T he publication of research is an open invi-tation for other scientists to build on it, or

as likely, challenge its validity. That’s especially true when the research concerns a disease whose very existence is in question.

In April 2011, Annals of Neurology pub-lished a paper by Steven E. Schutzer, MD, Pro-fessor of Neurology at the New Jersey Medical School, and colleagues refuting a controversial finding published in Science in 2009 that claims xenotropic murine leukemia-related virus (XMRV) has a strong association with chronic fatigue syndrome (CFS).¹,² Schutzer searched for the presence of the virus in CFS patients’ cerebrospinal fluid and found none. He noted that the origins of CFS remain inconclusive.

Schutzer’s paper was one of at least 10

published by various journals that failed to replicate the findings of biochemist Vincent C. Lombardi, PhD, and colleagues at the Whittemore Peterson Institute in Reno, Nevada, authors of the original Science paper.

Weighing the available evi-dence, Science Editor-in-Chief Bruce Alberts, PhD, called for a retraction of the Lombardi paper, to no avail. On May 31, Science retroactively attached an “expres-sion of concern” to the paper. “A number of studies published elsewhere have failed to replicate these findings,” Alberts wrote in the statement. “In conjunction with two new reports that strongly support the growing view

that the association between XMRV and CFS likely reflects contamination of laboratories and research reagents with the virus, Science is publishing an Editorial Expression of Concern about the Lombardi et al report.”³ Alberts wrote that “appropriate action” will be taken after the National Institutes of Health (NIH) completes its studies of the XMRV and CFS claim.

The Whittemore Peterson Institute con-tinues to defend the Lombardi study. Institute President Annette Whittemore said in a state-ment released to the public that the institute was “extremely disappointed” with Science’s decision.4 “Much of the work on this new ret-rovirus has yet to be performed, and we look forward to new studies which will support the results and findings described by these accom-plished scientists. There has been no attempt to fully replicate this study to date. All of the negative studies have failed to use the methods, materials, or processes used in the original study and many have been poorly designed. WPI re-searchers will continue to perform the critical research needed to help the patients who suffer from neuro-immune disease.”

According to Alberts, the journal makes the difficult decisions to retract a paper “when we are convinced that it is incorrect, based on powerful findings of other scientists and new information that comes to light about the origi-nal paper that provides an alternate explanation for the data provided in that work.” Although he acknowledges that, “everyone recognizes that the [peer-review] process can never be perfect if we are to keep exposing important scientific data to other scientists in an expeditious man-ner,” he stresses that Science’s editors “do the

best we can by using as many peer reviewers as we judge necessary to cover all the technical and the conceptual aspects.”

In defending his research, Lombardi says his

September 2011 A7

At leAst 10 studies published by vArious journAls fAiled to replicAte the findings

Paper Linking XMRV to Chronic Fatigue Syndrome

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team’s research was extensively evaluated over a 6-month period of time before it was published. In an email to NerveCenter, he wrote, “Many individuals resist new ideas especially when [they apply] to things we don’t understand such as chronic neurological disease. Oftentimes, the name of an illness can stand in the way of our understanding of the significance or seriousness of a new illness. For instance, there is confusion surrounding the disease called chronic fatigue syndrome, which has led many to believe that those who are impacted are simply chronically tired. This belies the fact that most patients with CFS are seriously ill and may suffer lifelong dis-ability. Most of the public does not realize that CFS is classified by the World Health Organi-zation as a neurological disease called myalgic encephalomyelitis, and that it was identified as such years before it was renamed ‘chronic fa-tigue syndrome.’ ”

Alberts confirms that the Lombardi et al

paper underwent an extensive review process and stresses that “the manuscript would not have been published had our editors believed that the referees had any valid concerns about the methodology.”

The research has become a magnet for scrutiny. Today’s research news is rapidly dis-seminated globally by researchers as well as by patients who scour the Internet for information about their illness.

