From The Wall Street Journal: the Saturday Essay, 5 March 2011 (story by Amy Dockser Marcus)
For 20 years, a doctor in upstate New York has been trying to prove that an outbreak of the strange syndrome in his community was caused by a virus. Now new evidence is reopening the case.
One snowy afternoon in October 1985, eight children from the tiny farming community of Lyndonville, N.Y., went sledding together. Within a few weeks, they all got sick.
David Bell, the local doctor who treated the children, recalls that their symptoms were similar to the flu: sore throats, fevers, muscle aches and severe fatigue. After three days, they hadn’t recovered. Then a week. A month. Ninety days.
Six months after their sledding trip, the children still couldn’t go back to the lone school in town. They had trouble getting out of bed. Light gave them a headache. Four of the eight were so sick that they were essentially disabled, Dr. Bell recalls. Tests ruled out mono and other infections. “We had no idea at all what it was,” he says.
Over the next two years, the mysterious illness spread throughout this rural village of 862 people halfway between Buffalo and Rochester. It eventually affected 214 people within a 30-mile radius, 46 of them children.
For the next 25 years, Dr. Bell, a Boston University-trained physician, would collaborate on studies, maintain a vast database of patients and write books, searching in vain for the cause of the illness from which some of his patients recovered and many did not. The illness would eventually be identified as chronic fatigue syndrome, but scientists still have not found its cause. “I figured I would never know why the kids got sick,” Dr. Bell says.
Chronic fatigue syndrome is an incredibly challenging disorder. There is no diagnostic test, no blood test and no scan, so diagnosis is made by excluding other conditions. The common symptoms, such as severe fatigue, muscle pain and weakness, rely on a patient’s perception and are hard to measure. In addition, many of the symptoms are also present in other conditions.
Some people diagnose themselves, mistakenly thinking they have chronic fatigue syndrome when in fact they have something else. Many others may have a wrong diagnosis, or none at all: The Centers for Disease Control and Prevention believes that of the estimated one million to four million Americans who have it, less than 20% have actually been diagnosed.
Now, patients with chronic fatigue syndrome are focusing on new research—and Dr. Bell hopes his lifelong quest to find the cause of the Lyndonville outbreak may eventually come to an end.
In 2009, researchers published a paper in the journal Science announcing that in 67% of the samples of 101 chronic fatigue syndrome patients, they had found a retrovirus called XMRV. Dr. Bell, who had previously suspected a link to retroviruses, wondered if it was the explanation he’d been looking for.
Lyndonville patients were elated by the discovery. “Holy smokes! Just when I want to retire this comes along,” Dr. Bell, 65, shared with patients on his website at the time. A retroviral link would not only prove a concrete cause but also open the possibility of treating it with anti-retroviral drugs.
Dr. Bell sought out his old patients to test them. Although the numbers tested were small, the preliminary results made him take notice: 70% of them came back positive for XMRV-related viruses.
Then came a major setback: Other labs trying to duplicate the results of the Science paper were unable to find the retrovirus in patients with the disease. In a high-profile paper published last July, scientists from the Centers for Disease Control and Prevention failed to find XMRV in either patients with the disorder or in healthy controls. The inability of other labs to confirm the results raised questions about the validity of the retroviral finding.
The debate over XMRV has become intertwined with the larger disagreement that touches almost every aspect of chronic fatigue syndrome. Not all researchers agree with the criteria the CDC uses to define patients with chronic fatigue syndrome, and use a different definition. Over the years, CFS has been called different names in other countries, including myalgic encephalomyelitis in the United Kingdom. Many patients hate the name chronic fatigue syndrome because they think it trivializes the condition.
Patients often report a sudden, flu-like onset, but one of the difficulties is that a diagnosis of chronic fatigue syndrome cannot be made unless symptoms persist for at least six months, making it challenging to determine the initial trigger. Some studies have indicated that CFS may be brought on by trauma like a car accident. A recent study by the CDC found that childhood trauma can be a risk factor—although the CDC points out that childhood difficulties do not cause the disorder.
It is still not understood how—or even if—the syndrome spreads. But since the 1930s, there have been at least 12 reported outbreaks in the medical literature of chronic fatigue syndrome in communities around the world. A 2004 outbreak in Norway occurred after one town’s public drinking water was contaminated with the Giardia lamblia parasite; 58 people diagnosed with what is called post-infectious fatigue syndrome are being followed there.
