This paper offers a contribution to debates around integrative aspects of systems biology and engages with issues related to the circumstances under which physicists look at biological problems. We use oral history as one of the methodological tools to gather the empirical material, conducting interviews with physicists working in systems biology. The interviews were conducted at several institutions in Brazil, Germany, Israel and the U.S. Biological research has been increasingly dependent on computational methods, high-throughput technologies, and multidisciplinary skills. Quantitative scientists (...) are joining biological departments and collaborations between physicists and biologists are particularly vigorous. This state of affairs raises a number of questions, such as: What are the circumstances under which physicists approach biological problems in systems biology? What kind of interdisciplinary challenges must be tackled? The paper suggests that, concerning physicists’ move to work on biological systems, there are common reasons to move, the transition must be understood in terms of degrees, physicists have a rationale for simplifying systems, and distinct conceptions of model and modeling strategies are recurrent. We identified problems regarding linguistic clarity and integration of epistemological aims. We conclude that cultural unconformities within the systems biology community have important consequences to the flow of scientific knowledge. (shrink)

Functional decomposition is an important goal in the life sciences, and is central to mechanistic explanation and explanatory reduction. A growing literature in philosophy of science, however, has challenged decomposition-based notions of explanation. ‘Holists’ posit that complex systems exhibit context-sensitivity, dynamic interaction, and network dependence, and that these properties undermine decomposition. They then infer from the failure of decomposition to the failure of mechanistic explanation and reduction. I argue that complexity, so construed, is only incompatible with one notion of decomposition, (...) which I call ‘atomism’, and not with decomposition writ large. Atomism posits that function ascriptions must be made to parts with minimal reference to the surrounding system. Complexity does indeed falsify atomism, but I contend that there is a weaker, ‘contextualist’ notion of decomposition that is fully compatible with the properties that holists cite. Contextualism suggests that the function of parts can shift with external context, and that interactions with other parts might help determine their context-appropriate functions. This still admits of functional decomposition within a given context. I will give examples based on the notion of oscillatory multiplexing in systems neuroscience. If contextualism is feasible, then holist inferences are faulty—one cannot infer from the presence of complexity to the failure of decomposition, mechanism, and reductionism. (shrink)

This paper offers a contribution to debates around integrative aspects of systems biology and engages with issues related to the circumstances under which physicists look at biological problems. We use oral history as one of the methodological tools to gather the empirical material, conducting interviews with physicists working in systems biology. The interviews were conducted at several institutions in Brazil, Germany, Israel and the U.S. Biological research has been increasingly dependent on computational methods, high-throughput technologies, and multidisciplinary skills. Quantitative scientists (...) are joining biological departments and collaborations between physicists and biologists are particularly vigorous. This state of affairs raises a number of questions, such as: What are the circumstances under which physicists approach biological problems in systems biology? What kind of interdisciplinary challenges must be tackled? The paper suggests that, concerning physicists’ move to work on biological systems, there are common reasons to move, the transition must be understood in terms of degrees, physicists have a rationale for simplifying systems, and distinct conceptions of model and modeling strategies are recurrent. We identified problems regarding linguistic clarity and integration of epistemological aims. We conclude that cultural unconformities within the systems biology community have important consequences to the flow of scientific knowledge. (shrink)

One central aim of science is to provide explanations of natural phenomena. What role(s) does mathematics play in achieving this aim? How does mathematics contribute to the explanatory power of science? Rules to Infinity defends the thesis, common though perhaps inchoate among many members of the Vienna Circle, that mathematics contributes to the explanatory power of science by expressing conceptual rules, rules which allow the transformation of empirical descriptions. Mathematics should not be thought of as describing, in any substantive sense, (...) an abstract realm of eternal mathematical objects, as traditional platonists have thought. In Rules to Infinity, this view, which I call mathematical normativism, is updated with contemporary philosophical tools, and it is argued that normativism is compatible with mainstream semantic theory. This allows the normativist to accept that there are mathematical truths, while resisting the platonistic idea that there exist abstract mathematical objects that explain such truths. Furthermore, Rules to Infinity defends a particular account of the distinction between scientific explanations that are in some sense distinctively mathematical – those that explain natural phenomena in some uniquely mathematical way – and those that are only standardly mathematical, and it lays out desiderata for any account of this distinction. Normativism is compared with other prominent views in the philosophy of mathematics such as neo-Fregeanism, fictionalism, conventionalism, and structuralism. Rules to Infinity serves as an entry point into debates at the forefront of philosophy of science and mathematics, and it defends novel positions in these debates. (shrink)

