ME Action news article, by Simon McGrath, 4 June 2016: Ron Davis: Preliminary data shows problems with energy metabolism
Professor Ron Davis presented new findings from his Big Data study at Friday’s Invest in ME 2016 conference. Davis’s preliminary data show serious problems with the biochemical processes needed to convert sugars and fats from food into energy the body can use. If these findings are replicated, this could prove a major step forward in understanding ME/CFS.
Davis’s study is unusual: it’s small with just twenty patients and ten controls, yet generated two billion data points; in fact, the researchers’ biggest problem is dealing with so much data.
The strategy for the study was to focus on severely ill patients because their biology would show the greatest differences compared with healthy controls. In the past, bedbound, severely ill ME/CFS patients have often been viewed as simply too difficult to study, rather than as key to making progress.
The purpose of the study was to collect a prodigious amount of data and use it to identify biomarkers. The study examined a huge number of aspects of patient biology including immunology, proteomics (the production and interplay of proteins), and gene expression. But the main finding revealed at the conference related to metabolomics, the “systematic study of the unique chemical fingerprints that specific cellular processes leave behind”. Metabolomics can help to reveal what’s going on, and what’s going wrong in cells.
Metabolomics is very expensive because it needs some very high-tech equipment, and that limits sample size. The study was only possible because the work was done at cost by new company Metabolon. In fact, Ron’s son Whitney Dafoe was the first person ever studied using Metabolon’s new process. So far, just three sick patients were studied, and were compared with 43 controls.
Tiny sample, huge differences
To find a meaningful difference in such a small sample would usually be impossible – only an enormous difference between patient and controls could be statistically significant because so much variation could be down to the “random noise” of chance. In this case, the differences were vast enough to be considered significant; and, as Professor Davis told the audience, studying three people is not a big study but in personalized medicine, you can learn from just one patient.
Professor Davis illustrated just how big the difference is by using standard deviations, the most common measure of differences in science. The standard deviation is a measure of how much the data within a sample varies on a particular variable, such as people’s height or blood sugar. At least one data point from Whitney Dafoe’s energy metabolism molecules was 16 standard deviations away from the average of the control group. To put that into perspective, 99.7% of all data should fall within three standard deviations away from the average in either direction, and only 0.3% beyond that boundary. The more standard deviations the data is from the average, the less likely that the difference is due to chance. Findings from ill patients that are sixteen standard deviations away from the average in healthy patients is extraordinary.
The metabolomic data in the three patients who were examined highlighted that the main metabolic engine of energy molecule generation – the citric acid cycle in mitochondria – isn’t working properly. Glycolysis also does not look like it’s working very well in patients.
Researchers were able to determine these errors by looking at the molecular byproducts of the cell and noting abnormalities in the compounds usually consumed and generated by these reactions. The basic biochemical process to turn sugars from food into energy molecules just wasn’t delivering for patients.
This might not surprise many patients, but it’s big news in the world of ME/CFS research. There have been findings along these lines before, notably on the second of a two-day maximal exercise test (the day one test results look normal), and in a study on the products of glycolysis in the blood and urine of ME patients by Christopher Armstrong and colleagues.
More research is needed to replicate these findings, and such a study is already in the works; but this could be the start of a dramatic shift in the field.
Ron Davis, who has previously studied patients with physical trauma also noted that mitochondria “shut down” in these patients and said that a key question is why they don’t start up again in ME/CFS patients.
Davis said that his son Whitney showed errors in B-vitamin metabolism, resulting in a very rare deficiency of biotin; this is important, because enzymes in the citric acid cycle are dependent on biotin. In another patient, tryptophan metabolism was a problem.
Professor Davis’s talk generated excitement both at the conference and among those following the Twitter coverage. His wife, Janet Dafoe, commenting on his talk, said that his team hoped to work quickly towards tests for personal biomarkers for all patients. She said of the research,
“We know it’s frustrating and that people are rightfully chomping at the bit! So am I! Every morning… when I wake up, he brings me coffee and I quiz him about what has happened that day so far. I wish you could all be flies on the wall. It’s so exciting. If everyone knew all of what he’s doing, I can’t believe he wouldn’t get big funding.”
Donations can be made to Professor Davis’s work via the Open Medicine Foundation. Janet Dafoe has noted some confusion in regards to the OMF, the OMI, and the CFS Research Center; donating to the Open Medicine Foundation is the best way to make contributions.
And get your conference DVD here!
Invest in ME has just published its annual journal, which includes abstracts from the conference.
Please note that this article is based solely on tweets from Phoenix Rising’s team and Maija Haavisto, who were at the conference. Huge thanks to them: tweeting on the fly about a technical presentation is not easy. The article has not been checked with Professor Davis, and any errors are ours. Jaime S and Alex made significant contributions to this article.
