by Tracie White
My meeting was scheduled with a legislative aide for Congresswoman Jackie Speier, (D-CA Fourteenth District) at two thirty p.m. As I had prepared for the short presentation, my mind had wandered even further back, to just before Whitney was born, and my own journey to become a science writer, a job that now made me proud. I was a premed student at Berkeley who fell in love with anatomy, then grew discouraged by a basic chemistry class. I went on to study mostly public health and stayed an extra year to get a second major in English, burying myself in books the way I had as a child.
By then I knew I wanted to tell stories that helped change people’s lives, so I became a reporter and wrote about health and social justice and the things that mattered to me. Years later, when the bottom fell out of the newspaper industry, I was freelancing from home with two small children writing mostly for parenting magazines. I needed a job, and Stanford offered me this one. As unprepared as I was for the job, I worked hard for more than fifteen years to understand science and scientists. Along the way, I came to realize the great value of both in a world filled with disease and loss. A deep love and respect for scientists, and the promise their work holds, now sits solidly within my heart. I’ve seen how medical scientists can wipe out so much pain and suffering firsthand. I would come to know, all too well, what hell the world could suffer when it refuses to listen to them.
Still, for me, on this day my true heroes remained the patients, those with chronic, ongoing diseases, who somehow manage to get up each morning and go on. And I listened with awe and respect as each one told me their story that day.
Our team met in the hallway just outside Speier’s office a few minutes early to discuss our plan. There were three of us: me; Alison Dykens, a young woman who’d gotten sick with ME/CFS as a child; and John Amodio, who was there on behalf of his wife, who had been sick for twenty years. The plan was for John to discuss the problem. Then I’d tell my story about Ron and Whitney, and Alison would tell her personal story. Molly Fishman, Speier’s legislative aide, welcomed us in when we opened the door.
John started to talk about this “neglected illness” and how badly a laboratory test was needed to help convince physicians and the public that it is a real disease. It had taken five years and literally dozens of doctor visits before his wife had finally received her diagnosis. Then it was my turn. So I showed photos of an emaciated Whitney lying sick in bed, with Ron kneeling on the floor next to him.
“I’m writing a book about this young man and his father,” I told her, pointing to the photos. “He’s been sick with ME/CFS for about a decade. He can’t eat or speak and has been bedridden for about five years now. His father, a brilliant scientist at Stanford, is trying to find a cure.” Molly nodded her head with interest.
“Congresswoman Speier and I are familiar with their story,” she said.
Then thirty-four-year-old Alison told her tale. Alison didn’t look sick, other than the folded up metal cane in her lap. She was quite beautiful, with glossy, long dark hair. She smiled broadly and spoke in a quiet voice. She got sick with the flu when she was just eleven years old and living with her family in Iowa. Then she started fainting and sleeping up to twenty hours a day. Somehow her mother kept her in school as she struggled through the many years of illness, but Alison never got better. More recently, she had tried working in Los Angeles as a creative manager for Sony, but she had to quit as a result of the ongoing exhaustion. Often she was so worn out that she couldn’t do her laundry and would stop at Kmart on the way to work to buy clothes.
Now she lives in a trailer on a bluff overlooking the ocean in Northern California, where she met her fiancé. She didn’t think anything this wonderful could ever have happened for her, and she ended her story pleadingly. She told us, “I just want to be able to stand up on my wedding day.”
Ron Davis, legendary geneticist, stands before an auditorium on the NIH campus, head bowed to the microphone before him. The room is filled with scientists from around the world studying ME/CFS and, sitting among them, people sick with the disease, who too have traveled from far away to get answers. The crowd grows silent.
“This is an example of a severe patient,” Ron says. Behind him, the screen changes from the series of scientific graphs and charts he’s been showing to a photograph of Whitney, larger than life, lying on one of his soft brown blankets in the back bedroom of his Palo Alto home. He’s wearing nothing but gray shorts and covering his eyes with his hands. He’s so thin he looks flattened, as if run over by a steamroller.
