*A CALL FOR ACTION!* We need the isolates sequenced!

[VillageLife]

WE NEED ACTION!
XMRV Isolates need to be sequenced!



Doctor Coffin at the NIH CFS meeting last week said, We cant address whats going on with viruses and proteins of sequences that I dont know of. If we get these sequences over of these other viruses to Genbank where people can look at them, then we can continue to do analysis

So there is one thing that has to be done now. The WPI's isolates of XMRV & any other isolates they have found, need to be sequenced. I think its a priority and cannot wait any longer.

Sequencing these isolates would reveal the true diversity of xmrv.

The WPI has said before they have 500 isolates.

I have no idea why these isolates havent been sequenced, I have heard the WPI very much want this to happen. Perhaps its money as doing these kind of experiments is expensive.

However, this cant be put off any longer, people are suffering, XMRV is possibly in the blood supply and the government must fund this.
It should be made the highest priority to get this work done.

Maybe we need some kind of email action campaign, perhaps we need to contact the NIH and ask that they fund this important work.

To me personally, it seems really crazy that this work hasn't been done yet. There are millions of people suffering and yes this work is expensive, but no amount of money is too much for the value of a human life.

We must get these XMRV isolates sequenced!! We must get the contamination arguments put to rest!

Email your concerns about this to:

CDC: cdcinfo@cdc.gov

NIH: dennis.mangan@nih.gov

The Blood Working Group: Jerry.Holmberg@hhs.gov

 

[toddm1960]

To me personally, it seems really crazy that this work hasn't been done yet. There are millions of people suffering and yes this work is expensive, but no amount of money is too much for the value of a human life

Funny how so much CRAZY stuff goes on with CFS huh

 

[Deatheye]

Did I understand mikovits wrong? Didn't she say she got them but can't publish them? Sadly she didn't say why she can't but I assume its about thecontroversy if this thing is real or not... So to prove it's real they need to publish it but they are not allowed cause it's not proven that it is real? At least I understood it that way from the NIH state oof knowledge conference.

 

[eric_s]

But i think she could add them to that database (GenBank, http://www.ncbi.nlm.nih.gov/genbank/) nevertheless, if she has them, even if journals don't accept her papers at the moment. On the GenBank homepage it even says that many journals "require submission of sequence information to a database prior to publication so that an accession number may appear in the paper".

So where's the problem? Either the isolates are not sequenced, the WPI and the other groups that have reported to have found MRVs don't want to upload the sequences to GenBank or GenBank doesn't accept them (if this is possible at all). I don't know which one and for what reason.

If the WPI or other groups want to sequence them and make the sequences public, but can't do so because they are lacking the money and this would help end the controversy, i'm pretty sure the CDC and NIH would be aware of that. So if they don't help out, it's probably because they don't want to.
This does not mean they or some other place could not be convinced, pressured whatever to enable the WPI to do that.

So i think firstly we would have to know if the WPI and other groups that have found something want to sequence what they have found (or have already done it) and wheter they want to make the sequences public at this point.

 

[Bob]

The WPI has sequenced some more XMRV isolates but, for whatever reason, this work has not been published.
Judy has said that she can't get her work published, in a general sense, but I don't know if this applies specifically to the new sequences.
I've no idea how GenBank works, so I don't know if the WPI are also having problems publishing the data there as well.

I believe that the WPI also has many more XMRV isolates (hundreds, if I remember correctly) that I believe they are unable to sequence purely due to budget constraints.
But it doesn't seem like it will be much use having all of those isolates sequenced unless they can get the existing sequences published.

So maybe it would be helpful to know more about what the problems are, so we can write informed letters?
I think that a bit more information would be helpful.
Does anyone have any insight into the situation?

 

[ukxmrv]

This is one example of how the current "adversarial system" of Science isn't helping things. Money is being squandered on the negative attempts which are not full replications. How much have Mclure, Towers, Coffin etc spent so far?

It's not a level playing field. Wellcome Trust etc have large pockets.

If the WPI cannot afford to do this work then it is holding up the science.

 

[Waverunner]

According to Vincent Racaniello it isn't too expensive:

"You might want to ask WPI why they have not sequenced the 500 XMRV isolates in their possession. A sequencing run costs about $5, which gives 500 bases. At that rate it would cost $81 to sequence each entire genome, or $40,500 to sequence the whole lot. I was told by an NIH official that WPI has a $1.5 million grant to work on XMRV."

