How Darwin's “endless forms most beautiful” have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field (...) of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating “evolutionary thinking” into bacterial cell biology in the genomic era. (shrink)

The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently (...) redundant mechanisms over evolutionary time may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses. (shrink)

Evolutionary systems biology (ESB) aims to integrate methods from systems biology and evolutionary biology to go beyond the current limitations in both fields. This article clarifies some conceptual difficulties of this integration project, and shows how they can be overcome. The main challenge we consider involves the integration of evolutionary biology with developmental dynamics, illustrated with two examples. First, we examine historical tensions between efforts to define general evolutionary principles and articulation of (...) detailed mechanistic explanations of specific traits. Next, these tensions are further clarified by considering a recent case from another field focused on developmental dynamics: stem cell biology. In the stem cell case, incompatible explanatory aims block integration. Experimental approaches aim at mechanistic explanation while dynamical system models offer explanation in terms of general principles. We then discuss an ESB case in which integration succeeds: search for general attractors using a dynamical systems framework synergizes with the experimental search for detailed mechanisms. Contrasts between the positive and negative cases suggest general lessons for achieving an integrated understanding of developmental and evolutionary dynamics. The key integrative move is to acknowledge two complementary aims, both relevant to explanation: identifying the space of possible dynamic states and trajectories, and mechanistic understanding of causal interactions underlying a specific phenomenon of interest. These two aims can support one another in a joint project characterizing dynamic aspects of evolving lineages. This more inclusive project can lead to insights that cannot be reached by either approach in isolation. (shrink)

The increasing place of evolutionary scenarios in functional biology is one of the major indicators of the present encounter between evolutionary biology and functional biology (such as physiology, biochemistry and molecular biology), the two branches of biology which remained separated throughout the twentieth century. Evolutionary scenarios were not absent from functional biology, but their places were limited, and they did not generate research programs. I compare two examples of these past scenarios (...) with two present-day ones. At least three characteristics distinguish present and past efforts: An excellent description of the systems under study, a rigorous use of the evolutionary models, and the possibility to experimentally test the evolutionary scenarios. These three criteria allow us to distinguish the domains in which the encounter is likely to be fruitful, and those where the obstacles to be overcome are high and in which the proposed scenarios have to be considered with considerable circumspection. (shrink)

We characterize a type of functional explanation that addresses why a homologous trait originating deep in the evolutionary history of a group remains widespread and largely unchanged across the group’s lineages. We argue that biologists regularly provide this type of explanation when they attribute conserved functions to phenotypic and genetic traits. The concept of conserved function applies broadly to many biological domains, and we illustrate its importance using examples of molecular sequence alignments at the intersection of evolution and (...) class='Hi'>cell biology. We use these examples to show how the study of conserved functions can integrate knowledge of a trait’s causal effects on fitness and its history of natural selection without invoking adaptation. We also show how conserved function provides a novel basis for addressing objections against evolutionary functions raised by Robert Cummins. (shrink)

Phylogenetics has inherent utility in evolutionary developmental biology (EDB) as it is an established methodology for estimating evolutionary relationships and for making comparisons between levels of biological organization. However, explicit phylogenetic methods generally have been limited to two levels of organization in EDB—the species and the gene. We demonstrate that phylogenetic methods can be applied broadly to other organizational levels, such as morphological structures or cell types, to identify evolutionary patterns. We present examples at and (...) between different hierarchical levels of organization to address questions central to EDB. We argue that this application of “hierarchical phylogenetics” can be a unifying analytical approach to the field of EDB. BioEssays 27:1158–1166, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

This is a wide ranging and deeply learned examination of evolutionary developmental biology, and the foundations of life from the perspective of information theory. Hermeneutics was a method developed in the humanities to achieve understanding, in a given context, of texts, history, and artwork. In Readers of the Book of Life, the author shows that living beings are also hermeneutical interpreters of genetics texts saved in DNA; an interpretation based on the past experience of the cell ( (...) class='Hi'>cell lineage, species), confronted with and incorporating present environmental clues. This approach stresses the history, not only of the digital record saved in the DNA, but also of the flesh - the cellular organization which has a direct time-continuity with the very origins of life. This book is aimed at reconciling two opposite approaches to life. The first strictly sticking to a belief that all phenomena observed in the realm of the living can be explained from laws of physics. The opposite stressing the importance of features characteristic for a given level of description. To bring both views into a common understanding, the first part gives a comparison of the two problem solving strategies. The second part surveys the development of 20th century biology, bringing to light branches that never became part of the research mainstream. The third section of the book reviews a large body of recent evidence that can be interpreted in favor of the hermeneutic arguments. (shrink)

Biology is seen not merely as a privileged oppressor of women but as a co-victim of masculinist social assumptions. We see feminist critique as one of the normative controls that any scientist must perform whenever analyzing data, and we seek to demonstrate what has happened when this control has not been utilized. Narratives of fertilization and sex determination traditionally have been modeled on the cultural patterns of male/female interaction, leading to gender associations being placed on cells and their components. (...) We also find that when gender biases are controlled, new perceptions of these intracellular and extracellular relationships emerge. (shrink)

At the beginning of this special issue of Acta Biotheoretica carrying the above title, we present a brief overview on currently important topics that have been brought up during the last “European Conference on Mathematical and Theoretical Biology” in Edinburgh. After emphasizing the need for a “synthetic biology” also from the side of theory, model building and analysis, we survey most plenary talks of this Conference and a selected series of eigth review articles, which are mainly related to (...) corresponding minisymposia, reflecting the current state of the art and the lively discussion within this interdisciplinary field. (shrink)