“This particular severe patient happens to be my son,” Ron continues. “He’s covering his eyes because looking at me can cause him great pain.… It always annoys me when people say it’s not such a bad disease. This is a very, very bad disease.”
Sitting in the audience, I too bow my head. I’ve seen the photo many times before, and it disturbs me still—not only for how sick Whitney looks but for how exposed he is. Like any mother, I want to cover him up. But he would just push me away. Whitney longed to use photographs to document injustice in the world and would be proud to see his own stark photograph displayed before this distinguished crowd. It’s been used by Ron at conferences in Australia, England, Sweden, and elsewhere around the world. Whenever it appears, I imagine the crowd goes silent like this.
Ron begins his lecture on the molecular basis of ME/CFS and his lab’s continuing journey to understand it with the Big Data study of severely ill patients. He describes the massive amounts of scientific data collected using the advanced technological tools at hand.
“Severe patients can’t even get out of bed,” Ron says. “We have to go to them.” He tells the audience how, in collaboration with Whitney’s former doctor Andy Kogelnik—who made home visits to collect the blood and other bodily fluids of a number of very sick patients like Whitney—they successfully ran advanced lab tests on the urine, blood, and saliva samples from twenty such patients and healthy controls. He expected that the molecular signals would be strongest from these sickest of patients, and he was pleased by the results. “We’ve been processing and analyzing that data ever since,” he says.
Before stepping up to the podium, Ron was introduced at the NIH conference as someone who “really didn’t need an introduction” as a leader in the field of ME/CFS research and many other areas of science and technology. The applause was loud, and the crowd seemed to listen hard throughout his speech. He continued on, talking about several of the other studies being conducted in his lab, including one called “the metabolic trap hypothesis” developed by one of his researchers, Robert Phair. He hypothesizes that a mutation discovered in the IDO2 gene may impact the molecular process involved in energy production.
Ron has discussed the complicated theory with me several times. It involves the gene IDO1, which in humans processes the amino acid tryptophan into other compounds that do important things for the body like regulate the immune system, reduce brain inflammation, and produce ATP, the energy juice for the body.
If for some reason there’s too much tryptophan in the cell, the IDO1 gene can’t process it anymore, which decreases the body’s ability to make those other necessary compounds. Fortunately, there is another gene, IDO2, which acts as a backup and keeps the body running as it should. With this two-gene system, all of the necessary compounds continue functioning to keep the immune system healthy and the body producing the necessary ATP.
Unfortunately, about 65 percent of the population has a mutation in that second gene, Ron told me. Most of the time this doesn’t matter because the tryptophan levels never get high enough to inhibit IDO1. But with a powerful trigger, like a viral infection, tryptophan can increase and inhibit IDO1. Without the backup gene, tryptophan is not processed into those other important compounds. It’s a kind of metabolic trap that can cause extreme fatigue and a dysfunctional immune system. The only way to get out of this trap is to decrease tryptophan levels or somehow reactivate IDO1.
Next at the conference, he skimmed over his lab’s
metabolomics research, and I thought of how much that first test had meant to him and Janet. He mentions Laurel Crosby’s newest study—measuring levels of potentially toxic heavy metals in hair samples taken from patients—and I remember Laurel at a rally held on the steps of San Francisco City Hall, where she was asking for hair samples from the crowd. Nearing the end of his lecture, Ron talked about a study of a potential new diagnostic device, referred to as the nanoneedle. It was developed by Rahim Esfandyarpour, an engineer leading a team in Ron’s lab. Ron says that the study had recently been submitted for publication in the Proceedings of the National Academy of Sciences. “Today, the journal called me and the study has been accepted for publication,” Ron announced. “We should be seeing that out anytime now.”
I have to tell my office about the study, I thought. This news needs to get out to the media.
On the morning after Advocacy Day at the Capitol, those of us who were healthy enough had taken shuttle rides from the Marriott to the NIH campus just a mile away—ten miles away from the center of Washington, DC. (Some of the sick folks, just too exhausted by Advocacy Day, stayed behind trying to recuperate in bed in their hotel rooms.)
