Hoping that everyone can relax a little, here’s yesterday’s song that I couldn’t figure out how to post from my iPhone. We could use a little levity, I think.
When I started writing this blog, it was with a sense of astonishment that the physicians treating the patients, Lyme and CFS, didn’t seem to recognize that they had a new quiver for their arrows. The few that did were quickly censured, or swore a few patients to secrecy. I had been housebound, sometimes bedbound, for years and never expected to return to work, so I didn’t care who I pissed off. Anything was better than the isolation. The good thing about not caring was that I learned to write authentically.
During my 25 years in practice, I didn’t interface at all with the scientific community. Doctors only. I had no idea about the realities of this parallel universe that so impacts what clinical choices are open to us. I thought that the Science paper would be hailed as a great breakthough; scientists and doctors would come together, bringing different things to the table. The pace of progress would accelerate. If only that had happened!
The scientists that I’ve criticized by name were Coffin, Stoye and Racaniello. The first two put themselves out there very early on in a way that appeared designed to stop progress. They also have a long history of publishing things together that minimized the risk, so aren’t clean on the issue and their opinions shouldn’t carry much weight. Dr. Coffin also took it upon himself to try to limit treatment options, my pet peeve.
Professor Racaniello is a media figure, so fair game. I admit to being influenced by hurt feelings in his case, because I wrote to him when I started arv’s, in the midst of the first blush of excitement, wanting to have a discussion with him about the science and he shut me down, much the way Jason did. And to me, the tee-shirt still seems over the top thoughtless, though I think now that he probably didn’t understand what he was doing. There are signs that he is growing, e.g. publishing Dave Tuller’s important piece on his blog.
I was angry at Dr. Singh when she published her negative paper, for the reasons I expressed back then, but essentially the same thing again; scientists trying to call the clinical shots, though in this case I understand that she felt that her former paper was too strongly in favor. I sent her testimonials from patients improving on arv’s at that time. My understanding from Dr. Enlander is that she is back on the case. I thought her a lovely person when I met her and I am glad she is again working on our behalf. The Mt. Sinai initiative is very exciting. It is difficult not to fantasize about Dr.’s Shadt and Lipkin putting their heads together.
And Jason. Sorry Jason, I didn’t mean to hurt your feelings. I hope you learned something from our scuffle. No hard feelings on my end.
I hope I haven’t forgotten anyone. A virtual olive branch offered to all, even those most aghast at my choices…
Believe it or not, there are scientists that share with me, and I protect their privacy. I swear I’ll disavow knowledge of our friendship to my dying day if that’s what any scientist willing to share wants. At risk of scaring off the people we want to be here, there is a tracker on the blog, that allows me to see the IP address, location and the name of the server that loads each blog page, as well as how many prior visits from that address. Institutional servers give the name of the institution. There are at least a dozen readers at the NCI and another dozen who connect from NIH servers in a few different cities. A couple at the CDC in Atlanta. Readers at many universities and teaching hospitals, including a few at Columbia and Harvard. Cancer institutes around the country. Only a few of these people participate in the discussion. This is a potentially powerful thing. When I worked for the WPI, one of things I most wanted to do was establish lines of communication between physicians and scientists with all kinds of points of view. There is little to be learned from consensus when the truth isn’t even on the table. If there is a way to salvage some part of that dream, I’d like to.
Many of the scientists came to read about Dr. Mikovits’ travails, but I am asking them to think about the science with us. In particular, I’d like to know your reactions to Dr. Snyderman’s data. Please adopt a handle and share with us. Your secret is safe with me. I ask you for the sake of the patients that you are now beginning to know, be bold. I realize that you are constrained by the knowledge that a patient community can do what we did, but there are 17 million patients worldwide in the ME/CFS cohort alone, who need creative thinking from you. There is every indication that our disease is reversible until it is very advanced. The unclaimed talent in the patient community is staggering, if only the disease could be calmed, not even cured. Look at me. I am productive after years of being almost unable to care for myself, let alone anyone else.
I would like to put an end to the discussion about the lab science in the Science paper, the WPI, VIP Dx. Nobody knows the answers, including the protagonists. I certainly have no basis for evaluating any of it. I defer to the scientific community to figure it out; discussing it here is not productive. At this point, it is non-contributory and boring. Take it someplace else. This is also not the place to argue about whether Dr. Mikovits should be canonized or not, though she is my friend, and I am very sorry for what is happening to her. But from a clinical point of view it is irrelevant. This blog is about developing a model for treatment and how to best live with the disease.
Thank you to our mold warriors for giving it another shot here, and for keeping it appropriate this time. I for one, think that your experiences of improvement without medication are significant. I also understand why you feel the need to tell others in the hope of reducing their suffering, as well as your frustration when you feel you aren’t being heard. I have been interested in Ritchie Shoemaker’s pioneering work, since 2002 when we shared a couple of patients with Ciguatera poisoning.
And a big thank you to In Vitro Infidelium for the considered comment this morning. No invective or politics at all. Just a reply about the scientific discussion at hand. It was a breath of fresh air. Thank you for the excellent paper by Voisset et al. The quote you lifted in your comment is precisely the point. Although it clearly isn’t a simple, straight forward infection, there is epidemiological evidence that it is an emerging disease of very great proportions, not a stable situation. AIDS isn’t simple and straightforward either, without a test, in that infected people can remain apparently healthy for a long time, or even indefinitely. Only a small percentage of people with HTLV ever become clinically ill from it. Inbred sick mice don’t get sick from their MLV’s, but wild mice and some other rodents can. All I am asking for is that it be studied, not shut down if this attempt fails. Also, that our therapeutic options not be limited by how slow the science will be to unfold, even in a best case scenario in which Dr. Lipkin finds something.
