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)

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)

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)

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)

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)

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)

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)

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)

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)

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.

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)

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)

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 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 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)

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)

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)

ABSTRACT 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)

© Copyright 2015, Mary Ann Liebert, Inc..Signal transducer and activator of transcription factor 3 is hyperactivated in head and neck squamous cell carcinomas. Cumulative evidence indicates that IL-6 production by HNSCC cells and/or stromal cells in the tumor microenvironment activates STAT3 and contributes to tumor progression and drug resistance. A library of 94,491 compounds from the Molecular Library Screening Center Network was screened for the ability to inhibit interleukin-6 -induced pSTAT3 activation. For contractual reasons, the primary high-content screening campaign (...) was conducted over several months in 3 distinct phases; 1,068 primary HCS actives remained after cytotoxic or fluorescent outliers were eliminated. One thousand one hundred eighty-seven compounds were cherry-picked for confirmation; actives identified in the primary HCS and compounds selected by a structural similarity search of the remaining MLSCN library using hits identified in phases I and II of the screen. Actives were confirmed in pSTAT3 IC50 assays, and an IFNγ-induced pSTAT1 activation assay was used to prioritize selective inhibitors of STAT3 activation that would not inhibit STAT1 tumor suppressor functions. Two hundred three concentration-dependent inhibitors of IL-6-induced pSTAT3 activation were identified and 89 of these also produced IC50s against IFN-γ-induced pSTAT1 activation. Forty-nine compounds met our hit criteria: they reproducibly inhibited IL-6-induced pSTAT3 activation by ≥70% at 20 μM; their pSTAT3 activation IC50s were ≤25 μM; they were ≥2-fold selective for pSTAT3 inhibition over pSTAT1 inhibition; a cross target query of PubChem indicated that they were not biologically promiscuous; and they were ≥90% pure. Twenty-six chemically tractable hits that passed filters for nuisance compounds and had acceptable drug-like and ADME-Tox properties by computational evaluation were purchased for characterization. The hit structures were distributed among 5 clusters and 8 singletons. Twenty-four compounds inhibited IL-6-induced pSTAT3 activation with IC50s ≤20 μM and 13 were ≥3-fold selective versus inhibition of pSTAT1 activation. Eighteen hits inhibited the growth of HNSCC cell lines with average IC50s ≤ 20 μM. Four chemical series were progressed into lead optimization: the guanidinoquinazolines, the triazolothiadiazines, the amino alcohols, and an oxazole-piperazine singleton. (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)

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)

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)

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)

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 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)

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)

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)

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)

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)

Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has a prima facie moral (...) obligation to do so. (shrink)

The differentiation of mammalian neurons during development is a highly complex process involving regulation and coordination of gene expression at multiple steps. The P19 mouse embryonal carcinoma cell line is a suitable model system with which to analyze regulation of neuronal differentiation. These multipotential cells can be maintained and propagated in tissue culture in an undifferentiated state. Exposure of aggregated P19 cells to retinoic acid results in the differentiation of cells with many fundamental phenotypes of mammalian neurons. Undifferentiated P19 (...) cells are amenable to genetic manipulations such as transfection and establishment of stable clonal cell lines expressing introduced genes. Proteins that play a key role in the neuronal differentiation of P19 cells are beginning to be identified. These include retinoic acid receptors, the epidermal growth factor receptor and the transcription factors Oct‐3 and Brn‐2. The biological and technical advantages of this system should facilitate deeper analysis of the activities of proteins that play a role in neuronal differentiation. (shrink)

The recent discussions about alternative sources of human embryonic stem cells , while stirring new interest in the developmental potential of the various abnormal embryos or constructs proposed as such sources, also raise questions about the potential of the derived embryonic stem cells. The data on the developmental potential of embryonic stem cells that seem relevant for ethical considerations and aspects of patentability are discussed. Particular attention is paid to the meaning of “totipotency, omnipotency and pluripotency” as illustrated by a (...) comparison of the developmental potential of three-dimensional clusters of blastomeres , embryonic stem cells, somatic or stem cells or other somatic cells. This paper focuses on embryoid bodies and on direct cloning by tetraploid complementation. Usage and patenting of these cells cannot be considered to be ethically sound as long as totipotency and tetraploid complementability of embryonic stem cells are not excluded for the specific cell line in question. Testing this poses an ethical problem in itself and needs to be discussed in the future. (shrink)

