ME/CFS meeting at the Royal Society of Medicine - March 18th 2015

[Jonathan Edwards]

@Jonathan Edwards since we're talking theories, what do you think about macrophagic myofascitis?



Accumulation of alum in the brain presumably leads to chronically activated microglia.

About 50% of MMF patients meet the international consensus criteria for ME.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318414/

I doubt that long term persistence of alum would explain ME, and I doubt much would ever get into microglia because any circulating alum particles ought to get filtered off in the lung before getting to the brain. However, alum is a potent adjuvant and adjuvant signals are very important in triggering immune responses.

 

[rosamary]

I have been thinking hard about that and was thinking more in terms of a budget of £20 million over ten years as a starter. What I would put top of the list is the identification of a ring fenced population based cohort in a region of the UK based on primary trawling of an entire population base using multiple sets of criteria but with a focus on patients with something like Canadian criteria disease (maybe IOM). I would set in place resources for longitudinal analysis of the cohort. I would then look to replicate basic findings like NK function, cytokine profiles, B cell function and antibodies, and HPA axis disturbance to see if these really are replicable and if so look at detailed mechanisms using the longitudinal analysis. I would also want to look at the demographics in detail in terms of incidence patterns to try to pin down genetic , environmental and stochastic components

That may all sound very boring but I think it needs doing so that we know which of these 'leads' is really worth pursuing.

With the next £20 million you offer I would get my friends at Queen Square National Hospital for Nervous Diseases (who would lap up the grant money) to home in on fMRI analysis of ME brains longitudinally - again trying to replicate, but also go further than, the interesting studies already in print from Baraniuk, Stanford and the University of Sussex (effects of interferon and fatigue). We could do some PET studies too.

As for the next £60 million - there are plenty of drug trials we could do and maybe even with dose response curves that would really give something hard.

No surprises really, but then the girl in the lab hasn't come into the coffee room just yet.

Ok. You can be on the interview panel to ensure that the applicant is up to date with research in this area and also to promote clinical research within this clinic.

We can ask the MRC etc to shift some funding across from other areas. They'll be keen if they know it's for a good cause I hope.

Didn't professor Holgate manage to get 2 million? If there's a definite plan, then the MRC will leap into action maybe?

Perhaps we should ask.

 

[jimells]

Here in the UK the DoH, DWP and government ministers are painfully aware of the huge cost to the economy of ME/CFS in terms of DWP benefits, lost taxes, medical costs etc.

So why won't they fund medical research, and encourage the Americans to do so?

In the U.S. the agencies involved have taken decisive action to not fund research. It is not just a matter of, "We didn't notice all those sick people". It was a deliberate policy decision to rename the illness after the Lake Tahoe outbreak.

It was a deliberate policy decision to move the research program from the National Institute for Allergy and Infectious Disease to the catch-all (from what I can understand) Office for Research on Women's Health (not to be confused with the Office for Women's Health which is under HHS not NIH - got it?) where nothing has happened since forever.

The CDC didn't accidentally redirect 13 million dollars to "other public health emergencies".

It was a deliberate policy decision to close three CFS Research Centers.

Even the most esteemed and celebrated researchers can not get funding for this illness. Why? Who decided this?

Why aren't government ministers who are concerned about the cost to the public treasury asking these questions? They have the power to investigate and demand real answers - why aren't they using it?

The 2006 report by the UK Parliamentary Group on Scientific Research into Myalgic Encephalomyelitis stated that, "CFS/ME is defined as a psychosocial illness by the Department for Work and Pensions (DWP) and medical insurance companies. Therefore claimants are not entitled to the higher level of benefit payments. We recognise that if CFS/ME remains as one illness and/or both remain defined as psychosocial then it would be in the financial interest of both the DWP and the medical insurance companies." The Group called for investigation of what they called, "numerous cases where advisors to the DWP have also had consultancy roles in medical insurance companies. Particularly the Company UNUMProvident. Given the vested interest private medical insurance companies have in ensuring CFS/ME remain classified as a psychosocial illness there is blatant conflict of interest here."

I assume that UK Parliamentary Groups are considered authoritative. This one seemed to think UNUM has something to do with the situation, and here we are nine years later still waiting for the investigation.

 

[Aurator]

That may all sound very boring but I think it needs doing so that we know which of these 'leads' is really worth pursuing.

