The Economist
Chronic-fatigue syndrome
A new test may diagnose a mysterious illness, and also help to explain it
Sep 3rd 2016 | From the print edition
·
CHRONIC-FATIGUE SYNDROME, or CFS, which afflicts over 1m people in America and 250,000 in Britain, is certainly chronic and surely fatiguing. But is it truly a syndrome, a set of symptoms reliably associated together and thought to have a single underlying cause—in other words, a definable disease?
CFS’s symptoms—debilitating exhaustion often accompanied by pain, muscle weakness, sleep problems, “brain fog” and depression—overlap with those of other conditions. These include fibromyalgia (itself the subject of existential doubt), clinical depression, insomnia and other sleep disorders, anaemia and diabetes. These overlaps lead some to be sceptical about CFS’s syndromic nature. They also mean many people with CFS spend years on an expensive “diagnostic odyssey” to try to find out what is going on.
Scepticism about CFS’s true nature is reinforced by the number of causes proposed for it. Viruses, bacteria, fungi and other types of parasite have all had the finger pointed at them. So have various chemicals and physical trauma. Evidence that CFS truly does deserve all three elements of its name has accumulated over the years but a definitive diagnostic test has remained elusive. Until, perhaps, now. For in this week’s Proceedings of the National Academy of Sciences Robert Naviaux of the University of California, San Diego, and his colleagues published evidence that the metabolisms of those diagnosed with CFS are all changing in the same way. Their data suggest it is this cellular response to CFS-triggering traumas, and not the way the response is set in motion, which should define the illness. They also show that this response produces a chemical signal that might be used for diagnosis.
Dr Naviaux and his team collected and analysed blood samples from 45 people who had been diagnosed with CFS, and also from 39 controls who were free of any CFS-related symptom. They then trawled through those samples looking at the levels of 612 specific chemicals, known as metabolites, which are produced during the day-to-day operations of living cells.
These metabolite profiles, they found, differed clearly and systematically between the patients and the controls. Some 20 metabolic pathways were affected, with most patients having about 40 specific abnormalities. The biggest differences were in levels of sphingolipids, which are involved in intercellular communication, though other molecules played a role as well. These differences should give clues as to what is happening at a cellular level during CFS. More immediately, a handful of the abnormalities—eight in men and 13 in women—were enough, collectively, to diagnose with greater than 90% accuracy who had the disease.
That is a good start. If this discovery is to lead to a reliable test for CFS, though, Dr Naviaux’s experiment will have to be repeated to compare those diagnosed as having CFS with those who are not so diagnosed yet display some of its symptoms. The answer should soon become apparent, for he is already applying his method to people who have depression, autism, traumatic brain injury and post-traumatic-stress disorder.
One crucial question that needs an answer if CFS is to be understood better is: what cellular changes are these metabolic abnormalities bringing about? Here, Dr Naviaux has already made an intriguing and slightly disturbing discovery. Similar metabolite profiles to those seen in CFS are characteristic of a state known as “dauer” that occurs in one of biology’s most-studied animals, a soil-dwelling threadworm called C. elegans (pictured). In dauer, which is reminiscent of hibernation in larger creatures, the worm puts its development on hold and enters a state of suspended animation in response to threats such as reduced food, water or oxygen levels. It can survive this way for months, though the lifespan of an active worm is mere weeks.
It may be a coincidence, but six of the diagnostic metabolites whose levels are low in CFS are also low in dauer. If it is not a coincidence, though, that suggests a biochemical overlap between the two conditions. If this were true, it could be of great value both in understanding CFS’s underlying biology and (because C. elegans is so well examined and easy to study) in experimenting with potential treatments.
From the print edition: Science and technology
Chronic-fatigue syndrome
A new test may diagnose a mysterious illness, and also help to explain it
Sep 3rd 2016 | From the print edition
·
CHRONIC-FATIGUE SYNDROME, or CFS, which afflicts over 1m people in America and 250,000 in Britain, is certainly chronic and surely fatiguing. But is it truly a syndrome, a set of symptoms reliably associated together and thought to have a single underlying cause—in other words, a definable disease?
CFS’s symptoms—debilitating exhaustion often accompanied by pain, muscle weakness, sleep problems, “brain fog” and depression—overlap with those of other conditions. These include fibromyalgia (itself the subject of existential doubt), clinical depression, insomnia and other sleep disorders, anaemia and diabetes. These overlaps lead some to be sceptical about CFS’s syndromic nature. They also mean many people with CFS spend years on an expensive “diagnostic odyssey” to try to find out what is going on.
Scepticism about CFS’s true nature is reinforced by the number of causes proposed for it. Viruses, bacteria, fungi and other types of parasite have all had the finger pointed at them. So have various chemicals and physical trauma. Evidence that CFS truly does deserve all three elements of its name has accumulated over the years but a definitive diagnostic test has remained elusive. Until, perhaps, now. For in this week’s Proceedings of the National Academy of Sciences Robert Naviaux of the University of California, San Diego, and his colleagues published evidence that the metabolisms of those diagnosed with CFS are all changing in the same way. Their data suggest it is this cellular response to CFS-triggering traumas, and not the way the response is set in motion, which should define the illness. They also show that this response produces a chemical signal that might be used for diagnosis.
Dr Naviaux and his team collected and analysed blood samples from 45 people who had been diagnosed with CFS, and also from 39 controls who were free of any CFS-related symptom. They then trawled through those samples looking at the levels of 612 specific chemicals, known as metabolites, which are produced during the day-to-day operations of living cells.
These metabolite profiles, they found, differed clearly and systematically between the patients and the controls. Some 20 metabolic pathways were affected, with most patients having about 40 specific abnormalities. The biggest differences were in levels of sphingolipids, which are involved in intercellular communication, though other molecules played a role as well. These differences should give clues as to what is happening at a cellular level during CFS. More immediately, a handful of the abnormalities—eight in men and 13 in women—were enough, collectively, to diagnose with greater than 90% accuracy who had the disease.
That is a good start. If this discovery is to lead to a reliable test for CFS, though, Dr Naviaux’s experiment will have to be repeated to compare those diagnosed as having CFS with those who are not so diagnosed yet display some of its symptoms. The answer should soon become apparent, for he is already applying his method to people who have depression, autism, traumatic brain injury and post-traumatic-stress disorder.
One crucial question that needs an answer if CFS is to be understood better is: what cellular changes are these metabolic abnormalities bringing about? Here, Dr Naviaux has already made an intriguing and slightly disturbing discovery. Similar metabolite profiles to those seen in CFS are characteristic of a state known as “dauer” that occurs in one of biology’s most-studied animals, a soil-dwelling threadworm called C. elegans (pictured). In dauer, which is reminiscent of hibernation in larger creatures, the worm puts its development on hold and enters a state of suspended animation in response to threats such as reduced food, water or oxygen levels. It can survive this way for months, though the lifespan of an active worm is mere weeks.
It may be a coincidence, but six of the diagnostic metabolites whose levels are low in CFS are also low in dauer. If it is not a coincidence, though, that suggests a biochemical overlap between the two conditions. If this were true, it could be of great value both in understanding CFS’s underlying biology and (because C. elegans is so well examined and easy to study) in experimenting with potential treatments.
From the print edition: Science and technology