"ME/CFS Funding Worsens As NIH Maintains Status Quo"

[Trish]

If the researchers who have NIH funding are not encouraging young researchers to apply for NIH funding, how can we make progress?

While I agree with your concern, I think it is unrealistic to expect young researchers, for example those who have just finished a PhD to apply for funding from NIH. They can't do research unless they have a job with access to lab facilities and more experienced colleagues to work with.

As far as I can see, all a young researcher just setting out on a research career can do is apply for post doc positions where there is already a funded project in place for them to work on. That requires more experienced researchers with tenured positions to do the applications, then employ young researchers as part of the research team to work on it once funded.

 

[Midnattsol]

While I agree with your concern, I think it is unrealistic to expect young researchers, for example those who have just finished a PhD to apply for funding from NIH. They can't do research unless they have a job with access to lab facilities and more experienced colleagues to work with.

As far as I can see, all a young researcher just setting out on a research career can do is apply for post doc positions where there is already a funded project in place for them to work on. That requires more experienced researchers with tenured positions to do the applications, then employ young researchers as part of the research team to work on it once funded.

This. Too tired to write a lot, but as someone thinking about gjetting a phd, I am also dependent on being able to make a living for myself when I am done. As interesting as ME is to me from my cell biology background, I don't see how I would be able to support myself following that direction as it is now.

Maybe in the future, one year left of my master's degree and I am thinking too far ahead

 

[Wilhelmina Jenkins]

I’m thinking of things like this.

https://www.nimh.nih.gov/funding/training/funding-opportunities-for-early-career-investigators.shtml

Of course you have to find a job after you PhD, but this field shouldn’t be considered off limits for young researchers.

 

[Guest 2176]

Want to emphasise here that I’m playing devil’s advocate here and don’t hold these views but....why *would* you want to enter the field?

It’s a field that at present is:

- mired in controversy
- little direction
- no real foundation to build upon
- doesn’t have the ‘glamour’ of curing something like cancer
- doesn’t have any big name charity attached to it or celebrity awareness

I’m just trying to see it from the perspective of an early career researcher and someone trying to map out what their career might look like. In any field, most people want to take the path well trodden, perhaps with some level of innovation and unique contribution of their own. Very few people seem to want to be the first to stand up and say, yeah this thing hasn’t been explored but I think it’s important and here’s why and here’s how I’m going to do it. I’m saying that about all industries really.

So I guess it’s a challenge of how do you address those very valid qualms of someone who wants to research it.

Agreed.

Also it's hard to find patients and controls because the studies involved will often be invasive and difficult.

I still see this as a funding issue. They should pay patients more to participate in research to make up for the possible semi permanent crashes from it. The NIH study has been slow bc of trouble finding patients to participate in such an invasive study. Some other studies like jarred youngers drug trials have been slow for this reason.

Every time I talk about funding on this board I an reminded that you cant simply "throw money" at an issue , but realistically, so many of these problems with speed and depth/breadth of research and replication have to do with funding. If people with ME would get paid a couple thousand (on top of the stipends for travel etc) to participate in some of the more in depth/invasive studies, then they would happen faster.

We have a patient community who probably doesn't see a cure coming from any of this research soon so are they really gonna sacrifice their health for a really uncertain , distant future scientific payoff?

 

[Guest 2176]

I really think there are so many problems that come back to funding however you slice it. When I've said this in the past I've been told that serious scientists that work a problem correctly dont need tons of funding to motivate them. That may be true.

But the funding for ME is so scant it's on another level. One cant expect scientists that dont have personal connections to the disease to devote their entire career to something with so little pay or glory. There has to be some sort of middle ground, we dont need to just throw money at people but it would be nice if labs that we know are doing good work could not face tangible financial impediments... like ron Davis speaks of with needing new expensive equipment, also needing to hire new people to work on different projects simultaneously, the fact that some people at OMF are working other jobs too... bc it probably isn't always enough to pay a full time salary.

There are so many tangible financial problems scientists and clinicians in this field face idk why we dont take their word for it. When Michael van elzakker has said that the rate of turning down NIH Grant's is so high that he'd rather not apply ... that's a problem

 

[Guest 2176]

Which is why I wholeheartedly support the #notenough4ME campaign and the work meaction is doing. Hopefully they will continue to ramp up the pressure and fight hard, despite the challenges posed to doing activism while having ME.