 

[Bob]

According to Vincent Racaniello it isn't too expensive:

"You might want to ask WPI why they have not sequenced the 500 XMRV isolates in their possession. A sequencing run costs about $5, which gives 500 bases. At that rate it would cost $81 to sequence each entire genome, or $40,500 to sequence the whole lot. I was told by an NIH official that WPI has a $1.5 million grant to work on XMRV."

But $40k is quite expensive, and NIH grants are given for specific purposes, so unless the grant was given specifically to sequence the isolates, then the NIH money can't be used for that.

 

[VillageLife]

I've no idea how GenBank works, so I don't know if the WPI are also having problems publishing the data there as well

It has nothing to do with publishing the isolates.

Dr Coffin kindly replied to my email yesterday and said, Sequences didn't need to be published to get into Genbank.

So basically its about money. I think the NIH need to realize that this is bigger then CFS, these retroviruses could be causing cancer and other neurological illnesses, Doctor Coffin said at the NIH meeting last week, he wants to see the sequences but it seems our health comes at a price and no one has the money, so Dr Coffin and his team cannot look in to this like he wants too.

We cannot see the diversity of XMRV, We are literally left in the dark.

Has anyone got any ideas?

The blood supply is potentially being ruined here, I would think the government can find the money? They find the money for natural disasters & wars.

 

[Bob]

Has anyone got any ideas?

Hi VillageLife,
I think your original idea was a good one...
I think it's a good idea for us to write to the relevant authorities and highlight the issues.
It might be worth writing to Amy Dockser Marcus as well, in case she wants to highlight the issue.

The only question I have is why the WPI haven't got their existing sequences into GenBank?
Is it because they don't want to yet? And if not, then why?

 

[shannah]

Maybe someone knowlegeable about this material could contact the WPI to discuss the reasons and see what we as a community can best do to help move this along.

 

[eric_s]

If the WPI have sequences that they did not upload to any database, then i think they have their reasons for doing so. I hope those reasons are in our best interest and if i'd have to make a bet, i would bet that they are.
So, if it's like that, i don't think it would make sense to pressure the WPI, because if they don't want to upload the sequences, they also probably don't want their reasons for not doing it to be made public. But those are just my thoughts at this moment and might not be smart...
If the WPI want to sequence their isolates and upload the data but are not able to, for any reason, then it's a different case.

 

[Bob]

If the WPI have sequences that they did not upload to any database, then i think they have their reasons for doing so. I hope those reasons are in our best interest and if i'd have to make a bet, i would bet that they are.
So, if it's like that, i don't think it would make sense to pressure the WPI, because if they don't want to upload the sequences, they also probably don't want their reasons for not doing it to be made public. But those are just my thoughts at this moment and might not be smart...

Yes, that's exactly what I was thinking... Which is why I suggested we need more information before asking for sequencing...
But I think the WPI is playing this one close to their chest... and I don't think they are going to make the info about the sequences public yet.

 

[eric_s]

It's always very difficult for us to know what to do because we have no idea what they really know in the different labs, gov't agencies etc. and what their intentions are...

 

[VillageLife]

from everything i've heard the WPI do want there 500 isolates sequenced, it will put the contamination arguments to rest and will show the diversity of XMRV.

 

[ixchelkali]

What about the ones that Alter & Lo found? Have they been sequenced and put into the GenBank?

 

[Cort]

It has nothing to do with publishing the isolates.

Dr Coffin kindly replied to my email yesterday and said, Sequences didn't need to be published to get into Genbank.

So basically its about money. I think the NIH need to realize that this is bigger then CFS, these retroviruses could be causing cancer and other neurological illnesses, Doctor Coffin said at the NIH meeting last week, he wants to see the sequences but it seems our health comes at a price and no one has the money, so Dr Coffin and his team cannot look in to this like he wants too.

We cannot see the diversity of XMRV, We are literally left in the dark.

Has anyone got any ideas?

The blood supply is potentially being ruined here, I would think the government can find the money? They find the money for natural disasters & wars.

I can't imagine its about money...Remember you don't need to do all 500 strain or even 100 strains or even 50 strains. I think Dr. Mikovits said there are only what 6 or eight fully sequenced strains?...All you need are 10 or 20 more...Maybe even 5 more would do the trick - to show that the variability in XMRV is such that not all the samples have descended from the 22RV1 cell line - and that is all you need to show. That will take the monkey off of XMRV's back.

