Cancer is not one, but many diseases, and each is a product of a variety of causes acting at distinct temporal and spatial scales, or ‘‘levels’’ in the biological hierarchy. In part because of this diversity of cancer types and causes, there has been a diversity of models, hypotheses, and explanations of carcinogenesis. However, there is one model of carcinogenesis that seems to have survived the diversification of cancer types: the multi-stage model of carcinogenesis. This paper examines the history of (...) the multistage theory, and uses the theory as a case study in the limits and goals of unification as a theoretical virtue, comparing and contrasting it with ‘‘integrative’’ research. (shrink)

Around 540 million years ago there was a sudden, dramatic adaptive radiation known as the Cambrian Explosion. This event marked the origin of almost all of the phyla (major lineages characterized by fundamental body plans) of animals that would ever live on earth, as well the appearance of many notable features such as rigid skeletons and other hard parts, complex jointed appendages, eyes, and brains. This radical evolutionary event has been a major puzzle for evolutionary biologists since Darwin, and while (...) our understanding of it has recently improved with new fossil finds, richer molecular phylogenies, and better grasp of ecological, evolutionary, and developmental processes generally, unanswered questions remain. In this paper I argue that a basic cognitive toolkit for embodied, object-oriented, spatial cognition (what I call Basic Cognitive Embodiment) is a practical necessity for control of a large, mobile, complexly articulated body in space. This hypothesis allows us to relate the complexification of animal bodies to the complexification of perception, cognition and behavior in a way that can help to fill in gaps in our emerging picture of the Cambrian Explosion, as well as shed light on the deep evolutionary origins of the mind. (shrink)

In earlier work ( Cleland [2001] , [2002]), I sketched an account of the structure and justification of ‘prototypical’ historical natural science that distinguishes it from ‘classical’ experimental science. This article expands upon this work, focusing upon the close connection between explanation and justification in the historical natural sciences. I argue that confirmation and disconfirmation in these fields depends primarily upon the explanatory (versus predictive or retrodictive) success or failure of hypotheses vis-à-vis empirical evidence. The account of historical explanation that (...) I develop is a version of common cause explanation. Common cause explanation has long been vindicated by appealing to the principle of the common cause. Many philosophers of science (e.g., Sober and Tucker) find this principle problematic, however, because they believe that it is either purely methodological or strictly metaphysical. I defend a third possibility: the principle of the common cause derives its justification from a physically pervasive time asymmetry of causation (a.k.a. the asymmetry of overdetermination). I argue that explicating the principle of the common cause in terms of the asymmetry of overdetermination illuminates some otherwise puzzling features of the practices of historical natural scientists. (shrink)

Uniformitarianism is a dual concept. Substantive uniformitarianism (a testable theory of geologic change postulating uniformity of rates or material conditions) is false and stifiqng to hypothesis formation. Methodological uniformitarianism (a procedural principle asserting spatial and temporal invariance of natural laws) belongs to the definition of science and is not unique to genic~~. Methodological uniformitarianism enabled Lyell to exclude the miraculous from geologic explanation; its invocation today is anachronistic since the question of divine intervention is no longer an issue in science. (...) Substantive uniformitarianism, an incorrect theory, should be abandoned. Methodological uniformitarianism, now a superfiuous term, is best confined to the past history of geology. (shrink)

The paper works towards an account of explanatory integration in biology, using as a case study explanations of the evolutionary origin of novelties-a problem requiring the integration of several biological fields and approaches. In contrast to the idea that fields studying lower level phenomena are always more fundamental in explanations, I argue that the particular combination of disciplines and theoretical approaches needed to address a complex biological problem and which among them is explanatorily more fundamental varies with the problem pursued. (...) Solving a complex problem need not require theoretical unification or the stable synthesis of different biological fields, as items of knowledge from traditional disciplines can be related solely for the purposes of a specific problem. Apart from the development of genuine interfield theories, successful integration can be effected by smaller epistemic units (concepts, methods, explanations) being linked. Unification or integration is not an aim in itself, but needed for the aim of solving a particular scientific problem, where the problem's nature determines the kind of intellectual integration required. (shrink)

