It is considered in some quarters that hypothesis‐driven methods are the only valuable, reliable or significant means of scientific advance. Data‐driven or ‘inductive’ advances in scientific knowledge are then seen as marginal, irrelevant, insecure or wrong‐headed, while the development of technology—which is not of itself ‘hypothesis‐led’ (beyond the recognition that such tools might be of value)—must be seen as equally irrelevant to the hypothetico‐deductive scientific agenda. We argue here that data‐ and technology‐driven programmes are not alternatives to hypothesis‐led studies in (...) scientific knowledge discovery but are complementary and iterative partners with them. Many fields are data‐rich but hypothesis‐poor. Here, computational methods of data analysis, which may be automated, provide the means of generating novel hypotheses, especially in the post‐genomic era. BioEssays 26:99–105, 2004. © 2003 Wiley Periodicals, Inc. (shrink)

Mechanistic philosophy of science views a large part of scientific activity as engaged in modelling mechanisms. While science textbooks tend to offer qualitative models of mechanisms, there is increasing demand for models from which one can draw quantitative predictions and explanations. Casini et al. (Theoria 26(1):5–33, 2011) put forward the Recursive Bayesian Networks (RBN) formalism as well suited to this end. The RBN formalism is an extension of the standard Bayesian net formalism, an extension that allows for modelling the hierarchical (...) nature of mechanisms. Like the standard Bayesian net formalism, it models causal relationships using directed acyclic graphs. Given this appeal to acyclicity, causal cycles pose a prima facie problem for the RBN approach. This paper argues that the problem is a significant one given the ubiquity of causal cycles in mechanisms, but that the problem can be solved by combining two sorts of solution strategy in a judicious way. (shrink)

Vitalism was long viewed as the most grotesque view in biological theory: appeals to a mysterious life-force, Romantic insistence on the autonomy of life, or worse, a metaphysics of an entirely living universe. In the early twentieth century, attempts were made to present a revised, lighter version that was not weighted down by revisionary metaphysics: “organicism”. And mainstream philosophers of science criticized Driesch and Bergson’s “neovitalism” as a too-strong ontological commitment to the existence of certain entities or “forces”, over and (...) above the system of causal relations studied by mechanistic science, rejecting the weaker form, organicism, as well. But there has been some significant scholarly “push-back” against this orthodox attitude, notably pointing to the 18th-century Montpellier vitalists to show that there are different historical forms of vitalism, including how they relate to mainstream scientific practice (Wolfe and Normandin, eds. 2013). Additionally, some trends in recent biology that run counter to genetic reductionism and the informational model of the gene present themselves as organicist (Gilbert and Sarkar 2000, Moreno and Mossio 2015). Here, we examine some cases of vitalism in the twentieth century and today, not just as a historical form but as a significant metaphysical and scientific model. We argue for vitalism’s conceptual originality without either reducing it to mainstream models of science or presenting it as an alternate model of science, by focusing on historical forms of vitalism, logical empiricist critiques thereof and the impact of synthetic biology on current (re-)theorizing of vitalism. (shrink)

A high profile context in which physics and biology meet today is in the new field of systems biology. Systems biology is a fascinating subject for sociological investigation because the demands of interdisciplinary collaboration have brought epistemological issues and debates front and centre in discussions amongst systems biologists in conference settings, in publications, and in laboratory coffee rooms. One could argue that systems biologists are conducting their own philosophy of science. This paper explores the epistemic aspirations of the field by (...) drawing on interviews with scientists working in systems biology, attendance at systems biology conferences and workshops, and visits to systems biology laboratories. It examines the discourses of systems biologists, looking at how they position their work in relation to previous types of biological inquiry, particularly molecular biology. For example, they raise the issue of reductionism to distinguish systems biology from molecular biology. This comparison with molecular biology leads to discussions about the goals and aspirations of systems biology, including epistemic commitments to quantification, rigor and predictability. Some systems biologists aspire to make biology more similar to physics and engineering by making living systems calculable, modelable and ultimately predictable—a research programme that is perhaps taken to its most extreme form in systems biology’s sister discipline: synthetic biology. Other systems biologists, however, do not think that the standards of the physical sciences are the standards by which we should measure the achievements of systems biology, and doubt whether such standards will ever be applicable to ‘dirty, unruly living systems’. This paper explores these epistemic tensions and reflects on their sociological dimensions and their consequences for future work in the life sciences. (shrink)

