The causes that aren't genetic or pathogenic

Even if there is "true stochasticity" happening at the quantum level and if this would have any effects as @Jonathan Edwards describes, I suppose what researchers will be looking at are results of the positive feedback amplifications and the end state this leads to and how this can be fixed, so I don't think you have much to worry about. After all you either have an autoimmune disease or you don't and either that autoimmune disease has a good treatment or it doesn't, the treatments and diseases itself aren't described by a quantum state, you either have them or you don't.

 

I lived my first eight years in a city where winter smoke from chimneys sat thick in the air and wasn't blown away normally due to the geography. Then I moved to an apple growing area for the next eight years where DDT and other 1950s era pesticides were sprayed with abandon. I would have been outside riding my horse or fishing while breathing in this chemical fog. At this stage some odd health issues started to emerge - nothing life threatening or immune related as far as I know.

A bit later I lived in a university college for 4 years. My room was just a few feet from the junction of two major roads, one being the main route between Sydney and Melbourne, so I would have been breathing in filthy diesel and leaded petrol fumes day and night. At this point I knew there was something not right about the way I felt. Fifty five years on I can't describe it accurately but I had the beginnings of peripheral neuropathy, felt vaguely unwell and had many strange aches and pains that came and went. I didn't dwell on it though.

The 1970s were spent living under the flight path near a busy airport so more pollution I imagine. My husband worked at Monsanto and would have come into contact with many various chemicals so I was exposed to them as well from his clothes. There weren't many precautions taken in those days!

I started noticing I needed to rest the day after going for a long walk, for example and that's not normal in your 30s and 40s. It all went on through the 1980s and around 1990 I had an unusually bad cold or possibly flu, didn't rest, and that's when I didn't really recover. All the previous symptoms became worse, and have continued to do so.

My point being that I have no idea what caused what, or when. The rest of my family have had nothing similar as far as I know. I'm sure it all wasn't due to emotional stress or over-activity etc., but I don't discount pollutants.

 

Aha! Dear Roger is very convinced of his ideas and they have had a good run in terms of fashionability but almost everyone now in the consciousness studies community reckons they don't add up. Interestingly, if you read his Shadows of the Mind you can see that, very much like Einstein, Roger simply does not understand quantum theory. He asks why the world does not seem fuzzy if particles are superposed. He has completely misunderstood what the theory is about. It has nothing to do with things being in two places at once. Roger's orchestrated objective reduction theory is a simple contradiction in terms as a scientific theory because it is the ultimate in untestability in principle.

 

There aren't any 'wave functions' that collapse and any good quantum theoretician will tell you that. Once an excitation has occurred and annihilated (which they do do) you are left with the randomness caused by the necessary stochasticity of the occurrence. If every move on a chess board is a bit random you will end up with a game that is a bit random. Nothing 'classically deterministic' happens after the excitation (particle if you like) has occurred. You just get another necessarily stochastic excitation and another on for ever.

 

It is not only left but it takes over the whole picture, hence the advance of entropy.

There is a lot of intuitive resistance to the idea that fundamental events have to be partly random and that this is the reason why our world is awash with randomness but it has to be true.

The most interesting thing is that it was Einstein who proposed that light was made of photons - the real birth of quantum theory. And when he did he immediately realised (he said so) the argument that I have been making - that quantisation of light entailed randomness. They could go either over there or over that way - and at an infinity of angles. Like Leibniz he would have realised that any attempt to tame this randomness ultimately leads to an infinite regress. You can't. Yet Einstein wanted to keep randomness out of physics for another fifty years. He finally made peace with his own brainchild in his last years.

 

Indeed there are processes for fixing the awareness and we know a lot about them. One is a process called receptor editing, which put rogue B cells back on a sensible track. Another is complement mediated deletion. Receptor editing is dependent on PTPN22, which is a risk factor for RA and complement genetics is a key risk factor for lupus. So yes we can see much of how things are kept in control as well as allowed to be random.

But there is an interesting analogy with computer systems that raises a problem worked on by my old school friend David Rosenthal. The more you make a system complicated to control for random 'bugs' the more opportunities you generate for creating new sorts of bugs. The net result is that there is no perfect way of storing digital information. The more you try to make it foolproof the more you introduce ways that it might not be. Basically, if you make a backup copy you now have two things that can be wrong.

