BackgroundContinuous cell lines are indispensable in basic and preclinical research. However, cross-contamination, misidentification, and over-passaging affect the validity and reproducibility of biomedical results. Although there have been efforts to highlight this problem for decades, definitive prevention remains a challenge. The International Cell Line Authentication Committee (ICLAC) registry (version 13, 26 April 2024) lists nearly 600 misidentified or contaminated cell lines. The inappropriate use of such cells has led to countless publications containing invalid data, creating a ripple (...) effect of wasted resources, misleading follow-up studies, and compromised evidence-based conclusions.MethodsThe ICLAC registry was consulted to identify commonly misidentified cell lines. A literature search of PubMed was performed to identify recent papers using these lines in liver-related experiments. Four publications with questionable conclusions were highlighted, and the editors of the respective journals were informed with short comments or letters to the editor.ResultsReactions from journal editors varied widely. In two cases, the editors quickly published the comments, resulting in transparent corrections. In the third example, the editor conducted an internal investigation without immediately publishing a correction. In the fourth example, the journal declined to address concerns publicly. ConclusionsMisidentified cell lines pose an ongoing threat to scientific rigor. Despite some responsible editorial interventions, the lack of universal standards fosters the dissemination of erroneous data. However, authors, reviewers, and editors have some important tools to prevent publications with misidentified cells by consulting available resources (e.g., ICLAC, Cellosaurus, Research Resource Identification Portal, SciScore™), and adopting consistent procedures to maintain research integrity. (shrink)

Cell line immortalisation is a growing component of African genomics research and biobanking. However, little is known about the factors influencing consent to cell line creation and immortalisation in African research settings. We contribute to addressing this gap by exploring three questions in a sample of Xhosa participants recruited for a South African psychiatric genomics study: First, what proportion of participants consented to cell line storage? Second, what were predictors of this consent? Third, what (...) questions were raised by participants during this consent process? 760 Xhose people with schizophrenia and 760 controls were matched to sex, age, level of education and recruitment region. We used descriptive statistics to determine the proportion of participants who consented to cell line creation and immortalization. Logistic regression methods were used to examine the predictors of consent. Reflections from study recruiters were elicited and discussed to identify key questions raised by participants about consent. Approximately 40% of participants consented to cell line storage. The recruiter who sought consent was a strong predictor of participant’s consent. Participants recruited from the South African Eastern Cape, and older participants, were more likely to consent; both these groups were more likely to hold traditional Xhosa values. Neither illness nor education were significant predictors of consent. Key questions raised by participants included two broad themes: clarification of what cell immortalisation means, and issues around individual and community benefit. These findings provide guidance on the proportion of participants likely to consent to cell line immortalisation in genomics research in Africa, and reinforce the important and influential role that study recruiters play during seeking of this consent. Our results reinforce the cultural and contextual factors underpinning consent choices, particularly around sharing and reciprocity. Finally, these results provide support for the growing literature challenging the stigmatizing perception that people with severe mental illness are overly vulnerable as a target group for heath research and specifically genomics studies. (shrink)

Abstractp53 has a determinant role in cancer prevention and is among the most studied proteins in the world. The majority of studies devoted to this protein are carried out in cell lines because they are easy to use and have naturally emerged as the main research tool in laboratories. However, the p53 pathway is commonly deregulated in cancer cells, from which the experimental cell lines are generally derived. The fact that the pathway is deregulated challenges the relevance of (...) using cancer‐derived cell lines to study wild‐type p53 activities, or, in a broader sense, to study any normal cellular process. In the present article, we identify and discuss a number of limitations of cell lines using examples related to p53. Finally, we point out the general limitations of cell lines and propose solutions as alternatives to these cells. (shrink)

Human cell lines are well-characterized laboratory cultures of human cells derived from a single source. In recent years, much moral controversy has surrounded human cell lines and biological materials obtained from aborted fetuses and destructive human embryo research. Dignitas personae instructs scientists of good conscience to avoid using biological materials of illicit origin, to distance themselves from evil, and to avoid scandal. The author suggests that the Instruction allows a scientist to delay discontinuing the use of a morally (...) controversial cell line for a reasonable amount of time and allows a citizen of conscience to financially support—in a limited and restricted manner governed by prudence—philanthropic organizations that fund controversial biomedical research programs. National Catholic Bioethics Quarterly 10.2 : 265–272. (shrink)

A March of 2021 “Statement from Pro-Life Catholic Scholars on the Moral Acceptability of Receiving COVID-19 Vaccines,” released by the Ethics and Public Policy Center argued that in accepting one of the Covid vaccines that had recently become available, one would not be “in any way endorsing or con­tributing to the practice of abortion, or... in any way showing disrespect for the remains of an unborn human being.” That statement received criticism from some opponents of abortion. Here, I raise six (...) questions about the claims or implications of the “Statement” in order to defend it in its main assertions, correct it in some minor matters, and extend its analysis as needed. (shrink)

The rise of genomic studies in Africa – not least due to projects funded under H3Africa – is associated with the development of a small number of biorepositories across Africa. For the ultimate success of these biorepositories, the creation of cell lines including those from selected H3Africa samples would be beneficial. In this paper, we map ethical challenges in the creation of cell lines.

