ME/CFS Research Review

Simon McGrath explores the big biomedical stories

A brightening future: the state of ME/CFS research


Although there are no treatments for ME/CFS on the horizon, things are looking up thanks to recent findings and a substantial increase in the amount of high-quality research. The field still needs much more funding.

Do you remember the buzz around rituximab? Oncologists Dr Fluge and Professor Mella had noticed something interesting when they treated their cancer patients who also had ME/CFS with the cancer drug rituximab: the patients’ ME/CFS symptoms improved dramatically. In 2011, Fluge and Mella’s small trial of rituximab as a treatment for ME/CFS produced promising results. A larger clinical trial followed but, last November, the researchers revealed that the treatment was not effective for ME/CFS.

As a result, things feel a bit flat right now for patients. People with ME remain desperate for treatments but there is no clear path to effective therapies. Yet I’m optimistic that things will improve. The ME/CFS research field is the strongest it’s been and there are good reasons to expect progress in understanding the illness – understanding that should drive the development of treatments.

Reasons to be cheerful, Part 1: promising findings

Most of the first 20 years of my illness have seemed like a long night of ignorance when it comes to understanding ME/CFS. Despite the efforts of small and dedicated but underfunded research groups, I saw little progress.

But things have really picked up in recent years, with several promising findings. A major focus for researchers has been on the ability of ME/CFS patients to produce energy. The two-day maximal exercise tests by Workwell and others show an unusual drop-off in the performance of ME/CFS patients on the second day. Findings from other research groups studying energy production at the molecular level, using metabolomics and the Seahorse technology, indicate problems with energy metabolism.

An analysis using a large biobank found that women with ME/CFS were slightly more likely to have one gene variant of the mitochondrial ornithine transporter protein. Such a genetic association, if confirmed, would demonstrate a causal role for the protein in the disease, in some. The ornithine transporter plays a key role in the urea cycle, which removes ammonia from the body.

There have been many findings of modest immune dysfunction over many years, notably a reduced ability of the killing effectiveness of natural killer cells. But in 2017, Dr Mark Davis at Stanford reported substantial levels of T-cell clonal expansion in patients, similar to that seen in multiple sclerosis and infections. If these dramatic findings are confirmed, this sign of immune activation could be a breakthrough in understanding the illness. It could even lead to identifying what is activating the immune system, and then to treatments.

One active theory is that the core problem of ME/CFS is in the brain, which drives the rest of the problems in the body. The most striking finding in support of this is the 2014 finding of activation of the brain’s main immune cells, the microglia.

And, of course, Dr Ron Davis’s research has generated a lot of attention, particularly his work aiming to find cheap diagnostic tests. One of these, the nanoneedle chip, reveals remarkable differences between blood samples from ME/CFS patients and those from healthy controls – but only when an energy demand was placed upon the white blood cells. In a linked “plasma swap” experiment, plasma from ME/CFS samples made healthy cells behave like sick ones, while plasma from healthy samples made ME/CFS cells behave like healthy ones.

Reasons to be cheerful, Part 2: the research field is getting stronger

These are all promising findings that might in time lead to treatments. But the ME/CFS research field itself is getting stronger, substantially increasing the chances of further important discoveries.

There are good things happening across the board in research. New blood is coming into the field: for example, Dr Derya Unutmaz, an immunologist specialising in the role of T cells in chronic disease, joined the fray within the last five years and now heads one of the new NIH collaboratives. New and existing researchers are also applying new technologies such as omics (including metabolomics). These new technologies are helping researchers to identify disease abnormalities that simply couldn’t be seen before.

Researchers are also scaling up their studies, recruiting larger cohorts, and diagnosing those cohorts more rigorously. The UK ME/CFS Biobank is making such large, well-defined patient cohorts available to many more researchers. Bigger studies using carefully diagnosed patients are more likely to produce findings that hold up over time.

In the past, isolated research groups often applied a single approach to a problem, such as using cytokines to look at the immune system. Dr Alain Moreau compared this approach to blindfolded men feeling different parts of an elephant and all reaching different conclusions about what it was.

elephant parable

Increasingly, researchers are collaborating to apply several techniques at once, giving a better chance of seeing the whole elephant. For example, Dr Maureen Hanson’s NIH-funded collaborative brings together experts who between them will look at gene expression, neuroinflammation, extra-cellular vesicles and the impact of a two-day exercise test.

Researchers are also coming together in other ways. This year has seen four conferences: the Canadian collaborative conference in Montréal, Invest in ME Reseaech’s in London, the CMRC’s in Bristol and the Open Medicine Foundation’s Working Group Meeting at Stanford. The three NIH collaboratives will be working together on a single, shared project. Europe has its growing EUROMENE network to foster collaborations.

And, at last, replication attempts of findings are becoming more common. For example, Dr Bob Naviaux and colleagues have a replication in hand of their original, striking metabolomics finding. Several other groups are pursuing or have published similar work using metabolomics. Mark Davis is looking to replicate his approach on T-cell clonal expansion in a larger cohort, and in the UK, Professor Chris Ponting is planning an independent replication of the work. Meanwhile, Dr Shungu, in Dr Hanson’s collaborative, will replicate the brain immune activation study – as will Dr Michael VanElzakker at Harvard Medical school.

Such replication attempts are critical in establishing what is real and worth pursuing, and what is not.

Even the funding situation has improved somewhat. The NIH has roughly doubled its spending on ME/CFS and is planning to invest around $35 million in its three new collaboratives. That’s still nowhere near enough money, given the disease burden and the lack of progress to date, but it is an important start.

Meanwhile, the Open Medicine Foundation has already raised over $14 million for ME/CFS research and is investing in programmes at both Stanford and Harvard universities.

In the UK, things are moving much more slowly. Research remains on a small scale, but even here there is hope. The CMRC is striving to persuade the Medical Research Council (MRC) to commit substantial funds to ME/CFS research.

Future prospects

Overall, and internationally, ME/CFS research is gathering momentum. The buzz of rituximab has been replaced by the growing hum of work on several lines of promising research. There’s no knowing when there’ll be a breakthrough leading to treatment, but I’m optimistic that there’ll be substantial progress over the next five years.

At worst, there should be a better grasp of key areas, including immunology, energy metabolism and the microbiome. As Professor Jonathan Edwards told me in an email, there are now “[E]nough people working on the problem of ME/CFS for the big negatives to firm up and the real leads to emerge.”

At best, as Dr Ian Lipkin predicts, researchers could identify the cause of the illness in some subtypes, with one or more of these subtypes being readily treatable.

There is, I believe, a brightening future for patients. How bright, and how soon it will arrive, remain to be seen – much will depend on the big funders, including the NIH and the MRC, investing properly in ME/CFS.

Comments are open. Please do join the discussion here or at the Science for ME forum.

Image credits: Sky, (c) Can Stock Photo / floyduk;  Elephant cartoon,

Significant association of DNA variants with self-reported ME/CFS

Guest blog by Professor Chris Ponting and colleagues.


A new analysis using data from UK Biobank indicates that one version of a particular gene increases the risk of ME/CFS in women. The gene codes for a transporter protein in the mitochondrial membrane and plays a critical role in the urea cycle, which is important for removing ammonia from the body. Reduced levels of the transporter protein, which are expected for the gene variant associated with ME/CFS, are likely to impair mitochondrial function. If replicated later, this finding would provide the first evidence that a person’s risk for ME/CFS is caused by changes to mitochondrial function.


On June 11 2018 we posted a blog describing an analysis of the UK Biobank’s data, drawn from half-a-million individuals from around the UK. The data implied that there is a genetic contribution to an individual’s risk of ME/CFS but it did not provide strong evidence that change in any one section of DNA explained this risk.

This analysis is called a genome-wide association study, or GWAS for short. When there is an association between a biological factor, such as cytokine changes, and an illness, it is not normally possible to say whether the factor is a cause of the illness or simply a consequence of being ill.  But because the genetic variation comes first it must contribute to a cause rather than being an effect of the illness.


A GWAS asks whether the frequency of a DNA letter difference predicts whether a person has, or has not, a disease;

This prediction is not perfect and almost always reflects only a slight preference for people with this DNA difference to part of the disease cohort;

Importantly, GWAS predictions indicate genetic cause. This is because inherited disease (except cancer) does not predictably cause DNA mutation.

We are blogging again because a new analysis has revealed a promising finding.

This new analysis is again of the UK Biobank data and has been posted by Ben Neale’s lab. After discarding data that they considered lower quality, they were left with data from 194,174 females and 167,020 males and kindly made their results freely available to all.

Female-only GWAS

Considering males and females together they identified no specific region of the human genome whose DNA variants were significantly associated with self-reported CFS/ME. (One variant, rs148723539, is possibly indicated [p = 2.3×10-9] but this is not supported by adjacent variants.)

However, the female-only analysis revealed a single region, on chromosome 13. Ten DNA variants (single nucleotide variants, SNVs) were significantly associated [SNVs with minor allele frequency <0.001 or that were “low confidence” were filtered out] using a probability threshold of p < 5×10-8.

These 10 SNVs are inherited down the generations together (they are in “linkage disequilibrium” [LD]) and so this looks like just one association, rather than ten different ones. The 10 SNVs all lie in a 51,000 base region that surrounds the SLC25A15 gene (Figure 1 below).


Figure 1

Their conclusion is that DNA variation in this part of the genome slightly changes a woman’s risk of having a ME/CFS diagnosis. This must mean that one or more DNA differences in this part of the genome cause this risk change. But because all 10 differences are inherited together, it is not clear which one or ones are causing the increase in disease risk. Pinning down the causal DNA changes will require detailed experimental research.