This thematic issue addresses questions of constraints on the evolution of form—physical, biological, and technical. Here, form is defined as an embodiment of a specific structure, which can be hierarchically different yet emerge from the same processes. The focus of this contribution is about how developmental biology and paleontology can be better integrated and compared in order to produce hypotheses about the evolution of form. The constraints on current EvoDevo research stem from the disconnect in the focus of study (...) for developmental geneticists and evolutionary morphologists; the former being interested in early developmental events at a molecular level in a model animal, the latter in late developmental events or comparison between adult forms, at a structural level in non-model animals. In order to truly integrate information from both fields in our understanding of evolutionary processes, morphology needs to be reintegrated in the study of gene expression, and its time frame needs to be extended beyond early developmental stages. Gene expression in non-model organisms also needs to be studied in order to gain perspective into primitive patterning at evolutionary nodes. Hypotheses formed by the comparison of expression patterns and morphologies seen in extant species can then be tested against forms found in the fossil record, coming closer to understanding the mechanisms underlying evolution. (shrink)

Evolutionary epistemology has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework. In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: ontogenetic considerations, key ideas from cognitive biology, and the framework of the Extended Evolutionary Synthesis. EE, in particular the program of the evolution of epistemological mechanisms, seeks to provide a (...) phylogenetic account of the generation of cognitive processes underlying knowledge creation. Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM’s agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution and can provide a more suitable framework for EEM to draw from. In recent years, cognitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a “vertical” approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a “horizontal” approach that focuses on phylogenetic explanations of cognition and knowledge acquisition. Linking EEM with the key ideas of cognitive biology could make EEM’s research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories and understands the increase in human knowledge, such as scientific theories, as naturalistic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adaptationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution. (shrink)

Traction forces developed by most cell types play a significant role in the spatial organisation of biological tissues. However, due to the complexity of cell-extracellular matrix interactions, these forces are quantitatively difficult to estimate without explicitly considering cell properties and extracellular mechanical matrix responses. Recent experimental devices elaborated for measuring cell traction on extracellular matrix use cell deposits on a piece of gel placed between one fixed and one moving holder. We formulate here a mathematical (...) model describing the dynamic behaviour of the cell-gel medium in such devices. This model is based on a mechanical force balance quantification of the gel visco-elastic response to the traction forces exerted by the diffusing cells. Thus, we theoretically analyzed and simulated the displacement of the free moving boundary of the system under various conditions for cells and gel concentrations. This modelis then used as the theoretical basis of an experimental device where endothelial cells are seeded on a rectangular biogel of fibrin cast between two floating holders, one fixed and the other linked to a force sensor. From a comparison of displacement of the gel moving boundary simulated by the model and the experimental data recorded from the moving holder displacement, the magnitude of the traction forces exerted by the endothelial cell on the fibrin gel was estimated for different experimental situations. Different analytical expressions for the cell traction term are proposed and the corresponding force quantifications are compared to the traction force measurements reported for various kind of cells with the use of similar or different experimental devices. (shrink)

The purinergic signalling system, which utilises ATP, related nucleotides and adenosine as transmitter molecules, appeared very early in evolution: release mechanisms and ATP‐degrading enzymes are operative in bacteria, and the first specific receptors are present in single cell eukaryotic protozoa and algae. Further evolution of the purinergic signalling system resulted in the development of multiple classes of purinoceptors, several pathways for release of nucleotides and adenosine, and a system of ectonucleotidases controlling extracellular levels of purinergic transmitters. The purinergic signalling (...) system is expressed in virtually all types of tissues and cells, where it mediates numerous physiological reactions and contributes to pathological responses in a variety of diseases. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (shrink)

When the history of life on earth is viewed as a history of cell division, all of life becomes a single cell lineage. The growth and differentiation of this lineage in reciprocal interaction with its environment can be viewed as a developmental process; hence the evolution of life on earth can also be seen as the development of life on earth. Here, in reviewing this field, some potentially fruitful research directions suggested by this change in perspective are highlighted. (...) Variation and selection become, for example, bidirectional information flows between scales, while the notions of “cooperation” and “competition” become scale relative. The language of communication, inference, and information processing becomes more useful than the language of causation to describe the interactions of both homogeneous and heterogeneous living systems at any scale. Emerging scale‐free theoretical frameworks such as predictive coding and active inference provide conceptual tools for reconceptualizing biology as the study of a unified, multiscale dynamical system. (shrink)

In this chapter we offer a critical analysis of organizational models about the process of origins of life and, thereby, a reflection about life itself (understood in a general, minimal sense). We begin by demarcating the idea of organization as an explanatory construct, linking it to the complex relationships and transformations that the material parts of (proto-)biological systems establish to maintain themselves under non-equilibrium dynamic conditions. The diverse ways in which this basic idea has been applied within the prebiotic field (...) are then reviewed in relative detail. We distinguish between “network” and “protocell” approaches, discussing their specific implications and explaining the greater relevance of the latter in the current state of affairs. Despite the key role that such organizational approaches play (and should keep playing) to advance on the problem of primordial biogenesis, the second half of our contribution is devoted to argue that they must be combined with other explanatory accounts, which go beyond the physiology of any single (proto-)organism. With that aim, we underline the fundamental differences between the autonomous, metabolic dynamics that individual (proto-)cells perform and the evolutionary and ecological dynamics that take place in a collective and trans-generational dimension. Apart from obvious gaps in the characteristic temporal and spatial scales involved, the corresponding causal and interactive regimes also reveal themselves as neatly distinct, what is reflected in the unpaired functional integration and the agent behavior displayed by biological individuals. Nevertheless, any living organism (and life in a wider, general sense) derives from the deep interweaving of those two phenomenological domains: namely, the “individual-metabolic” and the “collective-evolutionary” domains. At the end of the chapter, we propose the principle of dynamical decoupling as the core idea to develop a more comprehensive theoretical framework to understand how this intricate, causally asymmetric connection must be articulated during the actual process of biogenesis (as it happened here on Earth or anywhere else in the universe), so that life’s minimal complexity threshold is reached. (shrink)