Reductionism encompasses a set of ontological, epistemological, and methodological claims about the relation of different scientific domains. The basic question of reduction is whether the properties, concepts, explanations, or methods from one scientific domain (typically at higher levels of organization) can be deduced from or explained by the properties, concepts, explanations, or methods from another domain of science (typically one about lower levels of organization). Reduction is germane to a variety of issues in philosophy of science, including the structure of (...) scientific theories, the relations between different scientific disciplines, the nature of explanation, the diversity of methodology, and the very idea of theoretical progress, as well as to numerous topics in metaphysics and philosophy of mind, such as emergence, mereology, and supervenience. (shrink)

Experimental research is commonly held up as the paradigm of "good" science. Although experiment plays many roles in science, its classical role is testing hypotheses in controlled laboratory settings. Historical science is sometimes held to be inferior on the grounds that its hypothesis cannot be tested by controlled laboratory experiments. Using contemporary examples from diverse scientific disciplines, this paper explores differences in practice between historical and experimental research vis-à-vis the testing of hypotheses. It rejects the claim that historical research is (...) epistemically inferior. For as I argue, scientists engage in two very different patterns of evidential reasoning and, although there is overlap, one pattern predominates in historical research and the other pattern predominates in classical experimental research. I show that these different patterns of reasoning are grounded in an objective and remarkably pervasive time asymmetry of nature. (shrink)

Accounting for the evolutionary origins of morphological novelty is one of the core challenges of contemporary evolutionary biology. A successful explanatory framework requires the integration of different biological disciplines, but the relationships between developmental biology and standard evolutionary biology remain contested. There is also disagreement about how to define the concept of evolutionary novelty. These issues were the subjects of a workshop held in November 2009 at the University of Alberta. We report on the discussion and results of this workshop, (...) addressing questions about (i) how to define evolutionary novelty and understand its significance, (ii) how to interpret evolutionary developmental biology as a synthesis and its relation to neo-Darwinian evolutionary theory, and (iii) how to integrate disparate biological approaches in general. (shrink)

Biologists studying complex causal systems typically identify some factors as causes and treat other factors as background conditions. For example, when geneticists explain biological phenomena, they often foreground genes and relegate the cellular milieu to the background. But factors in the milieu are as causally necessary as genes for the production of phenotypic traits, even traits at the molecular level such as amino acid sequences. Gene-centered biology has been criticized on the grounds that because there is parity among causes, the (...) “privileging” of genes reflects a reductionist bias, not an ontological difference. The idea that there is an ontological parity among causes is related to a philosophical puzzle identified by John Stuart Mill: what, other than our interests or biases, could possibly justify identifying some causes as the actual or operative ones, and other causes as mere background? The aim of this paper is to solve this conceptual puzzle and to explain why there is not an ontological parity among genes and the other factors. It turns out that solving this puzzle helps answer a seemingly unrelated philosophical question: what kind of causal generality matters in biology? (shrink)

Focusing primarily on papers and books discussing the evolutionary and systematic interpretation of the Cambrian animal fossils from the Burgess Shale fauna, this paper explores the role of epistemic values in the context of a discipline striving to establish scientific authority within a larger domain of epistemic problems and issues . The focal point of this analysis is the repeated claims by paleontologists that the study of fossils gives their discipline a unique ‘historical dimension’ that makes it possible for them (...) to unravel important aspects of evolution invisible to scientists who study the extant biosphere. The first part of the paper explores the shifting of emphasis in the writings of paleontologists between two strategies that employ opposing views on the classical positivist and physicalist ideal of science. The second part analyzes paleontologists’ claims of privileged access to life’s historical dimension in a situation where a theoretical upheaval occurring independent of the epistemical problem at hand completely shifts the standards for evaluating the legitimacy of various knowledge claims. Though the various strategies employed in defending the privileged historical perspective of paleontology have been disparate and, to an extent contradictory, each impinges on the acceptance of a specific epistemic ideal or set of values and success or failure of each depends on the compatibility of this ideal with the surrounding community of scientists. (shrink)

