Question concerning XMRV

Jonathan Edwards said:
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.
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Right, we are familiar with but that does not rule out what most are not familliar with.
 
large donner said:
Is it only 80% in positive studies or is it also equally bad in negative finding studies?
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I guess a negative study is not going to be following a fashion! The researchers usually keep repeating the experiment until it turns out positive. I had one patient who admitted to being the PhD student of a colleague who told him to go and do the experiment again if the results did not confirm the hypothesis. Not surprisingly the patient was depressed as well as having arthritis. He only ever got unpublishable negative results.
 
lansbergen said:
Right, we are familiar with but that does not rule out what most are not familliar with.
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It rules nothing out but it means there is not the slightest motivation for thinking it would be worth looking for such an infection. People do not go potholing in Derbyshire expecting to find a new species of hummingbird.
 
Jonathan Edwards said:
I guess a negative study is not going to be following a fashion! The researchers usually keep repeating the experiment until it turns out positive. I had one patient who admitted to being the PhD student of a colleague who told him to go and do the experiment again if the results did not confirm the hypothesis. Not surprisingly the patient was depressed as well as having arthritis. He only ever got unpublishable negative results.
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Really my question related to why would we would trust a negative finding more than a positive finding in science if, by quoting you.....

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.
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Inara said:
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.
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Yeah, I didn't mean to imply you were credulous about it.. I'm not sure the book is even her view - I think it's possible it's a more cynically constructed narrative than that. But I don't know.

Inara said:
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?
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From what I remember the blog did a pretty good job of going into the details. A really simplified version (from my memory from years ago, hopefully I don't mess this up):

An image was presented in the Mikovits XMRV science paper, claiming to show that samples from CFS patients were more likely to be positive for XMRV than those from healthy controls.

Another image was used by Mikovits in a slide at a presentation where she explained that the samples from CFS patients only showed up as positive after being treated with an epigenetic modifier (5-AZA) to help 'reveal' that XMRV was present.

As described, these images were purported to be results for very different experiments.

But someone spotted that the images were identical. Mikovits must have provided false information on at least one of the occasions she described what tests led to those results.

Inara said:
What were their arguments?
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Their arguments made so little sense it's hard to recount them. They tried to argue that, because the contrast and brightness were altered this was digital manipulation which made two different results merely appear to be from the same experiment. One person argued that such tricks could be used to make a mouse and an elephant look the same. If you go back to the images on that blog, and look at how all the little blotches are in the same patterns it really made no sense. At the time there was one patient who made some really weak arguments, but did so using complicated words, and they ended up being wrongly trusted by a small group of people who were really desperate for XMRV to work out. It was the argument that those images were not from the same experiment which meant that even the most desperate seemed to realise it was time to move on.
 
Jonathan Edwards said:
It rules nothing out but it means there is not the slightest motivation for thinking it would be worth looking for such an infection.
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I will just keep reading the literature of the infection I suspect. Maybe someday they can figure that one out and the pieces fall in place.

In the meantime I will look for what ME research brings.

For now I can only keep doing what works for me. Not ideal but I have not seen anything better.
 
large donner said:
Really my question related to why would we would trust a negative finding more than a positive finding in science if, by quoting you.....
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I was trying to imply that but may not have succeeded. Most bad science is due to people being overenthusiastic about having found something new and amazing. These days it seems it has to be something new and amazing that is also fashionable - maybe because nobody thinks originally any more.

But you are not going to be overenthusiastic about failing to find something new and amazing. So negative reports, when they are even published, are usually from people looking to see if they can confirm something that would be amazing but having to admit that no trace can be found. You do not do that if people can come back at you and say you did not look hard enough. You only do it if you have the sort of lab that has the resources to looks hard as anyone can.

In fact the study that killed the XMRV story was not a negative study. It was a study that showed in which lab the virus had originated - by using changes in sequence. It was not that they could not find the virus but they worked out where the contaminant virus had come from. That killed an entire new field of xeno-retrovirology, so nobody was going to do it through overenthusiasm. They may have been hoping to get big grants on xenogeneic viruses. But virologists' reputations rest on getting reliable results so rooting out contaminants is a necessary part of good practice.
 
 
It may well have been a mistaken discovery, but politics were definitely involved, even if the story has been sanitised over the years. It was not the usual (and desirable) give and take of science to find the truth. It has been too long for me to remember exactly and I am too ill to search for the details, but I do remember a lot of the indignation and shock at the sloppy science (from the negative studies) that I felt at the time. The study with Lipkin, apart from being done on blood, and the British guy (?) were done properly and were negative, fine, I mean the others.

They did their usual of making claims in the conclusions that went beyond the evidence. The first negative study came out in days! Then it seemed like every BPS team got a junior researcher to examine stored HIV samples and publish a negative result - where was all the contamination then.

Lo and Alter (discoverer of Hep C) were asked to retest their samples so many times they ran out of blood so their paper was "effectively retracted". Considering the way we cannot get the Pace trial paper even marked as dodgy despite it being shown as a fraud the sheer speed of the retractions proves it was political.