The urochordates, whose stem groups may have included the direct predecessors of the chordate line, serve as an excellent model group of organisms for a variety of scientific disciplines. One taxon, the botryllid ascidian, has emerged as the model system for studying allorecognition; this work has concentrated on the cosmopolitan species Botryllus schlosseri. Studies analyzing self–nonself recognition in this colonial marine organism point to three levels of allorecognition, each associated with different outcomes. The first level controls natural allogeneic rejections and (...) fusions, in which blood‐shared chimeras are formed. The second level leads to morphological resorption of partners within chimeras while the third allows the development of somatic and germ cell parasitic events. Recent studies on multi‐chimeric entities formed in allogeneic fusions reveal evolutionary links between allorecognition, stem cell biology and ecology. Thus, the Botryllus system generates perspectives from different biological disciplines to yield a unique life history portrait. BioEssays 24:730–740, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Two welcome extensions of evolutionary thinking have come to prominence over the last thirty years: the so-called ’extended evolutionary synthesis’ (EES) and debate about biological kinds and individuals. These two agendas have, however, remained orthogonal to one another. The EES has mostly restricted itself to widening the explanations of adaptation offered by the preceding ’modern evolutionary synthesis’ by including additional mechanisms of inheritance and variation; while discussion of biological kinds has turned toward philosophical questions of essential vs. (...) contingent properties of life forms and realist vs. epistemological approaches to categorization and classification. Here we attempt to broaden the explanatory scope of evolutionary theory by linking these two agendas. We expand on the mechanistic orientation of the EES, using new understandings of networked systems of components in order to engage the distinct intellectual challenge of the origination of “historical kinds”. With this phrase we designate a subset of natural kinds that acquires, through evolutionary processes, a quasi-independent lineage-history. Such kinds emerge in both biology and culture, and we enlarge the limited number of historical kinds that have thus far been recognized in evolutionary biology in a series of paradigmatic exemplars, from genes and cell types to rituals and music. For each exemplar we discern specific mechanisms by which it arose and persists; comparing these, we suggest a general unity in the ways in which diverse historical kinds originate. (shrink)

With a previous paper (Niu & Wang, 1995), a general, hypothetical outline of the mechanism of carcinogenesis was proposed. With reference to the fact of starvation-induced hypermutation in micro-organisms, we propose that the hypoxia commonly seen in the cells at the centre of solid tumours might also result in hypermutation, and then p53-dependent programmed cell death. Like the apparently adaptive mutations in micro-organisms, only those genes (e.g. p53) that enable the cells to escape from apoptosis may be selected.

Lattice-gas cellular automaton (LGCA) and lattice Boltzmann (LB) models are promising models for studying emergent behaviour of transport and interaction processes in biological systems. In this chapter, we will emphasise the use of LGCA/LB models and the derivation and analysis of LGCA models ranging from the classical example dynamics of fluid flow to clotting phenomena in cerebral aneurysms and the invasion of tumour cells.

Talk of different types of cells is commonplace in the biological sciences. We know a great deal, for example, about human muscle cells by studying the same type of cells in mice. Information about cell type is apparently largely projectible across species boundaries. But what defines cell type? Do cells come pre-packaged into different natural kinds? Philosophical attention to these questions has been extremely limited [see e.g., Wilson (Species: New Interdisciplinary Essays, pp 187–207, 1999; Genes and the Agents (...) of Life, 2005; Wilson et al. Philos Top 35(1/2):189–215, 2007)]. On the face of it, the problems we face in individuating cellular kinds resemble those biologists and philosophers of biology encountered in thinking about species: there are apparently many different (and interconnected) bases on which we might legitimately classify cells. We could, for example, focus on their developmental history (a sort of analogue to a species’ evolutionary history); or we might divide on the basis of certain structural features, functional role, location within larger systems, and so on. In this paper, I sketch an approach to cellular kinds inspired by Boyd’s Homeostatic Property Cluster Theory, applying some lessons from this application back to general questions about the nature of natural kinds. (shrink)

Stem cell research has entered the public consciousness through the media. Proponents and opponents of all such research, or of human embryonic stem cell research specifically, engage in heated exchanges in the modern public forum where stakeholders negotiate, the agora. One common claim that emerges from the fray is that a particular type of stem cell research should be pursued as the most promising path toward the reduction of suffering and untimely death for all of humanity. Upon (...) evaluation, experimental data regarding the potential role of stem cells in regenerative therapies for three conditions—spinal cord injury, type 1 diabetes, and cardiovascular disease—tell distinct, complex, and inconclusive stories. Further analyses in this article incorporate realistic considerations of a broad range of relevant factors--limited funding for biomedical research, media motives, the discordance hypothesis of evolutionary medicine, the relationship between religion and science, medical care in developing nations, and culture wars over abortion. Holistic investigation inspired by the current agora conversation supports the need to drastically change interactions regarding stem cell research so that its potential to benefit humanity may be more fully realized. (shrink)

