The most anticipated speaker late last month at an international conference devoted to the mysterious malady commonly known as chronic fatigue syndrome (CFS) was not a scientist with a hot new finding—although there was excitement about new research in the air. Rather, it was a National Institutes of Health (NIH) official bearing good news to a community that has long existed on the margins of the biomedical research establishment. Vicky Whittemore, the agency's CFS point person in Bethesda, Maryland, delivered on a promise that NIH Director Francis Collins made last year by announcing that NIH spending for research on the poorly understood disease should rise to roughly $15 million in 2017, doubling the estimated $7.6 million handed out in 2016.

What's more, the NIH emissary said to those gathered here, the biomedical agency will in December solicit CFS proposals from outside scientists to establish several collaborative centers for basic and clinical research, and another center to manage their data on the illness. The calls for applications, which will come with dedicated funds from the planned budget increase, are the first of their kind for CFS from the United States's major medical research funder since 2005. "There is a shifting tide at NIH with regard to ME/CFS," Whittemore told the conference, incorporating the term that many with the multisystem illness prefer. (ME stands for "myalgic encephalomyelitis," and the meeting was convened by the International Association for CFS/ME.)

Some scientists working on the disease agree. "The fact that there is a budget for it at all means that the agency is taking it seriously. And it's not coming only out of Francis Collins's discretionary fund, but from the individual NIH institutes," says Ian Lipkin, an immunologist at Columbia University, who serves on the Advisory Committee to the Director, Collins's key group of external advisers. Lipkin is also a principal investigator, with Columbia psychiatrist Mady Hornig, on a $766,000 grant from NIH's infectious diseases institute to collect samples from hundreds of patients and controls, looking for biomarkers that could be used to diagnose the disease and searching for clues to its causes.

It has been nearly 3 decades since a group of researchers led by the U.S. Centers for Disease Control and Prevention (CDC) coined the term "chronic fatigue syndrome" after an investigation of two outbreaks in the United States. Typified by exhaustion that commonly worsens with physical, mental, or emotional exertion, the condition is also often characterized by short-term memory and concentration problems and profound fatigue that sleep does not relieve. Sufferers may experience widespread muscle and joint pain, immune system problems, headaches, and many other symptoms. The onset of the disease frequently follows an infectious illness.

Ever since it was given a name, many researchers and physicians have viewed the malady, which has no Food and Drug Administration–approved treatment and no diagnostic test, as psychosomatic. Then, in 2015, the Institute of Medicine (IOM) dismissed the "misconception" of the disease as psychological in a report informed by a review of more than 9000 articles from 64 years of medical literature. "Remarkably little research funding has been made available to study the etiology, pathophysiology, and effective treatment of this disease, especially given the number of people affected," the authors noted. CDC estimates that ME/CFS affects more than 1 million Americans, a majority of them women.

The IOM report "had an unbelievable effect," because it validated patients' experiences—"it told them that they weren't crazy," says geneticist Ronald Davis, who directs the Genome Technology Center at Stanford University in Palo Alto, California, and was one of the report's 15 authors. Davis became a passionate advocate for ME/CFS research and shifted his own studies to the topic after his now 33-year-old son fell ill with ME/CFS in 2008; he is now bedridden. "It also did a lot to NIH and the CDC, who had been ignoring this disease."

Not long after the IOM report was published, NIH issued its own written assessment, concluding that research has neglected many of the biological factors behind ME/CFS and urging more basic science aimed at teasing out the mechanisms of the disease. Collins also announced a "strengthening" of the agency's ME/CFS effort. He moved oversight of the research out of the agency's small Office of Research on Women's Health and into the $1.7 billion National Institute of Neurological Disorders and Stroke (NINDS), and launched an intramural study that began enrolling people late last month. Forty patients who have developed the disease within the last 5 years, after an infection, will be run through a battery of exams at the Clinical Center, the NIH's research hospital. The assessments, from exercise stress tests to brain magnetic resonance imaging tests, will probe the biological and clinical characteristics of the disease—for which there is not even a broadly agreed-upon definition. For comparison, the study will also include healthy controls and people who have recovered from Lyme disease, which can cause similar symptoms.

The disease remains a beggar when it comes to budget. Deborah Waroff, retired Wall Street energy analyst

Some ME/CFS patients remain skeptical that the NIH moves reflect a genuine commitment to research on the disease. They have criticized what they call the narrow eligibility criteria being used for the Clinical Center study, and they complain that even $15 million scarcely begins to fund the research they say is needed. Critics such as Deborah Waroff, a retired Wall Street energy analyst who fell ill with ME/CFS in 1989, point, for instance, to multiple sclerosis, a similarly chronic, debilitating disease, which affects fewer than half as many Americans, according to one recent estimate. It received about 13 times as much NIH funding in 2016: $98 million. "ME still floats in space, belonging fully to no NIH institute and therefore having de jure claim to no budget," Waroff says. "The disease remains a beggar when it comes to budget."

Any goodwill won by Whittemore's appearance in Florida may have evaporated after anger erupted last week when ME/CFS patients learned NIH had invited Edward Shorter, a medical historian at the University of Toronto in Canada, to give a 9 November talk at the agency. Shorter last year called the IOM report affirming the biological basis of ME/CFS "valueless; junk science at its worst." He traces the disease to a 1970s "brew of toxic beliefs about being tired all the time."

Walter Koroshetz, the director of NINDS, defended the talk, writing in a letter to ME/CFS patients that "inclusion in the scientific conversation is not an endorsement." In an email to Science, he wrote that Shorter's talk was not "an official ME/CFS lecture. [An] announcement went out to the contrary. That was recalled. End of story."

Tangible scientific progress on unraveling ME/CFS might be the best medicine to heal the current divisions. A study published in the Proceedings of the National Academy of Sciences in August found depressed blood levels of scores of metabolites in people with the disease compared with healthy controls, suggesting that the disease may push the body into a low-energy state some have compared with hibernation. Scientists and patients are eagerly waiting for the results of a similar study by Lipkin's team. If replicated, the tantalizing finding could fit with an emerging theory that subpar function by mitochondria, the organelles that provide energy for cells, drives the disease.

Hints that the monoclonal antibody rituximab, a drug that destroys antibody-producing B cells, may help some people with ME/CFS have also sparked optimism. ME/CFS patients have a slightly elevated risk of developing B-cell lymphoma, and Norwegian researchers accidentally found that treating a woman who had both conditions with rituximab markedly improved her ME/CFS symptoms. The group went on to do a nonblinded study of the antibody in 29 ME/CFS patients, 18 of whom reported major or moderate improvements in their symptoms. The researchers are now running a larger, double-blind, randomized clinical trial of the drug in 152 patients, planning to evaluate its effectiveness next October.

Øystein Fluge, one of the Norwegian trial's leaders and an oncologist at the University of Bergen's Haukeland University Hospital in Norway, remains cautious. "Many places on the internet say this is an autoimmune disease. We haven't said that. We think some features fit, probably, with some autoimmune mechanism. But that's a hypothesis. We aren't sure." Only one thing is sure: After decades of frustration, the mysterious disease remains maddeningly elusive.