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Xmrv Is Not The Cause Of Chronic Fatigue Syndrome, Culture Have Contaminated..


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#1 Zac

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Inviato 22 dicembre 2010 - 00:10:03

21 December 2010

http://www.meassocia....org.uk/?p=3581

Nuovo studio che sembra confermare che non ci sia un legame tra l'XMRV e la ME/CFS e' che c'e stata contaminazione nel laboratorio che l'ha suggerito.

Since the original study suggesting a possible link between CFS/ME and the XMRV retrovirus, there have been six published reports from reputable groups in three continents that have failed to find evidence of this virus. These studies have used appropriate techniques in well characterised CFS/ME patients. One study found evidence of two different retroviruses, the significance of which is unclear.
Four very recent further studies (two of them including as author one of the original commentators on the first report) have provided strong evidence to suggest that laboratory and/or reagent contamination are the likely explanation for the original findings.
The current view of informed observers is that the research evidence does not support the idea that XMRV or other retroviruses have a role in the causation or manifestations of CFS/ME. This type of virus is especially liable to be found as a result of inadvertent laboratory contamination, and there is now direct evidence to support this explanation. There is an ongoing study in which samples from the same patients are sent to multiple laboratories, and this – together with the latest reports – may conclude the matter.
There is currently no basis for using tests or treatment based on the initial findings in clinical practise. The original findings raised high expectations, but the hopes now seem to have been dashed. We have been here many times before.
Professor Greg Towers, an author of one of the recent studies comments appropriately in a press release. "Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome. All our evidence shows that the sequences from the virus genome in cell culture have contaminated human chronic fatigue syndrome and prostate cancer samples. It is vital to understand that we are not saying chronic fatigue syndrome does not have a virus cause – we cannot answer that yet – but we know it is not this virus causing it."
The main benefit of the episode has been an increased awareness of the need for more substantial understanding of the biological basis for CFS/ME, and for better tests and treatments. For the CFS/ME community, the strong health warning must be not to rush to embrace new research findings until they have been confirmed.

Professor Anthony J Pinching

Prof Pinching is a medical advisor to the Sussex & Kent ME/CFS Society

Zac
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#2 Zac

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Inviato 22 dicembre 2010 - 00:16:27

Risposta del Whitmore Petersen Institute www.wpinstitute.org

The WPI, who conducted the initial XMRV research (published in Science) quickly put out a statement saying that the new research does not prove there is no link between CFS and XMRV: "The coauthors stand by the conclusions of Lombardi et al. Nothing that has been published to date refutes our data." Judy A. Mikovits.
The Lombardi et al. and Lo et al. studies were done using four different methods of detection. They were not simply PCR experiments, as were the studies by McClure et al. and others who have recently reported their difficulties with contamination. Experienced researchers such as Mikovits, Lombardi, Lo and their collaborators understand the limitations of PCR technology, especially the possibility of sample contamination. As a result, we and Lo et al. conducted rigorous studies to prevent and rule out any possibility that the results reported were from contamination.
In addition to the use of PCR methodology, the Lombardi team used two other scientific techniques to determine whether, in fact, we had found new retroviruses in human blood samples. We identified a human antibody response to a gamma retroviral infection and we demonstrated that live gamma retrovirus isolated from human blood could infect human cells in culture. These scientific findings cannot be explained by contamination with mouse cells, mouse DNA or XMRV-related virus-contaminated human tumor cells. No mouse cell lines and none of the human cell lines reported today by Hue et al. to contain XMRV were ever cultured in the WPI lab where our PCR experiments were performed. Humans cannot make antibodies to viruses related to murine leukemia viruses unless they have been exposed to virus proteins. Therefore, recent publications regarding PCR contamination do not change the conclusions of the Lombardi et al. and Lo et al. studies that concluded that patients with ME/CFS are infected with human gammaretroviruses. We have never claimed that CFS was caused by XMRV,only that CFS patients possess antibodies to XMRV related proteins and harbor infectious XMRV, which integrates into human chromosomes and thus is a human infection of as yet unknown pathogenic potential.

