What do you mean by "increased sensitivity"?
In your opinion, what has changed, if anything, in ME/CFS research in the last 10 years? If it has, what do you think was the catalyst?
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What do you mean by "increased sensitivity"?
Jonathan Edwards
Senior Member (Voting Rights)
Yes, I think that is plausible, since the hypothalamus controls the autonomic system.
Yes, I am genuinely optimistic. In my own career I spent nearly twenty years being rather pessimistic about ever making a breakthrough. When we did make a breakthrough I realised that much of it we could have arrived at long before if we had believed we could. And when the experiments started to make sense they made complete sense. When you are on the right track, suddenly you start getting black and white results according to the predictions of a narrow hypothesis.
The task for ME/CFS is different but my sense is that in a way DecodeME has broken the back of it. For RA all we really needed to do was to go over lots of old data and see how it fitted together - rather the way members here are going over the data from the genetics and other things besides. I cannot pinpoint exactly where things are going to end up but I think they will.
I think of the analogy of a hopper feeding something like grain. For lots of reasons it may seem not to be doing much and may indeed be clogged with input. But there comes a point if you shake things around abit when suddenly you start to see everything moving towards the exit, sliding down from all sides into the same place. That is the sense I have. OK, it may still take some time to find out exactly what the answer is but I see the situation now as totally different from what it was when I got interested ten years ago. To me this is exactly how you get to an answer for a disease.
Jonathan Edwards
Senior Member (Voting Rights)
I guess I just mean facilitated - in neural terms, reinforcement of synaptic activation making the pathways carry signals more easily.
neophyte32
Senior Member (Voting Rights)
When you say that the task is "different" for ME/CFS, what exactly do you mean ? Is it because the data are still too fragmented, or because we are still missing an essential piece that would allow us to connect the different findings, unlike what happened with PR ?
And regarding time… of course, no one can predict when we will have “the” answer. But do we really need to fully understand the entire disease before we can find effective treatments ? It seems conceivable that we could identify a few sufficiently important mechanisms and target them, even if the complete model of ME/CFS remains incomplete.
I'm trying to find the right way to put it, and the best I can come up is that despite the massive changes that Long Covid should have brought, there has been no visible change at all. About the biggest difference is that the medical profession has aggressively resisted changing anything.
There is more search and more funding. More studies are happening and papers are published. It doesn't show anywhere. Reading/skimming the research published today reads exactly the same as a decade ago. It's the exact same, just more of it. Aside from DecodeME, which is being actively resisted so far, although it may just be because things happen as slow as possible and the full paper hasn't been finalized.
But really it's remarkable how despite all the changes, nothing has changed. It's really hard to describe how that's even possible.
There is more search and more funding. More studies are happening and papers are published. It doesn't show anywhere. Reading/skimming the research published today reads exactly the same as a decade ago. It's the exact same, just more of it. Aside from DecodeME, which is being actively resisted so far, although it may just be because things happen as slow as possible and the full paper hasn't been finalized.
But really it's remarkable how despite all the changes, nothing has changed. It's really hard to describe how that's even possible.
Jonathan Edwards
Senior Member (Voting Rights)
It is different in all sorts of ways. There is no classical pathology to guide us. The data are in a very different form. The middle of research politics is different, although fairly comparable. The experiments that look most useful are more expensive and high tech but high tech is what we have now. Looking back, sorting out the relevant mechanisms, at least in broad terms, in RA should have been like shooting fish in a barrel. But I thin the same will seem to be true for ME/CFS in twenty years time.
No, but we want to have a grasp of the key dynamics. Interestingly, in RA I was pestering Roche to use rituximab in 1996, at a point when I had only established the weaker, less specific, half of our model. The more specific idea came in 1997. I managed to get a trial set up by 1998 mostly because Roche said definitely no thanks and so I got it started on my own. I think the extra evidence in 1997 was important in giving me the confidence to go ahead. For ME/CFS I think there is an appetite to try things on fairly speculative terms, so I don't see this as a big issue.
