NIH/FDA XMRV Paper by Dr. Alter Out!

[Sing]

V99 and LaurieM, the question in my mind is always about which critieria and case definition were used. This was NOT discussed, interestingly, (the elephant in the room, in my view) but the patient samples came from Dr. Komaroff and were said to be very well characterized as CFS.

I hope that many of us will make comments on these news articles as they appear. I just did with the one at Scientific American, and the focus of my comments was on the different clinical/research definitions still being used as a very probable source of the different findings.

 

[dannybex]

I was expecting a larger patient group too.

I'm still wondering about what Judy M. said to the press last week about something from the FDA being due to be published "in September."

And how Those Who Seem To Know Things around here said that there were actually *two* papers, this one in August and something else in September.

Hopefully!

I guess it's just that I can hear others arguing that this doesn't mean much because it was "only 32 (?) patients...which is indeed a very small group.

So hopefully larger studies, with a larger selection of patients and controls -- maybe 200 of each? -- are in the pipeline.

 

[urbantravels]

Per the notes from today's teleconference Alter's group is looking at 1,000 healthy controls.

 

[Sing]

Politics, Chris, I'd say. They don't want to make the CDC look bad either by pointing to the discrepancy in definitions being used in the research or by calling for a definition which is in contrast to the CDC's. It is outrageous given that the Canadian Consensus Definition was arrived at by an international panel of experts including Dr. Daniel Peterson, Nancy Klimas, Kenny De Meirleir, Martin Lerner and eight other doctors. It was highly praised by Dr. David Bell, Charles Lapp and Leonard Jason. This definition has widespread international acceptance as the most accurate to date. There is no sound scientific reason why this definition should not be consistently used in research.

 

[Mark]

Presumably there's enough detail in Alter's paper regarding the various genetic sequences to make it fairly easy for others to replicate it by PCR. Now that we know more detail about what to look for, and given that it only took Wessely and McClure 3 months to do their replication studies, there should be plenty of time to get a rash of PCR replication studies by the end of this year, no?

And what a shame the thing's been kept secret for the last 3 months - or we could have had all that info by now and settled the contamination question that way.

 

[Rrrr]

can someone set me straight: didn't they label the diff viruses they found CFS 1, CFS 2, CFS 3?

and at the same time they say these retroviruses are not necessarily the cause of CFS?

 

[Rrrr]

George,

CFS1, CFS2 etc are what he is calling the different strains of the virus, not different presentations of the disease.

I think I'm getting this from mindy's article and interview with alter. I definitely read it today. They found four types of the vrus, CFS1,2,3 and the fourth they are refering to as something else.

can someone set me straight: didn't they label the diff viruses they found CFS 1, CFS 2, CFS 3?

and at the same time they say these retroviruses are not necessarily the cause of CFS?

 

[Rrrr]

A great paper as far as I can tell (not very far!), but one disturbing statement: "Future studies should adhere to consensus definitions such as that developed by the Centers for Disease Control and Prevention (CDC)." Why and how did they write that? That damned definition has caused so much trouble over so many years.... why?? Chris

RIGHT! i agree!

 

[anciendaze]

Don't get too upset with the definition. If you go through the bibliography, you will notice that the entire body of Reeves' work on the empirical definition just disappeared. Remember also that the CCC is the Canadian Consensus Criteria, and Lo and Alter deliberately used the word consensus.

It looks to me like we are watching a seasoned campaigner at work. This isn't a matter of staking everything on a single battle. This is seige warfare: building earthworks, digging trenches, bringing in sappers. Once the defenders can see the outcome looming you can expect them to abandon the position.

 

[Sunshine]

A great paper as far as I can tell (not very far!), but one disturbing statement: "Future studies should adhere to consensus definitions such as that developed by the Centers for Disease Control and Prevention (CDC)." Why and how did they write that? That damned definition has caused so much trouble over so many years.... why?? Chris

Because the FDA and friends are 'the government', and one of the authors on this paper works for the US military. It's best not to screw the state, when they are your employee especially when they know naughty things you do with mycoplasma cultured from dying AIDS people to kill people as a weapon that you give to the Army. Hence he said it.

