DeFreitas 1991 Retrovirus/CFS Study

[fresh_eyes]

If her amplicons are still in the freezer, why the we could sequence em and see if theres any chance she actually amplified XMRV and thought, mistakenly, that it was something close to HTLV-II.

I'd love to see this happen.

 

[justinreilly]

CAV is Only Virus Ever Found in Animal Mitocondria

I'd also love to hear comments on the statement that CAV (?) were seen (?) associated with (?) : "inside large abnormally distended mitochondria in the cells." Is this common?

We know that mitochondria in CFS aren't working right, that people are profoundly fatigued.

Osler's Web said that only one other virus has ever been found inside a mitochondrion- and that was in a tobacco plant.

 

[justinreilly]

JerryH, that link goes to a MLV DG-75 - is that JHK? But either way you're right, I should have said they were never confirmed as a human infectious retrovirus.

JerryH- I'm wondering too- is MVV DG-75 another name for JHK?
Also, since it's been confirmed in a human cell line, has anyone looked for it in humans?

 

[starryeyes]

Osler's Web said that only one other virus has ever been found inside a mitochondrion- and that was in a tobacco plant.

Wow! It sure seems like CAV is very likely XMRV. I know the WPI says it isn't, but that just makes no sense.

 

[justinreilly]

Six or more Retroviruses/Retrovirus-Hybrids associated with ME/CFIDS?

Wow! It sure seems like CAV is very likely XMRV. I know the WPI says it isn't, but that just makes no sense.

I don't really understand why the WPI's annoucement isn't convincing to some people. For one thing, XMRV is a gammaretrovirus which is a C-type retrovirus. Osler's Web said DeFreitas went a long way toward sequencing CAV's genes and DeFreitas said it was not a C-type.

It looks to me, as a layman, that there is a good chance there are at least 3 retroviruses present in ME/CFIDS- CAV, XMRV and JHK with perhaps John Martin's SpumaRetrovirus/Herpesvirus hybrid, HHV6A (perhaps physically containing retroviruses or sequences of retroviruses) and Michael Holmes' retrovirus (which I believe was reported on this thread to probably be a Lentivirus- as is HIV) throwing in more retroviruses and retroviruslike viruses into the etiological mix. I do realize that will challenge people's paradigm of one virus, one disease especially since no disease has yet been suspected to be caused by more than one retrovirus (as far as I know, please correct me) and the diseases that are known to be caused by retroviruses are severe- AIDS and T cell lymphomas and leukemias.

 

[usedtobeperkytina]

Ironic, I was thinking the same thing this morning. I suspect that there is more than one retrovirus that causes CFS. That might explain the variety of symptoms, different to each person. I believe CFS is not directly caused by XMRV, but is the immune system / CNS abnormal loop in response to XMRV. So the virus can go dormant, but the CFS remain. Just my theory.

Of course, now WPI is saying 98% of CFS has XMRV, which would dispute the different retroviruses theory. But DeFreitas saw something in Bell's patients. And she could measure it differently in different patients. She found patters with the virus.

All so interesting.

Tina

 

[HowToEscape?]

Ironic, I was thinking the same thing this morning. I suspect that there is more than one retrovirus that causes CFS. That might explain the variety of symptoms, different to each person. I believe CFS is not directly caused by XMRV, but is the immune system / CNS abnormal loop in response to XMRV. So the virus can go dormant, but the CFS remain. Just my theory.

Of course, now WPI is saying 98% of CFS has XMRV, which would dispute the different retroviruses theory. But DeFreitas saw something in Bell's patients. And she could measure it differently in different patients. She found patters with the virus.

All so interesting.

Tina

Apologies for being unclear on the details -- but who were the subjects in the WPI study? Were they all from Incline Villiage or otherwise had very specific symptoms?
Since there's been so little research done into "CFS" there may be several causes for the disease, or even several related but not identical diseases.

I'm not a scientist, but all of your comments make intuitive sense. Something both complex and powerful (in a bad way) is going on with this disease(s). If it's ever truly understood I suspect that so much will be learned that other, different diseases will become treatable. Sort of like the unexpected offshoots from the space program.

 

[justinreilly]

Multi-retrovirus cause of ME/CFIDS?

Ironic, I was thinking the same thing this morning. I suspect that there is more than one retrovirus that causes CFS. That might explain the variety of symptoms, different to each person. I believe CFS is not directly caused by XMRV, but is the immune system / CNS abnormal loop in response to XMRV. So the virus can go dormant, but the CFS remain. Just my theory.

