Twentieth-century theoretical efforts towards the articulation of general system properties came short of having the significant impact on biological practice that their proponents envisioned. Although the latter did arrive at preliminary mathematical formulations of such properties, they had little success in showing how these could be productively incorporated into the research agenda of biologists. Consequently, the gap that kept system-theoretic principles cut-off from biological experimentation persisted. More recently, however, simple theoretical tools have proved readily applicable within the context of systems (...) biology. In particular, examples reviewed in this paper suggest that rigorous mathematical expressions of design principles, imported primarily from engineering, could produce experimentally confirmable predictions of the regulatory properties of small biological networks. But this is not enough for contemporary systems biologists who adopt the holistic aspirations of early systemologists, seeking high-level organizing principles that could provide insights into problems of biological complexity at the whole-system level. While the presented evidence is not conclusive about whether this strategy could lead to the realization of the lofty goal of a comprehensive explanatory integration, it suggests that the ongoing quest for organizing principles is pragmatically advantageous for systems biologists. The formalisms postulated in the course of this process can serve as bridges between system-theoretic concepts and the results of molecular experimentation: they constitute theoretical tools for generalizing molecular data, thus producing increasingly accurate explanations of system-wide phenomena. (shrink)

The biological sciences have always proven a fertile ground for philosophical analysis, one from which has grown a rich tradition stemming from Aristotle and flowering with Darwin. And although contemporary philosophy is increasingly becoming conceptually entwined with the study of the empirical sciences with the data of the latter now being regularly utilised in the establishment and defence of the frameworks of the former, a practice especially prominent in the philosophy of physics, the development of that tradition hasn’t received the (...) wider attention it so thoroughly deserves. This review will briefly introduce some recent significant topics of debate within the philosophy of biology, focusing on those whose metaphysical themes (in everything from composition to causation) are likely to be of wide-reaching, cross-disciplinary interest. (shrink)

This paper examines a case of failed interdisciplinary collaboration, between experimental stem cell research and theoretical systems biology. Recently, two groups of theoretical biologists have proposed dynamical systems models as a basis for understanding stem cells and their distinctive capacities. Experimental stem cell biologists, whose work focuses on manipulation of concrete cells, tissues and organisms, have largely ignored these proposals. I argue that ‘failure to communicate’ in this case is rooted in divergent views of explanation: the theoretically-inclined modelers are committed (...) to a version of the covering-law view, while experimental stem cell biologists aim at mechanistic explanations. I propose a way to reconcile these two explanatory approaches to cell development, and discuss the significance of this result for interdisciplinary collaboration in systems biology and beyond. (shrink)

We explore the crucial role of diagrams in scientific reasoning, especially reasoning directed at developing mechanistic explanations of biological phenomena. We offer a case study focusing on one research project that resulted in a published paper advancing a new understanding of the mechanism by which the central circadian oscillator in Synechococcus elongatus controls gene expression. By examining how the diagrams prepared for the paper developed over the course of multiple drafts, we show how the process of generating a new explanation (...) vitally involved the development and integration of multiple versions of different types of diagrams, and how reasoning about the mechanism proceeded in tandem with the development of the diagrams used to represent it. (shrink)

Novel computational representations, such as simulation models of complex systems and video games for scientific discovery, are dramatically changing the way discoveries emerge in science and engineering. The cognitive roles played by such computational representations in discovery are not well understood. We present a theoretical analysis of the cognitive roles such representations play, based on an ethnographic study of the building of computational models in a systems biology laboratory. Specifically, we focus on a case of model-building by an engineer that (...) led to a remarkable discovery in basic bioscience. Accounting for such discoveries requires a distributed cognition analysis, as DC focuses on the roles played by external representations in cognitive processes. However, DC analyses by and large have not examined scientific discovery, and they mostly focus on memory offloading, particularly how the use of existing external representations changes the nature of cognitive tasks. In contrast, we study discovery processes and argue that discoveries emerge from the processes of building the computational representation. The building process integrates manipulations in imagination and in the representation, creating a coupled cognitive system of model and modeler, where the model is incorporated into the modeler's imagination. This account extends DC significantly, and we present some of the theoretical and application implications of this extended account. (shrink)

We lay groundwork for applying ethnographic methods in philosophy of science. We frame our analysis in terms of two tasks: to identify the benefits of an ethnographic approach in philosophy of science and to structure an ethnographic approach for philosophical investigation best adapted to provide information relevant to philosophical interests and epistemic values. To this end, we advocate for a purpose-guided form of cognitive ethnography that mediates between the explanatory and normative interests of philosophy of science, while maintaining openness and (...) independence when framing such an investigation to achieve robust unbiased results. (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)

