Going Negative?

In this issue of Nucleic Acid Therapeutics (NAT), an article by Eric Kmiec and his colleagues (Livingston et al., 2012) represents a kind of study that is increasingly rare in the world of scientific publishing (FANELLI, 2012): It reports negative results. Their study explores the use of nucleofection as a potential delivery method to overcome the “reduced proliferation phenotype” (RPP) seen in cells subjected to gene editing using single-stranded oligonucleotides. Their data, derived through well-controlled experimentation, forces the conclusion that nucleofection is not significantly better than electroporation in overcoming RPP.

So why is this paper being published in NAT? After all, negative results can be a nightmare for everyone. Such papers are—rightly or wrongly—not as highly valued in the current reward systems of the academy or industry, and thus not very helpful to individual scientists in their career growth. Publishers are concerned that negative results papers are not as highly cited as positive results manuscripts and fear a compromising of the all-consuming impact factor. And editors absolutely dread refereeing the inevitable differences of opinion among the peer reviewers, who often move beyond their charge to determine whether the science is novel and well done to whether or not the findings are relevant to them or familiar colleagues.

In this particular case, the science is rigorously done and comes from one of the early pioneer labs trying to realize the significant potential of gene editing using oligonucleotides. As a methodology paper, the finding that a labor-intensive but promising approach like nucleofection is not discernibly better than other approaches could have significant impact on many other laboratories considering or even using the same method, allowing limited and precious resources (people and money) to be redirected to other promising avenues. Although it is a difficult—and controversial—decision to publish negative results, in this particular case it was decided that the positive aspects of publishing outweighed the “negative.”

All that said, the occasional manuscripts that are submitted to NAT that feature negative results will continue to receive as rigorous a review as possible, focused on their scientific merit and their importance to at least a significant subset of NAT readers. We continue to be fully committed to making NAT a home for solid scientific findings that help the field advance towards our shared goal of realizing the therapeutic potential of nucleic acids in their own right. It should not be surprising to anyone that our commitment requires that—on occasion—we have to go negative.