Dr Jonathan Kerr

What do you think would be the correct term to use regarding our immune system, if any?

 

All the suggestions that there is a problem with the immune system in ME have failed to be borne out by further studies. My guess is that it is normal near enough.

 

Could I take you back to another thread, I have forgotten which? I think we were discussing the cyclical relapsing/remitting symptoms- the sore throat, swollen glands, furry tongue etc It was suggested that the cause of these might be a persisting pathogen. As I recall, you thought it unlikely that this would be the case, and suggested that the immune system could produce the impression of persisting pathogen even in the absence of any continuing infection. How could this be accounted for by a "normal" immune system in the absence of something to set it in motion?

It may be that I misunderstood.

 

Dear Dr Edwards
Would you be willing to speculate where you think the problem might be in ME? If not viruses, if not the immune system, if not the GI tract, in your medical opinion, what do you think is going on in ME? I'm not trying to put you on the spot; I'm just wondering if your have any ideas you would be willing to share.

 

Immune-mediated inflammatory disease? Ron Davis suggested that our body feels as though it fighting an infection, but what we are experiencing is inflammation, that makes it 'feel' like a virus.

 

I realise this is confusing. The psychoneuroimmune model seems to cling to the idea that thoughts and the associated stresses could contribute to abnormal immune responses in the sense of failure to clear a virus or an autoimmune disease.

Those sorts of immune response are mediated by signalling mechanisms involving cytokines and nerve signals and other things. I think it is reasonable to suggest that the persistent 'viral symptoms' of ME are due to overenthusiastic signalling of this sort but not to the extent of actually mediating an abnormal immune response in the sense above. I also do not think one has to suggest that the immune system itself is at fault. It may be passing on signals generated in other systems - neural or endocrine.

Maybe one could make the analogy of a computer that has been used enough for the hard disk to be almost full. It is likely to keep flagging up all sorts of messages about things being wrong with this system or that. Software packages may crash repeatedly. There is nothing actually wrong with any system, its is just that the signalling pathways are gummed up.

 

There is no inflammation in ME as far as I know. I do not know what Davis is referring to. There is some signalling going on but it is not causing inflammation. That is the point I am trying to make in response to Chrisb above.

 

Mark Davis at Stanford has found T-cell activation. What do you make of this then?

 

Ron Davis 2018 Symposium

"The results of that is basically there aren't virus infections that are different from healthy controls. A few people do have them but healthy controls have more in this small study, so it makes me suspicious that in fact they don't have viral infections. They have something else going on that feels like a virus infection and a lot of inflammation things will make you feel like that. Most of these viruses probably, by themselves, don't really do anything by themselves. It's not to their advantage to give a signal to the body that they're there. The body is the one that does the signaling that there's something wrong. And I think if you have that signal like inflammation it may feel like a viral infection. The only reason I'm stressing that point is that if it's most likely you don't have a viral infection you shouldn't be taking antivirals probably, because they're probably not that healthy for you. And the reason they're probably not that healthy is that the antivirals generally target the synthesis of the DNA from the virus and it works because it's a very primitive DNA polymerase, and in fact you can inhibit it without inhibiting your human polymerase. The problem is the mitochondrial polymerase is also a primitive one and some of these may actually inhibit the mitochondrial polymerase to some extent and given the fact that there seems to be mitochondrial lack of activity that's the probably not a good thing to do, if you don't need it. So I don't think patients should be taking anything that they don't really need to take, it's probably not a good thing to do".

 

I think he is saying something very similar to what I am saying. He is not saying there is inflammation here. He is saying that there may be signals like those of inflammation. That is something very different.

 

I don't think Mark Davis found T cell activation. He reported finding clonal expansion. That might be interpreted as due to activation but it is actually something different and may have another explanation. Moreover, when Jo Cambridge and I tried to work out what his data actually showed we could not make out what the controls were and what the figures actually represented. I am not aware that this ever got published.

 

Thanks for the explanation @Jonathan Edwards . That now makes sense to me. It is probably the words that are confusing . My Interpretation then is that a normal immune system may give a normal response in relation to the signals which it is receiving, but abnormal in relation to the needs of the body of which it forms a part. It all depends on where you are standing and upon the aspect of normality under consideration.

 

I understand it was not known beforehand that only the enterovirus ME/CFS patients in the ME/CFS cohort would respond to interferon. That fact only became apparent after the study was conducted.

So I would not have thought any placebo effect would come into play.