In science policy, it is generally acknowledged that science-based problem-solving requires interdisciplinary research. For example, policy makers invest in funding programs such as Horizon 2020 that aim to stimulate interdisciplinary research. Yet the epistemological processes that lead to effective interdisciplinary research are poorly understood. This article aims at an epistemology for interdisciplinary research, in particular, IDR for solving ‘real-world’ problems. Focus is on the question why researchers experience cognitive and epistemic difficulties in conducting IDR. Based on a study of educational (...) literature it is concluded that higher-education is missing clear ideas on the epistemology of IDR, and as a consequence, on how to teach it. It is conjectured that the lack of philosophical interest in the epistemology of IDR is due to a philosophical paradigm of science, which prevents recognizing severe epistemological challenges of IDR, both in the philosophy of science as well as in science education and research. The proposed alternative philosophical paradigm entails alternative philosophical presuppositions regarding aspects such as the aim of science, the character of knowledge, the epistemic and pragmatic criteria for accepting knowledge, and the role of technological instruments. This alternative philosophical paradigm assume the production of knowledge for epistemic functions as the aim of science, and interprets ‘knowledge’ as epistemic tools that must allow for conducting epistemic tasks by epistemic agents, rather than interpreting knowledge as representations that objectively represent aspects of the world independent of the way in which it was constructed. The engineering paradigm of science involves that knowledge is indelibly shaped by how it is constructed. Additionally, the way in which scientific disciplines construct knowledge is guided by the specificities of the discipline, which can be analyzed in terms of disciplinary perspectives. This implies that knowledge and the epistemic uses of knowledge cannot be understood without at least some understanding of how the knowledge is constructed. Accordingly, scientific researchers need so-called metacognitive scaffolds to assist in analyzing and reconstructing how ‘knowledge’ is constructed and how different disciplines do this differently. In an engineering paradigm of science, these metacognitive scaffolds can also be interpreted as epistemic tools, but in this case as tools that guide, enable and constrain analyzing and articulating how knowledge is produced. In interdisciplinary research, metacognitive scaffolds assist interdisciplinary communication aiming to analyze and articulate how the discipline constructs knowledge. (shrink)

Which domains of biology do philosophers of biology primarily study? The fact that philosophy of biology has been dominated by an interest for evolutionary biology is widely admitted, but it has not been strictly demonstrated. Here I analyse the topics of all the papers published in Biology & Philosophy, just as the journal celebrates its thirtieth anniversary. I then compare the distribution of biological topics in Biology & Philosophy with that of the scientific journal Proceedings of the National Academy of (...) Science of the USA, focusing on the recent period 2003–2015. This comparison reveals a significant mismatch between the distributions of these topics. I examine plausible explanations for that mismatch. Finally, I argue that many biological topics underrepresented in philosophy of biology raise important philosophical issues and should therefore play a more central role in future philosophy of biology. (shrink)

This chapter shows that the experimental philosophy has much to offer to philosophy of science by reviewing the existing experimental‐philosophy work in the philosophy of science and by defending it against an important criticism. A natural way of extending experimental philosophy methods to the philosophy of science is to survey scientists’ judgments. The chapter presents two projects in the philosophy of science that can benefit from such surveys: analyzing the scientific concepts found in particular scientific communities and studying scientific cognition. (...) It explains how surveying lay people's judgments can bear on issues in the philosophy of science. The chapter examines the possible contributions of bibliometric, ethnographic and cliometric methods to the philosophy of science. Ethnographic methods are particularly useful to study the social structure of science, the nature and role of social norms in the production of scientific knowledge, and the discovery heuristics at work in everyday scientific practice. (shrink)

Evolutionary systems biology (ESB) aims to integrate methods from systems biology and evolutionary biology to go beyond the current limitations in both fields. This article clarifies some conceptual difficulties of this integration project, and shows how they can be overcome. The main challenge we consider involves the integration of evolutionary biology with developmental dynamics, illustrated with two examples. First, we examine historical tensions between efforts to define general evolutionary principles and articulation of detailed mechanistic explanations of specific traits. Next, these (...) tensions are further clarified by considering a recent case from another field focused on developmental dynamics: stem cell biology. In the stem cell case, incompatible explanatory aims block integration. Experimental approaches aim at mechanistic explanation while dynamical system models offer explanation in terms of general principles. We then discuss an ESB case in which integration succeeds: search for general attractors using a dynamical systems framework synergizes with the experimental search for detailed mechanisms. Contrasts between the positive and negative cases suggest general lessons for achieving an integrated understanding of developmental and evolutionary dynamics. The key integrative move is to acknowledge two complementary aims, both relevant to explanation: identifying the space of possible dynamic states and trajectories, and mechanistic understanding of causal interactions underlying a specific phenomenon of interest. These two aims can support one another in a joint project characterizing dynamic aspects of evolving lineages. This more inclusive project can lead to insights that cannot be reached by either approach in isolation. (shrink)

In this article, we provide a case study examining how integrative systems biologists build simulation models in the absence of a theoretical base. Lacking theoretical starting points, integrative systems biology researchers rely cognitively on the model-building process to disentangle and understand complex biochemical systems. They build simulations from the ground up in a nest-like fashion, by pulling together information and techniques from a variety of possible sources and experimenting with different structures in order to discover a stable, robust result. Finally, (...) we analyze the alternative role and meaning theory has in systems biology expressed as canonical template theories like Biochemical Systems Theory. (shrink)

