Anya Plutynski

Cancer is a paradigmatic case of a complex causal process; causes of cancer operate at a variety of temporal and spatial scales, and the respects in which these causes act and interact are diverse. There are, for instance, temporal order effects, organizational effects, structural effects, and dynamic relationships between causes operating at different temporal and spatial scales. Because of this complexity, models of cancer initiation and progression often involve deliberate choices to focus on one time scale, one causal pathway, or one aspect of cancer’s dynamics. As in most of biology, modeling cancer involves simplification and idealization. At the same time, theoretical perspectives inform the construction of these models. Such perspectives might involve viewing cancer ‘as’ a genetic disease, metabolic disease, stem cell disease, an infectious disease, or a disease of tissue disorganization. This paper will argue that purportedly competing theoretical views of cancer are not at odds, but can be viewed as mutually informative. Models are most often developed in the service of asking very specific questions, and this requires limiting our view of the phenomena to a specific temporal or spatial scale, a particular cause, or a particular outcome, dynamic, or pattern. Thus, while some models may seem at odds, often they are simply concerned with different questions, or, they are complementary and mutually informative. I hope to bring this case to bear on debates among philosophers of science over perspectivism and realism, as well pluralism about the aims and scope of scientific theory.

Huxley coined the phrase, the “evolutionary synthesis” to refer to the acceptance by a vast majority of biologists in the mid-20th Century of a “synthetic” view of evolution. According to this view, natural selection acting on minor hereditary variation was the primary cause of both adaptive change within populations and major changes, such as speciation and the evolution of higher taxa, such as families and genera. This was, roughly, a synthesis of Mendelian genetics and Darwinian evolutionary theory; it was a demonstration that prior barriers to understanding between various subdisciplines in the life sciences could be removed. The relevance of different domains in biology to one another was established under a common research program. The evolutionary synthesis may be broken down into two periods, the “early” synthesis from 1918 through 1932, and what is more often called the “modern synthesis” from 1936-1947. The authors most commonly associated with the early synthesis are J.B.S. Haldane, R.A. Fisher, and S. Wright. These three figures authored a number of important synthetic advances; first, they demonstrated the compatibility of a Mendelian, particulate theory of inheritance with the results of Biometry, a study of the correlations of measures of traits between relatives. Second, they developed the theoretical framework for evolutionary biology, classical population genetics. This is a family of mathematical models representing evolution as change in genotype frequencies, from one generation to the next, as a product of selection, mutation, migration, and drift, or chance. Third, there was a broader synthesis of population genetics with cytology, genetics, and biochemistry, as well as both empirical and mathematical demonstrations to the effect that very small selective forces acting over a relatively long time were able to generate substantial evolutionary change, a novel and surprising result to many skeptics of Darwinian gradualist views. The later “modern” synthesis is most often identified with the work of Mayr, Dobzhansky and Simpson. There was a major institutional change in biology at this stage, insofar as different subdisciplines formerly housed in different departments, and with different methodologies were united under the same institutional umbrella of “evolutionary biology.” Mayr played an important role as a community architect, in founding the Society for the Study of Evolution, and the journal Evolution, which drew together work in systematics, biogeography, paleontology, and theoretical population genetics.

There is an active research program currently underway, which treats cancer progression as an evolutionary process. This contribution investigates the ways that cancer progression is like and unlike evolution in other contexts. The aim is to take a multi-level perspective on cancer, investigating the levels at which selection may be acting, the unit or target of selection, the relative roles of selection and drift, and the idea that cancer progression may be a by-product of selection at other levels of organization.

Speciation—the origin of new species—has been one of the most active areas of research in evolutionary biology, both during, and since the Modern Synthesis. While the Modern Synthesis certainly shaped research on speciation in significant ways, providing a core framework, and set of categories and methods to work with, the history of work on speciation since the mid-twentieth century is a history of divergence and diversification. This piece traces this divergence, through both theoretical advances, and empirical insights into how different lineages, with different genetics and ecological conditions, are shaped by very different modes of diversification.

Compiled by an archaeologist and philosopher of science, Science at the Frontiers: Perspectives on the History and Philosophy of Science supplements current literature in the history and philosophy of science with essays approaching the traditional problems of the field from new perspectives and highlighting disciplines usually overlooked by the canon. William H. Krieger brings together scientists from a number of disciplines to answer these questions and more in a volume appropriate for both students and academics in the field.

