"The prevailing situation is that most of the authors warning about a Marek’s disaster for SARS-CoV-2, and reading the tea-leaves of government statistics to divine whether it has already arrived, do not seem deeply curious about actual virology or the immune system"
As someone who actually writes and fixes software I do not have the liberty to say "this bug is clearly another example of Original Antigenic Sin or a case of Antibody Dependent Enhancement!"
I actually have to understand what is going wrong and fix it and there does seem to be a lot of handwaving out there without reference to actual mechanisms.
Yes, Ruechel's piece seems quite good - though I've only skimmed it since it is essentially arguing the same case as Die Herd but without delving as far back into the history. Same reference to advantage of removing immune escape pressure but doesn't seem to acknowledge / analyze the distinct evolutionary situations for viruses that do and don't have immune escape. Even if so, he seems ahead of most of the "Marek's Disaster!" advocates in actually thinking about the virus instead of recycling theory.
"However, they also showed that the vaccine altered the production of inflammatory cytokines by innate immune cells following stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli.
Following vaccination, innate immune cells had a reduced response to toll-like receptor 4 (TLR4), TLR7 and TLR8 – all ligands that play an important role in the immune response to viral infection.
Neta and colleagues also found that cytokine responses to fungi were increased following vaccination."
* the current narrow spectrum vaccines will induce rapid evolution triggering a rapid never ending series of related pandemics
* rapid escape evolution increases the probability of worse variants and extinguishes variants that may be more mild and currently somewhat protective.
* in normal evolution no preference is made between large and small mutations but with vaccines, the mutations that confer survival become much more important and require complete escape.
* As a matter of fact, vaccines never allow the small changes that might promote co-existence with virus, because the vaccines remove these variants from the milieu.
Which seems weird to me, as surely if you only need to circumvent spike-based antibodies, the changes are only to the spike, and thus small changes?
I must be missing something more than a degree in microbiology / virology.
It’s the “Escape Mutant Disaster!” which, as you say, doesn’t have much relevance to natural immunity - especially naive/innate natural immunity which doesn’t care about spike variation. And I have argued since August is now only relevant if there is widespread “boosting” since no inhibition of transmission = no selection/escape pressure.
You wrote about Forever Spike about 3 weeks ago. Does this current article contradict that—has your thinking evolved?
I think there's no question that humanity has shown amazing hubris in regards to its attempted manipulations, of the immune system which is so incredibly complex. I struggle to stay above water with a lot of this stuff, despite having spent the last 12 years reading everything I can about the immune system after having been diagnosed with a mystery neuropathy that is thought to be autoimmune.
The idea of Immune Equilibrium is fascinating and I'll read about that next. I'm already open to the concept through familiarity with intentional self-infection with helminths (parasitic worms) in order to stimulate the immune system.
At age 67, I'm very glad that I had all the measles and chickenpox as a kid. The worst result for me of chickenpox was that I missed a trip to Disneyland. Now I wonder if my immune system might be compromised because I never managed to get the mumps (only half kidding.)
This article expands and reinforces my dismissal of the "Marek's Disaster!" scenario for SARS-CoV-2, because it is not an immune-evading-virus. The flip side of this dismissal is that such a disaster *is* being courted with vaccines against (verified or potential) immune-evading-viruses like herpesviruses, etc.
I haven't devoted much text to it yet but there are definitely overlaps between Immune Equilibrium and the "hygiene hypothesis" which go beyond the vaccine / virus focus - implications that microbiome dysregulation and general lack of "stress-testing" the immune system, and even intermittent sedentary behavior, decalibrate toll receptors and lead to incorrect classifaction of "self" into "not self," etc.
The only "benefit" left to Covid vaccination is the reduction in severe outcomes during infection, which still appears durable. This "benefit" disappears when you discount for effective therapeutics that, by all appearances, are better at preventing severe outcomes than the Covid-vaccines anyway. I think, based on that alone, no one should get the shot. Preventative medicine with a ? mark on whether you will ever even end up needing it and another ? mark on long term harms doesn't make sense.
