Whittemore Peterson Institute
Encyclopedia
The Whittemore Peterson Institute for Neuro-Immune Disease (WPI) is a research institute and charitable foundation known for its claims that the retrovirus xenotropic murine leukemia virus-related virus (XMRV) is associated with and may cause chronic fatigue syndrome
(CFS) and a variety of additional diseases. In 2009 researchers from WPI reported an association between CFS and XMRV in Science
. These results could not be replicated, despite many attempts to do so, leading to a consensus amongst scientists that the WPI results were due to contamination. In response, WPI personnel have criticised the methods and motives of other scientists, implying that the negative results are part of a "cover-up" or a "bias against this disease (CFS)".
WPI was created by the parents of a CFS patient, Annette and Harvey Whittemore
, and by Daniel Peterson
, an early researcher of the illness. Peterson left WPI in 2010 due to concerns related to the XMRV research. The institute is affiliated with the University of Nevada, Reno
. Judy Mikovits
joined as research director in 2006, but was terminated by WPI in October 2011 for not turning her work over to another scientist while also coming under investigation for alleged manipulation of data in her publications related to XMRV. WPI moved to the newly constructed Center for Molecular Medicine in August 2010. WPI plans to open a clinic in May 2011.
(CFS) at the age of twelve. Whittemore stated that numerous doctors were unable to help her daughter, and that the first major improvement came ten years after her diagnosis when she was treated by Peterson with the experimental antiviral drug Ampligen
. Hemispherx's new drug application
for Ampligen, which permits sale and marketing, was rejected by the FDA in December 2009 and the agency asked for another clinical study. Interviewed by The New York Times
, Whittemore said that "she had long believed that the syndrome was an infectious disease, but that scientists had rejected the idea." Frustrated by a lack of answers for the illness, Whittemore decided that, "if there was a place of our own where we could find the answers, we could do it more quickly." Her husband Harvey said that his wife also wanted to recognize Peterson for his history of treating the illness since 1984.
The Whittemores and Peterson established the Whittemore Peterson Institute in 2005 to aid patients with chronic fatigue syndrome, fibromyalgia
and related illnesses. Research at WPI began in 2006 with the opening of a small laboratory and an office on the University of Nevada, Reno campus, under the direction of Judy Mikovits. WPI registered as a 501(c)(3) public charity in 2006. The Institute's new facility opened in August 2010 in the University of Nevada's Center for Molecular Medicine. This 107000 sq ft (9,940.6 m²) facility includes 15000 sq ft (1,393.5 m²) for WPI office space, 8800 sq ft (817.5 m²) for the Nevada Cancer Institute as well as shared research laboratories and vivarium
. A detailed history behind the conception and funding of the institute as well as its ties to other medical institutions, including the University of Nevada’s Medical School and the Nevada Cancer Institute, has been written by President Annette Whittemore. A main suggestion is that non-traditional research entities can be most effective when they collaborate with more established entities.
Daniel Peterson left the Whittemore Peterson Institute for personal reasons in 2010. He had concerns about the "singular pursuit of XMRV" that was conducted without his input. His name was added to the Science paper only after a reviewer's comment. Peterson is working with Jay Levy, one of the original discoverers of HIV
, to try to determine whether XMRV is truly present, by testing the same patients used in the Science study.
, HTLV-1, SIV
infection, and other virus research. Vincent Lombardi, lead investigator and co-author of the 2009 Science paper, was appointed as Research Director in March 2011. Lombardi is a biochemist who earned his PhD in protein chemistry at the University of Nevada, Reno, in 2006. Prior to receiving his PhD, he co-founded RedLabs USA, Inc., now Viral Immune Pathology Diagnostics (VIP Dx). Donnica Moore
is WPI's celebrity spokesperson and advocate. Jamie Deckoff-Jones, a doctor who has CFS and takes antiviral medications, is director of clinical services.
The Institute states they have developed a research unit composed of scientists from the National Cancer Institute, the National Institute of Aging, the La Jolla Institute for Allergy and Immunology, and Kings College, UK.