Of course, now WPI is saying 98% of CFS has XMRV, which would dispute the different retroviruses theory. But DeFreitas saw something in Bell's patients. And she could measure it differently in different patients. She found patters with the virus.

All so interesting.

Tina

ME could be multifactorial in the sense that if you have one, but not two; or two, but not three viruses, you may not develop full blown ME/CFIDS (you may be asymptomatic, have idiopathic CF or maybe another disease/syndrome), but with both or all three you get ME. As Paul Cheney said "something happened in the late 70s" to cause a huge upsurge in ME cases and then a slow taper. This could be a new toxin introduced in the environment or, more likely a new pathogen or combination of pathogens, most likely a virus. If it's a virus, it's most likely a retrovirus.

 

[justinreilly]

Apologies for being unclear on the details -- but who were the subjects in the WPI study? Were they all from Incline Villiage or otherwise had very specific symptoms?

The patients were from four practices around the country- Peterson in Nevada, Levine in NYC, Cheney in NC and Klimas in Florida. They were atypical in that 20 had the otherwise rare B cell lymphomas strongly associated with ME. WPI claims they did not select patients for cancers, but if this is the case, it's a little weird that there were 20 patients with these rare ME associated cancers. The total patient cohort was 101 patients.

 

[VillageLife]

Dr. Elaine DeFreitas - Paper, 1990

Dr. Elaine DeFreitas paper 1990,

http://www.pnas.org/content/88/7/2922.full.pdf

 

[serenity]

thank you Village, i have mixed emotions about this - i have wanted to see the paper. thanks for posting.
but this along with Dr. Bell's letter are so disheartening to me, that we may have already waited for 2 decades or longer for something that should have already come to pass while we all suffered ... it's heartbreaking for me to think about it.
but to try to be positive, we have more & more good news coming out every day it seems. it's got to all finally come to light soon.

 

[starryeyes]

If there were other retroviruses that could be causing CFS the WPI would be saying so. The equipment we have today is very refined compared to back in 1991 thanks to AIDS research and the progression of technology.

I know the WPI explains that these are 2 different retroviruses but then that means that there are 2 retroviruses in CFS yet they aren't mentioning the other one nor looking for it.

No matter how you look at this it smells of a cover up.

 

[Overstressed]

The equipment we have today is very refined compared to back in 1991 thanks to AIDS research and the progression of technology

This might be true, however, what does this actually mean ? I've talked to a well known retrovirologist from Switzerland, and he told me they have in research a PERT-test(test for reverse transcriptase), something all retrviruses share, and it doesn't simply pick-up all retrovirus infections in humans. In fact, it is not even a very sensitive test, unless you have many virus circulating in your blood, which is often NOT the case with retroviruses, especially with HTLV. A retrovirolgist here in Belgium, studying HTLV performed a more sensitive test for detecting HTLV, but I forgot the name, it was something like leolia... That seems to be a more sensitive test for slow replicating viruses. But if it's applicable for other RV's ?

What has been confirmed, is that if the virus is only in cells, there is no test to find out, at least, that's what I understood. I don't know if you can get there through culturing, but I thought it was not possible.

OS.

 

[starryeyes]

Hi Overstressed, welcome to Phoenix Rising. :Retro smile:

You wrote: What has been confirmed, is that if the virus is only in cells, there is no test to find out, at least, that's what I understood. I don't know if you can get there through culturing, but I thought it was not possible.

I may be misunderstanding your post but if I do understand it.. (I'm not doing well at all today) then how on earth was DeFreitas able to find CAV multiple times in different patients with CFS in 1991?

At any rate, according to this PWC have 2 or 3 retroviruses that could be the cause of CFS:

History of CFS/ME and Retroviruses

The study group of Elaine DeFreitas reported a link between CFS/ME and retroviruses back in 1991. This virus was most closely related to HTLV-2 (human T-lymphotropic virus 2), which belongs to a different group of retroviruses, deltaretroviruses. None of the healthy controls in the study showed evidence of this virus.

Immunovirologist Michael Holmes described retroviral activity in cells of CFS/ME patients as early as 1986. However, he did not elucidate on the type of the retrovirus. Another researcher, John Martin, reported finding a spumavirus type retrovirus in CFS/ME in the early 1990s.