The detriments to Covid vaccination in terms of broad and specific (anti-SARS-CoV-2) immune competence are significant (especially w.r.t. the current signal for an increase in cancers). In the short term, clinically-measurable infection with SARS-CoV-2 seems to be increased by Covid vaccination, and in the long term, ADE may come into play (hopefully, this will still be treatable with therapeutics, but it still counts in the con column). I'll caveat that both these things are based on squinting at broad patterns, and may be confusing correlations for causation.
The detriments to Covid vaccination in terms of direct harms seem quite bad. I'm particularly worried about a direct link to carcinogenicity (as opposed to an indirect link based on taxing immune resources; I have a theory for the etiology which I will be posting at some point) and about under-diagnosed myocarditis among middle-aged and older women, based on widespread reports of jaw / neck / back / shoulder pain in VAERS (all of these can be symptoms of cardiac distress; almost none of them are being screened).
Nice catch - It seems very plausible that RSV is also flaring up from dormancy after Covid-vaccination. Unlike shingles, however, where an outbreak implies lysogenic exit by default, an RSV infection is presumably more ambiguous. It could even be naive infection + antibody-dependent-enhancement from the anti-spike antibodies, after all. I haven't looked into RSV yet. Seems like a friendly enough critter.
Thanks for this perspective. I have always found the Marek's outcome unlikely, and I have made some similar arguments albeit not from an immune equilibrium perspective.
In addition to the points that you make, a Marek's situation is an outlier: we have been vaccinating humans and animals with leaky vaccines against all manner of diseases for decades and Marek's is the only one that has become lethal in response. In a sense this is analogous to the outlier position of smallpox - a virus that was uniquely eradicable and is being used to suggest that SARS-CoV2 or other viruses will follow a similar trajectory to eradication if only we vaccinate hard enough.
Fear is rampant, and both sides want something to be afraid of. It's not difficult to see what this looks like from the mainstream perspective, but in the alternative camp it is taking the form of giving far more credence to the scariest conceivable outcome (a virus that kills unvaccinated people, vaccine treadmill forever, oh my!) than is justified by the facts on the ground.
Oh, but I am quite afraid of the outcome for Mumps, HHV-3, and HBV. At least for HHV-3 / chickenpox the naturally infected (from before 1995) are still walking around with a time-capsule version of the virus. My current rough impression is that HBV is in more of a liminal grey area between lifetime residency and transient infection, implying much faster possibilities for producing hotter strains. And there's no proven improvement to the allegedly relevant clinical outcome, cancer! I never even heard of the HBV vaccine before a month ago and now it drives me bonkers to think about it!
But in the context of SARS-CoV-2 the virus, I am sternly anti-fear. There is no productive action based on fear of a coronavirus possible anyway and never has been.
Agreed that this is a serious concern with regard to vaccination in general, especially with "onboarded" viruses as you call them. It is, however, a comparably slow process that will be driven by vaccination policy over years to decades, as was true of Marek's in chickens.
I have three serious concerns regarding overuse of vaccination in general. The first would be this one, that we will create an evolutionary imbalance between target microbes and the human immune system resulting in a breakdown of equilibrium and quite possibly the appearance of "hot" new strains. The second is that we will adversely impact the evolution of the human immune system, rendering it less able over time to manage natural infections. The third, and most pressing in my view, is that we are disrupting the normal infant/childhood development of the human immune system, rendering it more prone to allergy/autoimmunity and also less effective in terms of fighting off common infections and illnesses. You're probably familiar with this (now involuntarily retracted) paper which found an strong correlation between number of childhood vaccinations and a wide range of common problems.
Yes, point 3 sticks out - the inevitability of 0 benefit from "shielding" the immune system from the external menu of hazard is so obvious that there can be no question of malicious intent from the medical industry at large. Deficiencies in competence with the internal menu of hazard are always more profitable, so why wouldn't you sort your patients into the latter category? How dare nature attempt to rob you of God-granted revenue, after all. On the other hand, it's the thing that is easiest to course-correct from. No impact on the "super-genome."
I haven't read it yet, though I saw the link in your blog! At some point I will get around to it - as of now I have read only about 6 minutes of actual research/literature on vaccine harms.
