Marcel Weber

This Ph.D. thesis provides a pilosophical account of the structure of the evolutionary synthesis of the 1930s and 40s. The first, more historical part analyses how classical genetics came to be integrated into evolutionary thinking, highlighting in particular the importance of chromosomal mapping of Drosophila strains collected in the wild by Dobzansky, but also the work of Goldschmidt, Sumners, Timofeeff-Ressovsky and others. The second, more philosophical part attempts to answer the question wherein the unity of the synthesis consisted. I argue that it exemplifies a weak of form of explanatory unification.

Unlike in physics, the category of thought experiment is not very common in biology. At least there are no classic examples that are as important and as well-known as the most famous thought experiments in physics, such as Galileo’s, Maxwell’s or Einstein’s. The reasons for this are far from obvious; maybe it has to do with the fact that modern biology for the most part sees itself as a thoroughly empirical discipline that engages either in real natural history or in experimenting on real organisms rather than fictive ones. While theoretical biology does exist and is recognized as part of biology, its role within biology appears to be more marginal than the role of theoretical physics within physics. It could be that this marginality of theory also affects thought experiments as sources of theoretical knowledge. Of course, none of this provides a sufficient reason for thinking that thought experiments are really unimportant in biology. It is quite possible that the common perception of this matter is wrong and that there are important theoretical considerations in biology, past or present, that deserve the title of thought experiment just as much as the standard examples from physics. Some such considerations may even be widely known and considered to be important, but were not recognized as thought experiments. In fact, as we shall see, there are reasons for thinking that what is arguably the single most important biological work ever, Charles Darwin’s On the Origin of Species, contains a number of thought experiments. There are also more recent examples both in evolutionary and non-evolutionary biology, as we will show. Part of the problem in identifying positive examples in the history of biology is the lack of agreement as to what exactly a thought experiment is. Even worse, there may not be more than a family resemblance that unifies this epistemic category. We take it that classical thought experiments show the following characteristics: They serve directly or indirectly in the non-empirical epistemic evaluation of theoretical propositions, explanations or hypotheses. Thought experiments somehow appeal to the imagination. They involve hypothetical scenarios, which may or may not be fictive. In other words, thought experiments suppose that certain states of affairs hold and then try to intuit what would happen in a world where these suppositions are true. We want to examine in the following sections if there are episodes in the history of biology that satisfy these criteria. As we will show, there are a few episodes that might satisfy all three of these criteria, and many more if the imagination criterion is dropped or understood in a lose sense. In any case, this criterion is somewhat vague in the first place, unless a specific account of the imagination is presupposed. There will also be issues as to what exactly “non-empirical” means. In general, for the sake of discussion we propose to understand the term “thought experiment” here in a broad rather than a narrow sense here. We would rather be guilty of having too wide a conception of thought experiment than of missing a whole range of really interesting examples.

Causal selection is the task of picking out, from a field of known causally relevant factors, some factors as elements of an explanation. The Causal Parity Thesis in the philosophy of biology challenges the usual ways of making such selections among different causes operating in a developing organism. The main target of this thesis is usually gene centrism, the doctrine that genes play some special role in ontogeny, which is often described in terms of information-bearing or programming. This paper is concerned with the attempt of confronting the challenge coming from the Causal Parity Thesis by offering principles of causal selection that are spelled out in terms of an explicit philosophical account of causation, namely an interventionist account. I show that two such accounts that have been developed, although they contain important insights about causation in biology, nonetheless fail to provide an adequate reply to the Causal Parity challenge: Ken Waters's account of actual-difference making and Jim Woodward's account of causal specificity. A combination of the two also doesn't do the trick, nor does Laura Franklin-Hall's account of explanation (in this volume). We need additional conceptual resources. I argue that the resources we need consist in a special class of counterfactual conditionals, namely counterfactuals the antecedents of which describe biologically normal interventions.

