Researcher Interactions Science for ME written Q&A with Prof Chris Ponting

Science for ME are delighted to present our latest Q&A, this time with Professor Chris Ponting.

Professor Chris Ponting is Chair of Medical Bioinformatics, Edinburgh University and a Principal Investigator at the MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, as well as Deputy Chair of the CMRC.

As discussed in this thread, Prof Ponting has already analysed the genetic data available in the UK Biobank (not to be confused with the UK ME/CFS Biobank) and found evidence that suggests a genetic component in those people who report being diagnosed with CFS.

He has also secured funding from Action for ME and the Scottish Government for a replication of the findings from Dr Mark Davis on T-cells, announcement thread and thread on SimonM's blog on the subject.

As announced relatively recently, Prof Ponting has a direct connection to ME, having been friends with SimonM for a long time.

Questions were originally collected in this thread, the ten most 'popular' questions were then put to Prof Ponting.

 

About the CMRC itself.

Question 1.

S4ME: "A lot of unhappiness within the patient community with the CMRC, I believe, would seem to come from a misunderstanding of what the CMRC can and can't do, given that it is neither a funder of research, having no funds itself, nor is it a research 'centre', in the way that we might consider, in the UK, a university could be. Given it's 'virtual' status, what advantages does it gain from this format and what does that enable it to do?"

CP: "Good question. First off, it would be inappropriate of me to speak on behalf of the CMRC or its Board, so the following thoughts are on my behalf only. As I see it what is essential is that three communities come together to forge a common path: individuals living with ME, scientists and funding organisations. (There is a fourth community – industry – which will become increasingly important in the future.) There are several forums where this coming together is taking place: the Invest in ME meeting, for example, which I enjoyed attending recently.

Funders agree that there is a significant need for biomedical research on ME, so what we (together) need to do is to formulate a plan of research on which they can agree. Back to your question. The CMRC provides a “meeting place” for PWME, scientists, industry, charities and funders and this has recently led to three new priorities being put forward. Everyone on the CMRC Board has inputted into these priorities and these are now being pursued with a great deal of energy and common purpose. The CMRC currently has the ear of major UK funding organisations who have been very supportive of how these priorities have been reached. No one organisation – a funder, a charity, a University, a company – could, I think, have stimulated the active discussion that is ongoing. This, I think, will be how the CMRC will be seen once it has achieved its aim of catalysing a new research and funding strategy. The CMRC Board is agreed, I think, that the CMRC should not continue in its current form once this aim has been achieved"

 

Question 2.

S4ME: "The CMRC seems to have achieved very little since its inception beyond stoking controversy and alienating patients. As someone who appears to favour a patient-focussed, biomedical approach to ME research, why have you decided to try to do that through the CMRC rather than through any of the other existing organisations or by starting a new collaborative from scratch"

CP: "I joined the CMRC because I wanted to help, and because they asked me to contribute. I went in with, I hope, an open-mind and many questions, some of which remain unanswered. I would never have started a new organisation because I believe that it is important to join forces to effect change. I also wanted my preconceptions to be challenged by individuals who hold different perspectives. The value of the CMRC will be judged by its results, and I think we’ll know soon (within 6-12 months) whether it can catalyse the changes that everyone desires.

 

About CMRC research.

Question 3.

S4ME: "In his AfME Q&A, Chris said: “All that I have seen or heard tells me that change is desperately needed, and needed fast. Time will soon tell whether the Collaborative can help catalyse change. A window of opportunity is currently open, and we have to take advantage of it before it slams shut, before the attention of decision-makers and grant-funders naturally turns to other areas”. What can he tell us about what research the CMRC are proposing to the grant-funders and decision-makers, while that window remains open?"

CP: "The specific research questions and methods will need to be defined by researchers and PWME. More broadly, the CMRC advocates a platform, similar to the Dementias UK platform, which joins up and supports research from across the country. Many studies will need a Biobank, and I hope and expect the UK ME/CFS Biobank to form the basis to this. They will also need a Data Portal which will allow results to be shared and compared securely. The platform should also catalyse new methods development and experimental medicine approaches. In other words it is a framework within which research can be pursued and results compared.

Scientifically speaking, I think ME/CFS is crying out for a genetics study (a “genome-wide association study”) with a large number of participants (ten or twenty thousand or more). This is because such a study provides biological insight without prejudice as to what are the underlying causes of disease. We know that ME has a biological component (formally: the heritability of ME/CFS is not zero) as well as non-heritable biological causes so this type study is fully justified. I also wish to undertake a very large study into whether there are “immune signatures” in blood T-cells that predict disease severity and type, similar to the fantastic research being done in Stanford by Mark Davis and others."

 

Question 4.

S4ME: "Rather than 'reinventing the wheel' by creating a new data sharing platform, would the CMRC look seriously at collaborating with the new NIH funded centres in the USA which includes funding the setting up of such a platform?"

CP: "Yes, good idea. This is very much aligned with ongoing and frequent conversations that are being had with Vicky Whittemore at the NIH. I get the sense that once there is clarity whether the UK funders will help with a step-change in ME/CFS research, and once the new US centres “bed-in”, then these conversations will produce tangible outcomes. So, yes, hopefully over the next 12 months."

 

Question 5.

S4ME: "How does the CMRC plan to include patient input with regard to research proposals and achieving its overall goals?"

CP: "Input from PWME has been critical to formulating the CMRC’s overall aims. In particular, everyone is signed up to the idea that the first thing that we need to do is to discover biological mechanisms underpinning ME. The CMRC itself will not lead specific research projects but will do whatever it can to ensure PWME representation and voice in research consortia. The Patient Advisory Group of the CMRC is doing a fantastic job, in my view, representing a breadth of opinion from PWME. If a new UK platform for ME research comes to pass, I’d recommend that this has a newly convened group from the patient/carer community."