Dr. Thomas' earlier article on aluminum concentration/toxicity from the CDC infant schedule is also of interest.Try: doi.org/10.1016/j.temb.2019.126444. There is a corrigendum to the original article, but it gives a chemical viewpoint of the potential harms of escalating interference with the immune system.
It has me at "Previous modeling efforts are based on very little empirical data, with the model by Priest based on whole-body clearance rates estimated from a study involving a single human subject." Will definitely give it a read.
Was this essay in response to el gato malo's latest?
Also: is the basic premise of your essay that the vaccine really targets only the spike, so that's pretty much all that's evolving, which means there's not really any pressure on making it more virulent. And because natural immunity hits as many viral proteins as it can it will continue to develop a robust, ongoing response to any evolved variants?
As someone commented below I will need to re-read this a couple of times. This is my first attempt at confirming understanding.
Yes and no. I intended to offer only a "glancing" blow at egm's sloppy "Marek's Disaster!" Theory; today's egm post renders my argument an even more direct attack than it was when I composed it.
My argument is that natural (post-infection, adaptive cellular) immunity is both porous and non-spike-specific. Meanwhile, post anti-spike immunity is not just porous but nonfunctional and thus incapable of applying anti-cellular-immune pressure.
Yes the vaccine non-functionality is the biggest mind-boggling wtf for me in terms of peer pressure and what must be the most rampant case of cognitive dissonance ever recorded in human history: people I consider(ed???) friends post on FB, etc, completely non-medical exhortations for those self unvaxed anti-vaxers to get vaccinated, but will readily admit it does not stop infeciton or transmission.
Most people, before, only "cared what others think" in isolated spurts of performative altruism. Now it's a matter of literal baptism. I've only been driven to stop caring now that everyone else thinks it's cool. I never realized there was this widespread, subterranean urge to live in a Calvinist panopticon where life is one unending episode of pointlessly holding the door open for someone who is still five feet away, but there you have it.
Let us think of the multicellular organism as a hotel.
I started writing an essay and went with "world". I prefer your optimism to the marek doomsayers, and wonder how hard nocebo would work in this environment so deeply steeped in fear and propaganda.
"Nocebo" / mass psychosis are likely so powerful that the actual existence of viruses is not required, for the tangible "evidence" of their effect. Another reason why the study and contemplation of bacterial viruses (phages) has more to teach us than Germ Theory.
Excellent, well-written and helps my understanding of how viruses propagate and evolve. I find this more accessible than the previous articles. Thanks!
I also have not been concerned about the unvaccinated-for-covid in terms of Marek's-like evolution and losing immunity, both because of the broad antibody memory to prior encounters, and because of treatments which will continue to work. Even unvaccinated chickens are claimed to survive Marek's when treated so as to slow down the viral replication (e.g. with lysine).
For the covid-vaccinated, though, it seems like ADE and OAS are real possibilities, or am I missing something?
Glad to hear that - I think the "first argument" of Immune Equilibrium is the easiest to render to the page. But it also depends on the most verification with real-world research. It can be toppled by a single counter-example!
But explaining examples that match, like MD(H)V and SARS-CoV-2, is way easier than trying to do so with conventional evolutionary / immunological myths!
ADE is still "likely," in my eyes, per the simple "match to observation for category" argument. Coronavirus vaccines usually cause ADE after a bit of antigenic drift. So, these coronavirus vaccines are likely to cause ADE. OAS and everything else to do with influenza are not going to be fit into my theory until the end.
I liked this statement a great deal:
"The prevailing situation is that most of the authors warning about a Marek’s disaster for SARS-CoV-2, and reading the tea-leaves of government statistics to divine whether it has already arrived, do not seem deeply curious about actual virology or the immune system"
As someone who actually writes and fixes software I do not have the liberty to say "this bug is clearly another example of Original Antigenic Sin or a case of Antibody Dependent Enhancement!"
I actually have to understand what is going wrong and fix it and there does seem to be a lot of handwaving out there without reference to actual mechanisms.