, fibromyalgia
, atypical multiple sclerosis
and autism
. Other goals include: facilitating and advancing patient care; developing diagnostics and prevention strategies; and advancing and supporting medical education and physician training. The Institute considers such diseases "Neuro Immune Diseases", and posits that patients may share genetic susceptibilities, and have common aberrations in the innate immune response, manifesting in symptoms of disease. They intend to investigate the susceptibility in these patients to mechanisms of chronic immune system activation by infectious or environmental agents. There is currently no expert consensus on the complete etiology of these diseases.
Mikovits has suggested that the Institute's look at CFS from a neuro-immune perspective could reap wider dividends. She states that WPI researchers are "beginning to realize their research program will have a significant impact on a much larger number of diseases with similar etiologies such as autism, epilepsy and MS".
. The Nevada legislature agreed to provide $3 million to fund the institute, and additional funding is provided by private donations. $10 million was secured from the governor and legislature by the University of Nevada School of Medicine and the WPI for the Center for Molecular Medicine at the University of Nevada's medical institute, where WPI would share space. Nevada senators John Ensign
and Harry Reid
have separately introduced legislation requesting federal funding for the institute.
Supplemental funding for WPI comes from the sale of diagnostic tests by Viral Immune Pathology Diagnostics (VIP Dx), which is owned by the Whittemore family, with all net proceeds donated to the WPI. In September 2009, WPI announced that Mikovits and collaborator Jonathan Kerr of St. George’s College in London had been awarded a $1.6 million, 5-year grant by the National Institute of Allergy and Infectious Diseases
for their proposal to develop new "strategies to decipher the pathophysiology
of chronic fatigue syndrome".
(NCI) and moved to California
to get married in 2001. As WPI research director, Mikovits attempted to find a connection between CFS and infection
s. She met Bob Silverman, the co-discoverer of XMRV, at a conference
in 2007 and began to look for XMRV using Silverman's reagent
s. In late 2008, her team had two positive results out of twenty, and adjusted the experimental conditions until all twenty samples tested positive. Mikovits decided to focus all WPI resources on XMRV. She kept the project secret from Peterson and the Whittemores, fearful that skeptics would try to derail her work, but sent test samples to Bob Silverman and to the lab of her mentor at NCI, Frank Ruscetti. Mikovits submitted the first version of the Science paper in May, 2009.
in 68 of 101 (67%) CFS patients, versus 8 of 218 (3.7%) healthy control subjects. Co-authors included Mikovits, her former mentor Ruscetti at the NCI
, and Bob Silverman of the Cleveland Clinic
. The WPI study was followed by worldwide media coverage, including reports by the BBC
, National Public Radio, The New York Times
and The Wall Street Journal
. Discover Magazine listed it as one of the top 100 stories of 2009. Many CFS patients greeted the report enthusiastically, feeling that XMRV granted legitimacy to their condition and hoping that XMRV would be established as a treatable cause of CFS; some, assuming causation, even "hurry(ied) to doctors for tests and antiretroviral drugs". Others urged the need for more research before drawing conclusions. In the scientific community, initial reactions were mixed. Some were skeptical, noting the long history of proposed retrovirus-disease connections that were later debunked. John Coffin
and Jonathan Stoye in a Science commentary accompanying the WPI publication were cautiously optimistic.
In September 2011, the original authors published a "Partial Retraction" of their 2009 findings, in which they acknowledged that "some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA."
in 2010; it was conducted in the UK
and found no evidence of XMRV in CFS patients. The publication sparked what The Economist
dubbed a transatlantic "fight". Supporters of the two teams traded accusations of conflicts of interest, technical sloppiness, and failure to care about patients. The Reno Gazette-Journal
reported that Mikovits stated the PLoS ONE study team biased their study so as to not find the virus in its samples, and that Mikovits "suspected insurance companies in the United Kingdom are behind attempts to sully the findings of the Reno study". A steady stream of consistently negative results followed the PLoS One report. One study found no XMRV but did report evidence of murine retroviral
sequences in the blood of some CFS patients. Mikovits and Ruscetti attributed the failure to replicate their results to the use of different PCR reactions and to the examination of patient who did not satisfy the same CFS diagnostic criteria. A study using the original reaction conditions did not detect XMRV in UK patients who "not only had CFS, but had considerable disability".
