BETHESDA (United States) • Researchers hooked Mr Zach Ault to medical monitors as he slowly climbed onto a gym bike.
An invisible disease is sidelining this once avid athlete and he knew the simple exercise would wipe him out.
But Mr Ault, 36, was pedalling for science at the research-only hospital outside Washington, DC.
Chronic fatigue syndrome is one of medicine's most vexing mysteries. Now, doctors at the National Institutes of Health (NIH) in the United States are using volunteers like Mr Ault for a study that pushes their limits to find out what is stealing all their energy.
Up to 2.5 million Americans are estimated to have what is known as ME/CFS - "myalgic encephalomyelitis/chronic fatigue syndrome".
Its hallmark is profound fatigue, lasting more than six months, made even worse by any type of exertion.
Among other symptoms, patients tend to have difficulty staying upright or cognitive trouble often described as a "brain fog". Many go undiagnosed, misdiagnosed or dismissed by sceptical doctors.
Decades after it was first recognised, scientists do not know what causes it. There are no approved treatments or even tests to help diagnosis - and no way to predict who will recover and who will have a severe case that leaves them debilitated, even bed-bound, for years.
The NIH has more than doubled funding - to more than US$14 million (S$18.8 million) - for scientists around the country to unravel the biology of ME/CFS since 2015, when the influential Institute of Medicine decried "a paucity of research".
Part of the trouble is that varied symptoms make it hard to compare patients.
A patient advocacy group called Solve ME/CFS Initiative is preparing to open a registry where patients can send in medical information and blood and saliva samples to help scientists expand research.
Mr Ault fits the bill for the NIH study, which is focusing on people who came down with the disease after an infection, of any sort, within five years.
The initial infection is long gone but maybe, the body's normal reactions to illness went into a destructive tailspin.
"You're really capturing the disease at a specific point in time", in its crucial early stages, said Dr Sadie Whittaker, scientific director for the Solve ME/CFS Initiative. "No one has studied such a very specific population to such depth before."
There are some clues.
Earlier studies have found brain inflammation in patients and nervous system abnormalities that might explain why they feel worse upright than lying down.
The immune system seems to be on chronic alert.
Then there is the energy drain. Just last month, Cornell University researchers reported that patients' key immune cells do not make energy properly.
The NIH study is looking for more clues. It starts with a week-plus hospitalisation for blood and genetic tests, brain scans, a spinal tap, sleep tests and a check of gut bacteria.
Scientists pore over the results before deciding who to invite back for a longer and more rigorous visit.
"Go as far as you can, work as hard as you can," NIH physical therapist Bart Drinkard told Mr Ault as he climbed onto the exercise bike.
Cells, in particular little factories inside cells called mitochondria, use oxygen and nutrients to create energy.
While Mr Ault pedals, scientists can measure how his leg muscles use oxygen and see if that is different than in a healthy person.
After that, doctors fitted a special cap on him to track electrical activity in his brain and sent him to spend the night in an air-tight chamber.
Pipes draw out the room's air for analysis. How much oxygen is used and carbon dioxide is produced tells how much energy Mr Ault is using, minute by minute.
"We can calculate every molecule," said NIH's Dr Kong Chen, a metabolism specialist. "We're figuring out how his body adjusts to an exercise load or a stress load."
Researchers are clear. The study does not offer any treatments, although the hope is to find targets to eventually develop some.
But Mr Ault says it did help him to learn about the disease and tricks to conserve his energy and pace himself . Until research has an answer, he will "hope for the best, but live for right now".
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