I still cannot get the transcript from youtube directly, but I have got it via a transcript site and asked Claude 4.5 to tidy it up, produce a summary and critique.
Claude was quite slow in producing the transcript, but that may be because I have switched it into more analysis mode. Also it is long so posted in chunks.
Podcast Transcript Analysis: Lithium, Rapamycin, and Chronic Fatigue Syndrome
TIDIED TRANSCRIPT
Host: All right, John, thanks for coming back down to OptiSpan HQ for the podcast. It’s been a while. I can’t remember when we had our first go-around at this, but a couple of topics I want to dive into with you today. One, the paper that you were a co-author on about rapamycin and chronic fatigue syndrome, which I’ve talked about on the podcast before. And the other, of course, being lithium, which you touched on in our first interview. But a lot has happened in the lithium conversation recently, in particular related to Alzheimer’s disease. So I’m excited to get into it. I think maybe let’s start with lithium.
You’re a psychiatrist by training, so you probably thought a lot about lithium and used it in that context. What first got you to think about lithium beyond the sort of traditional way that it is used in psychiatry?
John: Well, lithium was always a metabolic drug. If you avoid getting lost in terminology, psychiatrists generally think about using uppers and downers. We use uppers—stimulants and antidepressants—for low activity syndromes and hibernation, and we use downers for manic symptoms and psychosis. It’s all cell surface signaling on nerve cells.
Then suddenly we have this very odd drug, lithium, that doesn’t fit within that framework. Lithium has been the graveyard for psychiatry for 20-30 years because we didn’t have a technology to understand what it was really doing. There were hypotheses that it affected glycogen synthase kinase, inositol signaling, and other things, but we just didn’t have a granular technology. Yet when you see lithium work in patients, it’s an amazing drug. You can have extremely ill people be essentially completely normal when you see them every couple of years, and that’s the way it rolls.
Then the data came out in dribs and drabs over the last 10 or 20 years that people on lithium had longer telomeres, had less atrophy on MRI, had decreased death rates, decreased rates of Alzheimer’s disease. It became clear that for all of us who care about biochemistry—biochemistry is life and life is biochemistry—you can’t disentangle the two. So I made it a real effort to try to go into the source code and understand lithium. I went a lot to the mitochondrial conferences and did a lot of my own clinical work looking at mitochondrial measures.
Very recently, the field has shifted. The Nature paper just came out maybe a month ago where a very well-funded Harvard group looking at a well-accepted model of Alzheimer’s showed that changes in lithium concentration dramatically reduced markers of Alzheimer’s and possibly changed the inflammatory response to amyloid and tau tangles. That’s fantastic.
Host: That was in mice, but they also had human data, right? In human brains of people with Alzheimer’s disease, you saw lithium depletion in certain regions and binding by amyloid. This is really a major breakthrough, right?
John: It’s a breakthrough because there’s this lack of interest in a generic drug that costs 40 bucks a year. I’ve talked with the drug reps about these treatments for Alzheimer’s disease—they’re $70,000 a year. They require multiple MRIs, they require a specialty team. The waiting list at Johns Hopkins is reportedly two years. The waiting list here at the UW to see a specialty neurologist in Alzheimer’s is six months.
Now we have interest that is perceived as legitimate and not fringe—that lithium is worth looking at again. That’s a major advance.
Host: It sounds like from your perspective, you’re not surprised by this, but probably pleased to see the attention.
John: I need all the help I can get. There’s no ego involved in just getting your patients better.
Host: We’ve spent billions of dollars on Alzheimer’s drugs, most of which have failed. We have a few now that are approved that don’t work particularly well, but at least they have some impact. Do you think lithium could actually succeed where these drugs have all failed?
John: We talked last time about this new biomarker, the ATN profile, where you’re looking at proteins that leak out of a stressed brain that has Alzheimer’s. I was very excited to have those proteins available because it allowed me to manage the patients that I’ve seen for 20 to 25 years and be with them at the next stage of their life.
The Chinese have some data out looking at these markers, and they estimate that about 25% of people between the age of 72 and 77 are going to start having personality change associated with Alzheimer’s, and that may not necessarily be cognitive impairment. Alzheimer’s is not a disease just of learning and memory—it’s of mood. One of the first signs of Alzheimer’s is actually anxiety.
We’re left in this terrible world where 25% of the population is going to be in psychic pain because of Alzheimer’s even if they don’t have cognitive impairment.