The alienation of body parts and their transformation into commodities raises questions about ownership, property rights, and about possible violation of the moral order. This article focuses on the `social life' of objects, including body parts, and the multiple meanings attached to them that are made visible in systems of exchange. The transformation of DNA obtained in blood samples into immortalized cell lines for use in the Human Genome Diversity Project is introduced as an illustration of contested commodification. The (...) meanings attached to the blood samples by those from whom they are procured and their worth to the scientists who create the cell lines are of an entirely different order. Disputes about the HGDP that have erupted since it was first planned are presented in detail, followed by a discussion of the ethics of gene prospecting and the associated politics of biocapitalism currently proliferating in the private sector. (shrink)

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding (...) studies, second messenger assays, ion imaging, patch‐clamp electrophysiology and gene silencing can readily be applied. Drosophila is also ideal for the study of new control strategies for insect pests since the receptors and ion channels that many new animal health drugs and crop protection chemicals target can be expressed in this cell line. In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. BioEssays 24:1066–1073, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

The recent Instruction Dignitas personae from the Congregation for the Doctrine of the Faith formally addresses the issue of the use of biological material of illicit origin. We now face the challenge of applying the principles it sets forth to daily realities. While the issue of vaccines that use such illicit cell lines has been addressed, other scenarios involving the everyday scientist or researcher in the laboratory or clinic will have to be confronted. It is a critical time for (...) the cell line issue, and much work is needed by the scientific community to find ethical solutions. This article hopes to encourage positive steps in that direction. National Catholic Bioethics Quarterly 10.2 (Summer 2010): 273–280. (shrink)

This essay argues that the racialized geopolitics of the rhesus monkey trade conditioned the trajectory of tissue culture in polio research. Rhesus monkeys from north India were important experimental organisms in the American “war against polio” between the 1930s and 1950s. During this period, the National Foundation for Infantile Paralysis expended considerable effort to secure the nonhuman primate for researchers’ changing experimental agendas. The NFIP drew on transnational networks to export hundreds of thousands of rhesus monkeys from colonial and later (...) postcolonial India amid the geopolitical upheavals of World War II, the 1947 Partition, and the Cold War. In this essay, I trace how NFIP officials’ anxieties about the geopolitics of the monkey trade configured research imperatives in the war against polio. I show how their anxieties more specifically shaped investment in tissue culture techniques as a possible means of obviating dependence on the market in monkeys. I do so by offering a genealogy of the contingent convergence between the use of rhesus monkeys and HeLa cell cultures in the 1954 Salk vaccine trial evaluation. Through this genealogy, I emphasize the geopolitical dimensions of the search for the “right” experimental organisms, tissues, and cells for the “job” of scientific research. The technical transformation of polio research, I argue, relied on the convergence of disparate, racialized biomedical economies. (shrink)

Stem cell banks curating and distributing human embryonic stem cells have been established in a number of countries and by a number of private institutions. This paper identifies and critically discusses a number of arguments that are used to justify the importance of such banks in policy discussions relating to their establishment or maintenance. It is argued (1) that ‘ethical arguments’ are often more important in the establishment phase and ‘efficiency arguments’ more important in the maintenance phase, and (2) (...) that arguments relating to the interests of embryo and gamete donors are curiously absent from the particular stem cell banking policy discourse. This to some extent artificially isolates this discourse from the broader discussions about the flows of reproductive materials and tissues in modern society, and such isolation may lead to the interests of important actors being ignored in the policy making process. (shrink)

Stem cells did not become a proper research object until the 1960 s. Yet the term and the basic mind-set—namely the conception of single undifferentiated cells, be they embryonic or adult, as the basic units responsible for a directed process of development, differentiation and increasing specialisation—were already in place at the end of the nineteenth century and then transmitted on a non-linear path in the form of tropes and diagrams. Ernst Haeckel and August Weismann played a special role in this (...) story. The first coined the term Stammzelle (stem cell), the second was the author of the first cellular stem-tree diagram. Even today, I shall argue, the understanding of stem cells, especially the popular perception, is to a large extent a Haeckelian–Weismannian one. After having demonstrated this, by analysing the terminology, in this essay I will focus on the use of cytogenetic tree diagrams between 1892 and 1925 and on the tacit understanding of stem cells that they transmit. (shrink)

