Interdisciplinary Interconnections in Synthetic Biology

Abstract

Synthetic biology is not a unified field. It involves many disciplines, from molecular genetics to biochemistry, and from engineering to bioinformatics. It includes xenobiological approaches that build and use artificial nucleic acids, metabolic reengineering of existing microbes, maybe using standardized parts and devices, creation of minimal organisms, bio-brick-biochemistry, and attempts to make synthetic organisms from scratch. The contributions to this thematic issue reflect on these scientific activities in synthetic biology and in related fields. They grew out of a workshop on the scientific, philosophical, and social dimensions of synthetic biology, including its research strategies, conceptual apparatus and societal implications. For many, the attraction of synthetic biology is its aim to apply in biology the methods of traditional engineering, especially rational engineering, using standardized components that allow plug-and-play modular design (Canton et al. 2008; Mutalik et al. 2013a, b). Rational engineering contrasts with creating desired systems through trial-and-error experimentation, which includes tried-and-true methods like tinkering and kludging, as well as sophisticated methods like generating and screening massive libraries of high-throughput wet-lab experimental data. Trial-and-error methods in synthetic biology also include familiar and widespread methods like in vitro (or directed) evolution (Yokobayashi et al. 2002), as well as new applications of machine-learning methods to make high-throughput experiments maximally intelligent and efficient (Caschera et al. 2010, 2011). Synthetic biology involves a plurality of experimental research programs. It includes top-down reengineering of existing life forms, for example, to mass-produce products such as pharmaceuticals (Martin et al. 2003) or biofuel (Savage et al. 2008). It also includes bottom-up attempts to create new minimal chemical life or ‘‘protocells’’ using nothing but non-living materials (Rasmussen et al. 2004, 2009a). Both top-down and bottom-up synthetic biology employ the two methods we contrasted above: rational engineering and trial-and-error experimentation. These two distinctions (top-down versus bottom-up, and rational engineering versus trial-and-error experimentation) define four quadrants in Table 1. These quadrants map achievements in synthetic biology and illustrate some of the field’s scientific plurality. Least familiar and least developed is the lower right quadrant of trial-and-error methods for bottomup synthetic biology, though some would argue that this quadrant also shows the most upside potential (e.g., Bedau 2013, this issue).