Like the pace trial people they finally found a good slogan (patient anonymity, long after destroying universities!) - contamination. They claimed that the merging of the virus in cell tissue lines could only have happened once, but there was a paper from years before that said retroviruses often have a favoured point where they get into the DNA. They also theorised as to how the contamination could have occurred (by mice running along the jars in warehouses) but never proved anything, just kept saying it must have. Evidence may have come in later but at the time, they were making claims that did not stand up.

I think there was a fear the public would be faced with a disease like HIV for which there was not test and no treatment and could suddenly infect anyone so there was a political will to discredit it as soon as possible.

Personally, I do not want it to be a retrovirus. I have grandchildren I want to cuddle and I don't want to be terrified of anyone touching my blood.
 
Jonathan Edwards said:
Yes, it was very different forty years ago.
[...]
What has changed is that the science community itself seems no longer to be able to distinguish between the good and the bad.
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This is a huge problem. It's one thing I read that stuff and think: "Well, okay", it's another if a scientist in this field has the problem to say whether it's substantiated or not.

My diploma thesis had its basis in a paper by a "big name" mathematician. My job was to implement it and develop it a tiny bit further. It wouldn't simply work. Of course I thought I made an error - I am not a brilliant programer. After discussing this with my supervisor, he implemented it himself (again) and agreed. The results weren't reproducible. So we developed a new algorithm which resulted in another paper. Of course we didn't say anything about the other one - never mess with "big names" in science as a beginner. :)

I learned something then: Never ever trust a paper. Don't care about "big names". Understand it.
But, in general, it will take a pretty while to understand a paper properly.

This leaves me with certain problems, as already @large donner pointed to: If you cannot say "good" from "bad", you are being left with believing (not my choice), not believing (hm...) or coming to no conclusion at all (preferred choice) - which actually means: no progress, no findings, no realizing etc. It's unsatisfactory.

[...] 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.
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That's one possible direction, to take into account what we already know. That's something one should always do, I agree.

Regarding ME, it must be something we don't know yet - that's what you say, too, isn't it? As a researcher one should be willing to think in other directions, too; implausible sounding ones, crazy ones...everything. Big scientific findings occurred when the "impossible was thought and later found". In the history of science, often new theories were discarded (and laughed about, at best) because they didn't fit the existing conviction.

One big problem in research is money - strictly, research is not about "is it useful, i.e. does it produce money?", it's about understanding. Today, many research projects (if not most) are financed via third parties. Often companies are involved. They are not interested in understanding, they want findings that produce money.
Next is the question of time. Proper research takes time. But funding may not cover that needed time.
Third come personal things, like egocentrism, status, power, riches...

And there remains one philosophic hypothesis :)
"Humankind gets regularly new problems in order to not get bored."
Which could mean: ME could be something completely new, there could be an unknown, new infectious agent that calls for a completely different reaction in the body, one we don't know yet. - Or not.
It could be exactly as you say, too.

I think the outcome will be surprising.
In the past, everything was about bacteria, and illness due to bacteria.
Then, the "virus age" - there is still so much to be understood. That's why I am disappointed the XMRV/retrovirus line wasn't further developed. (There are incountable infectious agents; I am sure we haven't found everything.)
And who knows what will come next? Maybe ME will be "this next". I don't know.

The open and creative mind - that's what we should keep, I would say.
 
Jonathan Edwards said:
The researchers usually keep repeating the experiment until it turns out positive. I had one patient who admitted to being the PhD student of a colleague who told him to go and do the experiment again if the results did not confirm the hypothesis. Not surprisingly the patient was depressed as well as having arthritis. He only ever got unpublishable negative results.
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Unfortunately, negative results aren't very welcome in science. (Our professor always said: "No negative results. These are not publishabIe.") I think this is stupid. This may contribute to experiments being repeated until they are "positive" and to scientists beinge fixed on a special outcome. Not good. :(

"Luckily", I didn't have to do experiments. But had enough frustrations nonetheless :)
 
Jonathan Edwards said:
I
In fact the study that killed the XMRV story was not a negative study. It was a study that showed in which lab the virus had originated - by using changes in sequence.
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"Using changes in sequence" - what is that?

It was not that they could not find the virus but they worked out where the contaminant virus had come from. That killed an entire new field of xeno-retrovirology,
[...]
But virologists' reputations rest on getting reliable results so rooting out contaminants is a necessary part of good practice.
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That's actually what I meant - it seems all research in this direction was dropped. But I wonder, with this information, how do we know earlier findings were real and not contaminations? What about publications today? Maybe virologists' attention to contamination increased, and they realized this might have been a problem in the past that was not taken care of?

You end up with believing nothing. That's not good.

Maybe, the most potential for reliable research is in treatment studies. But - but! We know the "buts". Which must lead to the question: Is science today really research about reality? Will science really find the cause of ME? Or is ME simply too complex?
 
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