We assume the existence of a specific G1 protein which is an initiator of DNA replication. This initiator is supposed to be synthesized according to Michaelis-Menten kinetics. In order to start DNA replication, it is assumed that this G1 specific protein must be produced in a required amount. Intra-cellular growth inhibitors and extra-cellular growth factors control the production of the initiator. This model allows to calculate the average G1 phase time as a function of the various chemical concentrations of nutrients, (...) enzymes, growth inhibitors and growth factors. This model is compared to cell kinetics experiments on a leukemic cell line responding to Interleukin 3 deprivation. The curves giving the experimental average G1 phase times with respect to Interleukin-3 concentrations are fitted by the mathematical model with a quite good agreement. (shrink)

This study shows that double thymidine block treatment efficiently arrests the EO771 cells in the S‐phase without altering cell growth or survival. A long‐term analysis of cell behavior, using 5(6)‐carboxyfluorescein diacetate N‐succinimidyl ester (CFSE) staining, show synchronization to be stable and consistent over time. The EO771 cell line is a medullary breast‐adenocarcinoma cell line isolated from a spontaneous murine mammary tumor, and can be used to generate murine tumor implantation models. Different biological (serum or (...) amino acid deprivation), physical (elutriation, mitotic shake‐off), or chemical (colchicine, nocodazole, thymidine) treatments are widely used for cell synchronization. Of the different methods tested, the double thymidine block is the most efficient for synchronization of murine EO771 cells if a large quantity of highly synchronized cells is recommended to study functional and biochemical events occurring in specific points of cell cycle progression. (shrink)

In this paper I analyse who should be able to control the use of human embryonic stem cell lines. I distinguish between different kinds of control and analyse a set of arguments that purport to show that the donors of gametes and embryos should not be able to control the use of stem cell lines derived from their embryos. I show these arguments to be either deficient or of so general a scope that they apply not only to (...) donors but also to those who derived the stem cell lines. Since we normally think that stem cell derivers have the right to control the use of the cell lines they derived, we have no justification for denying donors similar rights of control. In the final section I briefly discuss why informed consent is not an appropriate vehicle for transferring or alienating control rights. (shrink)

In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) (...) and subsequently analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the Gl-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle. (shrink)

The production of a number of vaccines involves the use of cell-lines originally derived from fetuses directly aborted in the 1960s and 1970s. Such cell-lines, indeed sometimes the very same ones, are important to on-going research, including at Catholic institutions. The cells currently used are removed by a number of decades and by a significant number of cellular generations from the original cells. Moreover, the original cells extracted from the bodies of the aborted fetuses were transformed to produce (...) the cell lines, since otherwise they would be incapable of the kind of culturing that is required. (shrink)

          The production of a number of vaccines involves the use of cell-lines originally derived from fetuses directly aborted in the 1960s and 1970s. Such cell-lines, indeed sometimes the very same ones, are important to on-going research, including at Catholic institutions. The cells currently used are removed by a number of decades and by a significant number of cellular generations from the original cells. Moreover, the original cells extracted from (...) the bodies of the aborted fetuses were transformed to produce the cell lines, since otherwise they would be incapable of the kind of culturing that is required.           It is generally acknowledged by ethicists, including many Catholic ones generally considered to be orthodox, and by the U.S. bishops, that the use of the cell-lines in connection with the production of vaccines is morally permissible. It does not appear that there is a relevant qualitative difference between the use of the cell-lines in vaccines and in research. One might argue that there is certainty of benefit from a vaccine while the benefits of research are uncertain. However, in any given case of the administration of a vaccine to an individual, it is far from certain that such administration will be of benefit to that individual. After all, the individual might never come in contact with someone infected with the disease in question, particularly if the disease is now uncommon in the individual’s locale. Yet, it is morally certain that some of the administrations of the vaccine will be beneficial. This is parallel to the fact that while any one research project might not be beneficial, the history of biomedical research makes it extremely probable, indeed morally certain, that some project involving the use of such cell-lines will be beneficial. There may, of course, be quantitative difference between the cases—the probabilities and benefits may not be equal—but the difference does not seem to be a qualitative one. Therefore, if one accepts the use of the cell-lines in vaccines, one should accept the use in research in at least some conceivable and perhaps actual circumstances.           The main argument I am interested in in favor of the use of the cell-lines proceeds by first granting that the initial abortion and extraction of cells from the deceased fetus was morally gravely illicit. However, the connection between the currently used derived cells and the abortion and original derivation is sufficiently remote that the use becomes licit. Not all fruit of a poisoned tree is poisoned: it can be morally.... (shrink)