He has to conform, that is the deal when you sign up for the Armed Forces, total loyalty. By sticking with Reeves disease, the % rate will drop. In time, the CDC will 'prove' the 'association with CFS' was 'lower than previously found'. Science then 'proves' people with MULV's and XMRV do not have CFS, but another retroviral infectious disease. This way, the history of the CDC is avoided. The WPI forced the FDA/NIH to commit acceptable levels of collatoral damage, rather than carpet bombing the patients as the CDC do.

Seriously ill and debilitated patients 'celebrate' over the Alter/Lo paper, yet if once considers the comments we can see what they are alluding to, and why the CDC have 'magic spelled' CFS into dust from what was a label that used to diagnose neuro immune disease. In time, CFS won't exist as nothing more than a psychiatric fatigue syndrome of ' chronic unwellness', this is only achieved via what Dr Lo suggested, by "Future studies should adhere to consensus definitions such as that developed by the Centers for Disease Control and Prevention (CDC)." That signals a 4 minute warning alarm bell. People with CFS are about to get nuked by the CDC, the syndrome will be wiped off the face of the earth. Anyone who has read Bill Reeves proposals for CFS knows this.

The CDC have stated anyone with neurological symptoms/XMRV cannot have CFS. XMRV/MLV's will cause neurological symptoms. Patients will be Nagasaki'd out of their own illness label.

Don't be under any illusion Dr Lo is on our side, he works for the bigger college jocks in the football team and the boot is still on our heads with studs on as we are the spectators not the players in the game. If we are lucky, we can get off the pitch half time and start our own little MULV/XMRV cheer leader club at the WPI, which will have nothing to do with CFS. CFS is about to be placed in DSM-V and there is nothing you and I can do about it. This was planned, once the WPI exposed the retroviral link to massive numbers of the populace infected with an incurable infection deriving from a mouse. CFS was a holding station to 'contain' XMRV and MULV's and it worked for nearly a quarter of a century. Once the truth was known these people with XMRV/MLV's need to be shifted out of the illness label, otherwise people ask questions.

As tax paying mice, it is not our place to ask the cat not to chase us. We should go back to our holes, nibble on the cheese and shut up. Just like we were doing, before the WPI came along............ As another military employee Professor Simon Wessely stated, who is in control of ME/CFS operations in the UK and commander of the UK press/media over XMRV through his flexible press officer Myra McClure.

''What lies behind all this talk of viruses and immunity ?... In consequence, talk of viruses and the immune system is now deeply embedded in popular consciousness ... Viruses are an attribution free from blame ... there's no blame, no shame and no stigma ...''

"Most CFS patients fulfil diagnostic criteria for psychiatric disorder. Other symptoms include muscle pain and many somatic symptoms, especially cardiac, gastrointestinal and neurological. .... Do any of these symptoms possess diagnostic significance? The answer is basically negative... The description given by a leading gastro-enterologist at the Mayo clinic remains accurate. 'the average doctor will see they are neurotic and he will often be disgusted with them.''

Control, is everything. The WPI are leading a silent revolution that smashes the Bell Jar. Outside of this horrific infection that consumes us, is the world. We weren't meant to see it, we were meant to remain under house arrest and not be seen by the public.

WPI opens the window and lets us peer out to the street below. Maybe oneday, someone will look up and see us.

 

[dannybex]

Per the notes from today's teleconference Alter's group is looking at 1,000 healthy controls.

thanks urban -- that's good news!

 

[Sing]

My understanding is that XMRV is one sequence of the family of Polytropic MLV's they spoke about. The Polytropic MLVs include xenotropic and the other kind, tropic?, which can infect the mice. These variations are all normal and expected, Lo explained, as retroviruses are frequently making bad copies of the RNA and creating variants. Still the same disease can be produced as with--he named some other examples--hepatitis?

Another thought about the politics in play. I bet they orchestrated a focus on the discrepancy between their not finding XMRV specifically vs. what the WPI found and how now the WPI is saying they found or are finding the variants too, in order to make that the center of attention rather than the discrepancies between research groups/clinical definitions among the studies with virtually opposite findings, which would have put the CDC in the headlights instead.

 

[penny]

I bet they orchestrated a focus on the discrepancy between their not finding XMRV specifically vs. what the WPI found and how now the WPI is saying they found or are finding the variants too, in order to make that the center of attention rather than the discrepancies between research groups/clinical definitions among the studies with virtually opposite findings, which would have put the CDC in the headlights instead.