One of the most interesting challenges facing paleobiologists is explaining the Cambrian explosion, the dramatic appearance of most metazoan animal phyla in the Early Cambrian, and the subsequent stability of these body plans over the ensuing 530 million years. We propose that because phenotypic variation decreases through geologic time, because microRNAs (miRNAs) increase genic precision, by turning an imprecise number of mRNA transcripts into a more precise number of protein molecules, and because miRNAs are continuously being added to metazoan genomes (...) through geologic time, miRNAs might be instrumental in the canalization of development. Further, miRNAs ultimately allow for natural selection to elaborate morphological complexity, because by reducing gene expression variability, miRNAs increase heritability, allowing selection to change characters more effectively. Hence, miRNAs might play an important role in shaping metazoan macroevolution, and might be part of the solution to the Cambrian conundrum. (shrink)

The Burgess Shale, a set of fossil beds containing the exquisitely preserved remains of marine invertebrate organisms from shortly after the Cambrian explosion, was discovered in 1909, and first brought to widespread popular attention by Stephen Jay Gould in his 1989 bestseller Wonderful life: The Burgess Shale and the nature of history. Gould contrasted the initial interpretation of these fossils, in which they were ‘shoehorned’ into modern groups, with the first major reexamination begun in the 1960s, when the creatures were (...) perceived as ‘weird wonders’, possessing unique body plans and unrelated to modern organisms. More recently, a third phase of Burgess Shale studies has arisen, which has not yet been historically examined. This third phase represents a revolutionary new understanding, brought about, I believe, by a change in taxonomic methodology that led to a new perception of the Burgess creatures, and a new way to comprehend their relationships with modern organisms. The adoption of cladistics, and its corollary, the stem group concept, has forged a new understanding of the Burgess Shale … but has it also changed the questions we are allowed to ask about evolution? (shrink)

This paper discusses what it means and what it takes to integrate data in order to acquire new knowledge about biological entities and processes. Maureen O’Malley and Orkun Soyer have pointed to the scientific work involved in data integration as important and distinct from the work required by other forms of integration, such as methodological and explanatory integration, which have been more successful in captivating the attention of philosophers of science. Here I explore what data integration involves in more detail (...) and with a focus on the role of data-sharing tools, like online databases, in facilitating this process; and I point to the philosophical implications of focusing on data as a unit of analysis. I then analyse three cases of data integration in the field of plant science, each of which highlights a different mode of integration: inter-level integration, which involves data documenting different features of the same species, aims to acquire an interdisciplinary understanding of organisms as complex wholes and is exemplified by research on Arabidopsis thaliana; cross-species integration, which involves data acquired on different species, aims to understand plant biology in all its different manifestations and is exemplified by research on Miscanthus giganteus; and translational integration, which involves data acquired from sources within as well as outside academia, aims at the provision of interventions to improve human health and is exemplified by research on Phytophtora ramorum. Recognising the differences between these efforts sheds light on the dynamics and diverse outcomes of data dissemination and integrative research; and the relations between the social and institutional roles of science, the development of data-sharing infrastructures and the production of scientific knowledge. (shrink)

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to (...) the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system. (shrink)

According to many biologists, explaining the evolution of morphological novelty and behavioral innovation are central endeavors in contemporary evolutionary biology. These endeavors are inherently multidisciplinary but also have involved a high degree of controversy. One key source of controversy is the definitional diversity associated with the concept of evolutionary novelty, which can lead to contradictory claims (a novel trait according to one definition is not a novel trait according to another). We argue that this diversity should be interpreted in light (...) of a different epistemic role played by the concept of evolutionary novelty—the structuring of a problem space or setting of an explanatory agenda—rather than the concept’s capacity to categorize traits as novel. This distinctive role is consistent with the definitional diversity and shows that the concept of novelty benefits ongoing investigation by focusing attention on answering different questions related to comprehending the origins of novelty. A review of recent theoretical and empirical work on evolutionary novelty confirms this interpretation. (shrink)

The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models—which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical (...) equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena, where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism’s ability to respond to perturbations. I offer general conclusions for philosophical accounts of explanation. (shrink)

