A Critique of WPI Research on XMRV in ScienceBlogs, from NYTimes

[Sing]

XMRV and chronic fatigue syndrome: Questions I have
Category: XMRV
Posted on: February 1, 2010 9:23 PM, by ERV

So here are my answers to The Brainstorm Challenge.

Some of you got real damn close to the 'answers' I was thinking of, but you all missed a great big one (which I think will make sense to you after I bring it up hehe!)

1-- Lets say youve isolated white blood cells from CFS patients. You treat these cells with chemicals that interfere with normal DNA/histone methylation. What do you think will happen? Do you think that is a good diagnostic test for retroviral infection?
The Reno groups decision to use this as a diagnostic test is absolutely baffling. The idiomatic definition of 'epigenetics', histone and DNA modifications, probably evolved as a method of controlling pirate DNA. Pirate DNA like endogenous retroviruses.

Put 'ERV methylation' into PubMed. 'LTR methylation'. You screw this up, you get particle production.

Treat cells with a chemical that messes up methylation... and you get retroviral particle production... XMRV or not.

2-- Magic Johnson was diagnosed 'early' and got on antiretrovirals. Do you think there is any chance Magic Johnson will develop AIDS?
Maybe he will, maybe he wont. I would not say "Magic Johnson will not develop AIDS" in a million years.

Heres what happens with HIV-1 infected individuals:
Lets say you are diagnosed early. Get on HAART, viral load goes down, CD4+ T-cells stay up, YAY!

Well, there are always drug resistant variants present in the patients quasispecies.

Drug resistance comes at a fitness cost.

So, there are still HIV-1 viruses replicating in the patient. They might be real shitty, replicating real slow and awkward like, but theyre still going.

Some people are very very very unlucky, and in those few crappy replication cycles, the virus stumbles upon a secondary compensatory mutation. A mutation that allows it to be drug resistant AND able to replicate at a normal rate.

Some people are very very very lucky, and in those few crappy replication cycles, the virus just keeps banging its head against a wall.

The latter is like Magic Johnson. But there is no guarantee, with anyone who takes their antiretrovirals religiously, that they wont be unlucky tomorrow.

With todays technology, with todays antiretrovirals, we can extend the lives and improve the quality of life of people with HIV-1. But we cannot say they will 'never' develop AIDS.

3-- Lets say you isolate a retrovirus from a sample from 1984. The sequence from that virus is not significantly different from sequences you are isolating from patients 25 years later. In other words, this 'retrovirus' is not acting as a quasispecies. What are possible explanations for this? If the virus does not mutate, why could the British group not find MLV sequences we know are conserved? If this virus does not mutate, why would the PI looking for this virus be worried about PCR giving 'false negatives'?
*sigh*

Fish gotta swim.

Birds gotta fly.

And retroviruses gotta act as a quasispecies.

They have to. They cannot help it. Its a side-effect of an error-prone reverse transcriptase and inter- intra-strand recombination. Even if it finds the most perfectest sequence EVAH!, it cannot keep it.

And that most perfectest sequence in Patient #1 might be awful in Patient #2, and Patient #3. Every individual is a different environment...

Certainly there are regions of a retrovirus that are functionally constrained-- if they do not have sequence ABC, then the proper structure doesnt form, and viruses are non-infectious, therefore, sequence ABC is always there, but in a region like env? There is genetic plasticity, there is functional plasticity, there is selective pressure by everyones individual antibody repertoire! You cant stop the virus from mutating! If the virus stops mutating, the Red Queen race between us/retrovirus stops, and the virus is gone. I am not currently aware of any instance of anyone or any organism being 'cured' of a retrovirus ever.

But, quote Mikovits, "XMRV doesnt act as a quasispecies."

I just dont see how this is possible.

