the loss of function and form that we define as “aging.” This, however, does not tell us if the benefit is more or less than the cost. As Prasad says, we really have no idea. But an obvious futility-based argument against trying to minimize “aging by virus” is that this aging also confers protective memory immunity to threats that will still be around when we are old. A youth of rugged wear and tear may be the best bet for a calm “immune retirement” in old age. In the end, it could all be a wash — at least before the stress and depression of the years of germaphobic behavior required to sustain a lifestyle free from infection is added to the ledger.

The Toll of Viral Safetyism

Back to the questions of [allergy,] “auto-immunity and cancer”: Of particular interest in these questions, at least for me, is the rash human decision to banish the measles virus without any forethought of the potential consequences. It is now understood that this virus, with which we were formerly co-evolved, itself imposes immune debt by erasing large swaths of the memory B Cell repertoire.⁴ Measles essentially uses the immune system’s filing cabinet as its birthing ward, leaving some portion of the records destroyed for good. In the eyes of an epidemiologist this can only be a bad thing; it results in apparent higher mortality in children in Africa (how could we possibly know whether it does the same in countries that already eradicated the virus). But what if some of the “records” that measles destroys includes problematic, self-targeting B Cells? We obviously have no idea.

All that is certain is that in the wake of banishing measles from Western childhood in the late 60s,⁵ things like allergies, auto-immunity, cancer, post-childhood-onset infection-induced disability (ME-CFS), and, oh yeah, literally AIDS, did not become less of a problem.

Bach, JF. (2002.)

Platts-Mills, T. (2015.) Fig. 3. Asthma rates in different data sets; (d) is among Finnish army recruits with pre-existing asthma (orange), exempted for asthma (blue), or discharged for asthma (green). Note that other graphs in the same paper are more suggestive of 1955 as the turning point for childhood allergies; also, I have no idea how quickly the measles vaccine was adopted in Finland, Australia or New Zealand — but in the case of Finland it certainly could not have impacted Army recruits as early as the 60s.

Hinman, A. et al. (2004.) Fig. 2. US Measles rates (log scale). Cases in the 70s are heavily distributed in older children and teens.

Meanwhile, any benefit beyond trend to childhood mortality is virtually invisible.

statista.com “Child mortality rate (under five years old) in the United States, from 1800 to 2020.” Don’t show this to any anonymous, pro-pharma online cats.

In fact, the leveling in the plots for 1965 and 1970 is curiously suggestive of an initial detriment (potentially related to the 1964 rubella outbreak that immediately followed licensure of the measles vaccine). But more to the point, if there was indeed a benefit after this initial period, is that actually good news?

After all, any protective effect from the measles vaccine must be rolled in with other social changes that corresponded to the rise in safetyism and helicopter parenting: Kids after 1970 increasingly lived in a bubble of security, including from viruses; all for a marginal benefit in the short term and who knows what detriment in the long term. If insulation from stress isn’t good for generating resilience in one chemically-based pattern recognition machine (the brain), why would it be good in another (the immune system)?

Background stolen from choosingtherapy.com. Author asserts fair use for reproduction and edits: Visualizes how common child psychology tropes translate to unspoken, unexamined health effects from insulating children from immune challenges.

If 99 children must be turned into steam-head up there to protect 1 from falling out of a tree and dying, is that a “win” or not? And what of the intrinsic value of both risk and illness — without these two experiences, humans go through life unfamiliar with death. Does this make them better able to cope with it — or, more likely, is it exactly what feeds the rampant insanity of the utopian Zero Covid cult to begin with?

Biodiversity, equity, and inclusion

Prasad’s remarks, at any rate, touched a nerve in germaphobe twitter.

Fact check:

The author actually has no idea if this is really the case. He does not follow the “scene” in Covid Is Not Over Twitter closely enough to know what is a backlash and what is just business as usual. Really, he just encountered some tweet threads and wanted to make a post about it.

At the same time, this month has featured another round of news stories that validate predictions that lockdowns, social distancing, and school closures would necessarily burden children with immune debt, with the result that they are all running around metaphorically covered with a 1,000 different bandaids waiting to be ripped off: Respiratory syncytial virus is surging out-of-season for the second year in a row; over 1 in 3 students in two San Diego high schools are home sick with flu;⁶ "have you noticed everyone is sick?" etc.

For the Zero Covid / Covid Is Not Over cult, the only thing worse than an actual lull in “Covid cases” is a surge in everything else. That is when they know that everyone else knows that immune debt is real; which means their promised land of a virus-free existence is a purgatory of self-imprisonment and immune dysfunction.