Read more at Suite101: CFS/ME and Retroviruses: New XMRV Study Not The First To Find a Retroviral Link http://chronic-fatigue-syndrome.suite101.com/article.cfm/cfsme_and_retroviruses#ixzz0nHMoFDST

Perhaps those with CFS who are testing negative to XMRV have 1 or 2 of these other retroviruses.

Perhaps all of us have different combinations of them explaining subgroups of CFS. No matter how you slice it, these other retroviruses were found in PWC.

 

[oerganix]

DeFreitas' retrovirus

Maybe off topic, but I've had this on my mind for some time, so here goes.

It's just a "rumor" as I don't remember where I read it, but somewhere I read that CAA held the blinding information for the failed DeFreitas experiments, where it was claimed that she couldn't differentiate the controls from the infected.

Has anyone any information about this? With their weird behavior I am prone to be paranoid about CAA's involvement in that, so I can't stop wondering if maybe they did something to make her discoveries "go away".

Vernon's weird responses to XMRV etc have only fueled my speculations on this. Anyone?

 

[starryeyes]

People said earlier in this thread that the CAA did have a hand in damaging the reputation of Defreitas as documented in Osler's Web. The CAA just keeps popping up everywhere.. I thought I could get away from their influence here in this subforum.. yikes.

that CAA held the blinding information for the failed DeFreitas experiments

What does this mean? What is "blinding information"?

Oerganix wrote: Vernon's weird responses to XMRV etc have only fueled my speculations on this.

Can you explain this better? Like how did Vernon's responses fuel your speculations that the CAA holds "blinding information"?

ETA:

Oerganix wrote: I can't stop wondering if maybe they did something to make her discoveries "go away".

Well they have made her discovery of a retrovirus in CFS go away, haven't they? What they did was explain that her retrovirus is not XMRV and then they told us to never bring up her discovery again and they certainly aren't. And by "they" I mean Dr. Bell, the WPI etc... The people I revere the most.

I find all this very confusing and intriguing.

 

[jspotila]

Maybe off topic, but I've had this on my mind for some time, so here goes.

It's just a "rumor" as I don't remember where I read it, but somewhere I read that CAA held the blinding information for the failed DeFreitas experiments, where it was claimed that she couldn't differentiate the controls from the infected.

Has anyone any information about this? With their weird behavior I am prone to be paranoid about CAA's involvement in that, so I can't stop wondering if maybe they did something to make her discoveries "go away".

Vernon's weird responses to XMRV etc have only fueled my speculations on this. Anyone?

To my knowledge, the Association did not have any blinding information on samples run by Dr. DeFreitas. The Association certainly did not do anything to make Dr. DeFreitas's discovery "go away." The Association was funding her research, and continued to do so until she was forced to leave research because of her health and the loss of her equipment in Hurricane Andrew. Interest in her work among researchers was negatively affected by the failure of several labs to distinguish CFS patients from controls using Dr. DeFreitas's methods.

My recollection is that it was WPI that said that XMRV was not the same virus as the one found by Dr. DeFreitas. The Association was not the origin of that statement.

 

[starryeyes]

Jennie,

This much I do know:

The refusal to fund [DeFrietas] along with the CFIDS Assoc. pulling her funding lost us more than a decade of work!" End Quote of the article by Alan Cochetto.

http://www.ncf-net.org/forum/revelations.html

Koan wrote:
November 15th, 2009, 03:06 PM
If I remember correctly, it was not just the CDC that rushed DeFreitas but also the CFIDS Assoc.

Didn't they encourage her to publish and do press conferences too early, in her estimation at the time, and then bail on her, distance themselves from her, and stop funding her work when her warnings proved to be accurate?

Elaine DeFreitas undoing was a joint effort. I believe that had the CIFDS Assoc. not allied itself so closely with the CDC, and had they supported the continuation of her remarkable work (done with 2 grad. students in a tiny lab) we would now be more than a decade ahead of where we are.

It's all hindsight, of course, but had people simply listened to this fine scientist, allowed her to work at a reasonable pace and not forced her to jump the shark, 15 years of suffering may have been prevented. 20/20 vision that even Elaine DeFreitas did not have at the time.

Nevertheless, had people listened to her...

Must history repeat itself so closely? Wasn't it the CAA who spilled the beans about XMRV sooner than the WPI wanted?

