The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

The somatic mutation theory has been the prevailing paradigm in cancer research for the last 50 years. Its premises are: (1) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations, (2) the default state of cell proliferation in metazoa is quiescence, and (3) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. From this compelling simplicity, an increasingly complicated picture has emerged as more than 100 (...) oncogenes and 30 tumor suppressor genes have been identified. To accommodate this complexity, additional ad hoc explanations have been postulated. After a critical review of the data gathered from this perspective, an alternative research program has been proposed. It is based on the tissue organization field theory, the premises of which are that carcinogenesis represents a problem of tissue organization, comparable to organogenesis, and that proliferation is the default state of all cells. The merits of these competing theories are evaluated herein. BioEssays 26:1097–1107, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

For the last 50 years the dominant stance in experimental biology has been reductionism in general, and genetic reductionism in particular. Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon, experimental data confirmed these misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems has now been tempered by the difficulties encountered when applying the same simple ideas to complex problems. We analyze three (...) examples taken from experimental data that illustrate the shortcomings of this sort of reductionism. In the first, alterations in the expression of a large number of genes coexist with normal phenotypes at supra-cellular levels of organization; in the second, the supposed intrinsic specificity of hormonal signals is negated; in the third, the notion that cancer is a cellular problem caused by mutated genes is challenged by data gathered both from the reductionist viewpoint and the alternative view proposing that carcinogenesis is development gone awry. As an alternative to reductionism, we propose that the organicist view is a good starting point from which to explore these phenomena. However, new theoretical concepts are needed to grapple with the apparent circular causality of complex biological phenomena. (shrink)

It would be ahistorical to ridicule vitalists. When one reads the writings of one of the leading vitalists like Driesch one is forced to agree with him that many of the basic problems of biology simply cannot be solved by a philosophy as that of Descartes, in which the organism is simply considered a machine…. The logic of the critique of the vitalists was impeccable.At the turn of the new millennium, concomitant with the development of the evo-devo and eco-devo disciplines (...) within developmental biology, critical appraisals of the reductionist stance of the molecular biology revolution became more numerous and noticeable. Several books and papers address the problems posed by this reductionist agenda and suggest... (shrink)

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

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 article, Carlos Pereda introduces the concept of “colonial reason” and explores how philosophical practices and modes of thought are entwined with colonial political structures of exploitation, exclusion, and oppression. Pereda argues that philosophy in Latin America risks perpetuating and reinforcing the colonial gesture, either by turning to the European centers of thought (thus pursuing debates that always take place elsewhere) or by isolating itself and idealising the “own.” According to Pereda, both approaches fail to dismantle colonial violence (...) within philosophy. In his alternative approach, Pereda outlines principles and methodological criteria for the decolonisation of reason and philosophy. He emphasises the importance of methodological prudence that discerns between innocent, paralysing, and strategic uses of identity expressions and advocates for modes of reading and argumentation that conceive philosophy as an inclusive and ongoing dialogue. In Pereda’s terminology, this entails fostering “permeable reason” that manifests itself through “nomadic thinking,” a form of thinking that is capable of questioning itself and being questioned. (shrink)

Many of the computing systems programmed using Machine Learning are opaque: it is difficult to know why they do what they do or how they work. Explainable Artificial Intelligence aims to develop analytic techniques that render opaque computing systems transparent, but lacks a normative framework with which to evaluate these techniques’ explanatory successes. The aim of the present discussion is to develop such a framework, paying particular attention to different stakeholders’ distinct explanatory requirements. Building on an analysis of “opacity” from (...) philosophy of science, this framework is modeled after accounts of explanation in cognitive science. The framework distinguishes between the explanation-seeking questions that are likely to be asked by different stakeholders, and specifies the general ways in which these questions should be answered so as to allow these stakeholders to perform their roles in the Machine Learning ecosystem. By applying the normative framework to recently developed techniques such as input heatmapping, feature-detector visualization, and diagnostic classification, it is possible to determine whether and to what extent techniques from Explainable Artificial Intelligence can be used to render opaque computing systems transparent and, thus, whether they can be used to solve the Black Box Problem. (shrink)

The received view of dynamical explanation is that dynamical cognitive science seeks to provide covering law explanations of cognitive phenomena. By analyzing three prominent examples of dynamicist research, I show that the received view is misleading: some dynamical explanations are mechanistic explanations, and in this way resemble computational and connectionist explanations. Interestingly, these dynamical explanations invoke the mathematical framework of dynamical systems theory to describe mechanisms far more complex and distributed than the ones typically considered by philosophers. Therefore, contemporary dynamicist (...) research reveals the need for a more sophisticated account of mechanistic explanation. (shrink)