We can talk about a DNA letter representing increased risk (this is the “risk allele”). For example, the 41,353,297th DNA letter on chromosome 13 is either G or A (the site is given the code rs7337312). You have two copies of chromosome 13, so also two versions of this DNA letter: you can have G twice (“GG”), A twice (“AA”) or G and A (“GA”). People across the world vary in the frequency of G or A but in the UK Biobank population it turns out that the frequency of G is about the same as that of A (~50%).

The Ben Neale lab result implies that having a DNA letter G at this position on chromosome 13 predicts a slight increase in risk of having a ME/CFS diagnosis; having two such letters G increases the risk further over having just one G. The frequency of G of ~50% means that roughly three-quarters of these UK Biobank females have at least one risk G.

Another of the Neale results is that women that have G at this position tend to have very slightly lower lymphocyte count (rs7337312; p = 4.6×10-7; other variants in LD have p < 5×10-8).  Lymphocytes are white blood cells, mostly B cells and T cells. They also show that G at this position significantly and slightly increases two biomechanical properties of the cornea (corneal hysteresis and corneal resistance factor).

ornt biofactors

Figure 2. Genetic effects on ME/CFS risk & blood cell counts, and additional predictions

Ornithine Transporter type 1

Figure 1 shows that the GWAS genetic associations are for DNA differences that lie in-or-around a particular gene called SLC25A15. There is another gene in this Figure which is a pseudogene (TPTE2P5) which does not make protein and is less likely to alter physiological function when mutated. This does not necessarily immediately implicate SLC25A15 as the gene through which this genetic effect is transacted.

However, other data indicates that people that have G at this position tend to produce slightly lower amounts of SLC25A15 RNA (in aorta, colon, hippocampus, transformed lymphocytes and other samples, but not in whole blood, liver, muscle, cerebellum etc; Figure 2). So SLC25A15 is an excellent candidate for the gene whose activity alters between GG, GA and AA individuals thereby changing ME/CFS disease risk.

ornt tp t1

3D model of ORNT1

So what do we know about SLC25A15? Interestingly, it encodes a protein called Ornithine Transporter type 1 (ORNT1). This transports ornithine (as well as lysine and arginine) across the inner membrane of mitochondria to the mitochondrial matrix. Ornithine is an amino acid (but not incorporated into proteins) that plays a role in the urea cycle. This cycle plays an essential part in removing ammonia from the body (see point iv below).

This analysis predicts that if you have a letter G at this position then (Figure 2):

(i) if you are female, then you have a greater risk of ME/CFS;

(ii) many of your cells (for example in the heart or hippocampus, but not in muscle or liver) would tend to produce less ORNT1 RNA and less ORNT1 protein; and,

(iii) if so, then ornithine would build up in these cells and mitochondrial function overall would be impaired; and,

(iv) ammonia would accumulate in the blood.

Some of these predictions are drawn from what is known about individuals whose SLC25A15 genes are both defective, causing ornithine translocase deficiency (also known as HHH syndrome). This is a severe disease often leading to coma due to hyperammonemia, learning difficulties and also lethargy. A good review of HHH syndrome can be found here.

So do these predictions agree with what others have found when comparing people with ME/CFS with control individuals? In large part yes, but not always:

(a) Yamano et al. (2016) showed that there is an increased ornithine/citrulline ratio in ME/CFS individuals

(b) Naviaux et al. PNAS (2016) found that ornithine is moderately high for males and for females

(c) Nevertheless, Armstrong et al. (2012) found the opposite, a significant reduction of ornithine (P<0.05) in the blood of CFS samples.

What are this study’s limitations?

  1. Only one genomic region was identified, so a much larger study is required with about 20,000 ME/CFS cases to find more.
  2. This association would need replication in an independent study.
  3. We do not know whether males with ME/CFS show this genetic association. Males in UK Biobank with self-reported ME/CFS are 2.4-fold fewer than females, so a male-only GWAS is substantially less well powered to find true results.
  4. Even if true, then this association would alter risk for ME/CFS by only a small amount and certainly not for most people.
  5. The urea cycle occurs mostly in mitochondria in liver cells, yet SLC25A15 expression is found not to be different between GG, GA and AA in this organ. SLC25A15 is expressed also at moderate levels in pancreas and small intestine, yet these are not major sites of the urea cycle.
  6. We do not know whether slightly lower amounts of SLC25A15 RNA (in aorta, colon, hippocampus, transformed lymphocytes and other samples) result in lower amounts of SLC25A15 protein. This would need to be true for the hypothesis to be correct.
  7. We do not know whether the various observations on ME/CFS, lymphocyte percentage and cornea biomechanics are relevant to one another.
  8. Its findings should not be used to alter clinical treatment without consulting with a GP.

What are its strengths?

  1. If replicated, this would be the first piece of genetic evidence that mitochondrial dysfunction (specifically ornithine transport) is causal of ME/CFS susceptibility (as opposed to being a consequence of ME/CFS disease).
  2. It would focus clinicians’ attention on these cellular processes for diagnosing and stratifying ME/CFS cases.

With thanks to Ben Neale and his lab for making their results freely available, and to Simon McGrath for comments and hosting this blog.

Chris P. Ponting1, Neil Clark1, Mark Jones2.

1 MRC Institute of Genetics & Molecular Medicine, MRC Human Genetics Unit. 2 UCB Pharma.

Image credits: ORNT1 3D computational model, Wang & Chou, 2012.

The heart of ME/CFS? Lipkin’s Collaborative probes the impact of exertion

Download PDF

The hallmark symptom of ME/CFS is post-exertional malaise (PEM), a prolonged, grim and disproportionate response to exertion. While Dr W. Ian Lipkin’s NIH-funded Collaborative – the Center for Solutions for ME/CFS – is focusing primarily on how problems in patients’ gut microbiomes might drive the disease, his team is also probing deeply what happens when patients exert themselves.​ Lipkin says that the exertion studies are so important that the Collaborative will devote a third of its research resources to them.

When I spoke to Lipkin about the Collaborative’s work, he also said he was very hopeful that there would be real progress for patients within five years. More on this later in the blog.

Exertion studies

The Collaborative has a simple idea for exploring PEM: use two different exertion tests that should provoke symptoms in patients and then see what happens, both to how patients feel and to their biology.

If biological changes, such as those to cytokines, ramp up along with symptoms then it’s more likely that the biological changes are directly related to the illness and should give clues as to their role. Any insights into the nature of PEM could lead to a much better understanding of ME/CFS.

bike-CPET-FFifty patients and controls will undergo a single maximal exercise test, a sure-fire way to provoke PEM. Patients’ symptoms will be measured before the test and then 24 hours, 48 hours and one week after the test. Crucially, researchers will collect blood, saliva and stool (poop) samples on two occasions: before the test, and 24 hours later.

The other, gentler exertion test, called LEAN, simply involves patients leaning against a wall for ten minutes. This test is designed to induce orthostatic intolerance – the development of symptoms when standing upright that ease when lying down – which is a common problem in ME/CFS.

Symptoms (including brain fog, tested using a special phone app) will be measured just before the test and at three time-points afterward. Researchers will also check blood pressure and take other clinical measures both before and immediately after the test.

The researchers running the Collaborative’s immune study will apply transcriptomics (which examines gene expression) and metabolomics to blood samples from both the exertion tests. And this should reveal any biological changes as symptoms kick off.

Patients and samples

The basis of any good study is to have samples from a large group of robustly diagnosed patients. The Collaborative already has such samples for the microbiome/immune work that was discussed in Part 1 of this blog and is assembling a new cohort of patients and controls for the additional work. This is necessary because many of the patients who provided samples for the earlier projects aren’t available for the exertion studies and other work discussed here.


Dr Komaroff

Dr Anthony Komaroff will head the team overseeing this work, and that team will also run the exertion tests. Patients will come from the clinics of expert physicians Drs Susan Levine, Jose Montoya, Dan Peterson and Cindy Bateman – some of the finest ME/CFS clinicians in the US. They will recruit 100 patients and 100 controls.

Dr Dana March, Assistant Professor of Epidemiology at Columbia University, is a key part of the team and their projects, which include mining existing patient data for insights, and creating a new app.

A new bioresource to power future research

With this work the project is also creating a “bioresource” of well-defined patients and of samples taken both before and after exercise. Lipkin says that researchers from both inside and outside the Collaborative can draw on the bioresource to power a new wave of studies.

Lipkin said that the Collaborative itself would like to make more use of the samples: for example, running epigenomics and proteomic profiling of the exertion-study blood samples, and analysing the stool samples, work that would have allowed his team to have the same data on these patients as for the microbiome study. As yet, he doesn’t have funds for this work.

The MyME/CFS app

app, iphoneThe Collaborative have more in store for this cohort of patients. Working with a tech company, they will create an app for patients that will help both patients and the clinicians to track the illness for an extended period.

The app will collect information in real-time from patients, covering their symptoms, activities, events in their lives, including other illnesses and any treatments they are trying. This detailed history could help identify what might be causing any setbacks, relapses or even improvements.

Komaroff has said that using technology like this will allow researchers to collect much more comprehensive information much more cheaply than was possible before. Work is already under way, and the team have started by asking patients what they really want from the app.

Mining data for insights

Lipkin has data from several previous studies that all used the same group of patients. The team will combine the data from these studies into one unified database, creating a rich seam of biological, clinical and survey data on a single set of patients. The team will then mine the combined data, looking in particular for patient subtypes and for risk factors.

