Genetic studies of diseases

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory.     

English engineer John Smeaton's experimental method(s): Optimisation,hypothesis testing and exploratory experimentation

In this paper I provide a detailed account of eighteenth-century engineer John Smeaton's experimental methods, with the aim of bringing our understanding of his work into line with recent research in the history and philosophy of science. Starting from his use of the technique of parameter variation, I identify three distinct methodological aims in the research he carried out on waterwheels, windmills and hydraulic mortars. These aims are: optimisation, hypothesis testing and maxim generation. The main claim of this paper is that Smeaton did more than merely improve engineering methods by systematising earlier artisanal approaches, which is the classic view of Smeaton's method developed by historians of technology in the 1990s. I argue instead that his approach bridged the divide between science and technology, by integrating both hypothesis testing and exploratory experimentation. This is borne out, in particular, by the way that Smeaton emphasised the exploratory side of the work he published in the Philosophical Transactions, in contrast to his account of the construction of the Eddystone lighthouse, which was aimed at a broader, non-specialist public. I contribute to recent research on exploratory experimentation by showing – in line with other work on this topic – that exploratory experimentation is not incompatible with hypothesis testing. This new perspective on Smeaton's method will hopefully lead to further research and new insights into the relation between science and technology at the start of the Industrial Revolution.     

The many encounters of Thomas Kuhn and French epistemology

The work of Thomas Kuhn has been very influential in Anglo-American philosophy of science and it is claimed that it has initiated the historical turn. Although this might be the case for English speaking countries, in France an historical approach has always been the rule. This article aims to investigate the similarities and differences between Kuhn and French philosophy of science or ‘French epistemology’. The first part will argue that he is influenced by French epistemologists, but by lesser known authors than often thought. The second part focuses on the reactions of French epistemologists on Kuhn’s work, which were often very critical. It is argued that behind some superficial similarities there are deep disagreements between Kuhn and French epistemology. This is finally shown by a brief comparison with the reaction of more recent French philosophers of science, who distance themselves from French epistemology and are more positive about Kuhn. Based on these diverse appreciations of Kuhn, a typology of the different positions within the philosophy of science is suggested.     

Kant and the scope of analogy in the life sciences

In the present paper I investigate the role that analogy plays in eighteenth-century biology and in Kant's philosophy of biology. I will argue that according to Kant, biology, as it was practiced in the eighteenth century, is fundamentally based on analogical reflection. However, precisely because biology is based on analogical reflection, biology cannot be a proper science. I provide two arguments for this interpretation. First, I argue that although analogical reflection is, according to Kant, necessary to comprehend the nature of organisms, it is also necessarily insufficient to fully comprehend the nature of organisms. The upshot of this argument is that for Kant our understanding of organisms is necessarily limited. Second, I argue that Kant did not take biology to be a proper science because biology was based on analogical arguments. I show that Kant stemmed from a philosophical tradition that did not assign analogical arguments an important justificatory role in natural science. Analogy, according to this conception, does not provide us with apodictically certain cognition. Hence, sciences based on analogical arguments cannot constitute proper sciences.     

Creativity,conservativeness & the social epistemology of science

The special issue Creativity, Conservatism & the Social Epistemology of Science collects six papers which, in different ways, tackle 'promotion questions' concerning scientific communities: which features shape those communities, and which might be changed to promote the kinds of epistemic features we desire. In this introduction, I connect these discussions with more traditional debate in the philosophy of science and reflect upon the notions of creativity which underwrite the papers.     

Collaborative explanation and biological mechanisms

This paper motivates and outlines a new account of scientific explanation, which I term ‘collaborative explanation.’ My approach is pluralist: I do not claim that all scientific explanations are collaborative, but only that some important scientific explanations are—notably those of complex organic processes like development. Collaborative explanation is closely related to what philosophers of biology term ‘mechanistic explanation’ (e.g., Machamer et al., Craver, 2007). I begin with minimal conditions for mechanisms: complexity, causality, and multilevel structure. Different accounts of mechanistic explanation interpret and prioritize these conditions in different ways. This framework reveals two distinct varieties of mechanistic explanation: causal and constitutive. The two have heretofore been conflated, with philosophical discussion focusing on the former. This paper addresses the imbalance, using a case study of modeling practices in Systems Biology to reveals key features of constitutive mechanistic explanation. I then propose an analysis of this variety of mechanistic explanation, in terms of collaborative concepts, and sketch the outlines of a general theory of collaborative explanation. I conclude with some reflections on the connection between this variety of explanation and social aspects of scientific practice.     