Host: I guess this is where the definition of Alzheimer’s gets murky as well, right? Is it necessarily the case that all of those people will go on to develop at least classical Alzheimer’s as it’s been defined historically, or is this really a whole spectrum of conditions?
John: Everything in biology is one web with no cut-off points. This is the problem in medicine when you recruit individuals who are good at memorization. Medicine is enriched for highly autistic people that like clear cut points. Biology laughs at that. Biology is a continuum.
What I’m seeing in my clinic now is that when you look for people above the age of 65, you can see stress markers very commonly in these patients. For some of those patients, if you give them lithium, my God, they feel better. Sometimes their Alzheimer’s markers get better within months.
Host: By Alzheimer’s markers, you mean in particular the ATN profile?
John: Yeah. Amyloid, tau, and neurofilament light (NFL).
Host: The question which is incredibly relevant is: what’s the dose?
John: There’s this sort of fantasy that there’s going to be some large study done by Harvard or done by a multi-center group, and it’s going to give us a protocol and it’s going to say you need this dose, and that’s the optimal dose to prevent Alzheimer’s. Biology laughs at that.
Host: Let me ask you a question. The study in Nature landed on lithium orotate as a particular salt of lithium that was resistant to the binding by amyloid. Is that does that line up with your experience, or does it matter, or maybe the dose is dependent on the salt of lithium?
John: I want to go really broad. I think it’s really important to think about the issue of locality. It’s maybe the difference between Newtonian physics and quantum mechanics. In Newtonian physics, you see these large objects and you have very clear equations that tell you exactly what’s going to happen. Quantum mechanics is fast time scales, very small objects, and it’s even worse—it’s a probability distribution.
What’s really great about this Nature paper is that it brings up the concept of locality—that there’s a distinction in medicine between endocrine signaling, where you have a chemical like thyroid hormone or insulin that affects every cell in the body at the same time, versus paracrine signaling, where there’s a chemical that’s excreted that is only meant to have a local effect.
They bring up this concept of paracrine signaling and locality in terms of the activation in the microglia and the activation of the synapses that are associated with Alzheimer’s. If you just look at CSF or if you just look at blood, are you looking at a global variable and you’re not really able to see the local signaling?
Host: In your experience, in your patients, do you use lithium orotate as a preferred form, and do you see any difference in efficacy?
John: Let’s look at their data. When you look at their data, they make an argument that the dissociation constant is different between an inorganic ion and an organic ion. On the market we have lithium citrate, which is available and essentially equivalent to orotate in terms of their raw data in terms of dissociation constants. I have not yet compared and contrasted the differences between an inorganic ion, which is typically lithium carbonate, with the citrate.
But there’s this kind of odd physical chemistry. In their paper they say, “Well, psychiatry typically produces lithium levels that are a thousand times the physiological level.” So they’re arguing the dissociation constant—maybe a hundred times different with the carbonate versus the orotate. If you increase the reactant concentration high enough, it doesn’t really matter whether it’s carbonate—you can overcome it.
Do you get more off-target side effects? Again, dose finding, dose finding, dose finding. How much available lithium is there in the microenvironment? Do you need 450 mg of lithium carbonate and 150 mg of lithium citrate? This is animal data. It’s a great idea, but until you hit the clinic, you don’t know anything.
Host: It sounds like maybe we just don’t have the data yet.
John: This paper just dropped. I don’t know enough about clinical practice to know whether lithium orotate or lithium citrate were commonly used. Orotate is usually used by the naturopaths because they’re probably prescribing much lower doses—40 to 50 mg, that kind of stuff.
I had an interesting conversation that your listeners might find thought-provoking. Somebody watched our podcast last year and they’re in Belgium and they wanted me to advise on the use of lithium. I can’t manage a patient in Europe for all sorts of reasons, but I talked to one of their representatives in England who was essentially a primary care doctor. She’s like, “Oh, it’s illegal for me to prescribe lithium in England.” It’s only allowed with psychiatrists. Lithium carbonate is illegal if you’re not a psychiatrist, but if it’s orotate, you can prescribe it.
Host: That’s crazy. I was just in Germany and I asked about lithium. There, they can prescribe it, but you can’t buy it over the counter like you can here. You can buy lithium orotate on Amazon in the U.S.