Not sure where I got this link, but it's very well written, very readable and pretty sure supports what you've written here:
https://www.juliusruechel.com/2021/09/the-snake-oil-salesmen-and-covid-zero.html
Yes, Ruechel's piece seems quite good - though I've only skimmed it since it is essentially arguing the same case as Die Herd but without delving as far back into the history. Same reference to advantage of removing immune escape pressure but doesn't seem to acknowledge / analyze the distinct evolutionary situations for viruses that do and don't have immune escape. Even if so, he seems ahead of most of the "Marek's Disaster!" advocates in actually thinking about the virus instead of recycling theory.
Mind you he is concerned about a Marek's variant - he describes it as a "dual-track" variant.
Let me know if this is inappropriate to comment but I found this interesting also:
https://www.news-medical.net/news/20210510/Research-suggests-Pfizer-BioNTech-COVID-19-vaccine-reprograms-innate-immune-responses.aspx
Pre-print study:
"However, they also showed that the vaccine altered the production of inflammatory cytokines by innate immune cells following stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli.
Following vaccination, innate immune cells had a reduced response to toll-like receptor 4 (TLR4), TLR7 and TLR8 – all ligands that play an important role in the immune response to viral infection.
Neta and colleagues also found that cytokine responses to fungi were increased following vaccination."
Sounds like a confused immune system to me?
Interesting twitter thread here: https://twitter.com/letsthinkdeeply/status/1447755555938967561
His argument (unsupported IMO):
* the current narrow spectrum vaccines will induce rapid evolution triggering a rapid never ending series of related pandemics
* rapid escape evolution increases the probability of worse variants and extinguishes variants that may be more mild and currently somewhat protective.
* in normal evolution no preference is made between large and small mutations but with vaccines, the mutations that confer survival become much more important and require complete escape.
* As a matter of fact, vaccines never allow the small changes that might promote co-existence with virus, because the vaccines remove these variants from the milieu.
Which seems weird to me, as surely if you only need to circumvent spike-based antibodies, the changes are only to the spike, and thus small changes?
I must be missing something more than a degree in microbiology / virology.
It’s the “Escape Mutant Disaster!” which, as you say, doesn’t have much relevance to natural immunity - especially naive/innate natural immunity which doesn’t care about spike variation. And I have argued since August is now only relevant if there is widespread “boosting” since no inhibition of transmission = no selection/escape pressure.
You wrote about Forever Spike about 3 weeks ago. Does this current article contradict that—has your thinking evolved?
I think there's no question that humanity has shown amazing hubris in regards to its attempted manipulations, of the immune system which is so incredibly complex. I struggle to stay above water with a lot of this stuff, despite having spent the last 12 years reading everything I can about the immune system after having been diagnosed with a mystery neuropathy that is thought to be autoimmune.
The idea of Immune Equilibrium is fascinating and I'll read about that next. I'm already open to the concept through familiarity with intentional self-infection with helminths (parasitic worms) in order to stimulate the immune system.
At age 67, I'm very glad that I had all the measles and chickenpox as a kid. The worst result for me of chickenpox was that I missed a trip to Disneyland. Now I wonder if my immune system might be compromised because I never managed to get the mumps (only half kidding.)
This article expands and reinforces my dismissal of the "Marek's Disaster!" scenario for SARS-CoV-2, because it is not an immune-evading-virus. The flip side of this dismissal is that such a disaster *is* being courted with vaccines against (verified or potential) immune-evading-viruses like herpesviruses, etc.
I haven't devoted much text to it yet but there are definitely overlaps between Immune Equilibrium and the "hygiene hypothesis" which go beyond the vaccine / virus focus - implications that microbiome dysregulation and general lack of "stress-testing" the immune system, and even intermittent sedentary behavior, decalibrate toll receptors and lead to incorrect classifaction of "self" into "not self," etc.
OK, bottom line for the rest of us; is it worthwhile to get vaxxed?
The only "benefit" left to Covid vaccination is the reduction in severe outcomes during infection, which still appears durable. This "benefit" disappears when you discount for effective therapeutics that, by all appearances, are better at preventing severe outcomes than the Covid-vaccines anyway. I think, based on that alone, no one should get the shot. Preventative medicine with a ? mark on whether you will ever even end up needing it and another ? mark on long term harms doesn't make sense.
