I want to point out two general ideas that keep popping up in discussions about XMRV research. I believe both of these ideas are factually inaccurate and threaten to undermine critical patient support for honest XMRV research.
Idea #1: Finding XMRV is easy
The first idea is that finding XMRV is simple, especially using PCR. There are two aspects to this idea.
The first aspect is that every researcher involved in this field is honest and competent and really wants nothing more than to validate the XMRV finding:
Despite frequent assurances that all these researchers are honest and smart, we are left with a burning question: why do these scientists continue to produce such deeply flawed research that, from an outside view, does not resemble an honest, competent attempt to find XMRV? Why have none of them even tried to replicated successful methods? Do their actions match the characterizations commonly put forth? I say no, not even remotely.
The second aspect is that finding XMRV should be easy and that all of their attempts should have found it if it was really there:
These types of statements are assertions of opinion, dressed up to look like fact. Generally, the only evidence offered to support these assertions is the claim that these techniques work fine for other well-understood and well-characterized viruses. But there is no reason, logically or historically, that this should be a priori true for a novel virus like XMRV.
Furthermore, none of these negative studies have shown that their PCR or serology methods are capable of finding XMRV in a known positive clinical sample. As such, none of these negative studies have properly ruled out false negatives.
This flaw is usually painted over with apparent incredulity over the fact that the WPI was able to detect XMRV via PCR with purported ease:
At a high level, these arguments assert that the future should pay heed to the past, that XMRV should behave according to our current state of knowledge. This is a fallacious argument.
On a more concrete level, these arguments fail to mention the macaque study, which shows that XMRV has a highly transient presence in the blood. They fail to mention that PCR is a very complex process open to many confounding factors (i.e. not all PCR methods are created equal). They fail to mention the Danielson et al study that showed PCR to be a very unreliable method of detecting XMRV in the blood. They fail to mention that the CFS cohort in the Science paper was highly viremic, which may have unintentionally helped the WPI find XMRV by an otherwise unreliable method.
Taken together, these aspects form an idea that artificially injects more credibility into the negative studies than is warranted. This idea glosses over the deep flaws in these studies and instead props them up on unsupported claims of goodwill and asserted simplicity.
Idea #2: True scientific replication is not important
This idea takes two forms. The first form is a mangling of what scientific replication truly is. Consider Wikipedia’s description of replication:
In comparison, consider the following description of replication found on this forum:
Note the stark difference. It is simply not true that different techniques constitute replication. Just because two studies use PCR (or serology), doesn’t mean they are the same methods. The devil is in the details.
The second and far more dangerous form of this idea that the XMRV hypothesis can be scientifically dis-proven without anyone actually replicating the WPI’s methods:
The idea that a finding can be scientifically dis-proven in this manner is fundamentally flawed. It is a perversion of the scientific method. It is a political argument, not a scientific argument. Often these claims will be accompanied by appeals to an unnamed researcher who confirms that this type of “science” is acceptable. It is not, and anyone who suggests otherwise does not believe in one of the most fundamental building blocks of the scientific method: reproducibility.
Conclusion
In conclusion, I believe these two broad ideas threaten to railroad much-needed public demand for legitimate XMRV research.
First, they threaten to convince people that finding XMRV is easy and therefore all negative studies should be considered equally as valid as the positive studies (even though they don’t replicate their methods). Secondly, they threaten to convince people that there exists some quantity of these flawed negative studies can override the lack of any true replication attempt.
This is, I believe, a dangerous recipe for short-circuiting XMRV research.
Idea #1: Finding XMRV is easy
The first idea is that finding XMRV is simple, especially using PCR. There are two aspects to this idea.
The first aspect is that every researcher involved in this field is honest and competent and really wants nothing more than to validate the XMRV finding:
This is science and not a courtroom where motives matter. A scientist's motives are almost irrelevant, what counts is their data. Besides that I think your analysis of motives is incorrect anyway from what I know of these people.
The points I am personally persuaded of after many interactions with people involved in this issue is that there is no conspiracy, and the level of competence in all these studies is generally high.