The recent discussions about alternative sources of human embryonic stem cells , while stirring new interest in the developmental potential of the various abnormal embryos or constructs proposed as such sources, also raise questions about the potential of the derived embryonic stem cells. The data on the developmental potential of embryonic stem cells that seem relevant for ethical considerations and aspects of patentability are discussed. Particular attention is paid to the meaning of “totipotency, omnipotency and pluripotency” as illustrated by a (...) comparison of the developmental potential of three-dimensional clusters of blastomeres , embryonic stem cells, somatic or stem cells or other somatic cells. This paper focuses on embryoid bodies and on direct cloning by tetraploid complementation. Usage and patenting of these cells cannot be considered to be ethically sound as long as totipotency and tetraploid complementability of embryonic stem cells are not excluded for the specific cell line in question. Testing this poses an ethical problem in itself and needs to be discussed in the future. (shrink)

Essays on stem cell policy seem to fall into three categories. Some essays in this collection are about logic and principles. Others are about practices and beliefs. The former group draws lines and defends them, a normative project. The latter group attempts to explain the lines that already exist, a descriptive project that may have important normative goals. Still other essays, by scientists, are about growing stem cell lines instead of drawing them.The purpose of this (...) essay is to situate the lines being drawn around stem cell science in the larger landscape of health policy. I am interested in the things that cause health policy to take particular directions and the consequences of those directions for cost, access, and quality — all of which are determined in part by biomedical innovations such as those potentially derived from stem cells. (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)

This paper queries why we are more reluctant to perform stem cell research on human than on nonhuman embryos, given their remarkable similarities together with the former's greater promise for addressing human illnesses. I begin by examining two leading arguments for prohibiting stem cell research on human embryos. The first type of argument suggests that we should not interfere with the potential for human life. This argument, advanced in different ways by both utilitarians and religious believers, inadequately grapples (...) with the moral complexities raised by current technologies, such as IVF and cloning. Moreover, it fails to address the significant adverse effects of human overpopulation to both human and nonhuman well-being. The second line of argument addressed here suggests that we are morally prohibited from "playing God." This argument overlooks the various ways in which we do—indeed, we must—make life and death decisions. Further, the argument rests on an undefended assumption that we are only prohibited from making such decisions with regard to human life, while remaining free to make such decisions with regard to animals without apparent moral qualms. On the contrary, I argue that, from a fully ethical Darwinian standpoint, we must treat both human and nonhuman life with respect. Far from requiring us to abstain from difficult moral decision making, an attitude of respect toward all life requires human willingness to take responsibility for making difficult—indeed, sometimes excruciating—moral decisions. (shrink)

The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20‐dependent degradation, I hypothesize that variations in Cdc20 protein levels, rather than mutations in checkpoint genes, could affect cell fate during prolonged mitotic arrest. This hypothesis is supported by experiments where manipulation of Cdc20 levels affects the response to antimitotic compounds. The (...) observed differences in Cdc20 levels between cell lines likely reflects differences in the rate of synthesis or degradation of the protein; therefore, understanding these pathways at a molecular level could pave the way for modulating the activity of Cdc20, in turn presenting novel therapeutic possibilities. (shrink)

The potential benefits of embryonic stem cell research have been clarified by the last ten years of research so that it is necessary to re-examine the foundations for the restrictions imposed on this research. Those who believe that life begins at the moment of fertilization and is imbued with a full complement of human rights have opposed all embryonic research. As one who accepts this premise, I will demonstrate that there are certain limited circumstances in which parents may donate (...) embryos to establish stem cell lines that fully respect the rights of the embryonic person. In these circumstances, their action is morally equivalent to organ donation from a dying child to save the lives of others. (shrink)