For example, subtypes might be based on how the illness started, symptom clusters, gender, types of other illness patients have had or how long people have been ill. Risk factors could include previously having a different disease. The idea is that the data will talk.

The team will also bring together and mine data from studies that used the same measures, but not necessarily the same patients. This could also help reveal subtypes and risk factors.

Bringing it all together

One of the most exciting things about this project is the wealth of data the Collaborative will have on every patient they study. For the first group of patients, this means the detailed molecular profiling of the microbiome and the immune system – including antibodies to “self” and to past infections – coupled with rich clinical data.

For the second, newly recruited cohort of patients, the Collaborative will have data on their molecular and physiological responses to exertion, along with clinical data, plus the same data on antibodies as the first group of patients – and the data tracking patients’ health in relation to a whole collection of factors.

Combining results from such different sources will provide researchers with a deep and rich source of data that will dramatically increase their chances of finding what’s going wrong in ME/CFS.

With so much new data to explore, it’s possible that Lipkin’s group will be able to identify any subtypes of patients, regardless of findings from the data-mining of existing studies.

The crystal ball


Dr W Ian Lipkin

I asked Lipkin how he thought things might look at the end of the five-year NIH funding for the Collaborative’s research program.

He was bullish about the prospects for significant progress. He made a comparison with the situation with cancer treatment 20 years ago.

He believes that in ME/CFS, as with cancer, a group of similar-looking patients will prove to have different causes or triggers for their illness but will share a final common pathway: “ME/CFS”.  As with cancer, he expects they will find the specific cause of ME/CFS for some groups of patients quite quickly – the low-hanging fruit.

On the other hand, Lipkin believes it may prove much harder to find causes for ME/CFS in other patients – the fruit higher up the tree.

precision medicine

Precision medicine: targeting treatments by patient subtype

Lipkin is aiming for precision medicine, where doctors try to establish each patient’s exact problem so that it can be treated in the most effective way. If for example, the microbiome is abnormal, there are already plausible treatments available, such as probiotics, antibiotics or antivirals that could have a profound impact on illness. Other patients may have abnormalities in immune system or mitochondrial function that will require the development of specific drugs or genetic therapies.

Lipkin said that he hoped that the Collaborative network could be starting clinical trials in three years’ time – assuming that results support that next step. He stressed that these trials should be as rigorous as those used for other diseases. To avoid bias in interpretation of results the trials should be blinded so that neither the patient nor the researcher knows whether the patient is receiving a specific treatment. And adverse events – patient harms – should be tracked by a data safety monitoring board.

Lipkin noted that his team and others are already working across the US and internationally to share ideas, expertise, data, samples and other resources. He asked me to assure the community that we have reached an inflection point in the history of ME/CFS research and wanted to specifically thank the community for its support.

In some ways, his programme of research represents a voyage of discovery, and Lipkin’s not sure what he’ll find. The Collaborative will set off in the most promising directions with the tools and the samples but will change course, if necessary, based on the results, following the evidence to see where it leads.

Whatever the final course taken, the goal remains the same. In a recent NIH briefing-call to patients, Lipkin stated the aim of the Center for Solutions for ME/CFS simply and clearly: to find “real solutions for real people so that we can make it possible for people to become active again.”


The microbiome hypothesis: Lipkin’s collaborative, part 1

Image credits: Exercise test, © Can Stock Photo / 4774344sean; Dr Komaroff, his Twitter profile; App, Pixabay; Dr Lipkin, Center for Infection & Immunity; Precision medicine, National Cancer Institute.

The microbiome hypothesis: Lipkin’s collaborative, part 1


Dr W. Ian Lipkin

A gut reaction is the problem in ME/CFS – that’s the main idea being pursued by Dr W. Ian Lipkin of the Center for Infection and Immunity at Columbia University. He believes that the body’s response to changes in the gut could be what’s driving ME/CFS for at least some patients.

Lipkin’s collaborative group, the Center for Solutions for ME/CFS, will test this theory as part of a $9.6 million, five-year research programme, which Lipkin was good enough to discuss with me via phone and email.

This huge research programme, which is funded by the National Institutes of Health (NIH), is made up of three main projects. This blog looks at the first two, which will use high-tech approaches to see if changes in the gut are causing changes in the body, particularly in the immune system. The third project, which looks at the biological response to exertion in ME/CFS, will be covered in the next blog.

Evidence from research supports the idea that gut problems could lead to ill health. Inside the gut, trillions of microbes – viruses, bacteria and fungi – form an ecosystem. Some are hitching a free ride, but many are useful, crowding out harmful microbes, helping us to digest our food or providing essential nutrients such as vitamin K.

A short video introduction to the microbiome from NPR

But sometimes the ecosystem can get out of balance, with too many of particular types of microbes or too few. This “dysbiosis” can play an important role in conditions such as inflammatory bowel disease.

This is where Lipkin comes in. He suspects dysbiosis as a possible cause for ME/CFS and sees two main possible mechanisms leading to disease. One could be through the metabolites produced by an unhealthy microbial ecosystem. Metabolites are small molecules that are a core part of the chemical processes that sustain life, and undesirable ones from microbes could enter the bloodstream from the gut.

Lipkin told me that these metabolites could be creating ME/CFS symptoms by, for instance, altering mitochondrial activity and so causing fatigue, or even affecting the brain, which could lead to brain fog and other cognitive problems.

The microbiome and the immune system: it’s complicated

A second way that Lipkin believes that dysbiosis could cause ME/CFS is via the immune system. Recent research on microbial numbers indicates that there are roughly as many microbes in the gut as there are cells in the human body. That represents a serious threat of infection and requires a delicate balancing act for the immune system, dealing with dangerous pathogens without starting an inflammatory war.  A fired-up immune system can lead to both fatigue and cognitive problems in many illnesses.

However, it’s a two-way relationship between the immune system and the microbiome. For instance, some gut bacteria produce the metabolite butyrate that stimulates certain types of T cells, helping to maintain the peace.


Microbiome dysbiosis might drive ME/CFS via the immune system.

So there are at least two possible ways that the microbiome could be driving ME/CFS in at least some patients: microbiome metabolites that enter the blood could directly cause fatigue and cognitive problems; or more complex interactions between the microbiome and the immune system could lead to similar problems. But is either of these possibilities actually happening?

Dr Ian Lipkin is a good scientist to have on your case. He has probably discovered more viruses than anyone else. The Chinese government hired him to deal with the 2003 SARS outbreak. And he’s pioneered new technology throughout his career, most recently with a new way of detecting just about any human virus in a patient using a small chip. Versions of that technology will be used in this study.

Project 1: Mapping the microbiome

Lipkin has been working on the gut microbiome in ME/CFS for some time (see this recent paper, for example). Now, in this first collaborative project, he and his colleagues aim to find out if some or all ME/CFS patients have dysbiosis in the gut, by comparing patients with healthy controls.

Gut microbiome computer

Bacteria, fungi and viruses make up the gut microbiota.

All the microbes of the microbial ecosystem are technically known as the microbiota, but are usually referred to as simply the microbiome – the collection of all the genes that make up all the organisms. Surprisingly, it’s easier to find out the microbial make-up of the gut by analysing this huge set of genes – the microbiome – rather than by studying individual organisms.

Lipkin and colleagues will take this approach, using DNA sequencing and analysis of the microbiome to create microbial maps for all 107 patients and 97 healthy controls in the study.

The team will use a range of high-tech approaches to map the microbiome in a more sophisticated way than has been done before for ME/CFS, to provide the most accurate data possible. The resulting microbial maps will reveal if some or all patients have an off-balance microbiome that could be causing their illness – and the research team are looking at the viruses and fungi in the microbiome, not just the bacteria.

In addition, the team’s deep-sequencing method will provide insights into what genes are present in the whole microbiome, and how those genes might then affect a patient’s biology.

Project 2: Total molecular mapping of the immune system

Microb-Immune-p1,2The next – and critical – step in Lipkin’s research programme will be to link any changes in patients’ microbiomes observed in Project 1 to changes in their immune systems, and this is the goal of Project 2.

Lipkin will be using “omics” technology – a big data approach – to probe the working of immune cells in many different ways.

Omics offers a huge advantage over more traditional approaches in which, for example, researchers would have looked at the level of a single protein in a sample, such as the level of haemoglobin in blood. But with a protein omics approach, called proteomics, researchers look at a huge number of proteins in the sample – here the sample is all the immune cells that make up the white blood cells.

This broad omics approach can reveal far more about what’s going on in the immune cells than just looking at one or a few proteins.

Lipkin’s team hope to find differences between the immune cell proteins in patients and those of healthy controls, and that could reveal what’s gone wrong in ME/CFS.

The real bite of this study is that it won’t just use proteomics; it’s also using epigenomics to probe gene regulation, transcriptomics to see which genes are active, and metabolomics to probe which cellular chemical reactions are taking place.

These four omics approaches cover almost all fundamental levels of a cell’s molecular biology, providing a detailed map of activity in immune cells. This should give researchers extraordinary insight into the problems in the biology of ME/CFS patients.

Most processes in a cell begin with genes, the cell’s instructions written into its DNA. Genomics – the first and best known omics – looks at these instructions. But this study will instead use epigenomics, which looks at a level of broad gene regulation carried out by epigenetic tags. These tags are added to either sections of DNA or their scaffolding proteins and switch sets of genes on or off. Differences in regulation of genes between patients and controls revealed by epigenomics work could give clues about where problems arise for patients. So epigenomics provides the first level of information, as shown in the figure below.