Organization figures centrally in the understanding of biological systems advanced by both new mechanists and proponents of the autonomy framework. The new mechanists focus on how components of mechanisms are organized to produce a phenomenon and emphasize productive continuity between these components. The autonomy framework focuses on how the components of a biological system are organized in such a way that they contribute to the maintenance of the organisms that produce them. In this paper we analyze and compare these two (...) accounts of organization and argue that understanding biological organisms as cohesively integrated systems benefits from insights from both. To bring together the two accounts, we focus on the notions of control and regulation as bridge concepts. We start from a characterization of biological mechanisms in terms of constraints and focus on a specific type of mechanism, control mechanisms, that operate on other mechanisms on the basis of measurements of variables in the system and its environment. Control mechanisms are characterized by their own set of constraints that enable them to sense conditions, convey signals, and effect changes on constraints in the controlled mechanism. They thereby allow living organisms to adapt to internal and external variations and to coordinate their parts in such a manner as to maintain viability. Because living organisms contain a vast number of control mechanisms, a central challenge is to understand how they are themselves organized. With the support of examples from both unicellular and multicellular systems we argue that control mechanisms are organized heterarchically, and we discuss how this type of control architecture can, without invoking top-down and centralized forms of organizations, succeed in coordinating internal activities of organisms. (shrink)

We provide three innovations to recent debates about whether topological or “network” explanations are a species of mechanistic explanation. First, we more precisely characterize the requirement that all topological explanations are mechanistic explanations and show scientific practice to belie such a requirement. Second, we provide an account that unifies mechanistic and non-mechanistic topological explanations, thereby enriching both the mechanist and autonomist programs by highlighting when and where topological explanations are mechanistic. Third, we defend this view against some powerful mechanist objections. (...) We conclude from this that topological explanations are autonomous from their mechanistic counterparts. (shrink)

This chapter provides a systematic overview of topological explanations in the philosophy of science literature. It does so by presenting an account of topological explanation that I (Kostić and Khalifa 2021; Kostić 2020a; 2020b; 2018) have developed in other publications and then comparing this account to other accounts of topological explanation. Finally, this appraisal is opinionated because it highlights some problems in alternative accounts of topological explanations, and also it outlines responses to some of the main criticisms raised by the (...) so-called new mechanists. (shrink)

According to the free energy principle, life is an “inevitable and emergent property of any random dynamical system at non-equilibrium steady state that possesses a Markov blanket” :20130475, 2013). Formulating a principle for the life sciences in terms of concepts from statistical physics, such as random dynamical system, non-equilibrium steady state and ergodicity, places substantial constraints on the theoretical and empirical study of biological systems. Thus far, however, the physics foundations of the free energy principle have received hardly any attention. (...) Here, we start to fill this gap and analyse some of the challenges raised by applications of statistical physics for modelling biological targets. Based on our analysis, we conclude that model-building grounded in the free energy principle exacerbates a trade-off between generality and realism, because of a fundamental mismatch between its physics assumptions and the properties of actual biological targets. (shrink)

Ongoing empirical discoveries in molecular biology have generated novel conceptual challenges and perspectives. Philosophers of biology have reacted to these trends when investigating the practice of molecular biology and contributed to scientific debates on methodological and conceptual matters. This article reviews some major philosophical issues in molecular biology. First, philosophical accounts of mechanistic explanation yield a notion of explanation in the context of molecular biology that does not have to rely on laws of nature and comports well with molecular discovery. (...) Second, reductionism continues to be debated and increasingly be rejected by scientists. Philosophers have likewise moved away from reduction toward integration across fields or integrative explanations covering several levels of organization. Third, although the gene concept has undergone substantial transformation and even fragmentation, it still enjoys widespread use by molecular biologists, which has prompted philosophers to understand the empirical reasons for this. At the same time, it has been argued the notion of ‘genetic information’ is largely an empty metaphor, which generates the illusion of explanatory understanding without offering an adequate explanation of molecular and developmental mechanisms. (shrink)

In the last couple of years a few seemingly independent debates on scientific explanation have emerged, with several key questions that take different forms in different areas. For example, the question what makes an explanation distinctly mathematical and are there any non-causal explanations in sciences (i.e. explanations that don’t cite causes in the explanans) sometimes take a form of the question what makes mathematical models explanatory, especially whether highly idealized models in science can be explanatory and in virtue of what (...) they are explanatory. These questions raise further issues about counterfactuals, modality and explanatory asymmetries, i.e. do mathematical and non-causal explanations support counterfactuals, and how to understand explanatory asymmetries in non-causal explanations. Even though these are very common issues in the philosophy of physics and mathematics, they can be found in different guises in the philosophy of biology, where there is the statistical interpretation of the Modern Synthesis theory of evolution, according to which the post-Darwinian theory of natural selection explains evolutionary change by citing statistical properties of populations and not the causes of changes. These questions also arise in philosophy of ecology or neuroscience in regard to the nature of topological explanations. The question here is whether in network models in biology, ecology, neuroscience and computer science the mathematical or more precisely topological properties can be explanatory of physical phenomena, or they are just different ways to represent causal structures. The aim of the special issue is to unify all these debates around several overlapping questions. (shrink)

