Yet you fail to explain how this is. Their probabilistic analysis shows (and only shows) that it is extremely unlikely that two recombination events that are
exactly the same occur multiple times, independently. They don't use this analysis for other purposes, as you previously
implied (and which is also implied by your lottery example by the way).
While the three possibilities are of course strictly true, by putting them side to side it appears that they are also equally likely, which is not backed by the evidence. For instance, option 1 is billions (!) of times more likely to have happened than option 3 (see the probabilistic analysis, which was (solely) used for testing this hypothesis).
Actually, the authors do address option 2, but they (understandably) restrict themselves to the possibility of mice being the source of the contamination. However, their arguments/evidence apply equally. In short (and without trying to be exhaustive), you'd expect to find some (reproducible!) source of the thing (or one of its descendants) that has infected your cell line. Since no one has found this source, it is highly unlikely that this other source existed before "22Rv1 XMRV", managed to infect humans and many years later managed to infect the 22Rv1 cell line.
Moreover, all found strains that are
almost identical to 22Rv1 XMRV can be subjected to phylogenetic analyses, which could provide evidence that 22Rv1 XMRV is not ancestral to these other found strains. Again, the faillure of obtaining data in support of this after analyzing countless XMRV sequences, is supportive of the notion that the XMRV in 22Rv1 is the source.
Finally, the fact that the lab where they did the xenograting was one of not many places where a "human" environment
and both preXMRV-1
and preXMRV-2 'were brought together on a regular basis' (so to say), is also a pretty strong indication that it happened "there" instead of from some other source (after which it had to first infect people and then travel to the lab where they were doing the xenografting to boot many years later).
Referencing the explanations I enumerated above (and ignoring #3, which was included for completeness and is largely inconsequential to the main point), we have two competing,
possible explanations: #1 and #2. As
possible explanations--neither is certain, as the first recombination in question was not (nor likely could have been) witnessed directly--both explanations have some implied
a posteriori probability (p1 and p2 respectively) of explaining the observed phenomenon: the "appearance" of VP62 in 22Rv1 between two time points.
Because these are mutually exclusive explanations, any claim of relative likelihood requires consideration of the relative probabilities p1 and p2. Hence, my lottery example. As presented, the probabilities of Alice and Bob winning are are both 1 in 1 million. Because their
relative probabilities are equal, both Alice and Bob have a 50% chance of being the owner of the winning ticket (i.e. comprising the source of the observed phenomenon of winning),
despite the observed event being extremely improbable a priori. If instead Charles had been given tickets from an additional 98 individuals (for a total of 100), then the probability of Bob owning the winning ticket drops to 1% because the relative probability of Bob not being the winner is 99 times higher (again, despite the
a priori odds of any of the 100 people winning being extremely small).
In the context of
Paprotka et al, this matters because the authors
made no attempt whatsoever to determine p2. Hence, any claims that #1 is more likely than #2 constitute pure, unfounded supposition. In the lottery example, this would be akin to Charles scratching off Bob's ticket and some
unknown number of other tickets. Maybe he only has Bob's ticket, or maybe he has 10 thousand other tickets. Without knowing, any claim to victory by Bob is, by definition, nothing more than speculation rooted in his biased desire to be the winner.
What about your points quoted above? In a nutshell, such specific exclusionary claims (to the extent they are supported by evidence) might have some effect on p2, but p2 remains unknown. This is because p2 comprises
all imaginable pathways that VP62 could have arrived in 22Rv1, minus the singular, mutually exclusive possibility of recombination taking place within the cell line as proposed by the authors (#1). These pathways include, but are not limited to, an identical
external recombination event, as well as other means of forming VP62 (mutation, deletion, other recombinations) and having it arrive at this cell line. Going back to the lottery example (with the unknown number of tickets), your claims are akin to Bob knowing that Danny, Emily, and Fred did
not give tickets to Charles. Even with this knowledge, Bob still does not know how many tickets Charles had and therefore his claims of victory are just as unfounded. (It is true that this knowledge constrains the scope of p2, but in the context of
Paprotka this scope is indefinitely large, implying that elimination/reduction of a fixed set of elucidated pathways still leaves an unknown probability: ? - X = ?).
