Biologists in the last 50 years have increasingly emphasized the role of historical contingency in explaining the distribution and dynamics of biological systems. However, recent work in philosophy of biology has shown that historical contingency carries various interpretations and that we are still lacking a general understanding of historicity, i.e., a framework from which to interpret why and to what extent history matters in biological processes. Building from examples and analyses of the long-term experimental evolution (LTEE) project, this paper argues (...) that historicity possess three essential conditions: (1) multiple possible pasts, (2) multiple possible outcomes at a given instant, and (3) a relationship of causal dependence between these two sets. These criteria can be further specified in two general forms of historicity: dependence on initial conditions and path dependence. More attention is devoted to developing a rigorous account of the latter, which captures the type of historicity displayed by stochastic processes. This paper also highlights that it is often more productive to adopt an instant-relative approach and think in terms of degree of historicity instead of trying to maintain a rigid and absolute dichotomy between historical and ahistorical (completely convergent) processes. (shrink)

The interests of synthetic biologists may appear to differ greatly from those of evolutionary biologists. The engineering of organisms must be distinguished from the tinkering action of evolution; the ambition of synthetic biologists is to overcome the limits of natural evolution. But the relations between synthetic biology and evolutionary biology are more complex than this abrupt opposition: Synthetic biology may play an important role in the increasing interactions between functional and evolutionary biology. In practice, synthetic biologists have learnt to submit (...) the proteins and modules they construct to a Darwinian process of selection that optimizes their functioning. More importantly, synthetic biology can provide evolutionary biologists with decisive tools to test the scenarios they have elaborated by resurrecting some of the postulated intermediates in the evolutionary process, characterizing their properties, and experimentally testing the genetic changes supposed to be the source of new morphologies and functions. This synthetic, experimental evolution will renew and clarify many debates in evolutionary biology: It will lead to the explosion of some vague concepts as constraints, parallel evolution, and convergence, and replace them with precise mechanistic descriptions. In this way, synthetic biology resurrects the old philosophical debate about the relations between the real and the possible. (shrink)

The present edition provides a detailed and accessible discussion ofhis theories and adds an account of the immediate responses to the book on publication.

A recurrent theme in the characterization of synthetic biology is the role of engineering. This theme is widespread in the accounts of scholars studying this field and the biologists working in it, in those of the biologists themselves, as well as in policy documents. The aim of this article is to open this black-box of engineering that is supposed to influence and change contemporary life sciences. Too often, both synthetic biologists and their critics assume a very narrow understanding of what (...) engineering is about, resulting in an unfruitful debate about whether synthetic biology possesses genuine engineering methodologies or not. By looking in more detail to the diversity of engineering conceptions in debates concerning synthetic biology, a richer perspective can be developed. In this article, I will examine five influential ways in which engineering is understood in these debates, namely engineering as applied science, as rational methodology, context-sensitive practice, cunning activity or design. The claim is first of all thus to argue that engineering must not be seen as something stable or characterized by a fixed essence. It rather has multiple meanings and interpretations. Secondly, the claim is that most of the debates on synthetic biology cannot be indifferent towards the question which conception of engineering is at play, since the specific questions and concerns that pop up depend to a great extent on the precise conception of engineering one has in account. Many of the existing debates around synthetic biology can thus be reinterpreted and readdressed once one is aware of which conception of engineering is at play. (shrink)

Much philosophical progress has been made in elucidating the idea of evolutionary contingency in a recent re-burgeoning of the debate. However, additional progress has been impaired on three fronts. The first relates to its characterisation: the under-specification of various contingency claims has made it difficult to conceptually pinpoint the scope to which ‘contingency’ allegedly extends, as well as which biological forms are in contention. That is—there appears to be no systematic means with which to fully specify contingency claims which has (...) led to a tendency for authors to talk past each other. Secondly, on the matter of evidence, recent research has focused on the evidential import of convergent evolution which is taken to disconfirm the evolutionary contingency thesis. However, there has been a neglect of convergent evolution’s converse: ‘evolutionary idiosyncrasies’ or the singular evolution of certain forms, which I argue is evidentially supportive of evolutionary contingency. Thirdly, evolutionary contingency has often been claimed to vary in degrees and that the debate, itself, is a matter of ‘relative significance’. However, there has been no formal method of evaluating the strength of contingency and its relative significance in a particular domain. In this paper, I address all three issues by proposing a systematic means of fully specifying contingency theses with the concept of the modal range. Secondly, I propose an account of evolutionary idiosyncrasies, investigate the explanations for their occurrences, and, subsequently, spell out their significance with respect to the evolutionary contingency thesis. Finally, having been equipped with the evidential counterpart to convergent evolution, I shall sketch a likelihood framework for evaluating, precisely on the basis of a sequence of opposing data, the strength and relative significance of evolutionary contingency in a particular domain. With this in hand, the relative observations of idiosyncrasies and convergences can be informative of the strength and relative significance of contingency in any particular domain. (shrink)

Several authors have used the notion of causal specificity in order to defend non-parity about genetic causes (Waters 2007, Woodward 2010, Weber 2017, forthcoming). Non-parity in this context is the idea that DNA and some other biomolecules that are often described as information-bearers by biologists play a unique role in life processes, an idea that has been challenged by Developmental Systems Theory (e.g., Oyama 2000). Indeed, it has proven to be quite difficult to state clearly what the alleged special role (...) of genetic causes consists in. In this paper, I show that the set of biomolecules that are normally considered to be information-bearers (DNA, mRNA) can be shown to be the most specific causes of protein primary structure, provided that causal specificity is measured over a relevant space of biological possibilities, disregarding physical as well as logically possible states of the causal variables. (shrink)