My hat is off to Dr. Lipkin. His finely worded communication to the patient community brought tears to my eyes. The only thing I would take exception with at all was the use of the word definitive. If by some quirk of fate, this study is completely negative, we beg you, use those specimens to take the next step.
Today’s song: Learning to Fly: by Tom Petty
>"As there is no published research on 293T cells and VP62/XMRV how do you know 293T cells pump out virions after the laboratory artefact VP62/XMRV is added? The explanation you are now giving is your own assumptions not published research. The example you give is for LNCaP cells not 293T."
From Schlaberg et al. This is Ila Singh'a paper:
"We constructed pXMRV1, a full-length XMRV molecular clone, using 2 overlapping clones from patient isolate VP62 (6) [gift of Don Ganem, University of California, San Francisco (UCSF)]. pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection"
Hey! The key sentence being: pXMRV1 was transfected into 293T cells. pXMRV1 is also the same thing as VP62.
Let's see what crazy thing you say state that I am wrong. I'm very curious.
>There is published research on 293T and Silverman's VP62 XMRV. Although, what it demonstrated was that LNCaP was a better line because it did not require high doses of androgens for replication. LNCaP had a natural tendency without manipulation.
http://jvi.asm.org/content/84/5/2556.full
>"Regardless of who you really are, to get an antibody response out of VP62 you would still need to transfect the plasmid into a permissive cell line and then inject the visions present into a patient."
Of course, who's going to do that? No one.
However if you inject XMRV into monkeys, you will get an immune response from the monkeys. Do you want me to cite Silverman's paper too? lol
>@Heidi
Thank you Heidi, but this was not the type of study I was saying hadn't been published. There is no published study showing 293T cells pump out virions after the laboratory artefact VP62/XMRV is added. Which raises the question as to why this anonymous person would claim their had seen this.
@Anon 3:07
"However if you inject XMRV into monkeys, you will get an immune response from the monkeys. Do you want me to cite Silverman's paper too? lol"
But you are not going to get an immune response any other way. The person would therefore be infected.
Another study you claim has been published is one showing that virus is integrated into 22Rv1. There is no such study. The closest was Knouf et al.
"Finally, production of XMRV by 22Rv1 and potentially other prostate cancer cell lines should be carefully considered from the standpoint of possible virus transmission to laboratory personnel, to other cells cultured in parallel, and as a confounding factor in the interpretation of experimental results. For example, 22Rv1 cells have been reported to produce 80- to 150-nm “exosomes” (9) which look very much like the presumed ∼100-nm retrovirus particles shown in Fig. Fig.1,1, and the possible role of XMRV in the phenomena ascribed to exosomes will need clarification."
The EM particles could be just about anything.
>"Hey! The key sentence being: pXMRV1 was transfected into 293T cells. pXMRV1 is also the same thing as VP62."
Anon are you Dusty Miller?
>"Anon are you Dusty Miller?"
lol no…
All I'm trying to do is bring some sense into the anon poster who has no clue about virology.
For example,
"There is no published study showing 293T cells pump out virions after the laboratory artefact VP62/XMRV is added. Which raises the question as to why this anonymous person would claim their had seen this."
This is funny because I copied and pasted from a paper proving that it does. Here, I'll do it again:
"From Schlaberg et al. This is Ila Singh'a paper:
"We constructed pXMRV1, a full-length XMRV molecular clone, using 2 overlapping clones from patient isolate VP62 (6) [gift of Don Ganem, University of California, San Francisco (UCSF)]. pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection""
PXMRV1 WAS TRANSFECTED INTO 293T CELLS…
Read it and weep.
>"All I'm trying to do is bring some sense into the anon poster who has no clue about virology."
What you are doing is making lots of statements without providing references to back up your statements.
No virions of VP62/XMRV were shown to be pumping out of 293T cells in Schlaberg et al. and if they were they wouldn't be MLVs because VP62/XMRV what is a synthetic virus never found in nature. It bears no relationship to any MLV found in mice.
>"No virions of VP62/XMRV were shown to be pumping out of 293T cells in Schlaberg et al."
Did you read the next sentence?
"Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection""
That means live INFECTIOUS virus was produced from 293T cells through detecting RT activity.
"It bears no relationship to any MLV found in mice."
Actually, it does. Two halves from what I can remember.
.
.
.
Despite proving that you were wrong in your wild and almost always false statements, you still fly in the face of what published and say the complete opposite.
Pretty clear you have only motive and ignore basic facts about virology.
You are exhausting and I have no intention of answering you back anymore. More fuel to fire I suppose.
.
.
.
Dr. Snyderman, I'm still open to your scientific query. Answer when you can. Specifically, I'm curious about your MLV antibody testing.
>"That means live INFECTIOUS virus was produced from 293T cells through detecting RT activity."
Yet, there was no evidence of virions being pumped out of 293T cells in that paper or any other paper, so why do you claim to have seen it?
"Actually, it does. Two halves from what I can remember."
VP62 is a laboratory artefact made in 2006, what MLV do you think it is identical to? It has never been found in nature so it is not identical to any MLV or MRV.
>Anon are you Andy Vaughan?
>Anon scientist is under no obligation to reveal his or her identity (though a handle would be helpful). Nor does every statement need to be referenced. I for one am grateful for the input from someone in the trenches. And for the expressed interest in Dr. Snyderman's evidence.
