Question concerning XMRV

What I wondered about, too - concerning the question "infectious agent: yes or no?" is the history of ME. One of the earliest cluster was in the 30s, if I recall correctly, in a hospital. Hospital staff was vaccined with a "new" polio vaccine. The staff got sick with ME. There was a lawsuit and an agreement to pay each sick staff member a certain amount in exchange for silence. That is suspicious and hints to politics.

I was always wondering if the ME then is the ME now? If yes, the history may suggest an infectious agent. If not - what did change?

Other opinions?

 

That's what I miss - evidence. There are several hints, several indications, you supplied much information (thanks!) - so I can build an opinion. But I would like to know how IT IS. At this point it is not possible, I think.

 

It's a bit interesting to look back on the XMRV thing. It was that which really got me paying more attention to CFS research, and was also a good crash course in learning about the importance of blinding, independent replication, etc. It probably was helpful for encouraging patients to learn about the processes of science, the need to think critically about exactly how experiments are conducted, etc.

It also made it seem natural to want to apply the sort of rigour expected in virology to psychiatry.

 

Dear @Esther12
Again so many thanks, most of all for your patience

The pictures do look similar, that was the first thing I thought. The next was: What actually is shown?

It is not easy to proove something is equal.

My questions that popped up:
Is the picture really identical? In my opinion this cannot be proven with graphical changes. I am no expert - maybe there are tiny diferences, and maybe tiny differences matter in gene technology?
There must be data sets behind those pictures, right? Are these identical, too?
What is the consequence if the pictures are identical? Does it mean Mikovits claimed to have found XMRV in ME, but later indirectly "added" this was only possible using a modifier named 5-Azacytidine? Which would lead to the correct statement "XMRV in ME only via a modifier". (And which would fit into what @Jonathan Edwards said about over-enthusiastic scientists.) What does that mean actually? If a modifier is used, is virus DNA/RNA really present or not?

I see hm...

 

I totally agree! I'm you, some years later
(I hope you don't misunderstand)

 

Another question:
I read somewhere (don't know where anymore ) that it is common to "send" virus DNA/RNA, that shall be used for vaccines, through mouse cells (e.g. brain cells?). Is this correct? If so, shouldn't it be quite common to find any virus-mouse rests in the human?

 

@Inara,
I don't think we have to give up because we cannot tell good from bad science. What I had said was 'What has changed is that the science community itself seems no longer to be able to distinguish between the good and the bad.'. What I meant by the scientific community consists of people sitting on grant committees and reviewing journals - the people who decide what gets done and published.

But amongst this community there are a small number of people just like before who have no particular difficulty telling bad from good science. If I listen to a talk at a scientific meeting I know within ten minutes whether or not the speaker understands what they are doing. About 40% do, I would guess - it varies hugely from meeting to meeting. And it all boils down, as you say (or was it someone else!), to ignoring 'big names' and just judging on the basis of whether or not the speaker explains what they are saying in common sense terms. Lots of jargon about new techniques is always a bad sign.

And it seems to me that is exactly what we do here - see if the papers make sense in common sense terms. You don't get a better journal club than this. Anyone can say what they like and in the end everyone can come to their own conclusion.

 

No worries. It can be helpful for ones own thinking to try to answer other people's questions.

Those images are PCR bands. Even if you were to conduct and identical experiment on identical samples you could not get images that looked the same like that. They're clearly the same image. All the little splatter, distortions? Those are meant to be just random. You don't get identical randomness like that (at least not without billions of attempts, and these were two images from the same researcher).

It might be helpful just googling for images of random PCR bands to see how they look, so you have a better idea of how to judge the replicated images?

eg: https://www.google.co.uk/search?q=P...kLLXAhXEWxoKHaXsBCYQ_AUICigB&biw=1536&bih=701

At the time this was happening, there had already been quite a bit of discussion of PCR amongst patients, so most following the story had some familiarity with them.

As an extreme example... these two images of a dog:




It's technically possible that such images could come from different dogs photographed at different times. That's very unlikely though. All the grass would have needed to coincidentally be in the same exact positions.

In the same way, all the random shapes in the two images from Mikovits were the same in her two images. There's no reason for sample 3's results doesn't look like sample 6's, but all the little random blobs around them are the same.

To illustrate that ERV put them into red and blue, then combined them:




If they were different, you would be able to spot red or blue bits that did not turn purple (as a result of having an equal amount of the other colour added), there is none. They're slightly different resolutions (the red one is lower quality than the blue), but it's still clear that they're the same image duplicated.

 

Hi @Esther12, thanks!

I thought about it, and I discussed this also with a Chemist (who is no expert in this area, but saw electrophoresis more often than I did). I wasn't sure with the scales in the pictures and possible data sets. He told me the data set is the picture itself, there's nothing "behind" it. Ok, understood. And I hypothesized about the possibility of getting two identical pictures out of two different experiments. As you say, we don't think this is very possible.

It is possible she was "lazy" and took one picture for two different experiments where she knew the outcome was the same. She wouldn't be the first to do it, but it is bad practice. There are also other possibilities, e.g. dearly wanting a positive outcome. Or what else...

Is it common to have such smeared sclices in the gel? The ones I saw had pretty disjunct slices. What does that mean?

 

I don't think that was really seen as important. I vaguely remember some discussion of this, and I think that there are ways of making things look 'neater', and maybe standards on this have changed over the last few years? I don't really know though. I've never done any lab work myself, so this is all just my dimly remembered impression from blogs/podcasts around the time of XMRV.

 

Hi @Jonathan Edwards,

Nah, give up science?

But thanks for clarifying. I wondered about the reviewers "in my time". Those who write the papers often work for long times in that field, about a certain topic. Reviewers are also frome the same field, but often work on completely different topics. In maths, reviewers have to understand and check proofs, most of them pretty complex. I wondered if they are just waving things through. (Hope this is correct English.)

But I still think there might be a problem for non-reviewers, i.e. scientists, to know which papers are "bad" or "good".

And I absolutely agree about what you say about talks and people who use "modern words", "new techniques", great sounding terms and so on. I always mistrust someone who uses the word "trivial".
My professor "hated" me because I wanted to explain things instead of writing down formulas. That's justified in that that maths is about being strictly exact (and words aren't). But every fool can write down a formula. To understand and to explain it...that's a different story.

You can say the ssme, I daresay, about the other sciences.

I once heard a talk by a nobel prize physicist and I already expected something like "oh my, I am so wunderful and great, you will never know". But he didn't. It was inspiring and nearly humble. You always had the luck to come across those people on conferences. And you're right, you knew quickly if they understood their topic or not.

 

There was a comment by Lipkin, supposedly on a CDC conference in 2013 (I couldn't find more):

Was there a follow-up or so?

Also, I found this:

from: http://www.cfs-aktuell.de/februar14_2.htm
(This is a well-known and esteemed German "blog" about ME/CFS that stopped in 2015.)

Would someone be willing to comment on that?

Are there human retroviruses that don't cause diseases (except HERV)?

 

My understanding is that we are all riddled with bits of retrovirus and it is entirely normal. For instance a common form of the complement factor 4 gene has a bit of retrovirus stuck in it.

 

As I understand it ERV's are involved in the immune response.

 

Interesting. In what way?

 

Thank you.

 

Undegenous retroviruses, ERV. Like mitochondria they are bits from elsewhere that got incorporated over the millennia.

 

@Jonathan Edwards - how common is it to get shingles aged 9/10?

 

Over the years I picked up bits and pieces but I can not reproduce it now. To much other things to do.

Was it not lately mentioned in the CDR talks/article?