AGING by Mael Lemoine
La biologie au défi de l'histoire, 2021
You can find here the English version of this chapter originally published in French.
Does Inflammation Contribute to Cancer Incidence and Mortality during Aging? A Conceptual Review
Cancers, 2022
Un problème fondamental en biogérontologie : mesure et explication du vieillissement:
Bulletin d’histoire et d’épistémologie des sciences de la vie, 2023
Frontiers in Genetics, 2021
The evolutionary theory of aging has set the foundations for a comprehensive understanding of agi... more The evolutionary theory of aging has set the foundations for a comprehensive understanding of aging. The biology of aging has listed and described the “hallmarks of aging,” i.e., cellular and molecular mechanisms involved in human aging. The present paper is the first to infer the order of appearance of the hallmarks of bilaterian and thereby human aging throughout evolution from their presence in progressively narrower clades. Its first result is that all organisms, even non-senescent, have to deal with at least one mechanism of aging – the progressive accumulation of misfolded or unstable proteins. Due to their cumulation, these mechanisms are called “layers of aging.” A difference should be made between the first four layers of unicellular aging, present in some unicellular organisms and in all multicellular opisthokonts, that stem and strike “from the inside” of individual cells and span from increasingly abnormal protein folding to deregulated nutrient sensing, and the last four layers of metacellular aging, progressively appearing in metazoans, that strike the cells of a multicellular organism “from the outside,” i.e., because of other cells, and span from transcriptional alterations to the disruption of intercellular communication. The evolution of metazoans and eumetazoans probably solved the problem of aging along with the problem of unicellular aging. However, metacellular aging originates in the mechanisms by which the effects of unicellular aging are kept under control – e.g., the exhaustion of stem cells that contribute to replace damaged somatic cells. In bilaterians, additional functions have taken a toll on generally useless potentially limited lifespan to increase the fitness of organisms at the price of a progressively less efficient containment of the damage of unicellular aging. In the end, this picture suggests that geroscience should be more efficient in targeting conditions of metacellular aging rather than unicellular aging itself.
Biology and Philosophy, 2020
Aging is an elusive property of life, and many important questions about aging depend on its defi... more Aging is an elusive property of life, and many important questions about aging depend on its definition. This article proposes to draw a definition from the scientific literature on aging. First, a broad review reveals five features commonly used to define aging: structural damage, functional decline, depletion, typical phenotypic changes or their cause, and increasing probability of death. Anything that can be called 'aging' must present one of these features. Then, although many conditions are not consensual instances of aging, aging is consensually described as a process of loss characterized by a rate and resulting from the counteraction of protective mechanisms against mechanisms that limit lifespan. Beyond such an abstract definition, no one has yet succeeded in defining aging by a specific mechanism of aging because of an explanatory gap between such a mechanism and lifespan, a consensual explanandum of a theory of aging. By contrast, a sound theoretical definition can be obtained by revisiting the evolutionary theory of aging. Based on this theory, aging evolves thanks to the impossibility that natural selection eliminates late traits that are neutral mainly due to decreasing selective pressure. Yet, the results of physiological research suggest that this theory should be revised to also account for the small number of different aging pathways and for the existence of mechanisms counteracting these pathways, that must, on the contrary, have been selected. A synthetic, but temporary definition of aging can finally be proposed.
DISEASE by Mael Lemoine
Philosophie de la médecine. Définitions de la santé et de la maladie
Les concepts de santé et de maladie : apports de la philosophie anglo-saxonne de la médecine
Defining disease beyond conceptual analysis: An analysis of conceptual analysis
Cinq éclaircissements sémantiques et syntaxiques du concept de guérison
L Ailleurs Du Corps, Feb 1, 2010
ABSTRACT Sans doute est-il attendu d'une analyse philosophique qu'elle traque les... more ABSTRACT Sans doute est-il attendu d'une analyse philosophique qu'elle traque les prestiges et les fausses promesses de concepts vagues tels que " guérir ". N'est-ce pas le travail de Socrate : expliquer au général qu'il ne sait pas ce qu'est le courage, et au sophiste pourquoi il ne sait rien de la sagesse ? C'est un jeu aisé auquel on se livrerait ainsi devant un lectorat déjà acquis de professionnels du soin revenus des illusions de toute-puissance de la science. Mais il y aurait une certaine prétention, dans tous les cas de l'indécence, à expliquer à un grand malade qu'il n'entend au fond rien de précis dans son vœu de guérir. C'est un avertissement pour le philosophe qui s'attelle à la tâche facile de détruire un concept. Car prendre au sérieux le concept vernaculaire de guérison est une contrainte morale, mais aussi bien un enjeu théorique. Les cinq remarques qui suivent visent donc à préciser le sens et l'usage des mots de la guérison et à en justifier les prétentions.