And this is no way a God of the gaps or deus ex machina approach because we have identified precisely what the bugs might be for each disease. We even know exactly which arginine residue in IgG is the target of the rheumatoid factor bug effect. We know that citrullination of arginines is crucial to a misrecognition in RA. We know exactly which complement genes promote lupus and why.

The situation is really much the same as cancer, where random mutation is accepted as central to the question of why one person gets cancer at a particular time. Smoking may have made it more likely but there is still no way of knowing when the mutation will occur if ever in Mary Bloggs. The epidemiology of RA is well enough defined to be able to say that it is about half genetic and otherwise mostly stochastic - the age incidence profile tells us that. There is an environmental effect from smoking too, but relatively small nowadays.

And with luck these Achilles heel points in the system can be targeted with specific drugs. We are almost there. It doesn't seem to me much like the BPS bullshit approach!!

 

I do think that three people in a family all getting ME at the same time must be significant, though. There is nothing in the immune model as I understand it that would explain that. But there are always surprises in science where a simple mechanism one had not thought of can explain something apparently inexplicable. The role of smoking in RA was completely unpredicted. We then realised that cigarette smoke contains chemicals that can induce changes like citrullination in proteins. The story is still not fully worked out but it is no longer perplexing.

 

Since you have clearly thought about these things and since I'm clearly not a quantum physicist, my views are most likely completely stupid and incoherent to begin with, but are you not assuming that certain problems have been resolved that haven't been resolved yet?

Whilst maybe far less popular then the Copenhagen interpretation, are there not people working on precisely this infinite regress and proposing that once you go back to some singularity “true randomness" could resolve?

Does this not depend on whether the interactions of all quantum states in which the quantum system is involved in dominates the "true randomness" of the system? In the sense that a sort of central limit theorem with a possibly deterministic limit may arise (of course it seems far more likely for the limit itself to be random) and that depending on the situation "a bit of randomness" might be rather negligible or not? Isn’t that what one wants to understand, what “a bit truely random” actually means?

I suppose you are saying that all physical activity is quantum activity and as such “a bit truely random”, that is of course unless you’re talking about general relativity and if I understand you correctly you are simultaneously talking about the microscopic as well as the macroscopic, since you are describing macroscopic “true randomness” via the microscopic “true randomness”, how does this resolve (this is my basic layman understanding I'm neither a physicist, nor a quantum physicist, nor a philosopher)? In which manner can one answer questions about the end of the chess game by referring to it's beginning written in different rules?

 

Not really. I am talking about a logical necessity that Einstein understood very well. A lot of people don't like it because it spoils intuitive realism. But as a physician aI am very aware that the representational nature of our experiences makes intuitive realism a very bad place to start.

Not that I am aware of. It is a logical regress that has no possible solution. Lots of people in popular physics keep trying to row back on interpretations but they just replace one impossible conception with another. Copenhagen has some good elements but it is still much too mechanistic. There are no wave functions collapsing. Leibniz's approach reveals a fundamental flaw in any interpretation that allows a 'quantum' to start out without knowing yet where it is going. He understood that the dynamics of indivisibles obey completely different rules from divisible. In essence everyone is confusing types of quanta (ensembleles) with token quanta.

It is all rather complex but I have confidence in my analysis for two reasons. Firstly, it was handed down to me personally by the physicist Michael Ellis Fisher, who was regarded as one of the half dozen greatest physicists of the latter twentieth century. He explained to me why all the popular interpretations miss the point. Secondly, my view is shared by the leading Leibniz philosopher, Richard Arthur, who similarly has seen how Leibniz's insights resolve all the muddle about quantum theory.

 

I am not quite sure what you are trying to get at. I realise it is complex and counterintuitive. The world consists of fields that 'advance' through spacetime stepwise through 'excitations' or 'changes' that used to be called 'particles' but are more 'actions'. For any pattern of the fields a number of different excitations have measurable possibilities/probabilities of occurring. Once one has occurred the probabilities change to a new set for new excitations. Some excitations more or less have to occur in some situations but as a rule there are always slightly different options and very often there are an infinite number of slightly different options going in all directions. Since only one excitation with a single negative charge (or whatever) can occur in a given situation the world has to toss a coin and choose. If it was not a matter of tossing a coin it would need to extra rules but it turns out that there is an infinite regress of needing more and more precise rules in a symmetric metric. The option of not having randomness built in to every event is just not available to the world. It may seem weird but only because our brains paint the world as if it was full of 'things' 'moving' and 'bumping'. We now know it isn't that at all. That is just a convenient fiction our brains find useful.

