Models for DNA Design Tools: The Trouble with Metaphors Is That They Don't Go Away

Synthetic biology relies heavily on DNA design tools to enable manipulation of DNA in silico. Existing tools, however, are falling short of enabling aspirations for the field that emphasize efficient, automated design pipelines. We review existing DNA design tools, identify underlying similarities in how they model correlations between DNA structure and function, and suggest that iterating the existing model is unlikely to overcome limitations in matching software applications to design aspirations. The current model is predicated on metaphors conceptualizing DNA as linear text, accounting for relatively little of the known complexity of DNA function. New models that can account for more of that complexity and thus enable more ambitious DNA design goals are likely to call for new underlying metaphors-a need that may be addressed by rethinking DNA in terms of human rather than computer languages.