4-- Lets say we just discovered a new virus in humans. While most laboratories are being conservative/cautious about their statements and approach to this discovery, another lab is verbally, though not scientifically, 'connecting' this virus to CFS, breast cancer, chronic lyme disease, autism, and a cadre of other 'medical mysteries'. Furthermore, the PhDs in these labs are giving medical advice like 'take supplements X, Y, Z and immune modulators' and suggesting 'detox'. They are also heavily emphasizing 'early detection' of this new virus to prevent this list of diseases, and why, they have a test for sale right here. Do you think that is the most scientific approach to this new virus? What advice would you give this group of scientists?
This is example #918356125 of how unprofessional the Reno group is. There has been nothing published connecting XMRV to autism. Nothing. There has been nothing published connecting XMRV to chronic Lyme disease. There has been nothing published connecting XMRV to breast cancer. So when youre talking to the general public, you say general things like "Lots of other labs are trying to see if there is a connection between XMRV and their disease of interest. None of this, including XMRV-->CFS, has proven to be causal yet. This is currently a neat phenomena in CFS that might turn out to be something real fantastic! But right now, everything is preliminary."

Standing up in front of a group of laymen saying "THEYVE CONNECTED XMRV TO AUTISM AND BREAST CANCER AND LIEK EVERYTING!" screams insecurity and immaturity.

And a PhD, in any field, giving medical advice? Thats down right irresponsible.

Look, my epigenetic research, I just tell people "You know what? I eat my broccoli, LOL!"

I do not tell people failing chemo "OMFG YOU NEED TO TAKE X, Y, Z SUPPLEMENTS AND DETOX WARBLEGARBLE!"

I have no doubt CFS is a real disease. PhDs are not medical physicians qualified to treat diseases. End of story.

Furthermore, Ive heard it through the grapevine that a nice, normal diagnostic test for XMRV is in the works. It looks for anti-XMRV antibodies. Awesome!

Its not from the Reno group.

It will be for research purposes only, at this point, to study the epidemiology of this virus.

There is also lots of nice, normal basic science, basic virology being done on XMRV.

Not from the Reno group.

There is going to be lots of information coming though the pipeline on XMRV. Maybe it causes CFS, maybe it doesnt. Maybe it causes certain kinds of leukemia, maybe it doesnt. Maybe it causes certain kinds of prostate cancer, maybe it doesnt.

This information is going to come out through hard work done by normal scientists doing normal scientist things.

Not by PR releases accusing other labs of fraud.

Not by doing confusing, scary, and misleading conferences for prostate cancer patients.

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Comments
1
There has been nothing published connecting XMRV to autism. Nothing. There has been nothing published connecting XMRV to chronic Lyme disease. There has been nothing published connecting XMRV to breast cancer.

Smith, on this issue you have been nothing short of brilliant. Clearly, this is a case of a "virus in search of a disease." These jerks are sub-par scientists trying to give false hope to CFS patients and make some big bucks by patenting a "test" for XMRV antibodies. Next thing, they'll try to convince the American Red Cross to use this "screening" test on the blood supply -- a lotta money to be made with this scam.

You have smoked out these quacks with facts, logic and good science. Well done.

Posted by: Ben Rabb | February 1, 2010 10:54 PM

2
I do not know who you are, I am not a scientist myself, and I get lost in most of your arguments. But for some reason it seems to me you have something personal against WPI and Judy M. which I do not understand why... maybe because you need visits into your blog that will generate traffic, which also will generate add revenues into your pocket? Could be... What I know is that WPI has no economical interest, is a foundation, the mother of a CFS patient is in charge. The benefits of the XMRV test are used for research, and you are wrong assuming that XMRV has not been linked to Autism, Fibromialgia or Rare Multiple Sclerosis. You are wrong because it was detected in 40%, 60% and 100% of the small samples they analyzed but was not published in Science, because in order to publish you need a big study as they did with CFS. But is worth to have a look given the small studies. In my view anybody can understand that...

Posted by: pochoams | February 2, 2010 7:28 AM

3
pochoams, if you read and understood erv's arguments about the handling of the science, you would understand why she's unimpressed.

100% of a small sample of people with autism had two legs. Let's start the amputations right away, shall we?