Jonathan Edwards
Senior Member (Voting Rights)
Long Covid research has been a washout. Unsurprisingly, since Long Covid does not even define a workable clinical pattern. This is just the normal boondoggling nonsense that takes up 95% of biomedical research. I just ignore it. For ME/CFS the change has been dramatic. The boondogglers may not notice for another twenty years (the situation for RA - 28 years on they have suddenly woken up to the 'new' idea of targeting B cells). But that does not stop progress. I think it is important to realise that the picture of biomedical research presented through social media, journals and whatever, is largely an irrelevance. That is not real science. DecodeME is.
Nothing remarkable. Just the herd following each other baa-ing out loud, as ever was.
neophyte32
Senior Member (Voting Rights)
Twenty years… for those of us who are severe, that sounds almost like a life sentence I really hope we find a few shortcuts before then !
Thanks @Jonathan Edwards
Thanks @Jonathan Edwards
hotblack
Senior Member (Voting Rights)
Yes I think that’s definitely a big factor. I’m really excited by the science. There are interesting things happening and people involved. I would live to and try to focus on that and have been able to for a while through family support and luck.
Meanwhile the reality of what I (and more broadly we but I don’t want to speak for others) face trying to interact with any service or professional that I need for even a basic quality of life is an absolute shit show. I hoped there would be changes in attitudes after NICE, Covid and DecodeME but if anything things have got worse. So I understand what @neophyte32 @rvallee @V.R.T. and others say.
Separating yourself from that and looking at the research we may be able to say there has been positive changes or developments. But being able to do so is a bit of a luxury because in terms of our day to day lives there really hasn’t been any.
Jonathan Edwards
Senior Member (Voting Rights)
That was before things started slipping down the hopper. After that it was 2 years!
I certainly expected a backlash from the psycho-behavioural cult, and a fairly robust one. But it has been truly disturbing and appalling to see just how ruthless, relentless, brazenly dishonest, and vicious it has been. And, very unfortunately, quite successful so far.
I also expected a little better from the rest of medicine, and broader society. But, thus far the overall response has been, well, woefully sub-par, tardy, and more than a little begrudging, and sometimes worse than that. The cult has very effectively exploited existing ignorance and prejudice and power structures, and indoctrinated the profession and wider world against the brutal realities the psycho-behavioural cult's central role in it.
Again, if I had not witnessed it first hand I would have trouble believing it was even possible, let alone had actually happened, and proved so hostile to reform.
But here we are.
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Nightsong
Senior Member (Voting Rights)
Others have mentioned DecodeME, but it has been the stand-out result, hasn't it? It's certainly the most hopeful thing that I can think of in >20 years. That clearly took a very unusual confluence of events to bring about, but the emergence of hard data devoid of anyone's preconceptions or biases is probably the most significant milestone in decades. I'm unsure what behind-the-scenes events took place to make it successful; if AfME were responsible for lobbying for funding, that's something that clearly worked well.
Greater recognition of the salience of PEM? In the days when most cohorts were Oxford you couldn't really say much about what the patients had in common other than persistent unexplained fatigue. (I think there's a lot of "TATT" cases in GP land.) While there's still no widespread understanding of what should & shouldn't be considered PEM there is an increasing recognition, in some quarters at least, that the illness has dynamics, patterns & features of its own, some of which are very unusual or do not occur at all in other fatiguing conditions.
A few institutions taking ME/CFS somewhat more seriously - IOM, for example; institutions have failed us badly, but I think it's undeniable that institutional support matters - it conveys a sense of legitimacy to researchers; it makes it more likely that we're heading in the direction of the mainstream of medicine rather than further out towards the fringes, it makes it easier to attract government/state-mediated funding. Conversely the Royal Colleges' hostility to ME/CFS has made everything far more difficult in the UK.
The perception of PACE has begun to change from settled to controversial, and more attention is being focussed on methodology and its weaknesses. And Fluge & Mella came along and proved again to everyone in the ME/CFS field what can happen when you actually have proper blinding & controls in your trials.
Disease specific biobanks - the UK ME/CFS one in particular - resources like that do reduce barriers to research, which is particularly important when you don't have interested physicians running proper clinics. I've seen them credited in a number of decent papers.