Introduction: working together on individuality / Lynn K. Nyhart and Scott Lidgard -- The work of biological individuality: concepts and contexts / Scott Lidgard and Lynn K. Nyhart -- Cells, colonies, and clones: individuality in the volvocine algae / Matthew D. Herron -- Individuality and the control of life cycles / Beckett Sterner -- Discovering the ties that bind: cell-cell communication and the development of cell sociology / Andrew S. Reynolds -- Alternation of generations and individuality, 1851 (...) / Lynn K. Nyhart and Scott Lidgard -- Spencer's evolutionary entanglement: from liminal individuals to implicit collectivities / Snait Gissis -- Biological individuality and enkapsis: from Martin Heidenhain's synthesiology to the völkisch national community / Olivier Rieppel -- Parasitology, zoology, and society in France, ca. 1880-1920 / Michael A. Osborne -- Metabolism, autonomy, and individuality / Hannah Landecker -- Bodily parts in the structure-function dialectic / Ingo Brigandt -- Commentaries: historical, biological, and philosophical perspectives -- Distrust that particular intuition: resilient essentialisms and empirical challenges in the history of biological individuality / James Elwick -- Biological individuality: a relational reading / Scott F. Gilbert -- Philosophical dimensions of individuality / Alan C. Love and Ingo Brigandt. (shrink)

An understanding of the factors behind the evolution of multicellularity is one of today’s frontiers in evolutionary biology. This is because multicellular organisms are made of one subset of cells with the capacity to transmit genes to the next generation and another subset responsible for maintaining the functionality of the organism, but incapable of transmitting genes to the next generation. The question arises: why do somatic cells sacrifice their lives for the sake of germline cells? How is germ/soma (...) separation maintained? One conventional answer refers to inclusive fitness theory, according to which somatic cells sacrifice themselves altruistically, because in so doing they enhance the transmission of their genes by virtue of their genetic relatedness to germline cells. In the present article we will argue that this explanation ignores the key role of policing mechanisms in maintaining the germ/soma divide. Based on the pervasiveness of the latter, we argue that the role of altruistic mechanisms in the evolution of multicellularity is limited and that our understanding of this evolution must be enriched through the consideration of coercion mechanisms. (shrink)

The aim of this paper is to assess the relevance of somatic evolution by natural selection to our understanding of cancer development. I do so in two steps. In the first part of the paper, I ask to what extent cancer cells meet the formal requirements for evolution by natural selection, relying on Godfrey-Smith’s (2009) framework of Darwinian populations. I argue that although they meet the minimal requirements for natural selection, cancer cells are not paradigmatic Darwinian populations. In the second (...) part of the paper, I examine the most important examples of adaptation in cancer cells. I argue that they are not significant accumulations of evolutionary changes, and that as a consequence natural selection plays a lesser role in their explanation. Their explanation, I argue, is best sought in the previously existing wiring of the healthy cells. (shrink)

In multicellular organisms, cells are frequently programmed to die. This makes good sense: cells that fail to, or are no longer playing important roles are eliminated. From the cell’s perspective, this also makes sense, since somatic cells in multicellular organisms require the cooperation of clonal relatives. In unicellular organisms, however, programmed cell death poses a difficult and unresolved evolutionary problem. The empirical evidence for PCD in diverse microbial taxa has spurred debates about what precisely PCD means in (...) the case of unicellular organisms. In this article, we survey the concepts of PCD in the literature and the selective pressures associated with its evolution. We show that definitions of PCD have been almost entirely mechanistic and fail to separate questions concerning what PCD fundamentally is from questions about the kinds of mechanisms that realize PCD. We conclude that an evolutionary definition is best able to distinguish PCD from closely related phenomena. Specifically, we define “true” PCD as an adaptation for death triggered by abiotic or biotic environmental stresses. True PCD is thus not only an evolutionary product but must also have been a target of selection. Apparent PCD resulting from pleiotropy, genetic drift, or trade-offs is not true PCD. We call this “ersatz PCD.”. (shrink)

Sponges branch basally in the metazoan phylogenetic tree and are believed to be composed of four distinct lineages with still uncertain relationships. Indeed, some molecular studies propose that Homoscleromorpha may be a fourth Sponge lineage, distinct from Demospongiae in which they were traditionally classified. They harbour many features that distinguish them from other sponges and are more evocative of those of the eumetazoans. They are notably the only sponges to possess a basement membrane with collagen IV and specialized cell‐junctions, (...) thus possessing true epithelia. Among Homoscleromorphs, we have chosen Oscarella lobularis as a model species. This common and easily accessible sponge is characterized by relatively simple histology and cell composition, absence of skeleton, and strongly pronounced epithelial structure. In this review, we explore the specific features that make O. lobularis a promising homoscleromorph sponge model for evolutionary and developmental researches. (shrink)

The origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras‐family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during eukaryote (...) evolution had secretory, and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented. BioEssays 25:1129–1138, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The eukaryote cell is one of the most radical innovations in the history of life, and the circumstances of its emergence are still deeply contested. This paper will outline the recent history of attempts to reveal these origins, with special attention to the argumentative strategies used to support claims about the first eukaryote cell. I will focus on two general models of eukaryogenesis: the phagotrophy model and the syntrophy model. As their labels indicate, they are based on claims (...) about metabolic relationships. The first foregrounds the ability to consume other organisms; the second the ability to enter into symbiotic metabolic arrangements. More importantly, however, the first model argues for the autogenous or self-generated origins of the eukaryote cell, and the second for its exogenous or externally generated origins. Framing cell evolution this way leads each model to assert different priorities in regard to cell-biological versus molecular evidence, cellular versus environmental influences, plausibility versus evolutionary probability, and irreducibility versus the continuity of cell types. My examination of these issues will conclude with broader reflections on the implications of eukaryogenesis studies for a philosophical understanding of scientific contestation. (shrink)

