Somebody posted on FaceBook a few days ago: I love my computer, because my friends live in it. For no one has that been more true than for me, despite the trolls. I started to write, because I was so excited about what was happening and thought sharing my experiences would be useful. My selfish motivation was to move it along as quickly as possible, so we could all get on with it. I thought the anecdotal clinical responses might drive it, along with fear of a contaminated blood supply and the lure of money for the drug companies. I actually felt a twinge of regret that by the time I was ready to work, it would be all figured out. Ha!
I wrote because it was all I could do at the time, and it didn’t matter what anyone thought about me. Work was an impossibility, a fantasy. Now I’m working part time and taking care of a very small number of patients. I am caring for them in a very hands on way, like they are all Ali:). I will be max’ed out very quickly. I am not selling a protocol or seeking patients on this blog. That will take care of itself word of mouth, as it did in my last practice. I am writing to share with people who could never get to me. Many readers are on the other side of the world. My approach to treatment is very moderate and non-invasive, having learned from the mistakes of the past. Primum non nocere. Why should that threaten anyone? Unless you disagree with my question authority point of view. Honestly, the idea that what I’ve been saying has ignited such a firestorm is a puzzle. You would think that people would be happy that a doctor is willing to share openly, not to mention hearing that someone is making progress. Instead the whole thing has spun into some weird parallel universe where the critters all have big, sharp teeth. That’s what has me scratching my head. The response is so off kilter to the message.
My interaction with Jason was a personification of the problem. After insulting me on my own blog to the point that I thought he was a troll, he sent me a request to review the science and post his thoughts. I responded as warmly as I knew how. The only thing I asked was that he learn something about the disease. I offered to share with him, so that the time he put into it would be meaningful. He said he would review the literature. Period. End of discussion. If it isn’t in the literature, it doesn’t exist. Below is my second letter to Jason.
Dear Jason,
I deeply appreciate your coming forward as yourself, and not an anonymous poster. I will publish what you write without editing. I will only state that it is opinion, not fact, and that I think you were brave and generous to do it. If I disagree, I’ll blog my thoughts after. The only way I wouldn’t post is if it was clearly written from a place of needing to prove me wrong. I am asking you to come to this project with a “beginner’s mind”.
“In the beginner’s mind there are many possibilities, but in the expert’s mind there are few.”
~ Shunryu Suzuki
In your quest for objectivity, please don’t forget that there are real people with a horrible disease, many trapped in their beds with no medical care and no hope. I am the CFS suicide hotline. The shoulder to cry on. I take calls and email regularly. I am not exaggerating the importance of what you write. Please take that responsibility very seriously, even if it makes you somewhat less “objective”. Think about why the hypothesis might be right, not just why it’s wrong. Don’t decide going into it what the answer is, even though I have attacked some of your heroes, you think unfairly, but I think they have shown an incredible lack of compassion, cruelty to oppressed people.
I don’t think that you can fully consider the hypothesis without understanding the pathophysiology of CFS, autism, Gulf War Illness, Lyme Disease. Also human and animal retroviral disease. The veterinary literature is very telling. What you will find when you start to look into viral etiology of CFS is literature proving it isn’t EBV or HHV-6. There is nothing but the recent furor to connect CFS to retroviruses. Other than Michael Snyderman’s data, published as a poster presentation. So the only choice is to start with a hypothesis and work backwards. Please bear in mind, I am a doctor, not a scientist. I sit in a room with people who want to die because they have lost everything, are suffering unbelievably and are laughed at by doctors and scientists. Imagine having the worst day of flu of your life and having it never go away (not the way I got sick btw). Then maybe a hundred other horrible symptoms, pain, nausea, intractable headache, chronic cramps and diarrhea, sleep deprivation. Then your doctor sends you to a psychiatrist who says you are too focused on your symptoms. Cowboy up. Only you can’t even sit up. Then your kids and husband start getting sick too, and nobody cares.
I have never claimed to be ‘objective’. It was an ah-ha for me. A 15 year mystery, that almost cost me my life (transfusion, emergency surgery, small bowel resection at midnight, TPN), beginning to give up its secrets. A mystery that ended any chance for a normal life for my beloved daughter at 13. I am tearing up as I write this, thinking of what she was like when she was the size of your precious baby. Not that she isn’t wonderful now, but her life is so diminished compared to the one she could have had. I was 41 and a successful doctor, so I had something to fall back on each time I’ve recovered enough to do something, but the kids who get sick in adolescence never get to live at all. The second generation is sicker. The youngest person I’ve heard of with CFS is 4, not autism, CFS, 3rd generation. Grandma is very sick. Mother, a doctor, a little sick. Doctors and nurses are over represented in the patient group. Also vets. You should be able to share in my outrage at the lack of epidemiological studies, since it doesn’t impact your field, once you start to hear what the patients are saying about their families (some on my blog). I am looking forward to your figuring out how little money has been spent on a disease that affects so many and causes so much disability. You wouldn’t believe the untapped talent in my mail.