The various controversies have led many patients to feel that they have been maligned—by friends who don’t understand why patients look well but cannot function, by doctors who doubt their symptoms, by scientists who still don’t understand why people get the syndrome. This is one of the reasons why a possible link between XMRV and chronic fatigue syndrome was so widely embraced by the patient community. It offered a clear-cut explanation for how someone might get sick and a possible path for a way to treat it.
The debate over XMRV has been felt deeply in Lyndonville, with its picturesque countryside, red barns, bales of hay, and Amish farmers driving horses and buggies. The community has become a laboratory for research on chronic fatigue syndrome. Scientists continue to study the village because the patients who got sick in the outbreak lived in the same geographic area, fell ill after an infection, and were all treated by one doctor.
Dr. Bell, who began working at the University of Rochester after finishing his medical training, wanted to become a country doctor. One afternoon in 1978, he was driving through Lyndonville when he saw a farmhouse with a view of Lake Ontario, and on a whim decided to buy it. Many of his patients were dairy farmers and factory workers who weren’t able to pay him in cash but would leave food on his doorstep or fix his broken tractor as payment. He had an office in town but made house calls on horseback.
When the outbreak began, Dr. Bell wasn’t sure what it was and researched any possible lead, including taking milk samples from the goat whose milk went into the hot cocoa the children drank after going sledding. He suspected an infectious cause because the children all got sick at the same time.
Don Duncanson was one of the children who went sledding that October day. At the time, Mr. Duncanson was a healthy 14-year-old on the school wrestling team who says he was used to pain from constant training.
The experience of getting sick shocked him. His lymph nodes were painfully swollen. The light gave him a headache. He missed weeks of school unable to move from the sofa. After he returned to school, he was often so tired that he fell asleep at his desk. Some teachers smirked when he told them he didn’t feel well. “You’re a kid. You think it might be in your head,” he says. “I tried not to talk about it.”
Ginger Burg was also 14 when she first fell ill in 1986. One summer afternoon, she recalls being a healthy teenager playing basketball and baseball. The next day, she couldn’t get out of bed. Her parents rushed her to the hospital, where doctors told her she had hepatitis, strep throat and pneumonia.
When she finally went home, she seemed to get sick constantly. Every time she stood up for longer than a few minutes, she felt dizzy. A neurologist who tested her couldn’t find anything wrong and suggested she was a hypochondriac, she says.
Perplexed by the cause of the outbreak—which lasted until the end of 1987—Dr. Bell tried to get health authorities to pay attention to Lyndonville. Dr. Bell’s office sent lymph-node biopsies of 12 of the sickest children to the CDC, but the biopsies came back normal.
Around the same time, CDC investigators studied a similar outbreak in Lake Tahoe, Nev. They couldn’t find a cause there, either. In 1988, a CDC-sponsored workshop led researchers to name the condition chronic fatigue syndrome.
In 1989, Dr. Bell sent blood samples of his Lyndonville patients to an immunologist named Elaine DeFreitas at the Wistar Institute in Philadelphia. She found evidence of a retrovirus in the blood of two-thirds of 30 pediatric and adult patients diagnosed with chronic fatigue syndrome.
This was a significant breakthrough because a retrovirus—unlike other viruses—integrates into a person’s DNA, where under certain circumstances it can suddenly start making a virus again. This might explain the waxing and waning of people’s symptoms over the years and the severity of their sickness. HIV, the best known retrovirus, is treated with a combination of anti-retroviral drugs that attack the virus at different stages of its replication.
Dr. DeFreitas’s findings were announced to great fanfare at a scientific conference in 1990 and made the nightly news shows. Then, in a devastating blow to this theory, scientists at the CDC could not replicate her discovery.
“We were all convinced for a while [Dr. DeFreitas] was on to it,” says Thomas M. Folks, who was one of the CDC scientists who couldn’t reproduce her findings. The researchers came to believe that the retrovirus she found was due to contamination that inadvertently got into the samples she tested. “These things happen,” says Dr. Folks.
Dr. DeFreitas could not be reached for comment. But Dr. Bell, who is listed as a co-author on the paper, disagrees. He says he still believes the CDC did not find the virus because scientists there did not follow Dr. DeFreitas’s exact protocol.
