Molecular biologists exploit information conveyed by mechanistic models for experimental purposes. In this article, I make sense of this aspect of biological practice by developing Keller’s idea of the distinction between ‘models of’ and ‘models for’. ‘Models of (phenomena)’ should be understood as models representing phenomena and are valuable if they explain phenomena. ‘Models for (manipulating phenomena)’ are new types of material manipulations and are important not because of their explanatory force, but because of the interventionist strategies they afford. This (...) is a distinction between aspects of the same model. In molecular biology, models may be treated either as ‘models of’ or as ‘models for’. By analysing the discovery and characterization of restriction–modification systems and their exploitation for DNA cloning and mapping, I identify the differences between treating a model as a ‘model of’ or as a ‘model for’. These lie in the cognitive disposition of the modeller towards the model: a modeller will look at a model as a ‘model of’ if interested in its explanatory force, or as a ‘model for’ if interested in the material manipulations it can possibly afford. (shrink)

The emerging area of network biology is seeking to provide insights into organizational principles of life. However, despite significant collaborative efforts, there is still typically a weak link between biological and computational scientists and a lack of understanding of the research issues across the disciplines. This results in the use of simple computational techniques of limited potential that are incapable of explaining these complex data. Hence, the danger is that the community might begin to view the topological properties of network (...) data as mere statistics, rather than rich sources of biological information. A further danger is that such views might result in the imposition of scientific doctrines, such as scale-free-centric (on the modeling side) and genome-centric (on the biological side) opinions onto this area. Here, we take a graph-theoretic perspective on protein-protein interaction networks and present a high-level overview of the area, commenting on possible challenges ahead. (shrink)

A view of evolution is presented in this paper (a two paper series), intended as a methodological infrastructure for modeling spatio-cultural systems (the design outline of such a model is presented in paper II). A motivation for the re-articulation of evolution as information dynamics is the phenomenologically discovered prerequisite of embedding a meaning-attributing apparatus in any and all models of spatio-cultural systems. An evolution is construed as the dynamics of a complex system comprised of memory devices, connected in an ordered (...) fashion (not randomly) by information-exchanges. An information-exchange transpires when the recipient system adopts a strategy (a continuum of events) that eventually changes its structure; namely, after the exchange, it contains and conveys different information. These memory devices—sub-systems—are also similarly constructed complex system. Only a part of the information is retained by a system in its physical-memory storage, which eventually loses this function too, when the ability to retrieve a common enough structure is lost. The entire amount of information is a system’s structure of connections (information exchanges); it is contained (apparently stored) dynamically when a system is observed in a temporarily stable state. This temporary permanence—robustness and resilience—is attained dynamically; namely, enabled by changes taking place in its sub-systems and in each of their sub-systems. Therefore, for modeling such a system a multi-layer/multi-scale approach is preferable. It enables the addition and subtraction of an interim scale and the consideration of such a scale as a micro or a macro (thus initiating a maneuver up or down scale) according to an ad-hoc requirement of the model, which imitates an envisaged sub system (called an ‘Inner World’), to which a certain range of decisions is relegated. This dynamics is driven (in time) by dynamically originated information growth, as defined by Shannon; i.e. by the fact that each of certain state transitions have occurred sometime in the past of the system just so and not otherwise, and by the fact that they have occurred in a certain order. Therefore, each ‘history’ and memory retrieval availability of information is unique, and thus can be used to differentiate meanings. Hence, there cannot be a comprehensive solution to the meaning attribution model-design challenge. However, the observation that at the core of each envisaged complex system, moving in time according to a rounded logic, there is an information manipulating device, operating necessarily according to a Boolean logic, can be copied into the design of a model. This observation enables, therefore, the embedding of a specific, locally fitted, meaning attributing device, which is an information manipulating mechanism (it splices/attaches one segment of information to another—its meaning). However, this is just a framework; the actual solution has still to be found locally—for each subject system. Such a solution is demonstrated for the change in location or layout in the Israeli city in paper II. (shrink)

