Preprint Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis or control serum, 2025, Ryback et al

[Jonathan Edwards]

@Jonathan Edwards I want to push back on that point about the critic at UCL. I wasn't at the UCL meeting of course but I don't get the impression this person was acting in good faith. The tone was aggressive to the point that people came up to Audrey after her talk to apologise for his behaviour.

Yes, @chillier, but I was there, listening to the comments, and chatting with Audrey, and she didn't seem to think much of it at the time, other than that a rather large physician had made what was probably a valid point in a rather vocal way. I think she was a bit surprised when the chair of medicine sent both of us an apology. The physician in question often raises questions rather forcefully. English is not his first language. I think some of those present mistook his usual manner for rudeness to a visitor.

He was warning Audrey not to use ME because it will put off medical people who might actually engage with the science. If my hearing was better and I had followed exactly what his roundabout outburst involved I would have turned to Audrey and said, yes, he is right, we should stick to ME. It may seem odd that he raised Simon Wessely but it makes sense. Wessely's original point was that although there was a real illness which he called CFS, ME was an idea of an illness that probably did not exist. In an important sense he was right, but the Canadian Consensus group had the insight to see that the real illness is the intersection of Wessely's CFS concept and a symptom of the chronic ME concept that Ramsay had not quite got clear - PEM.

I don't think this man was supporting Wessely. He was arguing for encouraging consensus rather than re-igniting the patient/doctor slanging match. His own approach to treatment is a bit unclear but I don't think he was acting in bad faith.

We have all used ME as less cumbersome, but we are at a critical point in the history of the science where we now have studies based squarely on the ME/CFS concept. They will show that ME/CFS is a real illness. I look forward to telling the sharpest sceptic in UK Medicine, Robert Souhami, that there is an answer to his question 'why treat it as a separate illness?' And any hint that we think ME/CFS can be equated with ME is going to seriously dent credibility. We are not going to be investigating ME as conceived by Acheson, or by Wessely, or indeed by 'ME specialists' or even some current ME charities. We are going to see the science of the real illness. Maybe it should be Science for ME/CFS, Action for ME/CFS, the ME/CFS Association but anachronisms can be tolerated in institutional names for longer than in the science. There may well be a completely new name soon enough - or more than one.

 

[Creekside]

I feel exhausted and doing activity becomes uncomfortable due a specific sensation that is very hard to overcome for long.

That's my feeling too: that my ME is producing a barrier to doing activities. My body is capable of the activity, but this ME effect is similar to being hungry, overheated, wearing uncomfortable shoes, being swarmed by mosquitoes, etc. It shifts activities from "I want to get this done" to "I don't feel up to doing this right now". That's why I consider this neurological rather than physical.

 

[Creekside]

I continue to use "ME" because "ME/CFS" takes much more effort to type, and to type correctly without having to do even more finger movements to backspace and correct.

 

[Creekside]

Some seriously inappropriate signals must be coming in from somewhere.

Why? Can't it be an inappropriate response to normal signals? Even small amounts of some food components will trigger serious worsening of my ME symptoms, but I doubt that my gut is sending seriously inappropriate signals; nothing that a lab test would flag as seriously abnormal.

Then there's cognitively-triggered PEM. Are the brain cells involved in that activity sending out seriously abnormal signals, or is it normal signals that a few other cells are hyperreacting to?

It also needn't be a single serious abnormality: in a feedback loop there could be multiple deviations that all add up in such a way as to cause a serious change in function. That's another possibility that won't readily show up on lab tests. For that situation, I think it would be necessary to have a theory first, to know which signals in which cells to monitor to the necessary degree.

 

[Jonathan Edwards]

It also needn't be a single serious abnormality: in a feedback loop there could be multiple deviations that all add up in such a way as to cause a serious change in function. That's another possibility that won't readily show up on lab tests. For that situation, I think it would be necessary to have a theory first, to know which signals in which cells to monitor to the necessary degree.

Which is why Jo, Jackie and I have tried to construct such a theory - to explain how things can go so wrong without anything showing up on lab tests.

I think you could argue that ultimately nothing is wrong except the brain mis-responding to anything and everything but nobody likes that idea much and I personally don't think it is very plausible, based on the various considerations we go through in the Qeios paper.

If T cells are playing around with all the input signals without generating any inflammation I think one could voter all stages including very severe. The test would be to track down the misbehaving T cells in ways that would catch them doing that sort of thing - maybe short term co-cultures.