[UK] A proposal for an ME/CFS, Long Covid, and Post-Infectious Disease research platform

[Jonathan Edwards]

but identifying that group is really hard

Not really. From my perspective as some who has worked on there mechanism of chronic disease it is very obvious which groups should be supported. Some are doing excellent work. Others aren't.

Start-ups is the model we already have. I am not sure these analogies are very useful.

 

[Kitty]

What would be more interesting to discuss and a more constructive discussion how we can create change and get some a sustainable research pipeline going

I'm one of the Nays, because I'm not convinced an artificially constructed pipeline is what's needed. I think what we need is bright people with ideas, and they cost nothing.

Someone making a fundamental discovery lobs a pebble into the pond, and ripples go out in all directions. In my mind, that's what a research pipeline looks like.

Have we - in the UK?

There are some very good people in the UK, but I don't see that it matters where they are.

Nor does it matter what area they work in. Ripples will reach people we didn't know existed, with knowledge we didn't know we needed, working on problems we didn't know were related. How do we plan for that?

 

[Adrian]

I'm one of the Nays, because I'm not convinced an artificially constructed pipeline is what's needed. I think what we need is bright people with ideas, and they cost nothing.

Someone making a fundamental discovery lobs a pebble into the pond, and ripples go out in all directions. In my mind, that's what a research pipeline looks like.

So how do we get bright people thinking about ME and doing experiments. Currently its researchers with connections to people with ME.

There are some very good people in the UK, but I don't see that it matters where they are.

There are some very good people my comment was related to a commend on increasing numbers which I don't see. It doesn't matter where they are but this discussion is in the context of people, charities and researchers in the UK trying to influence the UK government.

Nor does it matter what area they work in. Ripples will reach people we didn't know existed, with knowledge we didn't know we needed, working on problems we didn't know were related. How do we plan for that?

We can of course continue to wait and see if anything changes. If we want people to say thats an interesting idea then ripples may get to them but if we want others to start to work in an area to explore interesting ideas that is a very different proposition. There are lots of interesting ideas - as a researcher I would work on those that firstly pay my wage and secondly have a chance of having an impact and that means having good chances to get funding of the necessary scale to achieve useful outcomes. I guess these days many researchers view outcomes in terms of published papers in the right locations (that is how academics are judged) so perhaps even asking could funding be obtained with a likelihood of enabling the research for a publication in a high quality journal is a different consideration.

 

[Adrian]

In other words, it seems the NIHR would not fund things like genomics, and other omics biomedical research that I understand is still needed before there is anything to apply to health and social care. What we seem to need more at this stage is MRC funding for biomedical research including when there's a good indication, drug trials.

That is the point I was making about discovery research being the thing we need - hence the MRC. But the NIHR is more sympathetic to making an effort as the delivery plan is being pushed within the DHSC where they sit.

One of the hubs funded has as lead researcher, Rosmalen, who is a BPS supporter who doesn't seem to distingulsh ME/CFS from chronic fatigue and does dreadful research which is a real backward step.

So one hub isn't good but what about the other one? Which wouldn't otherwise exist without the funding.

But it does show the importance of patients and good researchers being actively involved in trying to develop a research strategy to help mitigate such possibilities. And I would argue actively working to try to get good researchers in adjacent areas involved.

 

[Utsikt]

I guess these days many researchers view outcomes in terms of published papers in the right locations (that is how academics are judged) so perhaps even asking could funding be obtained with a likelihood of enabling the research for a publication in a high quality journal is a different consideration.

I have to admit that I really don’t care where stuff gets published, and I’m not confident that researches that care about it are motived to do the best possible research for the patients.

The goal shouldn’t be to create the best circumstances for researchers, but to create the best circumstances for breakthroughs. The methods for achieving those outcomes might be very different and even directly conflicting in some cases.

 

[Utsikt]

So one hub isn't good but what about the other one? Which wouldn't otherwise exist without the funding.

But it does show the importance of patients and good researchers being actively involved in trying to develop a research strategy to help mitigate such possibilities.

How does a «research strategy» mitigate those issues? Who’s strategy is it and who has to follow it?

 

[Adrian]

I have to admit that I really don’t care where stuff gets published, and I’m not confident that researches that care about it are motived to do the best possible research for the patients.

