The 12th Invest in ME Conference, Part 1

OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.

IIMEC12The 12th Invest in ME International ME Conference (IIMEC12) was held at One Great George Street on Friday June 2nd, 2017.

You can view the full conference agenda (with photos and biographies of the speakers) here and the Conference Journal is available to download as a PDF or to view as a Flipbook. The highly-recommended DVD of the conference, which includes David Tuller’s pre-conference evening dinner presentation, as well as all of the presentations at the public conference, is now available for pre-order. BurnA tweeted the conference live for Phoenix Rising. Dr. Rosamund Vallings wrote the official IiME conference report.

This article covers the introduction from Dr. Ian Gibson, the two keynote speeches from Professor Ian Charles about the UK Centre of Excellence and Dr. Vicky Whittemore on NIH Research into ME, Professor Nancy Klimas’ talk about her direct patient participation genetic study, Dr. Jakob Theorell’s Swedish/Norwegian study on NK and cytotoxic T cells, Professor Warren Tate from NZ on his ‘precision medicine’ intense study of two small cohorts, and finally, Professor Ron Davis on his approach using innovative technology while studying severely ill ME patients.

Health Warning: I am not a technical person and have no scientific training, but I have done my best to include some of the details from the presentations. Apologies to the researchers for my mistakes and misunderstandings. I will be happy to hear about corrections from the many PR attendees and amend the article accordingly.

Dr. Ian Gibson (Chair): ‘Welcome to #IIMEC12’

Photo of Dr. Ian Gibson
Dr. Ian Gibson

Dr. Ian Gibson is a genial and amusing master of ceremonies. He kept things moving along at a brisk pace — essential with such a jam-packed agenda.

He is fully aware of the injustice and the politics affecting PWME, with his long involvement as a supporter. He remarked on what a happy, positive conference it is.

Everyone is excited and friendly — a big contrast to other big meetings he has chaired, because everyone REALLY wants to be there.


Professor Ian Charles: ‘Opening Keynote – A UK Centre of Excellence for ME’

Photo of Professor Ian Charles
Professor Ian Charles

Professor Ian Charles kicked off the day with an enthusiastic keynote speech about the development of the UK Centre of Excellence for ME in Norwich. The Norwich Research Park will have 3000 scientists, 14000 students and six major institutions, including a hospital.

The idea is a campus where communication and collaboration can thrive, working with the food and health (pharma) industries. There is a sparkly new building going up for the Quadram Institute, where they will focus on both basic research and translational science.

The initial focus for the Quadram Institute is going to be on the microbiome. As well as ME/CFS, they will also be looking at how our microbes influence other disease states such as obesity, diabetes and heart disease. The research will be very much human-based rather than animal, and as they will be doing up to 40,000 endoscopies a year onsite, they will have a huge number of samples with every patient potentially a research subject.

Apparently, Norwich is a really good location for this sort of research because it has a relatively static and ageing population, with good medical records ideal for quality metadata. They are currently grappling with issues of data accessibility and standardisation, looking at cloud-based technology, etc.

The new building is going up now and they expect to be fully moved in by the summer. Patients want to see a dedicated area of the building devoted to ME/CFS, to provide a focus for the work and for fundraising, as happens with cancer units. As usual, it all comes down to funding to ensure the ME Centre of Excellence gets its proper share of the Quadram Institute pie!

Dr. Vicky Whittemore: ‘Keynote Speech – NIH Research into ME’

Photo of Dr. Vicky Whittemore
Dr. Vicky Whittemore

Vicky Whittemore was presenting for a second year in a row, her keynote speech giving an overview of the NIH work in progress. She stressed that NIH director Francis Collins is “unbelievably committed” and a strong advocate for ME/CFS. It has been difficult with ME/CFS not having a ‘home’ at NIH, but now she feels it has 24 ‘homes’ in the institutes participating in the trans NIH Working Group.

Not much new news in this presentation, but to recap: there are two main parts to NIH’s effort on ME/CFS, firstly the intramural study led by Dr. Avi Nath (40 ME patients, 20 healthy controls, 20 recovered Lyme patients). The second round of patient visits, to do exercise and PEM testing will begin this summer and fall (autumn). The second part of the NIH programme is the extramural research based at a variety of locations around the United States and internationally.

NIH seminars are being held every month or two on various aspects of ME/CFS to educate and give perspective for both intramural and extramural researchers. The trans NIH Working Group meets monthly and implements goals and strategies to stimulate and support research.