Published as a tribute to the memory of Elisha Pazner, this book contains a collection of essays providing a comprehensive view of the design and evaluation of economic mechanisms, written and edited by the major contributors to the field. Amongst the topics included are bargaining theory and the economics of competitive bidding. The surveys are preceded by 'A Perspective', by Leo Hurwicz which contains a systematic account of the development of the literature on mechanism design, and this provides a context (...) for both the surveys and the six published papers authored or co-authored by Elisha Pazner that complete the book and demonstrate Pazner's interest in and contribution to the study of economic mechanisms. Leonid Hurwitcz is the Nobel Prize Winner 2007 for The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, along with colleagues Eric Maskin and Roger Myerson, for his work on the effectiveness of markets. (shrink)

Models developed using machine learning are increasingly prevalent in scientific research. At the same time, these models are notoriously opaque. Explainable AI aims to mitigate the impact of opacity by rendering opaque models transparent. More than being just the solution to a problem, however, Explainable AI can also play an invaluable role in scientific exploration. This paper describes how post-hoc analytic techniques from Explainable AI can be used to refine target phenomena in medical science, to identify starting points for future (...) investigations of causal relationships, and to generate possible explanations of target phenomena in cognitive science. In this way, this paper describes how Explainable AI—over and above machine learning itself—contributes to the efficiency and scope of data-driven scientific research. (shrink)

In a context of pervasive digitalization of the social world, both before and during the COVID-19 pandemic, the field of education has undergone major changes with the development of digital practices and settings. However, the physical presence of the subjects and the body remain something primordial and irreplaceable in traditional educational processes. Thus, it is often assumed that virtuality is opposed to the corporeal reality of the subjects involved in teaching, learning and studying. In this paper we aim to critically (...) challenge this assumption by addressing the phenomenon of virtuality in a more original sense: as a fundamental dimension of corporeality itself. Drawing on Merleau-Ponty’s phenomenological insights, we argue that the experience of the virtual is inherently embodied and fully real. We understand corporeality and virtuality as entangled and multidimensional phenomena. At the same time, this leads us to rethink the digital as only one possible medium in which virtuality can appear as inherent to embodied experience. We develop our phenomenological approach in three instances. First, we question and bracket two common assumptions about corporeality. From our critical perspective, assumptions about a disembodied digitality and a devirtualized corporeality represent extremes within which educational discourses currently move. Second, we address the inherent virtuality of embodied experience. We outline the heuristic concept of the virtual body to describe corporeality and virtuality as entangled and multidimensional phenomena that encompass extension, intercorporeality and intermediality. Finally, we make some remarks on the relationships of corporeality and virtuality considering the challenges of digital education. (shrink)

Bayesian reverse-engineering is a research strategy for developing three-level explanations of behavior and cognition. Starting from a computational-level analysis of behavior and cognition as optimal probabilistic inference, Bayesian reverse-engineers apply numerous tweaks and heuristics to formulate testable hypotheses at the algorithmic and implementational levels. In so doing, they exploit recent technological advances in Bayesian artificial intelligence, machine learning, and statistics, but also consider established principles from cognitive psychology and neuroscience. Although these tweaks and heuristics are highly pragmatic in character and (...) are often deployed unsystematically, Bayesian reverse-engineering avoids several important worries that have been raised about the explanatory credentials of Bayesian cognitive science: the worry that the lower levels of analysis are being ignored altogether; the challenge that the mathematical models being developed are unfalsifiable; and the charge that the terms ‘optimal’ and ‘rational’ have lost their customary normative force. But while Bayesian reverse-engineering is therefore a viable and productive research strategy, it is also no fool-proof recipe for explanatory success. (shrink)

A study in the logic of theory change, examining the properties of maxichoice contraction and revision operations.

The book is a comprehensive introduction to the work of the Estonian-German biologist Jakob von Uexküll. After a first introductory chapter by Morten Tønnessen and a second chapter on Uexküll's life and philosophical background, it contains four chapters devoted to the analysis of his main works; they are followed by a vast eighth chapter which deals with the influence Uexküll had on other philosophers and scientists, and by a conclusions focused on the possibility of updating Uexküll's work. The monograph combines (...) a careful reconstruction of the historical context in which the Uexküllian concepts emerged (the debate between mechanism and vitalism, contemporary scientific studies) and a thorough analysis of the philosophical contents of the Uexküllian views. As far as the key issue is concerned, Uexküll's notion of Umwelt refers to the perceptive and operative world which surrounds animal species; it is a subjective species-specific construction which provides living organisms with great security and behaviour stability. Moreover, the relationship that the animal carries out with its environment proves to be a complex system of semiotic interactions: its behaviour is not a set of mechanical reactions, but the result of a spontaneous attribution of meaning to the outside world, whose environmental elements are actively interpreted by the subject. The environment of animal species becomes a field of meaning, an exceedingly complex subjective elaboration; this can lessen the distance between animals and men, crediting both with the cognitive ability to grasp meanings and to use signs. (shrink)

