News of replication of WPI XMRV study...

[MEKoan]

I have wondered reading this thread if some of the rumors that have been picked up were intentionally "planted" -- I have found this not infrequently done in the hallowed halls of science. We judge Reeves' comment by its source. How can you evaluate something without a source?

Hey Ruth,

I could not help but wonder the same thing myself -- creating bias.

I know you are not saying that posters are planting but that posters may be repeating planted ideas from who knows how many generations back. Rumours go viral, too.

I do worry that we will become the vector.

If you google these issues, a lot of the hits you get are us musing, supposing and talking about rumours.

Makes me uncomfortable.

peace out,
Koan

 

[Advocate]

"A ton of software also needed to be written," DeRisi said. That's because the slide is best viewed on a computer screen after amplification under a laser microscope. The software also helps DeRisi interpret what he's seeing.

DeRisi at the time also presented the idea to the intellectual property office at the University of California, San Francisco. He said the lawyers saw little commercial value in the invention and declined to pursue a patent.

I wonder if those lawyers wish they had pursued a patent.

 

[Cort]

I imagine they did. Peterson said the chip is gonna be in commercial production pretty soon at a good price.

The history of XMRV and the WPI is interesting. Someone told me the WPI found something a couple of years ago (not through ViaCor) and if you remember there was talk from Dr. Mikovits or someone associated with the WPI that a novel virus had been found. I was told that upon further searching the 'novel virus' lead the WPI to XMRV (not the RNase L connection).

At the March IACFS/ME meeting Dr. Mikovits said 'there is no novel virus" but she told me "I have something that would knock your socks off but I'm not telling". So at that point they knew what they had.

I heard Peterson say it didn't show up through ViraCor which surprised them. ViraCor was a big part of their testing methodology; they apparently did it many times. I just heard him say that sentence - I don't know why it didn't show up. Perhaps they just missed it (?). Perhaps it was set up wrong. I have no idea.

But they did alot of tests on XMRV afterwards; I just put the Science paper on the Forums and looked at it more; both they and the Cleveland Clinic did PCR tests and phylogenetic tests ( whatever those are) and both indicated that the XMRV in CFS was very similar to the standard reference XMRV but was different enough from patient to patient to indicate that it was not a contaminant and that each patient had gotten it from a separate infection.

http://forums.aboutmecfs.org/showthread.php?t=1276

I guess you could say well maybe XMRV wasn't there when they were doing the ViraCor tests but somehow got in there later but the paper indicated that the XMRV they found came from different sources; there doesn't seem to be much possibility that a single strain of XMRV later got in and contaminated the blood

 

[Cort]

Reeves

Reeves appeared to be very confident that XMRV was not going to be found in most patients. His reasoning to some extent made sense; we've heard for years that this is a heterogeneous condition - that there are subsets just waiting to be dug out of the population.

We know that all sorts of different types of people get this disorder; some have an infectious onset - a good portion of them do not. Infectious onset can occur using a variety of different pathogens. Some people don't have infectious onset or gradual onset they just fall apart.

Yet now we hear that one virus is found is possibly responsible for 95% of chronic fatigue syndrome patients. Based on what we've heard for years this doesn't make sense. Reeves definitely has a point - it doesn't appear that heterogeneous conditions can usually be tied to a virus or a pathogen. But how to make sense of this 95% number?

One way is to assume that XMRV is much more common than we presume. If its in 95% of the very heterogeneous population that is chronic fatigue syndrome then we'd have to assume that its leaked out of the chronic fatigue syndrome population into other diseases and this is what the Whittemore Peterson Institute is proposing; they suggest that it could play a fundamental role in a variety of neuro- immune illnesses, one of which is chronic fatigue syndrome.

Dr. Reeves may simply be too focused on chronic fatigue syndrome; ie he can't see the forest for the trees - to get this.

It also brings a how important it is - if the XMRV finding is replicated - for researchers to focus on cofactors - there have probably got to be a variety of cofactors for XMRV to do its work in so many different ways in so many different types of people.

The flip side of this is that its not found in 95% of CFS patients but is found in a much smaller, more closely delineated population.

 

[Andrew]

I read some place that they used the virus signatures that NCI has. I don't know if this was all or just part of what they did. But it is interesting that DeRisi missed it. I hope they are looking into this. They give the impression that there technology is bullet-proof.

 

[Eric Johnson from I&I]

Cort,
Do you recall where/when Peterson said that? Any chance he said Virochip instead of ViraCor? Or maybe he misspoke? There sure is a ViraCor labs, but they dont seem to make a chip/microarray.

 

[Eric Johnson from I&I]

> phylogenetic tests ( whatever those are)

That would definitely be comparing the XMRV sequence to sequences of other MuLVs and other viruses.