Our understanding of how evolution acts on biological networks remains patchy, as is our knowledge of how that action is best identified, modelled and understood. Starting with network structure and the evolution of protein–protein interaction networks, we briefly survey the ways in which network evolution is being addressed in the fields of systems biology, development and ecology. The approaches highlighted demonstrate a movement away from a focus on network topology towards a more integrated view, placing biological properties centre‐stage. We argue (...) that there remains great potential in a closer synergy between evolutionary biology and biological network analysis, although that may require the development of novel approaches and even different analogies for biological networks themselves. (shrink)

In an instant classic paper ; 2002: 179–182) biologist Yuri Lazebnik deplores the poor effectiveness of the approach adopted by biologists to understand and “fix” biological systems. Lazebnik suggests that to remedy this state of things biologist should take inspiration from the approach used by engineers to design, understand, and troubleshoot technological systems. In the present paper I substantiate Lazebnik’s analysis by concretely showing how to apply the engineering approach to biological problems. I use an actual example of electronic circuit (...) troubleshooting to ground the thesis that, in engineering, the crucial phases of any non-trivial troubleshooting process are aimed at generating a mechanistic explanation of the functioning of the system, which makes extensive recourse to problem-driven qualitative reasoning possibly based on cognitive artifacts applied to systems that are known to have been designed for function. To show how to translate these findings into biological practice I consider a concrete example of biological model building and “troubleshooting”, aimed at the identification of a “fix” for the human immune system in presence of progressing cancer, autoimmune disease, and transplant rejection. The result is a novel immune system model—the danger model with regulatory cells— and new, original hypotheses concerning the development, prophylaxis, and therapy of these unwanted biological processes. Based on the manifest efficacy of the proposed approach, I suggest a refocusing of the activity of theoretical biologists along the engineering-inspired lines illustrated in the paper. (shrink)

Synthetic biology is an umbrella term that covers a range of aims, approaches, and techniques. They are all brought together by common practices of analogizing, synthesizing, mechanicizing, and kludging. With a focus on kludging as the connection point between biology, engineering, and evolution, I show how synthetic biology’s successes depend on custom-built kludges and a creative, “make-it-work” attitude to the construction of biological systems. Such practices do not fit neatly, however, into synthetic biology’s celebration of rational design. Nor do they (...) straightforwardly embody Richard Feynman’s “last blackboard” statement that without creating something it cannot be understood. Reflecting further on the relationship between synthetic construction and knowledge making gives philosophy of science new avenues of insight into scientific practice. (shrink)

A popular view presents explanations in the cognitive sciences as causal or mechanistic and argues that an important feature of such explanations is that they allow us to manipulate and control the explanandum phenomena. Nonetheless, whether there can be explanations in the cognitive sciences that are neither causal nor mechanistic is still under debate. Another prominent view suggests that both causal and non-causal relations of counterfactual dependence can be explanatory, but this view is open to the criticism that it is (...) not clear how to distinguish explanatory from non-explanatory relations. In this paper, I draw from both views and suggest that, in the cognitive sciences, relations of counterfactual dependence that allow manipulation and control can be explanatory even when they are neither causal nor mechanistic. Furthermore, the ability to allow manipulation can determine whether non-causal counterfactual dependence relations are explanatory. I present a preliminary framework for manipulation relations that includes some non-causal relations and use two examples from the cognitive sciences to show how this framework distinguishes between explanatory and non-explanatory, non-causal relations. The proposed framework suggests that, in the cognitive sciences, causal and non-causal relations have the same criterion for explanatory value, namely, whether or not they allow manipulation and control. (shrink)