The paper frames interdisciplinary research as creating complex, distributed cognitive-cultural systems. It introduces and elaborates on the method of cognitive ethnography as a primary means for investigating interdisciplinary cognitive and learning practices in situ. The analysis draws from findings of nearly 20 years of investigating such practices in research laboratories in pioneering bioengineering sciences. It examines goals and challenges of two quite different kinds of integrative problem-solving practices: biomedical engineering (hybridization) and integrative systems biology (collaborative interdependence). Practical lessons for facilitating (...) research and learning in these specific fields are discussed and a preliminary set of interdisciplinary epistemic virtues are proposed as candidates for cultivation in interdisciplinary practices of these kinds more widely. (shrink)

Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an interdisciplinary approach to solving complex problems. Interdisciplinary science is a recent topic in the philosophy of science. Determining what is philosophically important and distinct about interdisciplinary practices requires detailed accounts of problem-solving practices that attempt to understand how specific practices address the (...) challenges and constraints of interdisciplinary research in different contexts. In this paper we draw from our 5-year empirical ethnographic study of two systems biology labs and their collaborations with experimental biologists to analyze a significant problem-solving approach in ISB, which we call adaptive problem solving. ISB lacks much of the methodological and theoretical resources usually found in disciplines in the natural sciences, such as methodological frameworks that prescribe reliable model-building processes. Researchers in our labs compensate for the lack of these and for the complexity of their problems by using a range of heuristics and experimenting with multiple methods and concepts from the background fields available to them. Using these resources researchers search out good techniques and practices for transforming intractable problems into potentially solvable ones. The relative freedom lab directors grant their researchers to explore methodological options and find good practices that suit their problems is not only a response to the complex interdisciplinary nature of the specific problem, but also provides the field itself with an opportunity to discover more general methodological approaches and develop theories of biological systems. Such developments in turn can help to establish the field as an identifiably distinct and successful approach to understanding biological systems. (shrink)

If well-designed, the results of a Randomised Clinical Trial can justify a causal claim between treatment and effect in the study population; however, additional information might be needed to carry over this result to another population. RCTs have been criticized exactly on grounds of failing to provide this sort of information Evidence, inference and enquiry. Oxford University Press, New York, 2011), as well as to black-box important details regarding the mechanisms underpinning the causal law instantiated by the RCT result. On (...) the other side, so-called In Silico Clinical Trials face the same criticisms addressed against standard modelling and simulation techniques, and cannot be equated to experiments Philosophy of molecular medicine: foundational issues in research and practice, Routledge, New York, 2017; Parker in Synthese 169:483–496, 2009; Parke in Philos Sci 81:516–536, 2014; Diez Roux in Am J Epidemiol 181:100–102, 2015 and related discussions in Frigg and Reiss in Synthese 169:593–613, 2009; Winsberg in Synthese 169:575–592, 2009; Beisbart and Norton in Int Stud Philos Sci 26:403–422, 2012). We undertake a formal analysis of both methods in order to identify their distinct contribution to causal inference in the clinical setting. Britton et al.’s study :E2098–E2105, 2013) on the impact of ion current variability on cardiac electrophysiology is used for illustrative purposes. We deduce that, by predicting variability through interpolation, ISCTs aid with problems regarding extrapolation of RCTs results, and therefore in assessing their external validity. Furthermore, ISCTs can be said to encode “thick” causal knowledge —as opposed to “thin” difference-making information inferred from RCTs. Hence, ISCTs and RCTs cannot replace one another but rather, they are complementary in that the former provide information about the determinants of variability of causal effects, while the latter can, under certain conditions, establish causality in the first place. (shrink)

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)

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)

Modern integrative systems biology defines itself by the complexity of the problems it takes on through computational modeling and simulation. However in integrative systems biology computers do not solve problems alone. Problem solving depends as ever on human cognitive resources. Current philosophical accounts hint at their importance, but it remains to be understood what roles human cognition plays in computational modeling. In this paper we focus on practices through which modelers in systems biology use computational simulation and other tools to (...) handle the cognitive complexity of their modeling problems so as to be able to make significant contributions to understanding, intervening in, and controlling complex biological systems. We thus show how cognition, especially processes of simulative mental modeling, is implicated centrally in processes of model-building. At the same time we suggest how the representational choices of what to model in systems biology are limited or constrained as a result. Such constraints help us both understand and rationalize the restricted form that problem solving takes in the field and why its results do not always measure up to expectations. (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)

Computational modeling is one of the primary approaches to constructing protein–protein interfaces in the laboratory. The algorithm-driven computational protein design has been successfully applied to the construction of functional proteins with improved binding affinity and increased thermostability. It is intriguing how a computational protein modeling approach can construct and shape the reality of new functional proteins from scratch. I articulate an account of abstraction and exploration-driven strategies in this computational endeavor. I aim to show that how a computational modelling approach, (...) which is laden with mathematics and algorithms, can have a constructive force on the target protein. (shrink)