 

[dannybex]

Cort...

"The flip side of this is that its not found in 95% of CFS patients but is found in a much smaller, more closely delineated population."

???

 

[Esther12]

"The flip side of this is that its not found in 95% of CFS patients but is found in a much smaller, more closely delineated population."

???

I'm still a bit confused as to which patients the 95% referred to.

 

[Eric Johnson from I&I]

> I'm still a bit confused as to which patients the 95% referred to.

Right, it was actually 98.

As for subgroups, whats the concrete evidence that they exist, other than slow onset / fast onset, and maybe FMS vs CFS? (But probably not the latter, since FMS and CFS form more of a cline, I suspect).

As I see it, people talk about subgroups without much basis. Now, they certainly *could* exist; I'm talking about whether they actually do.

 

[Samuel]

Since XMRV is very homologous with MuLVs, it would be easy to look right past it using a viral gene chip unless you knew that you where actually looking for a closely related non-endogenous retrovirus that was not on the chip they were using.

What time periods are we talking about? Was XMRV on the chip?

 

[anne]

I don't find the variances in CFS to be so troubling, here. Because while there are differences, there are core similarities, too. So it doesn't seem unlikely that there's something in common that is predictable, and that that something also acts in unpredictable ways--like, for instance, affecting the immune system and awakening a lot of latent infections as well as letting in a bunch of other ones that do different things.

I am biased somewhat by our experience. Whatever I gave my husband--and no one can convince me I didn't give it to him--is the same illness; however it has manifested differently in him. (I had slow onset, he had acute, I was up and down, he was flat, etc etc...)

 

[Martlet]

I don't find the variances in CFS to be so troubling, here.

Anne - I totally agree with you. My friend went down with it first. I followed two years later.

My friend had more severe cognitive dysfunction, while my cognition cycled from normal to hilarious (like the day I thought I felt well and insisted on dressing myself, only to collapse in laughter on the bed, after struggling - one leg through each bra strap!) depending on how fatigued I was, or whether I was running on sensory overload.

I had more severe myalgias, more frequent sore throats and ended up in a wheelchair for four years.

But we both had the same illness. We knew it, but more importantly, both our husbands knew it. Mine would know when my friend was about to crash and hers would spot an imminent crash in me. I don't think we were different subsets, so much as two people with the same disease, with slightly different external expression.

 

[MEKoan]

No two people with MS have the same disease expression.
One person with Parkinson's will have only tremor but another will be plagued by dementia.
One person with HIV AIDS will remain well, another will develop Karposi.
One person with Crohn's disease will have bad episodes that are managable with medication, another will require a bowel resection.

Why should we be any different? I just don't get this.

 

[Martlet]

Koan - I have no doubt that there are people who have been diagnosed with CFS who simply don't have it, especially over recent years. But as for there being subsets, I don't understand that either.

Three weeks ago, we were in Florida and both got food poisoning. My husband had a mild attack while mine went to a full-blown IBS attack. Still food poisoning.

Sometimes, I think they think we're cars and any variation must mean we're a different model. :-(

 

[rebecca1995]

98% v. 95% v. 89%

> I'm still a bit confused as to which patients the 95% referred to.

Right, it was actually 98.

There are a few different figures being used by WPI. The 98% refers to the 99/101 who were found to be positive by at least one of four assays, according to the unpublished data Peterson presented at CFSAC.

The 95% apparently refers to antibodies in a different cohort (not the 101). This was in Nature News Oct. 8:

Mikovits believes the association may be even stronger than the present work indicates. DNA sequencing only picks up active infections, she says, so she wants to study CFS exposure to the virus more broadly. In an unpublished investigation, she and her colleagues analyzed blood cells in about 330 CFS patients and found that more than 95% expressed antibodies to XMRV, whereas about 4% of healthy controls did.

Also, this article uses a different figure-- 90/101, or 89%:

http://www.nytimes.com/2009/11/12/giving/12SICK.html?_r=1&scp=1&sq=Mikovits Whittemore&st=cse

XMRV, the scientists suggested, may cause or at least contribute to chronic fatigue syndrome. Further tests found the virus in 90 of the 101, Dr. Mikovits said.

Actually, Im wondering now if that 90 is the journalists error.

So, Im really eager not only for replication studies from independent labs, but for more published studies from WPI. Then well have more insight into the 98 v. 95 v. 89.

One concern I have is that apparently the antibody test has been used on controls, but I havent heard anything about the protein expression and transmissable virus in plasma tests being tried on controls. I worry the number of positive controls could go up, diminishing the data.

OTOH, the additional tests mentioned by Peterson raised the number of positive PWCs by 50%. If the same is true of controls, they shouldnt go above 6%--which, interestingly, is the figure found in one of the prostate cancer studies.