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. (shrink)

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, how-possibly 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. (shrink)

Due to the variation, contingency and complexity of living systems, biology is often taken to be a science without fundamental theories, laws or general principles. I revisit this question in light of the quest for design principles in systems biology and show that different views can be reconciled if we distinguish between different types of generality. The philosophical literature has primarily focused on generality of specific models or explanations, or on the heuristic role of abstraction. This paper takes a different (...) approach in emphasizing a theory-constituting role of general principles. Design principles signify general dependency-relations between structures and functions, given a set of formally defined constraints. I contend that design principles increase our understanding of living systems by relating specific models to general types. The categorization of types is based on a delineation of the scope of biological possibilities, which serves to identify and define the generic features of classes of systems. To characterize the basis for general principles through generic abstraction and reasoning about possibility spaces, I coin the term constraint-based generality. I show that constraint-based generality is distinct from other types of generality in biology, and argue that general principles play a unifying role that does not entail theory reduction. (shrink)

“Proof of concept” is a phrase frequently used in descriptions of research sought in program announcements, in experimental studies, and in the marketing of new technologies. It is often coupled with either a short definition or none at all, its meaning assumed to be fully understood. This is problematic. As a phrase with potential implications for research and technology, its assumed meaning requires some analysis to avoid it becoming a descriptive category that refers to all things scientifically exciting. I provide (...) a short analysis of proof of concept research and offer an example of it within synthetic biology. I suggest that not only are there activities that circumscribe new epistemological categories but there are also associated normative ethical categories or principles linked to the research. I examine these and provide an outline for an alternative ethical account to describe these activities that I refer to as “extended agency ethics”. This view is used to explain how the type of research described as proof of concept also provides an attendant proof of principle that is the result of decision-making that extends across practitioners, their tools, techniques, and the problem solving activities of other research groups. (shrink)

What do biologists want? If, unlike their counterparts in physics, biologists are generally wary of a grand, overarching theory, at what kinds of explanation do biologists aim? A history of the diverse and changing nature of biological explanation in a particularly charged field, "Making Sense of Life" draws our attention to the temporal, disciplinary, and cultural components of what biologists mean, and what they understand, when they propose to explain life.

The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by (...) drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice. (shrink)

Recently, several critics of the multiple realizability thesis 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. (shrink)

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is (...) typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more “biology inspired.”. (shrink)

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is (...) typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more “biology inspired.”. (shrink)

There appear to be no biological regularities that have the properties traditionally associated with laws, such as an unlimited scope or holding in all or many possible background conditions. Mitchell, Lange, and others have therefore suggested redefining laws to redeem the lawlike status of biological regularities. These authors suggest that biological regularities are lawlike because they are pragmatically or paradigmatically similar to laws or stable regularities. I will review these re-definitions by arguing both that there are difficulties in applying their (...) accounts to biology and difficulties in the accounts themselves, which suggests that the accounts are not adequate to redeem the lawlike status of biological regularities. Finally, I will suggest a new account of laws that also shows how non-laws might function in some of the roles of laws. (shrink)

Biological modalities (e.g., biological possibility, necessity and counterfactuality) play an important explanatory role in biological practice. However, biological modalities lack truth conditions and the inferential relationship between biological and other modalities is unclear. This thesis addresses these problems, first, by improving upon Daniel Dennett's Library of Mendel. Second, a family of modal logics is introduced. In the simplest model, states are interpreted as codons, the binary relation is interpreted as single substitution mutation and the valuation induces a partition of blocks (...) of codons that code for some amino acid. In addition, the proposed framework allows for a grading of biological possibility and captures various competing notions of biological possibility. Applications include a model checker and a lawless Lewis-style semantics for biological counterfactuals. In short, this thesis lays the groundwork for a theory of biological modalities. (shrink)

Synthetic biology and systems biology are often highlighted as antagonistic strategies for dealing with the overwhelming complexity of biology (engineering versus understanding; tinkering in the lab versus modelling in the computer). However, a closer view of contemporary engineering methods (inextricably interwoven with mathematical modelling and simulation) and of the situation in biology (inextricably confronted with the intrinsic complexity of biomolecular environments) demonstrates that tinkering in the lab is increasingly supported by rational design methods. In other words: Synthetic biology and systems (...) biology are merged by the use of computational techniques. These computational techniques are needed because the intrinsic complexity of biomolecular environments (stochasticity, non-linearities, system-level organization, evolution, independence, etc.) require advanced concepts of bio bricks and devices. A philosophical investigation of the history and nature of bio parts and devices reveals that these objects are imitating generic objects of engineering (switches, gates, oscillators, sensors, etc.), but the well-known design principles of generic objects are not sufficient for complex environments like cells. Therefore, the rational design methods have to be used to create more advanced generic objects, which are not only generic in their use, but also adaptive in their behavior. Case studies will show how simulation-based rational design methods are used to identify adequate parameters for synthesized designs (stability analyses), to improve lab experiments by ‘looking through noise’ (estimation of hidden variables and parameters), and to replace laborious and time-consuming post hoc tweaking in the lab by in-silico guidance (in-silico variation of bio brick properties). The overall aim of these developments, as will be argued in the discussion, is to achieve adaptive-generic instrumentality for bio parts and devices and thus increasingly merging systems and synthetic biology. (shrink)