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.

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This paper analyzes the notion of possibility in biology and demonstrates how synthetic biology can provide understanding on the modal dimension of biological systems. Among modal concepts, biological possibility has received surprisingly little explicit treatment in the philosophy of science. The aim of this paper is to argue for the importance of the notion of biological possibility by showing how it provides both a philosophically and biologically fruitful category as well as introducing a new practically grounded way for its assessment. More precisely, we argue that synthetic biology can provide tools to scientifically anchor reasoning about biological possibilities. Two prominent strategies for this are identified and analyzed: the design of functionally new-to-nature systems and the redesign of naturally occurring systems and their parts. These approaches allow synthetic biologists to explore systems that are not normally evolutionarily accessible and draw modal inferences that extend in scope beyond their token realizations. Subsequently, these results in synthetic biology can also be relevant for discussions on evolutionary contingency, providing new methods and insight to the study of various sources of unactualized possibilities in biology.

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.