Posted by: Stephen Wells | February 2, 2010 9:07 AM

4
pochoams - there's one thing I don't understand about your argument (OK, that's a lie) - why do you accuse this blog of having a conflict of interest, and in the same paragraph say that because the Reno group is led by a mother with CFS that is a good thing?

Surely they are both 'conflicts of interest'.

On a side note - as a (somewhat) medically trained person, your blog does a very good job of explaining virology. Keep up the good work.

Posted by: F Hamilton | February 2, 2010 10:08 AM

5
This was a fantastic post, Abbie. Very clear and emphatic. Too bad at least one person still doesn't get the point...

Posted by: minimalist | February 2, 2010 10:16 AM

6
Which branch of the shadowy international cabal is paying you to weave your web of lies?

Do they have any openings in legal?

Have robe, will travel.

Posted by: Prometheus | February 2, 2010 11:19 AM

7
One aspect of this issue confuses me. I've heard that CFS is kind of an umbrella diagnosis, and that people whose symptoms have no confirmed cause often get a CFS diagnosis.

Is it a disease, many diseases, a group of symptoms? I'm not a researcher, so I don't know whether one assumption is more practical than another. Is it best to assume all CFS diagnoses have the same cause until proven otherwise? Are researchers trying to find one identifiable marker (such as XMRV) and eject all non-XMRV-infected, chronically fatigued people from the CFS diagnosis? Was my impression about the umbrella diagnosis all wrong?

Posted by: Stella | February 2, 2010 3:31 PM

8
Excellent question, Stella. I have heard CFS refered to as a garbage can diagnosis, a receptacle for patients who insist on an answer but the science is not available to supply one. Certainly, once the science does come up with something (perhaps XMRV) to define the disease, patients given an incorrect diagnosis will be shuffled off into the next garbage can diagnosis.

And, erv, as for the connection to other diseases as mentioned in the original post, people with a diagnosis of CFS have scientifically and anecdotaly shown higher incidences of breast cancer, leukemia and other diseases. Families show evidence of being communally infected, and children in those families do have a higher occurance of Autism. Provided the connection between XMRV and CFS holds up, it is a legitimate theory, but, as of know, it is just a theory.

As for a test that looks for XMRV antibodies, that brings up an interesting dilemma. Many of the usual tests for other diseases are not effective on people with damaged immune systems, simply because they do not have the ability to produce antibodies. Now, as of today, I do not have a way to scientificly prove that I have CFS. But tests have proven beyond any doubt that my immune system is lacking several components. Here's another THEORY for you. Patients who become ill with CFS do so because they are unable to produce the antibodies needed to to stop XMRV in its tracks.

Posted by: heidi | February 2, 2010 4:10 PM

9
Heidi, antibody deficiency is not common in CFS (nor is it common in HIV). That notion would directly contradict the claim of opportunistic infections (EBV, HHV-6, CMV, etc) in CFS patients. Most of those opportunistic infections are detected, after all, via abnormal antibody tests. If your body is not producing antibodies to common pathogens, it would be extremely unlikely that you'd end up with a CFS diagnosis.

Posted by: thomas_bernhard | February 2, 2010 4:27 PM

10
Despite the media gaffes, the WPI has made a huge contribution to the sufferers of CFS, their families, and to those yet to become sick with this truly pernicious and misunderstood illness. It's a net positive, no matter how you break it down. More funding, more news, more hope, more research. Obsessively condemning a few speculations that J.M. made during a web seminar strikes me as really, really silly. Yeah, JM is not so savvy in front of the cameras. Are you?


Posted by: thomas_bernhard | February 2, 2010 4:46 PM

11
Also, during her lecture, JM went out of her way to advise CFS patients to wait for a better diagnostic test. I.e. an antibody test. She did not once explicitly recommend the VIP XMRV culture test for CFS patients.

Posted by: thomas_bernhard | February 2, 2010 4:52 PM

12
I enclose the last XMRV presentation given by WPI in case anybody is interested.
http://www.wpinstitute.org/news/docs/WPI_JAM_012210.pdf

Posted by: pochoams | February 2, 2010 5:19 PM

13
"Yeah, JM is not so savvy in front of the cameras. Are you?"

