CDC XMRV Retrovirology Study on CFS Published

VillageLife

Senior Member
Messages
674
Likes
36
Location
United Kingdom
I dont get it, when I went to bed last night the news was both papers have been held, I got an email last night from Jerry Holmberg telling me the papers were under review, I go to sleep and a few hours later the CDC paper is out!! whats going on???

Statement from Dr. Harvey Alter, transmitted by the NIH Office of Communication and Public Liaison: "Our paper has not yet been accepted for publication. My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy." Harvey A...lter, M.D

WHY HAS THE CDC NOT BEEN MADE TO GO OVER THERE STUDY AGAIN!!!!
 

Mark

Senior Member
Messages
5,238
Likes
6,199
Location
Sofa, UK
Haven't seen the mathematics of failure re-stated for some time, so...

Multiple studies in US, Germany and Japan, at least, have found levels of XMRV in the healthy controls varying 2-7%. Assuming from these results a modest background infection rate of 3%, the probability of a study using a test that can detect XMRV in human infection finding none at all in a random population sample of N=104 would be 4.2% (1 in 25):

(0.97)^N

In the case of the CDC Western Blot on plasma alone, N=104 (53+51)

3%....(0.97)^104 = 4.2%
4%....(0.96)^104 = 1.4%
5%....(0.95)^104 = 0.5%
6%....(0.94)^104 = 0.2%
7%....(0.93)^104 = 0.05%

For the entire antibody test with 251 subjects...

3%....(0.97)^251 = 0.05%
4%....(0.96)^251 = 0.004%
5%....(0.95)^251 = 0.0003%
6%....(0.94)^251 = 0.00002%
7%....(0.93)^251 = 0.000001%

A series of studies find a background rate of XMRV that is all within the limits of tolerance of a varying background rate of 2-7%.

Another series of studies all find none at all anywhere. These negative studies include some prostate cancer studies.

Possibilities (ordered by most to least likely IMO):-

1. Subtleties of the blood-draw and/or testing methodology are crucial to detection; the negative studies haven't got the trick of it.
2. Cohort selection and geography are crucial; XAND and XMRV are geographically clustered (note: controls are usually taken from same area as patients so if studying a clustered epidemic this would be possible) and the CDC have been studying a different group of patients.
3. The 6 positive studies are really finding something else, an artefact of detection technique.
4. The 6 (? WPI, NIH, FDA, German prostate, 2*US prostate, ...?) studies that found XMRV are all subject to some sort of systematic contamination (unimaginable really given the consistent significant differential between patients and controls using blinded samples).

By far the most likely is the first option, indeed further unpublished and leaked science seems to point in that direction, but the second could be an interesting possibility. The third is just feasible, and could become a complex question, if the XMRV genome is variable in a complex way - there could be lots of strains and some of them "aren't really XMRV as such", for example, but other MLVs, for example. The 4th just seems ridiculous and unfeasible, even if there were contamination of certain cell culture lines, it doesn't make sense...and seems to be the preferred option of Bad Scientits at the moment so far as I can tell, along with "they're all just making this up" (which didn't seem worthy of inclusion on my list above).

Although the idea that XMRV could not swim was ludicrous, the idea that it could be highly clustered is not; some RVs are known to be geographically clustered. What makes this interesting is the idea, recently mooted here, that XMRV might only be infectious/contagious for a limited time after infection. Such a virus might spread rapidly and infect multiple people over a short space of time and then become dormant re: infectivity, and even potentially dormant re: causing symptoms, for decades or even generations. This whole scenario is interesting because of the isolated epidemics notable in the history of CFS - this sort of story does seem to have some consistency with what little is known about the epidemiology of CFS.

Perhaps worryingly, if the CDC are able to maintain that "their" CFS contains no XMRV and we have been talking about different conditions all along, then that may become a fall-back position that is being attempted for the medium term: "their" CFS didn't have XMRV and they still could be psychosomatic. Or of course they might have YMRV, ZMRV,....
 

Esther12

Senior Member
Messages
13,774
Likes
28,351
Interesting that the serology test didn't turn anything up. The CFS cohort stuff is pretty funny. Are they trying to piss us off?

