The Ramsay Research Fund - What is it being used for?

Following Professor Hooper's comments about money being wasted on poor non-replication research (see below) my mind was cast back to not long after 8th October 2009.

Dr Charles Shepherd was ultra keen to hear from people approaching the ME Association for funds towards prospective XMRV research.

Dr Shepherd cited back then at least four interested groups who were wanting monies for XMRV research.

We should be asking the ME Association if they are giving their valuable research cash to ANY groups presently carrying out what is becoming known as "Quick and Dirty" non-replication research - research that has already demonstrated nothing more than 0% positive findings.

As we have already discussed here on MEActionUK, replication research requires that all patients tested should transparently meet both the Fukuda and the Canadian diagnostic criteria to ensure that the patient cohort is not diluted in any way by those who may be suffering from "Fatigue Syndromes" unrelated to Myalgic Encephalomyelitis or indeed ICD-10 G93 CFS.

As Mithriel said earlier.

<snip>

The WPI had a fairly robust test worked out before they started testing people with CFS.

This MRC group should have used a positive blood sample to test their methods until they were working well. Only then could they say anything
meaningful about CFS patients.

Before a test is optimised, patient samples should be the best quality available if there is going to be any chance of detecting virus and they
should be from those patients who are most likely to have the infection - in fact the group the WPI tested.

Just fulfilling the Fukuda definition is not enough.

Anyone who has been around ME patients should be able to pick out a consistent set of symptoms.

Once a test has been validated and shown to detect virus in ME/CFS THEN it would be reasonable to take random samples from the clinics to see if those patients had ME/CFS or something else. To use them to test the theory is back to front.

Mithriel

</snip>

We need to know what the Ramsey Research Fund is now being used for.

Is ME Association Funding being used for the current crop of "Quick and Dirty" research that fails to replicate Lombardi et al. yet tries to make
out that it is better than Lombardi et al.?

Or is Ramsay Research Fund money being used properly i.e. for genuine replication research that compares known positive samples from Lombardi et al with proposed tests over here in the UK until such tests in this country become competent enough to actually find XMRV positive patients over here?

We already know that there are XMRV positive CFS and ME patients over here in the UK - more and more people tested privately are finding themselves XMRV positive. To say that such people do not exist only confirms the failure of the present UK research thus far.

If Melvin Ramsay knew that his fund was quite possibly being used for the purposes of scoring political points due to monies in the fund that carries his name being used for "quick and dirty" sub-standard non-replication research then my view is that he would be greatly saddened.

Poor science does none of us any good except for those trying desperately to score expensive and deceptive political points by claiming headlines that imply doubtful or no link at all between XMRV, Myalgic Encephalomyelitis and ICD-10 G93.3 CFS.

If something is worth doing it is worth doing to the highest standards possible.

As Professor Hooper stated earlier today.

<snip>

I would expect such good experimental scientists to honour the Lombardi/Mikovits study by the most careful, replication of patient
characterisation/classification and methodological exactitude.

This does not appear to have been the case - what a waste of money and what a waste of an opportunity to substantiate the work of Lombardi et al.

No wonder such elementary failures regarding patients and method lead many to the conclusion that deception and skulduggery is afoot.

Malcolm.

</snip>

We all sincerely hope that the Ramsay Research Fund is being used for the highest quality research that will do its utmost to genuinely replicate
Lombardi et al.

With two 100% XMRV negative studies based on non-replication methods and patient selection it would seem a waste of money to simply repeat the series of mistakes that have already been observed by us all.

Yours sincerely,

Stephen Ralph DCR(D) Retired.

http://www.meactionuk.org.uk

Further Supporting Illustrations:-

Comment from the Whittemore Peterson Institute with regards to the two recent UK XMRV non-replication studies

1. The authors of the Science paper established the existence of XMRV as an infectious human blood borne retrovirus for the first time in blood of patients diagnosed with CFS. Previous studies had established the presence of XMRV sequences and protein in human prostate tissue. The basic premise that XMRV may be capable of causing disease has not been questioned.

2. In the Science paper, the presence of XMRV in well-characterized patients with CFS was established using multiple technologies:

a) PCR on nucleic acids from un-stimulated and stimulated white blood cells;

b) XMRV protein expression from stimulated white blood cells;

c) virus isolation on the LNCaP cell line; and

d) a specific antibody response to XMRV.

3. The authors of the two UK studies did not attempt to "replicate" the WPI study. Replication requires that the same technologies be employed.

4. The collection, preparation and storage of DNA were completely different between the Science and UK papers. The latter studies do not how data on how blood was harvested and stored. Nor do the studies disclose the quantity of isolated cells. Insufficient number of cells analyzed may result in failure to detect a low copy virus like XMRV, regardless of the sensitivity of the assay. Neither UK study provides detail to allow interpretation of how many white blood cells were analyzed.

5. Patient selection was based on different definitions of CFS.

6. The UK authors were unable to detect XMRV, even though 4% of healthy individuals were found to be infected in the US. Japanese scientists detected XMRV in 1.7% in healthy blood donors in Japan. The two previously identified human retroviruses have distinct geographical distribution.

7. Perhaps the most important issue to focus on is the low level of XMRV in the blood. XMRV is present in such a small percentage of white blood cells that it is highly unlikely that either UK study's PCR method could detect it using the methods described. Careful reading of the Science paper shows that increasing the amount of the virus by growing the white blood cells is usually required rather than using white blood cells directly purified from the body. When using PCR alone, the Science authors found that four samples needed to be taken at different times from the same patient in order for XMRV to be detected by PCR in freshly isolated white blood cells.

More importantly, detection methods other than PCR showed that patients whose blood lacks sufficient amount of XMRV detectable by PCR are actually infected. This was proven by the isolation of viral proteins and the finding of infectious XMRV isolated from the indicator cell line LNCaP.

The authors of the Retro virology paper admit that their neutralization assay did not detect bacterially expressed XMRV gag and that positive control sera was needed to validate their assay. The WPI's monoclonal antibodies specifically and sensitively competed the immune response demonstrating the assays sensitivity and specificity for XMRV envelope.

Neither UK study requested positive control blood, plasma or nucleic acids from the WPI.

Simply stated the only validated reliable methods for detecting XMRV in CFS patients, to date, are the methods described in Science. Failure to use these methods and validated reagents has resulted in the failure to detect XMRV. A failure to detect XMRV is not the same as absence of XMRV.