The Elephant In The Room

The arrogance continues with the latest “contribution” from our government at work:

Curr Opin Virol. 2012 Jul 17. [Epub ahead of print]

Recombinant origin, contamination, and de-discovery of XMRV.

Delviks-Frankenberry K, Cingöz O, Coffin JM, Pathak VK.

Viral Mutation Section, NCI, HIV DRP, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.


The discovery and de-discovery of the xenotropic murine leukemia virus-related virus (XMRV) has been a tumultuous roller-coaster ride for scientists and patients. The initial associations of XMRV with chronic fatigue syndrome and prostate cancer, while providing much hope and optimism, have now been discredited and/or retracted following overwhelming evidence that (1) numerous patient cohorts from around the world areXMRV-negative, (2) the initial reports of XMRV-positive patients were due to contamination with mouse DNA, XMRV plasmid DNA, or virus from the 22Rv1 cell line and (3) XMRV is a laboratory-derived virus generated in the mid 1990s through recombination during passage of a prostate tumor xenograft in immuno-compromised mice. While these developments are disappointing to scientists and patients, they provide a valuable road map of potential pitfalls to the would-be microbe hunters.

Game. Set. Match. Everyone can take a sigh of relief. The human race is safe, as they’ve said all along. Scientists in a power postition at the NIH have closed their minds to retroviruses other than HIV and HTLV contributing to human disease. Is this really a scientific assessment of all the available data? Or a ploy to keep the blinders on a while longer? Baffle ’em with bullshit.

There’s a giant elephant in the room. Several elephants actually. What if there’s more than this one virus that they acknowledge they created in the early 90’s? It seems likely that it’s happened more than once, given how many chances there have been to recombine and infect human cells? But they only infect human cells in tissue culture they say, not in vivo because we have restriction factors.

Here’s an experiment with human lymphoid tissue concluding we are safe:

Susceptibility of Human Lymphoid Tissue Cultured ex vivo to Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Infection. Curriu et al.


Background: Xenotropic murine leukemia virus-related virus (XMRV) was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored

Results: XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors.

Conclusions: Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus.

So maybe they’ll take a few extra biohazard precautions for themselves, since they are working directly with these lab anomalies, but nothing to worry about for the general public. Never mind the millions of human canaries illuminating the destructive path we are on. Never mind that this could explain the observed increase in neuroimmune diseases, autoimmunity and cancer. Never mind that we’ve been mainlining attenuated viruses cultured in animal cells which express exogenous retroviruses for eighty years now. Never mind that these viruses cause similar diseases in other mammals to that which we are observing in humans. Never mind all the clinical evidence that several large patient cohorts, ME/CFS, ASD, GWI, chronic Lyme Disease, PANDAS, RRMS are related and contagious diseases. Leave it in the realm of genetic weaknesses for now. Better to be an ostrich for a while longer since the cat is so out of the bag. Let’s remain in denial for as long as we possibly can, which I guess will be until Quest has a DNA sequencing test that insurance will pay for. They are allowed to be literal and have limited vision in the name of science.

Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice using deep sequencing. Mayer et al.


It has recently been reported that the xenotropic murine leukemia virus-related virus (XMRV) derives from a laboratory recombinant. However, sequences with characteristics of the 5′ half of XMRV (termed PreXMRV-2) have been identified in several laboratory mouse genomes and cell lines suggesting parts of the XMRV genome exist as naturally occurring retroviruses in mice. We compare here PreXMRV-2 gag sequence diversity in mice to that of reported XMRV-like sequences by testing a panel of wild mouse and common inbred laboratory mouse strain genomic DNAs and by using high throughput amplicon sequencing. Sequences with features typical of previously reported PreXMRV-2 sequences, among them a 24 nt deletion, were repeatedly identified in different wild mice and inbred mouse strains within a high background of non-XMRV-like sequences. However, Sanger sequencing of clones from amplicons failed to retrieve such sequences effectively. Phylogenetic analysis suggests that PreXMRV-2 gag sequences from mice, cell lines and patient samples belong to the same evolutionarily young clade and that such sequences are diverse and widespread within Mus musculus domesticus and laboratory mice derived from this species. No evidence of PreXMRV-2 like gag sequences could be obtained outside of the M. musculus lineage. The results suggest that accurate determination of presence, absence and relationships of specific murine retroviral strains benefit greatly from deep sequencing analysis.

Meaning that most of the work that has been done so far has been a meaningless waste of time, energy and money… More from this paper:

… in both the Sanger sequencing and high- throughput datasets, PreXMRV-2 like gag sequences were not majority sequences in any mouse DNA sample, even when account- ing for possible clonal artifacts due to PCR or emulsion PCR before GS FLX deep sequencing preferentially amplifying one sequence over another in a complex mixture. Thus, and also in the light of an often unknown sequence heterogeneity provided by mouse ERVs, we feel that high-throughput sequencing should generally be applied when attempting to detect relatively rare sequences such as PreXMRV-2 from complex retroviral mixtures. High-throughput sequencing is a common strategy used for identifying rare human immunodeficiency virus 1 variants and may need to be employed more broadly.