Ironically, the probability of a second event calculated by the authors (1.3 10[SUP]?12[/SUP]), must also serve as an estimate for p1 (the probability of their choice recombination having occurred). This is because, in making their calculation, they assume the
exact same preconditions that they purport to have led to #1 (the presence of the PreXMRVs). They offer no evidence that the PreXMRVs were more likely to recombine inside this cell line than in some theoretical situation outside the cell line where both of them are present. (One should argue that these probabilities are tempered by the relative number of chances, but you've already rejected this line of reasoning when presented by Alex to support #2. Furthermore, any concrete attempt would simply be speculation). So, within reason, we can estimate that p1 = 1.3 10[SUP]?12[/SUP].
If it were true that p2 >= 1.3 10[SUP]?12[/SUP], then as demonstrated by the lottery example the authors have essentially sold something no better than a coin toss as a certainty (this is comparable to the original scenario with only Bob and Alice). Furthermore, it must be noted that p2 encompasses the possibility that VP62 was introduced via the original prostate tumor and simply not detected in the earlier samples by the authors (hence the "appearance" is an illusion as it was there all along). If there is any truth to the finding of XMRV in ~20% of PC tumors, it is certainly not unreasonable to suspect that this possibility alone (serving as a lower bound on p2) is > 1.3 10[SUP]?12[/SUP]. Of course this is simply speculation, but when put in this light it should be clear just how spectacularly implausible and speculative the authors' conclusion really is.
No, I am not at all. Would you care to explain how you think I have done this?
I specifically stated that the "authors actually provide compelling evidence for the notion that XMRV arose in 22Rv1". You could actually dispute that there is "compelling evidence" or that I have failed to provide it (I just don't want my posts to get any longer than they already are), but I have not asserted or argued that "XMRV arose in 22Rv1 because it did".
After I asserted that the authors had provided compelling evidence for the above notion, I used this notion as a (partial) argument in favor of the position that XMRV is not a genuine human pathogen. Again, you can disagree with the conclusion because you don't agree with the supporting argument or because you don't agree that the supporting argument, while perhaps true, is unable to carry the conclusion.
However, I completely fail to see why my argument "commits" the fallacy of begging the question, and I would be very happy to hear why you would (still?) think this is the case.
Apologies on that. I originally misread your points a and b as being offered in support of your prior sentence.
You are right about this, but like I said, the authors really only use the probabilistic analysis in the context of the same event happening twice. You are therefore refuting a strawman, i.e. an argument that the authors haven't made in the first place.
As I've laid out above, there is actually compelling evidence in support of the notion that this event happened in 22Rv1 and not somewhere else.
From what I wrote above, it can be seen that their probabilistic analysis applies equally to their proposed recombination event as it does to a second identical event under identical circumstances (and this can be proven mathematically very simply). That they only care to apply it to the latter is merely sleight of hand (which they "get away with" by simply ignoring the relative probability p2 in its totality).
As for this being a strawman, it's hard to see how discussing a perfectly viable
alternative explanation (#2)--the elimination of which constitutes the backbone of the scientific endeavor--is a strawman. Such a claim amounts to embracing "science by bias" where one just accepts their preferred explanation and classifies the remainder as unworthy of discussion.
Actually, not only does this finding fail to undercut Paprotka et al. in any way, it even supports the notion that current and future detections of related but clearly distinct "HGRV's" (that are always at the limit of detection I might add), are the result of contamination.
After all, not only XMRV has been quietly hiding in in 22Rv1 cell lines in many labs, possibly contaminating experimental samples. We know now that there are actually many more X-MLV's that have been quietly and unknowingly "living" in many other cell lines that have been handled in many labs with experimental samples.
It was/is only a matter of time before one of these other X-MLV's from one of these cell lines did/will actually contaminate some samples in some labs.
Because of these dangers, it is important that any study that proposes an association of X-MLV viruses with any disease and that wants to be taken seriously, not only blinds their samples, but also only uses patient and control samples that were treated in the exact same way from start (collection) to finish (testing).
Or one could ask: how many X-MLV's are
quietly and unknowingly "living" within human hosts? After all, if our esteemed virologists have failed to notice these X-MLV's directly under their noses for decades, it's certainly plausible that they continue to miss variants residing in the far more complex environment of the human body.
The existence of multiple variants capable of infecting human cells further establishes the importance of continued study. The only argument made against further study is that we don't need to worry about them infecting humans (if they haven't already) because APOBEC and complement, purportedly, crush these viruses in the blood. Of course, as others have pointed out, these defenses are themselves merely probabilistic (one virion breaching the fold could be sufficient in establishing infection) and only relevant to blood-based modes of infection.
ligo dT template-primer and measuring RT activity by uptake of tritiated thymidine triphosphate. 