Synthetic biology offers a powerful method to design and construct biological devices for human purposes. Two prominent design methodologies are currently used. Rational design adapts the design methodology of traditional engineering sciences, such as mechanical engineering. Directed evolution, in contrast, models its design principles after natural evolution, as it attempts to design and improve systems by guiding them to evolve in a certain direction. Previous work has argued that the primary difference between these two is the way they treat variation: (...) rational design attempts to suppress it, whilst direct evolution utilizes variation. I argue that this contrast is too simplistic, as it fails to distinguish different types of variation and different phases of design in synthetic biology. I outline three types of variation and show how they influence the construction of synthetic biological systems during the design process. Viewing the two design approaches with these more fine-grained distinctions provides a better understanding of the methodological differences and respective benefits of rational design and directed evolution, and clarifies the constraints and choices that the different design approaches must deal with. (shrink)

Biochemists often adopt what may be called the “Strategy of Decomposition” for the causal discovery of biochemical pathway dynamic behaviours. This involves decomposing a pathway into a set of isolated parts, which are then analysed separately. It is assumed that knowledge gained of the isolated parts can then be used to explain the dynamic behaviours of the whole pathway. My thesis addresses the extent to which use of the Strategy of Decomposition is warranted. I evaluate two challenges contained in Bechtel (...) and Richardson’s Discovering Complexity. The first challenge is that pathways lack the ‘modular’ structure assumed in the Strategy of Decomposition. Bechtel and Richardson take biochemists to use a concept of modularity called ‘near decomposability’. The second challenge is that pathways have ‘Pathway Emergent’ behaviours. I reject both challenges. I show that near decomposability is the wrong type of modularity to apply to pathways, and that the occurrence of Pathway Emergence has not been established. I argue that an underlying problem with Bechtel and Richardson’s analyses is that they overstate the consequences of feedback and nonlinearity for the Strategy of Decomposition. Instead, the analysis of pathway modularity and emergence needs to be centered on the context-sensitivity of pathways’ ‘local causal laws’. I identify that the type of modularity assumed in the Strategy of Decomposition is ‘causal law modularity’, which requires the invariance of local causal laws. I also identify a necessary condition for Pathway Emergence: a pathway must manifest at least one local causal law that is not manifested by its isolated parts. I argue that the use of the Strategy of Decomposition may often be unwarranted. This is because the local causal laws of pathways are highly context-sensitive, and pathways might often not be causal law modular. This context-sensitivity also leaves open the possibility of Pathway Emergence. (shrink)