  • The seven administrative supplement awards which extended the scope of existing projects
  • The numerous high quality responses to the RFI from UK stakeholders after Vicky’s attendance at last year’s IiME conference.
  • Common Data Elements projects led by Beth Unger are being set up with patient and advocate input, and there will be opportunities for further public comment
  • International collaborations and discussions, for example, with the Canadians
  • Funding was up from $6M to $8M in 2016, and it will go up further in 2017. She knows there is still a long way to go on funding.
  • NIH Funding Opportunities (FOAs) were issued in January this year to fund three U.S. Centres (and 1 data centre?)

NIH focus is on etiology, pathogenesis, subsets, longitudinal work, outcome measures and treatment targets. There are no clinical trials planned in the next five years but that is the eventual goal. They were thrilled with the number and quality of applications. Review will begin in July, and hopefully funding will begin in September, 2017.

Personal commentary: This is the only presentation in the conference I found irritating. I’m sure Vicky is working very hard to turn around the attitudes and practices embedded by decades of neglect, so I don’t blame her, but I do feel NIH is ‘lurking’ at the back of the research pack. I think they should be trying to lead more strongly to make up for their scandalous treatment of our disease.

It’s good that things are improving at NIH, but I don’t see these funding increases as in any way adequate and I am not pleased to hear clinical trials are at least 5 years away and therefore access to treatments for the bulk of patients could be a decade away. NIH seems half-hearted, not fully committed to me!

Professor Nancy Klimas: ‘Genetic Signature Study’

Photo of Professor Nancy Klimas
Professor Nancy Klimas

Nancy Klimas had presented at the Colloquium earlier in the week, and for us Conference attendees, there was a change to the published topic as she spoke on investigating Genetic Risk in ME (and Gulf War Illness) with her “nearly zero dollar project.”

Gene mutation surveys need to study huge populations to find anything meaningful: 30,000 people as a minimum in a complex illness. Funding and methods are a big problem with these huge studies, which also involve lots of disciplines such as immunology, genomics and bioinformatics. But they could answer really important questions about diagnostic markers, risk, subgrouping and possible therapeutic targets.

So the team looked at how to do an “all virtual trial” where patients “donate data not dollars” using social media, online consent, online validated instruments (questionnaires) and existing genetic testing kits already available to the public like 23andMe or

This study began as a fellowship summer project, and Nancy still leaves the social media to the younger members of the team. Taking this approach has brought a lot of advantages. It’s a way of engaging the next generation of researchers, getting global coverage with data from a lot of different countries and ethnicities, and also partnering with the patient/advocate community.

Patients can easily be signed up and contacted for future studies, and it is a good way to tap into the patients’ healthy and sick family members whose data is particularly useful.

Current state:

  • Got IRB approval for the project in an unprecedented six weeks
  • The software was set up and beta tested
  • 600+ global participants made contact, from the US, Australia, New Zealand, UK, Ireland and Italy, of whom 50% have downloaded data
  • Preliminary data analysis has begun

Taking an initial look at this data has highlighted exactly what you would expect: sugar/energy pathways, calcium channel signalling and immune regulation (NK cells and B cells). The surprises and profound findings will not come until they have data from large numbers of patients. The data needs to lead the way.

The data provided by 23andMe and similar packages is not perfect, they have had to sift out the SNPs which might affect appearance rather than health, for example. A big challenge is that old bugbear — ME criteria.

Nancy is hoping that the data from expert-diagnosed individuals will help validate survey responses and help identify outliers who may be wrongly diagnosed patients. She is also keen to get funding to subsidise the genetics kits, reducing the financial barriers to ME patients’ participation.

Above all this needs to GO VIRAL to get the participant numbers. She asked for all patient online spaces to help publicise the project, and is actively partnering with Solve/CFS, The Open Medicine Group, etc. Jen Brea volunteered to help by providing questionnaire translation services.

Personal Commentary: I like that Nancy Klimas is trying to unlock direct patient community research  partnership. I think a lot of patients want to be able to contribute, and money is such a barrier for us. Should PR contact Nancy’s team and ask them for an article about this? There is already a PR thread with a few early adopters, but it’s pretty low-key.

Dr. Jakob Theorell: ‘Studies of NK cells and cytotoxic T-cells in ME patients from one Swedish and one Norwegian cohort’

Photo of Dr. Jakob Theorell
Dr. Jakob Theorell

Dr. Jakob Theorell is on the MD-PhD program at the Karolinska Institute. He presented on his two-centre Norwegian/Swedish study looking at NK cells and cytotoxic T cells in ME patients.