 

[Wilhelmina Jenkins]

When Michael van elzakker has said that the rate of turning down NIH Grant's is so high that he'd rather not apply ... that's a problem

This baffles me entirely. All NIH grant proposals have a high rejection rate. The rate for ME/CFS grants is higher than the average at this point. NIH is flooded with proposals in other fields.

I wholeheartedly support the 5 demands that ME Action made because they were specific actions that NIH could take using its current methods. NIH doesn’t have specific disease budgets. I have seen lots of people saying that NIH cut funding for ME/CFS research this year. The reality is that, with the exception of set-aside funding, the amount of funding that a disease receives depends on the number of proposals that are submitted. The number of proposals for ME/CFS research has plummeted. So the amount of funding granted goes down too.

All of the researchers know this. To say that it’s too hard to get funding confuses me entirely. If you want to do the work, you write a proposal. If it’s rejected, you rewrite and resubmit. Once you are funded and do good work, being approved gets easier. This is how NIH works and it’s not likely to change anytime soon. I don’t understand saying it’s too hard and throwing up your hands.

 

[Guest 2176]

Michael stated he essentially works sixty or seventy hour weeks at this point and did a lot of the imaging for aspects of his me/cfs study during weekends, using unpaid assistants, at his lab. I do not assume he just doesn't want to do work. I would assume that he may not have the time and energy to do a ton of grant writing, and that the way NIH Grant's are set up they want to only fund hypothesis testing and not more preliminary data gathering stuff, and that if hardworking researchers like him see a problem w the rate of applications approved, to the extent he wouldn't apply, maybe there is a problem.

 

[Wilhelmina Jenkins]

But where does he get funding for his other work? You are right in that NIH doesn’t like to find pilot studies. The ME/CFS community has been funding those since at least the late ‘80s. The Ramsay Grants from Solve and funding from OMF do a great job of that. among others. I assume that similar funding happens in other countries - I only know the US.

But that’s true for all diseases, not just ours. Taking the step from pilot studies to a major grant is a lot of work, no doubt. But it’s part of the job. The only way in which I see our disease differing is that NIH let our disease languish for so long that it needs to take additional steps to get us up to speed. We need researchers submitting proposals to help
make our case.

Dr Davis will continue to do so - he has a sick son and would do anything to help him. But we can’t just depend on family members of patients who happen to be researchers. We need to make a case to the scientific community that this disease is a problem that would be exciting to tackle. I believe that it is.

 

[Guest 2176]

But where does he get funding for his other work?

He works at Harvard researching PTSD which I assume is generally better career wise ... I'm sure Harvard and or mgh fund that work

But that’s true for all diseases, not just ours.

yes, but ME/CFS deserves special consideration based on the low quality of life measured in daly and low amount of funding--it needs the research to be kickstarted by better funding opportunities and different rate of approval of Grants.
One of the problems in me/cfs is that we dont have enough observational data that is replicated to even construct a solid disease model. So it's a major problem for our disease in particular for the NIH to only want to fund research that's further along.

I have no problem with saying me/cfs is a special case ethically and that exceptions can and should be made. But obviously they won't be made because of the kindheartedness of anyone at NIH. They will have to be fought for

 

[Wilhelmina Jenkins]

I agree - I have no problem saying that we are a special case. I generally say that they broke our research community and they have to fix it. And there are things that we can fight for and win. We desperately need more set-aside funding. But at the end of the day, proposals will still have to be submitted and approved. We need every researcher we can get to submit proposals.We are in deep trouble otherwise.

 

[Midnattsol]

Of course you have to find a job after you PhD, but this field shouldn’t be considered off limits for young researchers.

I don't think of it as "Off limits", just hard.

During the years I've been at university, ME has not been mentioned in lectures. I take subjects related to cell biology, biochemistry, metabolism, nutrition and general health. Cancer has been a "model illness" in many of my classes, metabolic syndrome and autoimmune disease have been so in others. I've learned about a lot of different diseases and health issues that needs help to be solved, ME has not been one of them. I don't know how this is handled at other universities, though.

