David Waldron Smithers was, among other things, a physician and a pioneer of cancer radiotherapy and a well-respected figure in British medicine and public health. From the 1940s until his retirement from medical practice in 1973, he was the director of the Radiotherapy Department at the Royal Marsden Hospital and London University Chair of Radiotherapy at the Institute of Cancer Research. Using massive amounts of clinical observations, which he interpreted from an organicist viewpoint, and his impressive synthetic thinking, he proposed (...) a coherent alternative perspective to the somatic mutation theory (SMT) which was then, and still is, the dominant theory of cancer. The purpose of this essay is to acquaint the modern audience with his seminal paper, published in 1962, because it deserves to be recognized as a true classic. In it, he examined the lack of fit between clinical observations and the SMT and proposed the rejection of this reductionist perspective. In addition, he built an organicist alternative in which carcinogenesis is seen as a problem of biological organization. His conceptual contribution to the cancer problem has inspired us and other authors over the last two decades. His essay “Cancer: An Attack on Cytologism,” originally published in The Lancet in 1962, is available as supplementary material in the online version of this article. (shrink)

In this study, we analyse the notion of “differential heterogenesis” proposed by Deleuze and Guattari on a morphogenetic perspective. We propose a mathematical framework to envisage the emergence of singular forms from the assemblages of heterogeneous operators. In opposition to the kind of differential calculus that is usually adopted in mathematical-physical modelling, which tends to assume a homogeneous differential equation applied to an entire homogeneous region, heterogenesis allows differential constraints of qualitatively different kinds in different points of space and time. (...) These constraints can then change in time, opening the possibility for new kinds of differential dynamics and the emergence of distinct entities and forms. Formally, we show that operators with different phase spaces can be assembled on the basis of a result of Rothschild & Stein (1976. Hypoelliptic differential operators and nilpotent groups. Acta Mathematica 137. 247–320). Furthermore, operators with different dynamics can be assembled by means of a partition of the unit.After stating the concept of differential heterogenesis in terms of contemporary mathematics, we show that this construction sheds light on the constitution of the semiotic function. In fact, both the Merleau-Pontian and the Deleuzian approaches share a common conceptualisation of the semiotic function and its emergence in terms of amorphodynamics of heterogeneous assemblages with a divergent actualisation. This divergent actualisation allows the co-constitution of various expression and content planes. Finally, we show that the divergent actualisation can be interpreted as the directions of principal eigenvectors of the actualized flow. (shrink)

We provide a new perspective on the relation between the space of description of an object and the appearance of novelties. One of the aims of this perspective is to facilitate the interaction between mathematics and historical sciences. The definition of novelties is paradoxical: if one can define in advance the possibles, then they are not genuinely new. By analyzing the situation in set theory, we show that defining generic (i.e., shared) and specific (i.e., individual) properties of elements of a (...) set are radically different notions. As a result, generic and specific definitions of possibilities cannot be conflated. We argue that genuinely stating possibilities requires that their meaning has to be made explicit. For example, in physics, properties playing theoretical roles are generic; then, generic reasoning is sufficient to define possibilities. By contrast, in music, we argue that specific properties matter, and generic definitions become insufficient. Then, the notion of new possibilities becomes relevant and irreducible. In biology, among other examples, the generic definition of the space of DNA sequences is insufficient to state phenotypic possibilities even if we assume complete genetic determinism. The generic properties of this space are relevant for sequencing or DNA duplication, but they are inadequate to understand phenotypes. We develop a strong concept of biological novelties which justifies the notion of new possibilities and is more robust than the notion of changing description spaces. These biological novelties are not generic outcomes from an initial situation. They are specific and this specificity is associated with biological functions, that is to say, with a specific causal structure. Thus, we think that in contrast with physics, the concept of new possibilities is necessary for biology. (shrink)

We characterize access to empirical objects in biology from a theoretical perspective. Unlike objects in current physical theories, biological objects are the result of a history and their variations continue to generate a history. This property is the starting point of our concept of measurement. We argue that biological measurement is relative to a natural history which is shared by the different objects subjected to the measurement and is more or less constrained by biologists. We call symmetrization the theoretical and (...) often concrete operation which leads to considering biological objects as equivalent in a measurement. Last, we use our notion of measurement to analyze research strategies. Some strategies aim to bring biology closer to the epistemology of physical theories, by studying objects as similar as possible, while others build on biological diversity. (shrink)

