Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system initiated by a single genetic mutation which results in the oncogenic fusion protein Bcr-Abl. Untreated, patients pass through different phases of the disease beginning with the rather asymptomatic chronic phase and ultimately culminating into blast crisis, an acute leukemia resembling phase with a very high mortality. Although many processes underlying the chronic phase are well understood, the exact mechanisms of disease progression to blast crisis are not yet revealed. In (...) this paper we develop a mathematical model of CML based on causal Bayesian networks in order to study possible disease progression mechanisms. Our results indicate that an increase of Bcr-Abl levels alone is not sufficient to explain the phenotype of blast crisis and that secondary changes such as additional mutations are necessary to explain disease progression and the poor therapy response of patients in blast crisis. (shrink)

Explanations in the life sciences frequently involve presenting a model of the mechanism taken to be responsible for a given phenomenon. Such explanations depart in numerous ways from nomological explanations commonly presented in philosophy of science. This paper focuses on three sorts of differences. First, scientists who develop mechanistic explanations are not limited to linguistic representations and logical inference; they frequently employ diagrams to characterize mechanisms and simulations to reason about them. Thus, the epistemic resources for presenting mechanistic explanations are (...) considerably richer than those suggested by a nomological framework. Second, the fact that mechanisms involve organized systems of component parts and operations provides direction to both the discovery and testing of mechanistic explanations. Finally, models of mechanisms are developed for specific exemplars and are not represented in terms of universally quantified statements. Generalization involves investigating both the similarity of new exemplars to those already studied and the variations between them. (shrink)

In this paper I argue that constitutive relevance relations in mechanisms behave like a special kind of causal relation in at least one important respect: Under suitable circumstances constitutive relevance relations produce the Markov factorization. Based on this observation one may wonder whether standard methods for causal discovery could be fruitfully applied to uncover constitutive relevance relations. This paper is intended as a first step into this new area of philosophical research. I investigate to what extent the PC algorithm, originally (...) developed for causal search, can be used for constitutive relevance discovery. I also discuss possible objections and certain limitations of a constitutive relevance discovery procedure based on PC. (shrink)

Using Gebharter’s representation, we consider aspects of the problem of discovering the structure of unmeasured submechanisms when the variables in those submechanisms have not been measured. Exploiting an early insight of Sober’s, we provide a correct algorithm for identifying latent, endogenous structure—submechanisms—for a restricted class of structures. The algorithm can be merged with other methods for discovering causal relations among unmeasured variables, and feedback relations between measured variables and unobserved causes can sometimes be learned.

This paper examines the adequacy of causal graph theory as a tool for modeling biological phenomena and formalizing biological explanations. I point out that the causal graph approach reaches it limits when it comes to modeling biological phenomena that involve complex spatial and structural relations. Using a case study from molecular biology, DNA-binding and -recognition of proteins, I argue that causal graph models fail to adequately represent and explain causal phenomena in this field. The inadequacy of these models is due (...) to their failure to include relevant spatial and structural information in a way that does not render the model non-explanatory, unmanageable, or inconsistent with basic assumptions of causal graph theory. (shrink)

We start this paper by arguing that causality should, in analogy with force in Newtonian physics, be understood as a theoretical concept that is not explicated by a single definition, but by the axioms of a theory. Such an understanding of causality implicitly underlies the well-known theory of causal nets and has been explicitly promoted by Glymour. In this paper we investigate the explanatory warrant and empirical content of TCN. We sketch how the assumption of directed cause–effect relations can be (...) philosophically justified by an inference to the best explanation. We then ask whether the explanations provided by TCN are merely post-facto or have independently testable empirical content. To answer this question we develop a fine-grained axiomatization of TCN, including a distinction of different kinds of faithfulness. A number of theorems show that although the core axioms of TCN are empirically empty, extended versions of TCN have successively increasing empirical content. (shrink)

Mechanism is undoubtedly a causal concept, in the sense that ordinary definitions and philosophical analyses explicate the concept in terms of other causal concepts such as production and interaction. Given this fact, many philosophers have supposed that analyses of the concept of mechanism, while they might appeal to philosophical theories about the nature of causation, could do little to inform such theories. On the other hand, methods of causal inference and explanation appeal to mechanisms. Discovering a mechanism is the gold (...) standard for establishing and explaining causal connections. This fact suggests that it might be possible to provide an analysis of causation that appeals to mechanisms. (shrink)

This monograph looks at causal nets from a philosophical point of view. The author shows that one can build a general philosophical theory of causation on the basis of the causal nets framework that can be fruitfully used to shed new light on philosophical issues. Coverage includes both a theoretical as well as application-oriented approach to the subject. The author first counters David Hume’s challenge about whether causation is something ontologically real. The idea behind this is that good metaphysical concepts (...) should behave analogously to good theoretical concepts in scientific theories. In the process, the author offers support for the theory of causal nets as indeed being a correct theory of causation. Next, the book offers an application-oriented approach to the subject. The author shows that causal nets can investigate philosophical issues related to causation. He does this by means of two exemplary applications. The first consists of an evaluation of Jim Woodward’s interventionist theory of causation. The second offers a contribution to the new mechanist debate. Introductory chapters outline all the formal basics required. This helps make the book useful for those who are not familiar with causal nets, but interested in causation or in tools for the investigation of philosophical issues related to causation. (shrink)