Prasad’s prodding and the bad vibes from the news thus has the cult rallying itself to rail against reality. Grab the prayer-scrolls! The heretics are claiming that children are in immune debt; that infection is inevitable in childhood; that life free from virus is an illusion! The natural effigy to represent all of these demons is the hygiene hypothesis, which is typically characterized as proposing that childhood infections promote immune competence (reduce allergy and auto-immune disorders). A thread from Lisa Iannattone on Saturday generated thousands of retweets:

source: twitter.com

Iannattone’s argument, which as we will see below merely recycles pre-existing work by others, is that rather than absence of infection, absence of beneficial microbes is a better account for the different outcomes observed between rural and sub/urban children. She wants to reframe the hygiene hypothesis to unseat the common interpretation that implies infections are beneficial. The truth, in other words, is that dirt is good, not viruses.

So then why is “hygiene” a misnomer? — it doesn’t actually correspond to the interpretation she wants to refute! And why is “biodiversity” a “better name”? — it could arguably better apply to the interpretation she wants to refute! What could be more “biodiverse” than a huge, raging co-surge of flu, RSV, and monkeypox? No matter, “misnomer” is like, a really big, reasonable word, that reflects really being reasonable and having a good argument, unlike the other side with their dumb intuition or whatever. And “biodiversity” has the d-word in it, granting magic properties. “Nature!” isn’t dirty (yuck!); it’s biodiverse (yay!).

But to be fair, these contradictions are actually not Iannatone’s own creation. She is recycling them from a manifesto issued in 2016 by Sally Bloomfield, Graham Rook, and four other authors.⁷

Bloomfield, SF. et al. (2016.)

Although evidence supports the concept of immune regulation driven by microbe–host interactions, the term ‘hygiene hypothesis’ is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures.

Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term ‘hygiene hypothesis’ must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members.

How does this demonstrate that “hygiene” a misnomer?!

Or rather — isn’t it that the misnomer does not apply to Bloomfield and co’s preferred interpretation, but to the prevailing one? They aren’t upset with the name of the hygiene hypothesis, but the interpretation — that infections promote immune competence. In other words, they ought to be eager to claim the name for themselves, and propose that the prior interpretation be renamed in order to refer explicitly to infection.

Setting aside these semantic ironies, what is important is whether or not the anti-hygiene hypothesis revolt brings any evidence to support their viewpoint.

Rook is the founder of the “old friends” hypothesis, which I had not realized purports to be a true counter-theory to the hygiene hypothesis. The old friends model proposes that dirt- and mud-free environments impair the acquisition of a functional microbiome to regulate the immune system; and that this accounts for the entirety of the immune dysfunction experienced in the modern age.

And, sure. I’m as pro-microbiome as the next person. Kids need dirt; they need temperate bacteria to promote anti-inflammatory, pro-regulatory and repair behavior in tissue-resident immune cells. But how does this refute a long-term benefit to viral infection? (It doesn’t.) It could obviously be true that there are multiple benefits to a non-hygienic life.

Moreover, how on Earth does “old friends” actually account for the post-60s rise in allergy and auto-immunity?

None of the “evidence” gathered in “Time to abandon” appears compelling. The conclusion sums it up:

Changes in lifestyle and environment, along with rapid urbanisation, have all contributed to changes in our exposure to essential microbes [this preceded the 1960s by decades]. In addition, altered diet and excessive antibiotic use have also sustained detrimental effects on the content and diversity of the human microbiome [diet changes preceded the 1960s by decades; penicillin by 2 decades]. Together, these factors have had profound effects on the immune system, which are likely to have contributed to the onset of allergic disease.

Why not blame secularism, exposure to incandescent light, or the abandonment of child sacrifice, if the entirety of history is up for grabs in explaining a phenomenon that manifests after the 1960s? Even hygiene itself obviously predates the era in question by decades, unlike true banishment of viruses — again showing that the “misnomer” of the hygiene hypothesis is a failure to mention infections by name.

Granted, diet seems plausible — but it is not like processed foods and bad eating did not exist before 1960, either. The rise might match; but not the baseline — there should have been more auto-immunity before. It is prima facie obvious that there is no more dramatic change to childhood in the era of concern other than the war on bacteria and viruses. The best rescue against the latter is that penicillin is the real culprit; and the effect on microbiome health was merely delayed until a few decades after its first use in 1944. But arguing against both these factors is that antibiotics and processed foods can be and have been exported to other countries without a rise in the same ails. From a news item that followed in the heels of “Time to abandon,” authored by Science Journalist™ Megan Scudellari:⁸

Prevalence of food allergy in preschool children is now as high as 10% in Western countries, but remains just 2% in areas like mainland China. The number of new cases of type 1 diabetes (T1D) in Finland per year is 62.3 per every 100,000 children, compared with just 6.2 in Mexico and 0.5 in Pakistan. Ulcerative colitis, a form of inflammatory bowel disease (IBD), is twofold higher in Western Europe than in Eastern Europe—6.5 per 100,000 people versus 3.1 per 100,000.

Antibiotics, like many other drugs, were long available over-the-counter in Mexico.