Judy Mikovits heard the pain of the patients. Too much for her own good. She took all the desperate mail and was terribly affected by it. She visited horribly ill patients in the UK and Norway, who are being abused by their doctors and governments. Patients lying in dark rooms with ear protection and feeding tubes, for years; too weak to roll over, begging to be let out of their bodies. I kid you not. I got involved with the WPI because Judy was answering all this mail, from people who were writing to me also, and she was really bad at it, while it was a reflex for me. Judy Mikovits is a gifted scientist, with human frailties. She was working in an impossibly toxic environment with no help and the entire old boys network coming down on her. She did lots of things wrong from a PR point of view. What she did or didn’t do right scientifically will all come out in the wash. It is the finding the novel pathogen, or more likely pathogens, the theory that matters now and that must be investigated. Even though you prefer deductive reasoning, genius requires induction. There is an enormous opportunity here for you, both as a scientist and as a humanitarian. It is possible to be both.
I have brainstormed with Frank Ruscetti. He thinks it’s real. Sandy Ruscetti thinks it’s real and she understands the murine retrovirology better than almost anyone. I had dinner with Ian Lipkin. He said “it smells viral”. He was clearly very interested. It isn’t one of the known pathogens…
I know you are in the lion’s den and need not to get eaten. But always question authority:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/?tool=pubmed
The ‘souless freak’,
Jamie
PS. I didn’t send any letters.
PPS. Another Suzuki Roshi quote:
If you want to enjoy the movie, you should know that it is the combination of film and light and white screen, and that the most important thing is to have a plain, white screen.
~ Shunryu Suzuki
I sent our correspondence to five trusted friends for reality testing, two of whom are well known advocates, before I answered Jason’s response to my letter. Complete consensus. One of them called him a ‘snot’ and I did pass it on to him, I confess. If the shoe fits. I suggested he start his own blog. I’m sure, in fact, Jason is a very nice young man, with a young family, trying to get by, like all of us. He doesn’t even really know what hit him, removed as he is, working in an ivory tower environment. He was unwilling to take off the blinders and my readers don’t need any more negativity. Plenty of that to go around. Patients, with no medical help, have to decide what to do, in real time, with incomplete information, in a very imperfect world. And I have to treat patients in the here and now.
The attacks are an energy suck. Not just my energy, but readers’ precious energy. Any suggestions about how to deal with it are greatly appreciated. It is very strange to be judged by anonymous people. It’s not just me that they are judging, but the uppity patients who agree with me. If nobody was reading, they wouldn’t bother with me. It is the growing sense of community that is spooking them, not lil ol me. Being forced to defend myself again and again, to prove I’m right, when I’ve never said that I am, serves no one. Being right is the booby prize.
I want to get better. I want my daughter, my patients and my readers to improve. If somebody has better ideas, please share them. The name of the blog is X Rx. I think it is still appropriate. Virologists call an unknown pathogen X. Elaine De Freitas called her virus X. I concede the URL is obsolete. But the point is, it does me no good to be right if it doesn’t result in treatment, at least an approach to the illness. We can start to look at our NK cells, number and function, as well as cytokines. There are many things that can be done for AIDS, in the alternative medicine world, in addition to HAART. Let’s look at those. One of the reasons we are better is the excellent help we’ve had from our FP, Russ Canfield, a smart, young doctor in Santa Fe, who has a profound understanding of the functional medicine piece, which I didn’t find cost effective when I was in practice last time, but which, he is slowly convincing me, has made progress since then. I have a longstanding interest in herbs. Trying to put it all together, like everyone else. The blog is an assist, bilaterally, except for anonymous attacks and gratuitous insults. I will persevere, as the vast majority of the feedback I get is positive, even from people who disagree with me.
>Kathy D said: "Can't folks discuss all of this objectively, without criticizing anyone here?"
You mean like yourself, who just got done calling Jason "arrogant"?
Isn't that at the very least, hypocritical Kathy?
>To Robin, the inteview you mentioned with Dr. Mikovits must have been from a very looong time ago. I can attest personally that she knows the illness better than ANY physician I have ever encountered, Dr. Deckoff-Jones being the only exception.
>The CDC, NICE, Trans-NIH, Cfids Ass, ME Ass, MRC, all claim to know ME and then they talk and study fatigue. Puts things into perspective a bit doesn't it.