Retracting a published paper often leads to contention within the medical community and indignant patients who resent the loss of a vali-dation of their symptoms. One example of this is an online petition asking Science to retract the Editorial Expression of Concern. In addition, the publicly waged battles surrounding The Lancet’s 2010 retraction of a paper that linked the childhood MMR vaccine, gastrointestinal disease and autism is an extreme example of how far people will go to defend research, even

after it is deemed a fabrication.5

References1. lombardi vc, ruscetti fW, da gupta j, et al.

detection of an infectious retrovirus, XMrv, in blood cells of patients with chronic fatigue syn-drome. Science 2009;326:585-589.

2. schutzer se, rounds MA, natelson bh, ecker dj, eshoo MW. Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xe-notropic murine leukemia-related virus. Ann. Neurol. 2011;69:735–738

3. Alberts A. editorial expression of concern. Sci-ence. published online ahead of print May 31, 2011. doi: 10.1126/science.1208542

4. Whittemore peterson institute press release, May 31, 2011, www.wpinstitute.org/news/docs/Wpi_pressrel_053111.pdf. Accessed july 25, 2011.

5. Wakefield Aj, Murch sh, Anthony A, et al. re-trActed: ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637–641.

KaThLyn STone

doi: 10.1002/ana.22599

R ichard Olney, MD, dedicated his profes-sional life to treating patients with amyo-

trophic lateral sclerosis (ALS) and understand-ing its underlying causes. He founded the ALS Treatment and Research Center at the Univer-sity of California–San Francisco in 1993. After being diagnosed with ALS himself in 2004, he shouldered on as the center’s director while also receiving care as a patient from the doctors he once trained. He retired in summer 2010 as the disease, which had plateaued for several years, resumed its progression.

Since his diagnosis, Olney has publicly shared through his essays and interviews the experience of being a patient with ALS and all it entails. He has also continued to work from home with his son, Nicholas, a recent medical school graduate, on compiling clinical data on 26 cases of early stage ALS that will be helpful to future researchers studying neurogenetics. Nich-olas may continue his father’s work, as a neu-rologist if not an ALS specialist. “He is strongly inclined to enter ALS research but is keeping his mind open until he has at least completed his first year of residency,” Olney says.

From his unique position as a patient who has 25 years of experience treating ALS patients behind him, Olney has insights in abundance

and he knows time is short. “I have a lot that I want to say to neurologists,” he writes in an email to NerveCenter, reminding the reader to be patient as he writes with his eyes, using a computer tablet.

Olney says neurologists must encourage their patients with ALS to hold on to hope, be-ginning with the initial consultation. “Accept-ing the diagnosis of ALS is one of the two most difficult aspects of having the disease,” he says. When patients with suspected ALS are referred to him by neurologists who are not ALS spe-cialists, Olney prefers that the neurologist has presented the patient with several possible diag-noses before referral—both curable and noncur-able conditions. “Depending on how well the patient accepts the diagnosis, I usually prefer to tell them [they have ALS] on their second visit

to me,” he notes. “This gives them the chance to prepare themselves for the diagnosis of ALS.” Although Olney does make it clear to these patients that they most likely have ALS during their first visit with him, he stresses that “it is im-portant to always leave the patient with hope.”

Patients may cycle through “three stages of hope” as they learn to deal with the illness. The first hope is that they don’t really have ALS. “This is why I prefer to wait until the second visit to tell patients of the diagnosis,” he says. The second stage is the hope that a significant treatment will be discovered while they are liv-ing with ALS. “For those with rapid progres-sion, this hope is over in a short period of time. For those who have slow progression, it can be true for years,” says Olney, whose own illness followed this path.

The last hope is that death will be peace-ful. He says this final hope can be true for the vast majority of patients if the ALS team works in partnership with hospice staff. “When I managed patients, I emphasized that symptomatic treatment is available for most symptoms. At early stages of the disease, I would encourage them to think about and clarify their religious or spiritual beliefs. I related to patients in a lighthearted manner as if they did not have

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A Volume 70, No. 3

Richard olney’s Perspective as Physician-Scientist and Patient sAys neurologists Must encourAge their pAtients With Als to hold on to hope

i have thought about it and i have a lot that i want to say to neurologists.—Richard Olney, MD

8

a fatal disease, except when their forced or slow vital capacity approached 50% of predicted. Then I would discuss with them for the second time if they wanted to pursue ventilation with a tracheotomy, because now would be the time to initiate plans for that.”

