Marie Darrason est à pneumologue et philosophe de la médecine. Elle est interne de médecine des hôpitaux de Paris et Ancienne doctorante de l’Institut d’Histoire de Philosophie des Sciences et des Techniques (Paris 1/ENS/CNRS).
Voir son profil et ses publications.
Résumé :
L’essor récent des thérapies ciblées, fondé sur le concept de mutation actionnable, a fait émerger à nouveau le rêve de classifications moléculaires des maladies.
En effet, une thérapie ciblée est dirigée contre une altération moléculaire (mutation, réarrangement, amplification, etc) dite “actionnable”, c’est à dire une altération qui est essentielle au développement de la maladie et dont l’activation ou l’inactivation vont avoir un effet spectaculaire sur le cours de la maladie. Ainsi dans l’exemple du cancer du poumon, on distingue à présent plusieurs types de mutations actionnables (les adénocarcinomes EGFR mutés, ALK réarrangés), auxquels correspondent plusieurs types de thérapies ciblées (les anti EGFR, les anti ALK), qui permettent des réponses tumorales remarquables.
Dès lors, il est tentant de conclure que l’avènement des thérapies ciblées correspondrait à une redéfinition moléculaire de la maladie : à chaque phénotype particulier correspondrait une mutation actionnable et une thérapie ciblée spécifiques. Loin des distinctions anatomocliniques et sémiologiques grossières, il serait enfin possible de reclassifier une même entité chimérique en plusieurs maladies distinctes, de délimiter au sein de ce qui était considéré comme une seule maladie une multitude de phénotypes auxquels correspondraient des altérations moléculaires spécifiques.
L’objectif de ma présentation sera de discuter la réalité et la pertinence de cette redéfinition moléculaire de la maladie au prisme de l’analyse du concept de « mutation actionnable ». Je soutiens ainsi que le concept de mutation actionnable est un concept pragmatique, fondamentalement dynamique et qui est amené à se modifier dans le temps et dans l’espace, comme le montrent les phénomènes d’hétérogénéité intra et inter tumorale et l’émergence quasi inéluctable des résistances aux thérapies ciblées. Plutôt que de proposer une classification moléculaire de la maladie, je propose donc d’explorer le concept de trajectoire évolutionnaire de la maladie, qui me paraît particulièrement pertinent en oncologie médicale. J’essaierai notamment de distinguer le concept de trajectoire évolutionnaire de celui de signature moléculaire et je discuterai l’intérêt d’un tel concept hors du domaine de la cancérologie.
Samir Okasha is Professor of Philosophy of Science at the University of Bristol (UK). Most of his research falls into two main areas: (i) philosophy of biology / evolutionary theory; and (ii) epistemology /philosophy of science.
Abstract
It is striking that evolutionary biology often uses the language of intentional psychology to describe the behaviour of evolved organisms, their genes, and the process of natural selection that led to their evolution. Thus a cuckoo chick ‘deceives’ its host; a worker ant ‘prefers’ to tend the queen’s eggs to those of other workers; a swallow ‘realises’ that winter is approaching and ‘wants’ to escape it; an imprinted gene ‘knows’ whether it was inherited paternally or maternally; and natural selection ‘chooses’ some phenotypes over others. This intentional idiom is a symptom of a broader way of thinking about and modelling evolution, which I call ‘agential’. This involves treating evolved entities, paradigmatically individual organisms, as if they were agents trying to achieve a goal, namely maximisation of reproductive fitness (or some proxy). The use of rational choice models, originally intended to apply to deliberate human action, in an evolutionary context, is one symptom of agential thinking. I offer a cautious defence of agential thinking in evolutionary biology. I argue that this mode of thinking does genuine intellectual work, and is not ‘idle metaphor’; however it must be used with care, for it rests on an implicit empirical assumption that is not always satisfied.
Valerie Hardcastle is Professor of Philosophy, Psychology, and Psychiatry & Behavioral Neuroscience at the University of Cincinnati. An internationally recognized scholar, Valerie is the author of five books and over 150 essays. She studies the nature and structure of interdisciplinary theories in the cognitive sciences and has focused primarily on developing a philosophical framework for understanding conscious phenomena responsive to neuroscientific, psychiatric, and psychological data.
