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)

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions that (...) uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. (shrink)

In the discussion about consequences of the release of genetically modified (GM) crops, the meaning of the term “environmental damage” is difficult to pin down. We discuss some established concepts and criteria for understanding and evaluating such damages. Focusing on the concepts of familiarity, biological integrity, and ecosystem health, we argue that, for the most part, these concepts are highly ambiguous. While environmental damage is mostly understood as significant adverse effects on conservation resources, these concepts may not relate (...) directly to effects on tangible natural resources but rather to parameters of land use or ecological processes (e.g., the concept of biological integrity). We stress the importance of disclosing the normative assumptions underlying damage concepts and procedures for the evaluation of damages by GM crops. A conceptualization of environmental damage should precede its operationalization. We recommend an unambiguous definition for damage developed earlier and recommend that evaluation criteria be based on this. However, a general damage definition cannot replace case-specific operationalization of damage, which remains an important future challenge. (shrink)

This fine collection of essays by a leading philosopher of science presents a defence of integrative pluralism as the best description for the complexity of scientific inquiry today. The tendency of some scientists to unify science by reducing all theories to a few fundamental laws of the most basic particles that populate our universe is ill-suited to the biological sciences, which study multi-component, multi-level, evolved complex systems. This integrative pluralism is the most efficient way to understand the different and (...) complex processes - historical and interactive - that generate biological phenomena. This book will be of interest to students and professionals in the philosophy of science. (shrink)

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

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)

We introduce a new type of pluralism about biological function that, in contrast to existing, demonstrates a practical integration among the term’s different meanings. In particular, we show how to generalize Sandra Mitchell’s notion of integrative pluralism to circumstances where multiple epistemic tools of the same type are jointly necessary to solve scientific problems. We argue that the multiple definitions of biological function operate jointly in this way based on how biologists explain the evolution of protein function. To (...) clarify how our account relates to existing views, we introduce a general typology for monist and pluralist accounts along with standardized criteria for judging which is best supported by evidence. (shrink)

The idea of integrating evolutionary biology and psychology has great promise, but one that will be compromised if psychological functions are conceived too abstractly and neuroscience is not allowed to play a contructive role. We argue that the proper integration of neuroscience, psychology, and evolutionary biology requires a telelogical as opposed to a merely componential analysis of function. A teleological analysis is required in neuroscience itself; we point to traditional and curent research methods in neuroscience, which make critical use of (...) distinctly teleological functional considerations in brain cartography. Only by invoking teleological criteria can researchers distinguish the fruitful ways of identifying brain components from the myriad of possible ways. One likely reason for reluctance to turn to neuroscience is fear of reduction, but we argue that, in the context of a teleological perspective on function, this concern is misplaced. Adducing such theoretical considerations as top-down and bottom-up constraints on neuroscientific and psychological models, as well as existing cases of productive, multidisciplinary cooperation, we argue that integration of neuroscience into psychology and evolutionary biology is likely to be mutually beneficial. We also show how it can be accommodated methodologically within the framework of an interfield theory. (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 notion of a physiological individuals has been developed and applied in the philosophy of biology to understand symbiosis, an understanding of which is key to theorising about the major transition in evolution from multi-organismality to multi-cellularity. The paper begins by asking what such symbiotic individuals can help to reveal about a possible transition in the evolution of cognition. Such a transition marks the movement from cooperating individual biological cognizers to a functionally integrated cognizing unit. Somewhere along the way, (...) did such cognizing units simultaneously have cognizers as parts? Expanding upon the multiscale integration view of the Free Energy Principle, this paper develops an account of reciprocal integration, demonstrating how some coupled biological cognizing systems, when certain constraints are met, can result in a cognizing unit that is in ways greater than the sum of its cognizing parts. Symbiosis between V. Fischeri bacteria and the bobtail squid is used to provide an illustration this account. A novel manner of conceptualizing biological cognizers as gradient is then suggested. Lastly it is argued that the reason why the notion of ontologically nested cognizers may be unintuitive stems from the fact that our folk-psychology notion of what a cognizer is has been deeply influenced by our folk-biological manner of understanding biological individuals as units of reproduction. (shrink)

