Systems medicine is a promising new paradigm for discovering associations, causal relationships and mechanisms in medicine. But it faces some tough challenges that arise from the use of big data: in particular, the problem of how to integrate evidence and the problem of how to structure the development of models. I argue that objective Bayesian models offer one way of tackling the evidence integration problem. I also offer a general methodology for structuring the development of models, within which the objective (...) Bayesian approach fits rather naturally. (shrink)

Morphogenesis is one of the fundamental processes of developing life. Gastrulation, especially, marks a period of major translocations and bustling rearrangements of cells that give rise to the three germ layers. It was also one of the earliest fields in biology where cell movement and behaviour in living specimens were investigated. This article examines scientific attempts to understand gastrulation from the point of view of cells in motion. It argues that the study of morphogenesis in the twentieth century faced a (...) major dilemma, both epistemological and pictorial: representing form and understanding movement are mutually exclusive, as are understanding form and representing movement. The article follows various ways of modelling, imaging, and simulating gastrular processes, from the early twentieth century to present-day systems biology. The first section examines the tactile modelling of shape changes, the second cell cinematography, mainly the pioneering work of the German embryologists Friedrich Kopsch and Ernst Ludwig Gräper in the 1920s but also a series of classic, yet not widely known, studies of the 1960s. The third section deals with the changes that computer simulation and live-cell imaging introduced to the modelling of shape change and the study of cell movement at the turn of the twenty-first century. Although live-cell imaging promises to experiment upon and represent the living body simultaneously, I argue that the new visuals are an obstacle rather than a solution to the puzzle of understanding cell motion. (shrink)

Over the course of the last three decades, computer simulations have become a major tool of doing science and engaging with the world, not least in an effort to predict and intervene in a future to come. Born in the context of the Second World War and the discipline of physics, simulations have long spread into most diverse fields of enquiry and technological application. This paper introduces a topical collection focussing on simulations in the life sciences. Echoing the current state (...) of tinkering, fast developments, segmentation of knowledge and interdisciplinary collaboration, and in an effort to bridge the science-humanities divide, the contributors to this collection come from multiple disciplinary backgrounds, including information studies, cognitive sciences, philosophy and biology. The ambiguous character of simulations, their cutting across scientific disciplines, analysis and prediction, understanding and doing, gave rise to their success in contemporary life sciences and has been the object of much scientific debate. One of the main aims of this topical collection, by contrast, is to call into question the assumption of an obvious use and easy transfer of methods between fields of knowledge as diverse as, e.g. physics and biology. The collection presents historical case studies from various biological sub-fields. The articles study how simulations are used and the ways they contribute specifically to our understanding of life. Taking up Sergio Sismondo’s description of simulations as “compromises” and “glue”, they also critically engage with the question of what exactly the life sciences have been gluing together over the last two decades. (shrink)

Evolutionary systems biology (ESB) is a rapidly growing integrative approach that has the core aim of generating mechanistic and evolutionary understanding of genotype‐phenotype relationships at multiple levels. ESB's more specific objectives include extending knowledge gained from model organisms to non‐model organisms, predicting the effects of mutations, and defining the core network structures and dynamics that have evolved to cause particular intracellular and intercellular responses. By combining mathematical, molecular, and cellular approaches to evolution, ESB adds new insights and methods to the (...) modern evolutionary synthesis, and offers ways in which to enhance its explanatory and predictive capacities. This combination of prediction and explanation marks ESB out as a research manifesto that goes further than its two contributing fields. Here, we summarize ESB via an analysis of characteristic research examples and exploratory questions, while also making a case for why these integrative efforts are worth pursuing. (shrink)

In this paper we review and argue for the relevance of the concept of open-ended evolution in biological theory. Defining it as a process in which a set of chemical systems bring about an unlimited variety of equivalent systems that are not subject to any pre-determined upper bound of organizational complexity, we explain why only a special type of self-constructing, autonomous systems can actually implement it. We further argue that this capacity derives from the ‘dynamic decoupling’ (in its minimal or (...) most basic sense: the phenotype–genotype decoupling) by means of which a radically new way of material organization (minimal living organization) is achieved, allowing for the long-term sustenance of systems whose individual-metabolic and collective-historical pathways become thereafter deeply intertwined. (shrink)

Evolutionary systems biology is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context (...) of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB’s progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology. (shrink)

Although it may seem like a truism to assert that biology is the science that studies organisms, during the second half of the twentieth century the organism category disappeared from biological theory. Over the past decade, however, biology has begun to witness the return of the organism as a fundamental explanatory concept. There are three major causes: (a) the realization that the Modern Synthesis does not provide a fully satisfactory understanding of evolution; (b) the growing awareness of the limits of (...) reductionism in molecular biology; and (c) the renewed interest in the nature of life as a genuine scientific problem. This essay examines these recent developments and considers the new epistemological roles being played by the organism in each of them. It also reflects on what the present resurgence of the organism means for the philosophy of biology. (shrink)

This paper explores the similarities between the conceptual structure of quantum theory and relational biology as developed within the Rashevsky-Rosen-Louie school of theoretical biology. With this aim, generalized quantum theory and the abstract formalism of (M,R)-systems are briefly presented. In particular, the notion of organizational invariance and relational identity are formalized mathematically and a particular example is given. Several quantum-like attributes of Rosen’s complex systems such as complementarity and nonseparability are discussed. Taken together, this work emphasizes the possible role of (...) self-referentiality and impredicativity in quantum theory. (shrink)