The dependence on history of both present and future dynamics of life is a common intuition in biology and in humanities. Historicity will be understood in terms of changes of the space of possibilities as well as by the role of diversity in life’s structural stability and of rare events in history formation. We hint to a rigorous analysis of “path dependence” in terms of invariants and invariance preserving transformations, as it may be found also in physics, while departing from (...) the physico-mathematical analyses. The idea is that the invariant traces of the past under organismal or ecosystemic transformations contribute to the understanding of present and future states of affairs. This yields a peculiar form of unpredictability in biology, at the core of novelty formation: the changes of observables and pertinent parameters may depend also on past events. In particular, in relation to the properties of synchronic measurement in physics, the relevance of diachronic measurement in biology is highlighted. This analysis may a fortiori apply to cognitive and historical human dynamics, while allowing to investigate some general properties of historicity in biology. (shrink)

The Free Energy Principle (FEP) states that all biological self-organizing systems must minimize variational free energy. The acceptance of this principle has given rise to a popular and far-reaching theoretical and empirical approach to the study of the brain and living organisms. Despite the popularity of the FEP approach, little discussion has ensued about its ontological status and implications. By understanding physicalism as an interdisciplinary research program that aims to offer compositional explanations of mental phenomena, this paper articulates what it (...) would mean for the FEP approach to be part of research program physicalism and to corroborate a physicalist outlook. In doing so, this paper contributes both to philosophical discussions regarding the FEP approach and to the literature on physicalism. It does the former by explicating the metaphysical standing of the FEP approach. It does the latter by showing how cutting-edge research in the empirical sciences of the mind can inform our attitudes regarding physicalism. (shrink)

Several authors have made claims about the compatibility between the Free Energy Principle and theories of autopoiesis and enaction. Many see these theories as natural partners or as making similar statements about the nature of biological and cognitive systems. We critically examine these claims and identify a series of misreadings and misinterpretations of key enactive concepts. In particular, we notice a tendency to disregard the operational definition of autopoiesis and the distinction between a system’s structure and its organization. Other misreadings (...) concern the conflation of processes of self-distinction in operationally closed systems and Markov blankets. Deeper theoretical tensions underlie some of these misinterpretations. FEP assumes systems that reach a non-equilibrium steady state and are enveloped by a Markov blanket. We argue that these assumptions contradict the historicity of sense-making that is explicit in the enactive approach. Enactive concepts such as adaptivity and agency are defined in terms of the modulation of parameters and constraints of the agent-environment coupling, which entail the possibility of changes in variable and parameter sets, constraints, and in the dynamical laws affecting the system. This allows enaction to address the path-dependent diversity of human bodies and minds. We argue that these ideas are incompatible with the time invariance of non-equilibrium steady states assumed by the FEP. In addition, the enactive perspective foregrounds the enabling and constitutive roles played by the world in sense-making, agency, development. We argue that this view of transactional and constitutive relations between organisms and environments is a challenge to the FEP. Once we move beyond superficial similarities, identify misreadings, and examine the theoretical commitments of the two approaches, we reach the conclusion that far from being easily integrated, the FEP, as it stands formulated today, is in tension with the theories of autopoiesis and enaction. (shrink)

The free-energy principle states that all systems that minimize their free energy resist a tendency to physical disintegration. Originally proposed to account for perception, learning, and action, the free-energy principle has been applied to the evolution, development, morphology, anatomy and function of the brain, and has been called a postulate, an unfalsifiable principle, a natural law, and an imperative. While it might afford a theoretical foundation for understanding the relationship between environment, life, and mind, its epistemic status is unclear. Also (...) unclear is how the free-energy principle relates to prominent theoretical approaches to life science phenomena, such as organicism and mechanism. This paper clarifies both issues, and identifies limits and prospects for the free-energy principle as a first principle in the life sciences. (shrink)