 

If you meant that there is first time for everything, I'd agree. But not too many of them are pandemic like SARS-COV-2. That is not to say that the virus has to be novel to cause ME/CFS. We do know in fact that most of infection-triggered cases in fact are from known viruses, like Mono/EBV. But they don't turn as big a portion of the infection into ME/CFS as COVID does. I suspect prolonged inflammation is at least partly responsible, and novel viruses are probably more likely to result in longer inflammation.

 

It's also muddied by the apparent existence of a post EBV-like group, who have significant symptoms but they do eventually resolve. There's still a major impact on their lives—six months to a year is quite long enough to lose your job or be forced out of a home you can't afford on sick pay—but the eventual recovery seems to be complete, as it can be after glandular fever.

It's hard to separate this group from those who're still just as ill after two, three, or four years and might turn out to have a prognosis more like that of ME.

 

I recalled these comments* from Vicky Whittemore re Wenzhong Xiao's talk (part of the metabolism webinar) - basically there are a lot of ways to get epilepsy & ME/CFS may be the same.
One of my suggestions (in response to NINDS request for research to be prioritised) was family genetic studies (whole genome sequences/rare variant study) - families with more than 1 member affected & at least 1 severe @Hutan

*"Vicky Whittemore: Yeah. So, this is like, I guess, question, comment from -- so, the other hat I wear at NINDS is to oversee grants on the genetic epilepsies. And there are now, I think, 110, 120 known genes. That when there are mutations in those genes can lead to seizures and epilepsy syndromes. So, looking at the complexity of the metabolic pathway, it's not at all surprising to me to think that there could be problems in -- or any different parts of that pathway that could lead to potentially similar symptoms that we diagnosis ME/CFS. So, it's like thinking about your pipeline picture. There could be leaks at many different joints in that --

Wenzhong Xiao: Exactly.

Vicky Whittemore: It's still leads to a leaky pipe. So, just your thoughts about that. And is that what we're seeing? In part one, we see this heterogeneity, potentially, between individuals with ME/CFS.

Wenzhong Xiao: Yes. I definitely say agree. And, you know, I think we see this for some of the other so-called complexity disease as well, where, you know, you could potentially have multiple places, you know, almost like we were driving a car there, you know. If the car is broken, there could be, you know, multiple places that can, you know, make the car to stop.
So, that seems to be, you know, something that we should, you know, definitely talk about. I know, you know, there are at least six or eight different seminars that you're organizing. You know, I think this is not only an issue with metabolism, but also with some of these other, you know, aspects of the -- yeah, of the research. It's relevant to those topics as well.
But the bottom line is, definitely, it seems like we're seeing more than one place that could be relevant to the mechanism of ME/CFS. And we also see some of the, you know, whole genome sequencing data of ME patients. And, indeed, as you said, you know, there seems to be, you know, neurological components that, you know, might cause similar symptoms in at least some of the patients."
https://www.ninds.nih.gov/sites/def...esearch_Roadmap_Webinar_3_Metabolism_508c.pdf

 

I agree and from what I can see that indeed makes the whole Ebola situation possibly even more interesting. The above viruses have a survival rate close to 100% whilst that of Ebola is somewhere around 50%, so the available community that could even develop post-Ebola is naturally 50% lower then for the other viruses (ignoring how less comon Ebola is). If Ebola caused ME/CFS at the same rate of Covid or EBV it seems likely we would have never heard of post-Ebola, especially since post-Ebola has received 0 attention and 0 funding. Of course there may be a strong confounding factor with the severity of the acute illness itself causing organ damage, PICS and all subsequent problems and in that sense being entirely different and not a entity worthy of study, but it does seem like something someone should at least have a proper look at.

On the other hand the only reason why I probably heard of post-Ebola was due to viral persistence and following outbreaks due to that, so what I'm describing above might not really be the case...

 

One of the problems is the definition of Long COVID vs. ME/CFS. I've seen anything from 9% to something absurd like 40%, and the recent CDC estimate includes all chronic fatigue including ME/CFS. I have no idea what portion of that is true ME/CFS, to tell you the truth. I'd think it would be a useful information to tabulate the prevalence rate for each disease. Do you have any such a thing that you can point me to?

Multiple infections probably won't matter. What's important would be the chance of getting ME/CFS after an infection. OK, it probably matters to the person who get hit, but not to the prevalence/incidence rate.