http://xmrv.me.uk/xm...virus-or-is-it-

Zac
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"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
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#3 Zac

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Inviato 22 dicembre 2010 - 18:01:06

http://www.nhs.uk/ne...s-disputed.aspx


Chronic fatigue syndrome 'not virus'

“A new study has cast further doubt on the idea that a virus called XMRV causes chronic fatigue syndrome,” BBC News has reported. In 2009 the condition, also known as myalgic encephalomyelitis (ME), was linked to a virus similar to one found in mice after a study discovered it was present in blood samples from people with the condition. However, well-conducted research has now suggested that this link was made because of lab contamination in earlier research. The study authors have made a strong conclusion from their work and have reportedly stated that “our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome".

The complex laboratory research examined the debated link by assessing the purity and ancestry of viral samples isolated from human cells. Scientists concluded it is very likely that the human cells had been contaminated with DNA from mice cells or by cells that contained a virus very similar to XMRV.
On this basis they call for the use of more rigorous detection methods during testing.

The cause of chronic fatigue syndrome is still unknown, and this research does not rule out the possibility that other viruses are involved.



Where did the story come from?
The study was carried out by researchers from University College London, the Wellcome Trust Sanger Institute in Cambridge and the University of Oxford. The study was funded by the European Community’s Seventh Framework Programme, the UK National Institute for Health Research, the Wellcome Trust, the Medical Research Council and The Royal Society.

The study was published in the peer-reviewed medical journal Retrovirology.

The newspapers have all reported this story well, emphasising the strength of the researchers’ conclusion that ME is not caused by this virus. The authors themselves did not actually get hold of the samples from the study that had suggested a causal link. As a result, they cannot prove conclusively that the samples were contaminated, but their finding that the contamination is highly likely sheds doubt on the theory that XMRV causes ME.



What kind of research was this?
The cause of myalgic encephalomyelitis (ME), now more commonly termed chronic fatigue syndrome (CFS), is largely unknown, but one theory has suggested that a virus called XMRV (xenotropic murine leukaemia virus-related virus) may be involved. This virus has been linked with other diseases, but not all studies on its potential role in ME have found an association. The 2009 study that first linked XMRV to ME involved examination of blood cells from ME patients, finding that most samples contained DNA from the virus.

The XMRV virus circulates among mice, although in the laboratory it has been found to infect cells from a variety of animal species. The researchers say that the link between the virus and human disease is controversial, and that studies in this area have not produced consistent results. The virus is also found in up to 6% of healthy humans. In this study the researchers undertook a laboratory study to demonstrate that viruses from mice can contaminate human samples.



What did the research involve?
Researchers examined the DNA from different types of mice to see whether they could detect the presence of the virus. All of them were positive. They also investigated how frequently several lines of human cells (samples of extracted human cells cultured for experimentation) were contaminated with the XMRV virus. They tested contamination among nine different human cell lines, including tumour cells. They then investigated the presence of the XMRV virus using complex methods of detection, and also set out to see whether the human cells included viruses that could be mistaken for XMRV.

The researchers then undertook an evolutionary analysis of how the viral DNA comes to be in certain human cells lines. It is reported that XMRV is regularly found in prostate cancer cells, so the researchers cloned these cells and purified the viral DNA from them. They then used complex statistical methods to examine the evolutionary relationships between the sequences they had isolated from these cells.




What were the basic results?
DNA in human cells was frequently contaminated with DNA from different viruses, some of which originated from XMRV but some of which could be mistaken for having an XMRV origin. When cloning pure XMRV from the prostate cancer cells for testing purposes the researchers found that the viral DNA thought to be from XMRV was actually a mix of DNA from two different viruses. They say that this strongly suggests that contamination is the source.

Further analysis showed that viral sequences reported to be coming from unlinked patients actually seemed to be derived from the same original cell line, also suggesting that contamination was a likely reason for detection of this virus in human samples. Finally, the researchers found that the type of XMRV that is derived from human samples is less diverse than that from mouse cells. This is unexpected for a virus thought to cause an infectious disease.