Cancer is typically spoken of as a “complex” disease. But, in what sense are cancers “complex”? Is there one sense, or several? What implications does this complexity have – both for how we study, and how we intervene upon cancers? The aim of this paper is first, to clarify the variety of senses in which cancer is spoken of as "complex" in the scientific literature, and second, to discover what explanatory and predictive roles such features play.

In this paper, I outline a heuristic for thinking about the relation between explanation and understanding that can be used to capture various levels of “intimacy”, between them. I argue that the level of complexity in the structure of explanation is inversely proportional to the level of intimacy between explanation and understanding, i.e. the more complexity the less intimacy. I further argue that the level of complexity in the structure of explanation also affects the explanatory depth in a similar way (...) to intimacy between explanation and understanding, i.e. the less complexity the greater explanatory depth and vice versa. (shrink)

In this essay I propose that what design principles in systems biology and systems neuroscience do is to present abstract characterizations of mechanisms, and thereby facilitate mechanistic explanation. To show this, one design principle in systems neuroscience, i.e., the multilayer perceptron, is examined. However, Braillard contends that design principles provide a sort of non-mechanistic explanation due to two related reasons: they are very general and describe non-causal dependence relationships. In response to this, I argue that, on the one hand, all (...) mechanisms are more or less general, and on the other, many design principles are causal systems. (shrink)

Cancer—and scientific research on cancer—raises a variety of compelling philosophical questions. This entry will focus on four topics, which philosophers of science have begun to explore and debate. First, scientific classifications of cancer have as yet failed to yield a unified taxonomy. There is a diversity of classificatory schemes for cancer, and while some are hierarchical, others appear to be “cross-cutting,” or non-nested. This literature thus raises a variety of questions about the nature of the disease and disease classification. Second, (...) philosophers of science have historically taken the aim of science to be arriving at true theories. However, scientists studying cancer come from a variety of disciplines, with different scientific as well as practical aims. Perhaps it is not surprising, then, that historians and philosophers of science do not seem to agree on how best to characterize the aim and structure of cancer research; it is far from clear whether the appropriate characterization of the aim is arriving at true theories, or even whether the proper units of analysis are “theories”, or instead, “models”, “explanatory frameworks”, “research programs”, “paradigms”, or perhaps, “experimental traditions”. With the rise of “big data” science—such as the Cancer Genome Atlas Project (or TCGA)—and “systems” approaches to the study of disease, both philosophers and historians of science are rethinking how best to describe and explain these distinctive kinds of scientific inquiry. -/- Third, cancer is in part a byproduct of our developmental and life history, as well as our evolutionary history. Cancer progression can be compared to a reversion of development, or, to the evolution of multicellularity. Thus, cancer raises intriguing questions about how we conceive of “functions”, “development”, and the role of our evolutionary history and particularly, selective trade-offs, in vulnerability to disease. -/- Last but not least, cancer research provides a case study for consideration of the roles of values at the science-policy interface. Epidemiological and toxicological research on cancer’s causes informs toxics law and regulatory policy, which raises a variety of questions about the nature of evidence and inductive risk in such contexts. (shrink)

Philosophical discussions of systems biology have enriched the notion of mechanistic explanation by pointing to the role of mathematical modeling. However, such accounts still focus on explanation in terms of tracking a mechanism's operation across time (by means of mental or computational simulation). My contention is that there are explanations of molecular systems where the explanatory understanding does not consist in tracking a mechanism's operation and productive continuity. I make this case by a discussion of bifurcation analysis in dynamical systems, (...) articulating the distinctive way in which explanatory understanding is provided, especially about the reversibility or irreversibility of molecular processes. (shrink)