In this article, we argue, first, that there are very different research projects that fall under the heading of “systems biology of cancer.” While they share some general features, they differ in their aims and theoretical commitments. Second, we argue that some explanations in systems biology of cancer are concerned with properties of signaling networks and how they may play an important causal role in patterns of vulnerability to cancer. Further, some systems biological explanations are compelling illustrations of how “top-down” and “bottom-up” approaches to the same phenomena may be integrated.

The modern synthesis in evolutionary biology is taken to be that period in which a consensus developed among biologists about the major causes of evolution, a consensus that informed research in evolutionary biology for at least a half century. As such, it is a particularly fruitful period to consider when reflecting on the meaning and role of chance in evolutionary explanation. Biologists of this period make reference to “chance” and loose cognates of “chance,” such as: “random,” “contingent,” “accidental,” “haphazard,” or “stochastic.” Of course, what an author might mean by “chance” in any specific context varies. In the following, we first offer a historiographical note on the synthesis. Second, we introduce five ways in which synthesis authors spoke about chance. We do not take these to be an exhaustive taxonomy of all possible ways in which chance meaningfully figures in explanations in evolutionary biology. These are simply five common uses of the term by biologists at this period. They will serve to organize our summary of the collected references to chance and the analysis and discussion of the following questions: • What did synthesis authors understand by chance? • How did these authors see chance operating in evolution? • Did their appeals to chance increase or decrease over time during the synthesis? That is, was there a “hardening” of the synthesis, as Gould claimed (1983)?

Population geneticists investigate the conditions for the possibility of evolution. They use mathematical models to describe how natural selection, mutation, migration, and drift may change the genetic constitution of populations of organisms. As such, population genetics serves as the theoretical core of evolutionary biology. This dissertation investigates the conditions for the possibility of population genetics. A history of the conceptual and empirical origins of the discipline is followed by an examination the work of R. A. Fisher and Sewall Wright, two key figures in the history of the discipline. My aim is to gain a better philosophical understanding of the role of mathematical models in biological theory and explanation. ;Only recently have philosophers turned to the study of evolutionary biology as an exemplar of scientific theory and practice. My work differs from much of this recent work in being historical. By examining one particular episode in the history of evolutionary biology, I uncover the different ways in which theoretical population geneticists use models, different aims of scientific explanation, and whether and in what sense it is appropriate to say that evolutionary biology is "unified" or provides "unifying" explanations. ;Morrison has recently claimed that while Fisher and Wright gave us a unified mathematical theory, they offered competing explanations of evolution in populations. She uses this alleged disunity at the level of explanation combined with unity at the level of the mathematical theory to make a case that unification and explanation are often at odds in science. Morrison's assessment rests on two, related assumptions: first, that all explanations are causal, and second, that mathematical theories are not explanatory to the extent that they "leave out the causes." I defend a pluralistic and pragmatic conception of explanation according to which mathematical models may explain, even when they do not provide the causal machinery behind some process. I argue that standard approaches to explanation, and relatedly, to the structure of theory and the role of models in science, need serious reconsideration. There is a diversity of types of understanding sought in the sciences; and in parallel, there is a diversity of types of explanation

Sahotra Sarkar’s Biodiversity and environmental philosophy, An introduction is an important and timely book. The book is unique in that it is genuinely interdisciplinary: Sarkar is not only an observer, but also an active participant in the new field of conservation biology, and so, his book not only reviews the best recent science, but also advances it. The book is thus exemplary of both a naturalized approach to philosophy of science and a scientifically informed approach to environmental ethics. The book has four parts: a defense of biodiversity preservation, a systematic overview of ecological theory as it pertains to conservation, a critical history of conservation biology, and a discussion of how to prioritize places for conservation. Sarkar integrates nicely the normative and scientific aspects of the problem of conservation.