These days careers seem to depend on the tier of journal or conference where things are published and so for career progression researchers need the right publications. That is just the system and researchers who don't play the game either need to be very good (in which case they probably have the right publications) or their careers don't advance which in academic and mean lots of short term contracts which also implies an inability to influence research directions.

We need to remember that researchers need jobs, job security and money to live and often have career aspirations. Universities already don't pay well at least at the lecturer/senior lecturer/reader levels.

The goal shouldn’t be to create the best circumstances for researchers, but to create the best circumstances for breakthroughs. The methods for achieving those outcomes might be very different and even directly conflicting in some cases.

Given breakthroughs are done by people creating incentives for people to work in research is part of creating the circumstances for breakthroughs.

How does a «research strategy» mitigate those issues? Who’s strategy is it and who has to follow it?

Ultimately we need governments to think strategically about research needs for the country and identify what areas are important (underserved for the needs etc) and then have strategies for ensuring research happens in these areas. If we can persuade government that research in ME is important (due to the personal costs to patients or more likely the economic costs (and opportunities) for the country then having the right people help shape the strategy and being involved in decision making can help mitigate against dodgy groups getting funding.

 

[Utsikt]

These days careers seem to depend on the tier of journal or conference where things are published and so for career progression researchers need the right publications. That is just the system and researchers who don't play the game either need to be very good (in which case they probably have the right publications) or their careers don't advance which in academic and mean lots of short term contracts which also implies an inability to influence research directions.

We need to remember that researchers need jobs, job security and money to live and often have career aspirations. Universities already don't pay well at least at the lecturer/senior lecturer/reader levels.

I know that is how academia works - but the people that are good at playing the game might not be good researchers. And the good people often don’t like playing games so they find positions where they can do their thing without it. At least that’s my experience from other industries.

Given breakthroughs are done by people creating incentives for people to work in research is part of creating the circumstances for breakthroughs.

Breakthroughs are created by excellent researchers, not just any researchers in general. My question is still how to attract and fund the right people - people that actually can make a difference. More mediocre research isn’t going to make a difference and it might actually harm the long term prospects of funding because they don’t have anything to show for their previous work.

Ultimately we need governments to think strategically about research needs for the country and identify what areas are important (underserved for the needs etc) and then have strategies for ensuring research happens in these areas.

My job was to write and implement strategies both in the private and public sector. I wasn’t able to do it for too long before Covid took that away from me, but I never saw a strategy that ever achieved anything without the right people pushing for concrete measures. An usually they would ignore the strategy when they knew better themselves.

Strategies are also extremely high level and rarely tell you anything about how you’re going to achieve your goals.

If we can persuade government that research in ME is important (due to the personal costs to patients or more likely the economic costs (and opportunities) for the country then having the right people help shape the strategy and being involved in decision making can help mitigate against dodgy groups getting funding.

If MRC is going to decide on the funding - how does their current track record look? Judging by examples in the letter you shared earlier - it’s appalling.

I don’t see anything in this proposal that directly targets decision making at MRC.

If MRC gets a big pot of ME/CFS-funding, it’s going to be impossible to deny the BPS-lobby because they will just claim that they are doing bio research with a holistic viewpoint based on bio neuroscience etc. And everyone will accept it.

And they will keep denying the good projects like they do today.

 

[Amw66]

We can push for more research money through projects. Is this about trying to get earmarked funding?

Norway got a BPS-led national competency service a few years after Fluge and Mella kickstarted the biomed angle and everyone were talking about how we need to take these patients seriously for once. They are still around and cause tremendous amounts of damage.

That’s why I’m cautious about asking for infrastructure that we frankly don’t have control over the staffing of.

This .
I live in the land of Carson and Stone and their ever expanding empire .

 

[rvallee]

Second: why is a «research pipeline» desirable? What does «research pipeline» even mean?

It means not this:

From what I've read on the forum (possibly this thread), high-quality biomed researchers are having their proposals turned down by BPS proponents who think there's no need for biomed research. I don't blame those researchers for not bothering to submit proposals in such a situation.