New mechanical philosophy posits that explanations in the life sciences involve the decomposition of a system into its entities and their respective activities and organization that are responsible for the explanandum phenomenon. This mechanistic account of explanation has proven problematic in its application to mathematical models, leading the mechanists to suggest different ways of aligning abstract models with the mechanist program. Initially, the discussion centered on whether the Hodgkin-Huxley model is explanatory. Network models provided another complication, as they apply to (...) a wide number of materially diverse systems. In this article, we examine the various attempts to integrate abstract models within the mechanist program, also presenting a further challenge: the Heimburg-Jackson model, which was introduced as an alternative to the Hodgkin-Huxley model. We argue that although the notion of abstraction as the omission of irrelevant mechanistic details appears to give a mechanistic solution for accommodating abstract models, this notion does not suit models whose epistemic strategy is not decompositional. As a result, the mechanist has to choose whether to dilute the mechanistic approach nearly beyond recognition or to claim that many, if not most, abstract theoretical models do not deliver mechanistic explanations, or qualify as explanatory at all. (shrink)

Research on diseases such as cancer reveals that primary mechanisms, which have been the focus of study by the new mechanists in philosophy of science, are often subject to control by other mechanisms. Cancer cells employ the same primary mechanisms as healthy cells but control them differently. I use cancer research to highlight just how widespread control is in individual cells. To provide a framework for understanding control, I reconceptualize mechanisms as imposing constraints on flows of free energy, with control (...) mechanisms operating on flexible constraints in primary mechanisms. I argue that control mechanisms themselves often form complex, integrated networks. (shrink)

Despite the importance of network analysis in biological practice, dominant models of scientific explanation do not account satisfactorily for how this family of explanations gain their explanatory power in every specific application. This insufficiency is particularly salient in the study of the ecology of the microbiome. Drawing on Coyte et al. (2015) study of the ecology of the microbiome, Deulofeu et al. (2021) argue that these explanations are neither mechanistic, nor purely mathematical, yet they are substantially empirical. Building on their (...) criticisms, in the present work we make a step further elucidating this kind of explanations with a general analytical framework according to which scientific explanations are ampliative, specialized embeddings (ASE), which has recently been successfully applied to other biological subfields. We use ASE to reconstruct in detail the Coyte et al.’s case study and on its basis, we claim that network explanations of the ecology of the microbiome, and other similar explanations in ecology, gain their epistemological force in virtue of their capacity to embed biological phenomena in non-accidental generalizations that are simultaneously ampliative and specialized. (shrink)

In 1966 Richard Levins argued that applications of mathematics to population biology faced various constraints which forced mathematical modelers to trade-off at least one of realism, precision, or generality in their approach. Much traditional mathematical modeling in biology has prioritized generality and precision in the place of realism through strategies of idealization and simplification. This has at times created tensions with experimental biologists. The past 20 years however has seen an explosion in mathematical modeling of biological systems with the rise (...) of modern computational systems biology and many new collaborations between modelers and experimenters. In this paper I argue that many of these collaborations revolve around detail-driven modeling practices which in Levins’ terms trade-off generality for realism and precision. These practices apply mathematics by working from detailed accounts of biological systems, rather than from initially idealized or simplified representations. This is possible by virtue of modern computation. The form these practices take today suggest however Levins’ constraints on mathematical application no longer apply, transforming our understanding of what is possible with mathematics in biology. Further the engagement with realism and the ability to push realistic models in new directions aligns well with the epistemological and methodological views of experimenters, which helps explain their increased enthusiasm for biological modeling. (shrink)

. Early microbiome research found numerous associations between microbial community patterns and host physiological states. These findings hinted at community-level explanations. “Top-down” experiments, working with whole communities, strengthened these explanatory expectations. Now, “bottom-up” mechanism-seeking approaches are dissecting communities to focus on specific microbes carrying out particular biochemical activities. To understand the interplay between methodological and explanatory scales, we examine claims of “dysbiosis,” when host illness is proposed as the consequence of a community state. Our analysis concludes with general observations about (...) how methodologies relate to explanations, and the implications for microbiome research. (shrink)

Even though complexity is a concept that is ubiquitously used by biologists and philosophers of biology, it is rarely made precise. I argue that a clarification of the concept is neither trivial nor unachievable, and I propose a unifying framework based on the technical notion of “effective complexity” that allows me to do justice to conflicting intuitions about biological complexity, while taking into account several distinctions in the usage of the concept that are often overlooked. In particular, I propose a (...) distinction between two kinds of complexity, “mechanical” and “emergent”, which can be understood as different ways of relating the effective complexity of mechanisms and of behaviors in biological explanations. I illustrate the adequacy of this framework by discussing different attempts to understand intracellular organization in terms of pathways and networks. My framework provides a different way of thinking about recent philosophical debates, for example, on the difference between mechanistic and topological explanations and about the concept of emergence. Moreover, it can contribute to a proper assessment of metascientific arguments that invoke biological complexity. (shrink)