The XMRV study conducted by the NIH and the FDA has been delayed for publication by its authors. The CDC XMRV study publication has also been put on hold for publication by its authors at the 11th hour. The Wall Street Journal (WSJ) picked up on this information and wrote an article about it here: http://online.wsj.com/article/SB10001424052748703374104575337160225739290.html?mod=googlenews_wsj#articleTabs%3Darticle

It has been reported that the CDC failed to find XMRV in the blood of CFS patients. This contrasts the FDA/NIH confirming the original Lombardi- Mikovits study in finding XMRV in the blood of a significant number of CFS patients.

After devoting many months to a scientific paper, scientists tend to be confident of their results and the icing on the cake for them comes when their study is published in a scientific journal. It is therefore rather suspicious that both study groups’ authors, the FDA/NIH and the CDC asked for their papers to be put on hold for publication. The WSJ article reports that “senior public-health officials” were the reason that both papers were thwarted from an imminent publication.

Possible Reasons for the Delay

I will explore the possible different reasons for the delay of publication of these two studies. I am assuming that the WSJ is correct in that “senior public-health officials” were the reason that the papers were put on hold.

1. The government may now know that XMRV causes disease and between 3% and 7% of the population are infected with XMRV. If both studies were released, the government may have felt unprepared for the consequences of a Lombardi-Mikovits confirmation study. In order to “regain control” of the situation, the government may have delayed both studies to give itself extra time to be fully prepared for the XMRV threat. Very little is known about XMRV and the government may have wanted a 100% reliable XMRV test to be available to the public before revealing the XMRV threat. The government may have also wanted to gain more knowledge regarding the ease of transmissibility of XMRV to avoid further public fear. It may also have wanted a definitive list of illnesses XMRV can be responsible for.

2. Another possible reason for the delay concerns the different conclusions on XMRV by different government departments. For the government to release two conflicting studies (1 of which has to be flawed) may be seen as failing to be an appropriate medical authority. The government may also feel a level of embarrassment at presenting contradictory findings. This situation would be problematic for the government regarding its recommendations on XMRV and an official XMRV stance.

Why They Should Release the Studies

1. Scientific progress is a collaborative, world-wide effort. Scientists around the entire world contribute to scientific knowledge. The US government not releasing the XMRV studies results in the consequence of all scientists outside of the US government not being able to build upon, replicate, improve and critique the US government scientists work. One of the attractive aspects of a scientific journal is that the readership is generally an expert in the specific field. The government preventing these experts from analysing the studies,thwarts or at least delays scientific progress.

2. Science is known for is objectivity and separation from political agendas. The act of the US government not releasing the XMRV studies is a slap in the face to science. Science is played out in the public yet professional arena (as opposed to the private arena.) To solve scientific issues behind closed doors leads to the possibility of government agendas dictating the scientific results to suit themselves. This is as opposed to the way science should work in scientific results dictating government agendas.

3. By not releasing the studies into the public arena, the government is directly delaying the scientific process. If only a few scientists (as opposed to scientists around the world)are to decide if the FDA/NIH or CDC study is correct then a longer time will lapse before a conclusion by the wider scientific community on XMRV is settled upon.

4. The delay mentioned in (3) means a delay of treatment for CFS patients and those patients infected with XMRV. The delay also means that more people will become infected with XMRV while the government decides on this issue within their own time frame.

5. If the government released the FDA/NIH study, a numerable amount of scientists and institutions would put a large amount of money towards XMRV research. At the moment the Lombardi-Mikovits study remains officially unconfirmed. If the FDA/NIH study was released, the Lombardi-Mikovits study would become officially confirmed resulting in a wave of immediate worldwide research towards XMRV.

6. The question now arises on the timeframe until the government reaches an internal consensus on XMRV. There is little external pressure on the government to hurry along with its XMRV research and consensus. If the Lombardi-Mikovits confirmation study was released by the government, they would have to work swiftly on XMRV as the public would demand this. If the general population is not aware of an XMRV threat (as the situation is like at the moment) then the government can do things at a leisurely pace.

The delay may be good for the superficial government image but is bad for the people the government agencies are meant to be helping- the CFS patients and potentially the XMRV positive patients. The misperception of the misnomer that is CFS means the wider public probably wouldn’t be too worried about catching CFS, although they should be.

What May Have Been Wrong With the CDC Study

I am assuming the CDC study is flawed in its conclusions and will examine where they may have went wrong. This is all speculation as I haven’t read the CDC XMRV paper. I am hypothesising on where the CDC may have gone wrong in not finding XMRV in CFS patients.

Cohorts

The CDC are notorious for using flawed CFS definitions as well as controversial methods of finding patients for their CFS studies. Let’s assume the CDC used their normal cohorts for this XMRV study.