Experimental modeling in biology involves the use of living organisms (not necessarily so-called "model organisms") in order to model or simulate biological processes. I argue here that experimental modeling is a bona fide form of scientific modeling that plays an epistemic role that is distinct from that of ordinary biological experiments. What distinguishes them from ordinary experiments is that they use what I call "in vivo representations" where one kind of causal process is used to stand in for a physically different kind of process. I discuss the advantages of this approach in the context of evolutionary biology.

I examine to what extent accounts of mechanisms based on formal interventionist theories of causality can adequately represent biological mechanisms with complex dynamics. Using a differential equation model for a circadian clock mechanism as an example, I first show that there exists an iterative solution that can be interpreted as a structural causal model. Thus, in principle, it is possible to integrate causal difference-making information with dynamical information. However, the differential equation model itself lacks the right modularity properties for a full integration. A formal mechanistic model will therefore have to leave out either noncausal or causal explanatory relations.

This paper examines causal theories of reference with respect to how plausible an account they give of non-physical natural kind terms such as ‘gene’ as well as of the truth of the associated theoretical claims. I first show that reference fixism for ‘gene’ fails. By this, I mean the claim that the reference of ‘gene’ was stable over longer historical periods, for example, since the classical period of transmission genetics. Second, I show that the theory of partial reference does not do justice to some widely held realist intuitions about classical genetics. This result is at loggerheads with the explicit goals usually associated with partial theories of reference, which is to defend a realist semantics for scientific terms. Thirdly, I show that, contrary to received wisdom and perhaps contrary to physics and chemistry, neither reference fixism nor partial reference are necessary in order to hold on to scientific realism about biology. I pinpoint the reasons for this in the nature of biological kinds, which do not even remotely resemble natural kinds (i.e., Lockean real essences) as traditionally conceived.

John Searle has argued that functions owe their existence to the value that we put into life and survival. In this paper, I will provide a critique of Searle’s argument concerning the ontology of functions. I rely on a standard analysis of functional predicates as relating not only a biological entity, an activity that constitutes the function of this entity and a type of system but also a goal state. A functional attribution without specification of such a goal state has no truth-value. But if completed with a goal state, functional attributions understood as four-place relations attain a truth-value. The truth conditions of all attributions of function involve a dependence claim of the goal state on the function bearer’s activity. The nature of this dependence may differ; I consider five different possibilities: causality, mechanistic constitution, mereology, supervenience and metaphysical grounding. If these dependency relations are objective, Searle’s central ontological thesis fails. What he ought to have said is that our valuing survival or other goal states may be the reason why biology seeks functional knowledge, but this has nothing to do with ontology. I will show further that Searle also raised an interesting challenge concerning the relationship of functional and causal truths, but it does not threaten the objectivity of functions either. At best, it could show that functional vocabulary is eliminable. However, I will show that functional vocabulary is not so eliminable.

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity.

I want to exhibit the deeper metaphysical reasons why some common ways of describing the causal role of genes in development and evolution are problematic. Specifically, I show why using the concept of information in an intentional sense in genetics is inappropriate, even given a naturalistic account of intentionality. Furthermore, I argue that descriptions that use notions such as programming, directing or orchestrating are problematic not for empirical reasons, but because they are not strictly causal. They are intentional. By contrast, other notions that are part of the received view in genetics and evolutionary theory are defensible if understood correctly, in particular the idea that genes are the main replicators in evolution. The paper concludes that dropping all intentional or intentionally laden concepts does not force us to accept the so-called causal parity thesis, at least not in its stronger form.

I examine different arguments that could be used to establish indeterminism of neurological processes. Even though scenarios where single events at the molecular level make the difference in the outcome of such processes are realistic, this falls short of establishing indeterminism, because it is not clear that these molecular events are subject to quantum mechanical uncertainty. Furthermore, attempts to argue for indeterminism autonomously (i.e., independently of quantum mechanics) fail, because both deterministic and indeterministic models can account for the empirically observed behavior of ion channels

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.