>When is Science magazine going to retract John Coffin's paper Paprotka et al. for failing to describe or name the only assay that was used on the later xenografts? A reverse transcriptase PCR assay.
>How about Retuximab anyone? What do folks think?
Have you read the articles about the Norway study?
And also how does Herpes 1 relate to CFIDS? Is it common among us? How does one even get Herpes 1 when in solitary and homebound for the last few months, getting food, prescriptions and newspaper deliveried. Maybe delivery folks are carrying it; they're handling change and bills when delivering.
Or is it from my childhood? Apparently most adults have it dormant, and it pops up when exhausted, have malnutrition, or immune system weakened. Am wondering here.
>Ritximab supports the human gammaretrovriuses hypothesis for ME/CFS. MLVs infect B cells.
The treatment will deplete B cells and then once it is stopped they will return. Still infected with HGRVs.
>just popping in to wave a hello,
and drop of a hug.
and herdy-gerdy-gerdy, thats me practising my Norwegian, where I shall be Living the minute I win the lottery.
>The apology from the Norwegian assistant director of the Health Directorate is not what people think it is.
>>The apology from the Norwegian assistant director of the Health Directorate is not what people think it is.
What is it then?
http://www.euro-me.org/news-Q42011-003.htm
>There is another translation. He only says chronic fatigue and says that care could be better. It comes down to what they do next.
>Anonymous @ October 22, 2011 8:53 AM stated " There is no mention of the processing methods used for the Lo patients in the blood working groups paper."
There certainly is mention of the processing methods in the BWG paper. Might want to actually read the study. The authors repeatedly point readers to source (4)in both the body of the paper and the supplemental information. From the BWG "These blood samples, which were drawn
from persons who were previously reported to be XMRV- (2)
or P-MLV-positive (4) and from blood donors who
previously tested negative for XMRV, were aliquoted into
replicate tubes and assembled into coded panels together with
replicates of experimentally prepared positive control
samples." BWG also stated that they froze all the samples. So they are referring to the Lo samples in the body of their paper.
Regarding the use of trizol, take a look at the methods from the Lo 2010 paper.
"In the mid-1990s, we obtained serum and whole-blood samples from CFS patients for the investigation of possible mycoplasmal infections (11). Whole-blood, peripheral blood mononuclear cell (PBMC), and plasma samples from 37 CFS patients in the mycoplasma studies were maintained in frozen storage at −80 °C. Twenty-five patients were from an academic medical center and 12 were referred by community physicians. Repeat blood samples were obtained from the academic medical center patients: four samples were obtained 2 y later and similarly kept in frozen storage, eight were obtained ∼15 y later, in 2010, and processed for XMRV/MLV-related virus testing without being frozen."
OMG, no use of trizol, does this make the results useless? Can't have it both ways. BWG followed the same preservation methods of Lo. They are either both wrong or both right.
Seriously V99 or anonymous, you really need to be able to back up your statements with facts and proof, not magical thinking and Dunning Kruger effect.
>@Anon 8:53 PM
There is no description of the collection and processing of the Lo patients. If you fail to understand why this is crucial to understanding the failures of the paper, then it is to be expected you would not notice it is missing.
This is the description for the WPI patints and lab controls, where is the equivalent? Where the tubes pre-screened? Who screened them? Who anonymized the samples and when? How long from collection to processing? What were the samples processed into and how?
"A single lot of EDTA BD Vacutainer Blood collection tubes (BD Biosciences) was purchased and distributed to two laboratories (CDC and NCI/DRP) for testing to ensure contamination with XMRV or mouse DNA was not present. Following validation, these tubes were used for all blood collections from the WPI and laboratory controls. Collection kits, including the XMRV-free certified tubes, were distributed to independent phlebotomists (Phlebotomy Services International, Central Point, OR). Phlebotomies were performed in patient homes in accordance with IRB approval, with anonymizing of the samples performed by Phlebotomy Services International. Samples were then shipped by overnight courier to BSRI. Immediately upon arrival, all samples were processed into plasma, peripheral blood mononuclear cells (PBMC) and whole blood (WB). After centrifugation, initially 1mL and 0.25 mL plasma aliquots were made, using most of the plasma. This was followed by mixing each blood tube five times and then making two 0.5 mL WB aliquots per tube. Finally, the tubes were reconstituted to the original volume using Dulbecco’s phosphate buffer saline (DPBS) without calcium and magnesium salts. PBMCs were isolated from these tubes using the traditional ficoll paque gradient technique. The PBMCs were aliquoted at 5.0×106 cells/mL. All aliquots were stored at – 80°C."