Bloomfield, et al. is somewhat more compelling on the attack than on defense, pointing to a handful of studies that fail to show any association between infection-prevention and increased asthma rates. This is evidence that seems to refute a benefit to immune competence from childhood viral infection.

However, are Bloomfield, et al. playing fair in this fight? The “old friends” hypothesis reflects additional decades of discoveries of the immune system — if it is going to be compared to the hygiene hypothesis, the “opponent” should be allowed use of the same developments. Refuting the hygiene hypothesis should not just require evidence regarding early life allergies, but teen and adult-onset immune dysfunction of all types, as these have overcome allergies as the ailments defining a generation.

Likewise, Scudellari's “news item” reviews the fate of one of the sub-theories offering a mechanistic explanation for the hygiene hypothesis:⁹ First, it was believed that infections promote T Helper 1 responses and suppress T Helper 2 responses. Predictably, this sub-theory was found not to hold water. TH1 is strongly implicated in auto-immunity; and helminth infections are strongly promoting of TH2 responses without a corresponding increase in allergies. But this simply refutes a (sophomoric, 90s-vintage) explanation for the hygiene hypothesis, not the thing itself. It is still the case that people with “less worms” are more hygienic, less often infected with other stuff in childhood, and more immune-dysfunctional throughout life. The hypothesis obviously stands.

The Moving Target

Perhaps neither the hygiene (infection) hypothesis or “old friends” is more satisfactory at explaining modern trends in disease than the other. The measles vaccine, much like penicillin and processed food, has also been exported to low-hygiene countries without a corresponding surge in allergy, autoimmunity, etc.

Likewise, both theories have intuitive strengths, even if the latter won’t acknowledge any in the former. It makes sense that viral infections promote immune homeostasis and competence; it makes sense that early establishment and continued promotion of a healthy microbiome would have outsized impacts on the same. (Really, I don’t see any reason why “old friends” shouldn’t be considered a sub-theory of the hygiene hypothesis.) But what does not make sense is the remedy Bloomfield, et al. propose: “Targeted hygiene.” If good bacteria are necessary for health, then a window must be left open for “bad” bacteria and for viruses as well. Hands must go unwashed. Noses must be wiped with unwashed hands. People must touch each other, even though this will spread infections. You can obviously still get a virus from “increased social exposure through sport, other outdoor activities.”

Targeted hygiene is a meaningless fantasy. In fact, I don’t know what to make of “Time to abandon” besides either an extremely subtle work of pro-vaccine propaganda or a neurotic attempt to reconcile germaphobia with acceptance of the microbiome. The following quote captures the essence of the resulting irony:

While [the rise in allergic diseases] is frequently presented as an ‘epidemic’, epidemiological data indicate the situation is more complex. […] Indeed, there are emerging data that in some areas (mostly in ‘Western’ countries) these increases may have plateaued and even begun to subside.

Platts-Mills, T. (2015.) Fig. 3. (annotated.) Hospital admissions for asthma in the United Kingdom. (Colorized from Anderson, HR. et al.) Given that medication use does not fall in the same time, this actually probably just reflects fewer episodes resulting in hospital admission. I still insist on playing the irony card.

What is lastly certain is that the war on microbes of the last two years has, in fact, been followed by the predicted manifestations of a disturbance in balance between viruses and their hosts. If this isn’t immune debt, I don’t know what is.

If you derived value from this post, please drop a few coins in your fact-barista’s tip jar.

click button or visit https://ko-fi.com/unglossed

1. Prasad, Vinay. “I am going to mask because I want to get fewer colds & other flawed ideas.” (2022, October 1.) Vinay Prasad's Observations and Thoughts.

2. Presumably, given Prasad’s normal rhetoric.

3. Richardson, BE. Lehmann, R. (2010.) “Mechanisms guiding primordial germ cell migration: strategies from different organisms.” Nat Rev Mol Cell Biol. 2010 Jan; 11(1): 37–49.

I don’t know if this is a good read; I recently lost a lot of my bookmark libraries including genetics / embryogenesis stuff.

4. Mina, MJ. et al. (2019.) “Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens.” Science. 2019 Nov 1;366(6465):599-606.

5. Measles outbreaks continued into the 80s, prompting more and more extreme school vaccine mandates. However, these outbreaks frequently affected unvaccinated teens who had missed out on the normal infection schedule due to the unnatural immunization of their peers. See “Die Herd” (which is in need of a rewrite; but the portions regarding smallpox and Measles all stand).

6. Etienne, Vanessa. “San Diego High School Reports 1,100 Absences This Week Due to Respiratory Outbreak.” (2022, October 14.) people.com

7. Bloomfield, SF. et al. (2016.) “Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene.” Perspect Public Health. 2016 Jul;136(4):213-24.

8. Scudellari, Megan. (2017.) “Cleaning up the hygiene hypothesis.” Proc Natl Acad Sci U S A. 2017 Feb 14; 114(7): 1433–1436.

9. ibid.