The detriments to Covid vaccination in terms of broad and specific (anti-SARS-CoV-2) immune competence are significant (especially w.r.t. the current signal for an increase in cancers). In the short term, clinically-measurable infection with SARS-CoV-2 seems to be increased by Covid vaccination, and in the long term, ADE may come into play (hopefully, this will still be treatable with therapeutics, but it still counts in the con column). I'll caveat that both these things are based on squinting at broad patterns, and may be confusing correlations for causation.
The detriments to Covid vaccination in terms of direct harms seem quite bad. I'm particularly worried about a direct link to carcinogenicity (as opposed to an indirect link based on taxing immune resources; I have a theory for the etiology which I will be posting at some point) and about under-diagnosed myocarditis among middle-aged and older women, based on widespread reports of jaw / neck / back / shoulder pain in VAERS (all of these can be symptoms of cardiac distress; almost none of them are being screened).
An interesting example of the sorts of things you're discussing here - looks like (?) RSV hides + gets reactivated by COVID or vaccine - Japan major RSV outbreak: https://twitter.com/GreatBillDixon/status/1446626420839616516
Nice catch - It seems very plausible that RSV is also flaring up from dormancy after Covid-vaccination. Unlike shingles, however, where an outbreak implies lysogenic exit by default, an RSV infection is presumably more ambiguous. It could even be naive infection + antibody-dependent-enhancement from the anti-spike antibodies, after all. I haven't looked into RSV yet. Seems like a friendly enough critter.
Thanks for this perspective. I have always found the Marek's outcome unlikely, and I have made some similar arguments albeit not from an immune equilibrium perspective.
In addition to the points that you make, a Marek's situation is an outlier: we have been vaccinating humans and animals with leaky vaccines against all manner of diseases for decades and Marek's is the only one that has become lethal in response. In a sense this is analogous to the outlier position of smallpox - a virus that was uniquely eradicable and is being used to suggest that SARS-CoV2 or other viruses will follow a similar trajectory to eradication if only we vaccinate hard enough.
Fear is rampant, and both sides want something to be afraid of. It's not difficult to see what this looks like from the mainstream perspective, but in the alternative camp it is taking the form of giving far more credence to the scariest conceivable outcome (a virus that kills unvaccinated people, vaccine treadmill forever, oh my!) than is justified by the facts on the ground.
Oh, but I am quite afraid of the outcome for Mumps, HHV-3, and HBV. At least for HHV-3 / chickenpox the naturally infected (from before 1995) are still walking around with a time-capsule version of the virus. My current rough impression is that HBV is in more of a liminal grey area between lifetime residency and transient infection, implying much faster possibilities for producing hotter strains. And there's no proven improvement to the allegedly relevant clinical outcome, cancer! I never even heard of the HBV vaccine before a month ago and now it drives me bonkers to think about it!
But in the context of SARS-CoV-2 the virus, I am sternly anti-fear. There is no productive action based on fear of a coronavirus possible anyway and never has been.
Agreed that this is a serious concern with regard to vaccination in general, especially with "onboarded" viruses as you call them. It is, however, a comparably slow process that will be driven by vaccination policy over years to decades, as was true of Marek's in chickens.
I have three serious concerns regarding overuse of vaccination in general. The first would be this one, that we will create an evolutionary imbalance between target microbes and the human immune system resulting in a breakdown of equilibrium and quite possibly the appearance of "hot" new strains. The second is that we will adversely impact the evolution of the human immune system, rendering it less able over time to manage natural infections. The third, and most pressing in my view, is that we are disrupting the normal infant/childhood development of the human immune system, rendering it more prone to allergy/autoimmunity and also less effective in terms of fighting off common infections and illnesses. You're probably familiar with this (now involuntarily retracted) paper which found an strong correlation between number of childhood vaccinations and a wide range of common problems.
https://www.mdpi.com/1660-4601/17/22/8674
Yes, point 3 sticks out - the inevitability of 0 benefit from "shielding" the immune system from the external menu of hazard is so obvious that there can be no question of malicious intent from the medical industry at large. Deficiencies in competence with the internal menu of hazard are always more profitable, so why wouldn't you sort your patients into the latter category? How dare nature attempt to rob you of God-granted revenue, after all. On the other hand, it's the thing that is easiest to course-correct from. No impact on the "super-genome."
