Design Methodologies and the Limits of the Engineering-Dominated Conception of Synthetic Biology

Abstract

Synthetic biology is described as a new field of biotechnology that models itself on engineering sciences. However, this view of synthetic biology as an engineering field has received criticism, and both biologists and philosophers have argued for a more nuanced and heterogeneous understanding of the field. This paper elaborates the heterogeneity of synthetic biology by clarifying the role of design and the variability of design methodologies in synthetic biology. I focus on two prominent design methodologies: rational design and directed evolution. Rational design resembles the design methodology of traditional engineering sciences. However, it is often replaced and complemented by the more biologically-inspired method of directed evolution, which models itself on natural evolution. These two approaches take philosophically different stances to the design of biological systems. Rational design aims to make biological systems more machine-like, whereas directed evolution utilizes variation and emergent features of living systems. I provide an analysis of the methodological basis of these design approaches, and highlight important methodological differences between them. By analyzing the respective benefits and limitations of these approaches, I argue against the engineering-dominated conception of synthetic biology and its "methodological monism", where the rational design approach is taken as the default design methodology. Alternative design methodologies, like directed evolution, should be considered as complementary, not competitive, to rational design.

Exploring biological possibility through synthetic biology

“…This complexity manifests itself both in the higher number of relevant traits, parts and interactions, but also in the increased integration of system design, decreased modularity and stronger coupling between organism and its environment. Rational design allows synthetic biologists to reduce biological complexity and simplify their systems through the use of modular parts, and by designing systems to be more engineerable (Ijäs, 2019). One of the main goals of rational design synthetic biology is to separate natural systems to simpler well-defined parts that can be manipulated and recombined with predictable outcomes.…”

“…In the case of rational design, as new synthetic systems are constructed bottom-up almost from scratch, it requires synthetic biologists to have access to a toolkit of relevant well-defined biological parts and devices. Synthetic biologists also require detailed mechanistic understanding of the systems that they are constructing (see Ijäs, 2019). In turn, for directed evolution to access a certain outcome, there must be a pathway of incremental detectable beneficial mutations from start to endpoint (Dougherty & Arnold, 2009).…”

“…One could argue that rational design can make these "huge leaps through design space" (Dennett, 1995: 76-77) creating organisms that would never have evolved by 'ordinary' means, but only when the endpoint is already known. This is further hampered by the effect of context-sensitivity to rational design: biological components and devices are susceptible to losing their functionality upon reaggregation or moving to another environment (Ijäs, 2019). Consequently, many parts of the rational design toolkit have limited functional ranges, a factor that limits the "free exploration" of design space.…”

Influence of quantity of additional food in achieving biological conservation and pest management in minimum-time for prey-predator systems involving Holling type III response

“…These natural enemies are provided with additional food supplements, which affect their survival, gustatory response, fitness, fecundity and longevity Landis et al (2000) ; Urbaneja-Bernat et al (2013) ; Winkler et al (2005) and this in turn helps in controlling pests in the system. Some of the outcomes of the mathematical studies of additional food systems Das and Samanta, 2018a , Das and Samanta, 2018b , Das and Samanta, 2020 ; Liu et al (2018) ; Mondal and Samanta, 2019 , Mondal and Samanta, 2020 ; Prasad and Prasad (2019) ; Sahoo and Poria (2014) ; Sen et al (2015) ; Srinivasu et al, 2007 , Srinivasu et al, 2018 ; Vamsi et al (2019) reveal that the provision of additional food to the predators affects the global dynamics of the system causing indirect interaction of species. These findings are in line with the experimental observations when additional food is provided Harwood et al (2004) ; Wade et al (2008) ; Toft (2005) .…”

Multiple Realizability as a design heuristic in biological engineering

“…However, the evolving sample is systematically biased at each step, due to selecting for further refinement only mutations with desired functions. For a methodological discussion of the comparative merits of rational design and directed evolution, seeIjäs (2018).4 Another partly overlapping characterizing perspective is provided by the concept of modularity. A module is something whose own function can be understood in relative isolation from other parts of the system(Cambray et al 2011: 628; see also Hartwell et al 1999).…”