John: When lithium first came out in Denmark, it was actually illegal because they didn’t know how to dose it. This was maybe in the '20s or the '30s. Then I think Mogens Schou figured out you just need to dose a little lower. This whole issue of dose finding is literally a hundred years old with all sorts of interesting regulatory starts and stops. It’s just human frailty at large.
Host: You mentioned the ATN profile. I wanted to dive a little bit deeper on that. Is it your experience that you feel like you see consistent changes in that biomarker with lithium, or at least in some people you see changes in ATN?
John: I think the problem is that I’m so busy and I’m such a generalist. I’m doing this to some degree because these are people I’ve worked with for 20-25 years. I have a responsibility for them, and I’m not going to pretend that there’s nothing to do and send them off to Harvard as if Harvard’s going to save them. It won’t. I know better.
What we see in our patients is that we see many people that have elevations of the amyloid or they have elevations of phosphorylated tau, and they don’t yet have cell death. So they don’t have neurofilament light—they don’t have fragments of the axons in their blood. I think it’s going to turn out that if you don’t have elevations of NFL, you tend not to have atrophy on MRI. That’s a really lovely place to be. Theoretically, your disease is reversible because there’s no cell death. Nobody wants to get Alzheimer’s and nobody wants to get older, but to know that you have time—that’s such a gift.
Then the Harvard paper comes out and suddenly it’s no longer wackiness to try that bipolar drug that crazy people take.
Host: Is it your guess that the people who are in that sort of stage—prior to significant neuron loss—they’re the ones who are going to get the best outcome from something like lithium?
John: Well, once cells are dead, they’re dead. You’re not going to bring those back, and you have a damaged brain. It doesn’t repair quite as well as something like stroke. You see this in clinical practice all the time—quite significant strokes, but if the general brain is healthy, you rewire very well. But you’ve got an Alzheimer’s brain and you get cell death—boy, that’s a tough road to go. You’ve got to really reverse the underlying process. Obviously you want to catch this early.
Host: Given what at least what we think we understand about how lithium is probably working here, it’s going to be much more effective prior to significant neuron loss.
John: We just want to fix the underlying problem. If people are having stress markers leaking out of their brain into their blood more than the 95th percentile, that’s a problem. Do I see a reasonable group of people try lithium and they’re on lithium and they sure feel better and they tell you right away? They’ll say, “I’m thinking clearer. I handle stress better,” and they don’t have bipolar. These are not bipolar patients, but they’re on lithium. It’s health span rather than necessarily lifespan.
Is something like the ATN a marker of somebody who is like, “Yeah, maybe you should try a little bit of lithium and see whether you just feel better”? Now, if the markers reverse, that’s a plus. But we haven’t had time yet to do the kind of studies that say, “What if they just stop?” That’s still a plus, right? If you don’t get cell death and they don’t progress and you’re feeling better on a drug that costs 40 bucks a year that’s been used for more than a hundred years, my God, that’s a win.
That’s what the Harvard paper is telling us—that there may be a $20 bill that’s just on the ground that anybody can pick up who has some reasonable degree of medical skill.
Host: When you and I talked a year ago, I read in your voice like, “Oh, this is kind of an unusual claim that lithium is potentially one of the best anti-aging drugs.” Things have changed, certainly for Alzheimer’s. We could talk about the anti-aging potential effects of lithium as well. Alzheimer’s is one age-related disease, but I think there’s reason to think lithium can go beyond Alzheimer’s.
Although, if we look specifically at the Nature paper, at least the mechanism they propose seems to be very specific for Alzheimer’s disease in the sense of amyloid depleting lithium in specific brain regions. Again, could be a lot more going on than what they proposed in that paper, but that was the mechanism that they landed on.
John: There was a couple things that really bothered me about that paper. Number one, when you looked at their pathway analysis in their supplement, they talked a lot about the Wnt pathway or the wingless pathway, which implies that when you block glycogen synthase kinase-3 beta, which is a downstream product to mTORC2, you’re making cells less differentiated. I think that fits with a lot of what we know in terms of how lithium works in bipolar patients—that it differentiates the astroglia in bipolar patients, so it becomes a speed governor on excitatory nerve cells.
The other major pathway is autophagy. Autophagy was massively upregulated with lithium, and they don’t even mention that in the paper. I thought that’s really strange because autophagy is everybody’s—it’s like motherhood. Everybody’s into autophagy, and then they left it out of the paper.
