Second Email Exchange Between
Dusty Miller and CFS Central
CFS Central: You wrote: "Regarding the data in Lombardi et al., I was initially convinced by their extensive analysis, in particular, their ability to grow virus from patient materials. Indeed, we entered the CFS/XMRV field largely on the basis of these data. However, published and unpublished data now indicate that all of these methods were flawed.”
As far as I'm aware, no published or unpublished data indicates that the methods of Lombardi et al. were flawed. To what studies are you referring?
Dr. Dusty Miller: In the recent Science Express paper by Knox, ..., and Levy, the authors used three techniques to detect XMRV and related retroviruses in humans with CFS, and found none. These techniques included nested PCR, an assay for infectious virus, and assays for neutralizing antibodies and other inhibitory factors in blood. Importantly, many of the CFS subjects they studied came from Dr. Peterson's practice in Incline Village, and represent some of the same patients that Lombardi et al. studied. Therefore, this is a close replication of the Lombardi et al. study. The Knox study is in addition to many other negative studies cited in this paper (refs. 7-12).
Lastly, the XMRV viral sequences deposited by Lombardi et al. in GenBank all are very closely related the VP62 XMRV sequence (see the supplemental material in Knox et al.), and the VP62 plasmid from Robert Silverman was apparently present in the labs of Lombardi et al., strongly indicating contamination of the Lombardi et al. PCR assays by VP62 plasmid DNA. Putting all of this together leads me to conclude that the methods of Lombardi et al. must have been flawed.
CFS Central: You also wrote: "Regarding the constant accusation that no one has carefully replicated Lombardi's methods, this is not true as far as most scientists are concerned. Initial reports attempting to replicate the study did have flaws, but many later studies are convincing.”
The problem with these later studies as I see it is that not one of the so-called replication studies was a bona fide replication. The patient cohorts and/or methods used were not identical. I learned in 9th grade science that being identical in cohort and methods are necessary for a true replication—otherwise you’re introducing variables that may account for the different findings. In your view, could the different methods/cohorts account for the differences in the findings? Why or why not?
CFS Central: You also wrote: "Regarding the constant accusation that no one has carefully replicated Lombardi's methods, this is not true as far as most scientists are concerned. Initial reports attempting to replicate the study did have flaws, but many later studies are convincing.”
The problem with these later studies as I see it is that not one of the so-called replication studies was a bona fide replication. The patient cohorts and/or methods used were not identical. I learned in 9th grade science that being identical in cohort and methods are necessary for a true replication—otherwise you’re introducing variables that may account for the different findings. In your view, could the different methods/cohorts account for the differences in the findings? Why or why not?
Miller: Please see my response above. It is difficult to perform an exact replication study, which would involve going to the Mikovits lab and watching whoever did the previous study repeat it with the same patient samples. Besides which, you may have also learned in 9th grade science that scientific results must be generalizable, that is, competent scientists must be able to repeat the experiments under somewhat different conditions and obtain similar results. If the claimed result can only be obtained by performing the experiment in one spot in the Mikovits lab, perhaps while singing a particular song, then the results are not generalizable and should be looked on with suspicion.