This paper examines the logic and morality of the German Stem Cell Act of 2002. After a brief description of the law’s scope and intent, its ethical dimensions are analysed in terms of symbolic threats, indirect consequences, and the encouragement of immorality. The conclusions are twofold. For those who want to accept the law, the arguments for its rationality and morality can be sound. For others, the emphasis on the uniqueness of the German experience, the combination of absolute and (...) qualified value judgments, and the lingering questions of indirect encouragement of immoral activities will probably be too much. (shrink)

Dans les cinquante dernières années, les progrès de l’informatisation ont renforcé l’accessibilité de la jurisprudence via des bases de données juridiques, maintenant concurrencées par des plates-formes de diffusion du droit sur internet. La loi pour une République numérique du 7 octobre 2016 a prévu la généralisation de la diffusion des décisions des juges du fond au titre du processus d’ open data. Toutefois les obstacles sont nombreux : conceptuels, techniques, matériels. D’abord, un glissement s’est opéré d’une problématique d’anonymisation des décisions (...) juridictionnelles vers celle de leur pseudonymisation. Ensuite, la pseudonymisation pourrait constituer un frein au mouvement d’ open data judiciaire, du fait de la lourdeur technique nécessaire pour la réaliser. Juridiquement, sa mise en œuvre s’avère de surcroît délicate. Le renvoi législatif à la protection de la vie privée doit se combiner avec l’application du droit des données personnelles, au titre duquel il faut limiter le risque de réidentification des justiciables. Enfin, matériellement le curseur de la pseudonymisation est malaisé à placer. Quelles indications convient-il de masquer : celles relatives aux parties, ou plus largement aux personnes citées et professionnels du droit impliqués? (shrink)

La traçabilité, définie par la norme Iso 8402 comme « l'aptitude à retrouver l'historique, l'utilisation ou la localisation d'une entité au moyen d'identifications enregistrées » implique une forme de surenchérissement technique dans les modes de production : visant à créer une confiance fondée sur la preuve du respect de certaines normes techniques codifiant les procédures de fabrication, elle nous éloigne par là même encore plus d'un mode de production artisanal, soumis aux aléas et aux défauts inhérents à la reproduction humaine (...) des mêmes gestes. On analysera dans le cas de la filière viande bovine, les discours des acteurs impliqués ainsi que le contenu concret des procédures, afin de comprendre l'apport du dispositif de traçabilité en matière de restauration de confiance. En se référant simultanément à d'autres cas de mise en place de traçabilité, on fera enfin l'hypothèse que ces procédures, assurant une forme de transparence et de responsabilisation des activités techniques, peuvent recréer une confiance dans ces activités en répondant à une exigence d'ordre politique propre à la 'société du risque' . On rappellera rapidement en premier lieu l'évolution de la réglementation en matière de traçabilité et d'étiquetage des viandes bovines, afin de situer le contexte des pratiques des professionnels. On verra ensuite quelles sont les différentes stratégies associées par les acteurs de la filière à la notion de traçabilité : si un certain nombre d'agriculteurs, assimilant traçabilité et proximité, se sont lancés dans la vente directe de leurs produits, l'organisation de la traçabilité dans le circuit industriel, dirigée vers la communication d'un certain nombre de critères codifiés, intensifie au contraire certaines pratiques industrielles. On verra enfin que ce dispositif de traçabilité implique concrètement des modifications profondes dans le travail des acteurs, fortement bureaucratisé, codifié et contrôlé, permettant ainsi de produire un ensemble de traces renvoyant à une responsabilisation collective de la filière. On développera alors une hypothèse suggérant que le concept de traçabilité, médiatisé lors des crises et accidents technologiques récents, peut fonder une confiance du consommateur profane dans les systèmes d'activités techniques , en remplaçant la notion d'autorité ou de compétence spécialistes dont l'émergence des risques technologiques marque la faillibilité, par celle de transparence collective. (shrink)

Le philosophe, que caractérise selon Nietzsche la vertu d’indépendance, se trouve par là condamné à la solitude. Celle-ci toutefois ne doit pas être conçue de manière négative, comme un simple retrait hors du monde, ou comme un refus de toute relation et de toute altérité. L’individu n’est pas une substance, mais un complexe de forces, c’est-à-dire un « corps » qui est non seulement structuré à la manière d ’une communauté, mais aussi par les relations sociales externes dans lesquelles l’individu (...) se trouve d’abord engagé. La solitude ne doit pas en conséquence être confondue avec un simple état d’ isolement. Elle consiste en une épreuve, en un mouvement de conquête de la singularité, contre les valeurs du « troupeau » qui ont été incorporées. Une telle conquête requiert que soient considérés et questionnés les autres hommes et valeurs dans leur diversité. Et elle fait surgir l’exigence d’une communauté qui apparaît comme la condition paradoxale d’une solitude authentique. (shrink)