The campus spread out wide across the hillside, quiet and peaceful, looking much like a college campus, dotted with historic red buildings, blossoming cherry trees, and energetic young researchers briskly walking by wearing backpacks. The NIH is the largest funder of biomedical research in the world, investing nearly $40 billion annually in medical research. Just the fact that a conference on ME/CFS research was being held here, I knew, brought with it a certain level of much-needed credibility to this long-neglected field. As I had walked up the hill to the conference auditorium, I caught a glimpse of the same stately building where FDR in 1940 had broadcast that prophetic speech to the nation on the brink of war: “We cannot be a strong nation unless we are a healthy nation.” I figured director Francis Collins must have his office there.
Walking into the conference auditorium felt, to me, like entering the drawing room at the end of an Agatha Christie novel, where all the characters in the book finally gather together to solve the mystery. I didn’t expect this mystery to be solved that day, but at least some brilliant researchers had gathered together to try. Over the next two days, in addition to Ron, hotshot researchers from Harvard and Cornell, from Australia and Sweden, talked on and on about their new research findings in the fields of neurology, microbiology, exercise physiology, and more. Low-level inflammation in the brain was reported by one. Another spoke of abnormal anaerobic thresholds as a possible cause for the adverse effects of exercise in patients. During each presentation, the sick folks stayed seated in their chairs, some in wheelchairs, listening hard. They applauded silently by shaking their hands in the air, out of deference for others oversensitive to sound.
At one point, I gasped when I recognized Osler’s Web author Hillary Johnson walking slowly and painfully up to the microphone set up for audience participation. She had told me she would try to come if she had the strength, but I was still surprised she made the trip. Somehow it made me feel proud to see her there. “People at the NIH may not understand the depths of our despair,” she said into the microphone, speaking to the researchers up on stage. “Patients feel this is a public health emergency. AIDS gets $28 billion compared to ME/CFS’s $8 million annually. You’ve got to do better.”
Sitting in the back of the room I nodded my head in agreement. We’ve got to do better, I thought. This story of injustice had continued on far too long. It’s time for the misinformation and stigmatization surrounding ME/CFS to stop. Our leaders need to step up to the plate, acknowledge past mistakes, and fix them. All the evidence is there in black and white. More research funding to find a cure would prevent so much unnecessary suffering and save lives.
I spotted the ruddy face of Dan Peterson, who was up front waiting for his turn at the podium. What a day of vindication it must be for him, I thought. When his turn came, he took a moment to reflect on the past. “I’m reminded of coming back here thirty years ago, when I brought a patient for diagnosis and potential treatment,” he told the audience. “I saw Dr. Stephen Straus, and he left me with the wisdom that science would prevail. I think that’s come true as we’ve seen in the last two days, but it’s a shame it took thirty years.”
Throughout the two-day conference Ron wore his dressy black cowboy hat. He likes it when patients can pick him out easily and come talk to him, so he always wears a hat, he said. This could have been an occasion for him to celebrate recent hard-won successes, but for Ron, the only success he longed for—a cure, a treatment for his son—still hadn’t come.
After the results from the Big Data study began to roll in, Ron and his ever-growing list of collaborators had shared the data and put it to work, just as he had planned. More studies and more hypotheses began to flow from there. Among them, one by his Stanford colleague Mark Davis—also there to speak at the conference that day—had shown results of an overactivation of those infection-fighting immune cells known as T-cells. This newest evidence of an abnormally functioning immune system needed further investigation. And it was time to submit another NIH grant. I’d asked Mark once what had pushed him into this new field of study. He replied with a smile. “When Ron Davis asks you to do something, you say yes.”