I argue that reconciling nature with human experience requires a new ontology in which nature is refigured as being in and of itself meaningful, thus reconfiguring traditional dualisms and the . But this refiguring of nature entails a method in which nature itself can exhibit its conceptual reconfiguration—otherwise we get caught in various conceptual and methodological problems that surreptitiously reduplicate the problem we are seeking to resolve. I first introduce phenomenology as a methodology fit to this task, then show how (...) life manifests a field in which nature in and of itself exhibits meaningfulness, such that this field can serve as a starting point for this phenomenological project. Finally, I take immunogenesis as an example in which living phenomena can guide insights into the ontology in virtue of which meaning arises in nature. (shrink)

Neutron Therapy: An Experimental System in Radiooncology. The history of the use of neutrons in radiotherapy will be revisited by focusing on the ideas, theories and experiments that led to first clinical studies. For addressing epistemological questions regarding biological effects of fast neutrons, the notion of an “experimental system” is employed and its evolution over time discussed. Taking up the analytical framework of Hans-Jörg Rheinberger, biological effects and the physical instrument “cyclotron” are conceptualized in terms of epistemic and technical objects. (...) It is shown that the epistemic object “biological effects of neutrons” could never reach the status of a technical object and – more strikingly – that the cyclotron itself returned to being an epistemic object in the context of medicine. So there is a misunderstanding of the different roles epistemic and technical objects have to play in the framework of an experimental system. This misunderstanding led to today's highly controversial discussions about the application of neutrons in radiotherapy. (shrink)

Although the interdisciplinary nature of contemporary biological sciences has been addressed by philosophers, historians, and sociologists of science, the different ways in which engineering concepts and methods have been applied in biology have been somewhat neglected. We examine - using the mechanistic philosophy of science as an analytic springboard - the transfer of network methods from engineering to biology through the cases of two biology laboratories operating at the California Institute of Technology. The two laboratories study gene regulatory networks, but (...) in remarkably different ways. The research strategy of the Davidson lab fits squarely into the traditional mechanist philosophy in its aim to decompose and reconstruct, in detail, gene regulatory networks of a chosen model organism. In contrast, the Elowitz lab constructs minimal models that do not attempt to represent any particular naturally evolved genetic circuits. Instead, it studies the principles of gene regulation through a template-based approach that is applicable to any kinds of networks, whether biological or not. We call for the mechanists to consider whether the latter approach can be accommodated by the mechanistic approach, and what kinds of modifications it would imply for the mechanistic paradigm of explanation, if it were to address modelling more generally. (shrink)

The inclusion of the practice of “developing and using models” in the Framework for K-12 Science Education and in the Next Generation Science Standards provides an opportunity for educators to examine the role this practice plays in science and how it can be leveraged in a science classroom. Drawing on conceptions of models in the philosophy of science, we bring forward an agent-based account of models and discuss the implications of this view for enacting modeling in science classrooms. Models, according (...) to this account, can only be understood with respect to the aims and intentions of a cognitive agent, not solely in terms of how they represent phenomena in the world. We present this contrast as a heuristic—models of versus models for—that can be used to help educators notice and interpret how models are positioned in standards, curriculum, and classrooms. (shrink)

Depuis le début de l’expérimentation en biologie, les animaux sont utilisés pour étudier des phénomènes inabordables chez l’homme. Le développement, depuis 1985, de procédures d’inactivation chez la souris de gènes suspects d’un rôle en pathologie humaine a produit des souris dites « modèles de maladies humaines » avec l’implicite d’une identité des processus physiopathologiques entre homme et souris. Le passage du modèle pour au modèle de est discuté dans cet article ainsi que le retour nécessaire à une forme d’expérimentation sur (...) l’homme pour tenir compte des spécificités de ce dernier.Since the beginning of experimentation in biology, animals have been used to study processes that cannot be approached on human beings. The development, since 1985, of techniques aimed at precisely inactivating mice genes suspected to be involved in human diseases has produced mice « model of human diseases », under the implicit assumption of an identity of physio-pathological processes in man and mice. The passage from model for to a model of is discussed in the present paper, along with the compulsory comeback of a kind of experimentation on man, so as to take into account human specificities. (shrink)