Comprised of essays by top scholars in the field, this volume offers concise overviews of philosophical issues raised by biology. Brings together a team of eminent scholars to explore the philosophical issues raised by biology Addresses traditional and emerging topics, spanning molecular biology and genetics, evolution, developmental biology, immunology, ecology, mind and behaviour, neuroscience, and experimentation Begins with a thorough introduction to the field Goes beyond previous treatments that focused only on evolution to give equal attention to other areas, such as molecular and developmental biology Represents both an authoritative guide to philosophy of biology, and an accessible reference work for anyone seeking to learn about this rapidly-changing field

The recent literature in philosophy of biology has drawn attention to the different sorts of explanations proffered in the biological sciences—we have molecular, biomedical, and evolutionary explanations. Do these explanations all have a common structure or relation that they seek to capture? This paper will answer in the negative. I defend a pluralistic and pragmatic approach to explanation. Using examples from classical population genetics, I argue that formal demonstrations, and even strictly “mathematical truths,” may serve as explanatory in different historical contexts.

In 1968, Motoo Kimura submitted a note to Nature entitled “Evolutionary Rate at the Molecular Level,” in which he proposed what has since become known as the neutral theory of molecular evolution. This is the view that the majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral or nearly neutral alleles. Kimura was not proposing that random drift explains all evolutionary change. He does not challenge the view that natural selection explains adaptive evolution, or, that the vertebrate eye or the tetrapod limb are products of natural selection. Rather, his objection is to “panselectionism’s intrusion into the realm of molecular evolutionary studies”. According to Kimura, most changes at the molecular level from one generation to the next do not affect the fitness of organisms possessing them. King and Jukes (1969) published an article defending the same view in Science, with the radical title, “Non- Darwinian Evolution,” at which point, “the fat was in the fire” (Crow, 1985b). The neutral theory was one of the most controversial theories in biology in the late twentieth century. This chapter will review the debate over the netural theory subsequent to Kimura.

In the past five years, there have been a series of papers in the journal Evolution debating the relative significance of two theories of evolution, a neo-Fisherian and a neo-Wrightian theory, where the neo-Fisherians make explicit appeal to parsimony. My aim in this paper is to determine how we can make sense of such an appeal. One interpretation of parsimony takes it that a theory that contains fewer entities or processes, (however we demarcate these) is more parsimonious. On the account that I defend here, parsimony is a ‘local’ virtue. Scientists’ appeals to parsimony are not necessarily an appeal to a theory’s simplicity in the sense of it’s positing fewer mechanisms. Rather, parsimony may be proxy for greater probability or likelihood. I argue that the neo-Fisherians appeal is best understood on this interpretation. And indeed, if we interpret parsimony as either prior probability or likelihood, then we can make better sense of Coyne et al. argument that Wright’s three phase process operates relatively infrequently.

Biological diversity - or ‘biodiversity’ - is the degree of variation of life within an ecosystem. It is a relatively new topic of study but has grown enormously in recent years. Because of its interdisciplinary nature the very concept of biodiversity is the subject of debate amongst philosophers, biologists, geographers and environmentalists. The Routledge Handbook of Philosophy of Biodiversity is an outstanding reference source to the key topics and debates in this exciting subject. Comprising twenty-three chapters by a team of international contributors the _Handbook_ is divided into six parts: Historical and sociological contexts, focusing on the emergence of the term and early attempts to measure biodiversity _What is biodiversity? _How should biodiversity be defined? How can biodiversity include entities at the edge of its boundaries, including microbial diversity and genetically engineered organisms? _Why protect biodiversity? _What can traditional environmental ethics_ _contribute to biodiversity?_ _Topics covered include anthropocentrism, intrinsic value, and ethical controversies surrounding the economics of biodiversity _Measurement and methodology: _including decision-theory and conservation, the use of indicators for biodiversity, and the changing use of genetics in biodiversity conservation _Social contexts and global justice: _including conservation and community conflicts and biodiversity and cultural values _Biodiversity and other environmental values_: How does biodiversity relate to other values like ecological restoration or ecological sustainability? Essential reading for students and researchers in philosophy, environmental science and environmental studies, and conservation management, it will also be extremely useful to those studying biodiversity in subjects such as biology and geography.