Yes, she is.

Posted by: Prometheus | February 2, 2010 5:50 PM

14
Prometheus, even us lurkers know you're in love with her.

Posted by: thomas_bernhard | February 2, 2010 6:19 PM

15
"But, quote Mikovits, 'XMRV doesnt act as a quasispecies.'"

What? Just, what?

Posted by: Vene | February 2, 2010 6:51 PM

16
Thomas-- You are not a lurker. Lurkers dont comment, or do so rarely. Youve only commented on a few XMRV posts, a very new topic on this blog, so technically, youre a newb.

Also, your 'newb dead giveaway' is lurkers know that Ive done/do lots of presentations to the general public, which are available here on ERV, and some of them I didnt even know I was being recorderd. So Prom was poking fun at your newbness.

hehe. Newb.

Vene--


One of the really interesting things about these studies is we only isolate one thing out of these people. When we do the sequencing, it’s clean. We don’t isolate quasi-species. We don’t have the virus have these changes here in one week or one year… we have patient samples across dozens of years. We isolated XMRV from a 1984 plasma sample from a patient. So we got it in 2008 and we got it in 1984, which again suggests that the virus has been around at least 25 years and it might have a role in disease. But it’s not plausible, so yes indeed, it could play a role in other things… Did I answer the rest of that question?

Posted by: ERV | February 2, 2010 7:28 PM


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[kurt]

I hope this mean-spirited blog post is not an example of what is to come when the critics start to dissect the Science article. Mikivitz's talk was helpful, it clarified some of the methods used in the Science article. Just as some of the supporters of the XMRV hypothesis have been overly optimistic, some of the critics will be overly pessimistic.

But although the tone was pretty antagonistic, there is some truth I think in some of the criticisms mentioned, several of those issues have come up in discussions I have had with a researcher, they are real problems. Unfortunately there are other issues as well, more than just the few mentioned here.

WPI is finding something with their MuLV antibody tests, but just what they are finding is not easy to prove yet. The conclusion that they are finding XMRV and that is causal in CFS appears to be based on a lot of assumptions right now.

One of the reasons multiple confirmation studies, both replication and validation studies, are important is that a consensus must be reached by people who are not biased in any way, and who have evaluated ALL of the issues raised by both sides in the debate over a new scientific finding. Until that happens XMRV remains an interesting hypothesis and I think the CFS world would do well to treat it that way. In my opinion that is also what Mikovitz was backhandedly requesting in her presentation, she of course is biased and optimistic about her research, but at the same time she made clear that commercial testing is premature. That maybe has become more obvious the past few months to everyone.

 

[CBS]

Do not read this if you are feeling fragile today.

My most sincere apologies to anyone who is upset by either the language used by the Blog author, the quotes or the link in my post. I weighed whether or not to post this. I did so because I feel like we need to fight this head on and let those who would sponsor such language know that we will not sit idly by and continue to support those that would denigrate us or to provide others the platform to do the same.

I would recommend that you not read any further if you are having a bad day or you are on the brink (or in the middle or coming out) of a crash and are feeling fragile. Leave the fighting to those of us who are up for it at the time. Take care of yourself!

My Response to the "blog" and the link on the NY Times:

Write the NY Times and tell them you want a response - I did.

NYT - letters@nytimes.com
SB - editorial@scienceblogs.com
Natl Geo - ngsline@customersvc.com

Dear Editor,

I was quite dismayed today to see that one of the 'Selected Posts' from Science Blogs linked on your Science web-page was by a blogger that goes by the name of ERV.

Are you familiar with ERV and her ongoing personal attacks on the researchers at the WPI as well as her attacks on people with CFS? Here is just one example where she repeatedly refers to Judy Mikovits in the most vulgar terms ('a gigantic f****** ***t,' and as 'a deceitful, conniving, gigantic f****** ***t') and dismisses it as just the way that scientists talk about each other: http://scienceblogs.com/erv/2010/01/xmrv_and_chronic_fatigue_syndr_5.php.