The Garching nuclear egg: Teaching contemporary history beyond the linguistic turn

In my paper I argue for mobilising recent material heritage at universities in teaching history of contemporary science. Getting your hands dirty in the messy worlds of the laboratory and the storage room, and getting entangled with the commemorative practices of scientists and technicians does not belong to the common experiences of students in history and philosophy of science. Despite the recent material turn in cultural studies, students’ engagement with the material world often remains a linguistic exercise, extending at most to an excursion to the sanitised and academically encultured world of the museum exhibit.I contrast this approach by drawing on experiences of taking students to the Atomei, Germany’s oldest research reactor at the Garching campus of the Munich University of Technology. Decommissioned since 2000, the installation and its history are still controlled by scientists. Studying contemporary laboratories and their materiality has so far been the domain of sociologists and ethnographers. I argue for opening these spaces to historians of science and engaging with the ‘unfinished’ material world of contemporary science. Taking the material seriously beyond the linguistic turn and asking students to explore laboratories and other sites of knowledge production challenges existing histories and historiographies. By exploring local university departments and their recent histories through their material heritage, we can observe everyday science and confront scientists and technicians’ cultures with those of historians’. By engaging with recent material heritage as historians and archivists, students can make an important contribution to enhancing the awareness about this heritage, its implications for history writing, as well as its documentation and preservation.     

Hermeneutic strategies in Gerd Buchdahl’s Kantian philosophy of science

Gerd Buchdahl’s international reputation rests on his masterly writings on Kant. In them he showed how Kant transformed the philosophical problems of his predecessors and he minutely investigated the ways in which Kant related his critical philosophy to the contents and methods of natural science. Less well known, if only because in large part unpublished, are the writings in which Buchdahl elaborated his own views on the methods and status of the sciences. In this paper I examine the roles of hermeneutics in Buchdahl’s reconstruction of Kant’s philosophical system and in his own ‘transcendental methodological’ approach to the philosophy of science. The first section looks at Buchdahl’s views on the theory and practice of historical interpretation and at the Husserlian hermeneutic scheme of reduction and realisation that he used in his later accounts of the philosophies of science of Kant and himself. The second section concentrates on Buchdahl’s treatment of the grounds of science in Kant; and the third on the hermeneutic strategies Buchdahl employed in articulating and justifying his own views. The paper closes with reflections on the impact and importance of Buchdahl’s interpretation of Kant’s critical philosophy in relation to the sciences and of his own hermeneutically based philosophy of science.     

Will the real scientists please stand up? dead ends and live issues in the explanation of scientific knowledge

Reflection on the method of science has become increasingly thinner since Kant. If there's any upshot of that part of modern philosophy, it's that the scientists didn't have a secret. There isn't something there that's either effable or ineffable. To understand how they do what they do is pretty much like understanding how any other bunch of skilled craftsmen do what they do. Kuhn's reduction of philosophy of science to sociology of science doesn't point to an ineffable secret of success; it leaves us without the notion of the secret of success.Relativism is the view that every belief on a certain topic, or perhaps, about any topic, is as good as every other. No one holds this view. Except for the occasional co-operative freshman, one cannot find anybody who says that two incompatible opinions on an important topic are equally good. The philosophers who get called ‘relativists’ are those who say that the grounds for choosing between such opinions are less algorithmic than had been thought.Richard Rorty1,2     

From Cutting Nature at Its Joints to Measuring It: New Kinds and New Kinds of People in Biology

In the received version of the development of science, natural kinds are established in the preliminary stages (natural history) and made more precise by measurement (exact science). By examining the move from nineteenth- to twentieth-century biology, this paper unpacks the notion of species as ‘natural kinds’ and grounds for discourse, questioning received notions about both kinds and species. Life sciences in the nineteenth century established several ‘monster-barring’ techniques to block disputes about the precise definition of species. Counterintuitively, precision and definition brought dispute and disrupted exchange. Thus, any attempt to add precision was doomed to failure. By intervening and measuring, the new experimental biology dislocated the established links between natural kinds and kinds of people and institutions. New kinds were built in new places. They were made to measure from the very start. This paper ends by claiming that there was no long-standing ‘species problem’ in the history of biology. That problem is a later construction of the ‘modern synthesis’, well after the disruption of ‘kinds’ and kinds of people. Only then would definitions and precision matter. A new, non-linguistic, take on the incommensurability thesis is hinted at.     

Analogical reflection as a source for the science of life: Kant and the possibility of the biological sciences

In contrast to the previously widespread view that Kant's work was largely in dialogue with the physical sciences, recent scholarship has highlighted Kant's interest in and contributions to the life sciences. Scholars are now investigating the extent to which Kant appealed to and incorporated insights from the life sciences and considering the ways he may have contributed to a new conception of living beings. The scholarship remains, however, divided in its interest: historians of science are concerned with the content of Kant's claims, and the ways in which they may or may not have contributed to the emerging science of life, while historians of philosophy focus on the systematic justifications for Kant's claims, e.g., the methodological and theoretical underpinnings of Kant's statement that living beings are mechanically inexplicable. My aim in this paper is to bring together these two strands of scholarship into dialogue by showing how Kant's methodological concerns (specifically, his notion of reflective judgment) contributed to his conception of living beings and to the ontological concern with life as a distinctive object of study. I argue that although Kant's explicit statement was that biology could not be a science, his implicit and more fundamental claim was that the study of living beings necessitates a distinctive mode of thought, a mode that is essentially analogical. I consider the implications of this view, and argue that it is by developing a new methodology for grasping organized beings that Kant makes his most important contribution to the new science of life.     