He started with a quick immune 101 review — (that works for me!) — T cells are part of the adaptive immune system, they have the individual’s memory of pathogens, developed over a lifetime. NK cells are part of the innate immune system, pre-programmed with “species memory” of immune threats. So for these types of cell, what they do is similar (killing foreign cells) and they use a similar mechanism. They also release pro-inflammatory cytokines.

For these cells to do their job properly, they need to have their perforins and granzymes present and able to be released. If they are able to latch onto a pathogen but not kill it because of some impairment, you get what Jakob described as “immune frustration,” where there is more and more signalling without the ability to kill the intruder. The whole immune system spins out of control.

For a long time, medicine has recognised genetic diseases of cytotoxic lymphocytes (sometimes caused by a single mutation) which are expressed soon after birth and are fatal if not treated. But now researchers are identifying and studying more subtle immune impairments which can reveal themselves later in life. Jakob’s hypothesis is that a substantial subset of people with ME have impaired lymphocyte toxicity, that they are unable to deal with pathogens (or perhaps other immune insults??) properly.

Jakob went on to describe some, perhaps controversial, negative results. He found no significant difference between patients and controls in their levels of perforins and granzymes, nor with cytotoxic granule release under his test conditions. Surprisingly, there was no difference in cell-killing ability either. But like a good researcher does, he started looking at why this might be (rather than inventing myths about false illness beliefs).

Perhaps the freezing, thawing and resting of cells before testing had differentially killed off “sick” or impaired NK cells, leaving only normal ones which would behave … well … normally. But there was no difference in the percentage of NK cells between ME patients and controls, so this seems unlikely.

Perhaps some serum factor makes the NK cells functionally incompetent in patients, but not when cells have been separated out. Jakob didn’t test for this, but recognises the importance of this for future experiments (and I think it was Mary Ann Fletcher who reinforced the importance of whole blood assays in the Q&A session).  There are many candidates for the serum factor in Jakob’s view, as NK cells have a wide variety of receptors (including lactate and adrenaline) and are regulated by many things.

He speculated that adrenaline could be an important factor here. Adrenaline is known to be important in inhibiting NK cells, and getting to a doctor’s surgery/office is such a major effort for ME patients they are likely to be running on adrenaline or, as he put it, having a major catecholamine event.

It’s well known that ME patients have HPA dysfunction and he did find one difference in his experiments — the ME patients’ cells were less responsive to adrenaline. This is only a small study, but he suggested this is a worthwhile angle to follow up.

Personal Commentary: Jakob spoke fast and had quite a strong Norwegian accent (there was some banter about him being Norwegian and his supervisor Swedish, so I hope that’s right). But I got the impression that he was both a clear thinker and a good communicator. I enjoyed his presentation a lot, despite it being right at the limit of what I (as an absolute lay person) can understand.

It’s really important that young researchers get ahead in this field, and as other presenters also pointed out during the conference, negative results are important and can tell us much, not least about methodology. So well done, Jakob!

Skipping forward to the afternoon …

As we went into the final session of a busy day, the patients were tired, of course (and my writing thumb was completely unbendable) but we were all looking forward to hearing from two researchers who have the strongest personal interest in the field — trying to help their sick children.

Professor Warren Tate: ‘Intense molecular study of well characterised patients to understand the acute phase, perpetuation, and relapse/recovery cycles in ME/CFS’

Photo of Professor Warren Tate
Professor Warren Tate

First of all came Professor Warren Tate from New Zealand, an experienced and successful researcher, but perhaps less well known than some. His daughter became ill at the age of 14 not long after an EBV infection, and from being a vibrant and “intimidatingly bright” teenager became quite severely ill, unable to maintain homeostasis. Her glucose levels fluctuated wildly, she became allergic to much of her normal diet, and her cognitive dysfunction was marked.

As a researcher, Warren thought about this analytically: What physiological control centre dysfunction could cause such severe and diverse symptoms? Why doesn’t it resolve? What triggers relapse cycles? And later on, at a more hopeful time, Why do her symptoms improve so markedly with pregnancy? He was impressed with Olav Mella’s observation earlier in the Conference that when people respond to Rituximab or Cyclophosphamide, all their symptoms improve together.

Of course, he reviewed the published results in the ME field and he concluded that he had jigsaw pieces but no picture was emerging. He needed to make a new start and not do more research with a narrow focus. With his background as a molecular biologist he decided to make an intense molecular study of some well characterised patients (diagnosed by Ros Vallings, the NZ expert) to understand the acute phase, perpetuation and relapse/recovery cycles in ME/CFS. He describes this as a precision medicine approach utilising genetic, genomic and other technologies, which should have relevance for diagnostic tests as well as better therapies and patient management.