>There was no trizol used in the blood working group with the PBMCs. That would degraded the RNA and defeat the WPI's method. Lo's team used the wrong method from Lo et al.
There has been no replication study of Lombardi et al.
>Obviously "anonymous", you have no idea what you are talking about when it comes to Trizol.
Lets review.
1. The BWG froze their samples to preserve them.
2. The different labs used different methods to isolate RNA, namely a Viral RNA mini kit (Qiagen). This kit does the same thing as Trizol which is isolate RNA.
Trizol — "TRIzol® Reagent is a ready-to-use, monophasic solution of phenol and guanidine isothiocyanate suitable for isolating total RNA from cells and tissues. During sample homogenization or lysis, TRIZOL® Reagent maintains the integrity of the RNA, while disrupting cells and dissolving cell components"
Qiagen — "Optimized buffers and enzymes lyse samples, stabilize nucleic acids, and enhance selective RNA adsorption to the QIAamp membrane. To guarantee RNA integrity, samples are lysed under highly denaturing conditions to inactivate RNases. Alcohol is added and lysates loaded onto the QIAamp spin column. Wash buffers are used to remove impurities and pure, ready-to-use RNA is then eluted in water or low-salt buffer."
Therefore, the labs involved in the BWG used a product that does the exact same thing as trizol. Therefore, the argument that BWG used no trizol is not important. Many researchers freeze samples to preserve them and then add reagants when the are ready to run their tests.
Now Gerwyn and V99, do you freeze your samples first and then add reagents later or do you add trizol before you freeze your samples? Should we demand the retraction of all studies that freeze first and add reagents later — that would be hundreds of studies.
In short, yes the BWG used no trizol with the PBMC's but a Qiagen reagent was used instead, therefore the RNA was isolated in the samples and therefore the method was not defeated.
>The active ingredient in all these many products is guanidinium thiocyanate. Which is used to denature the many ubiquitous and voracious RNases which seem to exsist everywhere before they chew up your RNA. Important if intact RNA is required (e.g. RT-PCR or "Northern" blots) but not, as various rather monotonous Anonymouses (or perhaps just one rather monotonous Anonymous) have been repeating over and over and over ad naseaum, as a "PBMC preservative". If you want to preserve PBMCs (for culture assays) you freeze them.
And, just to complete the picture, if you want to preserve extracted DNA all you have to do is sequester any stray magnesium ions, typically with EDTA. Cheap, easy, simple.
Not really a big problem.
>@Anon 6:49 am
The Lombardi et al. assays used trizol. Without trizol the RNA would degrade and the WPIs assay would be defeated.
No assay used in the blood working group was validated.
No healthy controls in the blood working group could have been declared negative.
Collection tubes were in the same lab as 22Rv1.
>"Background: Although TRIzol is widely used for preservation and isolation of RNA,"
"in TRIzol-preserved samples"
"TRIzol preserves RNA quality well"
http://m.cebp.aacrjournals.org/content/19/10/2445.full
>So what anonymous, are you not understanding the points about trizol. It's not the be all and end all of preserving research samples. You don't need to use trizol to preserve samples. Freezing to – 80 centigrade will preserve any sample. Reagents like trizol or the simiar Qiagan reagent helps to isolate and preserve RNA for testing. Lo et al did the exact same thing as the BWG — froze samples, thawed samples, then added the reagent to isolate RNA. Lombardi et al only added trizol to some samples after they initially froze samples and they also use Qiagan reagents too.
I am beginning to think you keep posting the same statements over and over becase you really don't understand the research methods. You can't seem to grasp that freezing preserves samples, the reagents isolate the RNA. Look at the methods of Lo et al, Lombardi et al, and the BWG study, you will see very similar methods of preservation and isolation of RNA.
I guess you just can't admit when you are wrong. However, repeating the same tired old statements when you have been proven wrong makes you look silly.
I suppose people need information to make conclusions about what people are claiming. It seems what you have been claming about trizol and its lack of use in the BWG study is wrong. They used Qiagen reagents instead and isolated RNA for their purposes. Rather than repeating the same statements over and over, can you possibly provide some information why you believe that I might be wrong. I have taken information from each of the studies. It speaks for itself.
>Without Trizol RNA degrades. The failure of the blood group to use this with the PBMCs means the WPIs assays will have been defeated.
Despite this the blood study exposed certain results to contamination as 22Rv1 and a portion of the collection tubes were in the CDC lab together.
Controls could not have been declared negative as no PBMCs were screened prior to blinding.
No assay was validated for human gamma retroviruses, only VP62, a clone which cannot integrate, does not exist in nature and has no relationship to the findings of Lombardi and Lo et al.