It has been claimed that the intentional stance is necessary to individuate behavioral traits. This thesis, while clearly false, points to two interesting sets of problems concerning biological explanations of behavior: The first is a general in the philosophy of science: the theory-ladenness of observation. The second problem concerns the principles of trait individuation, which is a general problem in philosophy of biology. After discussing some alternatives, I show that one way of individuating the behavioral traits of an organism is by a special use of the concept of biological function, as understood in an enriched causal role (not selected effect) sense. On this view, a behavioral trait is essentially a special kind of regularity, namely a regularity that is produced by some regulatory mechanism. Regulatory mechanisms always require goal states, which can only be provided by functional considerations. As an example from actual (as opposed to folk) science, I examine the case of social behavior in nematodes. I show that the attempt to explain this phenomenon actually transformed it. This supports the view that scientific explanation does not explain an explanandum phenomenon that is given prior to the explanation; rather, the explanandum is changed by the explanation. This means that there could be a plurality of stances that have some heuristic value initially, but which will be abandoned in favor of a functional characterization eventually.

The recent literature on causality has seen the introduction of several distinctions within causality, which are thought to be important for understanding the widespread scientific practice of focusing causal explanations on a subset of the factors that are causally relevant for a phenomenon. Concepts used to draw such distinctions include, among others, stability, specificity, proportionality, or actual-difference making. In this contribution, I propose a new distinction that picks out an explanatorily salient class of causes in biological systems. Some select causes in complex biological systems, I argue, have the property of enabling coherent causal control of these systems. Examples of such control variables include hormones and other signaling molecules, e.g., TOR (target of rapamycin), morphogens or the products of homeotic selector genes in embryonic pattern formation. I propose an analysis of this notion based on concepts borrowed from causal graph theory.

Going back at least to Duhem, there is a tradition of thinking that crucial experiments are impossible in science. I analyse Duhem's arguments and show that they are based on the excessively strong assumption that only deductive reasoning is permissible in experimental science. This opens the possibility that some principle of inductive inference could provide a sufficient reason for preferring one among a group of hypotheses on the basis of an appropriately controlled experiment. To be sure, there are analogues to Duhem's problems that pertain to inductive inference. Using a famous experiment from the history of molecular biology as an example, I show that an experimentalist version of inference to the best explanation (IBE) does a better job in handling these problems than other accounts of scientific inference. Furthermore, I introduce a concept of experimental mechanism and show that it can guide inferences from data within an IBE-based framework for induction. 1. Introduction2. Duhem on the Logic of Crucial Experiments3. ‘The Most Beautiful Experiment in Biology’4. Why Not Simple Elimination?5. Severe Testing6. An Experimentalist Version of IBE 6.1. Physiological and experimental mechanisms6.2. Explaining the data6.3. IBE and the problem of untested auxiliaries6.4. IBE-turtles all the way down7. Van Fraassen's ‘Bad Lot’ Argument8. IBE and Bayesianism9. Conclusions.

The history of developmental biology is interwoven with debates as to whether mechanistic explanations of development are possible or whether alternative explanatory principles or even vital forces need to be assumed. In particular, the demonstrated ability of embryonic cells to tune their developmental fate precisely to their relative position and the overall size of the embryo was once thought to be inexplicable in mechanistic terms. Taking a causal perspective, this Element examines to what extent and how developmental biology, having turned molecular about four decades ago, has been able to meet the vitalist challenge. It focuses not only on the nature of explanations but also on the usefulness of causal knowledge – including the knowledge of classical experimental embryology – for further scientific discovery. It also shows how this causal perspective allows us to understand the nature and significance of some key concepts, including organizer, signal and morphogen. This title is also available as Open Access on Cambridge Core.

This article examines the role of experimental generalizations and physical laws in neuroscientific explanations, using Hodgkin and Huxley’s electrophysiological model from 1952 as a test case. I show that the fact that the model was partly fitted to experimental data did not affect its explanatory status, nor did the false mechanistic assumptions made by Hodgkin and Huxley. The model satisfies two important criteria of explanatory status: it contains invariant generalizations and it is modular (both in James Woodward’s sense). Further, I argue that there is a sense in which the explanatory heteronomy thesis holds true for this case. †To contact the author, please write to: SNF‐Professorship for Philosophy of Science, University of Basel, Missionsstrasse 21, 4003 Basel, Switzerland; e‐mail: [email protected].