Concerns with the use of engineering approaches in biology have recently been raised. I examine two related challenges to biological research that I call the synchronic and diachronic underdetermination problem. The former refers to challenges associated with the inference of design principles underlying system capacities when the synchronic relations between lower-level processes and higher-level systems capacities are degenerate. The diachronic underdetermination problem regards the problem of reverse engineering a system where the non-linear relations between system capacities and lower-level mechanisms are (...) changing over time. Braun and Marom argue that recent insights to biological complexity leave the aim of reverse engineering hopeless - in principle as well as in practice. While I support their call for systemic approaches to capture the dynamic nature of living systems, I take issue with the conflation of reverse engineering with naïve reductionism. I clarify how the notion of design principles can be more broadly conceived and argue that reverse engineering is compatible with a dynamic view of organisms. It may even help to facilitate an integrated account that bridges the gap between mechanistic and systems approaches. (shrink)

Design thinking in general, and optimality modeling in particular, have traditionally been associated with adaptationism—a research agenda that gives pride of place to natural selection in shaping biological characters. Our goal is to evaluate the role of design thinking in non-evolutionary analyses. Specifically, we focus on research into abstract design principles that underpin the functional organization of extant organisms. Drawing on case studies from engineering-inspired approaches in biology we show how optimality analysis, and other design-related methods, play a specific methodological (...) role that is tangential to the study of adaptation. To account for the role of these reasoning strategies in contemporary biology, we therefore suggest a reevaluation of the connection between design thinking and adaptationism. (shrink)

The term “synthetic biology” is a popular label of an emerging biotechnological field with strong claims to robustness, modularity, and controlled construction, finally enabling the creation of new organisms. Although the research community is heterogeneous, it advocates a common denominator that seems to define this field: the principles of rational engineering. However, it still remains unclear to what extent rational engineering—rather than “tinkering” or the usage of random based or non-rational processes—actually constitutes the basis for the techniques of synthetic biology. (...) In this article, we present the results of a quantitative bibliometric analysis of the realized extent of rational engineering in synthetic biology. In our analysis, we examine three issues: (1) We evaluate whether work at three levels of synthetic biology (parts, devices, and systems) is consistent with the principles of rational engineering. (2) We estimate the extent of rational engineering in synthetic biology laboratory practice by an evaluation of publications in synthetic biology. (3) We examine the methodological specialization in rational engineering of authors in synthetic biology. Our analysis demonstrates that rational engineering is prevalent in about half of the articles related to synthetic biology. Interestingly, in recent years the relative number of respective publications has decreased. Despite its prominent role among the claims of synthetic biology, rational engineering has not yet entirely replaced biotechnological methods based on “tinkering” and non-rational principles. (shrink)

Cognitive science givescomputational explanationsof the brain. Philosophers have treated these explanations as if they simply claim that the brain computes. We have therefore assumed that to understand how and why computational explanation works, we must understand what it is to compute. In contrast, I argue that we can understand computational explanation by describing the resources it brings to bear on the study of the brain. Specifically, I argue that it introduces concepts and formalisms that complement cognitive science's modeling goals. This (...) allows us to understand computational explanation without having to debatewhat it isto compute. (shrink)

Design patterns are generalized solutions to frequently recurring problems. They were initially developed by architects and computer scientists to create a higher level of abstraction for their designs. Here, we extend these concepts to cell biology to lend a new perspective on the evolved designs of cells' underlying reaction networks. We present a catalog of 21 design patterns divided into three categories: creational patterns describe processes that build the cell, structural patterns describe the layouts of reaction networks, and behavioral patterns (...) describe reaction network function. Applying this pattern language to the E. coli central metabolic reaction network, the yeast pheromone response signaling network, and other examples lends new insights into these systems. (shrink)