 

[Cloud]

As you know Ross it was the same with me too...almost the same yr and same Hep B vaccine trigger although unlike you I did have an acute viral onset. Also knowing that CMV has been a big problem for you makes me think that we are kind of similar as when I was tested for CMV 3 yrs ago which is the only time that I have ever been tested for CMV, I was found to have off the scale IGG titers. I also tested positive for EBV but the titres were not as high. I was -ve for HHV-6

But then again I also have lyme and the coinfections too...although my lyme tests were -ve but I tested +ve for bartonella and erhlichia, so I was diagnosed with lyme clinically. I did work in the North East of the USA (Catskill mountains) the yr I got ill and I believe this area is rife with lyme so I may have picked up those infections then. Though I was already ill at that point anyway so I dont really see myself as a classic lyme patient, more a viral one with the initial vaccine trigger disturbing my body's ecology which has perhaps allowed other critters to jump onboard and/or allowed latent infections in my body to become active.

Anyway it is very interesting and encouraging to me that you have done so well on the Vistide and it will be interesting to know if you test positive to XMRV.

Yes, other than the viral onset with the vaccine, we have very similar stories. High viral load CMV was obviously a big problem for me. But, Dr Peterson and I both believe the Vistide may have been suppressing some undiagnosed virus's other than the CMV because I continued to improve on the Vistide for several months after clearing the CMV. Killing other bugs, or wellness lag....who knows. But, I was negative for HHV6&7, and my EBV showed past chronic infection, but not currently reactivated (I think) CMV was my only detected infection. Lyme and it's buddies contribution to all this is definitely intriguing and may prove to have a role for many of us....Obviously does for you. Lyme is epidemic here in the Pacific Northwest too. My GP was not into Lyme at all until she moved here and began to see 100's of severely ill people with Lyme who were being refused help by anyone else. She's a wonderful person and doctor.

XMRV seems to explain a lot of this. It could explain every single confusing issue I have dealing with ME/CFS. It makes more sense than anything I have ever come across in 15 years dealing with this disease. I told Dr Peterson that, and he stopped me and said......maybe, maybe not. But I will be very surprised mine is negative. Let ya know soon.

 

[Eric Johnson from I&I]

> Actually, Im wondering now if that 90 is the journalists error.

Thats likely.


> but I havent heard anything about the protein expression and transmissable virus in plasma tests being tried on controls. I worry the number of positive controls could go up, diminishing the data.

All four assays were all used on healthy controls, though it was hard to impossible to tell from the paper's words whether the healthies who had the three assays other than PCR were PCR+ healthies or PCR- ones. In any case, all healthies used in all three assays other than PCR were negative. Although because of the small N's, the zero rates in the experiments may not represent zero rates in reality -- but they do represent low rates, for example if half of all healthies are seropositive in reality, than the odds of getting zero of seven positive is 0.5^7 = 0.008. I wrote a nice longwinded post about it here:

http://health.groups.yahoo.com/group/CFSFMExperimental/message/129311

 

[rebecca1995]

culture

Thanks, Eric. Can you tell from the paper whether they used the culture for latent virus now being offered by VIP Labs?

Also, do you know what Dr. P. meant when he referred to the "co-culture technique" the Cleveland Clinic/NCI later used on 15 pts? Was this technique used in the original Science study?

 

[Megan]

ViraCor vs gene chip/microarray

Cort,
Do you recall where/when Peterson said that? Any chance he said Virochip instead of ViraCor? Or maybe he misspoke? There sure is a ViraCor labs, but they dont seem to make a chip/microarray.

Cort, I agree with Eric's quote above. I assumed from reading your original post #153 that ViraCor and the virus gene chip/microarray were the same technology but if you google them it's hard to find a connection. Are you sure they're the same thing?

Also I went back and reviewed Judy Mikovits presentation from the 'Invest in ME' conference in May 2008. In the context of talking about the WPI gene chip microarray studies she said the following:
- they used a custom virus microarray with 10,000 known mamalian viruses (it was at the NCI Frederick Core Facility - no mention of ViraCor or De Risi, though it was implied that the technology had been used some time before to detect a novel virus in prostate cancer patients)
- they looked at 60 patients with either lymphoma or T Cell clonal rearrangements
- the array is 'highly sensitive' for viruses requiring very few DNA/RNA particles
- they designed their own EBV and HHV6 arrays for use in future studies (again at the NCI)
- they identified a novel herpes virus and a novel retrovirus in some of these patients

This sounds to me like they did find something relating to retroviruses in their microarray research? But if this is the same thing as the ViraCor technology talked about by Cort then this would seem to be contradictory to the comments he heard reported?


Megan.