I'm going to wait for the other studies before thinking too seriously about this.
 

Mark

Senior Member
Messages
5,238
Likes
6,199
Location
Sofa, UK
This, the song for today...
Featuring a cameo from George, and William Reeves in a parachute...

[video=youtube;etxd0z5TfiA]http://www.youtube.com/watch?v=etxd0z5TfiA[/video]
 

pollycbr125

Senior Member
Messages
353
Likes
185
Location
yorkshire
I dont get it, when I went to bed last night the news was both papers have been held, I got an email last night from Jerry Holmberg telling me the papers were under review, I go to sleep and a few hours later the CDC paper is out!! whats going on???

Statement from Dr. Harvey Alter, transmitted by the NIH Office of Communication and Public Liaison: "Our paper has not yet been accepted for publication. My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy." Harvey A...lter, M.D

WHY HAS THE CDC NOT BEEN MADE TO GO OVER THERE STUDY AGAIN!!!!
where is this quote from village I have read so much this morning I am starting to loose track
 

jspotila

Senior Member
Messages
1,099
Likes
778
Thanks I cannot say that I have read this elsewhere which makes me wonder how accurate a statement it is ? ? ? can anyone enlighten us :confused:
That statement from Dr. Alter was received directly from the NIH Office of Communication and Public Liaison. Authenticity of the message was confirmed by the same office and permission to publish was granted. That's a statement from Dr. Alter.
 

Frickly

Senior Member
Messages
1,049
Likes
39
Location
Texas
No one has been able to find a source for Dr. Alter's statement. I am waiting for the CFIDS to reply to our questions regarding the source. Seems odd....
 

VillageLife

Senior Member
Messages
674
Likes
36
Location
United Kingdom
Publication of XMRV papers should not be blocked
http://www.virology.ws/
(Virology blog)
30 June 2010

The findings by the NIH and FDA that XMRV is associated with chronic fatigue syndrome has been accepted for publication by the Proceedings of the National Academy of Sciences (PNAS). Release of the article has been blocked by PNAS due to work carried out by the US Centers for Disease Control and Prevention (CDC). That study, which was submitted to Retrovirology, failed to find a link between XMRV and CFS. Its publication has also been placed on hold. According to ScienceInsider:

The contradiction has caused nervousness both at PNAS and among senior officials within the Department of Health and Human Services, of which all three agencies are part, says one scientist with inside knowledge.

It is senseless to block publication because the two papers reach different conclusions. If both manuscripts were subjected to proper peer-review, and were deemed acceptable by the referees, then they should be published. The journal editorial offices must respect the opinions of the reviewers. By overriding their decisions, they have compromised the entire peer reviewer process.

Blocking publication also sends the wrong message to CFS patients, to the public, and scientists. Not only does this action raise suspicions about their motives are they trying to publish only the result they believe is correct? but it ignores the very important fact that science is self correcting. Scientists are humans, and they make mistakes. But eventually the right answer will come to the surface. And that is why PNAS and Retrovirology should respect peer review, publish the XMRV papers, and let science correct itself.
 

Mark

Senior Member
Messages
5,238
Likes
6,199
Location
Sofa, UK
Archived blood specimens were tested from persons with CFS defined by the revised 1994 CDC case definition and matched healthy controls from Wichita, Kansas and metropolitan, urban, and rural Georgia populations. Serologic testing at CDC utilized a Western blot (WB) assay that showed excellent sensitivity to MuLV and XMRV polyclonal or monoclonal antibodies, and no reactivity on sera from 121 US blood donors or 26 HTLV-and HIV-infected sera. Plasma from 51 CFS cases and plasma from 53 controls were all WB negative.
Archived samples. Notorious samples and notorious definition. But carry on...

Does the highlighted section imply that the WB assay was controlled/calibrated
- positively against samples containing purported antibodies to XMRV (and other MULVs)
- negatively against all sera from blood donors?

If the latter is implied then this WB test has been defined in such a way as to detect zero XMRV in the blood supply.