It's a Herculean task, clearly. Just investigating the genetic and environmental components looks endless, potentially. I can see the need for the full ten years, maybe longer. I'd be pinning some hope at least though on a serendipitous discovery bringing the lady from the lab rushing into the coffee room well before the decade has run its course. And I would be aware that there are other labs and other coffee rooms out there in the world as well.

You see how well adapted PWME are to getting by on crumbs of comfort.

 

[jimells]

Who knows how much things are really changing, but I thought there was room for optimism.

I'm saving my optimism for the day the program managers turn on the research money spigot.

In response to Ecoclimber, I would second Charles's view that a grand conspiracy theory may not be the reality. Certainly in the UK we do cock-up better than conspiracy, even if there is often a bit of conspiracy, often rather cocked up conspiracy, lurking but not doing much.

Well I certainly appreciate the role of incompetence. When I started working as a computer consultant decades ago, it didn't take me long to realize that most companies make money in spite of management's efforts, not because of them.

But Lady Mar seems to agree there is more than just incompetence restricting the research money:

It was when a small group psychiatrists from the UK, Europe and the USA purloined ME and renamed it CFS in the mid-1980s that the real problems began.

They insisted that it was a psychosocial behavioural problem that could be readily overcome with a course of cognitive behavioural therapy and graded exercise. From their earliest beginnings, they managed to attract the attention of the media and of their medical colleagues with their assertions. They found their way onto government advisory committees and research organisations; onto the boards of medical publications and into insurance companies where their message was greeted with apparent delight because these organisations would not have to think any more.

The cause and solution were at hand. No need for doctors to do too many investigations; no need to perform anything but psychological research; no need for social security payments by finding that claimants are really fit for work. They developed a means of stifling opposition by refusing to publish papers showing biological causation and, joy of joys for the insurance companies found that patients were reporting a psychological condition which was excluded in their policies. As recently as last year CFS was described as ‘a culturally driven disorder with no known organic cause’ in the BMJ.

@charles shepherd is there a public email address for Lady Mar? I would like to thank her for working on our behalf.

 

[Esther12]

re 'conspiracy' vs incompetence: People tend to be self-interested, and that leads to an inevitable form of 'soft-corruption' imo. Incompetence which serves the interests of those with power tends to be more influential than incompetence which goes against the interests of power. There's a steady bias, and this will also affect the sort of people who end up being promoted into positions of power themselves. Certain sorts are weeded out, while others rise to the top - this does not seem to be an entirely meritocratic system.

While I think that it's a tactical mistake to talk too much about corruption and dishonesty when we cannot really prove anything, personally I would be surprised if all the problems that occured around ME/CFS, welfare reform, insurance companies and disability, etc is a result of genuinely well meaning incompetence. When I first joined this forum I was deeply sceptical of talk of big financial firms wanting to influence these matters, and while I still think some people go to far, what I've read and seen since has made me think that there probably is an important story to be uncovered here.

I've still not read the Mar speech, but I think that things like this are wrong: "They developed a means of stifling opposition by refusing to publish papers showing biological causation.."

 

[jimells]

More from Lady Mar:

Researchers such as those funded by Invest in ME and ME Research UK, have funded excellent pilot and seedcorn studies on a shoestring, while a significant number of biomedical research applications have not been funded by the MRC in the past 20 years, including some targeted at pathophysiology. It is hard to believe that all were written so badly that they could be rejected, particularly as some came from established researchers with a track record in this and other fields.

Could it be that the expert reviewers were, once again, psychiatrists who appeared to have an interest in supressing research that counters their views? Many suspect this to be the case. This can only be political. It is also political suicide for researchers in major universities to suggest that they conduct studies into biological causes for ME.

 

[jimells]

I've still not read the Mar speech, but I think that things like this are wrong: "They developed a means of stifling opposition by refusing to publish papers showing biological causation.."

She's been in the House of Lords for 40 years, and working on ME and related issues for 20 years. Her testimony should be carefully considered.

While I think that it's a tactical mistake to talk too much about corruption and dishonesty when we cannot really prove anything,

If corruption is stopping up the flow of research money, how will we get the money flowing without removing the blockage?

A recent big scandal in Quebec involves (I think it's still ongoing) collapsing roadways and Mafia-controlled construction companies, mayors, judges, etc. People complained for years about shoddy road work, but it didn't stop until the people involved were arrested. Without getting to the bottom of a 30 year scandal surrounding this illness, how will we get the funding restored?

