Question concerning XMRV

[lansbergen]

I found everything that happened then very strange, too.

Me too and it did not convince me nothing was there.

 

[Esther12]

She offered to work alongside doubters but no one took up the offer.

The blood working group did work with her, and she was a co-author of the negative paper: http://science.sciencemag.org/content/early/2011/09/21/science.1213841

Do you say this with respect to ME or more generally?
Wrt ME my last information was (spontaneous and/or longterm) improvement is very uncommon.

Would you be willing to cite that here? I found a Dubbo study, but at first sight that doesn't look like the one you seem to mean.

There were a few papers from that study, and I've forgotten which ones show what. This is one:

https://www.ncbi.nlm.nih.gov/pubmed/16950834

It does track patients over time, after their initial infection, showing how appx half who have been ill for six months go on to recover, but that the longer people have been ill the less likely they are to recover.

Even if only 5% of people ever recovered, that would still lead to thousands and thousands of recovery anecdotes from patients around the world.

That's why I asked and from a scientific point of view - as a curious person - I am not entirely happy about stopping research in that direction.

The study claiming to show an association with CFS and XMRV was pretty thoroughly debunked. If I was in charge of allocating limited research funding, I probably wouldn't prioritise putting more money into that area without any evidence is was likely to be useful.

I share that.
I was wondering these days: How common are contaminations in labs? I guess not very uncommon. How is that being taken care off? How will I know when reading those papers that there is no contamination present?

I don't really know what I'm talking about, but just from science podcasts around that time, it sounded like part of the issue was that PCR testing was so good at picking up what it was looking for, that contamination became very difficult to control for.

You couldn't really tell from an individual paper whether contamination might be an issue. Identical collection of samples and blinded testing is useful, and then you need independent replication. XMRV/CFS fell down on both those fronts.

Me too and it did not convince me nothing was there.

You can't really prove that nothing is there, but we can say that the finding XMRV was associated with CFS did not hold up under blinded conditions at the WPI, or when independent labs attempted to replicate it.

In addition, there are the worrying aspects to Mikovit's work, like that replicated slide which seemed to indicate CFS patient samples had been treated differently to control samples. More recently, Mikovits seems to have gone over to alternative medicine, autism type stuff.

Actually, that reminds me, I think that scienceblogs, which hosted the blog which revealed the duplicated slide, is due to go offline soon, so this page might be lost: http://scienceblogs.com/erv/2011/09/30/xmrv-and-chronic-fatigue-syndr-29/

 

[lansbergen]

You can't really prove that nothing is there,

That is right but the way it was opposed made my alarmbells ring. I still think it stinks.

 

[Valentijn]

That is right but the way it was opposed made my alarmbells ring. I still think it stinks.

Yes, I wasn't impressed with one of the studies which claimed to disprove XMRV involvement. And the way some parties used the disproving of XMRV involvement to support their claim that ME is psychosomatic was particularly distasteful.

But the other studies debunking XMRV were methodologically sound, and have resulted in progress themselves. Lipkin found other signs of immune dysfunction while searching for XMRV, and consequently became much more involved in ME research. And it led to Kenny de Meirleir finding an apparent immune reaction to HERVs, part of our own DNA.

 

[Inara]

@Esther, thanks a lot for your info! At times a bit too fast for me, I am not deep in this topic, that's why I asked.

I am not focused on XMRV. My feeling is, taking into account what I know up til now, that there was something. It might be relevant for ME - but who knows.

Also thanks for linking the Dubbie study!

In addition, there are the worrying aspects to Mikovit's work, like that replicated slide which seemed to indicate CFS patient samples had been treated differently to control samples.

I don't know anything about this. I don't get the point from scienceblog.com. (I did have a good laugh when following the Guardian link about extremist people with ME; hope this is not misunderstood.) Would you be willing to explain?

More recently, Mikovits seems to have gone over to alternative medicine, autism type stuff.

After loosing all future in science and mostly all possibilities to earn money, I couldn't make an accusation. There are worse ways to earn money. I don't know the specifics about what happened at WPI, I just think it was strange. It shouldn't have affected research, but it did, and that's not good.

I read Micovits' book. It is HER view of the story, sure. Still, politics and power games were involved. It is very uncommon to get a scientist into jail even if he/she is a fraud (not saying she was a fraud). There were definitely bigger (proven) fraud scientists in history. Nothing comparable happened - well, I guess.


@Valentijn: That Lipkin got interested was a sign for me that there was something. I am relly interested in this HERV thing. Would you be willing to link the paper?


Note that HIV tests aren't really reliable at all, especially the "fast tests". This doesn't proove to me that HIV is crap, it shows it's not reliable and this should be improved via research.

Montagnier postulated (in an interview) that HIV alone won't lead to Aids, there have to be co-factors.

If retroviruses are involved research on it is probably pretty complex. If lab contaminations might be common this makes things even more difficult. If HERV is involved, I'd guess things would get even more complex. There are parallels between Aids and ME - at least that was my impression - but also between ME and MS. One could presume there might be a common cause; human body works in the main aspects similar. Why not take that information? HERV are also discussed for MS, a retrovirus is involved with Aids.