How did the researchers interpret the results?
The researchers have concluded that the XMRV found in patient samples is likely to be derived from contamination either by mouse DNA or by other cells infected with viruses that originate in mouse DNA. They conclude that XMRV is unlikely to be a human pathogen.

They acknowledge that without testing original samples it is difficult to establish whether human samples in previous studies have definitely been contaminated.



Conclusion
This well-described laboratory study has used complex methods to analyse DNA and to determine the evolutionary history of retroviruses found in the DNA of mouse and human samples. The researchers have concluded that it is possible, and likely, that samples in previous studies concluding that XMRV has a causal link with ME were actually subject to contamination with DNA from mice or from cells that had an identical virus in them.

Importantly, they note that while it is not possible to prove that previous samples have been contaminated they say they are sure of their conclusions, and a lead researcher is quoted in the papers as saying that: "Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome. Our evidence shows that the sequences from the virus genome in cell culture have contaminated human chronic fatigue syndrome samples”. They say that rigorous methods should be used when screening for the virus in future.

The causes of ME, or chronic fatigue syndrome, are unknown, and while this research provides evidence that XMRV is not the cause, this does not exclude any other as yet unidentified virus from having some role. Other possible contributing factors include genetic, environmental, lifestyle and psychosocial factors.


Zac
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"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
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#4 Zac

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Inviato 23 dicembre 2010 - 11:41:13

Source: http://www.investinm...0Conference.htm

International ME/CFS Conference 2011

T
he Way Forward for ME - A Case for Clinical Trials

Invest in ME Statement on Biomedical Research into ME Proper Science Will Prevail

December 2010

The journal Retrovirology has recently published (20 Dec 2010) results from four different groups (Hue et al., Sato et al., Oakes et al. and Robinson et al.) [1] which dispute the association of XMRV with ME/CFS or prostate cancer and suggest evidence of possible mouse contamination of PCR evidence. Hue et al. go as far as to say that XMRV might not be a genuine human pathogen.

Until now it has been accepted by the scientific community that an infectious XMRV exists and the only debate has been whether its association with ME/CFS can be replicated or validated by other researchers.

Invest in ME feel that it is good that the papers in Retrovirology have been published for closer scrutiny by other experts in the field as there are many distinguished scientist involved on both sides of the scientific debate. We only question the motives and timing of the publication of these papers.

We expect and demand that these papers will be scrutinised as thoroughly as has been the case of the papers stating an association of XMRV and ME/CFS or prostate cancer.

Many media outlets were astonishingly quick to pick up this story from the Retrovirology journal. The BBC quoted Professor Tim Peto as saying


"It now seems really very, very unlikely that XMRV is linked to chronic fatigue syndromepatients ."

It is worth pointing out that Professor Peto is in the Trial Management Group of the soon to be published PACE trials, a trial which was heavily criticised before it even started by patients and most ME charities. The Trial Management Group also includes proponents of ME/CFS being a somatoform illness.

Invest in ME firmly believe that the PACE trials are bogus science and are the culmination of a decade of squandered resources from biased policies toward ME/CFS research. The folly of the PACE trials was extensively illustrated by the "Magical Medicine - How to Make an Illness Disappear" document [2] and we feel they can be discarded for any sensible discussion about ME/CFS.

The WPI have issued a press release [3] in which they state that -

Humans cannot make antibodies to viruses related to murine leukemia viruses unless they have been exposed to virus proteins. Therefore, recent publications regarding PCR contamination do not change the conclusions of the Lombardi et al. and Lo et al. studies that concluded that patients with ME/CFS are infected with human gammaretroviruses."


The recent research studies in Retrovirology need to be viewed in context. We openly wonder about a possible coordinated establishment propaganda campaign to boost the forthcoming PACE trials publication by coordinating a number of research papers to be published simultaneously.
It is worth emphasising again that the original Science paper was extensively peer reviewed. Using the "contamination argument" not only attempts to impinge the reputation of the WPI but also the Cleveland Clinic and the National Cancer Institute as well as Science magazine - and such heavyweight researchers as Dr Harvey Alter. Contamination was carefully ruled out by Lo et al. and Lombardi et al. The peer reviewers at Science and PNAS made sure of this.