Apparently ERV is a 23 year old graduate student who has been given a megaphone by Science Blogs that is much too burdensome for someone with her level of maturity and she uses it in a way that does nothing to further an enlightened discourse. I have tried to contact the Science Blog editors about their policies regarding personal attacks and profane language that adds nothing to the discussion and have received no response. I have canceled my subscription to National Geographic because of their support of Science Blogs and a similar failure to respond.

I am asking you to carefully consider whether or not you consider this part of a constructive "scientific discourse" and if you can defend this as any part of a healthy dialog. If this type of debased attack is, as I feel it is, indefensible then why ought I continue to patronize your web-page and subscribe to your newspaper? I am not the only one that feels this way. I am sure that 1 million CFS patients and their families would find this similarly offensive.

I have always felt that the NY Times had set a higher standard than this. Unfortunately, the company you keep and their standards do reflect upon you.

I would appreciate a reply.

 

[Adam]

Well done CBS for writing the NY Times. I have dipped in and out of ERV's blog wondering who is this person. What is their status in the world of Virology? I also thought (like you decided to with sincere apologies) bringing it to the attention of members on the forum. Whilst there are many valid points raised I find the tone very unpleasant. I really hope the majority of researchers/virolgists/scientists are human! On balance I think it was a good (brave) decision to post this here.I guess you'll let us know if you get a response from NY Times. I hope that will be further discussion by Sciencey forum members to better inform the less acdemic ones like me.Thanks CBS and also Kurt for your views.And Sing too for having the guts to raise the debate seeming ly raging in the world of virology.

 

[CBS]

... to raise the debate seeming ly raging in the world of virology.

I seriously doubt that this blog represents any real debate raging in the world of virology. There are many points to be debated, questions to be asked and much to be confirmed or disconfirmed but in this case the raging is mainly going on between the ears of the blogger and her small cadre of worshipers.

That said, links to content like this in the NY Times are not benign.

 

[Hysterical Woman]

I seriously doubt that this blog represents any real debate raging in the world of virology. There are many points to be debated, questions to be asked and much to be confirmed or discinfirmed but in this case the raging is mainly going on betrewwn the ears of the blogger and her small cadre of worshippers.

That said, linkes to content like this in the NY Times are not benign.

Hi CBS and all,

We can only hope that the blog isn't considered a serious debate by most people. Unfortunately, there are some people in this world who are so unhappy or have such a lack of self confidence that they take pleasure in trying to tear down others. That doesn't mean that we accept any positive research that comes our way without question, nor does it mean that these people should get away with their meanness without a challenge. However, these people have always been a part of the world and probably always will be.

Take care,

HW

 

[Mark]

I have to agree with CBS that ERV's blog is an immensely important frontier for us. I have periodically reviewed a Google search for XMRV, and after going 5-10 pages deep, pages from ERV's blog seem to be the leading 'sceptic' information out there (ie. the most prominent voice against the WPI and its XMRV research, on the internet, by far).

And ERV's blog does indeed need to carry a health warning for ME/CFS patients, it is vitriolic, offensive, judgmental, and likely to be upsetting to many people, at the same time as being (apparently) scientific, challenging and highly credible (a combination which accounts for the popularity - or perhaps inversely, the popularity may explain ERV's personality which comes across as somewhat psychotic to me!).

So it is indeed important to respond to ERV. How to do so is another matter. Focusing too much attention might only serve to feed the monster in this case, since the blog seems to thrive on stirring up anger and controversy and on the resulting 'unscientific' comments from patients, which can then be produced as evidence of how ignorant and unscientific and nonsensical the patient lobby is. Unpleasant though ERV may be, the most effective and valuable responses in my view are the factual and scientific responses; outrage and insults seem to just spur this blogger on and confirm the prejudices of the readers. That said, a calm comment questioning ERV's confrontational approach is never out of place...