I've been thinking the same thing. The change in nomenclature could be how the paper was 'softened up' to help the CDC (and others) save face. Not that I think it would be done for the sake of the folks who did the failed studies personally, but the CDC's reputation as a government body.

 

[Mark]

My understanding is that XMRV is one sequence of the family of Polytropic MLV's they spoke about. The Polytropic MLVs include xenotropic and the other kind, tropic?, which can infect the mice.

No, polytropic and xenotropic seem to be mutually exclusive terms - I guess this is a further detail we all need to nail...reminds me of when we all learned what Xenotropic meant...

Here's wikipedia:
http://en.wikipedia.org/wiki/Murine_leukemia_virus

The MLVs include both exogenous and endogenous viruses.

Exogenous forms are transmitted as new infections from one host to another. The Moloney, Rauscher, Abelson and Friend MLVs, named for their discoverers, are used in cancer research.

Endogenous MLVs are integrated into the host's germ line and are passed from one generation to the next. Stoye and Coffin have classified them into four categories by host specificity, determined by the genomic sequence of their envelope region.

The ecotropic MLVs (from eco, "house") are capable of infecting mouse cells in culture.
Non-ecotropic MLVs may be xenotropic (from xeno, "foreign", infecting non-mouse species),polytropic or modified polytropic (infecting a range of hosts including mice).

Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of recombination of endogenous sequences.

So:

- Exogenous
- Endogenous
--- Ecotropic
--- Non-ecotropic
------ Xenotropic
------ Polytropic
------ Modified Polytropic

So it would seem that the difference between "Xenotropic" and "Polytropic" is simply that the Polytropic forms can still infect mice, as well as non-mice species, whereas the Xenotropic forms can't infect mice any more.

If the polytropic forms evolved from the xenotropic forms, then I guess that would mean they evolved inside us into forms that mice are not immune to (although perhaps that would be "modified" polytropic?). But I suppose there's no reason at present to assume which forms came first.

Also from the same page:

As with other retroviruses, the MLVs replicate their genomes with relatively low fidelity. Thus, divergent viral sequences may be found in a single host organism. MLV reverse transcriptases are thought to have a slightly higher fidelity than the HIV-1 RT.

 

[HowToEscape?]

It's causality that isn't proven, not the link. The evidence for the link (association) will just get stronger and stronger with more studies, it will never be "proven".

And please don't try to prove causality...

Koch's postulates are:

1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.
2. The microorganism must be isolated from a diseased organism and grown in pure culture.
3. The cultured microorganism should cause disease when introduced into a healthy organism.
4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

So it can't be proven until someone deliberately infects someone with it! Please don't do that! I don't need Koch's "proof" of causality that badly.

Causality is a red herring here anyway, since we already know the first criteria cannot be met - unless the healthy controls are all destined to get sick eventually (and I'm not waiting around for that...)

Nature may not have read Koch's postulates.

An infectious agent that does not satisfy Koch's test may yet be harmful.
Just a few such cases:

A pathogen might only affect some, might require a co-factor, might require a long incubation period, any of which would bollix Koch's test.
e.g: One could test challenging healthy people with a typical (small) exposure to HIV, then check the results at 1,2,5 and 10 years. Some may clear it before it becomes permanently entrenched. Some would still be healthy at 10 years, and virus isolated from them (if you had the technology to isolate a few virus particles in blood) would likely have mutated and no longer be exactly the original infectious agent. "Obviously" those people appearing to be just fine after a decade cause HIV to resoundingly flunk Koch's test. The study does not record what happens to them in the next decade... "everyone knows" that a disease can't hide for 20 years then spring up and kill you. (Please don't try doing this study).

Pathogens could have cascade effects which continue long after the bug is gone.
Check people who do not now have polio yet have shortened lifespan and disfigurement due to that virus.

You can think of other ways in which a pathogen can be quite harmful without fulfilling Koch's criteria.

 

[VillageLife]

can someone set me straight: didn't they label the diff viruses they found CFS 1, CFS 2, CFS 3?

and at the same time they say these retroviruses are not necessarily the cause of CFS?

yep CFS 1,2 and 3.....I think after 25 years we have finally nailed it!