Very large databases are a major opportunity for science and data analytics is a remarkable new field of investigation in computer science. The effectiveness of these tools is used to support a “philosophy” against the scientific method as developed throughout history. According to this view, computer-discovered correlations should replace understanding and guide prediction and action. Consequently, there will be no need to give scientific meaning to phenomena, by proposing, say, causal relations, since regularities in very large databases are enough: “with (...) enough data, the numbers speak for themselves”. The “end of science” is proclaimed. Using classical results from ergodic theory, Ramsey theory and algorithmic information theory, we show that this “philosophy” is wrong. For example, we prove that very large databases have to contain arbitrary correlations. These correlations appear only due to the size, not the nature, of data. They can be found in “randomly” generated, large enough databases, which—as we will prove—implies that most correlations are spurious. Too much information tends to behave like very little information. The scientific method can be enriched by computer mining in immense databases, but not replaced by it. (shrink)

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

Cognitive niche theories consist in a theoretical framework that is proving extremely profitable in bridging evolutionary biology, philosophy, cognitive science, and anthropology by offering an inter-disciplinary ground, laden with novel approaches and debates. At the same time, cognitive niche theories are multiple, and differently related to niche theories in theoretical and evolutionary biology. The aim of this paper is to clarify the theoretical and epistemological relationships between cognitive and ecological niche theories. Also, by adopting a constructionist approach we will try (...) to explain the shift from ecological to cognitive niches and their actual and theoretical overlaps. In order to do so, we will take two concepts expressing loose forms of causation in the interaction between organisms and their environment: the biological notion of “enablement” and the psycho-cognitive one of “affordance”. (shrink)

Both biosemiotics and evolutionary epistemology are concerned with how knowledge evolves. (Applied) Evolutionary Epistemology thereby focuses on identifying the units, levels, and mechanisms or processes that underlie the evolutionary development of knowing and knowledge, while biosemiotics places emphasis on the study of how signs underlie the development of meaning. We compare the two schools of thought and analyze how in delineating their research program, biosemiotics runs into several problems that are overcome by evolutionary epistemologists. For one, by emphasizing signs, biosemiotics (...) needs to delineate a semiotic threshold, which is a problem not encountered by evolutionary epistemologists. Instead, the latter recognizes that all organisms are knowers that evolve knowledge, which they recognize to extend toward phenomena produced by organisms such as behavior, cognition, language, culture, science, and technology. Secondly, biosemiotics attempts at continuing adaptationist notions on how organisms relate to their environment, while especially Applied Evolutionary Epistemology comes to redefine the nature of the organism–environment relationship in such a way that it recognizes the spatiotemporal boundedness of existence, which in turn makes adaptationist accounts obsolete. (shrink)

In the last decade, Systems Biology has emerged as a conceptual and explanatory alternative to reductionist-based approaches in molecular biology. However, the foundations of this new discipline need to be fleshed out more carefully. In this paper, we claim that a relational ontology is a necessary tool to ground both the conceptual and explanatory aspects of Systems Biology. A relational ontology holds that relations are prior—both conceptually and explanatory—to entities, and that in the biological realm entities are defined primarily by (...) the context they are embedded within—and hence by the web of relations they are part of. (shrink)

In this paper, I address the issue of the ontological status of qualitative properties. I discuss the prevalent approaches to the problem of qualia in philosophy of mind, in relation to the various attempts at naturalizing the mind and the various theories of perception. I compare these views with Husserl's phenomenology, highlighting the phenomenological distinction between phenomenal contents of mental states and sensory properties of the perceived objects. I present some open issues of this view, in order to show how (...) they can be addressed in the light of some developments of the phenomenological inquiry in Husserl and Merleau-Ponty. (shrink)

The intellectual act of imposing borders to contain and delimit objects has been a constituent factor in physics since its origins, and is also fundamental for philosophical reflection. However, the characteristics of the conceptual universe thus constructed (tendency towards the ideal limit, invariance in variation, a conception of matter as residue, etc.) seem inadequate in biology. The essential characteristic of the living thing is, in fact, that of having a history: that is, of being the concrete trace of a memory. (...) Making an epistemology of the living thing (and not of the inert) means identifying new categories which, being radically antithetical to disembodied notions like that of program and information, take account of the unpredictability and creativity which time introduces. This essay aims to bring some of these fundamental categories into focus. (shrink)