Interlevel Relations in Biology, Misc

One important aspect of biological explanation is detailed causal modeling of particular phenomena in limited experimental background conditions. Recognising this allows a new avenue for intertheoretic reduction to be seen. Reductions in biology are possible, when one fully recognises that a sufficient condition for a reduction in biology is a molecular model of 1) only the demonstrated causal parameters of a biological model and 2) only within a replicable experimental background. These intertheoretic identifications –which are ubiquitous in biology and form (...) the basis of ruthless reductions (Bickle 2003)- are criticised as merely “local” (Sullivan 2009) or “fragmentary” (Schaffner 2006). However, in an instructive case, a biological model is preserved in molecular terms, and a complex biological phenomenon has been successfully reduced. In doing this the molecular model remains valid in a broader range of background conditions and meaningfully unites disparate biological phenomena. (shrink)

We provide three innovations to recent debates about whether topological or “network” explanations are a species of mechanistic explanation. First, we more precisely characterize the requirement that all topological explanations are mechanistic explanations and show scientific practice to belie such a requirement. Second, we provide an account that unifies mechanistic and non-mechanistic topological explanations, thereby enriching both the mechanist and autonomist programs by highlighting when and where topological explanations are mechanistic. Third, we defend this view against some powerful mechanist objections. (...) We conclude from this that topological explanations are autonomous from their mechanistic counterparts. (shrink)

I attempt to characterize the relationship of classical experimental embryology (CEE) and molecular developmental biology and compare it to the much-discussed case of classical genetics. These sciences are treated here as discovery practices rather than as definitive forms of knowledge. I first show that CEE had some causal knowledge and hence was able to answer specific why?-questions. A paradigm was provided by the case of eye induction, perhaps CEE’s greatest success. The case of the famous Spemann-Mangold organizer is more difficult. (...) I argue that before the advent of molecular biology, knowledge of its causal role in development was very limited. As a result, there was no functional definition of the concept of organizer. I argue that, like the classical gene concept, it is best viewed as an operational concept. This means that an account of reduction such as Kim’s functional reduction, which is still a mainstay in scientific metaphysics, cannot work in these cases. Nonetheless, again like in the classical gene case, the operational concepts of CEE played an important heuristic role in the discovery of molecules involved in morphogenesis and cell differentiation. This was made possible by what I call inter-level investigative practices. These are practices that combine experimental manipulations targeting two (or more) different levels. I conclude that the two sciences are more closely related via their experimental practices than by any inter-level explanatory relations. (shrink)

An adequate understanding of the ubiquitous practice of mechanistic explanation requires an account of what Craver termed “constitutive relevance.” Entities or activities are constitutively relevant to a phenomenon when they are parts of the mechanism responsible for that phenomenon. Craver’s mutual manipulability account extended Woodward’s account of manipulationist counterfactuals to analyze how interlevel experiments establish constitutive relevance. Critics of MM argue that applying Woodward’s account to this philosophical problem conflates causation and constitution, thus rendering the account incoherent. These criticisms, we (...) argue, arise from failing to distinguish the semantic, epistemic, and metaphysical aspects of the problem of constitutive relevance. In distinguishing these aspects of the problem and responding to these critics accordingly, we amend MM into a refined epistemic criterion, the “matched interlevel experiments” account. Further, we explain how this epistemological thesis is grounded in the plausible metaphysical thesis that constitutive relevance is causal betweenness. (shrink)

Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in disease diagnostics and treatment, including DNA and RNA sequencing technology, treatment with drugs and natural products and vaccine development. The COVID-19 crisis, however, has also demonstrated the need for systemic thinking and transdisciplinarity and the limits (...) of MSM: the neglect of the bio-psycho-social systemic nature of humans and their context as the object of individual therapeutic and population-oriented interventions. COVID-19 illustrates how a medical problem requires a transdisciplinary approach in epidemiology, pathology, internal medicine, public health, environmental medicine, and socio-economic modeling. Regarding the need for conceptual integration of these different kinds of knowledge we suggest the application of general system theory (GST). This approach endorses an organism-centered view on health and disease, which according to Ludwig von Bertalanffy who was the founder of GST, we call Organismal Systems Medicine (OSM). We argue that systems science offers wider applications in the field of pathology and can contribute to an integrative systems medicine by (i) integration of evidence across functional and structural differentially scaled subsystems, (ii) conceptualization of complex multilevel systems, and (iii) suggesting mechanisms and non-linear relationships underlying the observed phenomena. We underline these points with a proposal on multi-level systems pathology including neurophysiology, endocrinology, immune system, genetics, and general metabolism. An integration of these areas is necessary to understand excess mortality rates and polypharmacological treatments. In the pandemic era this multi-level systems pathology is most important to assess potential vaccines, their effectiveness, short-, and long-time adverse effects. We further argue that these conceptual frameworks are not only valid in the COVID-19 era but also important to be integrated in a medicinal curriculum. (shrink)