This paper focuses on physiological integration in multicellular systems, a notion often associated with biological individuality, but which has not received enough attention and needs a thorough theoretical treatment. Broadly speaking, physiological integration consists in how different components come together into a cohesive unit in which they are dependent on one another for their existence and activity. This paper argues that physiological integration can be understood by considering how the components of a biological multicellular system are controlled and (...) coordinated in such a way that their activities can contribute to the maintenance of the system. The main implication of this perspective is that different ways of controlling their parts may give rise to multicellular organizations with different degrees of integration. After defining control, this paper analyses how control is realized in two examples of multicellular systems located at different ends of the spectrum of multicellularity: biofilms and animals. It focuses on differences in control ranges, and it argues that a high degree of integration implies control exerted at both medium and long ranges, and that insofar as biofilms lack long-range control (relative to their size) they can be considered as less integrated than other multicellular systems. It then discusses the implication of this account for the debate on physiological individuality and the idea that degrees of physiological integration imply degrees of individuality. (shrink)

This introduction to the special section on integration in biology provides an overview of the different contributions. In addition to motivating the philosophical significance of analyzing integration and interdisciplinary research, I lay out common themes and novel insights found among the special section contributions, and indicate how they exhibit current trends in the philosophical study of integration. One upshot of the contributed papers is that there are different aspects to and kinds of integration, so that rather than attempting to offer (...) a universal construal of what integrations is, philosophers have to analyze in concrete cases in what respects particular aspects of scientific theorizing and/or practice are ‘integrative’ and how this instance of integration works and was achieved. (shrink)

Robert Rosen’s relational biology and biosemiotics share the claim that life cannot be explained by the laws that apply to the inanimate world alone. In this paper, an integrated account of Rosen’s relational biology and Peirce’s semiosis is proposed. The ultimate goal is to contribute to the construction of a unified framework for the definition and study of life. The relational concepts of component and mapping, and the semiotic concepts of sign and triadic relation are discussed and compared, and a (...) representation of semiotic relations with mappings is proposed. The role of the final cause in two theories that account for what differentiates living beings, natural selection and relational biology, is analyzed. Then the presence of the final cause in Peirce’s semiosis is discussed and, with it, the similarities and differences between the theories of Rosen and Peirce are deepened. Then, a definition of a semiotic relation in an organism is proposed, and Short’s definition of interpretation is applied. Finally, a method to identify and analyze semiotic actions in an organism is proposed. (shrink)

The idea behind this special theme journal issue was to continue the work we have started with the INBIOSA initiative (www.inbiosa.eu) and our small inter-disciplinary scientific community. The result of this EU funded project was a white paper (Simeonov et al., 2012a) defining a new direction for future research in theoretical biology we called Integral Biomathics and a volume (Simeonov et al., 2012b) with contributions from two workshops and our first international conference in this field in 2011. The initial impulse (...) for this effort was given a year earlier by a publication of one of the guest editors of this issue (Simeonov, 2010) in this journal. This time we wish to provide a broader forum and more space to elaborate in detail some of the most interesting concepts we have encountered in our discussions, as well as to invite some new contributions of particular interest in the field. Another goal we had in mind was to collect and review as many provocative perspectives as possible on the same key topic we are interested before making a decision to follow a more focused notion that would lead to a funded research program. Therefore we welcomed the generous suggestion of Professor Denis Noble, FRS, who is also editor of this journal to prepare a special theme issue entitled: “Can biology create a profoundly new mathematics and computation?” It has taken a while to invite and collect the contributions. Most of them had a couple of revision cycles and adjustments after having been thoroughly discussed with colleagues, incl. the editors of this issue. We think that the result we have obtained at the end is a satisfactory one, since we succeeded to integrate a diversity of original, but sometimes controversial and mutually excluding concepts organized within chapters of a self-contained volume. The task of compiling all this was not easy at all. Despite our efforts to position the articles of different authors and themes in a way allowing their easy comprehension and relation to each other within the individual chapters, some of them still require a sort of introduction to dissolve possible ambiguities. This is what we are going to do in the following few paragraphs with the hope that the reader (and some of the authors) would excuse our failures. (shrink)

