JOURNAL CLUB: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Martin Fenner

Saturday, 22 Mar 2008 09:10 UTC

I would like to recommend another classic well-written paper

Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998;391:806-11

The full text can be found here. Both the title and abstract are very clear and someone not deeply involved with molecular biology should be able to follow along. The text itself has a nice structure. The text starts with an interesting and important observation that can’t be explained by the current knowledge. The authors then explain the steps that were taken to better understand this observation and they take the reader with them. The manuscript ends with the possible explanations and implications of the results, hinting at the experiments that should follow.

I wonder whether spectacular research findings (Andrew Fire and Craig Mello won the Nobel Price for Medicine in 2006) also make it easier to write a paper that is pleasant to read and easy to follow.

And it can be interesting to read a paper 10 years later. In 1998 it was not known how RNA interference works and that the method would transform the way we do research with mammalian cells. As we know now, the News and Views article that comes with the paper was pointing in the wrong direction

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    • Worth re-reading. I agree that it is clear and interesting (but I do have a molecular biological bias).

      What I find provocative in the abstract with respect to writing style is highlighted:

      To our surprise, we found that double-stranded
      RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few molecules…

      First, I like it when the surprise is not just a straw man but a real one. But this construction tends to be discouraged.

      The other things I highlighted were in reference to quantities. I had always believed that it was very important to be quantitative whenever possible in an abstract – not “a few”, but how many? Not “a modest” or “potent” effect, but how much interference?

      If the authors had heeded this rule of thumb, it would have made for a less readable abstract. The approach continues throughout the paper, though, and does lead to a hint of value judgment: “marginal interference activity”, “extremely specific” (but I can’t see how to avoid that adverb, “interesting coding regions”.

      I appreciate when authors really think about and discuss the implications of their work. Many journals discourage much of this in my experience, but I believe that the authors are best placed to have reflected on these questions and by sharing their ideas, are advancing science by proposing testable hypotheses, not all of which they might address themselves.

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