When the CAA learned of the WPI study and its imminent publication in Science, Kim McCleary and Susanne Vernon chose to violate a strict scientific embargo and sent copies of the paper to members of their board. This move can be construed as contempt for scientific protocol and disrespect for the scientists who labored to deliver this work.

Surely you're aware of this Jennie, since you're on the Board at the CAA.

http://www.jabs.org.uk/forum/topic.asp?TOPIC_ID=4533

Another virologist finds a retrovirus in CFS:

"In an earlier patent, Dr. Sidney Grossberg, a world renown virologist from the Medical College of Wisconsin, wrote (# 5,827,750 on 10/98) "The human virus on which the present invention is based has not been classified as to which virus family it belongs, but it most nearly resembles a retrovirus ....The present invention relates to the detection of the presence of an NMA (neuromyasthnia) virus that is associated with CFIDS." He goes on to talk of the "protein spikes in the envelope" which are called peplomers and these spikes are characteristic of a retrovirus. He calls this retrovirus the "JHK virus." He mentions that the retrovirus that is close to the same size is called the "mouse mammary tumor virus." In his only publication on the virus, one that went unannounced by the CFIDS Association despite their funding of him, Grossberg writes ( Res Virol, 1997; 148(3): 191-206 ), "The human B-lymphoblastoid cell line, designated JHK-3, with pre-B-cell characteristics, chronically produces two viruses, Epstein-Barr virus (EBV) and JHK virus, an apparently novel retrovirus...most nearly resembling C-type retroviruses."

http://www.ncf-net.org/forum/ncftruths.html

Replicating DeFreitas's finding:

A Finicky Virus - It didn't help* that the virus turned out to be rather finicky.* For example, Dr. DeFreitas used a machine called a DNA extractor which the CDC - a center of viral studies in the US - didn't own and wasn’t about to purchase. Dr. DeFreitas also stated that the virus needed seven days in the autoradiograph for the viral bands to appear. The CDC, on the other hand, apparently had never needed more than 4 days in the autoradiograph for a viral band to appear.* According to Osler’s Web the CDC never acquired a DNA extractor nor did they ever use the autoradiograph for more than four days.

In And The Band Played On, the CDC refused to purchase an electron microscope which is why it took them so long to find HIV.

A Breakthrough - Then came some big news; Dr. Folks announced he’d found the virus in all six of Dr. Bell’s samples, 2/3 of the Atlanta patients and none of the local controls. Rerunning the test at a different stringency yielded similar results - it appeared a legitimate breakthrough had occurred. At the CDC, Dr. Gunn reported that the CFS jokes had stopped and the agency began, for the first time, to bring its resources to bear on the disease.* They lined up the purest sample of patients they could find; people who met the definition but without any psychiatric overlays.* If Dr. DeFreitas’ test could differentiate these patients and healthy controls, both she and the CFS community would be in business. This, Asst. Director Dowdle said “is what we’re good at.”

There was still one looming problem; Dr. DeFreitas’ primers appeared to work on her patients and some CDC patients, but they still failed to identify HTLV-2 in a standard cell line - something Dr. Folks felt they should have done given the genetic similarity between the two viruses.* Finding HTLV-2 in a standard cell line would indicate that Dr. DeFreitas had found a legitimate virus instead of some gene sequences belonging to what is called an ‘endogenous retrovirus’.*

The Unraveling - in the midst of all this, trouble reared its head. In a Sept 1991 meeting of the CFS Advisory Council, a wide-ranging group containing the central figures in the viral hunt, a Scottish molecular biologist and CFS researcher, John Gow , who had been collaborating with Dr. DeFreitas on a separate replication study, announced that despite spending “many months and many thousands of pounds” he had been unable to find any sign of an exogenous (acquired) retrovirus.* Based on his results, he felt Dr. DeFreitas had found nothing more than an endogenous (benign) retrovirus.* All the major players, with the notable exception of Dr. DeFreitas - locked in a custody battle over her son - were there.

Upon questioning, it became clear that Dr. Gow had used a different (brand) of enzyme in one part of the study.* Later the Gow team insisted that it made no difference: an enzyme was an enzyme and the one that they'd used had worked for them for years. In the aftermath they blamed Dr. DeFreitas for not being forthcoming with all of her work, and reported that she had not responded to a request that they visit Wistar so they could do a hands-on overview of her techniques. They noted that as University scientists (and long-time CFS researchers) they had no axe to grind.