This edited collection showcases some of the best recent research in the philosophy of science. It comprises of thematically arranged papers presented at the 5th conference of the European Philosophy of Science Association (EPSA15), covering a broad variety of topics within general philosophy of science, and philosophical issues pertaining to specific sciences. The collection will appeal to researchers with an interest in the philosophical underpinnings of their own discipline, and to philosophers who wish to study the latest work on the (...) themes discussed. (shrink)

Mechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse. Multiple data sources might be required, and data may not be in a uniform (...) or desirable format. We describe a calibration strategy to address the challenges of scarcity and heterogeneity of calibration data. Our strategy focuses on parameters whose initial values cannot be easily derived from the literature, and our goal is to determine the values of these parameters via calibration with constraints set by relevant data. When combined with a covariance matrix adaptation evolution strategy, this step-by-step approach can be applied to a wide range of biological models. We describe a stepwise, integrative and iterative approach to multiscale mechanistic model calibration, and provide an example of calibrating a pathophysiological lung adenocarcinoma model. Using the approach described here we illustrate the successful calibration of a complex knowledge-based mechanistic model using only the limited heterogeneous datasets publicly available in the literature. (shrink)

Philosophical theories about reduction and integration in science are at variance with what is happenign in science. A realistic approach to science show that possibilities for reduction and integration are limited. The classical ideal of a unified science has since long been rejected in philosophy. But the current emphasis on interdisciplinary integration in philosophy and in science shows that it survives in a different guise. It is necessary to redress the balance, specifically in biology. Methodological analysis shows that many of (...) the grand interdisciplinary theories involving biology actually represent pseudo-integration covered up by inappropriate, overgeneral concepts. Integrationism is not bad, but it must be kept within reasonable bounds. If the present analysis is appropriate, there will have to be fundamental changes in research strategy both in science and in the philosophy of science. (shrink)

Current ethical analysis tends to evaluate synthetic biology at an overview level. Synthetic biology, however, is an umbrella term that covers a variety of areas of research. These areas contain, in turn, a hierarchy of different research fields. This abstraction hierarchy—the term is borrowed from engineering—permits synthetic biologists to specialise to a very high degree. Though synthetic biology per se may create profound ethical challenges, much of the day-to-day research does not. Yet seemingly innocuous research could lead to ethically problematic (...) results. For example, Dolly the sheep resulted from a long series of research steps, none of which presented any ethical problems. The atomic bomb was developed as a result of Einstein’s uncontentions theoretical research that proved the equivalence of matter and energy. Therefore it would seem wise for ethicists to evaluate synbio research across its subfields and through its abstraction hierarchies, comparing and inter-relating the various areas of research. In addition, it would be useful if journals that publish synbio papers require an ethical statement from authors, as standard practice, so as to encourage scientists to constantly engage with ethical issues in their work. Also, this would allow an ethical snapshot of the state of the research at any given time to exist, allowing for accurate evaluation by scientists and ethicists, regulators and policymakers. (shrink)

Living organisms act as integrated wholes to maintain themselves. Individual actions can each be explained by characterizing the mechanisms that perform the activity. But these alone do not explain how various activities are coordinated and performed versatilely. We argue that this depends on a specific type of mechanism, a control mechanism. We develop an account of control by examining several extensively studied control mechanisms operative in the bacterium E. coli. On our analysis, what distinguishes a control mechanism from other mechanisms (...) is that it relies on measuring one or more variables, which results in setting constraints in the control mechanism that determine its action on flexible constraints in other mechanisms. In the most basic arrangement, the measurement process directly determines the action of the control mechanism, but in more complex arrangements signals mediate between measurements and effectors. This opens the possibility of multiple responses to the same measurement and responses based on multiple measurements. It also allows crosstalk, resulting in networks of control mechanisms. Such networks integrate the behaviors of the organism but also present a challenge in tailoring responses to particular measurements. We discuss how integrated activity can still result in differential, versatile, responses. (shrink)