Darwin famously held that his use of the term "chance" in evolutionary theory merely "serves to acknowledge plainly our ignorance of the causes of each particular variation". Is this a tenable view today? Or should we revise our thinking about chance in evolution in light of the more advanced, quantitative models of Neo-Darwinian theory, which make substantial use of statistical reasoning and the concept of probability? Is determinism still a viable metaphysical doctrine about biological reality after the quantum revolution in physics, or dowe have to abandon it in favor of an objective indeterminism? In light of such reflections, what is the relevant interpretation of probability in evolutionary theory? Do biologists use the concept of probability because they are finite cognitive agents or because the evolutionary process is fundamentally probabilistic? In this paper, I will show that we do not yet fully understand the nature of chance in evolution.

I attempt to characterize the relationship of classical experimental embryology (CEE) and molecular developmental biology and compare it to the much-discussed case of classical genetics. These sciences are treated here as discovery practices rather than as definitive forms of knowledge. I first show that CEE had some causal knowledge and hence was able to answer specific why?-questions. A paradigm was provided by the case of eye induction, perhaps CEE’s greatest success. The case of the famous Spemann-Mangold organizer is more difficult. I argue that before the advent of molecular biology, knowledge of its causal role in development was very limited. As a result, there was no functional definition of the concept of organizer. I argue that, like the classical gene concept, it is best viewed as an operational concept. This means that an account of reduction such as Kim’s functional reduction, which is still a mainstay in scientific metaphysics, cannot work in these cases. Nonetheless, again like in the classical gene case, the operational concepts of CEE played an important heuristic role in the discovery of molecules involved in morphogenesis and cell differentiation. This was made possible by what I call inter-level investigative practices. These are practices that combine experimental manipulations targeting two (or more) different levels. I conclude that the two sciences are more closely related via their experimental practices than by any inter-level explanatory relations.

Incommensurability of scientific theories, as conceived by Thomas Kuhnand Paul Feyerabend, is thought to be a major or even insurmountable obstacletothe empirical comparison of these theories. I examine this problem in light ofaconcrete case from the history of experimental biology, namely the oxidativephosphorylation controversy in biochemistry (ca. 1961-1977). After a briefhistorical exposition, I show that the two main competing theories which werethe subject of the ox-phos controversy instantiate some of the characteristicfeatures of incommensurable theories, namely translation failure,non-corresponding predictions, and different claims about what kinds ofentitiesexist in the world. By examining how the controversy was eventually resolved, Ithen show that at least this pair of incommensurable theories couldneverthelessbe empirically compared.

I present an attempt at an explication of the ecological theory of interspecific competition, including its explanatory role in community ecology and evolutionary biology. The account given is based on the idea that law-like statements play an important role in scientific theories of this kind. I suggest that the principle of competitive exclusion is such a law, and that it is evolutionarily invariant. The principle's empirical status is defended and implications for the ongoing debates on the existence of biological laws are discussed

Philosophy of Experimental Biology explores some central philosophical issues concerning scientific research in experimental biology, including genetics, biochemistry, molecular biology, developmental biology, neurobiology, and microbiology. It seeks to make sense of the explanatory strategies, concepts, ways of reasoning, approaches to discovery and problem solving, tools, models and experimental systems deployed by scientific life science researchers and also integrates developments in historical scholarship, in particular the New Experimentalism. It concludes that historical explanations of scientific change that are based on local laboratory practice need to be supplemented with an account of the epistemic norms and standards that are operative in science. This book should be of interest to philosophers and historians of science as well as to scientists.

Recent discussion of the statistical character of evolutionary theory has centered around two positions: (1) Determinism combined with the claim that the statistical character is eliminable, a subjective interpretation of probability, and instrumentalism; (2) Indeterminism combined with the claim that the statistical character is ineliminable, a propensity interpretation of probability, and realism. I point out some internal problems in these positions and show that the relationship between determinism, eliminability, realism, and the interpretation of probability is more complex than previously assumed in this debate. Furthermore, I take some initial steps towards a more adequate account of the statistical character of evolutionary theory