One thought raised, reading Kurt's reaction, is to wonder whether we have failed somewhat to explore on this forum these alleged flaws in the detailed methodology of the WPI study. Kurt, you seem to be agreeing they found something but whether it was XMRV or an MLV or something else, possibly endogenous, is very much an open question. That appears reasonable if ERV's queries are valid, but then it becomes crucial to go into all that detail and to define precisely what other possibilities might turn out to explain the WPI findings. ERV doesn't seem to be presenting any kind of rival theory to explain the test findings (which says a lot btw), but I have this sense that if one defined, for each test, what the other possible explanations of positive results might be, if you took all the results together then you'd still end up with something which, if not XMRV, is still evidence of a probable pathogen implicated in ME/CFS.

In other words, I'd love to see the scientists on this forum go through ERV's challenges point by point and explain to us what they might mean.

Final note: I'd love to hear what ERV thinks of John Coffin. I believe there's a blog post where ERV lumps Coffin in with all the other researchers and basically calls them all c**ts and idiots! Presumably an oversight in failing to realise who Coffin is! Worth tracking down and highlighting...Identifying Coffin's impeccable credentials and his close involvement and tacit support of the WPI methodology - that should be a key bullet to fire; I'd be very interested in ERV's analysis of the Coffin presentation at CFSAC...perhaps ERV really does think John Coffin is an idiot too, in which case that might help the scientific community decide how seriously they ought to take ERV's accusations of stupidity...

 

[George]

Chuckles

I remember being ERV's age and feeling like I knew it all. The thing about life is that it tempers us, it teaches us compassion, patients and understanding. ERV will get there, hopefully, one day. In the mean time these are the things that I take into consideration when reading ERV.

She tends to only look at parts or portions of anything she doesn't like. For instance She did not watch the rest of DR. Mikovitz presentation on prohealth. It is difficult to come up with a sane and balance view of anything if you only see what you want to see and nothing else.

Her science is incomplete. Many of the theory's she presents lack all of the relevant data she often chooses a few bits and pieces and attacks those without either understanding the context from which they are taken or ingnoring the bigger picture. This installment of her blog is a prime example. She talks about altering the DNA in a way that would cause HERVs to become active or to get a blob of goo. Neither of these things happened with the XMRV finding otherwise you would find the fragments in the healthy controls as well. Now the goo question is still out on the IC study. (chuckle)

She is quick to point out that DR. Mikovitz does not live up to her "ideal" of a researcher or Doctor. However she refuses to see that her own behavior and language only vaguely fits the "ideal" for a decent human being.

The people who communicate on her blog tend to be a small circle of friends (check past blogs and you will see the same names come up again and again) and those who are not from the industry who wander in from Google and make interesting points sometimes. This is NOT a debate among virologist or even researchers.

​

The way you treat anybody is the way you treat everybody. In general how we treat the waitress and the checkout guy are the way we treat ourselves and those around us. ERV has attacked anyone and everyone who doesn't agree with her. How long do you think a person can do that before the find themselves with no one left in the room???

 

[Sing]

I so appreciate your very intelligent responses, Kurt, CBS, Adam, Maxine and Mark!! I didn't know what to do with this blog, how really to evaluate it, when I ran across it yesterday in the NYTimes--but I felt sure that some people in this forum would be able to help with the science and the politics, and you have. Thanks also to Maxine for your psychological understanding. I am sure you are correct. Tearing others down is how some people feel important.

Thank you!

Sing

 

[Sing]

George, brilliant contribution--thank you too!

Sing

 

[Mithriel]

I don't find it easy to follow the science of retroviruses and their detection, but I would take the expertise of a twenty year veteran over that of a 23 year old any day.

I find it impossible to believe that the WPI would be slapdash or fraudulent. We know that the test was only offered because other labs were charging patients and they weren't doing it properly. It was because of patient desperation and profit was not the reason for the research. The Whittmores want a treatment for their daughter, no advantage to them to push fraudulent work.

The IC people attacked Mikovitz's paper by implying her results were due to contamination, she only responded.