Modularity has become a central and remarkably useful concept in evolutionary developmental biology, offering an explanation of how independent, interacting units make possible developmental events and evolutionary changes. These modules exist at several different levels of organization, from genes to signal transduction pathways to cell populations. Cell populations, which are multicellular modules, provide an opportunity both to clarify our notion of modularity and to reexamine such central concepts as cell-to-cell communication. Rosine Chandebois’s work (...) on “cell sociology” is reframed in the language of modularity in order to show how groups of cells maintain their collective identity during development and how signaling information from the group’s environment is received by the constituent cells. In a “test case” for our account of multicellular modules, we consider the vertebrate neural crest, a migratory cell population made up of several subpopulations. The neural crest proves yet again to be a complex case, showing the importance of taking into account both developmental and evolutionary transformations of multicellular modules. (shrink)

American biologists in the late nineteenth century pioneered the descriptive-comparative study of all cell divisions from zygote to gastrulation -- the cell lineage. Data from cell lineages were crucial to evolutionary and developmental questions of the day. One of the main questions was the ultimate causation of developmental patterns -- historical or mechanical. E. B. Wilson's groundbreaking lineage work on the polychaete worm Nereis in 1892 set the stage for (1) an attack on Haeckel's phylogenetic-historical notion (...) of recapitulation and (2) support for mechanistic explanations of cleavage patterns. As more lineage work -- especially Lillie's work on "Unio" and Conklin's on "Crepidula" -- became available in the mid-late 1890s, mechanism was tempered with more evolutionary, homology-based views. However, as I show by focusing on three major issues -- homology, body plans and life history -- these views were primarily based on the precocious segregation and prospective significance -- what the cell became not what it was. Even on issues like adaptation, most lineagists argued teleologically from the adult backward. Most cell lineage workers, by 1900, were to varying degrees mechanist/experimentalist and recapitulationist simultaneously. The exception was E. G. Conklin, whose views were more akin to a Darwinian evolutionist than either mechanist or recapitulationist. Lineage work eventually declined and by 1907 published accounts of new lineages had basically stopped. I argue that established workers and younger researchers stopped wanting to take on cell lineage projects because the general patterns were the same for all the spiralians while the specifics showed too much variation. It was hard to theoretically encompass or analyze the minutiae of variation in a recapitulationist or mechanist framework. The only established worker who continued to do comparative lineage studies was E. G. Conklin, perhaps because the variation could best be accommodated by Darwinian evolution. (shrink)

Evolutionary developmental biology (Evo-devo) is a loose conglomeration of research programs in the life sciences with two main axes: (a) the evolution of development, or inquiry into the pattern and processes of how ontogeny varies and changes over time; and, (b) the developmental basis of evolution, or inquiry into the causal impact of ontogenetic processes on evolutionary trajectories—both in terms of constraint and facilitation. Philosophical issues are found along both axes surrounding concepts such as evolvability, novelty, and (...) modularity. The developmental basis of evolution has garnered much attention because it speaks to the possibility of revising a standard construal of evolutionary theory, but the evolution of development harbors its own conceptual questions. This article addresses the heterogeneity of Evo-devo’s conglomerate structure (including disagreements over its individuation), as well as the concepts and controversies of philosophical interest pertaining to the evolution of development and the developmental basis of evolution. Future research will benefit from a shift away from global theorizing toward the scientific practices of Evo-devo. (shrink)

According to scientific procedure, each discipline first describes the phenomena of its research area, then analyzes them, and tinally categorizes them in a system. To date, biology has lacked such a system for its smallest building blocks, the cells. Although the theory of evolution explains certain central evolutionary mechanisms of the cell, there existed no generally accepted theory of the organization of the cell. The endoeytobiotic cell theory is suggested as a possible basis for a (...) satisfying explanation of the structure, function, information, and evolution of the cell. Furthermore, a hypothetical periodic system of the cell is developed. This system consists of eight groups, including the ecological niches fermentation, respiration, photergy, and photosynthesis (each aerobic and anaerobic) and seven periods with increasing numbers of protein biosynthesis machineries (cytoplasma, mitochondria, plastids, endocytobionts). We find furthermore, a division according to typical animal or plant cells and between these two in fungus-like cells. (shrink)

Research in the field of planarian regeneration on the one hand, and a general survey of embryology on the other, throw doubt upon the reality of supra-cellular controls, which are still at the basis of all modern concepts of morphogenesis. The necessity of referring to such controls, which have never been convincingly demonstrated, is probably due to the fact that two aspects of cell behaviour have been underestimated: 1) the capacity of cells to change their individualities for a time (...) independently of other cells; 2) the social behaviour of cells, which is the consequence of the reciprocal exchange of information. Pattern formation and pattern remodeling in normal development results from readjustments of cell populations to local or global changes. The common responses of cell populations to disturbances are enhanced mitotic activity, cessation of specific syntheses and cell migration. In the young embryo these may promptly restore the unity of the injured primordium, leading to so-called restitution; this is based on a normal sequence of further readjustments in the primordium. In older organisms the same responses give rise to cell interactions which may be the starting point for further sequential readjustments — in some instances these are comparable to those that originally organized the primordium in question during development. The desirability of giving up the notion of morphogenetic field is discussed. (shrink)