Here’s a paper that shows that mixing XMRV with Maloney MuLV produces a more dangerous virus. Simple animal retroviruses recombine and one can “rescue” another by providing missing pieces that evolution has silenced with mutations to protect us.

Moloney murine leukemia virus glyco-gag facilitates xenotropic murine leukemia virus-related virus replication through human APOBEC3-independent mechanism. Nitta et al.

Abstract Background

One of the unique features of gammaretroviruses is that they contain an additional extended form of Gag, glyco-gag, which initiates in the leader sequence. MuLV glyco-gag, gPr80Gag, promotes retrovirus replication and disease progression. Although virtually all infectious MuLVs encode glyco-gag, XMRV (xenotropic murine leukemia virus-related virus) lacks the classical gPr80Gag sequence. We examined XMRV to determine if its leader sequence contains glyco-gag activity, whether the presence of conventional gPr80Gag affects replication of XMRV, and we describe the evolution of glyco-gag-deficient MuLVs in Mus.


We introduced several mutations disrupting two putative but noncanonical glyco-gag proteins in the leader sequence region in XMRV and found that those mutations did not affect virus

release nor susceptibility to the antiviral activity of hA3G (human APOBEC3G). A chimeric XMRV encoding the Moloney MuLV (M-MuLV) leader sequence (MXMRV) demonstrated that M-MuLV glyco-gag facilitated MXMRV release and increased infectivity. Infectivity assays with several cell lines showed that glyco-gag increases XMRV infectivity in all cell lines tested, but the level of this increase varies in different cell lines. Because MuLV glyco- gag counteracts mouse APOBEC3, we investigated whether M-MuLV glyco-gag enhances XMRV infection by counteracting human APOBEC3. Comparison of hAPOBEC3 isoforms expressed in different cell lines indicated that hA3B was the most likely candidate for a restrictive hA3. However over-expression of hA3B showed no enhanced restriction of infection by XMRV compared to MXMRV. Endogenous MuLVs in the sequenced mouse genome were screened for canonical glyco-gag, which was identified in two clades of xenotropic MuLVs (X-MuLVs) and ecotropic MuLVs, but not in other X-MuLVs or in any polytropic MuLVs.


M-MuLV glyco-gag facilitates XMRV replication, and the leader sequence region in XMRV does not encode proteins equivalent to M-MuLV glyco-gag. The fact that the ability of glyco- gag to enhance XMRV infection varies in different cell lines suggests a glyco-gag sensitive restrictive factor that further reduces XMRV infectivity. The M-MuLV glyco-gag enhancement for XMRV replication is through a hAPOBEC3 independent mechanism. The absence of glyco-gag in MuLVs carried by western European mice suggests that loss of this sequence is a relatively recent event with limited subspecies distribution.

While the decades long coffee break continues at the CDC, I’m trying to be well enough to work, in order to care for members of the most medically underserved population I’ve ever taken care of, including medical school in the Bronx and 10 years in the ED at Santa Clara Valley Medical Center, the county hospital in San Jose, CA, where the patients are a composite of third world misery. Those patients had nothing on this group in terms of lack of informed care; almost every patient I have has received abysmal care, due to ignorance and a lack of compassion because they have an invisible disease. Benign neglect is as good as it gets.

The last blog was the least controversial I’ve ever written judging from the comments. I have received many expressions of concern for Andrew that the ball was dropped. I would like to reassure everyone that I forwarded my findings and recommendations to Andrew’s doctor in Northern Ireland. Andrew has been seen twice since he returned home and is reportedly much better than before his trip. So the most important thing happened. Taking it all at face value, Andrew improved with oxygen and Deplin. He received about 30 hours of oxygen. In hyperbaric practice, I used to do a series of 40 hours and expect it to last for at least several months if the response was robust. I only hope that if it fades, he will be able to access more oxygen and L-methylfolate, available over the counter, as explained in my last blog.