Prediction and control sufficient for reliable medical and other interventions are prominent aims of modeling in systems biology. The short-term attainment of these goals has played a strong role in projecting the importance and value of the field. In this paper I identify the standard models must meet to achieve these objectives as predictive robustness—predictive reliability over large domains. Drawing on the results of an ethnographic investigation and various studies in the systems biology literature, I explore four current obstacles to (...) achieving predictive robustness; data constraints, parameter uncertainty, collaborative constraints and system-scale requirements. I use a case study and the commentary of systems biologists themselves to show that current practices in the field, rather than pursuing these goals, frequently use models heuristically to investigate and build understanding of biological systems that do not meet standards of predictive robustness but are nonetheless effective uses of computation. A more heuristic conception of modeling allows us to interpret current practices as ways that manage these obstacles more effectively, particularly collaborative constraints, such that modelers can in the long-run at least work towards prediction and control. (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)

Life-science phenomena are often explained by specifying the mechanisms that bring them about. The new mechanistic philosophers have done much to substantiate this claim and to provide us with a better understanding of what mechanisms are and how they explain. Although there is disagreement among current mechanists on various issues, they share a common core position and a seeming commitment to some form of scientific realism. But is such a commitment necessary? Is it the best way to go about mechanistic (...) explanation? In this article, we propose an alternative antirealist account that also fits explanatory practice in the life sciences. We pay special attention to mechanistic models, i.e. scientific models that involve a mechanism, and to the role of coherence considerations in building such models. To illustrate our points, we consider the mechanism for the action potential. 1 Introduction2 Some Core Features of Mechanistic Explanation3 Scientific Realism and Mechanistic Explanation4 Antirealist Mechanistic Explanation: The Case of the Action Potential5 Some Outstanding Issues for the Antirealist Mechanist6 Two Problems for the Realist Mechanist7 Conclusions. (shrink)

The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models—which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical (...) equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena, where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism’s ability to respond to perturbations. I offer general conclusions for philosophical accounts of explanation. (shrink)

The Darwinian theory of evolution is itself evolving and this book presents the details of the core of modern Darwinism and its latest developmental directions. The authors present current scientific work addressing theoretical problems and challenges in four sections, beginning with the concepts of evolution theory, its processes of variation, heredity, selection, adaptation and function, and its patterns of character, species, descent and life. The second part of this book scrutinizes Darwinism in the philosophy of science and its usefulness in (...) understanding ecosystems, whilst the third section deals with its application in disciplines beyond the biological sciences, including evolutionary psychology and evolutionary economics, Darwinian morality and phylolinguistics. The final section addresses anti-Darwinism, the creationist view and issues around teaching evolution in secondary schools. The reader learns how current experimental biology is opening important perspectives on the sources of variation, and thus of the very power of natural selection. This work examines numerous examples of the extension of the principle of natural selection and provides the opportunity to critically reflect on a rich theory, on the methodological rigour that presides in its extensions and exportations, and on the necessity to measure its advantages and also its limits. Scholars interested in modern Darwinism and scientific research, its concepts, research programs and controversies will find this book an excellent read, and those considering how Darwinism might evolve, how it can apply to the human sciences and other disciplines beyond its origins will find it particularly valuable. Originally produced in French (Les Mondes Darwiniens), the scope and usefulness of the book have led to the production of this English text, to reach a wider audience. This book is a milestone in the impressive penetration by Francophone scholars into the world of Darwinian science, its historiography and philosophy over the last two decades. Alex Rosenberg, R. Taylor Cole Professor of Philosophy, Duke University Until now this useful and comprehensive handbook has only been available to francophones. Thanks to this invaluable new translation, this collection of insightful and original essays can reach the global audience it deserves. Tim Lewens, University of Cambridge. (shrink)

Evolutionary developmental biology (evo-devo) is considered a ‘mechanistic science,’ in that it causally explains morphological evolution in terms of changes in developmental mechanisms. Evo-devo is also an interdisciplinary and integrative approach, as its explanations use contributions from many fields and pertain to different levels of organismal organization. Philosophical accounts of mechanistic explanation are currently highly prominent, and have been particularly able to capture the integrative nature of multifield and multilevel explanations. However, I argue that evo-devo demonstrates the need for a (...) broadened philosophical conception of mechanisms and mechanistic explanation. Mechanistic explanation (in terms of the qualitative interactions of the structural parts of a whole) has been developed as an alternative to the traditional idea of explanation as derivation from laws or quantitative principles. Against the picture promoted by Carl Craver, that mathematical models describe but usually do not explain, my discussion of cases from the strand of evo-devo which is concerned with developmental processes points to qualitative phenomena where quantitative mathematical models are an indispensable part of the explanation. While philosophical accounts have focused on the actual organization and operation of mechanisms, properties of developmental mechanisms that are about how a mechanism reacts to modifications are of major evolutionary significance, including robustness, phenotypic plasticity, and modularity. A philosophical conception of mechanisms is needed that takes into account quantitative changes, transient entities and the generation of novel types of entities, feedback loops and complex interaction networks, emergent properties, and, in particular, functional-dynamical aspects of mechanisms, including functional (as opposed to structural) organization and distributed, system-wide phenomena. I conclude with general remarks on philosophical accounts of explanation. (shrink)

Emergence is a notorious philosophical term of art. A variety of theorists have appropriated it for their purposes ever since George Henry Lewes gave it a philosophical sense in his 1875 Problems of Life and Mind. We might roughly characterize the shared meaning thus: emergent entities (properties or substances) ‘arise’ out of more fundamental entities and yet are ‘novel’ or ‘irreducible’ with respect to them. (For example, it is sometimes said that consciousness is an emergent property of the brain.) Each (...) of the quoted terms is slippery in its own right, and their specifications yield the varied notions of emergence that we discuss below. There has been renewed interest in emergence within discussions of the behavior of complex systems and debates over the reconcilability of mental causation, intentionality, or consciousness with physicalism. (shrink)