The philosophical conception of mechanistic explanation is grounded on a limited number of canonical examples. These examples provide an overly narrow view of contemporary scientific practice, because they do not reflect the extent to which the heuristic strategies and descriptive practices that contribute to mechanistic explanation have evolved beyond the well-known methods of decomposition, localization, and pictorial representation. Recent examples from evolutionary robotics and network approaches to biology and neuroscience demonstrate the increasingly important role played by computer simulations and mathematical (...) representations in the epistemic practices of mechanism discovery and mechanism description. These examples also indicate that the scope of mechanistic explanation must be re-examined: With new and increasingly powerful methods of discovery and description comes the possibility of describing mechanisms far more complex than traditionally assumed. (shrink)

Many moral philosophers have criticized intensive animal farming because it can be harmful to the environment, it causes pain and misery to a large number of animals, and furthermore eating meat and animal-based products can be unhealthful. The issue of industrially farmed animals has become one of the most pressing ethical questions of our time. On the one hand, utilitarians have argued that we should become vegetarians or vegans because the practices of raising animals for food are immoral since they (...) minimize the overall happiness. Deontologists, on the other hand, have argued that the practices of raising animals for food are immoral because animals have certain rights and we have duties toward them. Some virtue ethicists remain unconvinced of deontic and consequentialist arguments against the exploitation of animals and suggest that a virtue-based approach is better equipped to show what is immoral about raising and using animals for food, and what is virtuous about ethical veganism. (shrink)

The project of growing meat artificially represents for some the next best thing to humanity. If successful, it could be the solution to several problems, such as feed- ing a growing global population while reducing the environmental impact of raising animals for food and, of course, reducing the amount and degree of animal cruelty and suffering that is involved in animal farming. In this paper, I argue that the issue of the morality of such a project has been framed only (...) in terms of the best conse- quences for the environment, animals, and humans, or in terms of deontic princi- ples. I argue that to appreciate how deep and difficult this issue is, it is necessary to consider it in terms of a virtue-oriented approach. Such an approach will reveal aspects that are not apparent, not contemplated by typical approaches, but are essen- tial to our understanding of the morality of lab-grown meat. As I argue, evaluating the issue from a virtue-oriented perspective suggests that the project of in vitro meat should not be supported because it stems from unvirtuous motivations. (shrink)

This chapter subsumes David Marr’s levels of analysis account of explanation in cognitive science under the framework of mechanistic explanation: Answering the questions that define each one of Marr’s three levels is tantamount to describing the component parts and operations of mechanisms, as well as their organization, behavior, and environmental context. By explicating these questions and showing how they are answered in several different cognitive science research programs, this chapter resolves some of the ambiguities that remain in Marr’s account, and (...) shows that many different areas and traditions of cognitive scientific research can be unified under the mechanistic framework. (shrink)

Marcus William Hunt argues that when co-parents disagree over whether to raise their child (or children) as a vegan, they should reach a compromise as a gift given by one parent to the other out of respect for his or her authority. Josh Millburn contends that Hunt’s proposal of parental compromise over veganism is unacceptable on the ground that it overlooks respect for animal rights, which bars compromising. However, he contemplates the possibility of parental compromise over ‘unusual eating,’ of animal-based (...) foods obtained without the violation of animal rights. I argue for zero parental compromise, rejecting a rights-oriented approach, and propose a policy that an ethical vegan parent and a non-vegan co-parent should follow to determine how to raise their children. (shrink)

Whereas most branches of neuroscience are thought to provide mechanistic explanations, systems neuroscience is not. Two reasons are traditionally cited in support of this conclusion. First, systems neuroscientists rarely, if ever, rely on the dual strategies of decomposition and localization. Second, they typically emphasize organizational properties over the properties of individual components. In this paper, I argue that neither reason is conclusive: researchers might rely on alternative strategies for mechanism discovery, and focusing on organization is often appropriate and consistent with (...) the norms of mechanistic explanation. Thus, many explanations in systems neuroscience can also be viewed as mechanistic explanations. (shrink)

This article discusses the relation between empirical and normative approaches in bioethics. The issue of dwarf tossing, while admittedly unusual, is chosen as a point of departure because it challenges the reader to look with fresh eyes upon several central bioethical themes, including human dignity, autonomy, and the protection of vulnerable people. After an overview of current approaches to the integration of empirical and normative ethics, we consider five ways that the empirical and normative can be brought together to speak (...) to the problem of dwarf tossing: prescriptive applied ethics, theoretical ethics, critical applied ethics, particularist ethics and integrated empirical ethics. We defend a position of critical applied ethics that allows for a two-way relation between empirical and normative theories. Against efforts fully to integrate the normative and the empirical into one synthesis, we propose that the two should stand in tension and relation to one another. The approach we endorse acknowledges that a social practice can and should be judged both by the gathering of empirical data and by normative ethics. Critical applied ethics uses a five stage process that includes: (a) determination of the problem, (b) description of the problem, (c) empirical study of effects and alternatives, (d) normative weighing and (e) evaluation of the effects of a decision. In each stage, we explore the perspective from both the empirical (sociological) and the normative ethical point of view. We conclude by applying our five-stage critical applied ethics to the example of dwarf tossing. (shrink)