As an ALS expert, Olney knew what to expect after his diagnosis and prepared for it. He followed the advice he had given his patients. “First, prepare for the worst by put-ting all of your affairs in order, but hope for the best,” he says. “Second, live one day at a time and enjoy each day as fully as you can. Third, focus on what you can do and things that you can influence; learn to accept those

things that you can’t influence.”During his career, Dr. Olney became aware

of many gene mutations discovered in familial ALS. He believes that progress toward identify-ing genes involved with sporadic ALS, the most common form, will be found through the study of different phenotypes. He was working in this line of research at the time he developed ALS. “I anticipate that when animal models are made from the recently identified mutations and we learn if they converge on a final common path-way or not, this will anticipate the case for the 90% of cases that are sporadic,” he says.

Olney says progress in the field of ALS has been relatively rapid from a scientific point of

view, particularly within the study of the neu-rogenetics. “But from a patient’s point of view, progress is slow.”

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doi: 10.1002/ana.22600

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September 2011 A89

Book Describes Unique Adventure of Patient with ALS

Walter bradley, Md, emeritus chair of the department of neurology at

the Miller school of Medicine at the uni-versity of Miami, estimates that about half of the Als patients he has encountered during his 45 years of practice wanted to complete a challenge or leave a mark on the world after receiving their diagnosis. but gib peters, a 61-year-old banker and humor columnist, surprised bradley.

peters announced in late 2003, seven months after his diagnosis, that he was embarking on a solo journey aboard a boat powered by two chevy v8 diesel en-gines. bradley says he had doubts about peters’ ability to complete the trip, and concerns about his personal safety. “gib was in a fairly advanced stage and already showing significant problems when he decided he was going to do the trip,” he recalls. “What was unique about him was that he insisted upon doing it despite ev-eryone telling him that it was stupid.” peters was on a feeding tube, was rapidly losing muscle control, and his speech was becoming unintelligible.

the book, Gib’s Odyssey: a Tale of Faith and Hope on the Intercoastal Waterway (lyons press, 2011), published in May, is part memoir and part travel adventure. it draws from peters’ newspaper columns that chronicled his 7-month journey and exchanges between doctor and patient that took place dur-ing office visits and through emails where they discussed the disease as well as the deeper meaning of life. the exchanges grew into a strong bond of friendship. everyone close to peters knew that he wanted his journey published into a book. When no good matches for the project stepped forward, bradley de-

cided to do it as public memorial to his patient and friend.

peters’ initial columns were amus-ing and full of adventure, but as the trip progressed, peters began to look deeper within himself. “he drew such extraordi-nary conclusions as he went along, spend-ing that time by himself,” bradley says.

these conclusions were captured in a column published in the Key West Citizen near the end of peters’ trip: “So how does a dying man find happiness? I am doing it this way: I’ve taken one part challenge, mixed it with two parts of planning, and stirred. After it steeps in its own natural juices for a while, I turn it into action and I don’t look back. My plan was designed to fill a couple of voids still left in my life. The first was a single-handed challenge of the sea that I love so much, together with a final test of my creativity in the face of the hundreds of challenges the sea offers;

challenges that are even more acute with only a failing body to meet them.

“So much for the recipe; how about the baking? How does one actually create happiness with all the reality competing for attention? I chose an old method known to many. I look carefully for that part of a situation that produces a feeling of gratitude.”

bradley hopes the book helps not only patients struggling to come to terms with their disease but that it also serves as a resource for neurologists caring for patients with difficult neu-rological diseases. it’s something doctors can give to patients that may give them hope, he says.

doi: 10.1002/ana.22601

Gib’s odyssey: a Tale of Faith and hope on the Intercoastal Waterway was pub-lished in May 2011.

in the february 2011 “nervecenter,” a map of “us telestroke hubs” incor-rectly listed site 23 as Medical college of georgia reAch, columbia, south carolina. it should be reAch Musc,

Medical university south carolina, charleston, south carolina.

CORRECTION