Genes themselves do nothing until their DNA is transcribed (copied) into a similar molecule called RNA in a process known as gene expression. All the RNA transcripts in the sample are known as the transcriptome, and most of it consists of messenger RNA (mRNA), which tells cells which proteins to make. Other types of RNA can play a number of roles in the cell. Previous ME/CFS studies have looked at gene expression by looking for a large number of prespecified mRNAs, but not all of them. Transcriptomics offers a more comprehensive approach to understanding which genes are active in a cell.

The third level of omics is proteomics, which looks at the proteins. Proteins are the body’s ‘doing’ molecules, such as antibodies, cell receptors and enzymes.

The final level is metabolomics, looking at metabolites, such as glucose and some amino acids. Metabolites are key molecules in the chemistry of life: for example, they make up the energy cycle in the mitochondria – where Professor Ron Davis and others have identified abnormalities in ME/CFS patients.

So a cell’s DNA gets regulated, in part, by epigenetic tags (looked at by epigenomics) and is transcribed by RNA (looked at by transcriptomics) to make proteins (looked at by proteomics). Then enzymes, which are a type of protein, catalyse reactions involving metabolites (looked at by metabolomics).

Using omics to look at these four different levels of immune cells’ molecular biology – genes, RNA, proteins and metabolites – hugely improves the odds of findings where the problem lies.

Lipkin told me that you can start by finding an issue with a metabolite and then “swim upstream” to see if that problem is driven by a change in proteins, in RNA or in gene regulation. Similarly, you can swim downstream if you find an issue with broad gene regulation – does it make a difference to RNA, proteins and/or metabolites?

To make this aspect of Project 2 happen, Lipkin has recruited an impressive roster of omics experts to his collaborative, namely Dr John Greally for the epigenomics and transcriptomics work, Dr Ben Garcia for the proteomics, and Dr Oliver Fiehn, who leads one of the largest metabolomics labs in the world, to analyse metabolites. All of them are relatively new to ME/CFS and will bring fresh perspectives.

Probing antibodies for signs of autoimmunity and infection

In addition to the microbiome and related immune work, Lipkin’s team will also use elegant new technology that he developed to look for  potential autoimmune problems and past infections that might have triggered the illness.

The approach focuses on antibodies, which bind very specifically to just one antigen – antigens are fragments of proteins, such as part of a virus’s protein coat, that trigger an immune response in the body. The antibody is like a specific lock that binds to just one antigen key.


“Antigen keys” could unlock antibody secrets.

The new technology essentially offers up a huge bunch of antigen keys (actually fragments of antigens called epitopes) and detects which one fits. If the antigen key is a protein from a pathogen, such as a flu virus, that indicates that the body has fought off an infection, possibly one that triggered ME/CFS. On the other hand, if the key is part of a “self” protein, that could be a sign of an autoimmune disease. Researchers will focus on any differences between patients and healthy controls.

And there’s more. The team will use additional technology – based on Lipkin’s high-tech way of detecting just about any human virus – to check the gut, saliva and blood for fungal or bacterial infections.

*     *     *

With these three approaches – a high-tech dive into the microbiome, linking changes in the microbiome to changes in the immune system at all molecular levels, and a search for what patients’ antibodies respond to – Lipkin’s investigation of what’s going on in ME/CFS patients is impressive. He hopes that this combination of depth and breadth will help to unlock ME/CFS.

One final point: Lipkin is not alone in thinking that problems with the microbiome might be driving ME/CFS via the immune system. Dr Derya Unutmaz is pursuing the same idea with his own collaborative. The main difference between the two researchers’ approaches is that while Lipkin has a more molecular focus, Unutmaz is focusing more on the different cells of the immune system, such as T cells and their subtypes. [Update:  Unutmaz and Lipkin have announced a collaboration – both will apply their techniques to the same patients to give the deepest possible profiling of immune cells.]

Part 2: The heart of ME/CFS? Lipkin’s Collaborative probes the impact of exertion

The blog also features Lipkin’s bullish views on the future for ME/CFS.

Image credits: Dr Lipkin, Center for Infection & Immunity; Microbiome, source unknown (please contact me if it is yours); Immune cells, © Can Stock Photo / Kateryna_Kon; Metabolite & protein molecules, also Can Stock; Dr Fiehn, UC Davis;

Dr Ron Davis’s big immune study is looking at HLA genes. Here’s why.

Dr Ron Davis has won a large NIH (US National Institutes of Health) grant for an immunology project with a strong focus on HLA genes. Which may have led some to wonder, ‘What are they?’

HLA (human leukocyte antigen) molecules play a critical role in the immune system, particularly by activating T cells. There is a huge amount of variation in the HLA genes that different people have, and Davis’s theory is that certain types of HLA genes could increase the risk of ME/CFS.

The following explanation of HLA molecules is taken from a piece I wrote a few years ago.

The short version

HLA molecules fire up T cells

HLA waiter1

HLA serves up an antigen, ready for a T cell receptor to recognise.

T cells play a key role in the immune system. Like antibodies, the receptors of T cells respond to very specific antigens (foreign proteins), much like a lock matching just one key.

However, while antibodies will recognise and bind to part of a whole protein, such as the protein coat of a virus, T cell receptors only recognise tiny fragments of proteins. And T cell receptors can’t respond to antigens unless they are presented in just the right way.

That’s where HLA molecules come in. At a very basic level, HLA molecules act like waiters, serving up the antigen on a plate. More precisely, HLA molecules – which sit on the cell surface – have a groove that cradles the small antigen, and the T cell receptor binds to the antigen and HLA molecule together.

If the T cell receptor recognises the antigen proffered by the HLA molecule (strictly speaking, several different molecules combine to make an HLA complex) then the T cell will snap into action. But without HLA molecules, T cells wouldn’t be able to take action against threats to the body.

HLA in ME/CFS and other diseases

We have six different types of HLA molecule that present to T cells, and there are many different versions of each of the six types. Ron Davis at Stanford believes that the version of HLA genes you have may influence the risk of getting ME/CFS, and certainly HLA gene variants have been linked to numerous diseases. One particular version of an HLA gene increases the risk of narcolepsy by 130 times. A version of another HLA gene conveys some protection against HIV developing into AIDS – though the same gene variant increases the risk of the autoimmune disease ankylosing spondylitis. In fact, HLA genes are linked to a number of autoimmune diseases.

More about the biology (it’s fun, really!)

HLA molecules help activate T cells

T cells are an important part of the immune system. T helper cells are ‘generals’, co-ordinating the immune system response. For instance, T helper cells play a critical role in firing up antibody-producing B cells and other types of T cell. Killer T cells are more like infantry, acting independently and killing off rogue cells such as those infected with a virus.

But T cells need to be activated first before they get going, and they are activated in part by antigens, which for T cells are peptides, short pieces of protein. And antigens are what HLA molecules are about: they sit on the cell surface and hold out the antigen morsels to the T cells.

If the T cell  receptor recognises the antigen –  in much the same way as an antibody recognises a specific antigen – then that will trigger activation of the T cell. In the case of killer T cells, that’s curtains for the cell doing the presenting – the cell has just signed its own death warrant, but that’s the whole idea.

By taking out the infected cell, the killer T cells are helping to contain an infection and protect other, healthy, cells.

Killer T cells also recognise cancerous cells. And when things go wrong, they can also recognise normal proteins as a threat, leading to autoimmune diseases.

‘Don’t kill me’: HLA class I and killer T cells

Apart from red blood cells and sperm, almost every cell in the body displays class 1 HLA molecules. HLA class I molecules acts as a kind of identity card: it’s the way a cell proves that it is healthy and should be left in peace by marauding killer T cells that will destroy any cell that doesn’t pass muster. You could see killer T cells as an internal security force that’s licensed to kill.

The whole system is pretty elegant and very hard to cheat as the key thing about HLA class I molecules is that they present little bits of whatever proteins the cell that bears them is producing. So if a cell is infected by a virus it will be manufacturing lots of viral proteins, and bits of these foreign proteins end up displayed on the HLA-I molecules. That’s ‘game over’ for the infected cell: once a killer T cell recognises that viral antigen it sends a signal to the infected cell to self-destruct.

So that’s HLA class I: cell-surface molecules that act as identity cards by displaying to killer T cells bits of whatever proteins the diseased cell is making. It’s a way for healthy cells to show that they are ‘clean’, so that the lethal killer T cells leave them alone, while infected cells mark themselves for destruction.

TCR HLA edit

A killer T cell in action against a cell infected by a virus. An HLA class I molecule offers up a viral antigen, and a T cell with a matching receptor binds to the HLA molecule and the antigen together. The T cell responds by killing the infected cell.

‘Here’s the threat, sort it out’: HLA class II

The other class of HLA molecules, class II, also display antigens, but while class I HLA are on almost all cells , class II are used by the ‘professionals’ – immune-system ‘antigen presenting cells’, such as macrophages, dendritic cells and B cells. Their role is to pick up foreign antigens and present them to other immune cells, particularly T helper cells to kickstart the adaptive immune response. (Adaptive immune responses are very specific, such as antibodies recognising a particular viral protein, as opposed to ‘innate’ responses that recognise classes of pathogens, such as recognising viral RNA or bacterial cells walls.)

Link to Mark Davis’s work on clonal expansion

Once they’ve been primed by class II HLA molecules, T helper cells don’t act directly against an infection. Instead, they help activate other immune cells, including the killer T cells we’ve just discussed and antibody-producing B cells. Killer T cells are the type of cells where Mark Davis has found clonal expansion. When killer T cells are activated (by both T helper cells and the antigen presenting cells) they copy themselves to form an army of clones ready to take on the threat: this is clonal expansion.