Additional blinded screening of the 51 cases and 53 controls at the Robert Koch Institute using an ELISA employing recombinant Gag and Env XMRV proteins identified weak seroreactivity in one CFS case and a healthy control, which was not confirmed by immunofluorescence. PCR testing at CDC employed a gag and a pol nested PCR assay with a detection threshold of 10 copies in 1 ug of human DNA. DNA specimens from 50 CFS patients and 56 controls and 41 US blood donors were all PCR-negative. Blinded testing by a second nested gag PCR assay at the Blood Systems Research Institute was also negative for DNA specimens from the 50 CFS cases and 56 controls.
The sensitivity looks way too low, no? Even with fresh blood, culture is often needed due to low copy count, way lower than this I thought, anybody have estimates of those numbers?

Hmm...and does all this make you want to gag, or does it make you want to not gag? ;)
 

Dr. Yes

Shame on You
Messages
868
Likes
46
That statement from Dr. Alter was received directly from the NIH Office of Communication and Public Liaison. Authenticity of the message was confirmed by the same office and permission to publish was granted. That's a statement from Dr. Alter.
Could you tell us the date of that statement, Jennie? And did he provide any further information?


 

eric_s

Senior Member
Messages
1,925
Likes
75
Location
Switzerland/Spain (Valencia)
Statement from Dr. Harvey Alter, transmitted by the NIH Office of Communication and Public Liaison: "Our paper has not yet been accepted for publication. My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy." Harvey Alter, M.D
Damn.. now i'm getting angry.
For days now, we could read that all the papers (the one by the CDC and the one (or two) by the NIH and FDA) have been accepted for publication but put on hold.
It was reported in many articles.
Here is a quote from "Science" (emphasis added)
Science has learned that a paper describing the new findings, already accepted by the Proceedings of the National Academy of Sciences (PNAS), has been put on hold because it directly contradicts another as-yet-unpublished study by a third government agency, the U.S. Centers for Disease Control and Prevention (CDC).
http://news.sciencemag.org/scienceinsider/2010/06/conflicting-papers-on-hold-as-xm.html

Now all of a sudden we see the CDC paper published and we get a statement by Dr. Alter himself, where he says that his paper is not yet accepted.
How is this possible??
I trust him and i think he is probably one of the best around, but this does not make sense. Something is wrong here, this information is contradictory.

Unfortunately this is not possible here, because it's not a criminal case, but i feel like we should have a judge send police in there and confiscate all the info, so we will know the truth.
I have never believed in conspiracy theories but now this is starting to look strange. If Dr. Alter comes out with something like "Oops, we've had it wrong", then i don't know what to believe anymore.
Let's hope that this will not happen. And there's still the WPI that will not give up and the other upcoming studies that are supposed to be positive, as CFS Central has reported.

Sorry, but now i'm starting to get nervous..
 

Mark

Senior Member
Messages
5,238
Likes
6,199
Location
Sofa, UK
http://online.wsj.com/article/SB1000...googlenews_wsj
Scientists at the Food and Drug Administration and the National Institutes of Health, including NIH infectious-disease specialist Harvey Alter, recently finished research that came to a conclusion similar to that of the Science paperthat XMRV, or xenotropic murine leukemia virus-related virus, is found in the blood of chronic-fatigue syndrome patients.

The paper was accepted for publication in the journal Proceedings of the National Academy of Sciences of the United States of America but is on hold, according to Ashley Truxon, media coordinator for the journal. She had no further comment.
Statement from Dr. Harvey Alter, transmitted by the NIH Office of Communication and Public Liaison: "Our paper has not yet been accepted for publication. My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy." Harvey A...lter, M.D
:confused:
 

CBS

Senior Member
Messages
1,513
Likes
849
The conclusion in the abstract reads:

Conclusions
We did not find any evidence of infection with XMRV in our U.S. study population of CFS
patients or healthy controls by using multiple molecular and serologic assays. These
data do not support an association of XMRV with CFS.
It really ought to read:
Conclusions
We did not find any evidence of infection with XMRV in our U.S. study population of CFS
patients or healthy controls by using multiple molecular and serologic assays. These
data do not support the existence of XMRV in the population.