Philosophical theories about reduction and integration in science are at variance with what is happenign in science. A realistic approach to science show that possibilities for reduction and integration are limited. The classical ideal of a unified science has since long been rejected in philosophy. But the current emphasis on interdisciplinary integration in philosophy and in science shows that it survives in a different guise. It is necessary to redress the balance, specifically in biology. Methodological analysis shows that many of (...) the grand interdisciplinary theories involving biology actually represent pseudo-integration covered up by inappropriate, overgeneral concepts. Integrationism is not bad, but it must be kept within reasonable bounds. If the present analysis is appropriate, there will have to be fundamental changes in research strategy both in science and in the philosophy of science. (shrink)

Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an interdisciplinary approach to solving complex problems. Interdisciplinary science is a recent topic in the philosophy of science. Determining what is philosophically important and distinct about interdisciplinary practices requires detailed accounts of problem-solving practices that attempt to understand how specific practices address (...) the challenges and constraints of interdisciplinary research in different contexts. In this paper we draw from our 5-year empirical ethnographic study of two systems biology labs and their collaborations with experimental biologists to analyze a significant problem-solving approach in ISB, which we call adaptive problem solving. ISB lacks much of the methodological and theoretical resources usually found in disciplines in the natural sciences, such as methodological frameworks that prescribe reliable model-building processes. Researchers in our labs compensate for the lack of these and for the complexity of their problems by using a range of heuristics and experimenting with multiple methods and concepts from the background fields available to them. Using these resources researchers search out good techniques and practices for transforming intractable problems into potentially solvable ones. The relative freedom lab directors grant their researchers to explore methodological options and find good practices that suit their problems is not only a response to the complex interdisciplinary nature of the specific problem, but also provides the field itself with an opportunity to discover more general methodological approaches and develop theories of biological systems. Such developments in turn can help to establish the field as an identifiably distinct and successful approach to understanding biological systems. (shrink)

Many studies of the unification of science focus on the theories of different disciplines. The model for integration is the theory reduction model. This paper argues that the embodiment of theories in scientists, and the institutions in which scientists work and the instruments they employ, are critical to the sort of integration that actually occurs in science. This paper examines the integration of scientific endeavors that emerged in cell biology in the period after World War II when the development of (...) cell fractionation and electron microscopy made serious investigations of cell organelles possible. One surprising feature of such integration is that it generated further disintegration as the new institutions of cell biology separated the practitioners of the new discipline from other, closely related biological disciplines. (shrink)

I introduce a range of examples of different causal hypotheses about human mate selection. The hypotheses I focus on come from evolutionary psychology, fluctuating asymmetry research and chemical signaling research. I argue that a major obstacle facing an integrated biology of human behavior is the lack of a causal framework that shows how multiple proximate causal mechanisms can act together to produce components of our behavior.

Geckos have gained ecological access to novel microhabitats by exploiting intermolecular van der Waals forces, which allow them to climb smooth vertical surfaces. They use microscopic surface‐based phenomena to thrive in a macroscopic mass‐ and kinetic energy‐based world. Here we detail this as a premier example of integrative biology, spanning seven orders of magnitude and a lot of interesting biology. Emergent properties arising from molecular adhesion include several adaptive radiations that have produced a great diversity of geckos worldwide. BioEssays 27:647–652, (...) 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In a previous paper, an integrated account of Rosen’s relational biology and Peirce’s semiosis has been proposed. Both theories have been compared and basic concepts have been posited for the definition of a unified framework for the study of biology, as well as a method for the identification and analysis of the presence of signs in an organism. The analysis of the existence of semiotic actions in an organism must, without a doubt, begin by considering each of the rules that (...) constitute the genetic code as a candidate for a semiotic relation. Transcription and translation, which constitute protein synthesis, are the basis of the specificity that the organism needs to maintain itself in its environment and reproduce, and the precondition of the existence of any other possible semiosis. Applying the concepts and method of the aforementioned work, this paper analyzes which of the biological processes involved in protein synthesis correspond to semiotic actions and the type of the signs identified, according to Peirce’s classification of icons, indices and symbols. The results of this work demonstrate the theoretical consistency and the practical utility of integrating the theories of Rosen and Peirce, offer a way to identify other signs in an organism, and support a critical analysis of code biology and protosemiosis, two accounts that deny the possibility of explaining the signs in an organism with Peirce’s semiosis. (shrink)