 

[Mark]

I've been thinking the same thing. The change in nomenclature could be how the paper was 'softened up' to help the CDC (and others) save face.

That's my feeling too, although we shouldn't lose sight of the fact that the change in nomenclature is (presumably) a more accurate description. We do make forward progress with the understanding of what's going on with this paper.

Alter admitted (somewhere) that the WPI are much more advanced in their work on other issues like antibodies; he was looking at this very specific question and seems to have drilled down far enough to get to the bottom of precisely what MLVs are present. Going into more detail on one particular question, whereas the Science paper covers broader ground.

But politically, it does seem that this exercise is very convenient, because that level of detail goes some way to explaining - even excusing - the negative studies. I always thought that there would need to be progress on answering that question before this could be published. They couldn't publish it saying they had found XMRV (which their first pass of results would have found I would imagine) so they had to dig deeper. Unfortunately, that makes it possible to misrepresent that the WPI didn't go into enough detail here, whereas in fact they covered a lot more ground in breadth rather than depth.

Reality is that this paper is a compromise solution, allowing everyone to present a story which defends their position. The negative studies can say it's not their fault they didn't find it because it wasn't quite XMRV. The Lombardi study is confirmed. Knowledge is advanced. And everybody's happy.

Truth is, though, that what has happened here is simple disrespect of the WPI slowing down research. Because they were small, independent, from Reno, behaving like mavericks...all these things played into the prejudices of the more 'establishment' scientists who couldn't believe that a group of motivated researchers could achieve what the authorities had failed to achieve. They also had a variety of preconceived beliefs about CFS - and that includes 'good' CFS researchers who thought a single cause was unlikely because CFS isn't really 'one condition'. So they didn't believe it - despite the ringing endorsements from the likes of Coffin, and the rigorous processes required by Science magazine. And since they didn't believe it, they didn't try hard enough to figure out what was really going on. When they didn't find it by the first simple tests, they jumped straight to theories of contamination, geographical distribution, and even fraud by the WPI. Their arrogance nearly buried us again - and maybe it would have done without Dr Alter.

 

[anciendaze]

...Future studies should adhere to consensus definitions such as that developed by the Centers for Disease Control and Prevention (CDC)." That signals a 4 minute warning alarm bell. People with CFS are about to get nuked by the CDC, the syndrome will be wiped off the face of the earth. Anyone who has read Bill Reeves proposals for CFS knows this...

Check the references. He goes back to the Fukuda definition, and mentions "consensus". Somehow, Reeves' new, improved empirical definition didn't make the cut. All current definitions claim to be consistent with the Fukuda definition. By using the word consensus, they have even alluded to the CCC.

If the CDC wants to drop about 16 years of history, he is giving them an opening. This is only the beginning of a campaign. With VIP Dx offering a serological test today which already covers all the gamma retroviruses mentioned, the CDC has been caught flat-footed. They simply weren't prepared, but WPI/VIP Dx was.

Harvey Alter has skillfully undermined the CDC position without becoming an official adversary. He has provided an unambiguous alternative to using artificial positive controls with 'spiked' samples. ("Just use the healthy blood donors with the infection I found.") This also undercuts the "no evidence the virus is in the blood supply" position. If they take another out, his admission that infection might possibly be the result of an immune defect, they will have to revise another pillar in their structure concerning immunology. The house of cards can't survive such changes.

 

[penny]

Their arrogance nearly buried us again - and maybe it would have done without Dr Alter.

And maybe would have without the leak...scary to think.

 

[Hope123]

No, polytropic and xenotropic seem to be mutually exclusive terms - I guess this is a further detail we all need to nail...reminds me of when we all learned what Xenotropic meant...

Here's wikipedia:
http://en.wikipedia.org/wiki/Murine_leukemia_virus

So:

- Exogenous
- Endogenous
--- Ecotropic
--- Non-ecotropic
------ Xenotropic
------ Polytropic
------ Modified Polytropic

I agree that polytropic and xenotropic are mutually exclusive terms but I'm not sure how accurate that wiki page is on classifying them as "endogenous" viruses, unless endogenous refers to being endogenous in mice and not referring to humans. It's in the recesses of my mind and none too clear but there were some very technical talks about this at the American Urology? CROI? conference and I was left with the impression that the researchers saw them as "exogenous" with respect to humans.