There are a variety of topics in the philosophy of science that need to be rethought, in varying degrees, after one pays careful attention to the ways in which computer simulations are used in the sciences. There are a number of conceptual issues internal to the practice of computer simulation that can benefit from the attention of philosophers. This essay surveys some of the recent literature on simulation from the perspective of the philosophy of science and argues that philosophers have (...) a lot to learn by paying closer attention to the practice of simulation. (shrink)

The Recursive Bayesian Net (RBN) formalism was originally developed for modelling nested causal relationships. In this paper we argue that the formalism can also be applied to modelling the hierarchical structure of mechanisms. The resulting network contains quantitative information about probabilities, as well as qualitative information about mechanistic structure and causal relations. Since information about probabilities, mechanisms and causal relations is vital for prediction, explanation and control respectively, an RBN can be applied to all these tasks. We show in particular (...) how a simple two-level RBN can be used to model a mechanism in cancer science. The higher level of our model contains variables at the clinical level, while the lower level maps the structure of the cell's mechanism for apoptosis. (shrink)

Modeling mechanisms is central to the biological sciences – for purposes of explanation, prediction, extrapolation, and manipulation. A closer look at the philosophical literature reveals that mechanisms are predominantly modeled in a purely qualitative way. That is, mechanistic models are conceived of as representing how certain entities and activities are spatially and temporally organized so that they bring about the behavior of the mechanism in question. Although this adequately characterizes how mechanisms are represented in biology textbooks, contemporary biological research practice (...) shows the need for quantitative, probabilistic models of mechanisms, too. In this paper we argue that the formal framework of causal graph theory is well-suited to provide us with models of biological mechanisms that incorporate quantitative and probabilistic information. On the ba-sis of an example from contemporary biological practice, namely feedback regulation of fatty acid biosynthesis in Brassica napus, we show that causal graph theoretical models can account for feedback as well as for the multi-level character of mechanisms. However, we do not claim that causal graph theoretical representations of mechanisms are advantageous in all respects and should replace common qualitative models. Rather, we endorse the more balanced view that causal graph theoretical models of mechanisms are useful for some purposes, while being insufficient for others. (shrink)

Using as case studies two early diagrams that represent mechanisms of the cell division cycle, we aim to extend prior philosophical analyses of the roles of diagrams in scientific reasoning, and specifically their role in biological reasoning. The diagrams we discuss are, in practice, integral and indispensible elements of reasoning from experimental data about the cell division cycle to mathematical models of the cycle’s molecular mechanisms. In accordance with prior analyses, the diagrams provide functional explanations of the cell cycle and (...) facilitate the construction of mathematical models of the cell cycle. But, extending beyond those analyses, we show how diagrams facilitate the construction of mathematical models, and we argue that the diagrams permit nomological explanations of the cell cycle. We further argue that what makes diagrams integral and indispensible for explanation and model construction is their nature as locality aids: they group together information that is to be used together in a way that sentential representations do not. (shrink)

book reveiw van boek met gelijknamige titel van Judea Pearl.

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

We have examined only a few of the basic questions about causal inference that result from Reichenbach's two principles. We have not considered what happens when the probability distribution is a mixture of distributions from different causal structures, or how unmeasured common causes can be detected, or what inferences can reliably be drawn about causal relations among unmeasured variables, or the exact advantages that experimental control offers. A good deal is known about these questions, and there is a good deal (...) more to find out. (shrink)

In this paper I offer an analysis of causation based upon a theory of mechanisms-complex systems whose internal parts interact to produce a system's external behavior. I argue that all but the fundamental laws of physics can be explained by reference to mechanisms. Mechanisms provide an epistemologically unproblematic way to explain the necessity which is often taken to distinguish laws from other generalizations. This account of necessity leads to a theory of causation according to which events are causally related when (...) there is a mechanism that connects them. I present reasons why the lack of an account of fundamental physical causation does not undermine the mechanical account. (shrink)

In this article I tackle the question of how the hierarchical order of mechanisms can be represented within a causal graph framework. I illustrate an answer to this question proposed by Casini, Illari, Russo, and Williamson and provide an example that their formalism does not support two important features of nested mechanisms: (i) a mechanism’s submechanisms are typically causally interacting with other parts of said mechanism, and (ii) intervening in some of a mechanism’s parts should have some influence on the (...) phenomena the mechanism brings about. Finally, I sketch an alternative approach taking (i) and (ii) into account. (shrink)

Mechanisms play an important role in many sciences when it comes to questions concerning explanation, prediction, and control. Answering such questions in a quantitative way requires a formal represention of mechanisms. Gebharter (2014) suggests to represent mechanisms by means of one or more causal arrows of an acyclic causal net. In this paper we show how this approach can be extended in such a way that it can also be fruitfully applied to mechanisms featuring causal feedback.

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)

The Recursive Bayesian Net formalism was originally developed for modelling nested causal relationships. In this paper we argue that the formalism can also be applied to modelling the hierarchical structure of mechanisms. The resulting network contains quantitative information about probabilities, as well as qualitative information about mechanistic structure and causal relations. Since information about probabilities, mechanisms and causal relations is vital for prediction, explanation and control respectively, an RBN can be applied to all these tasks. We show in particular how (...) a simple two-level RBN can be used to model a mechanism in cancer science. The higher level of our model contains variables at the clinical level, while the lower level maps the structure of the cell's mechanism for apoptosis. (shrink)

Carl F. Craver investigates what we are doing when we use neuroscience to explain what's going on in the brain. When does an explanation succeed and when does it fail? Craver offers explicit standards for successful explanation of the workings of the brain, on the basis of a systematic view about what neuroscientific explanations are.