New Zealand is a small country (less population than Scotland, geographical area similar to the UK) and research funding is always scarce, so Professor Tate had to conduct a tightly budgeted study trying to get insight into the dysfunctional pathways. He used two small (10 patients,10 controls in each)  geographically separate cohorts (Dunedin on the South Island and Palmerston North on the North Island).

The first cohort had data collected on their immune cell transcriptome (expressed genes) and proteins (proteome) as well as plasma microRNAs and cytokines with the aim of getting insight into the physiological changes.  He found that IL8, IL7 and IL13 were all elevated and of 781 microRNAs 2 were significantly elevated and one significantly decreased. In the transcriptome there were 2200 genes upregulated and 850 downregulated which is a major change in the molecular biology of immune cells. A number of important biochemical pathways were modulated, and the results were consistent with his cytokine and microRNA results.

Enriched: Immune, Inflammatory, Cytokine, Apoptosis

Decreased: mitochondrial function, general metabolism especially in the transcriptome, lipid metabolism was dramatically affected.

The second cohort (which was piggy-backing on an exercise intolerance study by exercise physiologist Lynette Hodges) looked at cytokines and microRNAs, which are key to the control of physiology.

The Exercise Intolerance study had patients on the exercise bikes at 15Watts and increasing 15Watts per minute until they had to stop. Blood was taken before exercise, day 1 after exercise and day 2 after exercise session. ME patients’ heart rates and power output were lower on day 2 (especially the power) which was the reverse of what was seen in MS patients and controls. At the molecular level, ME patients’ cytokines generally moved in the opposite direction to the controls.

Warren also talked about his candidate for a simple diagnostic test based on blood, something called PKR (Protein Kinase Receptor). This is in a clearly different molecular state depending on whether the immune system is activated (it becomes phosphorylated, known as high p-PKR). The different ratio of phosphorylated (activated) PKR to non-phosphorylated PKR in the lymphocytes of ME patients was almost significant, despite the small sample size of 10 patients.

Warren is currently extending both studies to include mitochondrial function and epigenetic changes in the DNA, following the recently published research suggesting energy delivery and change in expression of specific genes might be important factors in physiology changes of the chronic phase. His next move is to do a longitudinal study, with the potential biomarkers, still using a small number of patients.

When asked about how his daughter got on after her pregnancy, Warren told the conference that she maintained her improvement for a year while breastfeeding, and then relapsed. The transition was difficult (he mentioned that she had seizures again, I think) but her baseline has stabilised higher than it was before the pregnancy. He has two other patients with regular relapse/recovery cycles and thinks this phenomenon is worth investigating.

Personal commentary: I found this talk very interesting because, even though I live in NZ, I had not heard Professor Tate present before. With his strong motivation and the personal details about his daughter’s illness, it was a very human and moving presentation.

Who knows where the next breakthrough will come from? It might be this Professor from the little islands a long way from anywhere. 

Professor Ron Davis: ‘Big Data Approach: Severely ill ME Patient Cohort’

Photo of Professor Ron Davis
Professor Ron Davis

The conference finished on a real high note with the presentation from Professor Ron Davis of Stanford University in California. Although his son has been very severely ill for a long time, Ron still joked “how can I get my son pregnant?” His wide-ranging talk covered health politics and high-tech business, as well as ME research.

Ron thinks it’s tough to get grants because so many people don’t believe ME exists, and Vicky Whittemore of the NIH tries to help, but he is dependent on private donations. His approach is to focus on progress towards treatments rather than publications, and he puts his data up on the website for everyone to see, avoiding publication delays and the bias against negative findings.

The Stanford Genome Technology Center develops innovative technologies to cut health care costs. As they identify gaps in knowledge, they build technologies to solve the research problems (for example cheap, electrical biosensors). They have set up 34 technology companies as a result of their research with a 100% success rate, and have good relationships with other tech companies. Ron also highlighted that as tackling ME requires coverage from a lot of disciplines, so the Open Medicine Foundation advisory board covers a very wide range of experts (including some Nobel Laureates).

Ron’s focus is on genetics, and particularly on T cells, as other people are working on B cells. His latest study looked at 20 severely affected patients and 10 controls from eight families with multiple people affected. Using unaffected family members as controls is particularly helpful, as they have lots of shared genes and a shared environment which takes out some of the genetic variability introduced by randomly selected healthy controls. He hasn’t found any hugely striking results, but emphasised the value of negative findings.

He described himself as trying to find the best guess to go after.