They find their cohorts by phoning up a cross section of the population and asking them questions such as whether they are fatigued. (From http://www.cdc.gov/cfs/cfsgastudy.htm) They then give the positive respondents medical examinations that are intended to determine if their apparent “fatigue” is from an obvious organic source, to exclude a CFS diagnosis. The medical examination DOESN’T involve doing any specific testing for things considered to be potential CFS biomarkers such as NK cell function or SPECT scan tests. After their medical examination, if the subjects fit into the CDC criteria for CFS, they are included in a study. The CDC criteria for CFS is highly controversial and a world apart from the Canadian Criteria that has almost ubiquitously been recognised by CFS specialists as sufficient to diagnose CFS.

The former head of the CFS department of the CDC said 84% of the people they found through random phone interviews and the CDC diagnosed as having CFS didn’t know themselves they had CFS. (From http://www.cfidsreport.com/News/06-CDC_CFS_Reeves.htm)

Also the CDC researchers determined that the average workload of its CFS cohort was 48 hours per week. (http://www.cfidsreport.com/News/06-CDC-CFS-Controversy.htm)

If the CDC did use their traditional cohorts and techniques of diagnosing CFS patients, then their failure to find XMRV in their cohort isn’t surprising. If their XMRV retrovirus finding techniques were correct they would have by their own study shown their cohort to NOT represent CFS patients.

Did the CDC Find it in Anyone?

The CDC study according to the WSJ failed to find XMRV in their CFS patients. They may have failed to find it in their healthy controls. If this was the case, they would have used very dubious techniques similar to the European failed XMRV attempts that didn’t find XMRV in anyone. If the CDC didn’t find XMRV in anyone, it contradicts the findings of many groups such as: The Whittemore Peterson Institute, The National Cancer Institute, The Cleveland Clinic, the Japanese Study, The University Medical Centre-Hamburg, The Drug and Food Administration and The National Institute of Health. All of these groups found XMRV in a similar, comparable percentage of the healthy population.

Hindsight

When the CDC started their XMRV study, (not long after the 9th of October 2009) it wasn’t widely known how difficult it was to detect XMRV. Since the WPI study, the failure of many groups to detect XMRV in prostate cancer and CFS has highlighted the need for specific techniques. The CDC didn’t have this hindsight and may have overconfidently completed their study. The CDC study was completed before the start of February- a much shorter timeframe than the Lombardi-Mikovits study.

Techniques Used

Without having read the CDC XMRV study, I can only guess what mistake they made in managing not to find XMRV in CFS patients. The other studies that failed to find XMRV may have had comparably flawed methods to the CDC. The CDC may have messed up like these studies in areas such as:

Using the wrong cohort (i.e. not true CFS patients)

Failing to amplify, culture or activate their samples

Using old blood

Looking in non-replicating cells for XMRV

Using a PCR technique designed at detecting a lenti-retrovirus such as HIV as opposed to a gamma-retrovirus such as XMRV.

Using a PCR test not capable of detecting the low tire levels of XMRV

Looking for the primer pairs for ENV as opposed to a different primer pair

Looking for the primer pairs for ENV which may not have been sufficient to find XMRV due to diversity of that area

It becomes evident that finding XMRV requires a very specific technique and changing one variable even slightly from the original Lombardi-Mikovits paper may be sufficient to not find XMRV. Dr Suzanne Vernon highlighted this point when she talked about the differences between the Imperial College London XMRV study and the Lombardi-Mikovits XMRV study. She writes:

“

The blood was collected from CFS patients in different types of blood collection tubes.

The genomic DNA was extracted and purified using different techniques.

The amount of genomic DNA included in the amplification assay was different.

Different primer sequences were used that amplified different regions of the XMRV proviral DNA.

The conditions of the PCR amplification assay were different – from the numbers of cycles, to the type of polymerase used.”

Dr Vernon’s full article can be found here: http://www.cfids.org/cfidslink/2010/010603.asp

Lead Author

According the WSJ, the lead author of the CDC XMRV paper was the microbiologist, William Switzer. He was also involved in the study titled, “Prevalence of Xenotropic Murine Leukemia Virus in Prostate Cancer.” The abstract of the paper can be found here: http://www.retroconference.org/2010/Abstracts/37160.htm

In his prostate cancer study, Switzer found 1.2% of prostate cancer patients to be positive by ENV and POL PCR, which means they probably had XMRV. This number is distinctly different from other prostate cancer-XMRV studies which have found XMRV in as high as 40% of those suffering from prostate cancer.

Conclusion

Given the CDC’s history of treating and viewing CFS, their negative XMRV-CFS study is a further sign of their failure to understand the complexities of CFS. If the government had a scientific viewpoint they would let the scientific process take its natural course (releasing both papers) which would involve embarrassing the CDC. Instead the CFS patients must wait on bureaucracy rather than a global scientific effort.

UPDATE: Since writing this article, some new information has emerged. This new information is definitely worth reading and can be found on the CFS Central website http://www.cfscentral.com/2010/06/embargoed-studies-redux.html

This new information (although only a rumour at the moment) reveals the details of the FDA/NIH study and CDC study, including XMRV positive percentages.

UPDATE: If you’re interested in signing a petition urging the DHHS to allow both papers to be published, click here: http://healthcare.change.org/petitions/view/xmrv_allow_science_to_progress

This petition is only for U.S. residents only.