Cinq éclaircissements sémantiques et syntaxiques du concept de guérison
Sans doute est-il attendu d'une analyse philosophique qu'elle traque les prestiges et les... more Sans doute est-il attendu d'une analyse philosophique qu'elle traque les prestiges et les fausses promesses de concepts vagues tels que " guérir ". N'est-ce pas le travail de Socrate : expliquer au général qu'il ne sait pas ce qu'est le courage, et au sophiste pourquoi il ne sait rien de la sagesse ? C'est un jeu aisé auquel on se livrerait ainsi devant un lectorat déjà acquis de professionnels du soin revenus des illusions de toute-puissance de la science. Mais il y aurait une certaine prétention, dans tous les cas de l'indécence, à expliquer à un grand malade qu'il n'entend au fond rien de précis dans son vœu de guérir. C'est un avertissement pour le philosophe qui s'attelle à la tâche facile de détruire un concept. Car prendre au sérieux le concept vernaculaire de guérison est une contrainte morale, mais aussi bien un enjeu théorique. Les cinq remarques qui suivent visent donc à préciser le sens et l'usage des mots de la g...
The meaning of the opposition between the healthy and the pathological and its consequences
Medicine Health Care and Philosophy, 2009
If the healthy and the pathological are not merely judgments qualifiers, but real phenomena, it m... more If the healthy and the pathological are not merely judgments qualifiers, but real phenomena, it must be possible to define both of them positively, which, in this context, means as factual contraries. On the other hand, only a privative definition, either of the pathological as ‘non-healthy’, or of the healthy as ‘non-pathological’, can rationally circumscribe all possible states of an organism. This fluctuation between two meanings of the ‘healthy’–‘pathological’ opposition, factual vs. rational, characterizes the ordinary usage of these concepts and puts all philosophical definitions in a hopeless situation. Although a scientific definition may conceal this equivocation by adequately setting out the terms of the problem of discriminating between the ‘healthy’ and the ‘pathological’, it could explain some of the difficulties met in determining ‘gold standards’, in the choice of separators, and in the assessment of the diagnostic qualities of tests.
Is Boorse’s Biostatistical Theory of Health naturalistic?
Christopher Boorse’s biostatistical theory of health and disease (BST) puts forward a naturalisti... more Christopher Boorse’s biostatistical theory of health and disease (BST) puts forward a naturalistic definition of these two concepts. Indeed, ‘naturalism’ in the philosophy of medicine was initially defined in terms of the BST, and has often been since. This chapter is an attempt to clarify in what sense Boorse does in fact defend a naturalistic definition of health and disease. We identify different theses that make naturalistic claims regarding health and disease and which help analyze the core claims of Boorse’s naturalism. Some of them have mainly to do with the central role physiology plays in medicine. But, as no physiologist has hitherto proposed a satisfactory scientific definition of ‘disease’ and ‘health’, Boorse’s naturalism must at the same time: i) propose just such a definition; and ii) prove that it is central to medicine. Our claim is that even if Boorse’s definition possibly succeeds in (i), it merely assumes (ii). We conclude by examining the necessity that a naturalistic definition of health and disease takes into account not only physiology but also other medical sciences.
Science starts by using terms such as ‘temperature’ or ‘fish’ or ‘gene’ to preliminarily delimita... more Science starts by using terms such as ‘temperature’ or ‘fish’ or ‘gene’ to preliminarily delimitate the extension of a phenomenon, and concludes by giving most of them a technical meaning based on an explanatory model. This transforma- tion of the meaning of the term is an essential part of its naturalization. Debating on the definition of ‘disease’, what most philosophers of medicine have examined is the pre-naturalized meaning of the term: for that reason they have focused on the task of delimiting disease and non-disease (health), mainly used conceptual analysis as a method of choice, and considered the nosological level of ‘disease judgments’ rather than the pathophysiological or psychopathological level of disease mechanisms, thus making them impervious to most scientific discoveries. By focusing instead on the naturalized concept of disease and following some suggestions by philosophers of biology and scientists in cutting-edge fields of biomedical research, they could gar- ner results from a comparison of the mechanisms of diseases. This would ultimately result in a general theory of disease linked with our most general theories on living beings, among them, systems biology and network medicine. Before undertaking such a task, preliminary questions arise: is it likely that there are biological features common to different types of disease? Is it a philosopher’s job to determine what they consist in? What use would such a general theoretical definition of disease be?
PSYCHIATRY AND NEUROSCIENCE by Mael Lemoine
Is the Dysfunction Component of the “Harmful Dysfunction Analysis” Stipulative?
Defining mental disorder: Jerome Wakefield and his critics, 2021
The prospects of precision psychiatry
Theoretical Medicine and Bioethics, 2022
« La naturalisation de la dépression », in Pierre Thomas, Arnaud Biraben, Epilepsie et Psychiatrie, Dunod, Paris, 2015, pp. 24-41.