Patient's are desperate for a treatment so theorising about supplements is no bad thing. She is advising against antiretrovirals and continually saying she is not a medical person, though I am sure she will have discussed this sort of thing with medical doctors like Dr Petersen.

So the things I know about on this blog I can see how biased and wrong they are, so I have no confidence in her scientific take.

She doesn't like people with CFS, she is ignorant about it and she is just plain horrible.

This is not scientific debate.

Mithriel

 

[Adam]

Thanks CBS

This puts this chapter of the XMRV story in context. I think being nearer (geographically speaking) to the centre of this perhaps lends you a clearer understanding.

thanks again

 

[CBS]

The way you treat anybody is the way you treat everybody. In general how we treat the waitress and the checkout guy are the way we treat ourselves and those around us. ERV has attacked anyone and everyone who doesn't agree with her. How long do you think a person can do that before the find themselves with no one left in the room???

So true! I simply cannot imagine a calm rational inner dialog behind the vitriol, incomplete analysis often lacking context and the complete (and ironic) absence of self-awareness.

 

[Mark]

ERV's Scientific Questions

I've edited out all the comments and nonsense and garbage from ERV's blog page, leaving just the questions ERV is raising which seem to need an answer. I consider ERV's criticism of the WPI announcements of their findings and behaviour etc to be so unfounded and rabid that it's not worth mentioning other than to point out that a few Mikovits quotes should demonstrate well enough that this is just straw-manning, and the only criticism in ERV's question 4 is of sharing information honestly and openly with us, the patient community. I don't see how all the Magic Johnson stuff has any relevance to the WPI, so I've removed that too. Here's what's left - science questions that I vaguely understand and which sound sensible, and to which I'd like to hear the response...

Lets say youve isolated white blood cells from CFS patients. You treat these cells with chemicals that interfere with normal DNA/histone methylation. What do you think will happen? Do you think that is a good diagnostic test for retroviral infection?

The Reno groups decision to use this as a diagnostic test is absolutely baffling. The idiomatic definition of 'epigenetics', histone and DNA modifications, probably evolved as a method of controlling pirate DNA. Pirate DNA like endogenous retroviruses.

Put 'ERV methylation' into PubMed. 'LTR methylation'. You screw this up, you get particle production. Treat cells with a chemical that messes up methylation... and you get retroviral particle production... XMRV or not.

Lets say you isolate a retrovirus from a sample from 1984. The sequence from that virus is not significantly different from sequences you are isolating from patients 25 years later. In other words, this 'retrovirus' is not acting as a quasispecies. What are possible explanations for this? If the virus does not mutate, why could the British group not find MLV sequences we know are conserved? If this virus does not mutate, why would the PI looking for this virus be worried about PCR giving 'false negatives'?

Fish gotta swim. Birds gotta fly. And retroviruses gotta act as a quasispecies. They have to. They cannot help it. Its a side-effect of an error-prone reverse transcriptase and inter- intra-strand recombination. Even if it finds the most perfectest sequence EVAH!, it cannot keep it. And that most perfectest sequence in Patient #1 might be awful in Patient #2, and Patient #3. Every individual is a different environment...

Certainly there are regions of a retrovirus that are functionally constrained-- if they do not have sequence ABC, then the proper structure doesnt form, and viruses are non-infectious, therefore, sequence ABC is always there, but in a region like env? There is genetic plasticity, there is functional plasticity, there is selective pressure by everyones individual antibody repertoire! You cant stop the virus from mutating! If the virus stops mutating, the Red Queen race between us/retrovirus stops, and the virus is gone. I am not currently aware of any instance of anyone or any organism being 'cured' of a retrovirus ever.

But, quote Mikovits, "XMRV doesnt act as a quasispecies." I just dont see how this is possible.

Scientists?...