Back to the Ron Davis study: HLA and disease

There are three types of class I HLA molecules (HLA-A, HLA-B and HLA-C) – and three important types of class II HLA molecules (HLA-DP, HLA-DQ and HLA-DR). That makes six types, but there are huge numbers of different versions of each type.

Different versions of HLA are associated with increased risk (or even decreased risk) for certain diseases, particularly autoimmune diseases.

In 2014 Ron Davis reported that initial HLA profiling of 400 individuals indicated that patients had different versions of the genes that encode the HLA protein from healthy people – but that they needed to profile more people to confirm this finding. A new study that has just been announced should establish if particular versions of HLA molecules increase the risk of getting ME/CFS.

The project starts this month and is expected to complete by 2023. More information about the study at Health Rising.

(Image credits: Waiter –; HLA/TCR binding – adapted from Elemans et al.)

Analysis of data from 500,000 individuals in UK Biobank demonstrates an inherited component to ME/CFS

Guest blog by Professor Chris Ponting and colleagues.

UK Biobank – a national biobank different from the ME/CFS biobank – has data from around 500,000 individuals, including both healthy people and those with one or more of the many different diseases in the UK population. About 2,000 people in the sample reported that they had been given a diagnosis of CFS.​

Analysis of data from this biobank indicates an inherited biological component for ME/CFS. The results show only one statistically significant change in a particular section of DNA and even this is problematic. This analysis indicates that a much bigger study, with many more ME/CFS cases, will be needed to indicate which genes and biological pathways are altered in people with ME/CFS.​



Chris Ponting

Myalgic encephalomyelitis (ME, also described as chronic fatigue syndrome, CFS) is a devastating long-term condition affecting 250,000 UK individuals. People with ME experience severe, disabling fatigue associated with post-exertional malaise. A few make good progress and may recover, while most others remain ill for years and may never recover. There is no known cause, or effective treatment for most. Consequently, it is vital to try new approaches to understand the reasons for the development of the condition.

This blog sets out what we can glean from the release, last summer, of data from about 500,000 individuals who make up the UK Biobank. (This biobank is not to be confused with the UK ME/CFS Biobank, UKMEB.) The data were acquired from individuals between 40 and 69 years of age in 2006-2010 who live across the UK. These people provided samples (e.g. blood, urine and saliva) and answered questionnaires. In addition, for some of these people their electronic health record data are being linked in. Importantly for this blog, the DNA variation (‘genotype’) of all the volunteer participants has been determined.

Genetic variation can provide insights into the causes of disease when these have a heritable component (i.e. are inherited down through the generations). DNA sequence is not altered by disease (except in cancer) and so variants can reveal the causes, rather than consequences, of disease.


Here we draw heavily from an analysis of the UK Biobank data by Oriol Canela-Xandri, Konrad Rawlik and Albert Tenesa which is described in a preprint available from bioRxiv. (The authors have kindly shared their results in this way in order to share results with others before the findings have been peer reviewed.)

From this (specifically, Supplemental Table 1) we see that data were analysed from 1,829 people among the UK Biobank cohort who self-reported as having been diagnosed with ME/CFS. The table also provides five pieces of information:

(1) The prevalence of ME/CFS among UK Biobank individuals was 0.448%. In other words, picking any person randomly in the UK then there is an even chance that they know someone with ME/CFS if they know about 200 people.

(2) There is a reasonably strong female bias: the prevalence rates are female = 0.611%; male = 0.255%; so there are 2.4-fold more females than males with ME/CFS in the UK Biobank cohort.

(3) Extrapolating these numbers to the UK as a whole, here are the full population prevalence predictions (using 2016 estimates for UK census populations).

Female Male Total
ENGLAND 171,630 69,339 240,969
SCOTLAND 16,784 6,781 23,565
WALES 9,668 3,906 13,574
N IRELAND 5,783 2,336 8,119
UK (total) 203,865 82,362 286,227

There is one caveat that should be mentioned with respect to these numbers. This is that the 500,000 people assessed in the Biobank, despite being recruited for assessment at 22 centres in Scotland, Wales and England, are not fully representative of the general population. There appears to be a “healthy volunteer” selection bias which would imply that the prevalence estimates are lower-bound values. Furthermore, if ME/CFS prevalence is different in other groups then this is not accounted for in the numbers above.

(4) ME/CFS has a biological component because the heritability of ME/CFS is not zero. Canela-Xandri et al. estimate that the genetic heritability (liability scale) is 0.080. This is slightly lower than the median heritability of heritable binary traits (0.11; see Figure 1). So among all such things measured, it’s in the lower half of the heritability, but not zero. Note that this doesn’t rule out non-heritable biological causes.

(5) The analysis identifies one, and only one, DNA position whose genetic variation associates with (in part) ME/CFS susceptibility. (The plot below is called a Manhattan plot and any point above the dashed line is predicted to be a significant “hit”. Each dot represents a position (X axis) along a chromosome – shown alternatively in red and blue – and its position on the Y-axis indicates the statistical significance of the association: the higher the better.)

Manhattan plot biobank GWAS

Statistical significance for the association between each DNA position and ME/CFS across 22 chromosomes. The arrow highlights the one “significant hit”.

This proposed “significant hit” is on chromosome 10 (position 74828696; rs150954845). The calculated p-value is 2.5×10-12. This DNA change (A-to-T) is predicted to alter a protein called P4HA1, changing an aspartic acid (“D”; GAT) for a valine (“V”; GTT) at its 124th amino acid position.  P4HA1 is prolyl 4-hydroxylase subunit alpha 1: in other words, one part of prolyl 4-hydroxylase, a key enzyme in collagen synthesis. We know what this molecule looks like and where the aspartic acid (D124) occurs within it (below; courtesy of Luis Sanchez-Pulido).


We can even see at a resolution of 10-10 of a metre what effect such a change would have on the protein (below; courtesy of Luis Sanchez-Pulido).



So, should we believe that this amino acid change alters someone’s risk of developing ME? For five reasons we need to be cautious:

(a) ME is a complex condition, likely to be caused by many DNA changes each of small effect acting together with the environment, so the fact that only one association was found indicates that the study is under-powered. This means that it doesn’t have the number of patients sufficient to provide the statistical power needed to detect the major DNA changes associated with the illness: more individuals means greater statistical power.

(b) Second, this part of the protein is not conserved across evolution. There is even a nematode worm known that has a valine at exactly the position (124) that would be predicted to alter risk for ME in humans. This isn’t conclusive, but an amino acid change at a position that is shared across different species would have given us greater confidence in the prediction.

(c) Third, very few people have this amino acid change. Only 0.01% of the population have this alteration, and at such low levels it is difficult to calculate levels of significance accurately particularly when the numbers of people self-reporting with ME (here, n=1,829) are so much lower than the entire cohort (500,000).

(d) Fourth, this association was not reported to be significant in a separate study.

(e) The study relies of self-report of receiving diagnosis of chronic fatigue syndrome, so these cases have not been diagnosed by researchers as meeting any particular definition of ME/CFS.


  1. If the UK Biobank prevalence of ME/CFS is repeated across different populations, then 34 million people worldwide will have this disorder, 2.4-fold more women than men.
  1. ME/CFS has a biological component, as shown by its non-zero heritability in UK Biobank.
  1. To obtain robust indications of which genes and which biological pathways are altered in which cells or tissues in people living with ME/CFS, then a much larger study is required. A GWAS with ten- or twenty-thousand cases, is likely to be necessary. Results will then need to be replicated in a separate cohort.

Chris Ponting, Luis Sanchez-Pulido, Katie Nicoll-Baines, Thibaud Boutin and Shona Kerr.

With thanks to Cathie Sudlow, Veronique Vitart, Oriol Canela-Xandri and Albert Tenesa for helpful comments.

MRC Human Genetics Unit at the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK

A plan to replicate Mark Davis’s remarkable findings of immune activation in ME/CFS


Chris Ponting

A team led by Edinburgh University’s Professor Chris Ponting has won funding for a PhD student who would follow up and expand on remarkable recent findings made at Stanford University, where Dr Mark Davis may have pinpointed a major issue in the immune system in ME/CFS.

Last year, Davis produced strong evidence of T cell clonal expansion, similar to that seen in illnesses including multiple sclerosis and acute Lyme disease. His discovery came from a new and sophisticated way of looking at the immune system in ME/CFS, which revealed the strongest evidence yet for immune activation in this disease. These results could indicate autoimmunity or a response to infection in ME/CFS, and could point to the core problem in the disease.


Human T cell (photo: NIAID)

So if the results of the PhD work are as hoped then they could narrow down the cause of ME/CFS for some patients. The ultimate aim is for this research to form part of a concerted effort that provides affordable diagnostic tests and targets for treatment.

The PhD will be based at Ponting’s Computational and Disease Genomics lab in Edinburgh. The £90,000 cost of the PhD will be jointly funded by Action for ME and the Scottish Government’s Chief Scientist’s Office. Samples from patients will be provided by the UK ME/CFS Biobank, subject to a successful full application to the Biobank.

Ponting has drawn in impressive collaborators for this project: senior immunologist Professor Georg Höllander from Oxford University and molecular biologist Dr Lia Chappell from the prestigious Wellcome Sanger Institute. I am pleased to say that I have also been involved with this study from the outset and the successful PhD candidate will engage with more patients as the project gets underway.

The immune-system biology behind the study: T cells and their receptors

Many people have heard of B cells and the antibodies they produce; T cells are their cousins. T cells come in many forms, but the relevant ones here are called killer (CD8) T cells. These act like a security force, checking cells and killing off any that look sick because they are infected or cancerous. Much like with B cells and their antibodies, T cells are produced in countless varieties, each version specifically binding to just one molecule (called an antigen). It’s this specific binding that allows a T cell to pick off a cell infected with a particular pathogen (or affected by another problem) while avoiding collateral damage.