WPI has been included in a multi-center trial, led by Ian Lipkin
, that is intended to settle the XMRV-CFS question conclusively. Samples from 150 CFS patients and 150 healthy but comparable donors are to be tested at WPI, the NIH
, and the CDC
. In the preliminary phase of this project, published in Science in January 2011, four patients initially tested positive at WPI and the CDC, but no XMRV was detected at NCI and no patient was positive after repeated testing.
presented evidence that reported XMRV detection could be explained by contamination of laboratory reagents, tissue samples and blood. Samples that were positive for XMRV were also positive for mouse DNA contaminants. Furthermore, the striking identity of XMRV genomic sequences and their similarity to xenotropic MLVs in several human cell lines suggested that XMRV is not a transmissible human pathogen. The British Medical Journal
responded with an article entitled, "Chronic fatigue syndrome is not caused by XMRV virus, study shows". A fifth study supporting the contamination hypothesis was published in February, 2011, just ahead of the 18th Conference on Retroviruses and Opportunistic Infections
(CROI). At CROI, WPI representatives were absent, and a large amount of negative data was presented. Two groups showed evidence that XMRV is a recombinant of two mouse retroviruses, which infected a prostate cancer cell line during passage through nude mice. Virologist John Coffin, who had previously expressed optimism about the initial WPI data, declared, "It's all contamination." Robert Silverman, who was a co-author of the original XMRV-CFS article but is no longer collaborating with Mikovits, told the Chicago Tribune that he was "concerned about lab contamination, despite our best efforts to avoid it".
, Alzheimer's disease
, multiple sclerosis
, and other diseases. There is no evidence that XMRV is associated with these diseases: all studies that have looked for a connection have produced negative results. Virologist Vincent Racaniello
has accused Mikovits of "inciting fear".
In response to the contradictory British results, Mikovits stated that scientists had doctored their studies to reach a predetermined conclusion as part of an insurance company conspiracy. Annette Whittemore expressed the opinion that the response to her organization's claims was political, while the director of clinical services, Deckoff-Jones, characterized the negative research findings as a "cover-up and baseless attacks against Dr. Mikovits". Mikovits stated that those who reported negative findings did not "believe" in chronic fatigue syndrome and sought to discredit the disorder itself. Critics disputed these charges. A March 2011 editorial in the journal Nature
praised Mikovits's defense of her work, but also asked her and her critics to keep an open mind and to be motivated by patients without allowing their scientific programme to be influenced by patients' beliefs.
WPI has also generated criticism for statements defending the use of antiretroviral medications as a treatment for CFS. For some individuals, these medications can have substantial side effects. Jay Levy states that taking anti-HIV medications is "not like taking an aspirin". There is currently no consensus that XMRV is capable of infecting humans, much less causing disease; the rush to prescribe antiretrovirals has been described as premature and based on "an unproven hypothesis". Another criticism is that even if XMRV did cause CFS and antiviral medications were effective against the virus, rigorous trials would be needed to establish safety, efficacy, and optimal dosing. Anecdotal treatments, they say, are unhelpful and possibly harmful to "the million or more individuals experiencing these serious conditions".
The editors at Science in May 2011 requested that the authors of the 2009 Lombardi et al. study retract the article due to many independent studies that did not find an association of XMRV with CFS, and studies that have presented data showing contaminated laboratory reagents may have led to false positive results. Science reported that Mikovits declined the request on behalf of the original authors, labeled the request "premature", and asserted that the original study results were accurate. The editor-in-chief of the journal Science subsequently published an expression of concern, "Because the validity of the study by Lombardi et al. is now seriously in question".
As of June 13, 2011, future testing will be conducted by UNEVX Clinical Laboratory.
federal working group to determine the prevalence of XMRV in the blood supply and the suitability of different detection methods. The WPI is also collecting blood from CFS patients who received their diagnosis after a blood transfusion and are planning to conduct their own study on XMRV blood transmission. The association between XMRV and CFS reported in Science prompted Health Canada
, the New Zealand Blood Service, and The Australian Red Cross Blood Service
to restrict individuals with CFS from donating blood in 2010. In June 2010, the American Association of Blood Banks recommended actively discouraging persons diagnosed with CFS from donating blood or blood components. Similar action was taken in Norway in December 2010, when the Norwegian health agency Helsedirektoratet issued a letter of caution to all the blood banks.