We should also remember the observations from Dr David Bell made in May this year [4] where he commented on tactics being used to hamper the WPI research. Although the establishment bias of trying to promote ME/CFS as a behavioural illness has now clearly been discredited as a ridiculous smokescreen using poor research the efforts to thwart proper science are still going on.

Amy Dockser Marcus, a Wall Street journalist who has been following ME/CFS research closely, published an article [5] on this matter. This quotes other authors of this collection of Retrovirology papers, such as Professor John Coffin and assistant professor Robert Smith, author of the commentary, as being cautious of dismissing previous studies. This does not concur with Professor Peto's remark to the BBC above in which he seemingly dismisses any link between XMRV and ME/CFS.

Medical research has historically been in denial of new ideas and advancement due to dogma and inertia from establishment forces. Doctors, for example, would still be treating patients with peptic ulcers with stress reduction techniques and lifestyle management were it not for the example of Professor Barry Marshall, who infected himself with helicobacter pylori and subsequently treated himself with antibiotics to prove causality. [6]. Without such pioneering research progress is often stunted, or discarded.

How can we make progress? Patients need to be trialling treatments under proper supervision. A sensible approach might be to establish a few well controlled clinical trials to be performed on patients who are so ill that they have practically nothing to lose by trying out treatments such as antiretrovirals, where appropriate, to determine if there is improvement in their condition. It is about time something tangible is done to help these desperate patients and to progress proper science.

To this end Invest in ME will use the The Case for Clinical Trials as a theme for the 6th Invest in ME International ME/CFS Conference on 20th May 2011 [7]. We feel it is time to effect translational biomedical research and bring the benefits of such research to patients. It is also why we are trying to establish an examination and research facility to perform translational biomedical research into ME/CFS [8].

Invest in ME have invited the UK Secretary of State for Health, the Chief Medical Officer of England, the EU Commissioner for Health and many of Europe's health ministers to the conference. We have also invited the editor of the British Medical Journal to participate in a panel discussion - no longer can the BMJ publish poorly researched editorials on ME/CFS if it refuses to attend the annual IiME international ME/CFS Conference.

In May 2011 we will welcome again the President of the WPI Mrs Annette Whittemore and the Research Director Dr Judy Mikovits to London and will willingly (once again) provide the opportunity for politicians, the media and healthcare providers and researchers to attend the conference and listen and discuss with the foremost researchers on ME/CFS.

The WPI have shown themselves to be open and willing to cooperate - quite unique qualities in scientific research from what we can see. One thing that is clear is that the WPI is focused on helping ME/CFS patients to regain their lives - an attribute which seems often to be missing from some researchers, spokespersons and establishment organisations.

The WPI research on XMRV has offered new hope to people with ME/CFS that proper science is finally being performed to provide a future for patients.

Hopefully more funding will now be directed toward biomedical research into ME/CFS to enable progress regarding this devastating disease. As Dr Harvey Alter of National Institute of Health recently said his group had ruled out contamination and if whatever his group found is not MLV related viruses then scientists must find out what it is as the disease these ME/CFS patients have carry hallmarks of a viral disease.

We concur - virology and immunology are the likely keys to finding a treatment/cure.

We hope that scientific progress will continue at a much faster pace than in the past and that politics are not once again allowed to destroy all hope for ME/CFS patients.

We believe that proper science will prevail.
Look to the end.

-------------
1 http://www.retroviro...-4690-7-112.pdf
2 http://www.investinm...%20Medicine.htm
3 Statement Issued by Whittemore-Peterson Institute - 20 December 2010
4
http://www.investinm...-David-Bell.htm
5
http://blogs.wsj.com...f-contamination
6
http://tinyurl.com/2ebyegd
7
http://tinyurl.com/22kfekc
8
http://tinyurl.com/2f6gk66

Zac
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"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
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#5 Zac

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Inviato 23 dicembre 2010 - 19:17:01

Source: http://www.virology....ts-not-the-end/


XMRV and CFS – It’s not the end
22 December 2010

Yesterday the Chicago Tribune published my reaction to the four papers on the retrovirus XMRV published this week in the journal Retrovirology. I was quoted as saying ”These four papers are probably the beginning of the end of XMRV and CFS”. I wish to retract this statement and explain my reasons for doing so.