Host: Well, maybe they’ll watch the podcast and respond. I mean, when you do multi-omics, it’s really hard to see the forest for the trees. Often times the reality is to get your paper into a top tier journal like Nature or Science, you really do have to pick one relatively simple story and stick to it.
John: That’s sort of what I was getting at—I think there’s a lot going on with lithium. I think this model of amyloid beta depleting lithium in specific brain regions makes sense. It fits the data, but there’s probably a lot more to it. Fifty percent of Alzheimer’s genes are microglia, but I’m not sure that’s the proximal cause. I think the proximal cause is the excitatory nerve cells.
Host: I just had a really interesting podcast conversation with Corey Funk from Institute for Systems Biology. They’re doing a lot of work as well on cholesterol metabolism and membrane fluidity as being a key driver of at least early components of Alzheimer’s disease as well.
John: Yes, I think that’s right. The data on lithium impacting age-related processes independent of Alzheimer’s disease is also pretty interesting. There could be multiple mechanisms at play here. It’s an mTORC2—it’s a downstream mTORC2 inhibitor. It’s going to affect every cell in the body in different ways.
Host: There could be multiple ways. Why would we just focus on microglia?
John: We have another technology that’s out that’s commercially available that supplements the lithium story. We can now do a commercial RNA—microRNA—assay of about 400-500 species. The assay generates a vector of RNA abundance in blood, and the company has a very deep phenotype matrix that they’ve gathered over 5-10 years, 2,000-3,000 people.
What they’re seeing is a really large signal for lithium in a variety of psychiatric conditions and also in the aging area as well. We were stuck with proteomics that had low dimensionality—amyloid and tau and NFL. Now we get to blow up the dimensionality a little bit more. It’s a large enough dimensionality you can do gene set enrichment.
Host: So this is data from a variety of individuals, some of whom have been taking lithium. Is that what you mean?
John: No, let me go over the protocol. This was a group out of Indiana that followed let’s say 2,000 people, and they did serial microRNA estimates in these patients. They looked at things like suicide attempts and memory loss with age and divergence from biological age versus the aging clock stuff, hospitalization for bipolar disorder, chronic pain measures, ER visits for chronic pain.
Now they have an AI that has a large enough data set that you can start to do cluster analysis and you can cluster phenotypes. But you can also break the AI and look at each RNA species and say, “Hey, what drugs out of the 2,200 FDA approved drugs are going to move this vector towards the origin?”
I’ve done about 20 of these so far, and what just comes up over and over and over again is lithium. This is a prediction based on what we know about lithium that it would move the gene expression profile in the direction of health.
I think what they’re showing is that there’s a group of humans that have a gain of function in mTORC2. We’re all sort of comfortable with that in the rapamycin world—there’s a whole bunch of diseases where mTORC1 is upregulated, mitochondrial disorders and gain of function in mTORC1. But I’m looking at this data and saying there’s an mTORC2 gain of function that is part of the human condition, and lithium is a targeted drug across so many phenotypes because we really are hitting source code.
Host: That’s interesting. As you know, a lot less has been done on mTORC2 compared to mTORC1 in terms of understanding the biology of that complex.
John: I was at the aging conference and I was talking to some people about, “Hey, I need to know more about mTORC2.” They said, “Oh, John, you should go to a Gordon conference.” I’m like, “I’m a psychiatrist seeing patients.”
Host: Okay, so let’s go back kind of big picture with Alzheimer’s disease. Best case scenario for lithium, how much do you think it will move the needle for Alzheimer’s disease? Are we talking a year, five years, complete cure? What’s your best guess?
John: I think thinking in aggregates is just so dangerous. I have no doubt there is someone out there on lithium who is going to live 10 years longer because they’re on lithium. It’s an mTORC2 gain of function—you downregulate mTORC2 and the cells don’t go into senescence as quickly, and they die more cleanly. They die with apoptosis rather than screaming with their head on the spike because they’re overregulated.
I think most—if you really look granularly in the psychiatry literature, you would see this data—that there are certain bipolar patients you put on lithium and their lifespan goes up a lot. Not even their health span, but just the brain works better. They exercise more, they drive more safely. It’s not suicide attempts—it’s just the brain acts on the environment and they have a brain that works.