Endocrinologists apply the idea of feedback loops to explain how hormones regulate certain bodily functions such as glucose metabolism. In particular, feedback loops focus on the maintenance of the plasma concentrations of glucose within a narrow range. Here, we put forward a different, organicist perspective on the endocrine regulation of glycaemia, by relying on the pivotal concept of closure of constraints. From this perspective, biological systems are understood as organized ones, which means that they are constituted of a set of (...) mutually dependent functional structures acting as constraints, whose maintenance depends on their reciprocal interactions. Closure refers specifically to the mutual dependence among functional constraints in an organism. We show that, when compared to feedback loops, organizational closure can generate much richer descriptions of the processes and constraints at play in the metabolism and regulation of glycaemia, by making explicit the different hierarchical orders involved. We expect that the proposed theoretical framework will open the way to the construction of original mathematical models, which would provide a better understanding of endocrine regulation from an organicist perspective. (shrink)

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)

Has science already answered the fundamental questions about the concepts of Life, Cosmos and Evolution? Has science not relegated these fundamental questions by following up on more immediate, “useful” and practical endeavors that ultimately ensure that the wheel of capitalism keeps spinning in its frantic search for material and economic progress? There is something terribly wrong with the current theory of evolution, understood as the Darwinian theory with its successive versions and extensions. The concept of natural selection, the cornerstone of (...) Darwinism, is logically inconsistent. This has been demonstrated in some of my latest academic publications. The entire conceptual framework of Darwinism is inadequate. Organisms do not compete with each other for the survival of the fittest. The fundamental relationship in Nature is not competition or confrontation, but interconnectivity, complementarity, and relational meaningfulness. A new theory of evolution is necessary to explain how it is possible that organisms as simple as bacteria, protozoa and diatoms could have generated organisms as complex as primates, and among them, the human being, a being capable of feeling and thinking, of suffering and enjoying, a being capable of having ideals and purposes. A theory that explains how it is possible that this being so complex, rich, and to some extent still unknown, has emerged from a single cell, an egg-cell, lacking all the capacities, riches and depths of human existence. Such a theory already exists. (shrink)

A holobiont is a composite organism consisting of a host together with its microbiome, such as a coral with its zooxanthellae. To explain the often intimate integration between hosts and their microbiomes, some investigators contend that selection operates on holobionts as a unit and view the microbiome’s genes as extending the host’s nuclear genome to jointly comprise a hologenome. Because vertical transmission of microbiomes is uncommon, other investigators contend that holobiont selection cannot be effective because a holobiont’s microbiome is an (...) acquired condition rather than an inherited trait. This disagreement invites a simple mathematical model to see how holobiont selection might operate and to assess its plausibility as an evolutionary force. This paper presents two variants of such a model. In one variant, juvenile hosts obtain microbiomes from their parents (vertical transmission). In the other variant, microbiomes of juvenile hosts are assembled from source pools containing the combined microbiomes of all parents (horizontal transmission). According to both variants, holobiont selection indeed causes evolutionary change in holobiont traits. Therefore, holobiont selection is plausibly an effective evolutionary force with either mode of microbiome transmission. The modeling employs two distinct concepts of inheritance, depending on the mode of microbiome transmission: collective inheritance whereby juveniles inherit a sample of the collected genomes from all parents, as contrasted with lineal inheritance whereby juveniles inherit the genomes from only their own parents. A distinction between collective and lineal inheritance also features in theories of multilevel selection. (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)

I argue (1) that what (ontic) New Mechanistic philosophers of science call mechanisms would be material Gestalten, and (2) that Merleau-Ponty’s engagement with Gestalt theory can help us frame a standing challenge against ontic conceptions of mechanisms. In short, until the (ontic) New Mechanist can provide us with a plausible account of the organization of mechanisms as an objective feature of mind-independent ontic structures in the world which we might discover – and no ontic Mechanist has done so – it (...) is more conservative to claim that mechanistic organization is instead a mind-dependent aspect of our epistemic strategies of mechanistic explanation. (shrink)

