From The Washington Post | health and science pages | 5 October 2015 | Story by Miriam E Tucker.
Before he got sick, Whitney Dafoe was an award-winning photographer and a world traveler. He’d helped build a nunnery in India, ridden a motorcycle in the Himalayas and visited all 50 American states.
He also worked on Barack Obama’s 2008 presidential campaign, and although he was already ill by January 2009, pushed himself to travel to Washington from his California home to photograph the inauguration.
But now, at 31, Whitney lies in bed in a darkened room in his parents’ home, unable to talk, walk or eat. He is fed intravenously and is barely able to tolerate light, sounds or being touched. His parents and the medical personnel who see him wear plain clothing when they enter his room because bright colors, shapes or any kind of print make him feel even worse, as does any movement that he’s not expecting.
“It’s hard to explain how fragile he is,” says his mother, Janet Dafoe.
This isn’t the picture that people imagine when they hear “chronic fatigue syndrome,” which is often viewed by the public and the health-care community as a trivial or primarily psychological complaint.
In a February report, the Institute of Medicine gave the illness a new name — systemic exertion intolerance disease. Many patients have long criticized the name “chronic fatigue syndrome” for not reflecting the seriousness of the illness. The new name, some say, is not much of an improvement. Some patients call it by an older name, “myalgic encephalomyelitis.” Most official documents refer to it with a compromise term, “myalgic encephalomyelitis/chronic fatigue syndrome,” or ME/CFS.
The IOM report notes that doctors often lack understanding of the condition and are often skeptical that it is a true medical condition, believing instead that it’s partially or wholly psychological.
Some may therefore be surprised that the illness is now a major research focus for one of the world’s leading biomedical scientists.
That scientist, Ronald W. Davis, is Whitney Dafoe’s father.
Davis heads the Genome Technology Center at Stanford University. In the 1970s, he developed techniques for gene mapping that were later used in the Human Genome Project, for which he was a co-investigator. In 2013, the Atlantic magazine named him one of “Today’s Greatest Inventors, ” along with such people as Vint Cerf, sometimes called “the father of the Internet,” and Elon Musk, one of the founders of electric-car company Tesla Motors.
Using Stanford’s technology
Now the 74-year-old Davis has embarked on what may be the biggest challenge of his career: to help his son and others living with ME/CFS, a group that numbers, by various estimates, as many as 4 million Americans and as few as 836,000.
“It’s probably the last major disease that we don’t know anything about. . . . It’s remarkable how insidious this thing is, in the sense that people who have it don’t look sick, so nobody believes them,” Davis said at a recent fundraiser held in the yard of the family’s home in Palo Alto, Calif. The event drew about 100 people, including the city’s mayor.
Davis aims to use Stanford’s technology — and eventually collaborate with others — to study ME/CFS in an unprecedented way. He has recruited three Nobel laureates and other noted scientists to the advisory board of the Open Medicine Foundation, which is raising money for the project. In July and August, it received $1 million in donations, mainly from two anonymous sources, enough to begin the first phase of the study. Much more will be needed to understand this complex illness and develop treatments for it.
So far Davis has been unsuccessful in persuading the National Institutes of Health to provide funding.
Davis and his team will start out by studying 20 to 30 severely ill patients like Whitney, who has been the test case. While his case is extreme, bed-bound patients are believed to make up about a quarter of those with ME/CFS. Very little is known about them, since they haven’t been able to come to labs to participate in studies.
Davis’s team will make home visits to collect blood, sweat, saliva and fecal samples. The samples will be analyzed with sophisticated technologies such as mass spectrometry (which measures the amount and type of chemicals in a sample) and DNA and RNA sequencing.
“My plan is to collect more data on a group of patients than has ever been collected on a human being before, by orders of magnitude. . . . We’re going to be state-of-the-art on everything,” Davis says.
By studying just the sickest people, he hopes to identify a more consistent set of characteristics than has emerged from previous studies of more-diverse patient groups lumped under the “chronic fatigue syndrome” heading.