Chronobiology, especially the study of circadian rhythms, provides a model scientific field in which philosophers can study how investigators from a variety of disciplines working at different levels of organization are each contributing to a multi-level account of the responsible mechanism. I focus on how the framework of mechanistic explanation integrates research designed to decompose the mechanism with efforts directed at recomposition that relies especially on computation models. I also examine how recently the integration has extended beyond basic research to (...) the processes through which the disruption of circadian rhythms contributes to disease, including various forms of cancer. Understanding these linkages has been facilitated by discoveries about how circadian mechanisms interact with mechanisms involved in other physiological processes, including the cell cycle and the immune system. (shrink)

The inapplicability of variations on theory reduction in the context of genetics and their irrelevance to ongoing research has led to an anti-reductionist consensus in philosophy of biology. One response to this situation is to focus on forms of reductive explanation that better correspond to actual scientific reasoning (e.g. part–whole relations). Working from this perspective, we explore three different aspects (intrinsicality, fundamentality, and temporality) that arise from distinct facets of reductive explanation: composition and causation. Concentrating on these aspects generates new (...) forms of reductive explanation and conditions for their success or failure in biology and other sciences. This analysis is illustrated using the case of protein folding in molecular biology, which demonstrates its applicability and relevance, as well as illuminating the complexity of reductive reasoning in a specific biological context. (shrink)

What gets integrated in integrative scientific practices has been a topic of much discussion. Traditional views focus on theories and explanations, with ideas of reduction and unification dominating the conversation. More recent ideas focus on disciplines, fields, or specialties; models, mechanisms, or methods; phenomena, problems. How integration works looks different on each of these views since the objects of integration are ontologically and epistemically various: statements, boundary conditions, practices, protocols, methods, variables, parameters, domains, laboratories, and questions all have their own (...) structures, functions and logics. I focus on one particular kind of scientific practice, integration of “approaches” in the context of a research system operating on a special kind of “platform.” Rather than trace a network of interactions among people, practices, and theoretical entities to be integrated, in this essay I focus on the work of a single investigator, David Wake. I describe Wake’s practice of integrative evolutionary biology and how his integration of approaches among biological specialties worked in tandem with his development of the salamanders as a model taxon, which he used as a platform to solve, re-work and update problems that would not have been solved so well by non-integrative approaches. The larger goal of the project to which this paper contributes is a counter-narrative to the story of 20th century life sciences as the rise and march of the model organisms and decline of natural history. (shrink)

It is a common complaint that antireductionist arguments are primarily negative. Here I describe an alternative nonreductionist epistemology based on considerations taken from multidisciplinary research in biology. The core of this framework consists in seeing investigation as coordinated around sets of problems (problem agendas) that have associated criteria of explanatory adequacy. These ideas are developed in a case study, the explanation of evolutionary innovations and novelties, which demonstrates the applicability and fruitfulness of this nonreductionist epistemological perspective. This account also bears (...) on questions of conceptual change and theory structure in philosophy of science. †To contact the author, please write to: Department of Philosophy, University of Minnesota, 831 Heller Hall, 271 19th Ave. S., Minneapolis, MN 55455; e‐mail: [email protected]. (shrink)

Why has it been so difficult to integrate paleontology and mainstream evolutionary biology? Two common answers are: (1) the two fields have fundamentally different aims, and (2) the tensions arise out of disciplinary squabbles for funding and prestige. This paper examines the role of fossil data in phylogeny reconstruction in order to assess these two explanations. I argue that while cladistics has provided a framework within which to integrate fossil character data, the stratigraphic (temporal) component of fossil data has been (...) harder to integrate. A close examination of how fossil data have been used in phylogeny reconstruction suggests that neither explanation is adequate. While some of the tensions between the fields may be intellectual turf wars, the second explanation downplays the genuine difficulty of combining the distinctive data of the two fields. Furthermore, it is simply not the case that the two fields pursue completely distinct aims. Systematists do disagree about precisely how to represent phylogeny (e.g., minimalist cladograms or trees with varying levels of detail) but given that every tree presupposes a pattern of branching (a cladogram), these aims are not completely distinct. The central problem has been developing methods that allow scientists to incorporate the distinctive bodies of data generated by these two fields. Further case studies will be required to determine if this explanation holds for other areas of interaction between paleontology and neontology. (shrink)