In 2018, the year before the conference, Ron had finally got his big ME/CFS NIH grant. The five-year, 2.5-million-dollar project, shared with Mark Davis and another investigator, was designed to find the cause of the overactivated immune system, with Ron leading the gene sequencing arm of the study to help determine what triggered the cells. Meanwhile, fundraising at the Open Medicine Foundation had reached $9 million in donations, mostly from patients and other advocates, including a $5 million windfall from the Pineapple Fund, an anonymous bitcoin investor. The money had made all this research possible as well as funding the first two scientific meetings and community symposia focused on the molecular basis of ME/CFS ever hosted on the Stanford campus.
Beyond Ron’s personal efforts, and perhaps spurred on by them, there had also been signs of a shift within the mainstream scientific community toward a new understanding of ME/CFS. Two years earlier, the NIH had more than doubled funding, from $6 million up to $15 million for ME/CFS—still far below what the advocacy community was asking for, but it was at least a start. When I eventually asked Francis Collins about the trigger for the additional funding, he said it did help that he had been made aware of the much-needed budget increases for the study of ME/CFS through multiple factors. They included Ron going public with the early NIH grant rejections, Brian Vastag’s emotional plea in the Washington Post, and the publication of the National Academy of Medicine report—the prestigious committee that wrote it just couldn’t be ignored.
Finally, in July 2018, the CDC rewrote its treatment guidelines, officially changing the name of this disease from CFS to ME/CFS. Unlike its previous guidelines, it now warned that exercise must be approached with extreme caution for these patients. This came on the heels of what Ron calls a seriously flawed study published by a British research team supporting graded exercise and cognitive behavioral therapy for treatment. It was the same study that Ron and Whitney had discussed with something like shock back when Whitney first moved home and knew how much sicker he got with any kind of exercise.
I followed media reports that had begun to spring up, reporting on these changes. I had begun to note a radical change in the news headlines. “New Recognition for Chronic Fatigue Syndrome,” reported the New York Times. The journal Nature announced: “A Reboot for Chronic Fatigue Syndrome Research.” When the nanoneedle study was eventually published, similar headlines would begin to appear.
Before the conference ended, I got a chance to meet Harvard’s Tony Komaroff on the way to a dinner party. I’d been invited by Ron to the party sponsored by the Open Medicine Foundation. He too was meeting Tony for the first time. Together with Ron Tompkins, another Harvard researcher and longti
me collaborator of Ron’s, we took an Uber ride over to the Hyatt Regency in downtown Bethesda, where most of the researchers at the conference were staying. I kept my eyes and ears focused on Tony. It was like a ghost from the past. He did look much like Hillary Johnson had described him in her Rolling Stone articles, with bushy, dark eyebrows—plus the added gray in his hair that I had imagined. I’d heard him speak at the conference, where he was introduced as the “grandfather of ME/CFS research,” now the author of more than 150 highly regarded articles on ME/CFS. A dog with a bone that just wouldn’t let go, I thought. During the ride to the party, he talked about the need for change in medical insurance to cover the treatment of ME/CFS.
“Doctors just don’t get compensated for how much time it takes to treat them,” he said. “Things won’t change until they do.”
When we arrived at the dinner party up on the third floor of the hotel, I was excited when Ron introduced me to another ghost from the past: a redheaded researcher with glasses and a quick smile, Nancy Klimas, formerly an AIDS researcher at the University of Miami. She was one of the early ME/CFS physician-scientists I’d never managed to track down. Her name kept popping up throughout my research as both a collaborator with Komaroff and the first to publish a study linking the disease with abnormal levels of the innate immune cells known as natural killer cells. Whitney, too, had quoted her once on his photography website in the first years after his diagnosis. It’s a quote that the advocacy community has used many times, in which she compares her AIDS patients to those with ME/CFS: “I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses [in 2009] I would rather have H.I.V.”
While the others were up at the pasta bar filling their plates and sipping white wine, Nancy and I sat down together at a table, and I asked her to tell me about those early days. She was eager to oblige. She had continued her research ever since publishing her first ME/CFS study while at the University of Miami in the late 1980s. Now she was working at Nova Southeastern University, also in Florida. And, during those years, the patients had continued to seek her out.