Despite frequent assurances that all these researchers are honest and smart, we are left with a burning question: why do these scientists continue to produce such deeply flawed research that, from an outside view, does not resemble an honest, competent attempt to find XMRV? Why have none of them even tried to replicated successful methods? Do their actions match the characterizations commonly put forth? I say no, not even remotely.
The second aspect is that finding XMRV should be easy and that all of their attempts should have found it if it was really there:
...but these PCR tests used in ALL the XMRV studies have been capable of finding the level of XMRV infection claimed to be found by WPI.
This approach would find evidence of ANY entrenched XMRV infection.
These types of statements are assertions of opinion, dressed up to look like fact. Generally, the only evidence offered to support these assertions is the claim that these techniques work fine for other well-understood and well-characterized viruses. But there is no reason, logically or historically, that this should be a priori true for a novel virus like XMRV.
Furthermore, none of these negative studies have shown that their PCR or serology methods are capable of finding XMRV in a known positive clinical sample. As such, none of these negative studies have properly ruled out false negatives.
This flaw is usually painted over with apparent incredulity over the fact that the WPI was able to detect XMRV via PCR with purported ease:
The Science 'methods' included using PCR without culturing and finding XMRV sequences in 67% of banked CFS samples. This study was equal to that method and goes well beyond.
I have come to the conclusion that it really shouldn't be that hard to find. Why? Because it wasn't hard for the WPI to find.
They didn't have to go to extraordinary lengths to look for it. ..they didn't have to culture, they didn't have to use the 'wild-type' virus to validate it, they were able to validate it using VP62, they didn't have a particularly sensitive PCR...so why is the virus now, all of a sudden, on the limits of detection of PCR?
At a high level, these arguments assert that the future should pay heed to the past, that XMRV should behave according to our current state of knowledge. This is a fallacious argument.
On a more concrete level, these arguments fail to mention the macaque study, which shows that XMRV has a highly transient presence in the blood. They fail to mention that PCR is a very complex process open to many confounding factors (i.e. not all PCR methods are created equal). They fail to mention the Danielson et al study that showed PCR to be a very unreliable method of detecting XMRV in the blood. They fail to mention that the CFS cohort in the Science paper was highly viremic, which may have unintentionally helped the WPI find XMRV by an otherwise unreliable method.
Taken together, these aspects form an idea that artificially injects more credibility into the negative studies than is warranted. This idea glosses over the deep flaws in these studies and instead props them up on unsupported claims of goodwill and asserted simplicity.
Idea #2: True scientific replication is not important
This idea takes two forms. The first form is a mangling of what scientific replication truly is. Consider Wikipedia’s description of replication:
The results of an experiment performed by a particular researcher or group of researchers are generally evaluated by other independent researchers who repeat the same experiment themselves, based on the original experimental description. (emphasis mine)
In comparison, consider the following description of replication found on this forum:
Using different PCR tests is not a failure to replicate, but is actually what is required to replicate… (emphasis mine)
Note the stark difference. It is simply not true that different techniques constitute replication. Just because two studies use PCR (or serology), doesn’t mean they are the same methods. The devil is in the details.
The second and far more dangerous form of this idea that the XMRV hypothesis can be scientifically dis-proven without anyone actually replicating the WPI’s methods:
Exact replication of WPI's PCR test is less important than people realize...
This is like a cascading effect - the more the negative studies pile up and the more things people try that don't work - it gets harder and harder to see how XMRV will work out - even if they never replicate the study. (emphasis mine)
The idea that a finding can be scientifically dis-proven in this manner is fundamentally flawed. It is a perversion of the scientific method. It is a political argument, not a scientific argument. Often these claims will be accompanied by appeals to an unnamed researcher who confirms that this type of “science” is acceptable. It is not, and anyone who suggests otherwise does not believe in one of the most fundamental building blocks of the scientific method: reproducibility.
Conclusion
In conclusion, I believe these two broad ideas threaten to railroad much-needed public demand for legitimate XMRV research.
First, they threaten to convince people that finding XMRV is easy and therefore all negative studies should be considered equally as valid as the positive studies (even though they don’t replicate their methods). Secondly, they threaten to convince people that there exists some quantity of these flawed negative studies can override the lack of any true replication attempt.
This is, I believe, a dangerous recipe for short-circuiting XMRV research.