Because these varieties are produced randomly, most turn out to be completely useless. But all the T cells hang around, hoping to find a pathogen molecule (antigen) or tumour protein they happen to recognise, like a lock searching for the key that will open it. If a T cell finds its “key”, the T cell is activated and starts dividing to produce identical copies of itself – clones – in a process called clonal expansion. This new army of clones then heads off to target the infected or cancerous cells. And when things go awry with the immune system, T cells can end up targeting a person’s own molecules – “self” antigens – leading to autoimmunity.

Mark Davis’s study was comparing T cell clonal expansion in healthy people with that in several diseases, including multiple sclerosis (an autoimmune disease), and acute Lyme disease (an infection). At a late stage in the project, he won a grant to include samples from ME/CFS patients as well and discovered that clonal expansion in these patients was similar to that seen in these other diseases.

Measuring clonal expansion

But how do you measure clonal expansion? Every cell in a clone shares an identical T cell receptor (TCR) – the lock responsible for recognising the key of a specific molecule on the pathogen or tumour cell. So the process is to laboriously sequence the T cell receptor of every T cell and then count the matches. When a lot of T cells have matching TCRs then this means that there has been clonal expansion.

Mark Davis did this for six ME/CFS patients, and the results are shown in the figure below.

TCR Davis just mecfs

Image taken from a video of Davis’s presentation

The figure takes a little understanding, so here’s what the first pie chart shows. It’s for Patient L3-07. The white area of the chart shows that just over half of the tested cells were unique (no other cells had identical TCRs), indicating no clonal expansion for those cells. The coloured pie slices indicate the scale of clonal expansion. For example, there were two clones with more than 20 copies of the same TCR, as indicated by the two pie slices marked in red. The other coloured slices show the number of copies for clones with fewer copies.

The number underneath the chart shows that this patient’s sample contained 323 T cells.

After examining clonal expansion in ME/CFS, Davis then compared the results for ME/CFS with those for other illnesses. Examples from four patients with multiple sclerosis, ME/CFS, or a recent Lyme infection and from four healthy controls are shown below.

TCR Davis all diseases clearer

Image taken from a video of Davis’s presentation

The contrast between the disease patients – including the CFS patients – and the healthy group is striking. In the healthy individuals, about 90% of T cells are unique, with only a few expanded into clones. The ME/CFS patients look far more like patients with multiple sclerosis or Lyme. This is an astonishing result and, if replicated, could point firmly to the underlying disease process for at least some patients. It could also yield biomarkers.

Mark Davis is already trying to identify the antigen(s) that might be triggering clonal expansion, which could identify self-antigens (autoimmunity) or specific pathogens that have triggered the problem. That could pave the way to developing new treatments.

The new PhD project will use similar but improved technology. Because every cell must be sequenced separately, T cell sequencing is currently very expensive work, which effectively limits how many samples can be processed.

Dr Lia Chappell at Sanger will develop the method further in order to dramatically lower costs, allowing much bigger samples to be analysed, and the technique will be implemented by the PhD student. The goal is to sequence TCRs for 10,000 cells per patient and for many more patients. The initial target is 50 patients and 50 controls but the ultimate ambition is to eventually sequence the T cells for all samples in the UK ME/CFS Biobank, and possibly for other cohorts as well.

How the study came about

Chris Ponting is an old friend and I told him about Mark Davis’s remarkable study when I saw the video about it from last year’s Open Medicine Foundation symposium at Stanford. Chris also thought this work was exciting and important, though I hadn’t expected him to follow up on it with a research project. However, by a stroke of luck, Chris was part of a consortium at the Wellcome Sanger Institute that was looking to find a cheaper way to sequence T cell receptors. The consortium is headed by Höllander with Chappell developing the core technology and both agreed to collaborate with Chris on this new project. Chappell and Höllander are now adapting their technology to suit this new study.

Clonal expansion could be the smoking gun for what’s going wrong in ME/CFS. So if the findings of clonal expansion check out then this work could help to track down the cause of ME/CFS for at least some patients. The new technology being developed could also ultimately lead to an affordable way for doctors to measure clonal expansion, helping with diagnosis.

It’s impressive that Action for ME and the Scottish Government’s Chief Scientist’s Office are funding this important work. Replication is central to establishing robust results, and I can’t think of a more important finding to try to replicate than that of T cell clonal expansion.

There’s a yawning gap in ME/CFS research funding. Take action.

When I got ME more than 20 years ago, I thought that science would soon provide the answers to my illness. Instead, I saw little good research going on, and there’s been a spectacular lack of progress since then. We have no treatments and still don’t even know what causes the disease. Why not?

The fundamental reason for the lack of good science is that there is not enough funding: money is the sun that powers the research world. And inadequate funding is mostly down to neglect by government research-funders. That has to change, and patients can help make it happen.

An outsider might think that an illness that strikes in the prime of life, affecting so many people so severely, would be a priority for governments. Surely the multi-billion pound cost to the economy would focus minds? Not if your illness is ME/CFS, which many people in power don’t take seriously. In the US, research receives a feeble $8 a patient a year. In the UK, it’s £4 a year, which is mostly spent on psychosocial research.

Not enough action from the National Institutes of Health

The US National Institutes of Health (NIH), the world’s biggest funder of biomedical research, had been neglecting ME/CFS for years, but three years ago, it looked like that was all going to change. In 2015, ME/CFS patient, former NIH employee and Washington Post reporter Brian Vastag wrote a powerful open letter to NIH Director Dr Francis Collins that was published in the newspaper.

Collins was clearly moved and started to act. He promised to “ramp up” research funding, and oversaw the establishment of an in-depth, multi-million dollar study of ME/CFS at the NIH’s research hospital.The NIH recently funded three new collaboratives, whose researchers and research programmes are impressive. But the amount of money committed – $7.2 million in the first year and an estimated $36 million over five years of funding – is not. Not from an organisation with a $37 billion annual budget, which recently landed an inflation-busting $3 billion increase. An extra $7 million a year is not enough to address an illness where, as National Institute of Neurological Disorders and Stroke Director Walter Koroshetz acknowledged, “we are 50 years behind” on the research.

Fair funding for ME/CFS

What should the NIH spend on ME/CFS research? One obvious guide is what the organisation spends on illnesses with a similar level of “disease burden” – a technical concept that combines the number of people affected by an illness with how hard it hits them, both in terms of levels of disability and rates of early death.

Mary Dimmock and colleagues estimated the disease burden of ME/CFS, and their estimate is shown in the graph below, which also shows NIH spending by disease burden for a range of illnesses. The straight line indicates “fair funding” – that is, what each illness would receive if research funding was based solely on disease burden.

The graph also shows what “fair funding” for ME/CFS would be: $190 million a year.


Graph, Dimmock et al.; additional annotation by me for legibility

Dimmock and colleagues commented that there is a lot of uncertainty around their estimate, so let’s take a conservative view and assume $100 million a year represents fair funding for ME/CFS research. Disease burden isn’t the only factor driving research spending, though given how little is known about ME/CFS and how little has been spent on it in the past, it’s arguable that the figure should be higher.

Today, funding stands at $14 million a year, even after Director Collins has “ramped up” funding into ME/CFS. That’s a massive shortfall on what’s needed.


What next from the NIH?

On internet discussion site Reddit, Director Collins replied to a question about the slow rate of progress on ME/CFS by saying that “research, done correctly, takes time”. This relaxed attitude drew a strong response from several patient-advocates. Jen Brea, Director of Unrest, tweeted:

“I am probably going to feel like shit for the rest of my life (unless something dramatically changes) because ‘research takes time’ when you fund it with the change you found under the NIH Director’s sofa cushions.”

And Jennie Spotila lambasted Collins in her blog, pointing out that he recently showed far more urgency dealing with another health problem: “When the President asked you in March 2017 to direct the resources of NIH towards the opioid abuse epidemic, you didn’t tell him that you empathized with his frustration and that it would take time. No, you formed thirty new partnerships in 10 months to find new addiction treatments and alternatives to opioids.”

ME/CFS patients are sick of waiting, and now that the NIH has finally woken up to the problem of the disease’s funding, we want it to get on and invest the resources that the problem demands.

Protesting to the NIH directly is one way to press for change, but there are other ways too.

Take action

Even from your bed

Solve ME/CFS Advocacy day 15 May

#MillionsMissing protests 12 May

Find a protest in a city near you.

Brian Vastag believes that the best way to achieve a big increase in funding is to get Congress to earmark funds specifically for ME/CFS. He believes that “The bureaucracy at NIH is too slow and too hard to steer, and without a directive from Congress, boosting ME/CFS funding will be seen by many inside NIH as taking money away from other diseases”.

That’s the nub of the problem: many at the NIH still don’t seem to see ME/CFS as a priority. Director Collins’s push on ME/CFS involved setting up a trans-NIH working group with the apparent aim of bringing in contributions from Institutes, Centres and Offices across the NIH. Twenty-two of these were represented on the working group, but when the rubber met the road only three, including the Collins’s Office, contributed $1 million or more in the 2017 financial year. Of the rest, only the National Heart, Lung and Blood Institute managed as much as $0.5 million, with several groups contributing nothing. There seems to be little enthusiasm for research into our disease across the NIH.

