This authored monograph introduces a genuinely theoretical approach to biology. Starting point is the investigation of empirical biological scaling including their variability, which is found in the literature, e.g. allometric relationships, fractals, etc. The book then analyzes two different aspects of biological time: first, a supplementary temporal dimension to accommodate proper biological rhythms; secondly, the concepts of protension and retention as a means of local organization of time in living organisms. Moreover, the book investigates the role of symmetry in biology, (...) in view of its ubiquitous importance in physics. In relation with the notion of extended critical transitions, the book proposes that organisms and their evolution can be characterized by continued symmetry changes, which accounts for the irreducibility of their historicity and variability. The authors also introduce the concept of anti-entropy as a measure for the potential of variability, being equally understood as alterations in symmetry. By this, the book provides a mathematical account of Gould's analysis of phenotypic complexity with respect to biological evolution. The target audience primarily comprises researchers interested in new theoretical approaches to biology, from physical, biological or philosophical backgrounds, but the book may also be beneficial for graduate students who want to enter this field. (shrink)

Dynamics of Complex Systems is the first text describing the modern unified study of complex systems. It is designed for upper-undergraduate/beginning graduate-level students, and covers a broad range of applications in a broad array of disciplines. A central goal of this text is to develop models and modeling techniques that are useful when applied to all complex systems. This is done by adopting both analytic tools, including statistical mechanics and stochastic dynamics, and computer simulation techniques, such as cellular automata and (...) Monte Carlo. In four sets of paired, self-contained chapters, Yaneer Bar-Yam discusses complex systems in the context of neural networks, protein folding, living organisms, and finally, human civilization itself. (shrink)

Ontic structural realists hold that structure is all there is, or at least all there is fundamentally. This thesis has proved to be puzzling: What exactly does it say about the relationship between objects and structures? In this article, I look at different ways of articulating ontic structural realism in terms of the relation between structures and objects. I show that objects cannot be reduced to structure, and argue that ontological dependence cannot be used to establish strong forms of structural (...) realism. At the end, I show how a weaker, but controversial, form of structural realism can be articulated on the basis of ontological dependence. (shrink)

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

The somatic mutation theory has been the prevailing paradigm in cancer research for the last 50 years. Its premises are: (1) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations, (2) the default state of cell proliferation in metazoa is quiescence, and (3) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. From this compelling simplicity, an increasingly complicated picture has emerged as more than 100 (...) oncogenes and 30 tumor suppressor genes have been identified. To accommodate this complexity, additional ad hoc explanations have been postulated. After a critical review of the data gathered from this perspective, an alternative research program has been proposed. It is based on the tissue organization field theory, the premises of which are that carcinogenesis represents a problem of tissue organization, comparable to organogenesis, and that proliferation is the default state of all cells. The merits of these competing theories are evaluated herein. BioEssays 26:1097–1107, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The dominant position in Philosophy of Science contends that downward causation is an illusion. Instead, we argue that downward causation doesn’t introduce vicious circles either in physics or in biology. We also question the metaphysical claim that “physical facts fix all the facts.” Downward causation does not imply any contradiction if we reject the assumption of the completeness and the causal closure of the physical world that this assertion contains. We provide an argument for rejecting this assumption. Furthermore, this allows (...) us to reconsider the concept of diachronic emergence. (shrink)

In the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology. Systems biology is best understood as consisting of two streams. One, which we shall call ‘pragmatic systems biology’, emphasises large‐scale molecular interactions; the other, which we shall refer to as ‘systems‐theoretic biology’, emphasises system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems (...) and how causality operates at different levels of organisation. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realisation. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers. BioEssays 27:1270–1276, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology (‘mechanicism’), to the internal workings of a machine-like structure (‘machine mechanism’), or to the causal explanation of a particular phenomenon (‘causal mechanism’). In this paper I trace the conceptual evolution of ‘mechanism’ in the history of biology, and I examine how the three meanings of this term have come to be featured in the philosophy of biology, (...) situating the new ‘mechanismic program’ in this context. I argue that the leading advocates of the mechanismic program (i.e., Craver, Darden, Bechtel, etc.) inadvertently conflate the different senses of ‘mechanism’. Specifically, they all inappropriately endow causal mechanisms with the ontic status of machine mechanisms, and this invariably results in problematic accounts of the role played by mechanism-talk in scientific practice. I suggest that for effective analyses of the concept of mechanism, causal mechanisms need to be distinguished from machine mechanisms, and the new mechanismic program in the philosophy of biology needs to be demarcated from the traditional concerns of mechanistic biology. (shrink)