Jamie
>Jamie, how do you know this person is in the trenches?
>I see no evidence that the person I now think of as Billy is a scientist. His vocabulary is not that of a biomedical scientist and his ignorance of basic immunology belies his claim to be a virologist (he may of course be a lab tech). He makes no substantive points whatsoever and relies on bluster, deprecations and anecdote.
>When you point your finger at someone, three fingers are pointing back at you. ~ Anonymous
>Jamie, when a person starts to make claims that they have seen virions of VP62 being pumped out of 293T cells you would expect them to be able to quote the paper where this is recorded or explain where and how they have seen it occur. This person has not done that.
Here is their quote.
'Not in 293T cells per se, but researchers can transfect 293T cells with VP62 XMRV and the cell line will pump out plenty of virions that are infectious. This is what Ila Singh did. I saw this first hand."
They have also suggested a flaw in the serology assay, but have not provided any explanation of what that flaw would be.
"One possibility is that the assay to determine whether you have an MLV is flawed."
Do you not agree that we need less rhetoric and more substance?
A scientist would not mess with patients in this way. They would provide a through explanation.
>Dr. Snyderman, thanks so much for your comments.
I also object to the hostile barbs thrown at Dr. Mikovits. Am glad to see that she helped you.
And the nasty words thrown at you are absurd and do not belong here.
>As I see it, the "St. Judy" label is not being used as a criticism toward Mikovits herself, but it rather reflects the attitude of her supporters, in whose eyes she can do no wrong.
She is the holy exception in a world of corruption, so to speak.
Ironically, the post by Dr. Snyderman does not at all refute this image of St. Judy but rather reinforces it.
As to the antibody question: Ruscetti has tried to reproduce his serological assays for the BWG (as did Mikovits, but as there is some strange internet meme suggesting that Lombardi did all those tests in secret and they just misspelled his name into "Mikovits" on the paper, we'll disragard this).
He *horribly* failed, by designating more controls to be positive than patients (that were confirmed to be positive by Ruscetti himself)! This basically makes the earlier reported results from either studies or private tests meaningless.
>RRM, the use of St Judy is to undermine anyone who is discussing the real scientific merits of the published studies and to mask the large number of scientists who have also found these viruses. The same term could easily be applied to Coffin worshippers.
There was nothing wrong with Ruscett's serology assay in the blood working group. The issue was in having not pre-screened the PBMCs of the controls. They were never declared negative and consequently testing them positive would not undermine the testing. Mikovits still didn't do the blood study. You can personally ask Lombardi can you not. This failure to include negatives in what was only a blood study for a gamma retrovirus makes the blood study meaningless, well apart from their being MRVs in the blood supply.
>Who exactly is worshipping Coffin? At least I never saw an MD "testifying" on a patient's blog that Dr. Coffin saved his life because of a test that was based on some discredited and retracted paper. And I have not seen people handing out a tiara to him, either.
Moreover, if Coffin allegedly took materials from his lab without permission after he had been terminated, I sure hope they would prosecute him to the fullest extent possible. In any case, I would see nobody defending him with rather bizarre reasoning like 'whatever he did, he must have done it in my best interests'.
And Ruscetti and Mikovits surely did have a stretch of bad luck in that BWG study, boy. More than half of the included healthy blood turned out to be positive through the omission of PBMC screening by a combination of sheer chance and the fatal error of doing just something like 9 pre-screen tests? And let's not forget that two (out of three) controls were indeed pre-screened using PMBC samples and were still found positive by the same Ruscetti later on.
So yeah, totally credible case of bad luck. No worries and no irrational clinging to incredibly small chances to be seen here.
>"Who exactly is worshipping Coffin? At least I never saw an MD "testifying" on a patient's blog that Dr. Coffin saved his life because of a test that was based on some discredited and retracted paper. And I have not seen people handing out a tiara to him, either."
In your opinion. You do worship Coffin RRM. He tells everyone that a contaminant must have been the cause and you without having any evidence believe it.
"Moreover, if Coffin allegedly took materials from his lab without permission after he had been terminated, I sure hope they would prosecute him to the fullest extent possible. In any case, I would see nobody defending him with rather bizarre reasoning like 'whatever he did, he must have done it in my best interests'. "
Who ever said that? There is no proof anyone took anything and Mikovits would be entitled to the contents of her notebooks and they should be returned to her. Most scientists are not impressed with what is happening if you hadn't noticed.
"tretch of bad luck in that BWG study, boy."
Is that really the extent of your abilities to analyse a study or approach this scientifically? The serology assay will only find positive those infected with an MRV. There is nothing else it can identify.
"More than half of the included healthy blood turned out to be positive through the omission of PBMC screening by a combination of sheer chance and the fatal error of doing just something like 9 pre-screen tests? And let's not forget that two (out of three) controls were indeed pre-screened using PMBC samples and were still found positive by the same Ruscetti later on."
The 3 laboratory controls are lab techs. They can become infected with these viruses much more easily as they will be working with them. The same lab tech was positive using serology in both the NCI and WPI labs.
MLVs will in those seriously ill produce no immune response. The immune system of a healthy person who is infected is expected to have an immune response. Not pre-screening PBMCs means a person cannot be declared negative. Not all labs were given these controls to pre-screen, but those who ran the study would not say who had. As the NCI and WPI were the only ones using clinically validated assays for serology and culture, but no other lab was using clinically validated assays for the other methods, if they didn't screen them no one could declare the negative. Why only allow all labs and all methods to pre-screen only the 3 lab techs? That is a major flaw in the study.