Are there people that lithium has absolutely nothing to do with Alzheimer’s? 100%. I have some people that have markers and I give them this psychiatrically therapeutic, homeopathic dose—75 milligrams—and that’s all they can tolerate. Now, they’re still better, but it’s not anywhere near the typical psychiatric dosing.
I just can’t say it often enough: there isn’t a right dose and a right drug for aggregate populations. This is what you’re doing at Ora Biomedical—saying look, it’s not one drug, it’s a unique cocktail for each individual person.
Host: Do you think in the case of Alzheimer’s that’s because Alzheimer’s is a collection of many different diseases and lithium only works for some of them, or at least the cause related to mTOR2 is different in different people?
John: I think what it is—and I may even be deluding myself—a patient with Alzheimer’s disease is in a complicated n-dimensional biochemical space. That space is not linear. It has ridges and valleys, and none of our drugs are moving patients to the origin in a linear way. We’re in this very complicated nonlinear world.
It’s not that it’s a collection of diseases—it’s that our tools are not linear tools. When we combine them, we may be in a nonlinear world which I think biologists have to get their head around. I think the AI people understand that better than biologists do. The AI guys are like, “Hey look, if I don’t design my GPT or my ChatGPT somewhere, I’m going to hallucinate.” Whereas in biology, even the best people are just doing multivariate discriminant analysis and they just assume linearity, and that’s a mistake.
Host: What about side effects? I think lithium scares a lot of people. What are your thoughts there in terms of how concerned should people be—thyroid, kidney—at the doses that might be effective for Alzheimer’s?
John: Let’s talk about clinically who does poorly with lithium and what does it mean to do poorly. There was a study in the early '70s looking at lithium and temporal lobe epilepsy, and they had to stop the study because patients became too sick. There is a seizure model of lithium and pilocarpine exposure in rats where you can cause seizures.
In the temporal lobe epileptics, if you drive growth, you push toward the mTOR distribution—you dedifferentiate cells. Do you drive excessive cell growth in mesial temporal sclerosis and the temporal lobe epilepsy syndrome? There’s a problem differentiating cells in some patients that is related to excessive nerve biogenesis.
This is just to slap someone out of this idea—“Oh, it causes neurogenesis. That’s a good thing.” That’s really a dumb comment. Brains are—nerve cells are postmitotic for a reason. There’s only a few areas of the brain that have new nerve cells, the temporal lobe and the olfactory lobe, olfactory bulb. And those are the most epileptogenic regions in the brain. It’s not always obvious that you want to grow new nerve cells. That’s a problem in some people, and it can take months for seizure-like events from lithium to develop. It takes a lot of technical skill to pick that up.
Host: How frequent is that in people, would you say? These are high doses, right? Do we have any data on the lower doses of lithium?
John: Again, it’s a dimension, and the phenotypes are subtle. I once had a guy—he was in the prison, he was on lithium, and he was getting a great response to it. He says, “John, my nose is dripping on one side and I feel a little confused.” It turns out that in temporal lobe epilepsy monitoring units when someone’s having a seizure, you get neurogenic rhinorrhea on one side, ipsilateral to the seizure, and you can tell which side the seizure is on by just which side of the nose the patient wipes their nose.
So temporal epilepsy is a problem—this issue of excessive neurogenesis. But again, is that going to be primarily at the high psychiatric doses?
Host: We don’t know, right? It’s a continuum.
John: The other issue is in the migraine patients. Lithium with migraine is really tough. We had a real fantastic migraine specialist who’s retired since now who was just like, “Oh, John, please never give my patients lithium,” because not always, but often you make migraine worse.
Host: What’s the cause of that? Is that differentiation of the astroglia with fuel supply to the brain? Is it excessive autophagy?
John: That’s another interesting article because there is some cellular data that suggests that mitophagy and autophagy are distinct, and if you get too much autophagy, you drop the mitochondria below this energetic threshold, and that may be one of the lithium toxicities that happens.
Those are the two—you’ve got to be really careful with those syndromes. But migraine is 25% of women have migraine. One percent of the population has epilepsy. Ten percent of the population will have an epileptic seizure at some point in their life.
Host: I didn’t realize it was that high.
John: It’s high. And what if it takes four or five years? You’re just on the wrong gradient.
Host: So based on that, do you have concerns with the fact that people are going out and buying lithium on Amazon and taking it based on this Nature paper? Or do you think that the doses are low enough most people are not going to experience these kinds of side effects?