 

Question 6.

S4ME: "Numerous US reports from e.g. NIH, IOM and AHRQ (Agency for HealthCare research and quality) have noted that research has been confounded by inconsistent and inaccurate methods of selecting patients for research. What is CMRC doing to address this issue and ensure research cohorts are composed of people who have hallmark symptoms such as PEM and actually have ME? Note: IMO, NICE doesn't cut it cause it says it requires PEM but it also says that exacerbation of symptoms following exertion is optional. IOM and NIH both require this."

CP: "Everyone in the CMRC that I’ve talked to considers PEM a cardinal symptom of ME. But I agree that we need to redouble our efforts to make this clear. As a generalist, interested in (too) many things, I might become interested in doing a genetic study on individuals who do not have PEM, but wouldn’t then describe this as an ME study. It’s great that NICE is looking at this again, and I hope that they do so quickly."

 

Question 7.

S4ME: "Is there any way to make sure that future research includes severely affected housebound and bedbound patients in any research cohort?"

CP: "Yes. If a genetics study is done, and I truly hope that it will (soon), then the intent will be to recruit individuals via the internet and to obtain DNA samples by post. This should allow widespread participation. Studies that require other types of biological samples (e.g. blood) might be too expensive, and may not be funded, if large numbers of research nurses are required."

 

Other patient concerns.

Question 8.

S4ME: "People with ME are concerned about ME being classed under the Medically Unexplained Symptoms banner. In the light of current knowledge about ME does he and other researchers involved in CMRC consider this category is appropriate?"

CP: "Thanks. I can’t speak for others and I am not a clinician, but I cannot explain ME: I do not know its causes, its genetics, and how its effects can be ameliorated or cured but I am eager to find out. The problem, as I understand it, is that there is no definition for “Medically Unexplained Symptoms”. Having robust definitions is essential for pursuing good science, so this classification does not appear to me to be helpful."

 

Question 9.

S4ME: "Given that at least two CMRC members are writing papers about ME as a 'functional neurological disorder' (which the abstract confirms is another name for 'conversion disorder' or 'hysteria'), is the CMRC pledge to focus on biomedical research undermined by that approach?"

CP: "I wrote back to ask for clarification and was told that the questioner was referring to Neil Harrison and Mark Edwards. Neil Harrison completely refutes this view here. There is a lot of confusion about Mark Edwards because there are two individuals with this name who are working in this area. The person who the questioner likely is referring to is not on the CMRC board. Hope that clears that up. The CMRC is 100% committed to its focus on biomedical research. This is absolutely clear."

 

And finally

Question 10.

S4ME: "If you had infinite resources and could do (and could get done) any ME/CFS research you wanted in order to discover the disease's mechanisms and possible treatments, what would your research programme/strategy look like?"

CP: "(1) A large-scale genetics study to reveal which organ systems (immunological, neurological, metabolic?) contribute risk to ME. Such studies have proved powerful for other disorders and should do so once more for ME. (2) A large-scale study of immune signatures across different parts of the ME symptom spectrum, and over time. (3) Physiological studies pre- and post-exertion involving many participants, and exploiting the availability of cheap wearable devices. (4) Studies comparing PWME not only with healthy controls, but also with individuals diagnosed with other disorders."

 

I don't feel this question has been answered. The other Mark Edwards isn't on the board but has been involved with the CMRC. And whether Harrison refutes that he sees ME as an FND, the paper he's involved with explicitly says ME is FND/hysteria. He can refute it all he wants, but the paper has his name on and is crystal clear. Does this mean Harrison intends to disown the paper?

 

NICE doesn't require PEM , it requires PEM or PEF, PEF could be a deconditioning response and doesn't correlate with the global exacerbation of symptoms most experience

Previously Holgate with charity support wanted NICE criteria to form the basis of MEGA so this will be a big question for me.

I'm not hugely enlightened by the F & Q

Watching this over years MRC seems to do something a new reinvention/ initiative every few years, the ME expert group became the CMRC now they're looking at doing something new after refusing to input money for years. Until more facts are on the table and the CMRC tell us plans for investment beyond MEGA I'm very skeptical. And whatever they do now is ten years late, that's ten years extra rotting in bed pour moi.
It's supposed to be independent of the funders but the funders are on the board, fund the conferences and quote it as their "what's being done" , is it a coincidence that CMRC soundss like MRC because up to now to me the CMRC was a way of trying to manage /move cfs research without the state investing.

 

I also don't agree, as I've said, with the nows the time - it was before - or the window will shut talk. I don't think #MEAction have any intention of the patient movement doing anything but becoming louder until our aims are reached.

 

The question implies patients dissatisfaction comes from patients misunderstanding, I don't think that at all. However the CMRC define themselves, they've been naive, ineffective, weak and are ony now calling for more money to be put in, only now working more on biomedical research and Breaking with the BOS lot. They supported weak criteria over strong, fatigue over ME, marginalised the severe despite identifying them originally as a priority etc.
So far the CMRCs virtuaL status has been an excuse to achieve virtually nothing

 

I'm going to need to re-read this to absorb better what's been said when I'm fresher. In the meantime thank you to @Chris Ponting for taking the time to answer our questions.

Thank you @Andy for your work on this.

 

Urgh couldn’t bear to read that pile of crap but made myself do it.

I also found the responses generally quite diplomatic and very different to other Q&A threads. I guess since we had a lot of questions asking why the CMRC was so rubbish we would only get this back?

Thanks to @Andy and @Chris Ponting for the time taken. I’ll be looking carefully for a sea change in the next 6-12 months

 

It does sound like the MRC and CMRC have changed their attitude but until this translates into good research people will be skeptical.