New developments in molecular and cell biology during the past three decades have demonstrated that cells use a language of their own, namely"cell language". The essential features of the so-called cell language theory formulated in 1997 are reviewed as a prelude to establishing the concept ofmicrosemiotics'' and "microsemiosis''' the semiotics and sign processes, respectively, on the molecular level. Peircean semiotics is largely concemedwith macroscopic signs and hence is here referred to as macrosemiotics. The possibihty of extending (...) Peircean semiotics from macroscale to microscale was clearly foreseen by Sebeok in 1968 who also intuited the evolutionary, link between macro- and microsemiosis, leading to the formulation of what is here called the "Sebeok doctrine of signs" that contains 5 major testable propositions. The concept of "cosmosemiosis" as the sum of three terms, physiosemiosis, macrosemiosis, and microsemiosis, is defined and related to a theoretical model of the Universe known as the Shillongator, published in 1991, according to which superstrings serve as the primal source of free energy and information and hence as the Universal Sign Processor, similar to DNA acting as the primary biological sign processor in the living cell. Thus, the Shillongator as the physical effector or effectuator of cosmosemiosis appears to provide a coherent theoretical framework to integrate i) the Sebeok doctrine of signs, ii) Deely's theory of physiosemiotics, iii) macro- or Pericean semiotics, iv) the present author's microsemiotics, and v) Merleau-Ponty's ontology ofthe Flesh. (shrink)

Genesis: The Evolution of Biology presents a history of the past two centuries of biology, suitable for use in courses, but of interest more broadly to evolutionary biologists, geneticists, and biomedical scientists, as well as general readers interested in the history of science. The book covers the early evolutionary biologists-Lamarck, Cuvier, Darwin and Wallace through Mayr and the neodarwinian synthesis, in much the same way as other histories of evolution have done, bringing in also the social (...) implications, the struggles with our religious understanding, and the interweaving of genetics into evolutionary theory. What is novel about Sapp's account is a real integration of the cytological tradition, from Schwann, Boveri, and the other early cell biologists and embryologists, and the coverage of symbiosis, microbial evolutionary phylogenies, and the new understanding of the diversification of life coming from comparative analyses of complete microbial genomes. The book is a history of theories about evolution, genes and organisms from Lamarck and Darwin to the present day. This is the first book on the general history of evolutionary biology to include the history of research and theories about symbiosis in evolution, and first to include research on microbial evolution which were excluded from the classical neo-Darwinian synthesis. Bacterial evolution, and symbiosis in evolution are also excluded from virtually every book on the history of biology. (shrink)

Hydra are remarkable because they are immortal. Much of immortality can be ascribed to the asexual mode of reproduction by budding, which requires a tissue consisting of stem cells with continuous self‐renewal capacity. Emerging novel technologies and the availability of genomic resources enable for the first time to analyse these cells in vivo. Stem cell differentiation in Hydra is governed through the coordinated actions of conserved signaling pathways. Studies of stem cells in Hydra, therefore, promise critical insights of general (...) relevance into stem cell biology including cellular senescence, lineage programming and reprogramming, the role of extrinsic signals in fate determination and tissue homeostasis, and the evolutionary origin of these cells. With these new facts as a backdrop, this review traces the history of studying stem cells in Hydra and offers a view of what the future may hold. (shrink)

The fields of quantum biology and physics are now starting to unite to solve the mysteries associated with the field of evolutionary biology. One such question is the origination and propagation of consciousness which has always been ambiguous and in order to understand this concept, many theories have been proposed by several philosophers and scientists. This review paper agrees with the idea, that evolution is not a random process but hypothesizes, that its succession was managed by the (...) expanding level of consciousness due to cell division and cell differentiation. Several theories propose that the cytoskeleton and its proteins are promoters for consciousness in the brain, which propagates by means of super-conductance. A better correlation of cytoskeletal evolution and consciousness could help solve the enigma of the origination, propagation and existence of consciousness. This review is a compilation of theories, evidences and scientific studies which intends to bring an association between propagation of consciousness and the evolution of the cytoskeleton and its proteins. (shrink)

In the nineteenth century protozoology and early cell biology intersected through the nexus of Darwin's theory of evolution. As single-celled organisms, amoebae offered an attractive focus of study for researchers seeking evolutionary relationships between the cells of humans and other animals, and their primitive appearance made them a favourite model for the ancient ancestor of all living things. Their resemblance to human and other metazoan cells made them popular objects of study among morphologists, physiologists, and even those (...) investigating animal behaviour. The amoeba became the exemplar of the new protoplasmic cell concept of mid-century and because its apparent simplicity made it widely generalizable it became a popular subject in a breadth of experimental investigations and theoretical speculations. It was able to do this because "the amoeba" denotes not a particular organism, but a general type of behaviour common to the cells of a range of protozoa, simple plants and higher animals. Its status as an exemplary cell also rested upon auxiliary philosophical assumptions about what constitutes a primitive characteristic and the thesis that evolution is a progressive development of order from chaos. (shrink)

Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They (...) may originate as either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication. (shrink)

The subject of this edited volume is the idea of levels of organization: roughly, the idea that the natural world is segregated into part-whole relationships of increasing spatiotemporal scale and complexity. The book comprises a collection of essays that raise the idea of levels into its own topic of analysis. Owing to the wide prominence of the idea of levels, the scope of the volume is aimed at theoreticians, philosophers, and practicing researchers of all stripes in the life sciences. The (...) volume’s contributions reflect this diversity, and draw from fields such as developmental biology, evolutionary biology, molecular biology, ecology, cell biology, and neuroscience. The book presents wide-ranging novel insights on causation and levels, the hierarchical structure of evolution, the role of levels in biological theory, and more. (shrink)