The object of this paper is to reply to Morrison's ([2000]) claim that while ‘structural unity’ was achieved at the level of the mathematical models of population genetics in the early synthesis, there was explanatory disunity. I argue to the contrary, that the early synthesis effected by the founders of theoretical population genetics was unifying and explanatory both. Defending this requires a reconsideration of Morrison's notion of explanation. In Morrison's view, all and only answers to ‘why’ questions which include the ‘cause or mechanism’ for some phenomenon count as explanatory. In my view, mathematical demonstrations that answer ‘how possibly’ and ‘why necessarily’ questions may also count as explanatory. The authors of the synthesis explained how evolution was possible on a Mendelian system of inheritance, answered skepticism about the sufficiency of selection, and thus explained why and how a Darwinian research program was warranted. While today we take many of these claims as obvious, they required argument, and part of the explanatory work of the formal sciences is providing such arguments. Surely, Fisher and Wright had competing views as to the optimal means of generating adaptation. Nevertheless, they had common opponents and a common unifying and explanatory goal that their mathematical demonstrations served. Introduction: Morrison's challenge Fisher v. Wright revisited The early synthesis Conclusion: unification and explanation reconciled.

Speciation is the process by which one or more species arises from a common ancestor, and “macroevolution” refers to patterns and processes at and above the species level – or, transitions in higher taxa, such as new families, phyla or genera. “Macroevolution” is contrasted with “microevolution,” evolutionary change within populations, due to migration, assortative mating, selection, mutation and drift. In the evolutionary synthesis of the 1930’s and 40’s, Haldane , Dobzhansky , Mayr , and Simpson argued that the origin of species and higher taxa were, given the right environmental conditions and sufficient time, the product of the same microevolutionary factors yielding change within populations. Dobzhansky reviewed the evidence from genetics, and argued, “nothing in the known macroevolutionary phenomena would require other than the known genetic principles for causal explanation” . In sum, genetic variation between species was not different in kind from the genetic variation within species. Dobzhansky concluded that one may “reluctantly put an equal sign” between micro- and macroevolution. In this chapter, I review arguments for and against this "neo-Darwinian" consensus on speciation, as well as debates concerning macroevolution and punctuated equilibrium

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.

Debates concerning the character, scope, and warrant of abductive inference have been active since Peirce first proposed that there was a third form of inference, distinct from induction and deduction. Abductive reasoning has been dubbed weak, incoherent, and even nonexistent. Part, at least, of the problem of articulating a clear sense of abductive inference is due to difficulty in interpreting Peirce. Part of the fault must lie with his critics, however. While this article will argue that Peirce indeed left a number of puzzles for interpreters, it will also contend that interpreters should be careful to distinguish discussion of the formal and strictly epistemic question of whether and how abduction is a sound form of inference from discussions of the practical goals of abduction, as Peirce understood them. This article will trace a history of critics and defenders of Peirce’s notion of abduction and discuss how Peirce both fueled the confusion and in fact anticipated and responded to several recurring objections.

In 1966, Richard Levins argued that there are different strategies in model building in population biology. In this paper, I reply to Orzack and Sober’s (1993) critiques of Levins, and argue that his views on modeling strategies apply also in the context of evolutionary genetics. In particular, I argue that there are different ways in which models are used to ask and answer questions about the dynamics of evolutionary change, prospectively and retrospectively, in classical versus molecular evolutionary genetics. Further, I argue that robustness analysis is a tool for, if not confirmation, then something near enough, in this discipline.

This paper uses a number of examples of diverse types and functions of models in evolutionary biology to argue that the demarcation between theory and practice, or "theory model" and "data model," is often difficult to make. It is shown how both mathematical and laboratory models function as plausibility arguments, existence proofs, and refutations in the investigation of questions about the pattern and process of evolutionary history. I consider the consequences of this for the semantic approach to theories and theory confirmation. The paper attempts to reconcile the insights of both critics and advocates of the semantic approach to theories

There are several different ways in which chance affects evolutionary change. That all of these processes are called “random genetic drift” is in part a due to common elements across these different processes, but is also a product of historical borrowing of models and language across different levels of organization in the biological hierarchy. A history of the concept of drift will reveal the variety of contexts in which drift has played an explanatory role in biology, and will shed light on some of the philosophical controversy surrounding whether drift is a cause of evolutionary change.

Fisher’s ‘fundamental theorem of natural selection’ is notoriously abstract, and, no less notoriously, many take it to be false. In this paper, I explicate the theorem, examine the role that it played in Fisher’s general project for biology, and analyze why it was so very fundamental for Fisher. I defend Ewens and Lessard in the view that the theorem is in fact a true theorem if, as Fisher claimed, ‘the terms employed’ are ‘used strictly as defined’. Finally, I explain the role that projects such as Fisher’s play in the progress of scientific inquiry.