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
(CFS) and a variety of additional diseases. In 2009 researchers from WPI reported an association between CFS and XMRV in Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....
. These results could not be replicated, despite many attempts to do so, leading to a consensus amongst scientists that the WPI results were due to contamination. In response, WPI personnel have criticised the methods and motives of other scientists, implying that the negative results are part of a "cover-up" or a "bias against this disease (CFS)".
WPI was created by the parents of a CFS patient, Annette and Harvey Whittemore
Harvey Whittemore
Harvey Whittemore is an American lawyer and businessman in the Reno, Nevada area. As an influential lobbyist for the gambling, alcohol and tobacco industries, and for his own ventures, Whittemore has been called "one of Nevada's most powerful men"...
, and by Daniel Peterson
Daniel Peterson (physician)
Daniel Peterson is an American physician in private practice in the state of Nevada, and has been described as a "pioneer" in the treatment of chronic fatigue syndrome . He graduated from the University of Rochester School of Medicine, Rochester, New York, in 1976 and was an intern and resident at...
, an early researcher of the illness. Peterson left WPI in 2010 due to concerns related to the XMRV research. The institute is affiliated with the University of Nevada, Reno
University of Nevada, Reno
The University of Nevada, Reno , is a teaching and research university established in 1874 and located in Reno, Nevada, USA...
. Judy Mikovits
Judy Mikovits
Judy Anne Mikovits was the research director of the Whittemore Peterson Institute , a chronic fatigue syndrome research organization and clinic in Reno, Nevada, USA. Mikovits led a research effort that reported in 2009 that a retrovirus known as xenotropic murine leukemia virus-related virus is...
joined as research director in 2006, but was terminated by WPI in October 2011 for not turning her work over to another scientist while also coming under investigation for alleged manipulation of data in her publications related to XMRV. WPI moved to the newly constructed Center for Molecular Medicine in August 2010. WPI plans to open a clinic in May 2011.
History
Annette Whittemore, co-founder and president of the institute, states that the inspiration for the institute comes from her daughter, Andrea Whittemore-Goad, who was diagnosed with Chronic fatigue syndromeChronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
(CFS) at the age of twelve. Whittemore stated that numerous doctors were unable to help her daughter, and that the first major improvement came ten years after her diagnosis when she was treated by Peterson with the experimental antiviral drug Ampligen
Ampligen
Rintatolimod , is an experimental immunomodulatory double stranded RNA drug developed by Hemispherx Biopharma of Philadelphia, Pennsylvania...
. Hemispherx's new drug application
New drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
for Ampligen, which permits sale and marketing, was rejected by the FDA in December 2009 and the agency asked for another clinical study. Interviewed by The New York Times
The New York Times
The New York Times is an American daily newspaper founded and continuously published in New York City since 1851. The New York Times has won 106 Pulitzer Prizes, the most of any news organization...
, Whittemore said that "she had long believed that the syndrome was an infectious disease, but that scientists had rejected the idea." Frustrated by a lack of answers for the illness, Whittemore decided that, "if there was a place of our own where we could find the answers, we could do it more quickly." Her husband Harvey said that his wife also wanted to recognize Peterson for his history of treating the illness since 1984.
The Whittemores and Peterson established the Whittemore Peterson Institute in 2005 to aid patients with chronic fatigue syndrome, fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
and related illnesses. Research at WPI began in 2006 with the opening of a small laboratory and an office on the University of Nevada, Reno campus, under the direction of Judy Mikovits. WPI registered as a 501(c)(3) public charity in 2006. The Institute's new facility opened in August 2010 in the University of Nevada's Center for Molecular Medicine. This 107000 sq ft (9,940.6 m²) facility includes 15000 sq ft (1,393.5 m²) for WPI office space, 8800 sq ft (817.5 m²) for the Nevada Cancer Institute as well as shared research laboratories and vivarium
Vivarium
A vivarium is a usually enclosed area for keeping and raising animals or plants for observation or research...