This paper considers the way mathematical and computational models are used in network neuroscience to deliver mechanistic explanations. Two case studies are considered: Recent work on klinotaxis by Caenorhabditis elegans, and a longstanding research effort on the network basis of schizophrenia in humans. These case studies illustrate the various ways in which network, simulation and dynamical models contribute to the aim of representing and understanding network mechanisms in the brain, and thus, of delivering mechanistic explanations. After outlining this mechanistic construal (...) of network neuroscience, two concerns are addressed. In response to the concern that functional network models are non-explanatory, it is argued that functional network models are in fact explanatory mechanism sketches. In response to the concern that models which emphasize a network’s organization over its composition do not explain mechanistically, it is argued that this emphasis is both appropriate and consistent with the principles of mechanistic explanation. What emerges is an improved understanding of the ways in which mathematical and computational models are deployed in network neuroscience, as well as an improved conception of mechanistic explanation in general. (shrink)

The project of growing meat artificially represents for some the next best thing to humanity. If successful, it could be the solution to several problems, such as feeding a growing global population while reducing the environmental impact of raising animals for food and, of course, reducing the amount and degree of animal cruelty and suffering that is involved in animal farming. In this paper, I argue that the issue of the morality of such a project has been framed only in (...) terms of the best consequences for the environment, animals, and humans, or in terms of deontic principles. I argue that to appreciate how deep and difficult this issue is, it is necessary to consider it in terms of a virtue-oriented approach. Such an approach will reveal aspects that are not apparent, not contemplated by typical approaches, but are essential to our understanding of the morality of lab-grown meat. As I argue, evaluating the issue from a virtue-oriented perspective suggests that the project of in vitro meat should not be supported because it stems from unvirtuous motivations. (shrink)

The concept of dignity is notoriously vague. In this paper it is argued that the reason for this is that there are three versions of dignity that are often confused. First we will take a short look at the history of the concept of dignity in order to demonstrate how already from Roman Antiquity two versions of dignity can be distinguished. Subsequently, the third version will be introduced and it will be argued that although the three versions of dignity hang (...) together, they should also be clearly distinguished in order to avoid confusion. The reason for distinguishing the three versions is because all three of them are only partially effective. This will be demonstrated by taking the discussion about voluntary ‘dying with dignity’ as an example. Inspired by both Paul Ricoeur’s concept of ethics and the ethics of care a proposition will be done as to how the three versions of dignity may sustain each other and help achieve what neither one of the versions can do on its own. (shrink)

Este artículo plantea que el concepto de solidaridad, usualmente exaltado en tiempos de crisis, contiene en sí mismo el conjunto de límites que lo debilitan y lo convierten, paradójicamente, en una sutil manifestación del egoísmo. Para analizar esta contradicción, se abordan las posiciones emblemáticas de cinco autores contemporáneos: John Rawls, Richard Rorty, Jürgen Habermas, Charles Taylor y Hannah Arendt. A través de este análisis puede mostrarse que los grandes desafíos de nuestra civilización permiten advertir los dilemas y las contingencias que (...) afectan el nexo entre el liberalismo y la solidaridad. (shrink)

RESUMENEl trabajo critica la fundamentación liberal del a democracia. Por dos razones: la primera, por la imposible defensa de un modelo neutral del estado; y la segunda, por el componente individualista tanto de su epistemología como de su filosofía moral y política, que reduce de modo significativo las posibilidades emancipadoras del proyecto democrático. por último, señala que estos rasgos básicos del a fundamentación liberal se mantienen incluso en una de las versiones del liberalismo social más acordes con la democracia constitucional; (...) el liberalismo político de John Rawls. PALABRAS CLAVELIBERALISMO-DEMOCRACIA LIBERAL- HOBBES-RAWLS- ARENDTABSTRACTThe paper critiques the liberal foundation of democracy. For two reasons: the first, because of the imposible defense of a neutral model of the state; and the second, because of the individualist element both of its epistemology and of its moral and political phiosophy, that reduces significantly the emancipatory chances of the democratic project. Lastly, it points out that these basic features of the liberal foundation even remain in one the versions of liberalism more akin to constitutional democracy: John Rawls' political liberalism.KEYWORDSLIBERALISM-LIBERAL DEMOCRACY-HOBBES-RAWLS-ARENDT. (shrink)