There are also hints in the paper that there were two groups of controls. One lot is said to be " twelve whole blood donations from local blood donors ". the other "Similarly, fifteen control specimens from blood donors". Was that in an area where there was an ME outbreak? Were these people healthy? I see no comment to that affect?
What 9 pre-screen tests are you referring to?
>Jamie, I was trying to work out why you would think some people posting here are scientists when they are making very basic errors and have never said they are scientists. Then I remembered you can see where people are posting from. So for instance InVitro is probably something like Kings College, but that does not mean they are a scientist as all sorts of people work there.
The person posting about 293T cells however does sound exactly like the person calling themselves Billy on mecfsforums. That was the person who posted the raw Lombardi gel on October 4th when materials are meant to have been stolen. If this person is associated with either a university or the NIH how did they get hold of that and wouldn't they know exactly who has Judy's notebooks?
>No I was wrong it does mention healthy in two places, but why do they appear to be two groups of controls?
>RRM how do you interpret the use of the word "unlinked" in this sentence from the blood working group study?
" In addition, twelve whole blood donations from local blood donors were unlinked and then separated into a buffy coat and corresponding plasma unit "
>"The person posting about 293T cells however does sound exactly like the person calling themselves Billy on mecfsforums. That was the person who posted the raw Lombardi gel on October 4th when materials are meant to have been stolen. If this person is associated with either a university or the NIH how did they get hold of that and wouldn't they know exactly who has Judy's notebooks?"
Hate to burst your paranoid and scientific delusional bubble but I am not "Billy" nor have I ever gone on mecfsforums. I am just an anonymous scientist calling you out on the scientific lies that you state over and over again. I'm sure JDJ can backtrack who I am through IP addresses and such. Yes I do coem from a university. I'm sure she already knows who I am but will not divulge anonymous information.
Funny how you simply ignore how I proved to you, by citing the work, that VP62 is a plasmid and can produce virus from 293T cells once transfected. Here I'll quote Ila's paper again:
"We constructed pXMRV1, a full-length XMRV molecular clone, using 2 overlapping clones from patient isolate VP62 (6) [gift of Don Ganem, University of California, San Francisco (UCSF)]. pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection"
So tell me all-knowing one: How exactly do you argue this? I mean the sentence: "pXMRV1 was transfected into 293T cells." Its pretty clear isn't it?
I've transfected cells to make virus. So has Ila. Silverman. So has everyone else that studied this xeno MLV.
Go ahead and lie some more. All you do is spam JDJ blogs with nonsense messages that nobody pays attention to because they have no basis in science. All I'm doing is calling you out on that.
>" I am just an anonymous scientist calling you out on the scientific lies that you state over and over again. "
You are an anonymous person who is not backing up what they say. Lots of people have access to university computers, where is the proof you are a scientists of any kind. Where have you seen 293T cells transfected with VP62 and pumping out virions?
Stop changing what you said. It was virions that you said you had seen. This says nothing about virions.
"pXMRV1 was transfected into 293T cells." Its pretty clear isn't it?"
Go ahead and lie some more yourself. All you are doing is spamming nonsense. All I am doing is calling you out. Where is that flaw you wanted to point out in the serology assay? How do you expect to have an immune response if this person is not infected?
Here are your quotes again as you continually forget them.
'Not in 293T cells per se, but researchers can transfect 293T cells with VP62 XMRV and the cell line will pump out plenty of virions that are infectious. This is what Ila Singh did. I saw this first hand."
"One possibility is that the assay to determine whether you have an MLV is flawed."
>"You are an anonymous person who is not backing up what they say."
I JUST PROVED IT 20 TIMES!!!!
I'll quote the paper one more time for you:
"We constructed pXMRV1, a full-length XMRV molecular clone, using 2 overlapping clones from patient isolate VP62 (6) [gift of Don Ganem, University of California, San Francisco (UCSF)]. pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection"
This came from:
http://www.ncbi.nlm.nih.gov/pubmed/19805305
"Where have you seen 293T cells transfected with VP62 and pumping out virions?"
IVE SEEN IT WITH MY OWN EYES!! So has the post-doc in Ila's lab that I talk to regularly. Silverman has. So has countless other people that worked on XMRV.
"Go ahead and lie some more yourself. All you are doing is spamming nonsense. All I am doing is calling you out."
I find this amusing. It's literally what I wrote to you two minutes ago.
"Here are your quotes again as you continually forget them."
haven't forget them and I standby them. You're arguing against basic science fact that hundreds of researchers do every day.
All I wanted was to talk to Dr. Snyderman about his serology assay, which I don't know much about, until you continuously spam-attack anyone that thinks different from you.
"Stop changing what you said."
Never changed what I said. Does this really make any sense to anyone reading this:
"It was virions that you said you had seen. This says nothing about virions."
If there are any scientists on this blog reading, please back me up. This anon poster is clearly out of touch with scientific reality.
>"I JUST PROVED IT 20 TIMES!!!!"
No you have not. There is no evidence of virions budding from 293T cells transfected with VP62 in any published paper.
"IVE SEEN IT WITH MY OWN EYES!! So has the post-doc in Ila's lab that I talk to regularly. Silverman has. So has countless other people that worked on XMRV."
I have asked you where you have seen it. You still refuse to say. Now you are saying others have seen it. This is also not saying where you saw it. Who is this other postdoc?