Cognitive neuroscience increasingly relies on complex data analysis methods. Researchers in this field come from highly diverse scientific backgrounds, such as psychology, engineering, and medicine. This poses challenges with respect to acquisition of appropriate scientific computing and data analysis skills, as well as communication among researchers with different knowledge and skills sets. Are researchers in cognitive neuroscience adequately equipped to address these challenges? Here, we present evidence from an online survey of methods skills. Respondents (n= 307) mainly comprised students and (...) post-doctoral researchers working in the cognitive neurosciences. Multiple choice questions addressed a variety of basic and fundamental aspects of neuroimaging data analysis, such as signal analysis, linear algebra, and statistics. We analyzed performance with respect to the following factors: undergraduate degree (grouped into Psychology, Methods, and Biology), current researcher status (undergraduate student, PhD student, and post-doctoral researcher), gender, and self-rated expertise levels. Overall accuracy was 72%. Not surprisingly, the Methods group performed best (87%), followed by Biology (73%) and Psychology (66%). Accuracy increased from undergraduate (59%) to PhD (74%) level, but not from PhD to post-doctoral (74%) level. The difference in performance for the Methods vs. non-methods (Psychology/Biology) groups was especially striking for questions related to signal analysis and linear algebra, two areas particularly relevant to neuroimaging research. Self-rated methods expertise was not strongly predictive of performance. The majority of respondents (93%) indicated they would like to receive at least some additional training on the topics covered in this survey. In conclusion, methods skills among junior researchers in cognitive neuroscience can be improved, researchers are aware of this, and there is strong demand for more skills-oriented training opportunities. We hope that this survey will provide an empirical basis for the development of bespoke skills-oriented training programs in cognitive neuroscience institutions. We will provide practical suggestions on how to achieve this. (shrink)

What are scientific theories and how should they be represented? In this article, I propose a causal–structural account, according to which scientific theories are to be represented as sets of interrelated causal and credal nets. In contrast with other accounts of scientific theories (such as Sneedian structuralism, Kitcher’s unificationist view, and Darden’s theory of theoretical components), this leaves room for causality to play a substantial role. As a result, an interesting account of explanation is provided, which sheds light on explanatory (...) unification within a causalist framework. The theory of classical genetics is used as a case study. 1 Introduction2 The Theory of Classical Genetics3 Three Philosophical Accounts of the Theory of Classical Genetics3.1 The structuralist account3.2 Kitcher’s unificationism3.3 Darden and theory change in science4 A Common Lacuna: Where is Causality?5 Woodward’s Interventionist Account of Causation6 Causal Bayes Nets and Their Interrelations6.1 Causal Bayes nets6.2 Relations among causal nets6.3 Credal nets and their interrelations7 The Theory of the Gene and its Causal Graph8 A First Exemplar: Stem Length in Pea Plants8.1 Three crosses on stem length in pea plants8.2 The causal graph for stem length in pea plants8.3 Morgan’s explanatory principles and the credal net for stem length in pea plants9 Explaining Mendel’s Crosses: A Causal–Structural Account10 Monohybrid Crosses with Complete Dominance11 Exemplars,Explanatory Patterns, Generic Credal Nets, and Mechanism Schemas12 Incomplete Dominance13 Anomalies14 Multi-hybrid Crosses with Independent Assortment15 Multi-hybrid Crosses with Linkage and Crossing-Over16 Double Crossing-Over and the Linear Order of the Gene17 Causal–Structural Explanation18 Explanatory Unification19 Concluding Remarks. (shrink)

In the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a ‘system biology disease’. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, (...) but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted drug. (shrink)

Zwart uses Hegel’s dialectical method to develop a dialectical methodology for assessing biology as technoscience during the Anthropocene. In this paper I will evaluate this use of Hegelian dialectics in biology. I will first elaborate the meaning of Hegel’s method of “Dialectics”. This helps me to evaluate Zwart’s dialectical scientific methodology from the perspective of Hegel’s method of “Dialectics” and to evaluate Zwart’s dialectical scientific methodology from the perspective of the praxis of biology. Finally, I will oppose Zwart’s claim that (...) the synthetic cell is an appropriate case study to demonstrate the relevance of dialectics for understanding contemporary biological research. (shrink)