The progress of the molecular biosciences has been so enormous that a discipline studying how cellular functioning emerges out of the behaviors of their molecular constituents has become reality. Systems biology studies cells as spatiotemporal networks of interacting molecules using an integrative approach of theory , experimental biology , and quantitative network-wide analytical measurement . Its aim is to understand how molecules jointly bring about life. Systems biology is rapidly discovering principles governing the functioning of molecular networks and methods to (...) model and measure them. The application of the conceptual strength of systems sciences such as physics and engineering are opening up new ways of experimentally studying the design and functioning of molecular networks. Typically, in such studies models are used to highlight principles, design experiments, or to act in a predictive mode to specifically modify cellular behavior. In this trend article, theoretical approaches being applied in systems biology will be discussed. A number of books have recently appeared that deal with theoretical aspects of systems biology. In this article they are highlighted to facilitate the communication of systems biology to a broader audience. (shrink)

Integrative systems biology is among the most innovative fields of contemporary science, bringing together scientists from a range of diverse backgrounds and disciplines to tackle biological complexity through computational and mathematical modeling. The result is a plethora of problem-solving techniques, theoretical perspectives, lab-structures and organizations, and identity labels that have made it difficult for commentators to pin down precisely what systems biology is, philosophically or sociologically. In this paper, through the ethnographic investigation of two ISB laboratories, we explore the (...) particular structural features of ISB thinking and organization and its relations to other disciplines that necessitate cognitive innovation at all levels from lab PI’s to individual researchers. We find that systems biologists face numerous constraints that make the production of models far from straight-forward, while at the same time they inhabit largely unstructured task environments in comparison to other fields. We refer to these environments as adaptive problem spaces. These environments they handle by relying substantially on the flexibility and affordances of model-based reasoning to integrate these various constraints and find novel adaptive solutions. Ultimately what is driving this innovation is a determination to construct new cognitive niches in the form of functional model building frameworks that integrate systems biology within the biological sciences. The result is an industry of diverse and different innovative practices and solutions to the problem of modeling complex, large-scale biological systems. (shrink)

An important insight derived from Kant about the workings of the mind is that conscious activity involves both the selection of relevant information, and the integration of that information, so as to form mental coherency. The conscious mind can then utilize this coherent information to solve problems, invent tools, synthesize concepts, produce works of art, and the like. In this paper, it will be suggested that just as biological processes, in general, exhibit selective and integrative functions, and just as (...) visual integration performs the function of selecting and integrating visual module areas, so too, consciousness emerged as a property of the brain to act as a kind of meta-cognitive process that selects and integrates relevant information from psychological modules. The upshot is to establish a psycho-neuro-biological continuum by suggesting that the conscious psychological properties of selectivity and integration are possible because of similar properties that other neurobiological and biological processes exhibit. (shrink)

The mainstream rationale for equating brain death (BD) with death is that the brain confers integrative unity upon the body, transforming it from a mere collection of organs and tissues to an organism as a whole. In support of this conclusion, the impressive list of the brains myriad integrative functions is often cited. Upon closer examination, and after operational definition of terms, however, one discovers that most integrative functions of the brain are actually not somatically integrating, and, conversely, most integrative (...) functions of the body are not brain-mediated. With respect to organism-level vitality, the brains role is more modulatory than constitutive, enhancing the quality and survival potential of a presupposedly living organism. Integrative unity of a complex organism is an inherently nonlocalizable, holistic feature involving the mutual interaction among all the parts, not a top-down coordination imposed by one part upon a passive multiplicity of other parts. Loss of somatic integrative unity is not a physiologically tenable rationale for equating BD with death of the organism as a whole. (shrink)