À partir d’une analyse d’entretiens de recherche clinique, les auteures proposent une réflexion psychodynamique quant aux liens entre découverte tardive de grossesse et phobies d’impulsion. Les rencontres amènent un premier élément de compréhension en lien avec un report dans le temps de l’hypersensibilité maternelle et des possibilités d’identification mère-enfant. L’écoute clinique des vécus de ces femmes rappelle l’importance de situer la place des phobies d’impulsion dans l’économie psychique de celles-ci afin de différencier ce qui est de l’ordre d’une fantasmatique agressive (...) ordinaire d’une fantasmatique meurtrière révélant la fragilité des processus de refoulement. Ces propositions invitent à réfléchir aux dispositifs susceptibles d’accueillir et de favoriser un travail d’appropriation des affects et fantasmes parfois intensément mobilisés à la faveur de cette découverte. (shrink)

Let texted de Nietzsche se caractérise par l'usage de métaphors ed d'images multiples. Nietzshce affirme que nous n'avons accès à rien de plus qu'a des images. Il repense à la fois, de façcon polémique et contre tout dualisme, le statut de l'image, et la «connaissance» dont nous sommes susceptibles. L'image n'est alors que l'autre nom de l'«interprétation», nom qui permet de préciser en quel sens celle-ci doit être entendue. En conséquence, la tâche d'une philosophie neuve ne doid consister qu'a produier (...) de meilleures images, qui permettent de faire advenir un plus haut degré de culture - l'image apparaissant alors comme l'un des pivots essentiels du double versant, généalogique et créateur, de la pensée de Nietzsche.Nietzsche's text is characterized by the constant use of metaphors and images of various sorts; and he contends that we can know nothing more than images. He rethinks both the very concept of "image" in a controversial way and so the "knowledge" we are capable of. "Image" then is nothing but the other demonmination of "interpretation", a denomination which must be read as an enlightenment on how "interpretation" should be understood. Consequently, the task of a new philosophy should consist only in discovering better images, in order to create new values and a higher degree of culture - so that the image can indeed finally be understood as an essential axis of the two sides of Nietzsche's thought.Nietzches Text zeichnet sich durch den Gebrauch von vielfaltigen Bildern und Metaphoren aus, und er behauptet, dass wir nur zu Bildern Zugang haben. Er überdenkt - in oft polemischer und eindimensionaler Weise - den Stellenwert des Bildes und damit auch die "Erkenntnis", zu der wir imstande sind. Das Bild ist somit ein anderer Begriff für "Interpretation"; mit ihm interpertiert Nietzsche, wie "Interpretation" zu verstchen ist. Die Aufgabe einer neuen Philosophie kann so nur darin bestehen, bessere Bilder zu schaffen. Um ein höhere Kulturstufe zu erreichen, erscheint das Bild damit als ein esssentieller Dreh- und Angel-unkt von Nietzches zwischen Genealogie und Genialität angesiedeltem Denken. (shrink)

Tracer un parcours entre le début du XXe siècle et l'aube du XXIe siècle en compagnie de plusieurs artistes enseignants et de Rudolf Steiner en particulier, tel est l'objectif de cette étude. En mettant en connivence les grandes aventures que représentèrent la construction du Goethéanum près de Bâle à Dornach (1913-1918) et celle du Bauhaus à Weimar, Dessau, Berlin (1919-1933), l'auteur a voulu faire découvrir des territoires nouveaux d'où émergeait une Utopie de mission civilisatrice. Rudolf Steiner, tout comme Kandinsky, Klee (...) ou encore Beuys furent tout à la fois artistes et enseignants. Les témoignages de leurs contemporains permettent de les saisir dans cet instant fugace de la transmission, impalpable et magique à la fois, qui révèle la richesse de leurs êtres. Leur manière de vivre la transmission est imprégnée d'art : c'est un moment créateur dans l'échange. Alors que certains de ces idéaux perdurent d'un point de vue artistique, mais également pédagogique à travers l'existence des écoles Steiner-Waldorf, par exemple, qu'en est-il aujourd'hui de la question de la transmission par l'art? Cette immense liberté conquise par les artistes du XXe siècle ne devrait-elle pas faire valeur d'exemple lorsqu'il s'agit d'interroger son point de vue sur le monde? (shrink)