Early Monday a reporter for the Chicago Tribune, Trine Tsouderos, sent an email asking for my thoughts on four XMRV papers that had just been released (paper one, two, three, four). I read all four papers and decided that they raised serious concerns about the role of XMRV in human disease. Specifically, the four papers demonstrated different ways that assays for XMRV could be subject to contamination with murine viral sequences. I wrote an email to Ms. Tsouderos outlining my summary of the papers, and later that day her article was published. My statement was reproduced exactly from the email I had sent her, so I was not misquoted.

I then set out to write about the papers for my blog about viruses. I read the papers over again, and began checking XMRV sequences in Genbank. I also began an email correspondence with authors of three of the four papers, and spoke with my virology colleagues here at Columbia. As a consequence of this additional research I decided that my initial impression of the papers was incorrect, which is evident in my post entitled ‘Is XMRV a laboratory contaminant?‘. Almost immediately after publishing the piece readers began to ask why my comments to the Chicago Tribune had such a different tone. I concluded that a retraction and explanation were necessary.

Upon re-reading three of the four Retrovirology papers it became clear to me that they show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised by these findings. Clearly any new studies done on XMRV should keep in mind the potential for contamination from PCR kits and murine nucleic acids.

I was initially more troubled by the fourth paper by Hue and colleagues. There are four major findings in this paper (gag PCR primers are not specific for XMRV; the virus is present in 5 human tumor cell lines; two XMRV isolates are nearly identical to a virus from the human prostate cell line and also contain an insertion from the murine retrovirus MoMLV; and there is more nucleotide diversity in viral sequences from 22Rv1 cells than in all the patient XMRV sequences). The fact that two XMRV isolates seem to be laboratory contaminants – judged by the presence of MoMLV sequences – was initially unsettling until it became clear that other XMRV isolates do not have this insertion. That leaves the fourth finding – that XMRV from 22Rv1 cells appears ancestral to, and more diverse than, all the human XMRV sequences. I decided that this result was less troublesome than I had originally believed, in part because it is not clear that the differences among the 22Rv1 viruses did not arise during PCR amplification.

My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination.

In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others.

I would like to apologize to anyone who was offended, angered, or disappointed in any way by my statement to the Chicago Tribune. It is my goal to educate the public about virology, and clearly I did not do that very well.

There are at least two lessons that you can take away from this incident. First, that I make mistakes, and that I’m willing to admit it. Everyone does, including scientists. Second, if I had difficulties interpreting these papers, how would non-scientists fare?


Zac
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"In medicina tutto quello che è sconosciuto è malattia mentale" (...)
"Una delle malattie più diffuse è la diagnosi." (Karl Kraus)
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#6 Zac

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Inviato 05 gennaio 2011 - 22:19:49

January 4, 2011

XMRV: A Human Retrovirus with Unknown Pathogenic Potential, Not a Lab Contaminant