Vastag pointed out that lobbying recently paid off for Alzheimer’s disease, where Congress mandated an extra $414 million a year for research. As he said, it takes a lot of lobbying and consistent pressure on key purse-string holders in Congress so it won’t be an easy route, and certainly won’t be quick. But it might well be the best way.

Days of action: 12 and 15 May

Targeting Congress is exactly what the Solve ME/CFS Initiative (SMCI) is doing. It has recruited a professional lobbyist in its new Director of Advocacy and Communications, Emily Taylor, and has organised a mass lobby of Congress on 15 May to demand action, including more research funding. There will be more than 100 meetings with members of Congress and their staff.

In addition, #MEAction has organised protests all across the US on 12 May (and in other locations worldwide). It hopes to follow the protests with a meeting with Director Collins to put more pressure on the NIH. Find out how you can take part in these actions and the advocacy – even from your bed.

The UK: it’s even worse

Funding across the last decade stands at a feeble £4 per patient per year in the UK, and most of that has gone on psychosocial research. The Medical Research Council (MRC) granted £1.6 million to biomedical ME/CFS research back in 2011, but that work has produced nothing of note to date, and there’s been precious little funding since.

While there is less money available in the UK, the three big funders – the MRC, the National Institute for Health Research and the Wellcome Trust – have a combined research budget of around £2.5 billion. That’s plenty big enough to dramatically boost research into ME/CFS if the will is there.

Some hope?

The CFS/ME Research Collaborative (CMRC) is currently making a big push for more biomedical research funding. The CMRC has already pitched a plan for more money to the MRC and is also talking to other big funders. The CMRC’s Chair, Professor Stephen Holgate, has indicated there will be news by the time of the Collaborative’s September conference.

If the CMRC can’t secure funding, I think charities and patients need to look seriously at what can be done next. Unlike in the US, there is no mechanism in the UK for politicians to direct funds to a particular disease, making it harder to know how to push for more funding. But there will be a #MillionsMissing demonstration targeting the Health Secretary, Jeremy Hunt, and demanding government investment in biomedical research for ME/CFS.

Don’t wait, donate now and get more research, sooner!

The big money is always going to come from government-funded institutions, the NIH in particular. But money from patients and their supporters will also help. The Open Medicine Foundation is leading the way, building up from raising $3 million two years ago to $5 million last year and an estimated $10 million this year. To put that into perspective, $10 million easily beats what the NIH is spending on its new collaboratives in 2018.The SMCI has funded many small studies and has a good track record of its pilot studies being turned into larger, government-funded studies.

In the UK the sums are smaller. ME Research UK, the ME Association, Action for ME between them invest over £500,000 a year between them in biomedical research. Invest in ME Research raised an impressive £500,000 in donations and pledges for one study, its planned rituximab trial, which suggests the potential to raise even more within the UK.

Looking at comparable medical charities in the UK, the MS Society spends at least £5 million a year on research. Even muscular dystrophy, an illness that is ten times less common than ME/CFS (though with much higher mortality rates), receives nearly £2 million a year in research funding from the relevant charities.

Is it possible to raise more for ME/CFS in the UK, perhaps reaching the £5 million a year raised by the MS Society? And if so, how can we all pull together in the UK to make this happen? Donating now would be a good start.

Things won’t change unless we act

Funding for ME/CFS remains abjectly low. Despite some recent modest improvements, there’s no sign of this changing anytime soon. If we want the serious funds for research that are needed to find effective treatments for our illness, then we and our organisations need to act now.

We need to pressure governments to contribute, and we need those patients and supporters who can to donate. It’s down to us.

A new research landscape emerges in America

Things are changing in the US for ME/CFS research as four new collaboratives set up and get to work.

In September last year, the National Institutes of Health (NIH) announced $35 million of funding to establish three new ME/CFS research collaboratives and a supporting data centre. Since then, the Open Medicine Foundation (OMF) has helped to establish a fourth research collaborative, at Stanford, committing $2.4 million for the first two years. It aims to fund the collaborative at similar levels until the work is complete.

So that’s four new collaboratives based at leading institutions, using top researchers and clinicians and backed by a substantial amount of cash. The collaboratives will be using cutting-edge technology and large, well-defined samples of patients. This adds up to a game-changer for biomedical research in the US, putting it way ahead of the rest of the world.

The NIH-funded collaboratives are:

  • The Center for Solutions for ME/CFS headed up by Dr Ian Lipkin and based at Columbia University in New York City.
  • The Cornell ME/CFS Collaborative Research Center led by Dr Maureen Hanson at Cornell University, Ithaca, New York State.
  • The Jackson Laboratory ME/CFS Collaborative Research Center led by Dr Derya Unutmatz and based in Connecticut.

And the supporting centre for the NIH groups is the Data Management and Coordinating Center run by Dr Rick Williams at the Research Triangle Institute in North Carolina.

Each NIH-funded collaborative has been awarded around $10 million each over five years, with around $5 million for the data centre.

NIH director Dr Francis Collins said the collaboratives would “lead to knowledge about the causes and ways to treat people affected by this mysterious, heart-breaking, and debilitating disease”. All the collaboratives have said they aim to understand the mechanisms of the illness in order to develop treatments and to identify biomarkers.

  • The ME/CFS research collaborative at Stanford University will be run by Dr Ron Davis and funded by OMF through donations it receives from patients and supporters.

The four collaboratives

The Center for Solutions for ME/CFS, led by Lipkin, will investigate whether the bacteria, viruses and fungi of the gut microbiome are driving the illness.

Gut microbiome computerThe microbiome could lead to a disease process by firing up the immune system or even by producing chemicals (metabolites) that then get into the blood, where they would affect the nervous system. The collaborative will use state-of-the-art techniques including DNA-sequencing to look at gut microbes, and metabolomics to explore the chemical fingerprints left in the blood by cells or coming from the gut microbiome. The team will also investigate the immune system, including examining antibodies to identify any past infection that might have triggered problems.

The research team will look to see how exercise affects both gene expression and metabolites. The group will mine clinical data to try to identify different types of patients and will develop a mobile app to track patients’ symptoms over time. The collaborative has an impressive clinical team that includes Drs Anthony Komaroff, Jose Montoya, Lucinda Bateman, Susan Levine and Dan Peterson.

The Cornell ME/CFS Collaborative Research Center is combining an exercise challenge with a wide range of techniques to probe what’s happening in ME/CFS. Dr Shungu, who is a professor of physics and radiology, will use brain-imaging techniques. He’ll be looking for signs of neuroinflammation (following up this intriguing finding from 2014), mitochondrial problems and oxidative stress.

Dr Hanson, who leads the Cornell collaborative, is heading down an entirely new path, looking at extracellular vesicles. These are little sacs of molecules – including proteins, hormones and RNAs – that cells release and that fuse with other cells. Vesicles are released in response to exercise and could be contributing to disease symptoms. The team will also probe immune-system functioning by measuring gene expression in different types of immune cells in the blood.

All of these different approaches will be applied both before and after exercise, to identify any differences linked to the cardinal ME/CFS symptom of post-exertional malaise. Professor Betsy Keller, an expert in using the two-day exercise challenge, will co-lead the clinical set-up; expert physicians Dr Susan Levine and Dr John Chia are on the clinical team.


Dr Derya Unutmaz (Photo: Jax ME/CFS)

The Jackson Laboratory ME/CFS Collaborative Research Center is led by Dr Derya Unutmaz. As the name suggests, this collaborative is at the Jackson Laboratory, which might not be well known to patients, but is a well-established, independent, non-profit biomedical research institution that’s been around since 1929.

This collaborative will look to see if the interplay between the microbiome, the immune system and metabolism could be driving the illness. The team will use highly advanced analysis combining clinical and biological data to look for connections and will use the company to develop an app-based patients’ portal to collect and analyse data. Patients will come from Dr Cindy Bateman’s clinic in Utah.

While there are many similarities with the Lipkin project, Unutmaz is likely to approach some things in a different way. He’s an immunologist with experience of chronic inflammatory diseases and a focus on T cells in particular.

Research triangleThe Data Management Coordinating Center will be run by Dr Rick Williams of the Research Triangle Institute in Durham, North Carolina, and Dr John Rowe of Johns Hopkins University. The centre will pool and manage data from all the NIH-funded collaboratives, allowing data from different studies to be compared and combined: the data centre will be providing statistical tools for analysis. The centre will also be responsible for engaging with the wider research community, presumably making the data more widely available.

The ME/CFS Collaborative Research Center at Stanford is led by Dr Ron Davis. One of his impressive team, Dr Mark Davis, has already found clear evidence of T cell clonal expansion, though the findings are yet to be published. Mark Davis believes that the clonal expansion is being driven either by the T cells’ reaction to foreign invaders, such as a virus, or by a misguided response to “self” in the form of an autoimmune response.

He will continue to try to track down exactly what it is that’s firing up the T cells, using some very clever molecular detective-work. The collaborative will also expand its in-depth genetic and molecular study of 20 severely ill patients to include a wider group, to validate and extend the initial, tentative findings.

Finally, there’s Ron Davis’s goal of creating an affordable, accurate blood test for diagnosis and drug-screening, starting by developing the promising nanoneedle technology.


Four collaboratives and a data centre

Concentrating firepower for more reliable results

There’s a striking overlap in the approaches used by the different collaboratives, with two of them using an exercise challenge, two focussing on metabolomics and the microbiome, and all of the groups majoring on the immune system.

The overlap is no coincidence, at least not for the NIH Collaboratives, says NIH Director Collins. Referring to the dead end of XMRV back in 2012, he said, “We want to see immediately if something looks like it’s promising, is it promising really, or another false positive? We’ve had too many of those and we don’t want to make that mistake again.”