Living systems employ several mechanisms and behaviors to achieve robustness and maintain themselves under changing internal and external conditions. Regulation stands out from them as a specific form of higher-order control, exerted over the basic regime responsible for the production and maintenance of the organism, and provides the system with the capacity to act on its own constitutive dynamics. It consists in the capability to selectively shift between different available regimes of self-production and self-maintenance in response to specific signals and (...) perturbations, due to the action of a dedicated subsystem which is operationally distinct from the regulated ones. The role of regulation, however, is not exhausted by its contribution to maintain a living system’s viability. While enhancing robustness, regulatory mechanisms play a fundamental role in the realization of an autonomous biological organization. Specifically, they are at the basis of the remarkable integration of biological systems, insofar as they coordinate and modulate the activity of distinct functional subsystems. Moreover, by implementing complex and hierarchically organized control architectures, they allow for an increase in structural and organizational complexity while minimizing fragility. Finally, they endow living systems, from their most basic unicellular instances, with the capability to control their own internal dynamics to adaptively respond to specific features of their interaction with the environment, thus providing the basis for the emergence of minimal forms of cognition. (shrink)

The Hooks et al. review of microbiota-gut-brain literature provides a constructive criticism of the general approaches encompassing MGB research. This commentary extends their review by: highlighting capabilities of advanced systems-biology “-omics” techniques for microbiome research and recommending that combining these high-resolution techniques with intervention-based experimental design may be the path forward for future MGB research.

Over the last decade the modeling and the storage of biological data has been a topic of wide interest for scientists dealing with biological and biomedical research. Currently most data is still stored in text files which leads to data redundancies and file chaos.In this paper we show how to use relational modeling techniques and relational database technology for modeling and storing biological sequence data, i.e. for data maintained in collections like EMBL or SWISS-PROT to better serve (...) the needs for these application domains.For this reason we propose a two step approach. First, we model the structure (and therefore the meaning of the) data using an Entity-Relationship approach. The ER model leads to a clean design of a relational database schema for storing and retrieving the DNA and protein data extracted from various sources. Our approach provides the clean basis for building complex biological applications that are more amenable to changes and software ports than their file-base counterparts. (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 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)

Yasha Rohwer and Emma Marris argue there is no prima facie duty to preserve genetic integrity; they contend, rather, that preserving the integrity of specific genomes is only a mean...

Is integrative biology a good idea, or even possible? There has been much interest lately in the unifica- tion of biology and the integration of traditionally separate disciplines such as molecular and develop- mental biology on one hand, and ecology and evolutionary biology on the other. In this paper I ask if and under what circumstances such integration of efforts actually makes sense. I develop by example an analogy with Aristotle’s famous four “causes” that one can investigate concerning any object (...) or phenomenon: material (what something is made of), formal (what distinguishes that particular object from others), efficient (how was the object made) and final (why was the object made). The example is provided by ongoing research on different aspects of flowering time in the model system Arabidop- sis, a small weed belonging to the mustard family. I show that understanding how flowering time is controlled is an epistemologically different sort of question from why and how it evolved, and that the two research agendas can be pursued largely independently of each other. Toward the end, I propose that the real goal of integrative biology is to understand the boundary layers between levels of biologi- cal analysis, something to which modern philosophy of science can contribute significantly. (shrink)