. A detailed history behind the conception and funding of the institute as well as its ties to other medical institutions, including the University of Nevada’s Medical School and the Nevada Cancer Institute, has been written by President Annette Whittemore. A main suggestion is that non-traditional research entities can be most effective when they collaborate with more established entities.
Daniel Peterson left the Whittemore Peterson Institute for personal reasons in 2010. He had concerns about the "singular pursuit of XMRV" that was conducted without his input. His name was added to the Science paper only after a reviewer's comment. Peterson is working with Jay Levy, one of the original discoverers of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, to try to determine whether XMRV is truly present, by testing the same patients used in the Science study.
Organization
Annette Whittemore serves as president of the WPI. Judy Mikovits, who was previously the Research Director at the WPI, now holds the title of Director of Translational Research. Previously Mikovits worked with Francis "Frank" Ruscetti at the National Cancer Institute in Maryland for 22 years, during which time she earned a PhD in Biochemistry and Molecular Biology and completed postdoctoral research. Her work included studies of HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, HTLV-1, SIV
Simian immunodeficiency virus
Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...
infection, and other virus research. Vincent Lombardi, lead investigator and co-author of the 2009 Science paper, was appointed as Research Director in March 2011. Lombardi is a biochemist who earned his PhD in protein chemistry at the University of Nevada, Reno, in 2006. Prior to receiving his PhD, he co-founded RedLabs USA, Inc., now Viral Immune Pathology Diagnostics (VIP Dx). Donnica Moore
Donnica Moore
Donnica Moore is an American physician and women's health advocate, best known as an author and media commentator on women's health issues. Moore, who is known professionally as Dr. Donnica, has appeared multiple times on U.S. television shows such as CNN, the Tyra Banks Show, The View, ABC, and...
is WPI's celebrity spokesperson and advocate. Jamie Deckoff-Jones, a doctor who has CFS and takes antiviral medications, is director of clinical services.
The Institute states they have developed a research unit composed of scientists from the National Cancer Institute, the National Institute of Aging, the La Jolla Institute for Allergy and Immunology, and Kings College, UK.
Mission
The WPI's stated mission is to "bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of both the immune system and the nervous system, often resulting in life long disease and disability." They plan to research the pathophysiology of diseases such as ME/CFSChronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
, fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
, atypical multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
and autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. Other goals include: facilitating and advancing patient care; developing diagnostics and prevention strategies; and advancing and supporting medical education and physician training. The Institute considers such diseases "Neuro Immune Diseases", and posits that patients may share genetic susceptibilities, and have common aberrations in the innate immune response, manifesting in symptoms of disease. They intend to investigate the susceptibility in these patients to mechanisms of chronic immune system activation by infectious or environmental agents. There is currently no expert consensus on the complete etiology of these diseases.
Mikovits has suggested that the Institute's look at CFS from a neuro-immune perspective could reap wider dividends. She states that WPI researchers are "beginning to realize their research program will have a significant impact on a much larger number of diseases with similar etiologies such as autism, epilepsy and MS".
Funding and support
Initial funding for the institute was provided by the Whittemores, who in 2004 committed $5 million and successfully lobbied the Nevada legislature for support and arranged an affiliation with their alma mater, the University of Nevada, RenoUniversity of Nevada, Reno
The University of Nevada, Reno , is a teaching and research university established in 1874 and located in Reno, Nevada, USA...
. The Nevada legislature agreed to provide $3 million to fund the institute, and additional funding is provided by private donations. $10 million was secured from the governor and legislature by the University of Nevada School of Medicine and the WPI for the Center for Molecular Medicine at the University of Nevada's medical institute, where WPI would share space. Nevada senators John Ensign
John Ensign
John Eric Ensign is a former United States Senator from Nevada, serving from January 2001 until he resigned amid an investigation of an ethics violation in May 2011...
and Harry Reid
Harry Reid
Harry Mason Reid is the senior United States Senator from Nevada, serving since 1987. A member of the Democratic Party, he has been the Senate Majority Leader since January 2007, having previously served as Minority Leader and Minority and Majority Whip.Previously, Reid was a member of the U.S...
have separately introduced legislation requesting federal funding for the institute.