The first part of this paper finds Craver’s (2007) mutual manipulability theory (MM) of constitution inadequate, as it definitionally ties constitution to the feasibility of idealized experiments, which, however, are unrealizable in principle. As an alternative, the second part develops an abductive theory of constitution (NDC), which exploits the fact that phenomena and their constituents are unbreakably coupled via common causes. The best explanation for this common-cause coupling is the existence of an additional dependence relation, viz. constitution. Apart from adequately (...) capturing the essential characteristics of constitution missed by MM, NDC has important ramifications for constitutional discovery—most notably, that there is no experimentum crucis for constitution, not even under ideal discovery circumstances. (shrink)

Courtesy of its free energy formulation, the hierarchical predictive processing theory of the brain (PTB) is often claimed to be a grand unifying theory. To test this claim, we examine a central case: activity of mesocorticolimbic dopaminergic (DA) systems. After reviewing the three most prominent hypotheses of DA activity—the anhedonia, incentive salience, and reward prediction error hypotheses—we conclude that the evidence currently vindicates explanatory pluralism. This vindication implies that the grand unifying claims of advocates of PTB are unwarranted. More generally, (...) we suggest that the form of scientific progress in the cognitive sciences is unlikely to be a single overarching grand unifying theory. (shrink)

The premise of biological modularity is an ontological claim that appears to come out of practice. We understand that the biological world is modular because we can manipulate different parts of organisms in ways that would only work if there were discrete parts that were interchangeable. This is the foundation of the BioBrick assembly method widely used in synthetic biology. It is one of a number of methods that allows practitioners to construct and reconstruct biological pathways and devices using DNA (...) libraries of standardized parts with known functions. In this paper, we investigate how the practice of synthetic biology reconfigures biological understanding of the key concepts of modularity and evolvability. We illustrate how this practice approach takes engineering knowledge and uses it to try to understand biological organization by showing how the construction of functional parts and processes can be used in synthetic experimental evolution. We introduce a new approach within synthetic biology that uses the premise of a parts-based ontology together with that of organismal self-organization to optimize orthogonal metabolic pathways in E. coli. We then use this and other examples to help characterize semisynthetic categories of modularity, parthood, and evolvability within the discipline. (shrink)

According to the new mechanistic approach, an acting entity is at a lower mechanistic level than another acting entity if and only if the former is a component in the mechanism for the latter. Craver and Bechtel :547–563, 2007. doi:10.1007/s10539-006-9028-8) argue that a consequence of this view is that there cannot be causal interactions between acting entities at different mechanistic levels. Their main reason seems to be what I will call the Metaphysical Argument: things at different levels of a mechanism (...) are related as part and whole; wholes and their parts cannot be related as cause and effect; hence, interlevel causation in mechanisms is impossible. I will analyze this argument in more detail and show under which conditions it is valid. This analysis will reveal that interlevel causation in mechanisms is indeed possible, if we take seriously the idea that the relata of the mechanistic level relation are acting entities and accept a slightly modified notion of a mechanistic level that is highly plausible in the light of the first clarification. (shrink)

This chapter discusses several kinds of reduction that are often found in the biomedical sciences, in contrast to reduction in fields such as physics. This includes reduction as a methodological assumption for how to investigate phenomena like complex diseases, and reduction as a conceptual tool for relating distinct models of the same phenomenon. The case of Parkinson’s disease illustrates a wide variety of ways in which reductionism is an important tool in medicine.

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)

In this paper I argue that it is finally time to move beyond the Nagelian framework and to break new ground in thinking about epistemic reduction in biology. I will do so, not by simply repeating all the old objections that have been raised against Ernest Nagel’s classical model of theory reduction. Rather, I grant that a proponent of Nagel’s approach can handle several of these problems but that, nevertheless, Nagel’s general way of thinking about epistemic reduction in terms of (...) theories and their logical relations is entirely inadequate with respect to what is going on in actual biological research practice. (shrink)