The emergence of a post-viral syndrome following SARS-CoV-2 has certainly driven research and changed the direction of existing research; unfortunately, much of it has been of poor quality or has resulted in rehashing old ideas that really should have been abandoned by the 1990s, such as viral persistence, and the commonly used LC definitions such as the WHO definition have resulted in cohorts that are, I think, too broad to be useful. It has brought funding but much of that funding has been wasted. The story of LC is a story of shoddy thinking & missed opportunities.
Until recently there hasn't been much to grab onto. No-one has known where to start. And the stuff that is there to grab onto coming out of DecodeME looks mostly if not exclusively neural. (If I were involved in advocacy I might try to interest not only those studying BTNs etc but also some of the psychiatrists who who aren't interested in psychobehaviouralism but who are interested in neurotransmitters etc. There are some - there's a textbook and a journal called Biological Psychiatry.)
On the "lack of" part of the question - I think the lack of any sensible, interested physicians in the UK is a very serious bottleneck to research; no-one regards ME/CFS as something to specialise in, and the cycle of clinical observation informing research which in turn generates leads/insights on what to look for next in clinic - that cycle is completely broken. The UK clinics are wholly unsuitable and almost exclusively run by people with an psychobehavioural ideological view about what ME/CFS is - compare and contrast to, say, the well-established position of MS in both general neurology clinics, specialist services in tertiary care & and the research collaborations that have developed for that condition.
I actually think the existence of the current clinics will put off both physicians & researchers alike - in the UK ME/CFS is seen as the bailiwick of psychologists & physiotherapists. No medical specialism wants to take responsibility for us. Influential psychobehaviouralists have made sure that the study of ME/CFS remains controversial. Diagnostic quality is clearly extremely poor - lots of UKB participants with a self-reported CFS diagnosis clearly don't have ME/CFS.
Also going to the "lack of": the lack of high-quality researchers (until recently most researchers have only become involved when they have a personal interest or want to pursue some fringe theory; ME/CFS has been seen as too much of a backwater). There are researchers pursuing fringe theories in other conditions but we have an unusual number of them and it makes the whole field look like a bad choice. Funding levels have been historically low. MRC clearly doesn't look favourably on us. Charity funding is low & poorly managed. Patient organisations whom researchers might seek to work with - charities & other organisations - putting out fringe stuff & lacking suitable medical & scientific advisors to guide them.
The natural history of ME/CFS is still very poorly characterised.
Interesting things have happened in Germany & Austria recently. WE&ME might have some insights into the internal dynamics of that. Anything that can be learned from such successes should be.
Greater recognition of the salience of PEM? In the days when most cohorts were Oxford you couldn't really say much about what the patients had in common other than persistent unexplained fatigue. (I think there's a lot of "TATT" cases in GP land.) While there's still no widespread understanding of what should & shouldn't be considered PEM there is an increasing recognition, in some quarters at least, that the illness has dynamics, patterns & features of its own, some of which are very unusual or do not occur at all in other fatiguing conditions.
A few institutions taking ME/CFS somewhat more seriously - IOM, for example; institutions have failed us badly, but I think it's undeniable that institutional support matters - it conveys a sense of legitimacy to researchers; it makes it more likely that we're heading in the direction of the mainstream of medicine rather than further out towards the fringes, it makes it easier to attract government/state-mediated funding. Conversely the Royal Colleges' hostility to ME/CFS has made everything far more difficult in the UK.
The perception of PACE has begun to change from settled to controversial, and more attention is being focussed on methodology and its weaknesses. And Fluge & Mella came along and proved again to everyone in the ME/CFS field what can happen when you actually have proper blinding & controls in your trials.
Disease specific biobanks - the UK ME/CFS one in particular - resources like that do reduce barriers to research, which is particularly important when you don't have interested physicians running proper clinics. I've seen them credited in a number of decent papers.
The emergence of a post-viral syndrome following SARS-CoV-2 has certainly driven research and changed the direction of existing research; unfortunately, much of it has been of poor quality or has resulted in rehashing old ideas that really should have been abandoned by the 1990s, such as viral persistence, and the commonly used LC definitions such as the WHO definition have resulted in cohorts that are, I think, too broad to be useful. It has brought funding but much of that funding has been wasted. The story of LC is a story of shoddy thinking & missed opportunities.