We've been on our knees begging for crumbs from NIH for 30 years, and so far all we got is sore knees...

 

[user9876]

re 'conspiracy' vs incompetence: People tend to be self-interested, and that leads to an inevitable form of 'soft-corruption' imo. Incompetence which serves the interests of those with power tends to be more influential than incompetence which goes against the interests of power. There's a steady bias, and this will also affect the sort of people who end up being promoted into positions of power themselves. Certain sorts are weeded out, while others rise to the top - this does not seem to be an entirely meritocratic system.

While I think that it's a tactical mistake to talk too much about corruption and dishonesty when we cannot really prove anything, personally I would be surprised if all the problems that occured around ME/CFS, welfare reform, insurance companies and disability, etc is a result of genuinely well meaning incompetence. When I first joined this forum I was deeply sceptical of talk of big financial firms wanting to influence these matters, and while I still think some people go to far, what I've read and seen since has made me think that there probably is an important story to be uncovered here.

I've still not read the Mar speech, but I think that things like this are wrong: "They developed a means of stifling opposition by refusing to publish papers showing biological causation.."

I've never been involved in medical research but I've known many academics in other areas who have criticise the way research councils work. By having committees filled with the good and the great they tend to fund certain institutions and also tend to fund work following the latest fashion and don't like work that challenges perceived wisdom. This isn't about corruption but it is just a natural consequence of the committee structure. Publishing outside of a conventional research area can be hard as well as when there is not a natural journal or conference for work it can prove challenging. For example I remember talking with an academic in the US who ran a large research group but in the area we worked in (which was a sideline for him) he was having huge problems getting funding and publishing. Over time if people are persistent things get better so now there is a journal and a research community in that area. I would also add that this was a research direction that government was very supportive of and it was still very difficult.

 

[Jonathan Edwards]

I have great respect for Lady Mar and I see no harm in raising awareness of these issues. However, I am sceptical about the Lancet and BMJ being part of a conspiracy. Fiona Godlee is not a conspirator. Horton's problem is that he is a journalist. And it is hard to claim the Lancet is against biological research into neuropsychiatric disease when they published the Wakefield study - which was bad enough that people were surprised that any journal took it, let alone a high profile one. The Lancet refused to publish my initial trial of rituximab. I think the whole thing is much more of a muddle.

I'm saving my optimism for the day the program managers turn on the research money spigot.

But that never happens. There are no program managers. And turning on money is not what gets science moving. You do not solve a scientific problem just by throwing money at it - unless it is something with no intellectual content like sequencing the human genome. You have to start with an idea of what to do. I actually think we are now in a position to say we have some ideas what to do, but in the past there has been precious little. Grants were turned down and papers rejected because they really weren't very good. And when Lady Mar says that 'it is hard to believe .. all written so badly...' I am afraid she may be unaware that even top researchers get the vast majority of their grant applications refused. I never succeeded in getting money for the work that actually took my science forward. I always got money for pretend projects that I knew would be liked by committees and used the money for something else. It is all muddle. There is jealousy and bitchiness and all other sorts of human nature but it is mostly muddle.

There is only one way forward and that is for the relevant researchers to sit down yet again and write applications yet again and hope that this time something will hit the right button. They will do that and from time to time they will succeed. In the meantime debating the political issues probably does hep and I think the meeting last week may have been very fruitful. But overstating a case is to my mind the best way to put people off.

 

[Wildcat]

.
Is the UK Rituximab trial design of sufficient quality and medically important enough to be funded by the MRC?

If it is - why was there no application to the MRC?

Patients and their carers/families are busting a gut to fundraise for that trial. Many individual patients are donating out of their pitifully low sickness benefits.
.

 

[MeSci]

Roy S said: ↑
The reason that more biological science has not been done is lack of funding. There are reasons that has happened and is still happening. Some people have made it happen. Others have allowed it to happen.

I disagree. I managed to nail the fact that rituximab is useful for autoimmunity with essentially no funding (nobody would fund it). For the pilot study that got it off the ground I bought the rituximab myself with some money my father had given me because he wanted to see me succeed in my career where he had been disappointed. Otherwise I did everything myself - put up the IVs, took the blood pressures and the blood samples, since I had no staff. If people really want to find the answer to a question they will. We need the right people to be interested.