Supplemental funding for WPI comes from the sale of diagnostic tests by Viral Immune Pathology Diagnostics (VIP Dx), which is owned by the Whittemore family, with all net proceeds donated to the WPI. In September 2009, WPI announced that Mikovits and collaborator Jonathan Kerr of St. George’s College in London had been awarded a $1.6 million, 5-year grant by the National Institute of Allergy and Infectious Diseases
National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...
for their proposal to develop new "strategies to decipher the pathophysiology
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
of chronic fatigue syndrome".
Background
Judy Mikovits was introduced to Annette Whittemore at an HHV-6 Foundation conference in the spring of 2006, and soon after was hired as the research director of WPI. Mikovits had left the National Cancer InstituteNational Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
(NCI) and moved to California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
to get married in 2001. As WPI research director, Mikovits attempted to find a connection between CFS and infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s. She met Bob Silverman, the co-discoverer of XMRV, at a conference
Academic conference
An academic conference or symposium is a conference for researchers to present and discuss their work. Together with academic or scientific journals, conferences provide an important channel for exchange of information between researchers.-Overview:Conferences are usually composed of various...
in 2007 and began to look for XMRV using Silverman's reagent
Reagent
A reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
s. In late 2008, her team had two positive results out of twenty, and adjusted the experimental conditions until all twenty samples tested positive. Mikovits decided to focus all WPI resources on XMRV. She kept the project secret from Peterson and the Whittemores, fearful that skeptics would try to derail her work, but sent test samples to Bob Silverman and to the lab of her mentor at NCI, Frank Ruscetti. Mikovits submitted the first version of the Science paper in May, 2009.
Science publication and response
In 2009, Lombardi et al. reported in the journal Science that they had detected XMRV DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
in 68 of 101 (67%) CFS patients, versus 8 of 218 (3.7%) healthy control subjects. Co-authors included Mikovits, her former mentor Ruscetti at the NCI
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
, and Bob Silverman of the Cleveland Clinic
Cleveland Clinic Lerner Research Institute
The Cleveland Clinic Lerner Research Institute is home to all laboratory-based, translational and clinical research at the Cleveland Clinic.The Institute comprises 11 Departments: Biomedical Engineering, Cancer Biology, Cell Biology, Genomic Medicine Institute, Immunology, Molecular Cardiology,...
. The WPI study was followed by worldwide media coverage, including reports by the BBC
BBC
The British Broadcasting Corporation is a British public service broadcaster. Its headquarters is at Broadcasting House in the City of Westminster, London. It is the largest broadcaster in the world, with about 23,000 staff...
, National Public Radio, The New York Times
The New York Times
The New York Times is an American daily newspaper founded and continuously published in New York City since 1851. The New York Times has won 106 Pulitzer Prizes, the most of any news organization...
and The Wall Street Journal
The Wall Street Journal
The Wall Street Journal is an American English-language international daily newspaper. It is published in New York City by Dow Jones & Company, a division of News Corporation, along with the Asian and European editions of the Journal....
. Discover Magazine listed it as one of the top 100 stories of 2009. Many CFS patients greeted the report enthusiastically, feeling that XMRV granted legitimacy to their condition and hoping that XMRV would be established as a treatable cause of CFS; some, assuming causation, even "hurry(ied) to doctors for tests and antiretroviral drugs". Others urged the need for more research before drawing conclusions. In the scientific community, initial reactions were mixed. Some were skeptical, noting the long history of proposed retrovirus-disease connections that were later debunked. John Coffin
John Coffin (scientist)
John Coffin, PhD, is an American virologist. Raised in Boston, Massachusetts, Coffin is a professor of Genetics and Molecular Microbiology at Tufts University in Boston. He is also the director of the HIV Drug Resistance Program of the National Cancer Institute and serves as Special Advisor to the...
and Jonathan Stoye in a Science commentary accompanying the WPI publication were cautiously optimistic.
In September 2011, the original authors published a "Partial Retraction" of their 2009 findings, in which they acknowledged that "some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA."