With little/no mention of ME during the early years of studying, and few phd-positions available, how would early career researchers even get to know about this potentially interesting (but uncertain) field of study? I've met quite a few phd candidates that got into their field "somewhat by coincidence" as they applied to a project they thought looked interesting but didn't necessarily have an idea beforehand that they wanted to follow that path. Getting into the ME-field that way seems a slim chance right now.

But I agree we need more researchers, proposals must be submitted, funding acquired etc. I would say we need to make ME known not just to the scientific community, but also to students.

 

[FMMM1]

T


I f this is true, I am very unhappy about that message. If not now, when? Funding for ME/CFS will only grow if people submit proposals. If the researchers who have NIH funding are not encouraging young researchers to apply for NIH funding, how can we make progress?

While activists are pushing for more set-aside funding from the outside, we need the researchers to encourage more bright young minds to enter the field and let them know, first, that this is a field in which they can make a real difference, and, second, that there are ways to apply that will increase their likelihood of being funding.

I understand that people are angry with Dr. Collins for not doing more for our disease, but realistically, he won’t be head of NIH forever and he has done more that any other head. He is familiar with this disease. This may be the best time for a young researcher to apply. I can easily see a new head of NIH coming in who knows absolutely nothing about ME/CFS and cares even less. We need to take advantage of this moment - activists and researchers alike.

First of all, in general I agree with your comments.

I'm concerned that progress is made at this stage. Among other things I think that Ron Davis has recruited a group of very capable researchers, so now is the time to make progress. Also, recent discoveries offer hope e.g. the discovery of "something in the blood" - although it hasn't been identified - is an example of a promising research area which could be pursued. However, Ron has highlighted (talk to @Ben H ) that funding is required to develop the nano-needle to progress the search.

I haven't been able to find the comment regarding not being able to recommend that young researchers continuing in ME research. I think it was possibly in the context of a student, who completed their Ph.D in Maureen Hanson's laboratory - Seahorse analyser, moving out of ME Research. I did find a comment where Maureen Hanson says she hoped they would return to ME research.

 

[beverlyhills]

High approvals aren’t good.

Giving money to cell biologists and immunologists for a neurological Illness because they can bid lower is what’s happening. Lower consumable cost.

You’re not going to fix peoples outlook on CFS and increase funding. It’s not even in their top 100 priorities.

You can ask second year med students (they start next month) and they would pretty much say it is purely Neurological based on current evidence and inference from other disease - that’s free.

You have a bunch of like biochemists who maybe took psych 101 in college working on myalgic encephalitis <- it’s literally in the name.

These so-called metabolic discrepancies are in part wishful thinking because it lowers the barrier of entry to treatment hypothetically. the actual result is pushing the etiology further in the incorrect direction with a small amount of people dictating that trajectory. The result is increasing time to treatment.

 

[FMMM1]

High approvals aren’t good.

Giving money to cell biologists and immunologists for a neurological Illness because they can bid lower is what’s happening. Lower consumable cost.

You’re not going to fix peoples outlook on CFS and increase funding. It’s not even in their top 100 priorities.

You can ask second year med students (they start next month) and they would pretty much say it is purely Neurological based on current evidence and inference from other disease - that’s free.

You have a bunch of like biochemists who maybe took psych 101 in college working on myalgic encephalitis <- it’s literally in the name.

These so-called metabolic discrepancies are in part wishful thinking because it lowers the barrier of entry to treatment hypothetically. the actual result is pushing the etiology further in the incorrect direction with a small amount of people dictating that trajectory. The result is increasing time to treatment.

I was surprised by Maureen Hanson's [Center for Enervating Neuroimmune Disease] key note address at the 2019 Symposium [https://www.omf.ngo/2019/10/02/symposium-talks-now-available/] - i.e. surprised by the fact that Maureen pointed the finger at an immune cause. I think Maureen's son has ME? I'd put my faith in Maureen's view (albeit based on limited knowledge - we don't know the cause of ME/no biomarker etc.) rather than second year medical students.

There's a proposal to run a GWAS study for ME; I think GWAS studies have helped to establish the cause of other diseases @Simon M @Andy know more about the GWAS study than I do.

 

[lansbergen]

i.e. surprised by the fact that Maureen pointed the finger at an immune cause.

I was not. Have been waiting for it.

 

[FMMM1]

I was not. Have been waiting for it.