A recent application to the highlight notice, having taken into account advice from academic experts, UKRI funders and PPI groups about the imperative to align and synergise molecular pathogenesis approaches across both ME/CFS and Long Covid, and from an internationally recognised team with multiple relevant, recent publications in Science, Nature and Lancet, was declined with one referee allocating a score of ‘1/6; poor’. Another research team with a similar output profile has shelved all plans to work on ME/CFS after four attempts to obtain funding since 2020. Each application was revised in line with the feedback but then compromised by highly inappropriate reviews, two of which indicated that the reviewer had not read the grant (e.g., by criticizing experiments that were not proposed anywhere in the application), and one of which indicated that the reviewer had little or no relevant knowledge (e.g., by stating that there is a universal treatment for ME/CFS). Other reviews used earlier published research with conclusions based on highly questionable data to criticize the validity of the approach, which had already pinpointed a molecular signature of ME/CFS. This work remains unpublished without funds needed to push it through to completion.

The above is the opposite of a research pipeline, it's an ideological gate. There is nothing to work with here, the gate blocks everything reflexively.

ME/CFS research proposals can't be assessed properly by randos, it needs competent experts who understand the state of things. This would be the goal here.

 

[rvallee]

What is a «low evidence base» and why does it reduce the competitiveness of proposals?

The downward spiral where low funding means few results, leading to low interest from researchers because there isn't much to work with, which means few submissions, this keeping a state with few results to work with.

Basically it's asking to jumpstart a field that has been intentionally suppressed through dedicated funding. This is necessary. I assume that everyone involves know this, that the intentional suppression has been very effective at one thing and one thing only: at depressing the entire area of meaningful results. So to get out of this spiral, we need to generate interesting starting points.

Although it's hard to say how we can accomplish this when you look at RECOVER and how almost $2B later they haven't even shown a single thing worth a damn. It could be that the medical profession is just so completely out of its depth over a problem of this complexity that no amount of money will jumpstart anything. Most likely because about 90% of that money appears to have been badly misspent, but that's still almost $200M and still nothing at all worth showing.

Medicine is extremely conservative, and if there's one thing that defines a conservative approach, it's that it's never there early, it barely starts putting its slippers on to enter very late in the game. The general approach in medicine is clearly to just wait for someone to find one thing, and if that takes centuries then that's just the way they do it.

 

[rvallee]

While there is continuing influence from BACME as well to try to maintain the rehabilitiation model, tweaked to pretend to be NICE compliant, what is to say the NIHR won't allocate the funding for research hub to a BACME style therapy centre to fund ongoing research on the rehab model of care?

It's guaranteed that whatever amount is made available, even if it's explicitly marked as being for serious biomedical research only, a lot of it will be grabbed by ideologues, or wasted by newcomers with good intentions but no understanding of the situation, as we're seeing in LC. We can't avoid that. Any amount of money marked for serious research will have to be offset with some junk, as the reactionaries will throw a fit and get their way anyway.

The question is over how the balance is spread out. In a sane world no public funding would go to anything psychobehavioral, it serves absolutely no purpose and the near total absence of private funding for it (outside of investment ventures) says a lot about this, how almost no one is willing to put their own money on this. They depend entirely on hand-outs from big interests, who also see this as an investment.

But as I said above, any money they get will not see them move one bit. They don't even do real research, it's strictly marketing, and they will never move on from the state they have been since day 1. Whereas all it takes for us is one breakthrough, which makes it worth having some funding wasted on their marketing.

 

[Utsikt]

ME/CFS research proposals can't be assessed properly by randos, it needs competent experts who understand the state of things. This would be the goal here.

I can’t see anything in the proposal that addresses this point. Which is why I’m asking about it.

The downward spiral where low funding means few results, leading to low interest from researchers because there isn't much to work with, which means few submissions, this keeping a state with few results to work with.

I don’t understand how any of that matters when it comes to the decisions regarding funding for specific projects?

Even if we accepted that some funding would go to the BPS crowd, how do we ensure that funding actually gets to the good biomed researchers as well?

Nobody has given any answers for this as far as I can tell. And it’s the most important question, IMO.

 

[hotblack]

To be honest I was surprised at some of the responses to start with, but I've found it really useful and informative to talk through them and try to understand concerns. I hope it’ll make me better at making the positive case to others for what we need when I try to.

Setting up hubs or whatever will not solve things alone. Equally a scientific breakthrough by an individual will not solve things alone. I’ll keep on saying it but my view is we need a combination of things and we need to remove barriers as much as possible without introducing new ones. I see value in what those for and against this proposal have been saying.