Understanding modeling in biology requires understanding how biology is organized as a discipline and how this organization influences the research practices of biologists. Biology includes a wide range of sub-disciplines, such as cell biology, population biology, evolutionary biology, molecular biology, and systems biology among others. Biologists in sub-disciplines such as cell, molecular, and systems biology believe that the use of a few experimental models allows them to discover biological (...) universals, whereas biologists in sub-disciplines such as ecology and evolutionary biology believe that the use of many different experimental and mathematical models is necessary in order to do this. Many practitioners of both approaches misunderstand best practices of modeling, especially those related to model testing. We stress the need for biologists to better engage with best practices and for philosophers of biology providing normative guidance for biologists to better engage with current developments in biology. This is especially important as biology transitions from a “data-poor” to a “data-rich” discipline. If 21st century biology is going to capitalize on the unprecedented availability of ecological, evolutionary, and molecular data, of computational resources, and of mathematical and statistical tools, biologists will need a better understanding of what modeling is and can be. (shrink)

A physiological function can be described as a cycle based on a cusp bifurcation set in catastrophe theory. This cycle involves four phases that are successively developed along a functional potential, which is used to perform a given physiological act. The work we present is firstly based on a detailed study of the global function of vision, which covers a vast field extending from the molecular to cerebral scale. We then present other examples of generalised functions by expanding the frame (...) of reference, from the scale of an organ to the scale of a whole organism with predation function, and to the scale of a social group with crisis management. We observed that the criteria remain the same, whether the function is considered on the scale of a cell membrane or a group of individuals organised into a cohort. Moreover, a so-called generalised function can be broken down into simpler sub-functions, each phase of the initial function containing the physiological act of each sub-function. It seems thus that a fractal extension may characterise the four-cusp spiral. This spiral is increasingly large as the types of sub-functions are multiplied. In functions relative to sociological science, such as crisis management, which are not natural but built and designed by humans, close attention must be paid to following the rules of these generalised biological functions. (shrink)

Epigenetics is currently one of the fastest-growing fields in the sciences. Epigenetic information not only controls DNA expression but links genetic factors with the environmental experiences that influence the traits and characteristics of an individual. What we eat, where we work, and how we live affects not only the activity of our genes but that of our offspring as well. This discovery has imposed a revolutionary theoretical shift on modern biology, especially on evolutionary theory. It has helped to (...) uncover the developmental processes leading to cancer, obesity, schizophrenia, alcoholism, and aging, and to facilitate associated medial applications such as stem cell therapy and cloning. Above the Gene, Beyond Biology explores how biologists in this booming field investigate and explain living systems. Jan Baedke offers the first comprehensive philosophical discussion of epigenetic concepts, explanations, and methodologies so that we can better understand this "epigenetic turn" in the life sciences from a philosophical perspective. (shrink)

The chronologic age classically used in demography is often unable to give useful information about which exact stage in development or aging processes has reached an organism. Hence, we propose here to explain in some applications for what reason the chronologic age fails in explaining totally the observed state of an organism, which leads to propose a new notion, the biological age. This biological age is essentially determined by the number of divisions before the Hayflick’s limit the tissue or mitochondrion (...) in a critical organ (in the sense where its loss causes the death of the whole organism) has already used for its development and adult phases. We give a precise definition of the biological age of an organ based on the Hayflick’s limit of its cells and we introduce a desynchronization index (the cell entropy) for some critical tissues or membranes, which are mainly skin, intestinal endothelium, alveoli epithelium and mitochondrial inner membrane. In these actively metabolising interface tissues or membranes, there is a rapid turnover of cells, of their cytoplasmic constituents such as proteins, and of membrane lipids. The boundaries corresponding to these tissues, cells or membranes have vital functions of interface with the environment (protection, homeothermy, nutrition and respiration) and have a rapid turnover (the total cell renewal time is in mice equal to 3 weeks for the skin, 1.5 day for the intestine, 4 months for the alveolae and 11 days for mitochondrial inner membrane) conditioning their biological age. The biological age of a tissue is made of two major components: (1) first, its embryonic age based on the distance (in number of divisions) between the birth date of its first differentiated cell and the time until it reaches its final boundary at the end of its development and (2) second, its adult age whose complement until its death is just the lapse of time made of the sum of remaining cell cycle durations authorized by its Hayflick’s limit. From this definition, we calculate the global biological lifespan of an organism and revisit notions like demographic survival curves, duration and synchrony of cell cycles, living boundaries from proto-cells to organs, and embryonic and adult phases duration. (shrink)