Negative results
The first follow-up study was published in PLoS OnePLoS ONE
PLoS ONE is an open access peer-reviewed scientific journal published by the Public Library of Science since 2006. It covers primary research from any discipline within science and medicine. All submissions go through an internal and external pre-publication peer review but are not excluded on the...
in 2010; it was conducted in the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and found no evidence of XMRV in CFS patients. The publication sparked what The Economist
The Economist
The Economist is an English-language weekly news and international affairs publication owned by The Economist Newspaper Ltd. and edited in offices in the City of Westminster, London, England. Continuous publication began under founder James Wilson in September 1843...
dubbed a transatlantic "fight". Supporters of the two teams traded accusations of conflicts of interest, technical sloppiness, and failure to care about patients. The Reno Gazette-Journal
Reno Gazette-Journal
The Reno Gazette-Journal is the main daily newspaper for Reno, Nevada. It came into being when the Nevada State Journal and the Reno Evening Gazette were combined in 1983...
reported that Mikovits stated the PLoS ONE study team biased their study so as to not find the virus in its samples, and that Mikovits "suspected insurance companies in the United Kingdom are behind attempts to sully the findings of the Reno study". A steady stream of consistently negative results followed the PLoS One report. One study found no XMRV but did report evidence of murine retroviral
Murine leukemia virus
The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses...
sequences in the blood of some CFS patients. Mikovits and Ruscetti attributed the failure to replicate their results to the use of different PCR reactions and to the examination of patient who did not satisfy the same CFS diagnostic criteria. A study using the original reaction conditions did not detect XMRV in UK patients who "not only had CFS, but had considerable disability".
WPI has been included in a multi-center trial, led by Ian Lipkin
W. Ian Lipkin
W. Ian Lipkin is the John Snow Professor of Epidemiology at the Mailman School of Public Health at Columbia University and Professor of Neurology and Pathology at College of Physicians and Surgeons at Columbia University...
, that is intended to settle the XMRV-CFS question conclusively. Samples from 150 CFS patients and 150 healthy but comparable donors are to be tested at WPI, the NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, and the CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
. In the preliminary phase of this project, published in Science in January 2011, four patients initially tested positive at WPI and the CDC, but no XMRV was detected at NCI and no patient was positive after repeated testing.
Contamination
Some researchers were concerned about contamination from the first reports of XMRV-disease associations, and these concerns spread as study after study failed to replicate WPI's results. In December, 2010, four independent articles published in the journal RetrovirologyRetrovirology (journal)
Retrovirology is a peer-reviewed open-access scientific journal established in 2004 that specializes in publishing original and review articles on the basic research of retroviruses. Primate retroviruses are the subject of most publications in the journal, which is published by BioMed Central...
presented evidence that reported XMRV detection could be explained by contamination of laboratory reagents, tissue samples and blood. Samples that were positive for XMRV were also positive for mouse DNA contaminants. Furthermore, the striking identity of XMRV genomic sequences and their similarity to xenotropic MLVs in several human cell lines suggested that XMRV is not a transmissible human pathogen. The British Medical Journal
British Medical Journal
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
responded with an article entitled, "Chronic fatigue syndrome is not caused by XMRV virus, study shows". A fifth study supporting the contamination hypothesis was published in February, 2011, just ahead of the 18th Conference on Retroviruses and Opportunistic Infections
Conference on Retroviruses and Opportunistic Infections
The Conference on Retroviruses and Opportunistic Infections is an annual scientific meeting devoted to the understanding, prevention and treatment of HIV/AIDS and the opportunistic infections associated with AIDS. The 18th conference was held in Boston, Massachusetts from 27 February to 2 March 2011...
(CROI). At CROI, WPI representatives were absent, and a large amount of negative data was presented. Two groups showed evidence that XMRV is a recombinant of two mouse retroviruses, which infected a prostate cancer cell line during passage through nude mice. Virologist John Coffin, who had previously expressed optimism about the initial WPI data, declared, "It's all contamination." Robert Silverman, who was a co-author of the original XMRV-CFS article but is no longer collaborating with Mikovits, told the Chicago Tribune that he was "concerned about lab contamination, despite our best efforts to avoid it".