The problem is that when people have looked - and people have looked and it has been forgotten - if they are honest they found zilch. Zilch in the brain, zilch in the serum, zilch in the blood cells, zilch in the ... (At least in terms of replicated findings that is where we still are by and large.) That maybe because they are looking for the wrong things or because they are making methodological mistakes or it may be that the sorts of things you find in the other diseases just do not show up in ME. And when things do turn up a bit out of line, like cortisol levels, it does not seem to lead anywhere. However much you listen to patients if you cannot get any repeatable results in the lab that suggest a sensible hypothesis you are stuffed.

It is perfectly possible that all that is because researchers have been too focussed on the wrong theories and have missed things staring them in the face (that is the usual situation in biomedical science).

I agree with both of you, and partly disagree with @Jonathan Edwards.

I agree that the main reason we don't get funding for the right kind of research is the way research funding is decided. I expect that it is decided by people who are familiar with particular types and directions of research. If a research proposal is out of step with that, the people involved in deciding - who are probably conservative in nature - will not approve it.

I will quote again an analogy from my blog - and please don't take the thread off-topic by discussing animal models here - it's not the place. It's just an illustrative analogy.

Too many eminent laboratories and illustrious researchers have devoted entire lives to studying malignant diseases in mouse models and they are the ones reviewing each other's grants and deciding where the NIH money gets spent. They are not prepared to accept that mouse models are basically valueless for most of cancer therapeutics.

In the final analysis then, one of the main reasons we continue to stick to this archaic ethos is to obtain funding.

I also agree with Jonathan that there are ways round this - but only if, as he says

If people really want to find the answer to a question they will.

I applaud his efforts to get 'the right people interested'. I wish there were many more people like him!

 

[lansbergen]

There is jealousy and bitchiness and all other sorts of human nature but it is mostly muddle.

To many big ego's and to much tunnelvision and muddeling the water.

 

[MeSci]

Even the most esteemed and celebrated researchers can not get funding for this illness. Why? Who decided this?

Why aren't government ministers who are concerned about the cost to the public treasury asking these questions? They have the power to investigate and demand real answers - why aren't they using it?

I don't know, but suspect similar reasons to why UK governments repeatedly ignore the advice of their top scientific advisors, e.g. on legalising cannabis or controlling TB in cattle. Which I don't exactly know either.

 

[MeSci]

It's a Herculean task, clearly. Just investigating the genetic and environmental components looks endless, potentially. I can see the need for the full ten years, maybe longer. I'd be pinning some hope at least though on a serendipitous discovery bringing the lady from the lab rushing into the coffee room well before the decade has run its course. And I would be aware that there are other labs and other coffee rooms out there in the world as well.

And maybe when that girl's maturation into a lady is followed by her final emancipation into a woman, we will have the answers!

(I made sure to by-pass that intermediate stage )

 

[Sasha]

There are no program managers.

I was surprised when you said this because I thought that there were MRC (or Wellcome?) programmes (and hence, presumably, programme managers) proactively outlining what research they want as a priority and dangling money to get it.

Having looked again at the MRC website now, however, I'm not sure how to interpret it.

For example, obesity is flagged as one of several priorities for the MRC:

http://www.mrc.ac.uk/research/initiatives/obesity-research/

But does this mean they'll just react to obesity proposals as they come in, and aren't being specific enough to guide research? Or are they guiding a bit, but not enough to call it really 'running a programme'?

Just wondering how things work at that level. I think all of us are surprised (a surprise that has lasted 30 years or more, for many of us) that the MRC is not proactive in creating a programme for ME research.

 

[Valentijn]

Grants were turned down and papers rejected because they really weren't very good.

That isn't true, at least in the case of biological ME/SEID research. Grants have been turned down due to reviewers who systematically reject biological research into ME/SEID. This happened very recently to Dr Ian Lipkin in the US, and I seem to recall discussion of a similar problem in the UK.

 

[MeSci]

@charles shepherd is there a public email address for Lady Mar? I would like to thank her for working on our behalf.

I'm not Charles, but there is an email address on this page.

 

[MeSci]

By having committees filled with the good and the great they tend to fund certain institutions and also tend to fund work following the latest fashion and don't like work that challenges perceived wisdom.

For anyone unfamiliar with the expression 'The great and the good' - it does not necessarily mean people who are literally great or good. I'm not entirely sure what it does mean, but when I hear it used in the media it usually seems to mean well-known, well-off and well-connected, often 'establishment' figures.

 

[charles shepherd]

I'm not Charles, but there is an email address on this page.

Yes - all her contact details are in the public domain