My feeling increases that the retroviral/HERV direction might be interesting.

A doctor, who wouldn't believe in ME, said all about that topic seems so chaotic. And I had to agree - it is. I have the feeling research in ME still is a little un-coordinated, like a kestrel flying around a mouse but never dashing down to get it.

 

[Esther12]

[QUOTE="Inara, post: 14929, member: 62]
After loosing all future in science and mostly all possibilities to earn money, I couldn't make an accusation. There are worse ways to earn money. I don't know the specifics about what happened at WPI, I just think it was strange. It shouldn't have affected research, but it did, and that's not good.

I read Micovits' book. It is HER view of the story, sure. Still, politics and power games were involved. It is very uncommon to get a scientist into jail even if he/she is a fraud (not saying she was a fraud). There were definitely bigger (proven) fraud scientists in history. Nothing comparable happened - well, I guess.[/QUOTE]

I really don't like people making money from the sick and desperate by going beyond the evidence. There are always worse ways to make money though!

I'd be deeply suspicious of the claims in her book, and only believe those things that you can independently verify. It came out after Mikovits seemed to move from flawed science to myth-making.

The duplicated slide mattered because those identical slides had been claimed to be results for differently described experiments. They should not have been identical! Also, at the time there were a handful of patients who really didn't want to acknowledge that XMRV was being debunked so there was the slightly surreal experience of having them try to argue that these slides were not the same, but were actually from different experiments.

 

[large donner]

Did Lo and Alter also contaminate their samples in their initially positive claimed study?

 

[Inara]

Hi @Esther12

I really don't like people making money from the sick and desperate by going beyond the evidence.

I find that questionable, too. The reason why I don't have an opinion about Mikovits is because I don't know enough.

I'd be deeply suspicious of the claims in her book, and only believe those things that you can independently verify.

That holds for most sources. I didn't say I believed everything in the book, but that it's her own view. I will never know what really happened then.

The duplicated slide mattered because those identical slides had been claimed to be results for differently described experiments.

I didn't understand it, that's what I meant. Therefore I cannot say if it matters or not. Maybe you could explain it to me?

so there was the slightly surreal experience of having them try to argue that these slides were not the same, but were actually from different experiments.

What were their arguments?

It is very often very difficult to know the actual facts of a situation if you're an external. One can only collect as much information as possible and come to a conclusion, that most possibly will not be the exact reality. Therefore I am often careful with these things.

 

[Inara]

Did Lo and Alter also contaminate their samples in their initially positive claimed study?

Could you linķ to that study or say more about it? I am not so deeply informed as you all seem to be about this topic. (although I tried to search about it - I see there is more)

 

[Jonathan Edwards]

I don't know the specifics about what happened at WPI, I just think it was strange. It shouldn't have affected research, but it did, and that's not good.

Dear @Inara,
If you work in biomedical science you get to see that there is nothing unusual here. A scientist becomes convinced that they have the answer to a problem and so convinced that they miss the fact that they are using worse and worse methodology to confirm their idea. We had someone like this in our department - in fact we now have another. They are all over the place in science.

There was no politics in the story I heard. Someone claimed to have found something that sounded very unlikely to be valid, just on the basis of background knowledge of the field. Others tried to replicate it and it became clear it was all down to bad lab practice. Rare contaminants turn up all the time. There are usually mice on the next floor up in a medical lab. A rare contaminant in a lab turned into the last fatal case of smallpox known - in Birmingham.

The story may sound suspicious if you think everything in medical labs is done properly and rationally, but I am afraid that lab workers are human beings like any other. They make mistakes more often than not.

Fortunately this is five years ago. Things have changed a lot since then, and I think to a considerable extent because of the way the patient community has had this sort of conversation online. Really bad practice just is not going to be tolerated now.

But in another place we thrashed this out for so long that everyone thought it was time to put it to bed. Maybe that should be done again.

 

[lansbergen]

My feeling increases that the retroviral/HERV direction might be interesting.

I wonder why EVR's are involved in prion disease and how levamisole (the immunemodulator I use) decreases HIV infectivity in vitro.

 

[large donner]

In 2013 Lipkin found retroviruses in 85% of the sample pools in a study he did with Montaya. However four years later we still have no follow up on these samples and a conclusion to, "how they panned out".

this is his direct quote form 2013........

“It is very difficult at this point to know whether or not this is clinically significant. And given the previous experience with retroviruses in Chronic Fatigue, I am going to be very clear in telling you – although I am reporting this at present – in Professor Montoya’s samples neither he nor we have concluded that there is a relationship to disease …if I were to place bets and speculate, I would say that this is not going to pan out.”

http://phoenixrising.me/archives/19083

@Inara I think this is the Lo Alter initially positive paper that they later retracted themselves without explaining how they had contaminated their samples.

http://www.pnas.org/content/107/36/15874.abstract

 

[Inara]

Dear @Jonathan Edwards

I don't know biomedical science. I got a glimpse of physical and maths research.
I fear you're right.