La présente étude part d’une discussion de la thèse exposée par Catherine Colliot-Thélène dans son ouvrage La démocratie sans « demos » selon laquelle la démocratie moderne est « sans demos », composée uniquement de sujets de droits individuels. Appliquée à la construction européenne, cette thèse s’avère féconde, mais aussi problématique. Si elle conduit à sortir des mythes du contrat social et du pouvoir constituant et de poursuivre la démocratisation par la seule garantie du droit subjectif, elle le fait néanmoins (...) en maintenant l’un des axiomes principaux du contractualisme qu’elle réfute, à savoir l’idée que face à l’État seul l’individu est source de droit, non les corps intermédiaires, les communautés et les collectifs. Une autre tradition constitutionnelle fait pourtant plus efficacement l’économie du concept de pouvoir constituant, l’anglaise et l’allemande. Celle-ci développe l’idée d’une « constitution matérielle » ou « réelle », issue des rapports de la pluralité des puissances sociales et non de la volonté du législateur. On postule que cette tradition permet de mieux décrire l’intégration européenne et qu’elle livre des pistes précieuses pour démocratiser l’Europe. (shrink)

Parmi les nombreuses controverses qui affectent l’étude de la pensée économique naissante, la moindre n’est sans doute pas celle qui porte sur l’opportunité même du concept de « mercantilisme ». Les auteurs regroupés sous ce terme par les inventeurs de cette dénomination ne l’ont-ils pas été par leurs adversaires (Quesnay, Smith, E. F. Heckscher) ou par leurs défenseurs (G. Schmoller, W. Cunningham) qui, de surcroît, ne leur sont pas contemporains? Cette contribution se propose par conséquent de restituer la genèse du (...) concept polémique de « mercantilisme » et de présenter une synthèse des critiques qui lui ont été opposées (D. C. Coleman, J. Viner...). La question délicate de l’articulation entre théorie et pratique incitera à prendre la mesure des enjeux philosophiques soulevés par l’élaboration conceptuelle : ce sont alors les liens théoriques complexes entre machiavélisme et mercantilisme qui seront mis en lumière, afin de comprendre par quelles médiations la théorie politique de la raison d’État a pu trouver un champ d’application privilégié chez les auteurs et les acteurs dits mercantilistes. (shrink)

X chromosome inactivation (XCI) is an essential epigenetic process that ensures X‐linked gene dosage equilibrium between sexes in mammals. XCI is dynamically regulated during development in a manner that is intimately linked to differentiation. Numerous studies, which we review here, have explored the dynamics of X inactivation and reactivation in the context of development, differentiation and diseases, and the phenotypic and molecular link between the inactive status, and the cellular context. Here, we also assess whether XCI is a uniform mechanism (...) in mammals by analyzing epigenetic signatures of the inactive X (Xi) in different species and cellular contexts. It appears that the timing of XCI and the epigenetic signature of the inactive X greatly vary between species. Surprisingly, even within a given species, various Xi configurations are found across cellular states. We discuss possible mechanisms underlying these variations, and how they might influence the fate of the Xi. (shrink)

Dans cet ouvrage, science et musique dialoguent selon trois grandes lignes. La premiere est representee par la recherche des causes physiologiques de l'harmonie musicale, conformement au titre de la conference que donne Helmholtz en 1857 (expose synthetique des idees qu'il reprendra dans sa tres fameuse Theorie physiologique de la musique), et par la presentation populaire pour les musiciens qu'en propose Enst Mach, des 1866. Avec Helmholtz, le son acquiert une place centrale pour la musique - le son tel qu'entendu par (...) l'oreille, avec toute sa richesse harmonique - et la dissonance, qui n'est plus un simple rate de la consonance, devient des lors la cle de toute theorie musicale. Mais qu'en est-il aujourd'hui de la theorie physiologique de Helmholtz? Son examen par Patrice Bailhache, a l'aune de l'acoustique actuelle, forme la seconde ligne de force du present livre. Et la troisieme, retenue par Antonia Soulez, est celle tracee par Carl Dalhaus, qui en 1970, voit dans la demarche de Helmholtz une mise en question inaugurale de la naturalite d'un systeme de sons. C'est la musique qui, alors, questionne la science: quelle pertinence ces considerations sur la dissonance et ses causes, conservent-elles face au regne du timbre et de la dissonance depuis la musique atonale et le dodecaphonisme? (shrink)

Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re‐evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed ‘naïve’ human pluripotent stem cells to distinguish them from the conventional ‘primed’ cells. Here, several transcriptional and (...) epigenetic hallmarks of human pluripotent states in the recently described cell lines are reviewed and evaluated. Methods to derive and identify human naïve pluripotent stem cells are also discussed, with a focus on the uses and future developments of state‐specific reporter cell lines and cell‐surface proteins. Finally, opportunities and uncertainties in naïve stem cell biology are highlighted, and the current limitations of human naïve pluripotent stem cells considered, particularly in the context of differentiation. (shrink)