Philosophers of science diverge on the question what drives the growth of scientific knowledge. Most of the twentieth century was dominated by the notion that theories propel that growth whereas experiments play secondary roles of operating within the theoretical framework or testing theoretical predictions. New experimentalism, a school of thought pioneered by Ian Hacking in the early 1980s, challenged this view by arguing that theory-free exploratory experimentation may in many cases effectively probe nature and potentially spawn higher evidence-based theories. Because (...) theories are often powerless to envisage workings of complex biological systems, theory-independent experimentation is common in the life sciences. Some such experiments are triggered by compelling observation, others are prompted by innovative techniques or instruments, whereas different investigations query big data to identify regularities and underlying organizing principles. A distinct fourth type of experiments is motivated by a major question. Here I describe two question-guided experimental discoveries in biochemistry: the cyclic adenosine monophosphate mediator of hormone action and the ubiquitin-mediated system of protein degradation. Lacking underlying theories, antecedent data bases, or new techniques, the sole guides of the two discoveries were respective substantial questions. Both research projects were similarly instigated by theory-free exploratory experimentation and continued in alternating phases of results-based interim working hypotheses, their examination by experiment, provisional hypotheses again, and so on. These two cases designate theory-free, question-guided, stepwise biochemical investigations as a distinct subtype of the new experimentalism mode of scientific enquiry. (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 this paper we present a new framework of idealization in biology. We characterize idealizations as a network of counterfactual and hypothetical conditionals that can exhibit different “degrees of contingency”. We use this idea to say that, in departing more or less from the actual world, idealizations can serve numerous epistemic, methodological or heuristic purposes within scientific research. We defend that, in part, this structure explains why idealizations, despite being deformations of reality, are so successful in scientific practice. For illustrative (...) purposes, we provide an example from population genetics, the Wright-Fisher Model. (shrink)

A persistent criticism of radical embodied cognitive science is that it will be impossible to explain “real cognition” without invoking mental representations. This paper provides an account of explicit, real-time thinking of the kind we engage in when we imagine counter-factual situations, remember the past, and plan for the future. We first present a very general non-representational account of explicit thinking, based on pragmatist philosophy of science. We then present a more detailed instantiation of this general account drawing on nonlinear (...) dynamics and ecological psychology. (shrink)

In this paper we present a new framework of idealization in biology. We characterize idealizations as a network of counterfactual and hypothetical conditionals that can exhibit different "degrees of contingency". We use this idea to say that, in departing more or less from the actual world, idealizations can serve numerous epistemic, methodological or heuristic purposes within scientific research. We defend that, in part, this structure explains why idealizations, despite being deformations of reality, are so successful in scientific practice. For illustrative (...) purposes, we provide an example from population genetics, the Wright-Fisher Model. (shrink)

In this paper we present a new framework of idealization in biology. We characterize idealizations as a network of counterfactual and hypothetical conditionals that can exhibit different “degrees of contingency”. We use this idea to say that, in departing more or less from the actual world, idealizations can serve numerous epistemic, methodological or heuristic purposes within scientific research. We defend that, in part, this structure explains why idealizations, despite being deformations of reality, are so successful in scientific practice. For illustrative (...) purposes, we provide an example from population genetics, the Wright-Fisher Model. (shrink)

The aim of this paper is to argue that logic can play an important role in the “toolbox” of molecular biology. We show how biochemical pathways, i.e., transitions from a molecular aggregate to another molecular aggregate, can be viewed as deductive processes. In particular, our logical approach to molecular biology — developed in the form of a natural deduction system — is centered on the notion of Curry-Howard isomorphism, a cornerstone in nineteenth-century proof-theory.

This discussion paper proposes that a meaningful distinction between science and technoscience can be found at the level of the objects of research. Both notions intermingle in the attitudes, intentions, programs and projects of researchers and research institutions—that is, on the side of the subjects of research. But the difference between science and technoscience becomes more explicit when research results are presented in particular settings and when the objects of research are exhibited for the specific interest they hold. When an (...) experiment is presented as scientific evidence which confirms or disconfirms a hypothesis, this agrees with traditional conceptions of science. When organic molecules are presented for their capacity to serve individually as electric wires that carry surprisingly large currents, this would be a hallmark of technoscience. Accordingly, we propose research on the ontology of research objects. The focus on the character and significance of research objects makes this a specifically philosophical project. (shrink)

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine (...) the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.Keywords: Experimental organism; Genetics; Model organism; Modeling; Philosophy of biology; Representation. (shrink)