I tremendously appreciate all of the expressions of support from friends around the world. I did hear back channel from a few people who were upset that I said that some ME/CFS patients are difficult from a physician’s perspective. I almost didn’t leave it in after I wrote it, but decided to, because it is important grist for the mill. There are several perversions that have befallen us, by virtue of being seen as lazy, crazy and faking. One is the need to refute that therapy could be useful for us in some way, since it is being forced down throats by the same people who say there is no physical basis. Therapy with people trying to talk you out of what is real isn’t very useful, but in the context of being believed, it might do a lot of good. Same goes for exercise. It is the context that is the problem. Another perversion is the need to be good if we ever want to be seen as sick or worthy of help. Well, Alzheimer’s Disease doesn’t make most patients particularly nice, but the disease still gets studied, and not only by psychiatrists. Neuroinflammation has behaviorial consequences, just as cardiac inflammation produces palpitations and GI inflammation causes diarrhea. It is a lack of compassion on the part of the medical profession to blame this on the patients. It could never have happened except that the disease doesn’t cause true dementia even when very long standing. It happened because doctors blame patients for what they fear and don’t understand, pure and simple.

The need to reaffirm one’s illness all the time leads to a further distortion, oft repeated in the patient group, the view that ME/CFS is the worst disease in the world. This is far from the truth, but the degree of injustice makes for a need to catastrophize, that word used all the time to accuse us of making too much of our little nuisance complaints.

All chronic illness is superimposed on preexisting personality. When it comes to inflammation of the brain, dysfunction impacts thought content. My experiences treating brain injury and developmental disorders with EEG biofeedback and oxygen taught me that strong emotions are not unlike other types of paroxysmal brain activity and similar therapeutic interventions are effective across the board for patients living with unstable brain states. People with a lot of fear who get this disease are prone to recurrent or persistent panic states. PTSD is another manifestation of cortisol exacerbated neuroinflammation which shows up often in the patient group. It is organic. Difficult brain states make for tricky management from a doctor’s point of view. The word encephalomyelitis means inflammation of the brain and spinal cord. Of course there are behavioral consequences.

The truth is that it is not the worst disease in the world by any stretch of the imagination. It has the potential to become a living hell due to ignorance of what it is or what to do about it. The safest things we have at our disposal are oxygen, improved methylation, stress reduction and various antiinflammatory strategies, including addressing insulin problems and doing whatever possible to heal the leaky gut, a key factor. My early practice experience with a small number of patients is that these strategies are effective for reducing the degree of suffering.

Speaking of gut inflammation, our family is working on our diet. Patients who have tried everything for many years are often resistant to changing diet. It is so much more work than just about any other therapeutic intervention you can come up with. Physical work is a problem for the patient group and eating well is more work. Also the results of dietary interventions are usually slow. Food is gratification when everything else goes to hell. But you are what you eat. I advocate a whole foods, unprocessed, organic, if possible, diet that restricts sugar. Wash any sprayed produce carefully. Avoid chemicals, especially the excitotoxins MSG and aspartame. I tell my patients to read ingredient lists and don’t buy it if there are things in it that you don’t know what a handful of it looks like. The average American consumes pounds of chemicals a year. Whether there is a retrovirus or not, the disease doesn’t kill directly, life can go on for a very long time and the quality of life of human beings is dependent upon what they put in their mouths.

A member of my husband’s family brought my attention to a film called Forks Over Knives, available on instant Netflix. It proposes a vegan diet as the way to health. I was a vegan for a few years when I was young, and whether it is or isn’t a healthy lifestyle, the premise put forth in Diet For A Small Planet in 1971, which seemed true to me way back when, is still a good argument for not eating animals, but ethical considerations and attempts to save the planet aside, the movie doesn’t draw the correct conclusions from it’s own observations in my opinion, or at least it doesn’t prove it’s premise. It is just as likely that the avoidance of the sugar, chemicals, hormones and antibiotics involved in the eating of meat and processed foods in our culture is at the bottom of the adverse health consequences of our modern diet, not meat in and of itself. Still the movie is worth watching if you are thinking about food, and the review found here: “Forks Over Knives”: Is the Science Legit? is also worth a look.

I had a Crohn’s diagnosis at one point and spent a summer on TPN (total parenteral nutrition) before being saved by a surgeon. Afterwards, the diet that facilitated healing most was the SCD or Specific Carbohydrate Diet. It is based on the premise that the inflamed gut is harmed by exposure to disaccharides and polysaccharides, contributing to dysbiosis. It allows some simple sugars. It eliminates grains and dairy products, except for hard cheese and SCD yogurt, superfermented for 24 hours to break down the lactose. SCD yogurt is an excellent probiotic, unless you are cassein sensitive. The list of SCD legal/illegal foods is here. My family is cheating with brown and wild rice. It’s tough for me to keep weight on and I am grateful to my daughters for supporting this now, since I have a hard time doing the right things for myself. It has much to do with the many years of ritual abuse involved in becoming and being a doctor. I was trained to overlook the needs of my own body and carry on no matter what, relying on magical thinking to keep going:). It isn’t working too well for me now. A bit late in the game for repatterning, but I guess it’s never too late to learn, or at least I hope not.


Today’s song: Doubting Thomas by Nickel Creek