Controversial statements and criticism
The Whittemore Peterson Institute and its employees have issued statements that have generated additional controversy. Some of these statements have been made to the press, while others are made in presentations to patient groups. Although there is no consensus that XMRV is a human pathogen or even associated with any disease, Mikovits has stated her opinion that the virus "undoubtedly causes some of the symptoms that are associated with" CFS. Elsewhere, however, she notes that causation has not been proven. According to Mikovits, XMRV "is clearly circulating through the population as is our fear and your fear" and has entered the US blood supply. She has also associated XMRV not only with CFS, but also with autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, and other diseases. There is no evidence that XMRV is associated with these diseases: all studies that have looked for a connection have produced negative results. Virologist Vincent Racaniello
Vincent Racaniello
Vincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University’s College of Physicians and Surgeons...
has accused Mikovits of "inciting fear".
In response to the contradictory British results, Mikovits stated that scientists had doctored their studies to reach a predetermined conclusion as part of an insurance company conspiracy. Annette Whittemore expressed the opinion that the response to her organization's claims was political, while the director of clinical services, Deckoff-Jones, characterized the negative research findings as a "cover-up and baseless attacks against Dr. Mikovits". Mikovits stated that those who reported negative findings did not "believe" in chronic fatigue syndrome and sought to discredit the disorder itself. Critics disputed these charges. A March 2011 editorial in the journal Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
praised Mikovits's defense of her work, but also asked her and her critics to keep an open mind and to be motivated by patients without allowing their scientific programme to be influenced by patients' beliefs.
WPI has also generated criticism for statements defending the use of antiretroviral medications as a treatment for CFS. For some individuals, these medications can have substantial side effects. Jay Levy states that taking anti-HIV medications is "not like taking an aspirin". There is currently no consensus that XMRV is capable of infecting humans, much less causing disease; the rush to prescribe antiretrovirals has been described as premature and based on "an unproven hypothesis". Another criticism is that even if XMRV did cause CFS and antiviral medications were effective against the virus, rigorous trials would be needed to establish safety, efficacy, and optimal dosing. Anecdotal treatments, they say, are unhelpful and possibly harmful to "the million or more individuals experiencing these serious conditions".
The editors at Science in May 2011 requested that the authors of the 2009 Lombardi et al. study retract the article due to many independent studies that did not find an association of XMRV with CFS, and studies that have presented data showing contaminated laboratory reagents may have led to false positive results. Science reported that Mikovits declined the request on behalf of the original authors, labeled the request "premature", and asserted that the original study results were accurate. The editor-in-chief of the journal Science subsequently published an expression of concern, "Because the validity of the study by Lombardi et al. is now seriously in question".
XMRV testing
WPI was criticized for offering non-FDA-approved XMRV testing through its subsidiary, Viral Immune Pathology Diagnostics (VIP Dx), which was founded by WPI's Vincent Lombardi and was headed by Harvey Whittemore. The tests, which over 1000 patients purchased, cost $249 to $450. Virologist John Coffin observed that the original paper established the virus neither as a cause of CFS nor as a viable marker; in a Science news article, Sam Kean notes that the utility of the test for a patient or a physician is unclear. VIP Dx asserted that it introduced its XMRV test as a more expert alternative after a different company began offering one. Lombardi argued that the test is useful and that their 36% positive test results support the science in the original paper.As of June 13, 2011, future testing will be conducted by UNEVX Clinical Laboratory.
Blood supply safety
Mikovits has stated that XMRV has "almost certainly entered the U.S. blood supply system, but did not know whether it would be susceptible to the same heat treatments that successfully kill off the AIDS virus in blood products." The Wall Street Journal has reported that WPI and other laboratories are participating in a United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
federal working group to determine the prevalence of XMRV in the blood supply and the suitability of different detection methods. The WPI is also collecting blood from CFS patients who received their diagnosis after a blood transfusion and are planning to conduct their own study on XMRV blood transmission. The association between XMRV and CFS reported in Science prompted Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
, the New Zealand Blood Service, and The Australian Red Cross Blood Service
Australian Red Cross Blood Service
The Australian Red Cross Blood Service is a branch of the Australian Red Cross. It is the body primarily responsible for blood donation and related services in Australia.-History:...
to restrict individuals with CFS from donating blood in 2010. In June 2010, the American Association of Blood Banks recommended actively discouraging persons diagnosed with CFS from donating blood or blood components. Similar action was taken in Norway in December 2010, when the Norwegian health agency Helsedirektoratet issued a letter of caution to all the blood banks.