(English below)
Les troubles mentaux en général, la dépression en particulier, ont été souvent dé... more (English below)
Les troubles mentaux en général, la dépression en particulier, ont été souvent dénoncés par les sociologues de la santé comme des constructions sociales plutôt que des faits naturels. Mais comme tout fait naturel est d’abord nécessairement décrit par une construction sociale, la question est plutôt de s’interroger sur ce qui s’oppose à sa naturalisation. Le présent article décrit trois problèmes qui font obstacle à la naturalisation de la dépression, le caractère flou de l’extension du concept qui résulte de l’absence de gold standard, la difficulté à trianguler un état mal repéré en bidouillant les instruments de détection dont on dispose, et la difficulté à sélectionner les mécanismes qui entrent à bon droit dans l’image d’ensemble de ce trouble mental.
Abstract : Sociologists have often deemed mental disorders in general, depression in particular, to be social constructs rather than natural facts. Yet as every natural fact is necessarily described by a social construct at first, the question is rather what hinders its naturalization. This paper describes three obstacles to the naturalization of depression: fuzziness of the extension of this concept in the absence of a gold standard, difficulties in triangulating an ill-localized condition by tweaking detection instruments, and the issue of selecting mechanisms that should be part of the big picture of this mental disorder.
Because biologization of psychiatric constructs does not involve derivation of laws, or reduce th... more Because biologization of psychiatric constructs does not involve derivation of laws, or reduce the number of entities involved, the traditional term of ‘reduction’ should be replaced. This paper describes biologization in terms of redefinition, which involves changing the definition of terms sharing the same extension. Redefinition obtains through triangulation and calibration, that is, respectively, detection of an object from two different spots, and tweaking parameters of detection in order to optimize the picture. The unity of the different views of the same object does not occur through derivation from one of them, as reduction suggests, nor does it obtain through mechanistic unity or the goal of explaining one mechanism, as the phrase ‘mosaic unity’ suggests. Instead, it depends on finding a specific angle of observation, from which linguistic consistency matches sound localization in the brain, so that all observations make sense together, just as an anamorphic picture makes clear sense only when observed from the right spot.
« Molecular complexity: Why has psychiatry not been revolutionized by genomics (yet)? », in G. Boniolo & M. Nathan (ed), Foundational Issues in Molecular Medicine, Routledge, London, 2016, pp. 81-99.
This chapter looks into the results of Genome-Wide Associations Studies, one of the leading trend... more This chapter looks into the results of Genome-Wide Associations Studies, one of the leading trends in molecular psychiatry. The main reason for their limited achievements to-date is precisely what they have been designed to handle: complexity. Yet this much used term needs further clarification in the context of Genome-Wide Association Studies. A distinction should be made between 1) unreliable phenotypes, a problem that may eventually solve itself with a molecular approach, 2) complex inheritance processes, and 3) complex mechanisms, in the forms of genomic, etiological and pathophysiological complexity. This situation is of interest to the study of several traditional questions in the philosophy of medicine.
Extrapolation from animal model of depressive disorders: what’s lost in translation?
Animalmodelsofdepressionareproblematicandresultsdrawnfromthem is moderately convincing. The main ... more Animalmodelsofdepressionareproblematicandresultsdrawnfromthem is moderately convincing. The main problem, it is often argued, is that it is impossible to model a mental disorder, i.e. specifically human, in animals like rodents: it is a mat- ter of resemblance of symptoms. Yet in this field it is generally assumed that animal models of depression are more or less ‘valid’ according to three criteria: predictive, construct, and face validity, with only the latter concerned with the resemblance of symptoms. It is argued here that the problem is actually not with resemblance to the clinical features or to the factors of depression: it is not their being mental parameters. It lies, rather, in the fuzziness of the definition of a human entity and in the difficulty of linking together supposedly involved biological mechanisms into a consistent pic- ture of the underlying process of the disease. It is therefore not that we cannot model what we know to be depression, it is rather that we do not know what to model.
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AGING by Mael Lemoine
DISEASE by Mael Lemoine
PSYCHIATRY AND NEUROSCIENCE by Mael Lemoine
Les troubles mentaux en général, la dépression en particulier, ont été souvent dénoncés par les sociologues de la santé comme des constructions sociales plutôt que des faits naturels. Mais comme tout fait naturel est d’abord nécessairement décrit par une construction sociale, la question est plutôt de s’interroger sur ce qui s’oppose à sa naturalisation. Le présent article décrit trois problèmes qui font obstacle à la naturalisation de la dépression, le caractère flou de l’extension du concept qui résulte de l’absence de gold standard, la difficulté à trianguler un état mal repéré en bidouillant les instruments de détection dont on dispose, et la difficulté à sélectionner les mécanismes qui entrent à bon droit dans l’image d’ensemble de ce trouble mental.
Abstract : Sociologists have often deemed mental disorders in general, depression in particular, to be social constructs rather than natural facts. Yet as every natural fact is necessarily described by a social construct at first, the question is rather what hinders its naturalization. This paper describes three obstacles to the naturalization of depression: fuzziness of the extension of this concept in the absence of a gold standard, difficulties in triangulating an ill-localized condition by tweaking detection instruments, and the issue of selecting mechanisms that should be part of the big picture of this mental disorder.