 

[Dr. Yes]

Check This Thread:

Natasa778 has posted links to two articles from the "Age of Autism" blog about "Science" Blogs' owner, Seed Media Group, that I think you will find very revealing. Her thread is here:

http://forums.aboutmecfs.org/showthread.php?2811-About-Science-Blog

The first article, "'Science' Blogs: Seed Media's Aggressive Weed" sheds light on why they have a blogger like ERV writing for them. As one commenter said, they have more than a few 'shock jocks'. And it gets worse, apparently, in terms of Seed Media's ties to major pharmaceutical companies.

 

[George]

ERV

The Questions as outlined by Mark. (what up Mark,?(waves))


In other words, this 'retrovirus' is not acting as a quasispecies. What are possible explanations for this? First of all there are only 2 known RNA or retroviruses, that's a pretty small sample to be making such finite statements about. (grins)

I don't know the answer to the question but the debate about concept of quasi-species is on going.

Holmes and Moya claim that quasispecies is an unnecessary
and misleading description of RNA virus evolution, that virologists
refer to quasispecies inappropriately, and that there is
little evidence of quasispecies in RNA virus evolution. They
wish to look for other ideas in evolutionary biology and to set
down an agenda for future research. I argue here that real virus
quasispecies often differ from the theoretical quasispecies as
initially formulated and that this difference does not invalidate
quasispecies as a suitable theoretical framework to understand
viruses at the population level.
​

There are birds that don't fly and probably somewhere a fish that dosn't swim.



If the virus does not mutate, why could the British group not find MLV sequences we know are conserved?

I don't know the exact sequence that the IC study looked at but I do know that it was over 330n (nucleotides) shorter that the one from WpI as well in a different region. One of the things we don't know and never will is how many times the samples were run, Three is standard however Lombardi et al ran the PCR 4 times because of the fact that this virus has very low numbers and can easily be missed.

And then there are the patient cohort questions . . .

ERV isn't aware of the politics involved in this situation, I'll leave it at that.



If this virus does not mutate, why would the PI looking for this virus be worried about PCR giving 'false negatives'?

See above, this virus is very unique. In HIV the virus may make 50 or 60 copies in one cell, it's a machine a killing machine taking over the immune system. XMRV is not HIV, It makes one copy per cell then stays in that cell and simply copies itself when the cell divides. It does however make viral proteins and it looks as if the proteins may turn out to have more to do with the illness than viral production or load. Plus, WPI is worried because patients lives hinge on these finding sometimes.


All these questions have been asked and answered before. The quasi species question is what led to the question of contamination. However, the question of contamination has been answered and is being answered. Many of the question that ERV asks are questions that will be answered with good science later down the road for us as well as for her. She, like us is getting a bit ahead of herself. (chuckles)

 

[dancer]

George, my brain can't really grapple with the science today...but I just have to say that your gentle chuckles over the ruckus have been very comforting and reassuring. Thank you to all who are able to understand, dissect, explain. And to all for responding with calm and patience in the midst of the roller coaster of findings... it's helping me remain calm and patient (well, sort of).

 

[CBS]

George,

Again, well put:

In other words, this 'retrovirus' is not acting as a quasispecies. What are possible explanations for this? First of all there are only 2 known RNA or retroviruses, that's a pretty small sample to be making such finite statements about. (grins)

What? You don't actually mean to suggest that there may be something new to learn in such a thoroughly established field do you?

The fact that the WPI, NCI, Cleveland Clinic and other labs are able to culture whatever it is they have found and that it doesn't (reliably) show up on the standard PCR test leads me to suspect that the WPI has definitely found something unique but that the something they have found is still a bit of an unknown.

We'll all know quite a bit more in 6-12 months once the studies start coming out (and nothing written on the Science Blogs will have changed anything of substance). See Cort's list of ongoing XMRV research: http://aboutmecfs.org/Rsrch/XMRVStudies.aspx

 

[starryeyes]

I wish people would stop posting Erv's abusive blogs on this site. And if you do feel that you still have to post her, could you please warn us it's her blog at the very beginning of the thread?

 

[xanadu]

I wish people would stop posting Erv's abusive blogs on this site. And if you do feel that you still have to post her, could you please warn us it's her blog at the very beginning of the thread?

All it needed was the link - which was missing.