Falling down the Rabbit Hole: aTRIP Toward Lexiconic Precision in the “Gain-of-Function” Debate

Alice’s trip through the looking glass and her adventures in Wonderland represent fantastical journeys into an imaginary world where things are never as they seem, people run rapidly to stay in the same place, and eggs talk. A classic and often quoted exchange between Alice and that precocious egg revolves around the usage and definition of words. Humpty Dumpty has a rather egocentric approach to terminology: ‘“When I use a word,” Humpty Dumpty said, in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.”’ On hearing this, Alice was “too much puzzled to say anything” (1). Needless to say, in our day-to-day interactions, Humpty Dumpty’s approach to dialog is not a viable option. Unlike him, we do not sit isolated and alone on top of a wall. Rather, we inhabit a world where communication is rapid and clarity is critical. Lack of precision leads to misunderstandings which can be rapidly amplified in retweets, likes, and shares. Before you know it, scientists, governments, the media, and the public are like Alice, simply puzzled. At the 2014 National Science Advisory Board in Biosafety (NSABB) meeting in Washington (http://osp.od.nih.gov/office -biotechnology-activities/event/2014-10-22-121500-2014-10-22200000/nsabb-meeting), it was clear from the outset that terminology matters. Canvassing the opinions of microbiologists before that meeting made it apparent that they are uncharacteristically united in their dislike of the term “gain of function” (GOF). This is understandable and hardly surprising since it is not a term that they typically use. What is probably more interesting is that even though the consensus of opinion is that this terminology is getting in the way and that moving away from a phrase which has been hijacked to describe a small set of influenza virus experiments would be useful, how to address this problem is much less obvious, especially since the term has been coopted by general media and appears to have acquired a meaning of its own. Boundaries between biosecurity and biosafety have been blurred, and a debate which began with concerns about nefarious use has meandered in the direction of laboratory accidents and biocontainment errors. Through Humpty’s explanations in the poem “Jabberwocky” of words such as “mimsy” (flimsy and miserable) to Alice, Lewis Carroll is credited with introducing yet another new definition into the lexicon. ‘“You see it’s like a portmanteau,” said Humpty, “there are two meanings packed up into one word.”’ At the recent NSABB meeting in an effort to move toward more-acceptable terminology, the portmanteau “gain of function of concern” was suggested. As attractive as this moniker might be when written, it quickly became clear to the committee that “GoFoC” when spoken might not quite “fly.”