http://www.wpinstitu...ws_current.html

http://www.wpinstitu...s_cmmpress.html

1 January 2011
‘Where do we go from here?’ – answer from the Whittemore Peterson Institute

The recent proclamation that “XMRV is not the cause of CFS,” came from an individual who did laboratory experiments to show how PCR experiments can become contaminated. These results have nothing to do with the reality of a disease or the methods used by those who have detected XMRV in the blood and tissue of patients found to be infected. The positive studies, which cannot be explained away by PCR experiments, are those which have used multiple methods to show that XMRV is a live replicating gamma retrovirus in human blood and tissue samples using the gold standard methods of viral isolation and antibody testing, in addition to PCR. Unsupported conclusions, such as the one offered by the Wellcome Trust spokesman, often create sensational headlines but do little to move science forward. Authors of the positive XMRV studies have been extremely careful not to claim causality, realizing that more scientific research is required to make such a statement. However, one fact still remains clear. Not one of the negative studies changes the results of the scientific research done by Lombardi et al., Lo et al., Urisman et al., and Schlaberg et al.
The WPI-led scientific study, which rigorously ruled out contamination, revealed high associations of gamma retroviruses with physician-diagnosed CFS patients, using four different methods of detection. Recent commentary associated with the negative research papers on XMRV, which used only one testing method, claimed that these studies proved that XMRV was not the cause of human disease. On the contrary, what the authors of the “contamination studies” confirmed is something that most experienced scientists already know; there are risks associated with using PCR if one does not properly control for contamination. They cannot conclude that other research groups had the same problems or that “XMRV is not the cause of CFS”.
Most significantly, the recent Retrovirology publications failed to address the most important pieces of scientific evidence of human infection in the previous XMRV studies, including the fact that XMRV positive patients produce human antibodies to gamma retroviruses, XMRV integrates into human tissues, and infectious virus has been cultured from the blood of hundreds of patients with a diagnosis of Chronic Fatigue Syndrome and M.E. Humans do not make antibody responses to mouse DNA sequences from contaminated lab experiments. The Retrovirology studies only point out that XMRV research cannot be done in a mouse laboratory without extreme caution and should not rely solely on PCR methods.
Many researchers realize that the question of gamma retroviruses and human disease cannot and should not be dismissed lightly. Retroviruses integrate into their host’s DNA causing life long infection. Human retroviruses, such as HIV and HTLV-1, are causative for immune deficiencies, neurological disease and cancer. Animal studies involving XMRV demonstrate that the virus moves quickly away from the blood to various organs within the body, such as the spleen, lymph nodes, GI tract, and reproductive organs. This helps to explain why the virus is difficult to detect in blood even as it replicates in the tissues of those infected. Other studies using mouse models of Murine Leukemia Virus infection, a close relative of XMRV, have shown significant tissue involvement soon after infection, resulting in many physical symptoms of disease including cognitive deficits and immune deficiencies, symptoms which are well documented in patients with XMRV associated diseases.
Many anxious patients have asked, “Where do we go from here?” and “Is this the end of XMRV research?” The answer to the second question is an unequivocal “no.” As to the first question, a quick check of the status of ongoing research in various labs confirms that the research groups who have been working on XMRV over the past year are still hard at work developing better assays to check the world’s blood supply for the new retrovirus, finding correlates of immune dysfunction, engaging in animal studies, extending their findings to other groups of patients, and in general, enthusiastically continuing their research. They understand that novel scientific discoveries, which threaten current dogma, will continue to be challenged until the evidence can no longer be denied. For instance, there are still those few who question the fact that HIV is the cause of AIDS. It took Nobel Prize winner, Dr. Barry Marshall, 17 years and three trials in which he infected and then cured himself of H-Pylori associated ulcers, before the medical world would accept the fact that the bacterium causes the disease. Today we are engaged in a new battle to prove that human gamma retroviral infections, such as XMRV, are underlying pathogens in neuro-immune diseases and untold cancers.
It is clear that more research must be done to clarify the role of gamma retroviruses in human disease. However, when a pathogen such as XMRV is found in over 80% of those tested with the same diagnosis, causality is clearly a reasonable hypothesis that begs further scientific and medical research. It is a known fact that important questions of causality can often be answered through well designed clinical trials. For those who have suffered for years from these debilitating diseases, novel drug trials cannot begin soon enough.
WPI’s collaborative research projects are revealing the infectious and inflammatory nature of neuro-immune diseases, providing strong evidence against the use of CBT and exercise therapy as rational “treatments” for those who are ill. Such knowledge underscores the urgent need for much more private and federal funding of biological research to provide diagnostic tests and effective drug therapies for the millions who are ill, stop the spread of infectious retrovirus(es), and end the devastating cycle of disease.
Annette Whittemore
http://www.wpinstitute.org/news/docs/WPI_XMRV_010111.pdf


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#7 Falco

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Inviato 05 gennaio 2011 - 23:19:39

thanks Annette :)




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