Until recently there hasn't been much to grab onto. No-one has known where to start. And the stuff that is there to grab onto coming out of DecodeME looks mostly if not exclusively neural. (If I were involved in advocacy I might try to interest not only those studying BTNs etc but also some of the psychiatrists who who aren't interested in psychobehaviouralism but who are interested in neurotransmitters etc. There are some - there's a textbook and a journal called Biological Psychiatry.)
On the "lack of" part of the question - I think the lack of any sensible, interested physicians in the UK is a very serious bottleneck to research; no-one regards ME/CFS as something to specialise in, and the cycle of clinical observation informing research which in turn generates leads/insights on what to look for next in clinic - that cycle is completely broken. The UK clinics are wholly unsuitable and almost exclusively run by people with an psychobehavioural ideological view about what ME/CFS is - compare and contrast to, say, the well-established position of MS in both general neurology clinics, specialist services in tertiary care & and the research collaborations that have developed for that condition.
I actually think the existence of the current clinics will put off both physicians & researchers alike - in the UK ME/CFS is seen as the bailiwick of psychologists & physiotherapists. No medical specialism wants to take responsibility for us. Influential psychobehaviouralists have made sure that the study of ME/CFS remains controversial. Diagnostic quality is clearly extremely poor - lots of UKB participants with a self-reported CFS diagnosis clearly don't have ME/CFS.
Also going to the "lack of": the lack of high-quality researchers (until recently most researchers have only become involved when they have a personal interest or want to pursue some fringe theory; ME/CFS has been seen as too much of a backwater). There are researchers pursuing fringe theories in other conditions but we have an unusual number of them and it makes the whole field look like a bad choice. Funding levels have been historically low. MRC clearly doesn't look favourably on us. Charity funding is low & poorly managed. Patient organisations whom researchers might seek to work with - charities & other organisations - putting out fringe stuff & lacking suitable medical & scientific advisors to guide them.
The natural history of ME/CFS is still very poorly characterised.
Interesting things have happened in Germany & Austria recently. WE&ME might have some insights into the internal dynamics of that. Anything that can be learned from such successes should be.
hotblack
Senior Member (Voting Rights)
Really good overview @Nightsong thank you!
More reasons charities should be trying to shut down the existing services not prop them up.
More reasons charities should be trying to shut down the existing services not prop them up.
Pre-1950, people typically thought in terms of many decades. Now it's almost pointless to speculate about 20 years in the future. Will there be an economic crash that slows progress, or will there be a breakthrough in nanotechnology that, like AI has, cause dramatic changes in just a few years?
Looking at past progress in ME research gives a very gloomy outlook. I prefer to look at rate of development of technologies that might make finding the mechanism of ME easier. Maybe someone is already developing a nanobot that can be directed to move through the brain to map out chemical concentrations. Unlike developing an artificial heart, going from an idea to widespread usage does not need several decades. Would the typical lengthy approvals process apply to injecting a few picograms of silicon nanobots?
DMissa
Senior Member (Voting Rights)
truth will out, it only takes one paper to blow the doors off.
In the long run, no doubt. But you know the saying about the long run.
It also true that a prompt robust productive response to a critical empirical finding is not automatic. Sometimes such findings sit quietly ignored or underappreciated.
Though I agree it is less likely that would happen in the current ME/CFS & LC situation, with a lot more eyes and minds, and background science and tech, available to bring to the problem these days. Plus a lot more pressure from patients to get on with it, especially now LC is on the scene.
I would also not be surprised when the truth is finally revealed that we find some clues about where to look had been sitting in older papers for some time, possibly decades, due to a lack of insight and boldness to grasp their relevance and allocate the required resources to chase them up properly at the time.
DMissa
Senior Member (Voting Rights)
bless the forum because I get the sense that it is the greatest concerted effort to comb over the old stuff.
hotblack
Senior Member (Voting Rights)
You have summoned Michael Caine…
hotblack
Senior Member (Voting Rights)
Actually maybe we need eight powerful researchers to perform the Rite of AshCainte