Noted; however, the only big immune finding simply confirmed that ME is not a B-cell autoimmune (autoantibody) disease i.e. the rituximab trial [].

Also, Ron Davis highlighted that T-cell clonal expansion occurs in healthy controls i.e. early (preliminary) findings did not hold up in a larger study. Seems that the focus now is on whether the target of T-cell clonal expansion gives a clue to the cause of ME [].

If you've eliminated B-cell autoimmunity, and there's no evidence of T-cell autoimmunity, then what's left?

Possibly someone like @Jonathan Edwards could e.g. explain how the immune system could fail to re-set after an infection and cause ME --- or any other immune related hypothesis.

GWAS might be the way to find the cause of ME - at the moment we're not clear what causes ME.

 

[Jonathan Edwards]

If you've eliminated B-cell autoimmunity, and there's no evidence of T-cell autoimmunity, then what's left?

Possibly someone like @Jonathan Edwards could e.g. explain how the immune system could fail to re-set after an infection and cause ME --- or any other immune related hypothesis.

We have not eliminated B cell autoimmunity but I agree that it is not looking very likely.

T cell autoimmunity does not exist very much as far as I can see. There is a rare genetic condition called AIR where T cells react to self but in general autoimmunity is not associated with any evidence of more anti-self T cells.

What is left is the sort of thing that happens after shigella or yersinia infection - most typically manifesting as 'Reiter's syndrome'. Psoriasis may be another example in some cases. Long term immune dysfunction triggered by infection is well documented in these cases. There is no real evicdence of T cells becoming anti-self but it does seem as if they are jiggered up in some way such that they cannot quieten down.

That is why I think changes in MAIT T cell populations would be intriguing. I am not sure that is panning out but it is still in the air.

An intriguing feature of T cells is that we know there are four sorts that home to different places: to gut (Crohn's), to skin (psoriasis), to mucosae (Reiter's) and to everywhere else (ankylosing spondylitis). I have wondered whether maybe there is a fifth population that do not go anywhere beyond the lymphoid system - sort of stay-at-home T cells. They would be a bit like military administrators, never sent to the field but important for organising wars.

An illness based on stay-at-home T cells might look quite like ME. There would be no inflammation in any specific tissue but still a constant flow of alarming messages sent to the war room under Whitehall.

What I don't think happens is that infections trigger autoimmunity. That is a very old chestnut that has never had any basis, except perhaps in one or two very specific situations and even there I am sceptical.

 

[FMMM1]

We have not eliminated B cell autoimmunity but I agree that it is not looking very likely.

T cell autoimmunity does not exist very much as far as I can see. There is a rare genetic condition called AIR where T cells react to self but in general autoimmunity is not associated with any evidence of more anti-self T cells.

What is left is the sort of thing that happens after shigella or yersinia infection - most typically manifesting as 'Reiter's syndrome'. Psoriasis may be another example in some cases. Long term immune dysfunction triggered by infection is well documented in these cases. There is no real evicdence of T cells becoming anti-self but it does seem as if they are jiggered up in some way such that they cannot quieten down.

That is why I think changes in MAIT T cell populations would be intriguing. I am not sure that is panning out but it is still in the air.

An intriguing feature of T cells is that we know there are four sorts that home to different places: to gut (Crohn's), to skin (psoriasis), to mucosae (Reiter's) and to everywhere else (ankylosing spondylitis). I have wondered whether maybe there is a fifth population that do not go anywhere beyond the lymphoid system - sort of stay-at-home T cells. They would be a bit like military administrators, never sent to the field but important for organising wars.

An illness based on stay-at-home T cells might look quite like ME. There would be no inflammation in any specific tissue but still a constant flow of alarming messages sent to the war room under Whitehall.

What I don't think happens is that infections trigger autoimmunity. That is a very old chestnut that has never had any basis, except perhaps in one or two very specific situations and even there I am sceptical.

Thank you very much for sharing your thoughts.

 

[Hoopoe]

What is left is the sort of thing that happens after shigella or yersinia infection

Could exposure to yersinia cause problems later in life, with a delay of perhaps a decade?

I have wondered whether maybe there is a fifth population that do not go anywhere beyond the lymphoid system

I've also always had a few lymph nodes that are palpable and hard (on one side, with the corresponding lymph node on the other side of the body being unable to be found because it's not palpable and hard in the same way).