I know humans are not perfect. I know that power and status are important in science, too, besides technical and knowledge limits.

I have an ideal understanding of science - I know it's an ideal. But I love findings and understanding, so I'll keep my ideal.

Unfortunately I lack deep biomedical/biochemical understanding (amongst others), this makes it difficult to evaluate a paper properly. Knowing that there are thousand possible sources of errors doesn't make this easier.

Knowing this I am sometimes frustrated with science how it is today, while wondering at the same time if it ever was that different...

It is relevant for my question about XMRV that there probably (for some surely) was fraud science at work. For me, I can now answer the question about XMRV more clearly. There still remains the fact that forthcoming papers hinted to something else that may be relevant, and I'd love to know more about it. I think it would be worth going in that direction - it's just curiosity, not so much aboit if it may be useful.

I never discussed this topic elsewhere. I can imagine you and others may be fed up with this topic so I appreciate you take time to explain.

 

[Inara]

I wonder why EVR's are involved in prion disease and how levamisole (the immunemodulator I use) decreases HIV infectivity in vitro.

I am honest - I don't understand that. I will go searching, but would be thankful indeed if you would be willing to say more about that.

 

[Inara]

Thousand thanks, @large donner! More to read, try to understand and think about - great!

 

[Inara]

@Inara I think this is the Lo Alter initially positive paper that they later retracted themselves without explaining how they had contaminated their samples.

http://www.pnas.org/content/107/36/15874.abstract

Ah, that is interesting. Do you/Does anybody know more about that?

Does anybody know whether it was explained one day that retroviral finding etc. "have panned out", as Lipkin assumed?

Edit: Ah, I misread Lipkin's quote. He said, "this is NOT going to pan out".

 

[large donner]

Ah, that is interesting. Do you/Does anybody know more about that?

They retracted their paper after Mikovits paper was retracted and didnt offer an explanation as to how they only contaminated the patient samples and not the healthy control samples. Now Harvey Alter refuses to talk about MLVs saying its just time to move on from it.

 

[Inara]

They retracted their paper after Mikovits paper was retracted and didnt offer an explanation as to how they only contaminated the patient samples and not the healthy control samples. Now Harvey Alter refuses to talk about MLVs saying its just time to move on from it.

At first sight that sounds a little like "I don't want to go down like that one". Which would actually mean that the treatment of Mikovits (jail) chaised others off. Lipkin is not looked upon as a fraud scientist - why would he back off? He could be confident of his findings, unless he feared he might have the same problems with contamination.

By the way, is "Lo" an abbreviation?

 

[lansbergen]

By the way, is "Lo" an abbreviation?

As I recall it it is his real name

 

[Jonathan Edwards]

Knowing this I am sometimes frustrated with science how it is today, while wondering at the same time if it ever was that different...

Yes, it was very different forty years ago. Not that there was no bad science. There has always been bad and good stuff. What has changed is that the science community itself seems no longer to be able to distinguish between the good and the bad. The result is that 80%+ of research is poor quality fashion following. James Le Fanu wrote a very good book that pointed out that there was massive progress in biomedical science between 1970 and 2000 but that strangely the pace of progress has since seemed to get slower and slower (The Rise and Fall of Modern Medicine). I was very aware of this.

It is relevant for my question about XMRV that there probably (for some surely) was fraud science at work.

To me fraud implies an intent to deceive. There may have been some of that. But I do not think the original claim was an intent to deceive. The author passionate believed it to be the truth. That is just as bad for science but it is rather different in other ways.

When I first heard about the XMRV story I did not know I was about to hear a positive or a negative account - in fact it was an account of the debunking. But in the first minute or two of the presentation I remember thinking that the whole idea of a retrovirus causing ME was totally implausible. The reason has to do with the way diseases play out over time.

Virus infections follow certain understandable patterns. Number one is that the virus wins - smallpox. Number two is that you win - flu. Number three is that the virus is allowed to hide away as long as it causes no trouble - EBV. Number four is that the virus hides away as long as your immune system remembers to go on making antibodies, but if the immune system gets lazy in old age the virus pops up again - shingles. But it is very difficult to think of a host-virus relation that would lead to the sort of pattern of illness seen in ME. It would have to be a situation where the immune system is chronically trying to overcome the virus but never quite managing despite the immune reaction producing severe symptoms. Leprosy and tuberculosis are a bit like that but there is progressive tissue damage and I do not know of any way a virus could do it without showing any tissue pathology. On the other hand there are lots of autoimmune diseases that behave like this because the problem is a loop in the immune software itself. And there are neuroinflammatory diseases that also behave like this - maybe again from some sort of loop.

Now, arguing in that sort of way can turn out wrong and sometimes does. However, I still think that anyone who has studied the time course of a wide range of diseases would say that the idea of ME being due to a persistent infection just does not fit with anything else we are familiar with. It is not an obvious option, as some scientists around 1995-2000 seemed to think. ME is nothing like AIDS.