Sexually reproducing metazoans establish a cell lineage during development that is ultimately dedicated to gamete production. Work in a variety of animals suggests that a group of conserved molecular determinants act in this germ line maintenance and function. The most universal of these genes are Vasa and Vasa‐like DEAD‐box RNA helicase genes. However, recent evidence indicates that Vasa genes also function in other cell types, distinct from the germ line. Here we evaluate our current understanding of (...) Vasa function and its regulation during development, addressing Vasa's emerging role in multipotent cells. We also explore the evolutionary diversification of the N‐terminal domain of this gene and how this impacts the association of Vasa with nuage‐like perinuclear structures. (shrink)

Reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. However, a debate over which method is better, somatic cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still persists. Both approaches have the potential to generate patient‐specific pluripotent stem cells for replacement therapy. Yet, although SCNT has been successfully applied in various vertebrates, no human pluripotent stem cells have been generated by SCNT due to technical, legal and ethical difficulties. On the other hand, (...) human iPS cell lines have been reported from both healthy and diseased individuals. A recent study reported the generation of triploid human pluripotent stem cells by transferring somatic nuclei into oocytes, a variant form of SCNT. In this essay, we discuss this progress and the potentials of these two reprogramming approaches for regenerative medicine. (shrink)

In 1998, researchers established the first human embryonic stem cell line. Their scientific triumph triggered an ethics and policy argument that persists today. Bioethicists, religious leaders, government officials, patient advocates, and scientists continue to debate whether this research poses a promise, a threat, or a mixed ethical picture for society.Scientists are understandably excited about the knowledge that could come from studying human embryonic stem cells. Most of them believe these cells offer a precious opportunity to learn more about (...) why diseases develop and how they might be prevented or attacked. In their quest to gain support for stem cell research, scientists and others have claimed that the research could generate cures and treatment for everything from heart disease to cancer. (shrink)

Endothelial cells line the inside of all blood vessels, forming a structurally and functionally heterogenous population of cells. Their complexity and diversity has long been recognized, yet very little is known about the molecules and regulatory mechanisms that mediate the heterogeneity of different endothelial cell populations. The constitutive organ‐ and microenvironment‐specific phenotype of endothelial cells controls internal body compartmentation, regulating the trafficking of circulating cells to distinct vascular beds. In contrast, surface molecules associated with the activated cytokine‐inducible endothelial (...) phenotype play a critical role in pathological conditions including inflammation, tumor angiogenesis, and wound healing. Differentiation of the endothelial cell phenotypes appears to follow similar mechanisms to the differentiation of hematopoietic cells, with the exception that endothelial cells maintain transdifferentiating competence. The present review offers a scheme of endothelial cell differentially expressed endothelial cell molecules as targets for directed therapeutic intervention. (shrink)

The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors’ clinical information for research and regulatory purposes, and existing practices that limit research participants’ ability (...) to control what is done with their genetic data, amplify the privacy concerns. (shrink)

: In February 2004, South Korean researchers became the first in the world to successfully harvest stem cells and establish a stem cell line from a cloned human embryo. This is just one of eight possible policy options concerning human embryonic stem cell research. In practice, every kind of stem cell research can be done in one country or another. This paper evaluates the eight policy options concerning human embryonic stem cell research in light of (...) the arguments and decisions behind them. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 97-114 [Access article in PDF] Stem Cell Research in the U.S. after the President's Speech of August 2001 Cynthia B. Cohen On 9 August 2001, in a nationally televised speech, President Bush addressed the contentious question of whether to provide federal funds for human embryonic stem cell research (White House 2001).1 This research involves taking the primordial cells found in (...) embryos and transforming them into certain specialized cells, such as those of the heart, nerves, and muscles, with the ultimate goal of transferring these cells into patients to repair damaged cells and tissues. In his remarks, the President authorized funding for research only on stem cells already harvested from remaining embryos at in vitro fertilization (IVF) centers as of 9 August 2001, the date of the speech. In a "Fact Sheet" about embryonic stem cell research, he added the ethical requirements that (1) the donors of embryos gave informed consent to the derivation of stem cells from their embryos, (2) the embryos were created solely for reproductive purposes, and (3) no financial inducements were given to the embryo donors. The President also prohibited federally funded research on embryonic stem cells derived from embryos after 9 August 2001, as well as the creation of embryos for research purposes and the cloning of human embryos for both reproductive and research purposes. He did not seek to ban the pursuit of embryonic stem cell research with private funds. "This allows us to explore the promise and potential of stem-cell research without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of embryos," the President stated (White House 2001).The President's speech stirred intense controversy. Many applauded the new policy because it allowed some embryonic stem cell research to proceed, thereby raising hope that treatments might be developed for those suffering from such conditions as Parkinson's disease, Alzheimer's disease, and diabetes. Others supported it on grounds that it would discourage the future destruction of embryos in stem cell research. They maintained that although it was wrong to have derived stem cells from embryos, this wrong was no longer remediable and it therefore was justifiable to allow research using such embryos to proceed. Some, however, objected to the new policy because they held that it unduly limited the [End Page 97] number of embryonic stem cells available for federally funded research. Still others opposed it on grounds that it made the federal government complicit in what they took to be the wrongful destruction of human embryos that had taken place prior to 9 August 2001. The President established the President's Council on Bioethics by executive order in November 2001 and charged it, among other tasks, with monitoring stem cell research and recommending guidelines and regulations for biomedical innovations.Questions about the moral status of human embryos have so captured public attention since the President issued his remarks that other significant ethical and policy issues raised about stem cell research inside the Beltway have remained in the shadows. A number of individuals and organizations—legislators, scientists, patient groups, the President's Council on Bioethics, ethicists, religious task forces, and social commentators—have attempted to bring these other issues to legislative and public attention. They also have revisited the more publicly prominent question of what sorts of protections we owe to human embryos. In response, Congress has attempted to address several of these newly emerging issues at hearings and in legislation. I review these efforts, consider developing issues and arguments, and conclude by exploring possible future directions for federal and private sector stem cell policy. The Availability of Embryonic Stem Cell Lines to Federally Funded Researchers President Bush, in developing his stem cell research policy, accepted a distinction between the "derivation" and the "use" of embryos enunciated by the General Counsel of the Department of Health and Human Services toward the end of the Clinton administration. This distinction was adopted to avoid contravening the Dickey-Wicker Amendment (added... (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 This paper aims to (...) characterize the role of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (shrink)