"You're arguing against basic science fact that hundreds of researchers do every day. "
I asked where you had seen it. You provided a paper that did not show virions budding from 293T cells transfected with VP62 and you have not said where you saw it.
"All I wanted was to talk to Dr. Snyderman about his serology assay, which I don't know much about"
It will be the assay from Lombardi et al., as I said.
>@Anon 9:09
You cannot present unpublished evidence as fact unless you are going to accept all unpublished evidence. Do you understand that?
>"No you have not. There is no evidence of virions budding from 293T cells transfected with VP62 in any published paper."
OK. One more time. LOL
This sentence proves that virus is coming out of transfected cells. It is published from Schlaberg et al.
"Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection"
What this means is that virus came out from the cell and into the culture medium. This medium was then tested for RT activity. This enzyme is only present in ACTIVE VIRIONS. However, if this does not make sense to you or you simply ignore it then how about a picture from the same publication?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739868/figure/F1/
This is XMRV from TRANSFECTED 293T cells. That virus was used to infect LNCAP cells as well.
How can you just sit there and say no paper proves this when it is right in front of you.
Do I really need to cite 20 papers for you to believe it?
Are there any other scientists reading this that can help me out here proving to this nitwit that what he is saying makes no sense?
"I have asked you where you have seen it. You still refuse to say."
I JUST SAID IT! With my own eyes, in my own lab. In other peoples lab. What more do you want?
OK. If you are near me I would literally bring you into the lab and SHOW YOU how to make virus just to shut you up.
"It will be the assay from Lombardi et al., as I said."
Are you Dr. Snyderman? That don't answer questions that are not meant for you.
>If you anonymous geniuses can't get your act together sufficiently to think up some user-name to go along with your messages,
"wastebasket" is where they belong.
>Thank you, Anon scientist (9:09/9:32 AM), for participating. Dr. Snyderman will answer you soon. And yes, I can see the location, IP address and the name of the server, but of course cannot tell who anyone is. In your case, there are at least 4 readers that sign in from your fine institution of higher learning.
For my part, I do not require that you reference everything you believe to be true from your own experience, as long as it is stated as opinion. That experience is very valuable, whether it is published or not. I appreciate hearing your impressions. We already know that the answers are not yet in the literature. Lots of dots there to connect, but the work still needs to be done.
Jamie
>"This sentence proves that virus is coming out of transfected cells. It is published from Schlaberg et al."
No it does not. There is no mention of seeing virions.
" This enzyme is only present in ACTIVE VIRIONS"
There was still no virions seen.
"How can you just sit there and say no paper proves this when it is right in front of you."
Because you said you had seen this. You cannot provide a paper that shows this has occurred and will not say where you saw it.
"Do I really need to cite 20 papers for you to believe it?"
One would have been sufficient, but you have not provided one.
"I JUST SAID IT! With my own eyes, in my own lab."
Now you are saying in your own lab. Where is that? This is not published.
"OK. If you are near me I would literally bring you into the lab and SHOW YOU how to make virus just to shut you up."
Then you can say which lab that is?
"Are you Dr. Snyderman? That don't answer questions that are not meant for you."
You have asked on a blog. People answer all sorts of questions on a blog.
>Anon 9:48 AM,
Please cease and desist (and I can see where you are too). Your OCDish behavior is annoying everyone. We get it. You disagree with Anon scientist. Feel free to start your own blog.
Jamie
>And Anon 9:48 AM,
What are your credentials that you feel you are somehow the purveyor of "the truth"?
Jamie
>Jamie, are you saying that one person can continue to spam and another cannot anti spam? How do expect patients to know the facts when you let only those repeating lies post? I don't mind posting less believe me I don't, but you will be allowing only those who want to stop any more research into MRVs from having a voice. How will that lead to treatments or help people in dire need like Dr Snyderman?
I realise you are trying to reach out to them, but how can you think those few posting here care one bit if they are prepared to lie.
>"And Anon 9:48 AM,
What are your credentials that you feel you are somehow the purveyor of "the truth"?"
I thought people didn't have to say anything about themselves? I will provide all references to exactly where my information comes from. The truth is that there is no published study showing virions coming out of 293T cells transfect with VP62. Why else do you think he cannot provide the quote to back up his statement?
>Will you please use a handle if you want to continue this. And if you want credibility, tell us something about yourself. You are a poseur in my opinion. I don't think you are correct that Anon scientist is either lying or trying to hurt patients. He (or she) is sharing his opinions and he has stated that he is here to learn about something we have been discussing that he doesn't know the answer to. That can only be a good thing. Can you please leave the paranoia at the door, for a change? The name of this blog is An Olive Branch.
Jamie
>Okay, I will ask the dumb questions. One of you anons saw virions hatching out of a manmade retrovirus. Do I have this right? Probably not, but you have to start somewhere to learn.
So does that creation, assuming it is correct, mean that the lab retrovirus created could potentially be infective, indeed was infective to monkeys?
Does it mean that what Mikovits found was a lab contaminant and that is also why she found some blood samples produced antibodies?
What is the connection, if any, between virions and antibodies?
PS Erik Moldwarrior is one of the smarter human beings on the face of the earth and I am not stupid. We could follow this more clearly if all the anons would make up fake names. Hey, you can call yourself Dickinson which was my mom's maiden name, as in Emily. Surely you can think of a name, and "don't call me Shirley".
>I will use a handle, but will need to create one first. Doesn't the person now claiming to be a scientists also now need to gain some credibility too?