John: Saying I have concerns implies that I have some judgment on anybody. I don’t want to have judgment on anybody. This is an illness that’s going to kill a lot of people and it’s going to steal a lot of joy. You can’t find a specialist because the waiting list is two years, and there aren’t a lot of people like me.
I think we have to let a thousand flowers bloom and just do our best to have everybody work together and exchange information and try to learn in a logical way.
Host: Let me maybe frame it a different way. If people want to start taking lithium based on what they’ve heard and the latest research, what should they be paying attention to as potential side effects that might be worth watching? Let’s assume they don’t have access to you or somebody with your experience who can give them medical care. They’re buying it on Amazon. What should they pay attention to?
John: We’re in a desert. We’re in a specialist desert and people have to make their own decisions because they don’t have a choice. England makes it illegal—crazy stuff.
I think what we see in psychiatry with people that have bipolar disorder is you increase the dose until the risk becomes greater than the benefit. In general, the more lithium—this is well known—fewer hospitalizations, fewer suicide attempts, less mood swings. But once you get a blood level higher than 0.7 in a population of bipolar patients—and they’re not average, they have upregulated mTORC2—but the cut point is around 0.7 where you start getting tremor.
You start getting urinary—decreased urine concentration. You start getting brain fog which is different than Alzheimer’s, just sort of a fuzziness. Low-grade migraine symptoms are very common—just sort of photosensitive and kind of this soft cephalic pressure, maybe a little nausea. That’s kind of chronic daily headache, not migraine, but it’s definitely lithium-induced migraine.
In terms of thyroid, lithium is a blocker of the final step of adding iodine to the thyroxine molecule. So it’s a synthetic block. It doesn’t damage your thyroid—you just add thyroid back in. A medical student can do that. It’s a real side effect, but it’s not difficult to treat.
The kidney issue is probably again the “wet roads cause rain” story where the rates of spontaneous kidney failure in bipolar patients are elevated. When you stratify kidney failure in bipolar patients, lithium doesn’t have a higher rate of kidney failure than antipsychotics. This is classic age-related kidney failure, which actually correlates very highly in community samples with neurofilament light. That’s a $20 bill where we need to get our nephrologists in touch with our neurologists and really look at that population carefully.
Host: And directionality there could go either way or both ways, right?
John: Both ways. I’m assuming it’s a shared causality.
Host: What do you think is reasonable?
John: I think it’s reasonable if a primary care doc who has been managing illness for 20 or 30 years and has a generalist intuition and you want to work with a primary care doc—there’s nobody else out there, you don’t really have any choices—I don’t think anyone has the moral authority to say, “Oh, you shouldn’t do this.” But you want to have some sort of experienced sage advice, who can just say, “Hey, maybe you’re pushing this a little too hard.”
Host: Anything we haven’t talked about with lithium that you want to dive into before we shift gears to rapamycin?
John: No, I think we’re good.
RAPAMYCIN AND CHRONIC FATIGUE SYNDROME
Host: So, I want to talk about this chronic fatigue-rapamycin connection. I know you’re a co-author on the—I don’t think it’s been peer review published yet, but it’s in proofs.
John: It’s in. I just got an email about the proofs two days ago.
Host: Great. So, this first came across my radar as a pre-print. My recollection of this study—and obviously I’d like you to tell me the details because you were involved in the study—the take-home being that in a population of people with chronic fatigue syndrome who were being given rapamycin off label, a significant fraction—something like 75% of them—showed improvements in symptomology, which is striking. That seemed to be enriched for people whose chronic fatigue was associated with a prior viral infection, which I also think is pretty interesting given rapamycin’s connection to antiviral gene expression and chronic inflammation.
Then the other part of the paper that I thought was interesting was what was not seen, which was changes in glucose, insulin, lipids, which are side effects that people talk a lot about with rapamycin but that typically I think the data don’t actually show as being at least significant side effects across a population.
John: Great jumping off point. This paper is really a great paper because the core argument is 100% true. There’s a group of individuals who have a hyperinflammatory response to foreign RNA or DNA. It doesn’t matter whether it’s COVID, it doesn’t matter whether it’s flu, it doesn’t matter whether it’s Moderna or Pfizer. It doesn’t matter whether it’s a defect in the lamin A nuclear membrane. Too much DNA and RNA when exposed to certain individuals activates the STING pathway and other pathways, and you get a hyperinflammatory response.