After that, Davis plans to conduct the same studies in ME/CFS patients who are only moderately ill — to see what characteristics they share with the severely ill group — and also in people with other fatiguing illnesses such as lupus and fibromyalgia, to identify what is unique about ME/CFS and to separate out abnormalities due to inactivity alone.
“What we’re trying to do initially is find a biomarker, something that shows a clear indication of something uniquely wrong. . . . That would help the patients a lot. It would mean that physicians could no longer deny that they’re sick,” Davis says.
For some patients, ME/CFS starts suddenly, with an illness or a trauma from which they never fully recover. For others, like Whitney,the illness follows a series of ailments. He was healthy as a child but caught a bad case of mononucleosis in high school and had a spell of headaches and dizziness after a trip to Jamaica during college. He eventually recovered from both.
He’d been in India for several months in 2006 when he began experiencing stomach pain, bloating and nausea. He returned weighing just 115 pounds on his 6-foot-3 frame. Then, two years later, he developed what seemed like a cold and never felt normal again.
“He went downhill from there,” his mother says.
By 2011, he could no longer care for himself. “Moving home was really devastating for him. . . . He’d worked so hard to be independent,” she says.
All along, he’d been seeing a series of doctors, most of whom told him they could find nothing wrong and suggested he was depressed.
In fact, says Andreas Kogelnik, the infectious-disease specialist who diagnosed Whitney with ME/CFS more than a year after he returned from India, “this was a vibrant, successful young man. . . . His only depression was that he had to stop doing the things he loved to do.”
“He has some of the classic symptoms that we talk about with ME/CFS, but in him they’re amplified 10 or 100 times,” adds Kogelnik, president and founder of the Open Medicine Institute, the research/clinical institution affiliated with the fundraising foundation.
Whitney has extremely low levels of several small molecules associated with energy metabolism. He also has three mutations in a gene that codes for an enzyme that helps convert folate and vitamin B12 to their active forms, a process necessary for both metabolic and immune function.
Such mutations are present in about 5 to 10 percent of the general population, but Kogelnik has been finding them at much higher rates among his ME/CFS patients.
Several definitions for “CFS” and “ME” have been developed over the years, but none has been deemed ideal, in part because they rely on self-reported symptoms rather than objective measures. Davis served on the IOM panel, which was convened in 2014 to conduct a scientific review aimed at redefining the illness.
The 282-page report issued in February gave ME/CFS a new definition, which still hinges on reported symptoms but places central importance on “post-exertional malaise,” a crash that patients experience after even the slightest physical or even mental exertion, leaving them exhausted and feeling ill for days or weeks.
Such exertion can be a short walk, brushing one’s teeth or, in Whitney’s case, simply sensing someone else in the room.
Despite numerous previous studies showing biological abnormalities that could potentially be tested for, Davis says that the panel didn’t recommend an objective test as part of the diagnosis because most of those studies have been small and poorly funded and haven’t been replicated. And the patient samples have been defined in various ways, giving rise to inconsistent findings. Those are the problems he wants to overcome with the new project.
The National Institutes of Health allocates only about $5 million a year to ME/CFS research, slightly less than the amount it devotes to hay fever. Davis, who has submitted two applications for research funds without success, says he’ll try again for subsequent stages of the project.
Asked about the denial, the NIH responded by e-mail: “Unfortunately, in challenging budget times, NIH turns away many potentially meritorious research applications.”
Nonetheless, Davis says, “I’m in it for the long term. I’m not going to quit.”
‘Grieving . . . like a death’
As Whitney’s health declined, his sister, Ashley Davis, would stop by his apartment to help him with household tasks. After he moved back home, she’d drive him to doctor’s appointments. But once he could no longer speak, she had to stop going into his room because it became too upsetting for her.
“I used to talk to him every single day, and I now can’t even make eye contact or give him a hug. . . . He’s still there, but I’m grieving for him like a death,” Ashley, 27, said at the fundraiser.
“He used to say, when he could still talk, that he wished he had AIDS or cancer, because then people wouldn’t tell him that there was nothing wrong with him and he would at least know what was wrong with him.”
Tucker is a Bethesda-based freelance journalist specializing in medicine and health.