Ultimately we need governments to think strategically about research needs for the country and identify what areas are important

I wholeheartedly agree. Especially as we’re at a point where long term strategies and funding are being set out and competed for. This is also part of what I mean about being ready. You often need to work on people for a while until they come round, people can be hard work…and are often the obstacles. We need people who currently don’t understand, to understand, so that when things arrive in front of them it’s an easier ask. Research, education, hospitals, care, it’s all part of the picture.

 

[wigglethemouse]

I'd just like to share one example of a promising ME/CFS Biomarker from a UK group. It was published in 2018, 7 years ago. The team still does not have sufficient funding to properly progress this very promising work. Current status is they can separate ME vs MS vs healthy controls, and ME vs severity level, and need a much larger replication cohort. They need many many more samples. The lead researcher had to accept another position due to lack of funds and even with that person working remotely part time, they are still struggling.

A new approach to find biomarkers in (CFS/ME) by single-cell Raman micro-spectroscopy, 2018, Morten et al

One of the keys to good studies is being able to first stratify patients. This project looks like an essential platform to do that, pending a large replication study. Why hasn't it been funded. This is just one example.

 

[Utsikt]

I'd just like to share one example of a promising ME/CFS Biomarker from a UK group. It was published in 2018, 7 years ago. The team still does not have sufficient funding to properly progress this very promising work. Current status is they can separate ME vs MS vs healthy controls, and ME vs severity level, and need a much larger replication cohort. They need many many more samples. The lead researcher had to accept another position due to lack of funds and even with that person working remotely part time, they are still struggling.

A new approach to find biomarkers in (CFS/ME) by single-cell Raman micro-spectroscopy, 2018, Morten et al

One of the keys to good studies is being able to first stratify patients. This project looks like an essential platform to do that, pending a large replication study. Why hasn't it been funded. This is just one example.

The last post in that thread says that the findings did not replicate. But it certainly took a long time to get that done and money would have helped!

This team has replicated the study in a larger group. Unfortunately, the finding of higher phenylalanine in Me/CFS doesn't seem to hold up.
Developing a blood cell-based diagnostic test for ME/CFS using peripheral blood mononuclear cells 2023 Xu, Morten et al

 

[wigglethemouse]

Where is funding going to come from for this study?

https://twitter.com/user/status/1908207441231122600

"wrh.ox.ac.uk/news/mitox-2025 Great meeting yesterday! Sheeza Mughal's talk showing serum from severe ME/CFS & Long Covid patients impacts 3D muscle function, induces mitochondrial stress and eventual failure was one of the highlights. A bigger study is desperately needed."

"What is exciting about the model is that not only do we have a cell model that reflects some of the issues observed in patients when we add serum. But can also look to fractionate the serum into its components and test which specific component /factor triggers the response."

 

[wigglethemouse]

The last post in that thread says that the findings did not replicate. But it certainly took a long time to get that done and money would have helped!

Some findings did not replicate! My understanding from previous talks was that sampling handling was an issue. Metabolites used for energy are used up very quickly e.g. glucose. If you don't control sample processing time after collection, short half life metabolites used in the TCA cycle don't give consistent results. That is a problem for CureME Biobank samples which can have 0 to 14 hrs before being processed and frozen. Other long life metabolites are not affected.

I read recently somewhere that they have started a pilot project to try and decode the some of the unknown VIP metabolites but can't find the reference and don't know if it is funded. The Oxford ME/CFS web page for Karl Morten shows a project titled "Professor James McCullagh (Department of Chemistry). Using plasma mass spectrometry analysis to increase our understanding of ME/CFS.".

 

[hotblack]

Possibly a bit of a tangent but there was mention on a Financial Times podcast I was listening to of the UK gov looking at attracting teams of scientists from the US and supporting them in getting set up and finding their work in the UK. There seemed to be a particularly focus on life/bio-sciences, research leading into medicine etc.

 

[Kitty]

the people that are good at playing the game might not be good researchers. And the good people often don’t like playing games so they find positions where they can do their thing without it

This. It can't be said enough times.

We had 30-odd years of people suggesting structures to develop what was effectively applied creativity, and 30-odd years of explaining why it wouldn't work. Structures just get filled up with people who're good at working in structures.

The real job was to chase down the truth and tell it, regardless of how long it took or how unexpected or confronting the result was. The best practitioners were obstinate sods who'd walk rather than lower their standards, not people in polite suits.

I'd be surprised if scientific research was very different.