Harvesting human embryonic stem (hES) cells is a highly controversial field of research because it rests on the destruction of human embryos. Altering the procedure of nuclear transfer (NT) is suggested to generate hES cell lines without ethical obstacles by claiming that no embryo would be involved. While discussing the nature of an embryo and related central questions concerning their moral status and the respect they deserve, this paper argues that the entity created by somatic cell nuclear transfer (...) (SCNT) or altered nuclear transfer (ANT) is an embryo and has the same moral status as a natural embryo. Respect for the embryo is expressed by the ethical principles of proportionality, probability and subsidiarity. This paper argues that the human embryo should only be taken for research with high ranking goals, which are proven in animal experimentation and for which there are no alternatives. This makes ANT obsolete and shows that SCNT to produce hES cells is premature at the present time. (shrink)

In 2001, the U.S. House of Representatives passed the "Human Cloning Prohibition Act" and President Bush announced his decision to allow only limited research on existing stem cell lines but not on "embryos." In contrast, the U.K. has explicitly authorized "therapeutic cloning." Much more will be said about bioethical, legal, and social implications, but subtleties of the science and careful definitions of terms have received much less consideration. Legislators and reporters struggle to discuss "cloning," "pluripotency," "stem cells," and "embryos," (...) and whether "adult" are preferable to "embryonic" stem cells as research subjects. They profess to abhor "copying humans" or "killing embryos." Do they know what they are talking about? Do we? This paper explores the historical, philosophical, and scientific contexts that inform this heated discussion. (shrink)

The cytokine interferon‐γ (IFN‐γ), initiates both cell cycle arrest and cell death in certain cell lines. Through a novel strategy of cell transfection with episomal vectors expressing antisense cDNAs, Deiss et al.(1.2) have demonstrated that it is possible to isolate genes that are required for the initiation of cell death by the cytokine IFN‐γ. This approach, referred to as TKO, for Technical Knock Out, has identified several genes whose activity appears to be essential for the (...) induction of apoptosis by IFN‐γ in HeLa cells. Interestingly, these genes appear to mediate IFN‐γ‐induced apoptosis in HeLa cells, but their inhibition by antisense does not ameliorate the anti‐proliferative effects of IFN‐γ in these cells. The clever strategy employed by these authors holds promise for others who wish to isolate genes required for other differentiative processes in cultured cell lines. (shrink)

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem (...) class='Hi'>cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established. **NB we did not reccommend a NAC, we think it might be appropriate**. (shrink)

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. (...) What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant. (shrink)

Many strands of research by different groups, starting from teratocarcinomas in the laboratory mouse, later moving the corresponding human tumors, contributed to the isolation and description of human pluripotent stem cells (PSCs). In this review, I highlight the contributions from my own research, particularly at the Wistar Institute during the 1980s, when with my colleagues we characterized one of the first clonal lines of pluripotent human embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas, and identified key features including (...) class='Hi'>cell surface antigen markers that have since found a place in the study and exploitation of human PSC. Much of this research depended upon close teamwork with colleagues, many in other laboratories, who contributed different expertise and experience. It was also often driven by circumstance and chance rather than pursuit of a grand design. (shrink)