The results are meaningless due to these and other errors. Dr Busch is no doubt upset about such mistakes.
>No eqivelant preservative to Trizol was used in the blood study either.
But why should anyone be surprised that you have no understanding or basic grasp of retrovirology.
>What is this attitude about? Why these attacks? Most of us are not retrovirologists. We're sick people who want information and solutions.
It's getting laughable at this point.
Anyway, just read at Chronic Fatigue Syndrome Advocate website that Dr. Judy Mikovits will continue studying HGRV's. Also, that she went to Norway awhile back to find out about Retuximab.
Also, there is a list up at that website of some of the research going on in many spheres regarding CFIDS. Some of the efforts I'd heard about, not all.
>They attack to try and deflect attention from the mistakes in the blood working group design and to try and stop people from knowing that studies that used VP62/XMRV are invalidated so do not factor into HGRVs scientific research.
>Yes, but we're living in Ground Hog Day, the movie, in which every day repeats itself ad infinitum.
We need to find some new topics of interest.
>@Anon 2:49AM, I think you have it backward.
>@Kath d.
Then discuss something else. But to be fair HGRVs are the only hypothesis regarding ME, so I cannot see the topic disappearing. It also will not stop the scientifically illiterate continuing to argue that VP62 exists.
>Why do people have to be so cynical about the Norwegian apology? This is PROGRESS folks!! I think this is a big step forward. Ok, it will take the British establishment much longer to admit their gross negligence and incompetence regarding the treatment of people with ME but it will happen and I think it will be in my lifetime – the tide is turning.
Too little too late for many though – my thoughts are with those people and their loved ones xx
>Yes, but saying it 100 times rather than 4 or 5 times doesn't convince anyone. People's eyes just glaze over at a certain point and they move on.
We're not the ones doing the research — the majority of us. And we don't have control over it, although we can discuss the issues. And no one has control over other people's thoughts.
And why name call? Almost all of us are not retrovirologists, but people who are ill who want to get better.
>@ihave3kids said…
Progress is action, funding, biomedical research and care. Words shouldn't be used as a substitute and after 60 years of this, they shouldn't be trusted because we are desperate.
>@Kathy d.
I agree. They should stop their repeated attempts to disparage ME patients, scientists and the retroviral hypothesis because it doesn't fit within their wishes. It is also reprehensible that they would pass themselves off as scientists, or manipulate facts to achieve this.
>Most patients have an excellent grasp of scientific issues and fields. Many patients are doctors and scientists.. But then there are people who are commenting where they can and acting as if they were scientifically illiterate, i.e. they are prepared to lie. We should not assume they are patients or neutral in the power struggle of who gets to control HGRVs.
>Yes, but we don't have control of that.
All we can do is make our voices heard to the powers that be and keep the pressure on THEM to do research and find treatments, and fight for the reality that this disease is a physical one, caused by some infectious agent.
>Functional METHYLATION is the key.
Google is your friend.
>"PS. 95% of the people reading my blog think you are a "snot"."
Wow Jamie. How adult of you.
Not to mention biased and inaccurate.
I happen to think Jason has been a breath of fresh air. Also when you said to him "You're right, I'm wrong", aren't you basically saying the same thing to your readers? I'm right, he's wrong.
If I were you, for your own health and that of your daughter…I'd take a break and take care of yourselves. Your adrenals are probably fried and could use the rest. You have family wealth, so you don't need the income. You don't owe anyone anything.
Seriously. Take care of yourself and your daughter. How can we fix anyone if we can't fix ourselves first?
>Just ignore J.N. He's a breath of bad air. I love your blog Jamie and appreciate everything you have done for others.
>I've got to say, I thought Jason was sincere, and genuinely wanted to start a useful dialogue. I really don't respect the way he was treated here.
ella
>From small acorns, mighty oaks grow. Yes we have had 60 years of neglect and mockery but this could be one of those 'chance findings'- Rituximab and the like – that we have all been waiting for. I am naive in many respects I admit it – wanting to believe that every discovery is going to help me but I have to be this way or I'd just give up on life and I can't do that because I have 3 beautiful children who need me.
So I am going to allow myself to get excited at this new development because it means I still have hope. I have to keep believing that I will recover from this illness and I DO believe that I will, I genuinely do.
I will never give up on hope no matter what the cynics say – this disease has taken just about everything else away from me but it WILL NOT take my hope!!
>Jason was putting forth illogical unscientific commentary. I wish he had come here to start a useful dialogue.
>@Anon 9:54AM, that's funny because he was the only real scientist in the room. "In an insane society, the same man must appear insane."