"You are a poseur in my opinion."
No I am not. Not actually sure what that means?
" I don't think you are correct that Anon scientist is either lying or trying to hurt patients."
He is wrong that any paper has shown virions of VP62 budding out of transfected 293T cells. Reverse transcriptase is not a virion. He may not be lying about having seen this himself, which is why I asked where he had seen it. His response is only that he has, but there is nothing to indicate who he is and he is not using a handle either.
"He (or she) is sharing his opinions and he has stated that he is here to learn about something we have been discussing that he doesn't know the answer to. That can only be a good thing. Can you please leave the paranoia at the door, for a change? The name of this blog is An Olive Branch."
I would truly hope that is the case, but usually scientist don't start making underhand comments about other scientists experiments. He should explain what he means.
"Can you please leave the paranoia at the door,"
I know its easier to pretend nothing is going on. I can pretend here that is the case, but if someone says something was published in a study and it wasn't, surely I can say it wasn't. If they want to argue differently they should be able to provide a quote or reference to a figure that backs up their claim. If we don't know who this person is and the work isn't published even in an abstract or conference presentation taking their anonymous word for it is unrealistic. I wouldn't expect differently when I do the same.
>Dear Scientists,
I am hopeful that we can collaborate. I realize that much more data needs to be generated and that is what your laboratories have to offer. I am not a virologist or an immunologist and although I wish I was, I am not a scientist. However as a physician I have learned to be a detective to understand why my patients are sick, I try to connect the dots. I believe that our retrovirus participates in many disease processes, not just CFS. I am using the word participate rather that causes because human disease processes are very complex and multifactorial. The dots that I am trying to connect have been known for at least 20-30 years. First we accept that retroviruses that cause human disease can infect T-lymphocytes and monocytes. A search of the literature shows that monocytosis is often present in cancer and autoimmune disease and that clonal T-cell expansion is present in cancer, autoimmune disease and neuroimmune disease. I have monocytosis and a T-cell clonal expansion and they go up with worsening of my B-cell leukemia and decrease when my leukemia responds to ARVs. The rates of increase and decrease are different for each cell type.
We are at a juncture where we can go forward with these clues or bury the concepts.
My point is that with so many sick people with cancer, autoimmune disease and neuroimmune disease that we have in reality helped minimally, why not go forward? We will not cure these diseases by documenting the presence of a retrovirus and treating the retrovirus, but we will improve quality and quantity of life. This has been my own personal experience with antiretroviral therapy.
My motivations are pure. I am too old to benefit from fame and fortune, although those of you who make the discoveries are likely to reap these rewards. My motivation is to strike a blow against these cruel disease processes that have claimed the lives of my patients, my friends and my family. And of course, I would like to help myself.
I was asked about my personal results that were generated by Dr. Mikovits to whom I gave written consent to publish and post. Her slides are now in the public domain and if you put X Rx and Ottawa into Google, you will go directly to the slides. I assume I am patient 3058 as the graph of my CLL parameters is the next slide. There may be more of my data in other slides, but because of the legal issues I can’t discuss it with Dr. Mikovits so I don’t really know. If you wish to contact me privately, here is my email: mcs@buffalo.edu.
Michael Snyderman, MD
>"So does that creation, assuming it is correct, mean that the lab retrovirus created could potentially be infective, indeed was infective to monkeys?
Does it mean that what Mikovits found was a lab contaminant and that is also why she found some blood samples produced antibodies?
What is the connection, if any, between virions and antibodies?"
Yes it would mean the wild-type virus or synthetic virus is infective. There is no evidence that the viruses found by Mikovits and Ruscetti is a lab contaminate. They don't match any MLV, the serology results cannot have come from a contaminant, positive samples have been retested by the CDC and another independent lab and they were VP62 plasmid contamination free, the VP62 plasmid was never in either the Mikovits or Ruscetti labs, and they both independently found the viruses using blinded samples.
A virion is an infectious particle that carries the genetic information of the virus from cell to cell. An antibody is created by the immune system to attack foreign invaders such as viruses. Antibodies are therefore directed at virions to neutralise them, i.e prevent a retrovirus from attaching itself to a cell.
>Paula,
That was Anon non-scientist who won't identify him or herself. Or tell us anything about why he or she is so opinionated about the lab science. I have been reading this person's stuff for a long time now, ad nauseum, and am really, really annoyed by it.
Anon, Why do you see yourself as the protector of Judy Mikovits and Frank Ruscetti? Yes, I think everyone should be able to be anonymous if they choose, but in your case, your continual presentation as knowing the truth about the lab science seems nuttier and nuttier to me. You need to tell us about yourself, so we can evaluate your behavior. Otherwise, you are wasting everyone's time, and you've done enough of that already. We are on the same side, you and I, presumably, but you are not helping the cause. Personally, I wish you'd go away.
Jamie
>"Anon, Why do you see yourself as the protector of Judy Mikovits and Frank Ruscetti?"
I don't. The evidence is there is the papers. It is not my truth, but in the published papers.
"but in your case, your continual presentation as knowing the truth about the lab science seems nuttier and nuttier to me. "
Why are you being rude? What are you saying I have gotten wrong?
"You need to tell us about yourself, so we can evaluate your behavior. "
How would that tell you anything about behaviour?
"We are on the same side, you and I, presumably, but you are not helping the cause. "
Jamie, how do lies help the cause? Shouldn't we be asking for the truth?
>Anon 10:53,
I don't mean to be rude. I'm annoyed and want the behavior to stop.