I haven't read it yet, though I saw the link in your blog! At some point I will get around to it - as of now I have read only about 6 minutes of actual research/literature on vaccine harms.
Dr. Thomas' earlier article on aluminum concentration/toxicity from the CDC infant schedule is also of interest.Try: doi.org/10.1016/j.temb.2019.126444. There is a corrigendum to the original article, but it gives a chemical viewpoint of the potential harms of escalating interference with the immune system.
It has me at "Previous modeling efforts are based on very little empirical data, with the model by Priest based on whole-body clearance rates estimated from a study involving a single human subject." Will definitely give it a read.
Was this essay in response to el gato malo's latest?
Also: is the basic premise of your essay that the vaccine really targets only the spike, so that's pretty much all that's evolving, which means there's not really any pressure on making it more virulent. And because natural immunity hits as many viral proteins as it can it will continue to develop a robust, ongoing response to any evolved variants?
As someone commented below I will need to re-read this a couple of times. This is my first attempt at confirming understanding.
Yes and no. I intended to offer only a "glancing" blow at egm's sloppy "Marek's Disaster!" Theory; today's egm post renders my argument an even more direct attack than it was when I composed it.
My argument is that natural (post-infection, adaptive cellular) immunity is both porous and non-spike-specific. Meanwhile, post anti-spike immunity is not just porous but nonfunctional and thus incapable of applying anti-cellular-immune pressure.
His response to your comment on his article - ie from someone who literally asks to be peer reviewed - seems somewhat antagonistic.
I was going to say as much there to him directly, but tbh expected such a comment to receive the same serve of vitriol.
A most curious result.
Yes the vaccine non-functionality is the biggest mind-boggling wtf for me in terms of peer pressure and what must be the most rampant case of cognitive dissonance ever recorded in human history: people I consider(ed???) friends post on FB, etc, completely non-medical exhortations for those self unvaxed anti-vaxers to get vaccinated, but will readily admit it does not stop infeciton or transmission.
It's heart breaking.
Most people, before, only "cared what others think" in isolated spurts of performative altruism. Now it's a matter of literal baptism. I've only been driven to stop caring now that everyone else thinks it's cool. I never realized there was this widespread, subterranean urge to live in a Calvinist panopticon where life is one unending episode of pointlessly holding the door open for someone who is still five feet away, but there you have it.
*selfish unvaxed
* post-"vaccination" anti-spike immunity
Let us think of the multicellular organism as a hotel.
I started writing an essay and went with "world". I prefer your optimism to the marek doomsayers, and wonder how hard nocebo would work in this environment so deeply steeped in fear and propaganda.
"Nocebo" / mass psychosis are likely so powerful that the actual existence of viruses is not required, for the tangible "evidence" of their effect. Another reason why the study and contemplation of bacterial viruses (phages) has more to teach us than Germ Theory.
Excellent, well-written and helps my understanding of how viruses propagate and evolve. I find this more accessible than the previous articles. Thanks!
I also have not been concerned about the unvaccinated-for-covid in terms of Marek's-like evolution and losing immunity, both because of the broad antibody memory to prior encounters, and because of treatments which will continue to work. Even unvaccinated chickens are claimed to survive Marek's when treated so as to slow down the viral replication (e.g. with lysine).
For the covid-vaccinated, though, it seems like ADE and OAS are real possibilities, or am I missing something?
Glad to hear that - I think the "first argument" of Immune Equilibrium is the easiest to render to the page. But it also depends on the most verification with real-world research. It can be toppled by a single counter-example!
But explaining examples that match, like MD(H)V and SARS-CoV-2, is way easier than trying to do so with conventional evolutionary / immunological myths!
ADE is still "likely," in my eyes, per the simple "match to observation for category" argument. Coronavirus vaccines usually cause ADE after a bit of antigenic drift. So, these coronavirus vaccines are likely to cause ADE. OAS and everything else to do with influenza are not going to be fit into my theory until the end.
Nice write up. I am going to have to re-read this at least 2 or 3 times!