Biological atomism postulates that all life is composed of elementary and indivisible vital units. The activity of a living organism is thus conceived as the result of the activities and interactions of its elementary constituents, each of which individually already exhibits all the attributes proper to life. This paper surveys some of the key episodes in the history of biological atomism, and situates cell theory within this tradition. The atomistic foundations of cell theory are subsequently dissected and discussed, together with (...) the theory’s conceptual development and eventual consolidation. This paper then examines the major criticisms that have been waged against cell theory, and argues that these too can be interpreted through the prism of biological atomism as attempts to relocate the true biological atom away from the cell to a level of organization above or below it. Overall, biological atomism provides a useful perspective through which to examine the history and philosophy of cell theory, and it also opens up a new way of thinking about the epistemic decomposition of living organisms that significantly departs from the physicochemical reductionism of mechanistic biology. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate the non‐linear, stochastic (...) dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

A common reductionist assumption is that macro-scale behaviors can be described "bottom-up" if only sufficient details about lower-scale processes are available. The view that an "ideal" or "fundamental" physics would be sufficient to explain all macro-scale phenomena has been met with criticism from philosophers of biology. Specifically, scholars have pointed to the impossibility of deducing biological explanations from physical ones, and to the irreducible nature of distinctively biological processes such as gene regulation and evolution. This paper takes a step back (...) in asking whether bottom-up modeling is feasible even when modeling simple physical systems across scales. By comparing examples of multi-scale modeling in physics and biology, we argue that the “tyranny of scales” problem presents a challenge to reductive explanations in both physics and biology. The problem refers to the scale-dependency of physical and biological behaviors that forces researchers to combine different models relying on different scale-specific mathematical strategies and boundary conditions. Analyzing the ways in which different models are combined in multi-scale modeling also has implications for the relation between physics and biology. Contrary to the assumption that physical science approaches provide reductive explanations in biology, we exemplify how inputs from physics often reveal the importance of macro-scale models and explanations. We illustrate this through an examination of the role of biomechanics modeling in developmental biology. In such contexts, the relation between models at different scales and from different disciplines is neither reductive nor completely autonomous, but interdependent. (shrink)

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its (...) assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

Network analysis is increasingly used to discover and represent the organization of complex systems. Focusing on examples from neuroscience in particular, I argue that whether network models explain, how they explain, and how much they explain cannot be answered for network models generally but must be answered by specifying an explanandum, by addressing how the model is applied to the system, and by specifying which kinds of relations count as explanatory.

We will show that there is a strong form of emergence in cell biology. Beginning with C.D. Broad's classic discussion of emergence, we distinguish two conditions sufficient for emergence. Emergence in biology must be compatible with the thought that all explanations of systemic properties are mechanistic explanations and with their sufficiency. Explanations of systemic properties are always in terms of the properties of the parts within the system. Nonetheless, systemic properties can still be emergent. If the properties of the components (...) within the system cannot be predicted, even in principle, from the behavior of the system's parts within simpler wholes then there also will be systemic properties which cannot be predicted, even in principle, on basis of the behavior of these parts. We show in an explicit case study drawn from molecular cell physiology that biochemical networks display this kind of emergence, even though they deploy only mechanistic explanations. This illustrates emergence and its place in nature. (shrink)

In the last few years, the lack of a unitary notion of gene across biological sciences has troubled the philosophy of biology community. However, the debate on this concept has remained largely historical or focused on particular cases presented by the scientific empirical advancements. Moreover, in the literature there are no explicit and reasonable arguments about why a philosophical clarification of the concept of gene is needed. In our paper, we claim that a philosophical clarification of the concept of gene (...) does not contribute to biology. Unlike the question, for example, “What is a biological function?”, we argue that the question “What is a gene?” could be answered by means of empirical research, in the sense that biologists' labour is enough to shed light on it. (shrink)

The Somatic Mutation Theory has been challenged on its fundamentals by the Tissue Organization Field Theory of Carcinogenesis. However, a recent publication has questioned whether TOFT could be a valid alternative theory of carcinogenesis to that presented by SMT. Herein we critically review arguments supporting the irreducible opposition between the two theoretical approaches by highlighting differences regarding the philosophical, methodological and experimental approaches on which they respectively rely. We conclude that SMT has not explained carcinogenesis due to severe epistemological and (...) empirical shortcomings, while TOFT is gaining momentum. The main issue is actually to submit SMT to rigorous testing. This concern includes the imperatives to seek evidence for disproving one’s hypothesis, and to consider the whole, and not just selective evidence. (shrink)

An analysis of two heuristic strategies for the development of mechanistic models, illustrated with historical examples from the life sciences. In Discovering Complexity, William Bechtel and Robert Richardson examine two heuristics that guided the development of mechanistic models in the life sciences: decomposition and localization. Drawing on historical cases from disciplines including cell biology, cognitive neuroscience, and genetics, they identify a number of "choice points" that life scientists confront in developing mechanistic explanations and show how different choices result in divergent (...) explanatory models. Describing decomposition as the attempt to differentiate functional and structural components of a system and localization as the assignment of responsibility for specific functions to specific structures, Bechtel and Richardson examine the usefulness of these heuristics as well as their fallibility—the sometimes false assumption underlying them that nature is significantly decomposable and hierarchically organized. When Discovering Complexity was originally published in 1993, few philosophers of science perceived the centrality of seeking mechanisms to explain phenomena in biology, relying instead on the model of nomological explanation advanced by the logical positivists (a model Bechtel and Richardson found to be utterly inapplicable to the examples from the life sciences in their study). Since then, mechanism and mechanistic explanation have become widely discussed. In a substantive new introduction to this MIT Press edition of their book, Bechtel and Richardson examine both philosophical and scientific developments in research on mechanistic models since 1993. (shrink)

