Many scientific models in biology are how-possibly models. These models depict things as they could be, but do not necessarily capture actual states of affairs in the biological world. In contemporary philosophy of science, it is customary to treat how-possibly models as second-rate theoretical tools. Although possibly important in the early stages of theorizing, they do not constitute the main aim of modelling, namely, to discover the actual mechanism responsible for the phenomenon under study. In the paper it is argued that this prevailing picture does not do justice to the synthetic strategy that is commonly used in biological engineering. In synthetic biology, howpossibly models are not simply speculations or eliminable scaffolds towards a single how-actually model, but indispensable design hypotheses for a field whose ultimate goal is to build novel biological systems. The paper explicates this by providing an example from the study of alternative genetic systems by synthetic biologist Steven Benner and his group. The case will also highlight how the method of synthesis, even when it fails, provides an effective way to limit the space of possible models for biological systems.

Recently, several critics of the multiple realizability thesis (MRT) have argued that philosophers have tended to accept the thesis on too weak grounds. On the one hand, the analytic challenge has problematized how philosophers have treated the multiple realization relation itself, claiming that assessment of the sameness of function and the relevant difference of realizers has been uncritical. On the other hand, it is argued that the purported evidence of the thesis is often left empirically unverified. This paper provides a novel strategy to answer these worries by introducing a role for multiple realizability in the context of biological engineering. In the field of synthetic biology, bioengineers redesign the evolutionary realizations of biological functions, even constructing artificial chemical surrogates in the laboratory. I show how in the rational design approach to biological engineering, multiple realizability can function as a design heuristic in which the sameness of function and difference of realizers can be controlled. Although practically motivated, this engineering approach has also a theoretical, exploratory component that can be used to study the empirical limitations of multiple realizability. Successful realization of the engineering designs would amount to a concrete demonstration of multiple realizability, taking evidence for MRT beyond what is readily found in nature.

The recent discussion of fictional models has focused on imagination, implicitly considering fictions as something nonconcrete. We present two cases from synthetic biology that can be viewed as concrete fictions. Both minimal cells and alternative genetic systems are modal in nature: they, as well as their abstract cousins, can be used to study unactualized possibilia. We approach these synthetic constructs through Vaihinger’s notion of a semi-fiction and Goodman’s notion of semifactuality. Our study highlights the relative existence of such concrete fictions. Before their realizations neither minimal cells nor alternative genetic systems were any well-defined objects, and the subsequent experimental work has given more content to these originally schematic imaginings. But it is as yet unclear whether individual members of these heterogeneous groups of somewhat functional synthetic constructs will eventually turn out to be fully realizable, remain only partially realizable, or prove outright impossible.

Critics of multiple realizability have recently argued that we should concentrate solely on actual here-and-now realizations that are found in nature. The possibility of alternative, but unactualized, realizations is regarded as uninteresting because it is taken to be a question of pure logic or an unverifiable scenario of science fiction. However, in the biological context only a contingent set of realizations is actualized. Drawing on recent work on the theory of neutral biological spaces, the article shows that we can have ways of assessing the modal dimension of multiple realizability that do not have to rely on mere conceivability.

Recent epistemology of modality has seen a growing trend towards metaphysics-first approaches. Contrastingly, this paper offers a more philosophically modest account of justifying modal claims, focusing on the practices of scientific modal inferences. Two ways of making such inferences are identified and analyzed: actualist-manipulationist modality (AM) and relative modality (RM). In AM, what is observed to be or not to be the case in actuality or under manipulations, allows us to make modal inferences. AM-based inferences are fallible, but the same holds for practically all empirical inquiry. In RM, modal inferences are evaluated relative to what is kept fixed in a system, like a theory or a model. RM-based inferences are more certain but framework-dependent. While elements from both AM and RM can be found in some existing accounts of modality, it is worth highlighting them in their own right and isolating their features for closer scrutiny. This helps to establish their relevant epistemologies that are free from some strong philosophical assumptions often attached to them in the literature. We close by showing how combining these two routes amounts to a view that accounts for a rich variety of modal inferences in science.