De-synthesizing the relative a priori

This paper considers the question whether the notion of the relative apriori, central to Michael Friedman’s transcendentalist programme for philosophy of science, is available also to philosophers who reject appeals to a synthetic a priori. After tracing the rediscovery of the relative a priori and delineating its potential, the question is considered whether Friedman’s arguments against Quinean naturalism and Carnap’s attenuated logicism tell against a conception of philosophy as scientific metatheory that combines logical and empirical inquiries. Finding an opening here it is argued that this conception can also help itself to the notion of a relative a priori which, it is agreed, is central to historically informed theorising about science.     

A pragmatic account of mechanistic artifact explanation

A mechanistic artifact explanation is an explanation that accounts for an artifact behavior by describing the underlying mechanism. The article shows that there are different kinds of mechanistic artifact explanation: top-down and bottom-up explanation, and I also distinguish between less and more inclusive top-down explanations. To illustrate these different kinds of explanation, the behavior of a simple, fictional artifact is explained in different ways. I defend that which explanation is ideal, depends on pragmatic factors (e.g., the background knowledge of the explainee and the specific goal for which the explanation will be used). For each kind of explanation, the situations, goals and interests for which it is most appropriate are specified, resulting in a pragmatic theory of mechanistic artifact explanation. This theory is compared to Jeroen de Ridder’s account of the pragmatics of mechanistic artifact explanation.     

Biologist Edwin Grant Conklin and the idea of the religious direction of human evolution in the early 1920s

Edwin Grant Conklin, renowned US embryologist and evolutionary popularizer, publicly advocated a social vision of evolution that intertwined science and modernist Protestant theology in the early 1920s. The moral prestige of professional science in American culture — along with Conklin’s own elite scientific status — diverted attention from the frequency with which his work crossed boundaries between natural science, religion and philosophy. Writing for broad audiences, Conklin was one of the most significant of the religious and modernist biological scientists whose rhetoric went well beyond simply claiming that certain kinds of religion were amenable to evolutionary science; he instead incorporated religion itself into evolution's broadest workings. A sampling of Conklin's widely-resonant discourse suggests that there was substantially more to the religion-evolution story in the 1920s US than many creationist-centred narratives of the era imply.     

The National Science Foundation and philosophy of science's withdrawal from social concerns

At some point during the 1950s, mainstream American philosophy of science began increasingly to avoid questions about the role of non-cognitive values in science and, accordingly, increasingly to avoid active engagement with social, political and moral concerns. Such questions and engagement eventually ceased to be part of the mainstream. Here we show that the eventual dominance of ‘value-free’ philosophy of science can be attributed, at least in part, to the policies of the U.S. National Science Foundation's “History and Philosophy of Science” sub-program. In turn, the sub-program's policies were set by logical empiricists who espoused value-free philosophy of science; these philosophers' actions, we also point out, fit a broad pattern, one in which analytic philosophers used institutional control to marginalize rival approaches to philosophy. We go on to draw on existing knowledge of this pattern to suggest two further, similar, contributors to the withdrawal from value-laden philosophy of science, namely decisions by the editors of Philosophy of Science and by the editors of The Journal of Philosophy. Political climate was, we argue, at most an indirect contributor to the withdrawal and was neither a factor that decided whether it occurred nor one that was sufficient to bring it about. Moreover, we argue that the actions at the National Science Foundation went beyond what was required by its senior administrators and are better viewed as part of what drove, rather than as what was being driven by, the adoption of logical empiricism by the philosophy of science community.     

Using computational models to discover and understand mechanisms

Areas of biology such as cell and molecular biology have been dominated by research directed at constructing mechanistic explanations that identify parts and operations that when organized appropriately are responsible for the various phenomena they investigate. Increasingly the mechanisms hypothesized involve non-sequential organization of non-linear operations and so exceed the ability of researchers to mentally rehearse their behavior. Accordingly, scientists rely on tools of computational modeling and dynamical systems theory in advancing dynamic mechanistic explanations. Using circadian rhythm research as an exemplar, this paper explores the variety of roles computational modeling is playing. They serve not just to determine whether the mechanism will produce the desired behavior, but in the discovery process of hypothesizing mechanisms and in understanding why proposed mechanisms behave as they do.     

Biomimetic actuators: where technology and cell biology merge

The structural and functional analysis of biological macromolecules has reached a level of resolution that allows mechanistic interpretations of molecular action, giving rise to the view of enzymes as molecular machines. This machine analogy is not merely metaphorical, as bio-analogous molecular machines actually are being used as motors in the fields of nanotechnology and robotics. As the borderline between molecular cell biology and technology blurs, developments in the engineering and material sciences become increasingly instructive sources of models and concepts for biologists. In this review, we provide a--necessarily selective--summary of recent progress in the usage of biological and biomimetic materials as actuators in artificial environments, focussing on motors built from DNA, classical cellular motor systems (tubulin/kinesin, actin/myosin), the rotary motor F1F0-ATPase and protein-based 'smart' materials.