Tilte of the talk: “The Microbiome and the Brain: A New Revolution in Neuroscience?”
Part 1:
Part 2 (end of the talk, followed by comments made by Jan Pieter Konsman):
Abstract:
What counts as a revolution in a scientific domain like neuroscience? Thomas Kuhn’s views on scientific change are well known — and much challenged. Yet, his basic perspectives have remained guiding touchstones in the philosophy of science. In this presentation I examine whether advances in our understanding of the microbiome and its influence on brain function constitute a genuine scientific revolution. If they do not, is this a problem for neo-Kuhnian approaches to understanding scientific change? Are we perhaps witnessing a Kuhnian-style revolution in how we understand scientific progress in neuroscience? To answer these questions, I shall examine the putative connections between the microbiome and Autism Spectrum Disorder, anxiety, and normal brain development. I shall conclude that what constitutes progress in neuroscience is far more multifarious than many philosophers assume.
Valerie Hardcastle is invited by PhilInBioMed, ImmunoConcept, and Thomas Pradeu’s ERC-funded project IDEM.
Abstract
This talk will discuss some recent work on causation in biology from a broadly interventionist perspective. The basic idea of an interventionist account of causation is that causal relationships are relationships that are potentially exploitable for manipulation and control. I will use this general framework to discuss some issues having to do the modeling of causal relationships across different levels or scales, notions of causal specificity, and the role of a consideration that I call conditional independence which is closely related to the notion of causal proportionality discussed in the philosophical literature. A guiding theme throughout the talk will the importance of finding the right “level” or the right variables for framing causal hypotheses.
Leonardo Bich (ERC IDEM, ImmunoConcEpT, CNRS & University of Bordeaux)
“Minimal cognition and its foundations in regulatory mechanisms in basic living systems”
Abstract:
This talk addresses the question of minimal cognition by investigating the origin of some crucial cognitive properties in the very basic organisation of biological systems. Unlike other approaches to the origin of cognition, which are centred on movement (in unicellular systems) or on the role of the nervous system (in metazoans), I focus on specific molecular adaptive mechanisms that justify the attribution of cognitive capabilities already to prokaryotic organisms. More specifically, I propose a theoretical model of how a system can distinguish between specific features of its interaction with the environment, which is a fundamental requirement for the emergence of minimal forms of cognition, and I analyse its implications by comparing different possible mechanisms underlying chemotactic behaviours in synthetic-abiotic and unicellular living systems. I argue that the appearance of the capacity to functionally distinguish between different features of the environment is grounded in the molecular domain, and originates from basic mechanisms of biological regulation. In conclusion, I show how this framework can provide new and more accurate tools to discuss the Life=Cognition thesis.
Marc Daëron (Institut Pasteur, CIML & IHPST)
“Biological functions challenged by omics”
Abstract
Omics are technology-based large-scale analyses of structurally and/or functionally related populations of molecules designated by the suffix “ome” which have been increasingly used in life sciences. As a result, biological thinking has been radically changed with new biological practice. Noticeably, however, biological functions remain a cornerstone of omics approaches. Do omics appeal to the same functions that have always been used to understand the living? How are these functions compatible with the philosophical theories elaborated in the 1970s? Will the future development of omics redefine the concept of biological function?
When examined with the tools and concepts of molecular and systems biology that underlie omic approaches, biological functions appear as being relational, reciprocal, relative, contextual and probabilistic. Rather than a biological function, biological objects may therefore have a wide potential dispositional repertoire within which the context can select a variety of actual functional repertoires, depending on the conditions. Using antibodies as a case study, I will argue that rather than for a specific effect, a trait might have been selected for its ability to anticipate and respond to the unknown.
Such an account challenges the notion of function, as used by biologists and conceptualized by philosophers. The reason might stem from the orthogonal orientations of classical and omics’ biology. In classical biology, functional analysis is based on the multi-layer vertical integration of causally-linked molecular processes, whereas in omics it is based on the single-layer horizontal comparison of non-causally linked molecular clusters. Whether trans-omics, a recently developed multi-layer integration of data from several omics will reconcile old and new functions or generate radically different functions is a hard to answer but exciting question.