Why do you know things that even Dr. Mikovits doesn't? Please tell us. Your continual attacking of anyone who questions anything about the Science study is just plain dumb to me. Deaf and blind. Obviously, mistakes were made, or we wouldn't be in this mess. The travesty is that the scientists most directly involved aren't being allowed to unravel what happened, since now it's tied up in the courts! That's really going to help things. But your arguing that everything was perfect doesn't help a thing. The Science paper was retracted prematurely in my opinion, but clearly, there were problems with it. We should be fighting that the baby not be thrown out with the bath water, but trying to hold on to something so tenaciously that has such problems, doesn't help anyone. You are trying to discredit people that we need. Not helping. Misguided, IMO.
Acceptance. The past is the past. The fight now is to keep the work going, figure out what was right and what was wrong, not defend things that may not be true.
Jamie
>"Why do you know things that even Dr. Mikovits doesn't? Please tell us."
I don't know what that is about? What have I said that Mikovits wouldn't know about?
"Your continual attacking of anyone who questions anything about the Science study is just plain dumb to me."
If someone came along and said this study looked in the same samples from the paper and found contamination in those samples that would be evidence. If they could say oh yes the SFFV cross reacts with this or that, that would be evidence. It wouldn't necessarily be evidence that this has occurred, but it would be the first evidence that would question the results. The evidence gathered from those independent labs also shows the opposite.
When Silverman found he had VP62 plasmid contamination in his samples they went back and checked. It only extended to his experiments. If they could not have shown that or if the sequences were a match for VP62 that would again suggest something had gone wrong. But other blinded studies have been run and presented at conferences, new polytroipc env sequences have been added to the genbank. Again the weight of evidence doesn't show anything wrong in those other labs.
" Obviously, mistakes were made, or we wouldn't be in this mess. The travesty is that the scientists most directly involved aren't being allowed to unravel what happened, since now it's tied up in the courts! "
Yes, but they were only identified in Silvermans separate experiments, no where else. I agree these court cases are pathetic. It is hindering progress, even if that progress eventually concluded that all the experiments must have been wrong. But we are so far from that. Nothing from Mikovits or Ruscetti's experiments has been indicated to be wrong with any evidence.
"But your arguing that everything was perfect doesn't help a thing. "
That is definitely not what I am saying. Sorry, if I have given that impression, but it is not the case. The evidence still only weighs everything in favour of the viruses being present. It's not going to progress though without further research as you and I agree.
"The Science paper was retracted prematurely in my opinion, but clearly, there were problems with it. "
That was still only identified in Silverman's experiments, not the separate blinded results from the other two labs and experiments.
"We should be fighting that the baby not be thrown out with the bath water, but trying to hold on to something so tenaciously that has such problems, doesn't help anyone. "
Which is why I agree the paper should never have been retracted. Especially when the sequences identified by the other two labs are only polytopic. They should have been left to finish full sequencing on as many isolates as possible. I'm not sure what you think I am trying to hold onto?
"You are trying to discredit people that we need. "
By pointing out what was not done or what they have said which is not backed by evidence. Is that what you mean?
", not defend things that may not be true."
That is why it is important to stick to what the evidence is. It is not defending a truth but what is indicated. We all know there is never any absolute in science. If nothing is published to dissuade a piece of research it cannot be said to not be true. This is why I do keep saying research needs to continue.
>JDJ wrote: “All I am asking for is that it be studied, not shut down if this attempt fails. Also, that our therapeutic options not be limited by how slow the science will be to unfold ……..”.
But what is “it” ? It is somewhat ironic that for a blog with a readership and commentatorship that represents a strong dislike of M.E/CFS criteria that are ‘too wide’, that the scope of “it” (the illness) is considered as being caught in very widely cast net.
If the intent is to engage with scientists, then the discourse has to be one that invites a form of participation that acknowledges the values of the disciplines of those with whom engagement is sought. What we see in the discourse that takes place within the comments section of this blog, is anything but a valuing of science; if that is to change then that change has to led from the front (the blog owner) and that must require clearer definition of what “it” is. Does “emerging disease of very great proportions” serve as a distinction between M.E/CFS and an unnamed retroviral disease ? Or is this “emerging disease” a further descriptor which is being added to the characterisation of M.E/CFS ?
There seem two entirely contradictory cognitive processes being developed on this blog – on the one hand there is an expansive ‘description’ (are fungal toxicity and retroviral causation mutually exclusive or is it contended that both are relevant ? and how is it possible for Dr Snyderman to have a diagnosis of both CFS and cancer when by all agreed criteria the latter is exclusive of the former ?) while on the other (and in response to the expansive ‘description’) there is a circular semantic, onomastic and ontological argument about what is the ‘true’ ‘disease’ with which this blog is concerned.
The wish to simplify the ‘complexity of “it” by reducing the complexity into ‘just one thing’ is understandable, but it is precisely that fallacious approach that leads to the interminable arguments that the comments here so thoroughly demonstrate. There is an endless circularity of statements of who and who does not have ‘real’ CFS, or ‘real’ M.E, statements of which ‘experts’ have identified the ‘true’ nature of the illness, and of statements that there a single ‘right’ causation (infectious unidentified, infectious identified – retroviral etc, exogenous environmental unidentified, exogenous environmental unidentified – fungal toxicity etc, etc) . Unfortunately this circularity is never opened to examination of the core proposition on which all the differing contenders rely – that is: “M.E (or preferred term) is a single disease entity”.