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

We present a novel methodology for calculating the improvements obtained in successive versions of biomedical ontologies. The theory takes into account changes both in reality itself and in our understanding of this reality. The successful application of the theory rests on the willingness of ontology authors to document changes they make by following a number of simple rules. The theory provides a pathway by which ontology authoring can become a science rather than an art, following principles analogous to those that (...) have fostered the growth of modern evidence-based medicine. Although in this paper we focus on ontologies, the methodology can be generalized to other sorts of terminology-based artifacts, including Electronic Patient Records. (shrink)

Living organisms are exposed to numerous influencing factors. This holds also true for their infrastructures that are processing and transducing information like endocrine networks or nerval channels. Therefore, the ability to compensate for noise is crucial for survival. An efficient mechanism to neutralise disturbances is instantiated in form of parallel complementary communication channels exerting antagonistic effects at their common receivers. Different signal processing types share the ability to suppress noise, to widen the system’s regulation capacity, and to provide for variable (...) gains while leaving the transferred signal to a large extent unchanged. (shrink)

Any attempt to develop biosemiotics either towards a new biological ground theory or towards a metaphysics of living nature necessitates some kind of naturalization of its semiotic concepts. Instead of standard physicalistic naturalism, a certain kind of semiotic naturalism is pursued here. The naturalized concepts are defined as referring only to the objects of our external experience. When the semiotic concepts are applied to natural phenomena in biosemiotics, there is a risk of falling into anthropomorphic errors if the semiotic concepts (...) remain mentalistic. It is suggested that there really is an anthropomorphic error or “hidden prototype fallacy” arising from Peirce’s prototype for semiosis: the research process of an experimental scientist. The fallacy lies in the concept of the object of representation — it is questionable whether there are any objects of representation for bacteria and whether the DNA-signs have any objects. The conclusion is that Peircean semiotic concepts are naturalizable but only if they are based on some more primitive concept of representation. The causal origins of representations are not relevant, only their anticipative consequences (i.e. meaning). (shrink)

This Ph.D. thesis provides a pilosophical account of the structure of the evolutionary synthesis of the 1930s and 40s. The first, more historical part analyses how classical genetics came to be integrated into evolutionary thinking, highlighting in particular the importance of chromosomal mapping of Drosophila strains collected in the wild by Dobzansky, but also the work of Goldschmidt, Sumners, Timofeeff-Ressovsky and others. The second, more philosophical part attempts to answer the question wherein the unity of the synthesis consisted. I argue (...) that it exemplifies a weak of form of explanatory unification. (shrink)

Seit wenigen Jahren erfreuen sich in den Lebenswissenschaften mehrere Theorien eines immer weitergehenden Einflusses, die unter Etikettierungen wie Systembiologie, Netzwerktheorie oder Signalomics nur scheinbar unabhängige Herangehensweisen an komplexe Zusammenhänge darstellen. Navigation ist der übergreifende Gedanke, der so unterschiedliche Gebiete wie Regelungstheorie, Entscheidungstheorie und Systemwissenschaft verbindet. Navigation als Lage- und Kursbestimmung nebst den zugehörigen Signalverarbeitungsprozessen und Steuerkommandos ist die Grundlage dessen, was lebende Organismen von der blo§en Ansammlung materieller Ingredienzien unterscheidet – von der molekularen Ebene bis zum Sozialverhalten. Denn stets stellen (...) sich Prozesse des Lebens als solche des Suchens, Kommunizierens, Disponierens und Vervollkommnens dar, ob es sich nun um die Regulation der Sauerstoffspannung im Blut oder die Organisation eines Ameisenvolkes handelt. Navigationsaufgaben sind damit schließlich auch Fragestellungen ärztlicher Entscheidungsfindung, die sich in einem komplexen Raum aus individuellen, sozialen und ethischen Anforderungen entfalten. (shrink)

Ever since George Henry Lewes coined the term emergence, various notions have been associated with emergence that have little or nothing to do with emergence itself. These notions distract from the understanding of emergence to such a degree that very little progress was made in over a century of discussion. Emergence is the coming into existence of patterns-of-material-organization as a consequence of motion. The process of emergence plays major roles in the universe, such as the creation of the hierarchic organization (...) of the material universe from quarks, atoms, and molecules to planets, solar systems, and galaxies. Typical discussions about emergence in the literature are about the distracting notions and not actually about emergence itself. This essay has three primary parts. First is discussion of the intrinsic nature of emergence. The second part explains why the distracting notions are not really about emergence. The third part gives an introduction to methods that can provide understanding of the process of emergence. (shrink)