Do ME patients have a lot of DNA in their blood? Yes, but not as much as cancer patients, for example. Not enough for a biomarker. With multiplex viral sequencing he didn’t find much, no viruses were detected in most of his ME patient sample, just TT viruses. (Everyone has TT viruses, though at least that was a positive control on his methodology — in fact, ME patients’ levels were a bit lower probably because of our immune activation).

Do we have fewer mitochondria? Not really. He looked at cytokine levels and found that severe patients had higher levels, but nothing surprising there either.

Looking at metabolites, he found patients were more than 2 standard deviations lower in 183 metabolites, even though all the standard doctors’ tests came back normal. There is an issue of inconsistency with the Naviaux and Metabolon results though, and he needs to look at their methods to sort this out.

Ron knows that once there is an easy inexpensive biomarker, it will help both patients and research (as they can work with a more homogeneous set of patients). And since they are very much about leveraging biotechnology, he talked briefly about a Bluetooth smart sweat sensor which can measure lactate, glucose, sodium and potassium and induce sweat electrically so that ME patients don’t have to exercise.

Ron also spoke about stem cells, and a modification to an iPhone to turn it into a diagnostic device for measuring the weight of white blood cells. He talked about reducing the cost of a cell sorter assay from $150,000 to 5c a time.

Then he talked in more detail about the Nanoneedle, which was originally developed to test for sepsis and monitor whether antibiotics are working — important in this age of antibiotic resistance. It takes 200 measurements a second and has 2500 electrodes per cm, so the cells in a sample can move around — it doesn’t matter. Although state-of-the-art technology now, this is a potentially cheap real-time device that could also be useful for ME/CFS drug screening ahead of clinical trials. They plan to test all FDA drugs and some herbals at a variety of concentrations, including low doses.

Then Ron talked about some positive results. Measuring ME patients’ cell electrical impedance under normal conditions, they look the same as controls’ cells, but when the cells are stressed (from an increased salt concentration) you see quite a different response curve. So then they tried switching healthy cells into ME plasma and ME cells into healthy plasma and, sure enough, the ME cells in healthy plasma react almost like healthy cells — there is a really quick change in their reaction. So they deduce that the problem is in the serum not the cell, and it could be an antibody, among other things.

Ron described himself as “a shy person,” but he has realised that it is really important to raise the public profile of ME/CFS and make it visible. He knows the patients are often trapped in their homes, but we need to get the CDC and every country’s health system behind us somehow. He really values patient collaborations and mentioned Ben Howell, who is bedridden in the UK when he could be helped by the health system, and Jaime, who runs assays in his lab. He feels he has won over the Dean at Stanford, who is now a strong supporter.

Ron thinks that cracking ME/CFS may have an impact on all chronic diseases, because they share so many similarities. It will be embarrassing one day to governments that they have ignored something so significant for so long. He is optimistic, but thinks this is a hard disease to solve. It’s encouraging for him to hear about so much good, hard work going on.

In the Q & A, Ron was asked about the Naviaux hypothesis. He finds it very reasonable and is leaning in the same direction. There was also a lot of discussion about Suramin (used to kill trypanosomes in Africa) which he feels needs to be trialed in ME/CFS. It’s an IV drug which has a long half-life in the body. Its side effects at typical concentrations are not extreme. It’s dirt cheap, but he is having difficulty getting hold of it. (An audience member volunteered to help there.)

Ron was also asked in the Q&A to speculate why NIH have been unhelpful — for example, by not funding him. Ron thinks that the NIH are in the hot seat and get yelled at unfairly, although, like everyone, he gets annoyed when his grant applications are turned down.

The NIH can only fund 10% of studies, when in fact 90% should go ahead, and because of this the review process ends up nitpicking — looking for trivial flaws to justify turning people down. Medical research is not well enough funded and there is too much focus on publication rather than helping people.

Personal Commentary: Despite his low-key style, Ron is a very powerful presenter. For the best of reasons, he is a man in a hurry and is impatient with bureaucracy and blockers and the PACE crowd in the UK who are harming patients. On his side, he has advanced innovative technology and a wide network in the tech sector, a quality team at OMF and combines this with personal determination and empathy. It is heartwarming that he is so committed and sees things so clearly. His presentation was a great finale to the Conference day.

COMING UP SOON: In the other two articles in this series, MEMum covers the presentations by Don Staines, Jo Cambridge and Fane Mensah, Simon Carding’s Norwich PhD students, Mady Hornig, Olav Mella and Ingrid Rekeland (covering for the injured Oystein Fluge), and Over The Hills reflects on her experience as a patient attending the conference.



Share this!