Dr. Folks, who left the CDC in 2007, says the CDC should have been able to find the virus following their own protocol. He believes that researchers and doctors got close to patients and sincerely wanted to help them. That makes it hard to let go of a finding that appears to offer hope of a solution, he adds.
When the CDC couldn’t duplicate the findings, funding dried up and interest waned. Dr. DeFreitas eventually discontinued her research.
Over the next 25 years, some in Lyndonville would recover, but others would not. Many were stigmatized as having made their illness up. “We were [considered] crazy, delusional, lazy people,” recalls Ms. Burg.
During this time, some doctors and scientists advanced theories that, whatever the cause of the disorder, its duration and intensity could be influenced by a person’s coping style.
Nortin M. Hadler, a rheumatologist at the University of North Carolina Hospitals, says the fact that there is no diagnostic test for the syndrome can contribute to the way patients cope. Many patients feel like they must prove they have a disease to feel validated, he says. As a result, “they get sicker and sicker.”
Despite the CDC’s inability to find a retrovirus, Dr. Bell didn’t give up on his theory. He wrote books and maintained a database on the children who fell ill during the outbreak. In 2001, he published a follow-up report on 35 of them.
When the new discovery was published in Science in 2009, Dr. Bell went to work getting the word out, notifying as many patients from the original outbreak as possible.
At the same time, Maureen Hanson, a molecular biologist at Cornell University, also saw the Science paper. Dr. Hanson, who has a family member with chronic fatigue syndrome who had been diagnosed by Dr. Bell, asked him about working together on a retrovirus study. She wanted to test for the family of murine leukemia virus-related viruses, or MLVs, to which XMRV also belongs.
Dr. Bell contacted patients he treated over the years for Dr. Hanson to test. He identified 10 people who were still severely ill, 10 people who considered themselves recovered, and 20 healthy people to serve as controls.
One of the first calls went to Don Duncanson. Now 40 years old with salt-and-pepper hair, Mr. Duncanson works maintenance at a nearby school and coaches wrestling. Mr. Duncanson says he still feels some of the symptoms. Bright outdoor light hurts his eyes, and there are still days he has to force himself to get out of bed. “It’s normal to me now,” he says.
In the new study, Mr. Duncanson was classified as a recovered patient, based on his symptoms. He tested positive for MLV-like virus.
Dr. Bell also contacted Ginger Burg. Now 38, she is still severely affected by chronic fatigue syndrome. She spends hours every day lying down and has a constant headache. She can’t stand for long before she feels dizzy. Ms. Burg also tested positive.
At a meeting in December, an FDA advisory committee on blood issues invited Dr. Hanson to present the Lyndonville study. The committee was trying to determine if patients with chronic fatigue syndrome should be banned from donating blood.
In her presentation, Dr. Hanson said that seven of the 10 most severe Lyndonville patients, seven of the 10 recovered patients, and four of the 20 people in the control group tested positive for MLV-like virus.
The majority of committee members voted to recommend that people with the disease be banned from donating blood, even though the science remained uncertain. The FDA has not made a final decision, but the American Red Cross, the largest supplier of blood in the U.S., no longer accepts blood from people with the disorder.
Dr. Hanson’s study has not been published yet. She says she has not finished all the testing. A few days after the committee decision, some papers were published identifying several sources of possible mouse DNA contamination in XMRV studies. Dr. Hanson says she tested her samples for mouse contamination and did not find any.
In addition to Dr. Hanson’s study, there are large federally-led studies under way. One working group is studying whether XMRV or related viruses are affecting the blood supply. A different study, run by the National Institute of Allergy and Infectious Diseases, involves collecting and testing blood samples from chronic fatigue syndrome patients. These studies on the link between the family of retroviruses and the disorder are likely to carry significant weight in the scientific community.
In his office in Lyndonville, Dr. Bell keeps a picture of the virus that Dr. DeFreitas found growing in one of the cells of spinal fluid taken from a child who went sledding in 1985. The picture reminds him of what happened in the past, when conflicting studies caused scientists to lose interest in the retrovirus. “My greatest fear,” Dr. Bell says, “is that people will throw up their hands and say they are not going to pursue it.”Follow the ME Association on social media: