Interlevel Relations in Biology

Mechanisms play a crucial role in scientific research across various disciplines, and philosophers of science have devoted significant effort into understanding their ontology and epistemology. This paper examines the relationship between mechanisms and phenomena, highlighting the inherent dependence of mechanistic delineation on the characterization of phenomena. By acknowledging that characterizing phenomena is influenced by pragmatic considerations and research interests, the paper argues that mechanistic inquiry is inherently shaped by researchers’ perspectives. This dependence raises concerns about the possibility of a realist (...) view of mechanisms. To address these concerns, the paper explores how top-down constraints, rooted in researchers’ interests and pragmatic concerns, can be balanced by bottom-up constraints derived from empirical considerations. In conclusion, I argue that the interplay between these constraints forms an empirical and realist counterweight to the perspectival nature of top-down constraints. (shrink)

Recent trends in psychiatry involve a transition from categorical to dimensional frameworks, in which the boundary between health and pathology is understood as a difference in degree rather than as a difference in kind. A major tenet of dimensional approaches is that no qualitative distinction can be made between health and pathology. As a consequence, these approaches tend to characterize such a threshold as pragmatic or conventional in nature. However, dimensional approaches to psychopathology raise several epistemological and ontological issues. First, (...) we review major sources of evidence usually recruited in support of the dimensional trend (focusing on clinical observation and biological data), and we show that these are connected to different conceptualizations of how dimensional traits extend across health and pathology. Second, we criticize two unquestioned assumptions that stand at the core of the dimensional trend: a) that there is continuity from health to pathology at the symptomatic level; b) that such continuity reflects an underlying continuity in the genetic liability for pathological conditions. Third, we argue against the idea of a conventional threshold by showing that such a view implies a linear relationship between the genotype and the phenotype. Fourth, drawing on epigenetics and developmental biology, we offer a characterization of mental disorders as stable and dynamic constellations of multi-level variables that differ qualitatively from ‘healthy states’. We conclude by showing that our account has several theoretical advantages over both categorical and dimensional approaches. Notably, it provides crucial insights into psychological development over time and individual differences, with major implications in terms of intervention and clinical decision-making. (shrink)

Realists about mental disorder have been hasty about dismissing social explanations of how mental disorder is constituted. However, many social ontologies are realist ontologies. In order to create a meaningful distinction between realism and social metaphysics about mental disorder, I propose that realism about mental disorder is best understood as Individual Trait Realism (ITR) about them. For ITR, mental disorders exist in virtue of traits. I defend the view that ITR is compatible with social metaphysics, arguing that, in asking whether (...) constituents in the social sphere figure the metaphysics of psychopathology, we are asking questions on three different strata of explanation: the strata of demarcation, instantiation, and individual traits. Distinguishing between these strata allows for nuanced realism that need not reject the social constitution of mental disorder. (shrink)

Some New Mechanists have proposed that claims of compositional relations are justified by combining the results of top-down and bottom-up interlevel interventions. But what do scientists do when they can perform, say, a cellular intervention, but not a subcellular detection? In such cases, paired interlevel interventions are unavailable. We propose that scientists use abduction and we illustrate its use through a case study of the ionic theory of resting and action potentials.

Organization figures centrally in the understanding of biological systems advanced by both new mechanists and proponents of the autonomy framework. The new mechanists focus on how components of mechanisms are organized to produce a phenomenon and emphasize productive continuity between these components. The autonomy framework focuses on how the components of a biological system are organized in such a way that they contribute to the maintenance of the organisms that produce them. In this paper we analyze and compare these two (...) accounts of organization and argue that understanding biological organisms as cohesively integrated systems benefits from insights from both. To bring together the two accounts, we focus on the notions of control and regulation as bridge concepts. We start from a characterization of biological mechanisms in terms of constraints and focus on a specific type of mechanism, control mechanisms, that operate on other mechanisms on the basis of measurements of variables in the system and its environment. Control mechanisms are characterized by their own set of constraints that enable them to sense conditions, convey signals, and effect changes on constraints in the controlled mechanism. They thereby allow living organisms to adapt to internal and external variations and to coordinate their parts in such a manner as to maintain viability. Because living organisms contain a vast number of control mechanisms, a central challenge is to understand how they are themselves organized. With the support of examples from both unicellular and multicellular systems we argue that control mechanisms are organized heterarchically, and we discuss how this type of control architecture can, without invoking top-down and centralized forms of organizations, succeed in coordinating internal activities of organisms. (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)

I propose a dynamic causal approach to characterizing the notion of a mechanism. Levy and Bechtel, among others, have pointed out several critical limitations of the new mechanical philosophy, and pointed in a new direction to extend this philosophy. Nevertheless, they have not fully fleshed out what that extended philosophy would look like. Based on a closer look at neuroscientific practice, I propose that a mechanism is a dynamic causal system that involves various components interacting, typically nonlinearly, with one another (...) to produce a phenomenon of interest. (shrink)

What kinds of norms constrain mechanistic discovery and explanation? In the mechanistic literature, the norms for good explanations are directly derived from answers to the metaphysical question of what explanations are. Prominent mechanistic accounts thus emphasize either ontic or epistemic norms. Still, mechanistic philosophers on both sides agree that there is no sharp distinction between the processes of discovery and explanation. Thus, it seems reasonable to expect that ontic and epistemic accounts of explanation will be accompanied by ontic and epistemic (...) accounts of discovery, respectively. As we will show here, however, recent discovery accounts implicitly rely on both ontic and epistemic norms to characterize the discovery process. In this paper, we develop an account that makes explicit that, and how, ontic and epistemic norms work together throughout the discovery process. By describing mechanism discovery as a process of pattern recognition we demonstrate that scientists have to develop epistemic activities to distinguish a pattern from its background. Furthermore, they have to determine which epistemic activities successfully describe how the pattern is implemented by identifying the pattern’s components. Our approach reveals that ontic and epistemic norms are equally important in mechanism discovery. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

The organism against its environment. The organism against other organisms, competing and struggling for life. Antagonism and confrontment as the only possible relation in nature. The tendency to anthropomorphize nature and explain it using concepts and facts from the human sphere. A stroll through the worlds of Uexküll and Merleau-Ponty in the search of alternative knowledge that allow us to understand relation from another point of view. A counterpoint and identification of common tonalities between the research programs from both thinkers (...) as a way to demonstrate the possibilities of a more fruitful approach. Umwelt as a generative system of meaningful relations in which its participants are not mutually exclusive, but express a melody that include them all. (shrink)

Life is the center of our existence. One would be tempted to say that first of all we live. However, our existence does not seem to pass in that modality. The exacerbated materialism in which our existence takes place, displaces life from the center of the scene. Our society is organized around production, consumerism, exploitation, efficiency, trade and propaganda. That is to say, our existence seems to have economy as the center of organization of our activities. The struggle of this (...) century that is beginning is to put life at the center of our existence, and to put economy in its proper place, that is, in the service of life. (shrink)

Over the last decades, network-based approaches have become highly popular in diverse fields of biology, including neuroscience, ecology, molecular biology and genetics. While these approaches continue to grow very rapidly, some of their conceptual and methodological aspects still require a programmatic foundation. This challenge particularly concerns the question of whether a generalized account of explanatory, organisational and descriptive levels of networks can be applied universally across biological sciences. To this end, this highly interdisciplinary theme issue focuses on the definition, motivation (...) and application of key concepts in biological network science, such as explanatory power of distinctively network explanations, network levels, and network hierarchies. (shrink)

Many researchers consider cancer to have molecular causes, namely mutated genes that result in abnormal cell proliferation (e.g. Weinberg 1998); yet for others, the causes of cancer are to be found not at the molecular level but at the tissue level and carcinogenesis would consist in a disrupted tissue organization with downward causation effects on cells and cellular components (e.g. Sonnenschein & Soto 2008). In this contribution, I ponder how to make sense of such downward causation claims. Adopting a manipulationist (...) account of causation (Woodward 2003), I propose a formal definition of downward causation, and discuss further requirements (in light of Baumgartner 2009). I then show that such an account cannot be mobilized in support of non-reductive physicalism (contrary to Raatikainen 2010). However, I also argue that such downward causation claims might point at particularly interesting dynamic properties of causal relationships that might prove salient in characterizing causal relationships (following Woodward 2010). (shrink)

"Brower explores the way philosophers were inspired by entomological social systems and communication to reflect on human psyche, social behavior, community organization, communication, and inter-individual relationships. His essay rehearses the swarms of insects embedded in contemporary philosophy and literary theory, not only showing how many of the major concepts (or philosophemes) in continental philosophy – sexuality, politics, thinking, time, interdependence, and language – draw lessons from the world of insects, but also illustrating again how the insect world spurred human reflection.".

Bence Nanay has argued that we must abandon the etiological theory of teleological function because this theory explains functions and functional categories in a circular manner. Paul Griffiths argued earlier that we should retain the etiological theory and instead prevent the circularity by making etiologies independent of functional categories. Karen Neander and Alex Rosenberg reply to Nanay similarly, and argue that we should analyze functions in terms of natural selection acting not on functional categories, but merely on lineages. Nanay replies (...) that these lineages cannot be individuated except by reference to functional categories. Worryingly, Neander and Rosenberg themselves have previously argued persuasively that homology often depends on function. This article addresses their arguments and shows how to escape them: Regardless whether the arguments are right about long-term homological categories, they do not apply to generation-to-generation homology. The latter, moreover, is sufficient for individuating the lineages needed to explain teleological functions. (shrink)

The concept of the cortical column refers to vertical cell bands with similar response properties, which were initially observed by Vernon Mountcastle’s mapping of single cell recordings in the cat somatic cortex. It has subsequently guided over 50 years of neuroscientific research, in which fundamental questions about the modularity of the cortex and basic principles of sensory information processing were empirically investigated. Nevertheless, the status of the column remains controversial today, as skeptical commentators proclaim that the vertical cell bands are (...) a functionally insignificant by-product of ontogenetic development. This paper inquires how the column came to be viewed as an elementary unit of the cortex from Mountcastle’s discovery in 1955 until David Hubel and Torsten Wiesel’s reception of the Nobel Prize in 1981. I first argue that Mountcastle’s vertical electrode recordings served as criteria for applying the column concept to electrophysiological data. In contrast to previous authors, I claim that this move from electrophysiological data to the phenomenon of columnar responses was concept-laden, but not theory-laden. In the second part of the paper, I argue that Mountcastle’s criteria provided Hubel Wiesel with a conceptual outlook, i.e. it allowed them to anticipate columnar patterns in the cat and macaque visual cortex. I argue that in the late 1970s, this outlook only briefly took a form that one could call a ‘theory’ of the cerebral cortex, before new experimental techniques started to diversify column research. I end by showing how this account of early column research fits into a larger project that follows the conceptual development of the column into the present. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

We sketch the mechanistic approach to levels, contrast it with other senses of “level,” and explore some of its metaphysical implications. This perspective allows us to articulate what it means for things to be at different levels, to distinguish mechanistic levels from realization relations, and to describe the structure of multilevel explanations, the evidence by which they are evaluated, and the scientific unity that results from them. This approach is not intended to solve all metaphysical problems surrounding physicalism. Yet it (...) provides a framework for thinking about how the macroscopic phenomena of our world are or might be related to its most fundamental entities and activities. (shrink)

In a (2016) paper in this journal, I defuse allegations that theoretical ecological research is problematic because it relies on teleological metaphysical assumptions. Mark Sagoff offers a formal reply. In it, he concedes that I succeeded in establishing that ecologists abandoned robust teleological views long ago and that they use teleological characterizations as metaphors that aid in developing mechanistic explanations of ecological phenomena. Yet, he contends that I did not give enduring criticisms of theoretical ecology a fair shake in my (...) paper. He says this is because enduring criticisms center on concerns about the nature of ecological networks and forces, the instrumentality of ecological laws and theoretical models, and the relation between theoretical and empirical methods in ecology that that paper does not broach. Below I set apart the distinct criticisms Sagoff presents in his commentary and respond to each in turn. (shrink)

A recent evolution of computer simulations has led to the emergence of complex computer simulations. In particular, the need to formalize composite objects (those objects that are composed of other objects) has led to what the author suggests calling pluriformalizations, i.e. formalizations that are based on distinct sub-models which are expressed in a variety of heterogeneous symbolic languages. With the help of four case-studies, he shows that such pluriformalizations enable to formalize distinctly but simultaneously either different aspects or different parts (...) or different scales of the same object or system. From an epistemological standpoint, he suggests that this kind of computer-aided complex formalization of composite objects renew the traditional relations between computer simulations, theoretical models and operational models. (shrink)

The paper examines the main trends in the search for a theory of general biology throughout the 20th century — the physicalization on one hand, and the semiotization on the other. These two approaches had their predecessors and were formed already in the 19th century biology, as Darwinian and Baerian biology. In theoretical biology, there are co-existing (however, asymmetrical) trends toward specifying solutions and generalizing axioms. The inclusion of the biological organism as a subject into biological theory requires an analysis (...) of the concept of scientific fact. A cross-disciplinary typology of facts on the basis of their invariant features is provided. The main periods of development of theoretical biology are briefly characterised, and the trend towards the theory of biological communication and meaning outlined. (shrink)

Griffiths and Stotz’s Genetics and Philosophy: An Introduction offers a very good overview of scientific and philosophical issues raised by present-day genetics. Examining, in particular, the questions of how a “gene” should be defined and what a gene does from a causal point of view, the authors explore the different domains of the life sciences in which genetics has come to play a decisive role, from Mendelian genetics to molecular genetics, behavioural genetics, and evolution. In this review, I highlight what (...) I consider as the two main theses of the book, namely: genes are better conceived as tools; genes become causes only in a context. I situate these two theses in the wider perspective of developmental systems theory. This leads me to emphasize that Griffiths and Stotz reflect very well an on going process in genetics, which I call the “epigenetization” of genetics, i.e., the growing interest in the complex processes by which gene activation is regulated. I then make a factual objection, which is that Griffiths and Stotz have almost entirely neglected the perspective of ecological developmental biology, and more precisely recent work on developmental symbioses, and I suggest that this omission is unfortunate in so far as an examination of developmental symbioses would have considerably strengthened Griffiths and Stotz’s own conclusions. (shrink)

I show that the recent account of levels in neuroscience proposed by Craver and Bechtel is unsatisfactory since it fails to provide a plausible criterion for being at the same level and is incompatible with Craver and Bechtel’s account of downward causation. Furthermore, I argue that no distinct notion of levels is needed for analyzing explanations and causal issues in neuroscience: it is better to rely on more well-defined notions such as composition and scale. One outcome of this is that (...) apparent cases of downward causation can be analyzed away. (shrink)

Two senses of ‘ontology’ can be distinguished in the current literature. First is the sense favored by information scientists, who view ontologies as software implementations designed to capture in some formal way the consensus conceptualization shared by those working on information systems or databases in a given domain. [Gruber 1993] Second is the sense favored by philosophers, who regard ontologies as theories of different types of entities (objects, processes, relations, functions) [Smith 2003]. Where information systems ontologists seek to maximize reasoning (...) efficiency even at the price of simplifications on the side of representation, philosophical ontologists argue that representational adequacy can bring benefits for the stability and resistance to error of an ontological framework and also for its extendibility in the future. In bioinformatics, however, a third sense of ‘ontology’ has established itself, above all as a result of the successes of the Gene Ontology (hereafter: GO), which is a tool for the representation and processing of information about gene products and their biological functions [Gene Ontology Consortium 2000]. We show how Basic Formal Ontology (BFO) has established itself as an overarching ontology drawing on all three of the strands distinguished above, and describe applications of BFO especially in the treatment of biological granularity. (shrink)

Probably the most distinctive feature of synthetic biology is its being “synthetic” in some sense or another. For some, synthesis plays a unique role in the production of knowledge that is most distinct from that played by analysis: it is claimed to deliver knowledge that would otherwise not be attained. In this contribution, my aim is to explore how synthetic biology delivers knowledge via synthesis, and to assess the extent to which this knowledge is distinctly synthetic. On the basis of (...) distinctions between knowledge-how and knowledge-why, and between syntheses that succeed and syntheses that fail, I argue that the contribution of synthesis to knowledge is best understood when syntheses are construed as experimental interventions that aim at probing causal relationships between properties of the entities that are combined through these syntheses and properties of their target products. The distinctiveness of synthetic biology in its quest for knowledge through synthesis stems from its ability to sample at will a space of empirical possibilities that is not only huge but also that has been so scarcely sampled by nature. (shrink)

We argue that genuine biological autonomy, or described at human level as free will, requires taking into account quantum vacuum processes in the context of biological teleology. One faces at least three basic problems of genuine biological autonomy: (1) if biological autonomy is not physical, where does it come from? (2) Is there a room for biological causes? And (3) how to obtain a workable model of biological teleology? It is shown here that the solution of all these three problems (...) is related to the quantum vacuum. We present a short review of how this basic aspect of the fundamentals of quantum theory, although it had not been addressed for nearly 100 years, actually it was suggested by Bohr, Heisenberg, and others. Realizing that the quantum mechanical measurement problem associated with the “collapse” of the wave function is related, in the Copenhagen Interpretation of quantum mechanics, to a process between self-consciousness and the external physical environment, we are extending the issue for an explanation of the different processes occurring between living organisms and their internal environment. Definitions of genuine biological autonomy, biological aim, and biological spontaneity are presented. We propose to improve the popular two-stage model of decisions with a biological model suitable to obtain a deeper look at the nature of the mind-body problem. In the newly emerging picture biological autonomy emerges as a new, fundamental and inevitable element of the scientific worldview. (shrink)

Science and philosophy have a very long history, dating back at least to the 16th and 17th centuries, when the first scientist-philosophers, such as Bacon, Galilei, and Newton, were beginning the process of turning natural philosophy into science. Contemporary relationships between the two fields are still to some extent marked by the distrust that maintains the divide between the so-called “two cultures.” An increasing number of philosophers, however, are making conceptual contributions to sciences ranging from quantum mechanics to evolutionary biology, (...) and a few scientists are conducting research relevant to classically philosophical fields of inquiry, such as consciousness and moral decision-making. This article will introduce readers to the borderlands between science and philosophy, beginning with a brief description of what philosophy of science is about, and including a discussion of how the two disciplines can fruitfully interact not only at the level of scholarship, but also when it comes to controversies surrounding public understanding of science. (shrink)

An explicit formal-ontological representation of entities existing at multiple levels of granularity is an urgent requirement for biomedical information processing. We discuss some fundamental principles which can form a basis for such a representation. We also comment on some of the implicit treatments of granularity in currently available ontologies and terminologies (GO, FMA, SNOMED CT).

In this work I propose a theory of evolution as a process of unfolding. This theory is based on four logically concatenated principles. The principle of evolutionary order establishes that the more complex cannot be generated from the simpler. The principle of origin establishes that there must be a maximum complexity that originates the others by logical deduction. Finally, the principle of unfolding and the principle of actualization guarantee the development of the evolutionary process from the simplest to the most (...) complex. These logical principles determine the existence of a virtual ideological matrix that contains the sequence of the preformed and folded morphogenetic fields. In this manner, the evolutionary process consists of the sequential unfolding and actualization of these fields, which is motorized by a process of teleologization carried out by the opening consciousness of the forms included in the fields of the ideological matrix. This theory leads to a radical change of perspective regarding the materialist worldview, and places life at the center of the evolutionary process as an activity carried out by a consciousness that seeks to fulfill a purpose by actualizing its own potentialities. (shrink)

The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a (...) strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology. (shrink)

The idea of levels of organization plays a central role in the philosophy of the life sciences. In this article, I first examine the explanatory goals that have motivated accounts of levels of organization. I then show that the most state-of-the-art and scientifically plausible account of levels of organization, the account of levels of mechanism proposed by Bechtel and Craver, is fundamentally problematic. Finally, I argue that the explanatory goals can be reached by adopting a deflationary approach, where levels of (...) organization give way to more well-defined and fundamental notions, such as scale and composition. (shrink)

To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.