By David Tuller, DrPH
Last fall, a team from the University of Edinburgh released a pre-print called “Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity.” At the time, I posted an interview with the lead investigator, Chris Ponting, a professor of genetics at the university.
The peer-reviewed version of the study has just been published by the journal EMBO Molecular Medicine. According to a press release from the University of Edinburgh, “The largest ever biological study of ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) has identified consistent blood differences associated with chronic inflammation, insulin resistance, and liver disease.” The work involved collaboration between the university’s Institute of Genetics and Cancer and the Schools of Mathematics and Informatics.
The paper has received significant media coverage, including a report in The Times. A BBC article featured the following crisp summary of the implications of the research: “Prof Chris Ponting said: ‘For so long people with ME/CFS have been told it’s all in their head. It’s not. We see it in their blood.’”
The study is a complicated read for non-scientists. In short, the investigators examined levels of more than 3,000 blood-based molecular and cellular traits from a huge healthcare database repository called the UK Biobank. These biobank data were for more than 1400 people who reported having received an ME/CFS diagnosis and more than 130,000 people who did not. The analysis identified 116 traits that were significant among both female and male ME/CFS patients. Some of the findings were replicated in a separate, smaller dataset.
Furthermore, the investigators found that the results were not associated with reported levels of activity. This finding serves to undermine the long-standing theory that deconditioning is a major cause of the symptoms in ME/CFS. That theory, of course, formed the basis of the psycho-behavioral treatment approach embodied in the fraudulent PACE trial’s interventions–graded exercise therapy (GET) and a specialized form of cognitive behavior therapy (CBT).
Per the study: “Evidence of a large number of replicated and diverse blood biomarkers that differentiate between ME/CFS cases and controls should dispel any lingering perception it is caused by deconditioning and exercise intolerance.”
Although the study revealed population-level differences in the biomarkers between cases and controls, the investigators stressed that these biomarkers cannot currently be used to distinguish individuals with ME/CFS from those who don’t have it. However, they stressed the importance of expanding on their investigation, noting that the findings should help to “accelerate research into the minimum panel of blood traits required to accurately diagnose ME/CFS in real-world populations.”
The UK’s Science Media Centre, which has a long history of endorsing the discredited claims of the GET/CBT ideological brigades and whose former head compared critics of the PACE trial to Nazis, responded by posting two expert comments. One was from Alan Carson, a professor of neurology at the University of Edinburgh, a PACE truther, and a leader in the field of functional neurological disorder (FND). (Professor Carson blocked me on then-Twitter long ago because I criticized unwarranted claims from him and others about research into FND prevalence, diagnosis, and treatment.)
In his comment, with its snide and snippy tone, Professor Carson comes across as somewhat aggrieved. That wouldn’t matter much if he were right on the facts. But he is wrong. His main complaint is that, since the study investigated more than 3,000 traits, it “is not very exciting” that 116 would appear to be significant; that would happen by chance alone, he claims. This is false. Oops!
When a study involves a large number of tests, standard practice is to use specific statistical methods to reduce the likelihood of positive results arising by chance. Professor Carson apparently did not recognize or understand that the investigators took such steps to correct for the number of tests they conducted. His comment can be dismissed outright on the grounds of cluelessness. It is disturbing that the SMC has not acknowledged this indisputable error.
Luckily, the other expert—Professor Kevin McConway, an emeritus professor of applied statistics at the Open University–offered an extensive, thoughtful, and cautiously positive review of the study. As he noted:
“I think this is an important piece of research, but it’s also important to be careful not to claim too much from its findings. There’s a lot more to do.
“The press release and the research paper both make it clear that these findings could help in finding a set of blood biomarkers that can reasonably reliably distinguish people with ME/CFS from those who do not have that condition, but that, without a lot of further work, the findings do not in themselves provide such a set of biomarkers.”