Dr. Folks felt Dr. DeFreitas’ inability or unwillingness to attend the meeting or send a representative in her place hurt her.* He noted that the specific enzyme Dr. DeFreitas used had not been in her paper and he felt that any lab that followed the procedures based on her paper should be able to reproduce her results. In private, despite his earlier success, Dr. Folks reported that his team was finding much the same results as Dr. Gow's team."

Dejavu anyone?

The Final Blow - the final blow for Dr. DeFreitas at the CDC occurred when they broke the code on her analysis of the CDC's samples in March 1992. Not only had she found only three positives but they’d all come from healthy controls.* She noted that at a late stage she’d found a problem with their primaries but later getting good primers she repeated the test again and again and again with the same results: the CFS patients remained negative.

The Patient Question - the result was inexplicable to her. Dr. DeFreitas had come forth with her results for her paper only after extensive experimentation. She’d winnowed her assays down to the point where her samples had consistently tested positive or negative.* In her own internal blinded experiments she’d been able to pick out the CFS patients again and again. Why had she failed now?

Was because of the patients themselves? Had the CDC, in its attempt to pick out the ‘purest’ CFS patients, excluded, perhaps without realizing it, the very kinds of patients that would test positive? The CDC simply gathered patients on the strength of their ability to meet the definition.* In order to get the ‘purest’ CFS patient possible they excluded people with psychiatric conditions and in doing so they were simply following standard research protocols.

Still got that dejavu going?
Sure. They just couldn't replicate DeFreitas's work. The CDC couldn't afford to send any virologists out to DeFreitas to learn how to find the retrovirus either. Gee. It's obviously all DeFreitas's fault. She must not have known what she was looking at. It couldn't have been their methodologies that were wrong, nor their cohorts could it? Nah.. must be all just a wrong perception by DeFreitas et al.

"Still, some questions remained; why, a year earlier, had the CDC been able to duplicate Dr. DeFreitas results?"

http://aboutmecfs.org/Rsrch/RetrovirusFirst.aspx

Jspotilla wrote: My recollection is that it was WPI that said that XMRV was not the same virus as the one found by Dr. DeFreitas. The Association was not the origin of that statement.

Nobody on this thread has said that the CAA stated that.

At the last CFSAC it came up that no researcher was able to get funding to look any further for a retrovirus in CFS after DeFreitas was maligned and abandoned. Researchers could not get grant money from the CDC nor from the CAA for retroviral research so it took private funding to find XMRV. The the CAA had the gall to expose that info early and then discount it publicly later on.

We're supposed to be fine with this and view the CAA as our advocacy group?

 

[justinreilly]

"State Terrorism"

Maybe off topic, but I've had this on my mind for some time, so here goes.

It's just a "rumor" as I don't remember where I read it, but somewhere I read that CAA held the blinding information for the failed DeFreitas experiments, where it was claimed that she couldn't differentiate the controls from the infected.

Has anyone any information about this? With their weird behavior I am prone to be paranoid about CAA's involvement in that, so I can't stop wondering if maybe they did something to make her discoveries "go away".

Vernon's weird responses to XMRV etc have only fueled my speculations on this. Anyone?

In Osler's Web it said, for the first round (everyone but DeFreitas' results) that Gunn, Bell and Komoroff met at Komoroff's office to break the code and that seven other parties were on a conference call with them. I couldn't find the part where DeFreitas later came in with her own results. So, it sounded like Gunn, Bell and/or Komoroff had the codes (but it wasn't totally clear to me).

While looking that up I came across (on p. 614) that after Folks declined DeFreitas' invite to come to Wistar to try to get them synced up, that she offered to come down to CDC at her own (or Wistar's) expense to work in CDC's lab and get CDC's failure to find the retrovirus cleared up and Folks refused that offer too. I forgot about that.

Byron Hyde labeled CDC's subsequent attempt to bury DeFreitas' retrovirus research "state terrorism". Got to hand it to Byron Hyde; he makes me look understated. :innocent1: :victory: :victory:

 

[justinreilly]

Well they have made her discovery of a retrovirus in CFS go away, haven't they? What they did was explain that her retrovirus is not XMRV and then they told us to never bring up her discovery again and they certainly aren't. And by "they" I mean Dr. Bell, the WPI etc... The people I revere the most.

I find all this very confusing and intriguing.

Have Dr. Bell and WPI been discouraging talk about DeFreitas' retrovirus? Can you expand on that?

I would really like some more work on DeFreitas' rv.