The manifest appearance of function and purpose in living systems is responsible for the prevalence of apparently teleological explanations of organismic structure and behavior in biology. Although the attribution of function and purpose to living systems is an ancient practice, teleological notions are largely considered ineliminable from modern biological sciences, such as evolutionary biology, genetics, medicine, ethology, and psychiatry, because they play an important explanatory role. Historical and recent examples of teleological claims include the following: The chief (...) function of the heart is the transmission and pumping of the blood through the arteries to the extremities of the body. (Harvey 1616 [1928: 49]) The Predator Detection hypothesis remains the strongest candidate for the function of stotting [by gazelles]. (Caro 1986: 663) The geographic range of human malaria is much wider than the range of the sickle-cell gene. As it happens, other antimalarial genes take over the protective function of the sickle-cell gene in … other warm parts. (Diamond 1994: 83) Despite the substantial amount of data we now have on theropod dinosaurs, more information is necessary in order to determine the likelihood that early feathers served an adaptive function in visual display as opposed to other proposed adaptive functions such as thermoregulation. (Dimond et al. 2011: 62) The ubiquity of claims such as these raises the question: how should apparently teleological notions in biology be understood? Most post-Darwinian approaches attempt to naturalize teleology in biology, in opposition to nineteenth-century viewpoints which grounded it theologically. Nevertheless, biologists and philosophers have continued to question the legitimacy of teleological notions in biology. For instance, Ernst Mayr (1988), identified four reasons why teleological notions remain controversial in biology, namely that they are: vitalistic (positing some special ‘life-force’); requiring backwards causation (because goal-directed explanations seem to use future outcomes to explain present traits); incompatible with mechanistic explanation (because of 1 and 2); mentalistic (attributing the action of mind where there is none). A fifth complaint is that they are not empirically testable (Allen & Bekoff 1995). The current philosophical literature offers both Darwinian and non-Darwinian accounts of teleology in biology that aim to avoid these concerns. In this article, we hope to bring some clarity to the contemporary debates over the role of teleological notions in biology by sketching a taxonomy of the various accounts of biological function on offer (see Allen & Bekoff 1995 for a more comprehensive taxonomy that forms the basis of this presentation). We primarily focus on naturalistic accounts of biological function, since this is where we see the most lively and productive current debates (see, e.g., Garson 2016 for an extended survey). We also briefly discuss the notion of goal-directedness in section 2. (shrink)

The fitness of any evolutionary unit can be understood in terms of its two basic components: fecundity (reproduction) and viability (survival). Trade-offs between these fitness components drive the evolution of life-history traits in extant multicellular organisms. We argue that these trade-offs gain special significance during the transition from unicellular to multicellular life. In particular, the evolution of germ–soma specialization and the emergence of individuality at the cell group (or organism) level are also consequences of trade-offs between the two (...) basic fitness components, or so we argue using a multilevel selection approach. During the origin of multicellularity, we study how the group trade-offs between viability and fecundity are initially determined by the cell level trade-offs, but as the transition proceeds, the fitness trade-offs at the group level depart from those at the cell level. We predict that these trade-offs begin with concave curvature in single-celled organisms but become increasingly convex as group size increases in multicellular organisms. We argue that the increasingly convex curvature of the trade-off function is driven by the cost of reproduction which increases as group size increases. We consider aspects of the biology of the volvocine green algae – which contain both unicellular and multicellular members – to illustrate the principles and conclusions discussed. (shrink)

Description of the biologicalhierarchy of the organism has been extendedhere to included the evolutionary andecological sub-hierarchies with theirrespective levels in order to give a completehierarchical description of life. These newdescriptions include direction of formation,types of constraints, and dual levels. Constraints are produced at the macromolecularlevel of genes/proteins, some of which (a) aredescendent restraints which hold a hierarchytogether and others (b) interact horizontallywith selective agents at corresponding levelsof the niche. The organism is a dual levelconstrained by both the ecologicalsub-hierarchy (survival) (...) and evolutionarysub-hierarchy (fitness) while serving as thehighest level of the specializationsub-hierarchy, therefore, it is unique inbelonging to three sub-hierarchies. Organismsexperience birth, sometimes death, andparticipate in evolution. Birth of an organismis realized when a cell is removed from theconstraints of the organism and assumes itsown organismal constraints. Death occurs withthe cessation of protein synthesis becauseproteins and their products constitutecomponents at high levels of the hierarchy. Selection is of two types, natural selection,involving adaptive traits interacting withfeatures in a niche, and hierarchicalselection, requiring traits to be compatiblewith existing hierarchical constraints. (shrink)

The concept of complexity has become very important in theoretical biology. It is a many faceted concept and too new and ill defined to have a universally accepted meaning. This review examines the development of this concept from the point of view of its usefulness as a criteria for the study of living systems to see what it has to offer as a new approach. In particular, one definition of complexity has been put forth which has the necessary precision (...) and rigor to be considered as a useful categorization of systems, especially as it pertains to those we call living. This definition, due to Robert Rosen, has been developed in a number of works and involves some deep new concepts about the way we view systems. In particular, it focuses on the way we view the world and actually practice science through the use of the modelling relation. This mathematical object models the process by which we assign meaning to the world we perceive. By using the modelling relation, it is possible to identify the subjective nature of our practices and deal with this issue explicitly. By so doing, it becomes clear that our notion of complexity and especially its most popular manifestations, is in large part a product of the historical processes which lead to the present state of scientific epistemology. In particular, it is a reaction to the reductionist/mechanistic view of nature which can be termed the Newtonian Paradigm. This approach to epistemology has dominated for so long that its use as a model has become implicit in most of what we do in and out of science. The alternative to this approach is examined and related to the special definition of complexity given by Rosen. Some historical examples are used to emphasize the dependence of our view of what is complex in a popular sense on the ever changing state of our knowledge. The role of some popular concepts such as chaotic dynamics are examined in this context. The fields of artificial life and related areas are also viewed from the perspective of this rigorous view of complexity and found lacking. The notion that in some way life exists at the edge of chaos is examined from the perspective of the second law of thermodynamics given by Schneider and Kay. Finally, the causal elements in complex systems are explored in relation to complexity. Rosen has shown that a clear difference in causal relations exists between complex and simple systems and that this difference leads to a uniquely useful definition of what we mean by living. Rosen makes it very clear that the class of systems which are complex is a much larger class than those which we call living. For that reason, the focus of this review will be on complexity as a stepping stone towards the deeper question of what makes a system alive. (shrink)