Ruling out things that appear good but are not robust, as exemplified by the rituximab trial, is essential for progress in any scientific field.

Patients on board

All of the new collaboratives are working to involve patients. Lipkin’s team has involved the Microbe Discovery Project, #MEAction and the Solve ME/CFS Initiative (SMCI). Cornell also has the SMCI on board as well as patient-activist Erica Verillo. The Jackson group has activist Mary Dimmock, is closely linked to #MEAction and also runs a blog.

Ramping up ME/CFS research?

The NIH is funding its collaboratives and support centre to the tune of $35 million over 5 years, amounting to an increase in NIH funding for ME/CFS research of $7 million a year. That’s a lot less than many patients had expected when Collins pledged to “ramp up” funding for the disease, and does not seem enough given that ME/CFS is poorly understood and inflicts so much suffering on so many.

While the sums invested in the collaboratives aren’t impressive, the quality of the research programmes is. The NIH must have spent close to $100 million on ME/CFS research over the last two decades without having very much to show for it. That could be one reason why the NIH has argued that what’s needed most is to increase the capacity of the field to do high-quality research – and the collaboratives, including the OMF-funded one at Stanford, should do just that.

The groups bring in new talent. All are led by researchers relatively new to the field and are full of scientists who have honed their expertise in other areas, bringing new insights and skills to ME/CFS.

These new centres also bring researchers together to form a critical mass, and the three NIH centres are themselves working together, with plans to collaborate on at least one joint project. Critically, each collaborative also has a strong clinical aspect to ensure they have large cohorts of well-diagnosed patients that will surely be an invaluable resource for the future.

All of these things will increase the capacity of the field to do more high-quality research. That should mean more successful grant applications and more funding.

At worst, the findings that emerge from these comprehensive studies might simply enable the teams to rule out lines of enquiry, enabling the field to move on.

But with a fair wind, the centres could make real, substantive progress in finally understanding the biological basis of the disease, opening up the way to the development of treatments and diagnostic biomarkers.

The collaboratives are creating a new and more impressive research landscape in America. It’s one that should give ME/CFS patients everywhere real hope for progress.

Update: the 5th Collaborative

There will be a fifth collaborative, across the border in Canada. The Canadian Institutes of Health Research has invited researchers to apply for a grant of up to C$1.8 million (US$1.4 million) to form a new collaborative that will work with the three NIH collaboratives on a joint project and share the NIH data centre. The winning bid will be announced in July. Thanks to Cort Johnson for mentioning this in the comments below  

Thanks to Jennie Spotila whose meticulously researched blogs at Occupy ME provided much valuable information for this article.

COMING NEXT: Profiles of each of the four collaboratives

The CMRC embraces the biomedical

Republished from my Facebook page.

In a dramatic move on March 6, the UK CFS/ME Research Collaborative (CMRC) committed itself to a new, biomedical direction. It has started taking concrete action to engage with patients and also announced ambitious plans to enable much more biomedical research in the UK. These changes are enshrined in a statement of purpose, objectives and values (PDF) that replaces the Collaborative’s former charter.


Prof. Chris Ponting

Esther Crawley, the CMRC’s controversial deputy chair, is stepping down from that role and from the board, due to a change in her role at her university. From this April, she will be replaced by Chris Ponting, Professor of Medical Bioinformatics at the University of Edinburgh. He heads the multi-million-pound Biomedical Genomics research programme at the Medical Research Council (MRC) Institute of Genetics and Molecular Medicine.

The CMRC has set out its new purpose as promoting the discovery of the biological mechanisms and causal pathways that underpin ME/CFS, in order to develop targeted new treatments. While the organisation does continue to adopt the “big tent” approach favoured by its chair, Stephen Holgate, and supports research from all research areas, the important difference is that the biomedical part of the tent is now explicitly the priority.

After years of reluctance to engage with patients and their criticisms of psychosocial research, the CMRC will now have at least one patient on the board and wants its Patient Reference Group (PRG) to lead the process of setting its future priorities. The CMRC’s purpose statement invites all stakeholders to help shape its activity and the Collaborative is also looking at how it can consult with patients more widely, beyond its PRG.

  • A data-sharing “portal” bringing together data from many different studies with a total of over two million patients.
  • Networks linking sites across the UK, providing 30 new, state-of-the-art brain scanners, supporting stem cell research and using informatics to co-ordinate the best science possible.
  • A programme of experimental medicine to find out what works, and why – focusing on the most promising biomedical areas.

What’s a research platform and what would one mean for ME/CFS?

The MRC set up the Dementias Platform to scale up UK research efforts on dementia by “bringing together researchers from universities and industry in the fight to develop effective treatments for dementia fast”. The platform has three strands:

  • A data-sharing “portal” bringing together data from many different studies with a total of over two million patients.
  • Networks linking sites across the UK, providing 30 new, state-of-the-art brain scanners, supporting stem cell research and using informatics to co-ordinate the best science possible.
  • A programme of experimental medicine to find out what works, and why – focusing on the most promising biomedical areas.

The CMRC has yet to explain how such a platform would work for ME/CFS and patients will want to hear how this will directly lead to new studies that will uncover biological causal pathways. But if the ME/CFS platform mirrors the Dementias one in attracting large amounts of funding and making an impact, that’s got to be good news.

Will the CMRC’s plans succeed?

Making this happen won’t be easy. However, it appears that the CMRC has already made a promising start. It presented its ideas to the MRC last week and received a “positive” response. And perhaps the most interesting developments of all are hinted at in the minutes of the latest board meeting (PDF):

The CMRC praised the US National Institutes of Health’s (NIH’s) funding of the new centre of excellence collaborations in the USA and suggested the possibility of a partnership with the NIH. It’s not clear if this would mean the NIH funding some kind of collaboration in the UK.

Professor Chris Ponting – a key figure on the CMRC?

He and others have had contact with an individual who is meeting with “a high-level research funder decision-maker” and it appears that this individual has a similar vision to the CMRC.

I’ve never previously heard of such opportunities to directly influence high-level funders or senior politicians. Suddenly, things appear to be opening up, but the minutes give no more information about these opportunities: perhaps it’s too early to divulge details publicly. But these developments may explain the CMRC’s apparent confidence that it can turn its bold plans into reality.

Professor Chris Ponting – a key figure on the CMRC?

What makes the CMRC’s new moves towards a strong biomedical focus so surprising is that previously, patients have felt that the Collaborative has been too enthusiastic about psychosocial research, and very unwilling to engage with patients’ criticisms and concerns on that topic. As a result, there has been a long history of conflict between the two parties. On the Science for ME forum – a good litmus test, since the forum consists of hundreds of patients with a strong interest in good science – there has been a guarded welcome to the new changes from many, usually expressed alongside some scepticism. A minority of patients expressed scepticism only.

However, what has been notable is the support among patients for Chris Ponting as the new deputy chair, and this is particularly pleasing to me because he is my friend: we have known each other for many years and it is fair to say that I am the reason he first took an interest in ME/CFS. As a successful scientist running a large research programme, he certainly didn’t need to become involved in ME/CFS research in order to enhance his career, and I’m very grateful that he was willing to take on the extra work.

He recently helped to present the screening of Unrest at the Scottish Parliament and tweeted his own response to the film, to the approval of many patients:

I asked Chris to comment on the new developments, especially in response to patients’ concerns that the board might just be playing lip-service to a “biological” focus. I also mentioned patients’ worries that the CMRC would press ahead without engaging with patients and the wider community of researchers outside the Collaborative. Chris was travelling but produced this statement on the fly:

“I am very happy to listen to patients’ and carers’ concerns and see whether I can address them. But I only come into my CMRC Deputy Chair role from next month so my views are my own only.

“Having seen first-hand over 20 years how devastating ME can be, it is genuinely exciting to help craft a forward looking research strategy. I expect the CMRC to gather all – often differing – views from researchers and [people with ME] on this research strategy but its focus, as announced, will be biomedical. This is where, I think, I can help having grown into biomedical research from a background that has taken in everything from particle physics to human genetics.

“Once after full consultation we have our science strategy in place I expect us to design a research platform akin to the one for Dementias UK complete with independent oversight and patient advisory groups.

“Genetics, in particular, has revolutionised our understanding of many diseases that have an inherited component. Before we knew the results of Alzheimer’s disease genetics studies, for example, we did not understand that this appears to be a disease of brain immune cells (microglia) and not neurons. Using the same approach, we could find out in what cells ME originates. It would be a major step forward to locate the origins of this devastating disease in human physiology.

“So my own view is that a genetics study would lay down a foundation stone on which other biomedical findings could then be built. There are many and established ways of setting up such a study and we will need to work together as researchers and patients to make this a success.

“This will be only a first step along what could be a long path. Yet this is a journey that I am committed to taking together as quickly as we can.”

Coming from someone who will represent the CMRC, this willingness to engage and to listen, both to patients and other researchers, is a refreshing change. I can also say that this is very typical of him. And on the science side, I thought his comments about the potential of genetics to deliver insights into ME/CFS were particularly interesting.

What does this mean for the future?

Chris’s appointment appears to be just one of many signs of a big, positive change at the CMRC. But patients need the Collaborative to share more information about its plans, to be as open to engagement as it says it will, and above all, to deliver a major boost to biomedical research activity in the UK. Nonetheless, the new situation represents a radical break with the past and looks very promising to me.

For now, we can only watch and wait. But perhaps the UK will finally join the US and other countries in focusing on biomedical research as the way to crack ME/CFS.

Page 1 of 2

Powered by WordPress & Theme by Anders Norén