 

[Cort]

What about the ones that Alter & Lo found? Have they been sequenced and put into the GenBank?

Lo and Alter found sequences - not the full virus - so you can't tell as much from them.

 

[Cort]

If the WPI have sequences that they did not upload to any database, then i think they have their reasons for doing so. I hope those reasons are in our best interest and if i'd have to make a bet, i would bet that they are.
So, if it's like that, i don't think it would make sense to pressure the WPI, because if they don't want to upload the sequences, they also probably don't want their reasons for not doing it to be made public. But those are just my thoughts at this moment and might not be smart...
If the WPI want to sequence their isolates and upload the data but are not able to, for any reason, then it's a different case.

It would be good to get clear on what's going on. Low gene variability in XMRV is a huge problem. It is on the basis of gene variability alone that Hue et al determined that XMRV descended from the 22RV1 cell line. That lead to the work suggesting that it was accidentally created in the lab between 1992 and 1996.

THe low gene variability data is also what has prevented much of the research establishment from accepting that the Lo/ALter MLV sequences are part ofthe XMRV family.....right now there is too much of a gap between XMRV and the MLV sequences genetically for them to appear that they come from the same source. If that was true then there should be a gradation of sequences that are intermediate between the two. Instead in the analyses there's XMRV on one side and the MLV's on the other. If the WPI could fill in those spaces then they would get alot more agreement that these two findings are related.....

The lack of genetic variability also suggests that XMRV has not infected humans because viruses that infect humans are usually changed once they get into the body...but XMRV doesn't change much from person to person. As someone who studied population ecology as a graduate student the first time I saw the findings I thought 'uh oh' - the genetics are all the same - XMRV didn't look like a 'population' of viruses - because a population usually contains a good deal of variability...particularly if the population; ie the samples - come from people from across the country.

There are explanations for some of this....XMRV doesn't replicate much - so it has low variability - its a new virus - so we don't know what its variability really is....but for them to work out XMRV has to be something of an exception..it has to operate differently from most viruses....

Anyway....low gene variability is a major, major problem for XMRV....showing that it has higher gene variability would change a heck of a lot in the research community...and if they can get into Genbank I can't imagine why they wouldn't.

 

[Bob]

It would be good to get clear on what's going on. Low gene variability in XMRV is a huge problem. It is on the basis of gene variability alone that Hue et al determined that XMRV descended from the 22RV1 cell line. That lead to the work suggesting that it was accidentally created in the lab between 1992 and 1996.

THe low gene variability data is also what has prevented much of the research establishment from accepting that the Lo/ALter MLV sequences are part ofthe XMRV family.....right now there is too much of a gap between XMRV and the MLV sequences genetically for them to appear that they come from the same source. If that was true then there should be a gradation of sequences that are intermediate between the two. Instead in the analyses there's XMRV on one side and the MLV's on the other. If the WPI could fill in those spaces then they would get alot more agreement that these two findings are related.....

The lack of genetic variability also suggests that XMRV has not infected humans because viruses that infect humans are usually changed once they get into the body...but XMRV doesn't change much from person to person. As someone who studied population ecology as a graduate student the first time I saw the findings I thought 'uh oh' - the genetics are all the same - XMRV didn't look like a 'population' of viruses - because a population usually contains a good deal of variability...particularly if the population; ie the samples - come from people from across the country.

There are explanations for some of this....XMRV doesn't replicate much - so it has low variability - its a new virus - so we don't know what its variability really is....but for them to work out XMRV has to be something of an exception..it has to operate differently from most viruses....

Anyway....low gene variability is a major, major problem for XMRV....showing that it has higher gene variability would change a heck of a lot in the research community...and if they can get into Genbank I can't imagine why they wouldn't.

A nice summary of the issues Cort.

So, we have many questions, but not so many answers! As is always the case!

Judy seems so confident about her research, that I wonder if she has satisfied herself that she has adequate sequence variability to rebut the recent papers, such that she doesn't feel a need to hurry to publish? (She has consistently re-stated her confidence.)

Or maybe the WPI has their reasons for not publishing the sequences yet? Maybe it's for reasons of commercial or research confidentiality?

I read somewhere that sequencing an entire XMRV genome is more like $2500, rather than the figures quotes earlier, but even if it was this higher figure, it would still only put sequencing 10 viruses at around the $25,000 mark. It doesn't sound unaffordable for the WPI, does it?