But I think it also helps to look at a priori arguments for why chronic diseases in general (not just ME/CFS) are likely caused by infectious microorganisms.

Prof Paul W. Ewald provides a good evolutionary argument for why the causes of chronic diseases are likely to be due to infectious pathogens, rather than genes. In fact, he strongly counters the prevailing scientific fashion which assumes genes are the primary causes of disease.

Ewald says: "chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them."

In this very interesting presentation by Paul Ewald about infectious causes of cancer, he says that back in the 1970s, there were no cancers that had been attributed to infectious pathogens. As it stands at present, around 20% of cancers have now been shown to be caused by infectious microorganisms. So you can see where the trend is going. Ewald suspects that by 2050, we will have discovered that more than 80% of all human cancer is caused by infection.

I don't think it is unethical to try to pinpoint the cause of a horrible disease that destroys the lives of millions of people around the globe. I think it would be unethical not to pursue all avenues that might lead to identifying the cause (or at least a cause).

From what we know, interferon does not appear to be an effective long-term treatment, as patients tend to relapse. But some patients given interferon alpha plus interferon gamma in combination went for over a year without relapse. Two or three years in some cases. So there are benefits.

Also, not all patients develop depression as an interferon side effect; it's typically around one-third of patients who do so when interferon is given to treat chronic hepatitis C infection. So if we work with idea that patients can drop out of the study if they get depression or experience other side effects, then the side effects become less of an issue.

 

Come on, @Hip.

Dr Chia has been doing all these studies because he is convinced that enteroviruses are involved. Sadly, the great majority of what goes on in medical science labs is trying to prove a hobby horse, or just what is fashionable - the old adage 'hypothesis-driven evidence'.

To make anything useful of what goes on in medical science you have to take on board human nature. People want things to work out a certain way. The result here is obvsiouly what the study was designed to produce.

 

This belies the common misconception that causation in disease is just genes and environment. As I have said before, this simplistic account is useless. It is not even what you would find in a basic epidemiology textbook. As I said before you can always find something that will fit with a ramshackle sort-of hypothesis if you ignore basic negatives.

 

I see your point. The study in question was not by John Chia (the study was conducted in the UK in 1993), but yes, I guess with the emphasis on enterovirus research in the UK at that time, there is a possibility some placebo might be involved. But again, that just calls for better controlled studies.

Are there any other potential causal factors of disease other than genes, epigenetics, and environmental factors?

The basic concept of cause and effect implies that every disease must have at least one material factor that causes it. Diseases cannot just happen without a material cause, unless one believes in things like divine intervention, or bad karma.

If we look at environmental factors, these include:

Chemical toxins (man-made or naturally-occurring).
Various radiations (UV light, cosmic background radiation, etc).
Infectious pathogens (viruses, bacteria, fungi, protozoa and archaea).
Lifestyle factors like diet, exercise, and stress.

These environmental factors may affect a person directly, or they may have affected the mother during pregnancy, which may alter the development of the fetus (for example, cytomegalovirus or rubella infection in pregnancy are risk factors for autism).


So when searching for the causes of disease, that cause surely must involve one or more of those factors.

 

Yes, I advise reading a decent basic epidemiology text.
The other main cause is internal stochastic. The immune system is fundamentally dependent on stochastic processes, which are normally hidden but can readily manifest as disease. The nervous system is probably also heavily dependent on stochastic developmental processes, again hidden in normal function. Cancer is largely stochastic - random mutation.

The illnesses that remain hard to explain may well be mostly determined stochastically - which is why scientists who have not read epidemiology go round in circles looking for genes or microbes.

Epigenetics is a pretty meaningless buzzword that has become popular which does not correspond to any recognisable epidemiological category. Its use is a neat illustration of just how dumbed down medical science has become. It is often used to imply something in addition to environmental and not genetic but in the context of processes downstream of both.

 

If ME is due a stochastic process, it will be many decades before anyone has any clue what is going on.

 

Ah yes, I forgot about that one, but I do now remember you explaining this several years ago. So stochastic biological events are another line of research to pursue, in terms of possible causes of disease.

 

I don't think that follows. Peter Stastny's recognition that rheumatoid arthritis had a largely stochastic causation was what allowed us to work out how it works. In a sense recognising that ME may involve stochastic pathways might be the essential clue to what is going on. If Fluge and Mella's B cell idea had been right that would have involved a stochastic mechanism - all autoantibody production is stochastic.