The INBIOSA project brings together a group of experts across many disciplines who believe that science requires a revolutionary transformative step in order to address many of the vexing challenges presented by the world. It is INBIOSA’s purpose to enable the focused collaboration of an interdisciplinary community of original thinkers. This paper sets out the case for support for this effort. The focus of the transformative research program proposal is biology-centric. We admit that biology to date has been more fact-oriented (...) and less theoretical than physics. However, the key leverageable idea is that careful extension of the science of living systems can be more effectively applied to some of our most vexing modern problems than the prevailing scheme, derived from abstractions in physics. While these have some universal application and demonstrate computational advantages, they are not theoretically mandated for the living. A new set of mathematical abstractions derived from biology can now be similarly extended. This is made possible by leveraging new formal tools to understand abstraction and enable computability. [The latter has a much expanded meaning in our context from the one known and used in computer science and biology today, that is "by rote algorithmic means", since it is not known if a living system is computable in this sense (Mossio et al., 2009).] Two major challenges constitute the effort. The first challenge is to design an original general system of abstractions within the biological domain. The initial issue is descriptive leading to the explanatory. There has not yet been a serious formal examination of the abstractions of the biological domain. What is used today is an amalgam; much is inherited from physics (via the bridging abstractions of chemistry) and there are many new abstractions from advances in mathematics (incentivized by the need for more capable computational analyses). Interspersed are abstractions, concepts and underlying assumptions “native” to biology and distinct from the mechanical language of physics and computation as we know them. A pressing agenda should be to single out the most concrete and at the same time the most fundamental process-units in biology and to recruit them into the descriptive domain. Therefore, the first challenge is to build a coherent formal system of abstractions and operations that is truly native to living systems. Nothing will be thrown away, but many common methods will be philosophically recast, just as in physics relativity subsumed and reinterpreted Newtonian mechanics. -/- This step is required because we need a comprehensible, formal system to apply in many domains. Emphasis should be placed on the distinction between multi-perspective analysis and synthesis and on what could be the basic terms or tools needed. The second challenge is relatively simple: the actual application of this set of biology-centric ways and means to cross-disciplinary problems. In its early stages, this will seem to be a “new science”. This White Paper sets out the case of continuing support of Information and Communication Technology (ICT) for transformative research in biology and information processing centered on paradigm changes in the epistemological, ontological, mathematical and computational bases of the science of living systems. Today, curiously, living systems cannot be said to be anything more than dissipative structures organized internally by genetic information. There is not anything substantially different from abiotic systems other than the empirical nature of their robustness. We believe that there are other new and unique properties and patterns comprehensible at this bio-logical level. The report lays out a fundamental set of approaches to articulate these properties and patterns, and is composed as follows. -/- Sections 1 through 4 (preamble, introduction, motivation and major biomathematical problems) are incipient. Section 5 describes the issues affecting Integral Biomathics and Section 6 -- the aspects of the Grand Challenge we face with this project. Section 7 contemplates the effort to formalize a General Theory of Living Systems (GTLS) from what we have today. The goal is to have a formal system, equivalent to that which exists in the physics community. Here we define how to perceive the role of time in biology. Section 8 describes the initial efforts to apply this general theory of living systems in many domains, with special emphasis on crossdisciplinary problems and multiple domains spanning both “hard” and “soft” sciences. The expected result is a coherent collection of integrated mathematical techniques. Section 9 discusses the first two test cases, project proposals, of our approach. They are designed to demonstrate the ability of our approach to address “wicked problems” which span across physics, chemistry, biology, societies and societal dynamics. The solutions require integrated measurable results at multiple levels known as “grand challenges” to existing methods. Finally, Section 10 adheres to an appeal for action, advocating the necessity for further long-term support of the INBIOSA program. -/- The report is concluded with preliminary non-exclusive list of challenging research themes to address, as well as required administrative actions. The efforts described in the ten sections of this White Paper will proceed concurrently. Collectively, they describe a program that can be managed and measured as it progresses. (shrink)

Living systems employ several mechanisms and behaviors to achieve robustness and maintain themselves under changing internal and external conditions. Regulation stands out from them as a specific form of higher-order control, exerted over the basic regime responsible for the production and maintenance of the organism, and provides the system with the capacity to act on its own constitutive dynamics. It consists in the capability to selectively shift between different available regimes of self-production and self-maintenance in response to specific signals and (...) perturbations, due to the action of a dedicated subsystem which is operationally distinct from the regulated ones. The role of regulation, however, is not exhausted by its contribution to maintain a living system’s viability. While enhancing robustness, regulatory mechanisms play a fundamental role in the realization of an autonomous biological organization. Specifically, they are at the basis of the remarkable integration of biological systems, insofar as they coordinate and modulate the activity of distinct functional subsystems. Moreover, by implementing complex and hierarchically organized control architectures, they allow for an increase in structural and organizational complexity while minimizing fragility. Finally, they endow living systems, from their most basic unicellular instances, with the capability to control their own internal dynamics to adaptively respond to specific features of their interaction with the environment, thus providing the basis for the emergence of minimal forms of cognition. (shrink)

Over the last decade the modeling and the storage of biological data has been a topic of wide interest for scientists dealing with biological and biomedical research. Currently most data is still stored in text files which leads to data redundancies and file chaos.In this paper we show how to use relational modeling techniques and relational database technology for modeling and storing biological sequence data, i.e. for data maintained in collections like EMBL or SWISS-PROT to better serve (...) the needs for these application domains. (shrink)