Until this Rubicon of ‘single disease entity’ is crossed, there is no room for science in the discourse here. It doesn’t matter how many scientific papers, conference reports or favoured researchers are quoted, until the discourse is grounded in some basis that allows for a ‘testing’ of hypotheses in a reasoned way, then scientists have no ‘entry’ to make a contribution. The concept of the ‘one true disease’ is an artefact of ‘patient culture’, it has no basis in any scientific reference, except, with utter and profound irony – the historic position of the psychiatric perspective ! To allow a dialogue amenable to science, requires a definitive choice to be made about what “it” is: is it a disease of a single (albeit complex) aetiology which may be explicable of some cases of M.E/CFS, or is “it” M.E/CFS as broadly described (CDC, NICE) which is an illness description of symptomology, which symptomology must at this stage of knowledge, be considered to be likely engender by multiple causative agents producing multiple aetiologies across the patient population ? It is not enough to say ‘we don’t know, that’s what we need the scientists for”, because without the clarity provided by making the choice of definition, the discourse will remain circular and unamenable to any scientific resolution.
>Hey Anonymoi,
Did you know that you can put any name you want in?
Or sign like this?
Moonwalk
>Whoa, in vitro unbeliever,
What matters is what we find in vitro, not the labels we currently have. If we knew what caused autoimmune diseases, autism or myalgic encephalomyalitis then we could group ourselves. Right now we cannot form such groups, so we group as best we can and test for things.
I think I posted before that spinal fluid proteins are different in chronic Lyme and CFS BUT THE SYMPTOMS LOOK EXACTLY ALIKE. That's how one Lyme patient ended up in the ME/CFS group. I could get a fibro label if I allowed the doc to do so. Occasionally I do because it helps insurance to cover the bill. Who gives a rip.
If we get cancer do we then lose our CFS label? Does that mean that whatever CFS is we never had it. We really had precancer?
Okay let's KISS because this is not simple and we are not stupid.
>OK, for ease of identification I will identify myself as NotBilly. JDJ can verify through my IP address that I was posting before. I chose this as a juxtaposition against the anon poster who keeps making claims that are not based in real science – I have never been on any other CFS/ME forum.
For example he/she said:
"The truth is that there is no published study showing virions coming out of 293T cells transfect with VP62. Why else do you think he cannot provide the quote to back up his statement?"
For the umpteenth time, here is a figure form a PUBLISHED paper showing XMRV that originally came from 293T cells and a VP62 plasmid:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739868/figure/F1/
You keep saying that there is no published data on this, but here it is for everyone to see. For, like, the 25th time, the authors state:
"We constructed pXMRV1, a full-length XMRV molecular clone, using 2 overlapping clones from patient isolate VP62 (6) [gift of Don Ganem, University of California, San Francisco (UCSF)]. pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection"
@JDJ: I know I don't need to cite, but in this case its necessary. This individual is really divisive on the science and his/her paranoia against me is remarkable. This person is really dragging the discussion here on your blog. Someone needs to stand up to him.
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>@Paula:
"Okay, I will ask the dumb questions. One of you anons saw virions hatching out of a manmade retrovirus. Do I have this right? Probably not, but you have to start somewhere to learn.
So does that creation, assuming it is correct, mean that the lab retrovirus created could potentially be infective, indeed was infective to monkeys?
Does it mean that what Mikovits found was a lab contaminant and that is also why she found some blood samples produced antibodies?"
First of all, these are not dumb questions, but rather insightful. I'll answer the best way I can.
I didn't see virions hatching out of a manmade virus, but rather virus coming out of cells that were given instructions to make the virus. Specifically, the DNA was put into these cells. That DNA (namely a plasmid that encoded XMRV) expressed viral proteins that got together (inside the cell) to form virions. The virus then budded from the cell and matured. This technique is avery easy one, and one that virologists do everyday for since DNA and molecular biology was discovered. The process literally takes 15 minutes and virus is made 24 hours later (budding from the cell).
Another interesting note: the virus can be called manmande and mousemade. Man-made in the sense that we put cancer cells in a mouse to study the cancer. Mouse made because the virus recombined in a mouse and infected the prostate cancer.
YES any lab retrovirus produced from any cells can be infective. Including XMRV. I have grown the virus and infected cells. Those infected cells will always make XMRV because the virus integrates in human DNA. Those viruses can be used to infect more cells… and so on… and so on… You get the idea. But just to be clear, there are no runaway infections going on. Just enough so we can study XMRV.
"Does it mean that what Mikovits found was a lab contaminant and that is also why she found some blood samples produced antibodies?"
So blood samples by themselves can't produce antibodies. Only B-cells found in lymph nodes are capable of such feats. However, they can be found in plasma, and this is what Mikovits tested.
Now the tricky question is why are those antibodies there? I assume we are talking figure 4. This experiment in question relies on the ability to detect antibodies from the Env protein of spleen focus forming virus. This protein very similar to XMRV Env so they assumed that if patients had a signal then it would indeed be from XMRV.
Here is where this assumption is wrong and the anon poster always attacks me for.
That Env protein is also similar to other Env proteins from other retroviruses. The possibility of cross-reactivity is definitely there. This is all the more possible when endogenous retrovirus litter the human genome (they make up close to 8% of our genome). Is it possible that in CFS patient sera, the SFFV env protein cross-reacted with something else we have, that we don't even know about? Yes. At least this is my opinion. In my opinion, it was wrong for authors to conclude that those anitbodies and XMRV antibodies since the experiment itself is not very specific.
I hope this clears up a few things.