Self-organized criticality, the spontaneous development of systems to a critical state, is the first general theory of complex systems with a firm mathematical basis. This theory describes how many seemingly desperate aspects of the world, from stock market crashes to mass extinctions, avalanches to solar flares, all share a set of simple, easily described properties. "...a'must read'...Bak writes with such ease and lucidity, and his ideas are so intriguing...essential reading for those interested in complex systems...it will reward a sufficiently skeptical (...) reader." -NATURE "...presents the theory in a form easily absorbed by the non-mathematically inclined reader." -BOSTON BOOK REVIEW "I picture Bak as a kind of scientific musketeer; flamboyant, touchy, full of swagger and ready to join every fray... His book is written with panache. The style is brisk, the content stimulating. I recommend it as a bracing experience." -NEW SCIENTIST. (shrink)

A fascinating exploration of the very essence of life itself sheds new light on the order and evolution in complex life systems and defines and explains autonomous agents and work within the contexts of thermodynamics and information theory, setting the stage for a dramatic technological revolution. 50,000 first printing.

What is life? For four centuries, it has been believed that the only possible scientific approach to this question proceeds from the Cartesian metaphor -- organism as machine. Therefore, organisms are to be studied and characterized the same way "machines" are; the same way any inorganic system is. Robert Rosen argues that such a view is neither necessary nor sufficient to answer the question. He asserts that life is not a specialization of mechanism, but rather a sweeping generalization of it. (...) Above all, Rosen argues that renouncing mechanism does not mean abandoning science. A radical alternative is proposed, drawn equally from experience in biology, physics, and mathematics; an alternative which draws attention to a new class of complex systems, which are radically different from mechanism. (shrink)

[Time, the fundamental dimension of our existence, has fascinated artists, philosophers, and scientists of every culture and every century. All of us can remember a moment as a child when time became a personal reality, when we realized what a "year" was, or asked ourselves when "now" happened. Common sense says time moves forward, never backward, from cradle to grave. Nevertheless, Einstein said that time is an illusion. Nature's laws, as he and Newton defined them, describe a timeless, deterministic universe (...) within which we can make predictions with complete certainty. In effect, these great physicists contended that time is reversible and thus meaningless. (shrink)

NOW IN PAPERBACK"€"Starting from a collection of simple computer experiments"€"illustrated in the book by striking computer graphics"€"Stephen Wolfram shows how their unexpected results force a whole new way of looking at the operation of our universe.

The normal and the pathological are terms used for structures, activities, individual or collective situations proper to living beings and especially to man. The relation of a fact and a norm is its positive or negative value. Can the assessment of behaviours be reduced to noting a necessity? Is a living being's disease a fact similar to universal attraction? The author maintains that diseases are not merely predetermined effects, but are revealing of a normative regulation proper to living beings and (...) man. (shrink)

What is Life? This is the question asked by Denis Noble in this very personal and at times deeply lyrical book. Noble is a renowned physiologist and systems biologist, and he argues that the genome is not life itself: to understand what life is, we must view it at a variety of different levels, all interacting with each other in a complex web. It is that emergent web, full of feedback between levels, from the gene to the wider environment, that (...) is life. (shrink)

Symmetries play a major role in physics, in particular since the work by E. Noether and H. Weyl in the first half of last century. Herein, we briefly review their role by recalling how symmetry changes allow to conceptually move from classical to relativistic and quantum physics. We then introduce our ongoing theoretical analysis in biology and show that symmetries play a radically different role in this discipline, when compared to those in current physics. By this comparison, we stress that (...) symmetries must be understood in relation to conservation and stability properties, as represented in the theories. We posit that the dynamics of biological organisms, in their various levels of organization, are not just processes, but permanent (extended, in our terminology) critical transitions and, thus, symmetry changes. Within the limits of a relative structural stability (or interval of viability), variability is at the core of these transitions. (shrink)

The paper addresses the formation of striking patterns within originally near-homogenous tissue, the process prototypical for embryology, and represented in particularly purist form by cut sections of hydra regenerating, by internal reorganisation of the pre-existing tissue, a complete animal with head and foot. The essential requirements are autocatalytic, self-enhancing activation, combined with inhibitory or depletion effects of wider range – “lateral inhibition”. Not only de-novo-pattern formation, but also well known, striking features of developmental regulation such as induction, inhibition, and proportion (...) regulation can be explained on this basis. The theory provides a mathematical recipe for the construction of molecular models with criteria for the necessary non-linear interactions. It has since been widely applied to different developmental processes. (shrink)