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closeReferee comments: Referee 2
Posted by PLOS_ONE_Group on 08 Feb 2008 at 22:05 GMT
Referee 2's review:
This paper is quite weak. It presents a single experiment in which 5 reverse transcriptase inhibitors are added in different doses to a retrotransposition assay in cultured cells. A number of other variables should be checked,e.g., other L1s, different days in culture, varaiability of the assay. A more fundamental question is, How do we know that the effect on retrotransposition is due to an effect solely on reverse transcriptase? Also a number of key references are missing from the text on pg. 1 of the Intro, lines 16 and 18,line 13 of M and M on the LRE3 construct and line 8 of the second page of Discussion. In addition, a better reference on the effect of L1 on potential oncogenesis is Miki et al. on APC insertion in colon cancer. The Morse et al. paper reports what appears not to be an L1 insertion because of the unusual L1 sequence.
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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.
RE: Referee comments: Referee 2
rbjones replied to PLOS_ONE_Group on 09 Feb 2008 at 02:56 GMT
> How do we know that the effect on retrotransposition is
> due to an effect solely on reverse transcriptase?
Strictly speaking we don't. Reflecting this, the conclusion of this study is that nRTIs inhibit LINE-1 retrotransposition, not that nRTIs inhibit LINE-1 reverse transcription. That being said, termination of nascent LINE-1 DNA through incorporation of nRTIs is certainly the most likely mechanism underlying our observations.
> This paper is quite weak.
Please support this with an argument as to how our data does not fully support our conclusion that nRTIs suppress LINE-1 retrotransposition. I will most certainly agree that this study is limited in scope, but our conclusion is clearly demonstrated.
As an open question, should a publication always have to consist of a series of questions reflecting years of work? Or should there be room in the scientific record for well executed staccato points? I feel that the latter can both be valuable to scientific progress, and, perhaps more importantly, can help to maintain the sense of playful curiousity which started many of us down the road to science, but which is often lost when long-term projects crowd out any time to satisfy pure spontaenous curiousity.
If everytime one is inspired to perform an experiment, one is sombered by the reality that, unless the time and funding to complete extensive follow-up experiments can be committed, any resultant data could only possibly be published on the journal of their hard-drive, the experiment will not be performed. It is my opinion that this suppression of spontaneous curiosity is largely responsible for the unfortunate attitude of the majority of graduate students - that graduate school is something to push through rather than an incredible time to play, back the universe into a corner on questions we have, and compel it to answer. Sometimes those questions are big, and sometimes they are small - so why should a publication always be between 4-7 figures?
I would never pollute the scientific record with weak data. The data presented in this study is a brick in the wall - just, admittedly, quite a small brick.
The discussion presented in the paper is meant to be thought provoking - and in the spirit of the extended discussion encouraged by PLoS ONE - which will hopefully continue in this forum.
Brad Jones