Joseph Conrad spent much of an adventurous life seeking out the blank spots on maps. What he found in one of them formed the shattering message of Heart of Darkness. He had gone looking for strange and exotic aspects of the non-European world. What he found was pathological behavior by Europeans outside the constraints imposed by civilization, and by Africans whose traditional cultures were collapsing. To the present day, the Congo where he gained this experience has continued to be a source of revelations about human nature -- verging on horror. Everything which could go wrong with colonial government and the governments which replaced them seemingly has gone wrong. The story is a cautionary tale for those seeking adventure in troubled territory; indirectly, it carries a message for those interested in pathology: the blank spots on the map are places to find pathology you would not likely imagine. We've already seen the opposite approach used to ignore this disease, excluding anyone who is seriously ill. If you want to understand new pathology you look for it in places where there is no conventional explanation.
On maps of human retroviral pathogens there are a number of blanks. For example, the spuma viruses are so different and strange I would compare them to the wastes of central Australia, or the badlands of the western U.S, on geographical maps. Those most resembling the blank where Conrad found more than he bargained for seem to me to be the human beta and gamma retroviruses. We know nothing solid about what is going on there, but disturbing rumors have trickled out from many sources over many years. Genetic research on ERVs reveals that prehuman ancestors had quite a lot happening in that region, and our primate relatives still have very similar activity.
If the lack of human pathogens in that region is in fact a fact rather than an artifact it deserves to be carefully explained with clear reasoning. What I have read or heard so far reminds me of an expression physicists use -- hand-waving. When you don't have a solid argument for something you strongly believe you talk fast and wave your hands a lot.
The central problem with research in this region is that present pathology gets mixed up with ancient pathology. You can't easily track your quarry through this area because there are tracks all over the place, and you can't always tell the fossil trackways from fresh tracks. You might be following the tracks of an extinct dinosaur, not a living animal. This is not merely inconvenient, it is downright embarrassing to admit. The safe research strategy is to avoid such situations, and concentrate on pathogens which are unambiguously new, even if this causes you to avoid human diseases which could have been present since Adam. (Eve has been blamed for quite enough already.)
Conventional dogma concerning ERVs has internal contradictions worthy of abstruse theology. On the one hand these are said to be ancient fossils, and quite thoroughly defective. On the other hand they are said to be activated by damn near anything. (In this case, I mean reactivating a virus which had ceased to be replication competent, not simply activating transcription of defective genes. Sober publications actually imply that this takes place. Don't take my word for it, read what experts say, and compile your own list. Here are some places to start: 0,1,2,3,4,5. Don't be surprised at old references, confusion has been highly conserved.) I've spent considerable time scratching my head over the idea that a virus which is not replication competent can evolve into anything except gibberish in the time available in experiments. Even if random mutations move it in the direction of becoming replication competent these will not be preserved and transmitted better than random background noise unless the virus actually attains that goal.
When I look at sequences of known ERVs without corresponding exogenous relatives I find multiple handicaps to replication. There are deletions which need to revert, frameshifts which need to be corrected, and stop codons which need to be excised. It is rare to find even an ERV for a simple retrovirus with only a single such defect. This makes it hard for me to accept conventional opinions. As far as I can determine, the proposed conditions for activation of ERVs are precisely the same as for those activating a fully replication-competent provirus which just happens to lie below your threshold of detection.
Thresholds of detection are one of those scientific facts of life which pervade experimental science. If you don't know exactly what you are looking for you can easily miss evidence. If the data violate your assumptions you may see and dismiss evidence which could have won you a Nobel prize. (This actually happened with cosmic ray images showing the positron turning in the opposite direction from electrons in the same image. Anderson openly admitted that he had failed to follow up on Chao's anomalous gamma ray results, which occurred under the same conditions as such images on stacks of plates. Chao remains a footnote in histories.)
With that insight, the most parsimonious explanation for these reactivations is that similar exogenous viruses are present, below our threshold of detection, but are being held latent prior to the disturbing influence credited with activating an ERV. If we were talking in purely academic terms, about some other species, this possibility would be on the table. It is only when this reasoning is applied to human disease that such alternatives must be excluded for reasons which are largely medico-political.
There is another embarrassing analogy: looking for your keys under the lamppost, where the light is better than where you dropped them. Retroviruses are divided into two large groups called simple or complex. For those called simple a linear narrative can describe their path to replication. For those called complex, the narrative is more like Jorge Luis Borges' story, "The Garden of the Forking Paths". For reasons I will not even attempt to explain, complex retroviruses seldom become fully endogenized. This means the background clutter which makes work with beta and gamma retroviruses difficult is much reduced. If you find a sequence resembling a delta or lenti retrovirus, it did not come from a HERV. I've come to believe all our examples of active human retroviruses have been found among complex retroviruses largely because it is easier to separate them from the background. In the case of HIV, we are dealing with a virus which is unquestionably new. In the case of HTLV, the virus has apparently been around for centuries, but is different from any retrovirus which has become fully endogenized in human ancestors.
When I started this odyssey of investigating possible viral causes I held the opinion we were dealing with a fundamentally new pathogen. I've changed that belief. Now, I think similar, though not identical, viruses have been in humans for hundreds or even thousands of years, just as with influenza. I've traced reports of outbreaks back to the time period when far more deaths, perhaps most, were caused by bacterial infections. Without antibiotics many people who have mildly-impaired immunity would go on to develop bacterial superinfections into diseases which may result in death. Dramatically dropping rates of morbidity and mortality from secondary causes should be expected to reveal underlying diseases these masked which no one had previously suspected.
In pushing for broad research on leukemia viruses, I am going to go outside of ordinary nomenclature and include beta retroviruses. My primary reason is that these are also known to infect lymphocytes and myeloid cells. If a chronic disease caused by these viruses is missed, or attributed to other causes, the unmistakable progressive disease might well be classed with leukemias and lymphomas. (One such example of a chronic disease might be rheumatoid arithritis, which affects women three times as often as men, and carries a somewhat increased risk of lymphoma. A stronger correlation may occur in lupus erythrematosus, again affecting women more than men, and acute myeloblastic leukemia. In the case of MS, most reports of leukemia seem to be caused by treatment. This obscures, but does not rule out, a correlation between the diseases.) A second reason is my perception that the line between beta and gamma retroviruses is not as sharp and clear as between simple and complex retroviruses, which could be my own problem. A third reason is the existence of such an active virus in domesticated animals (JSRV/ENTV), as well as in other primates (Mason-Pfizer monkey virus).
This last point takes me into possible paths by which a retrovirus in these groups might reach humans, but that is the subject for another entry. This one has grown far beyond my original intent.
Blank Spots on the Map
Blog entry posted by anciendaze, Jun 9, 2012.
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