From fertilization to approximately the sixteenth day of development, human embryonic cells are said to have the capacities of totipotency and monozygotic twinning, both of which are problematic to a theory of ensoulment at fertilization. In this article I will address the problems which these capacities pose to such a theory and present an interpretation of the biological data which renders ensoulment at fertilization more plausible. I will then argue that not only is an ensoulment theory consistent with current biological (...) data on the human embryo, but it may offer an explanation for the phenomencon of monozygotic twinning. (shrink)

Chromosomes are not randomly packed and positioned into the nucleus but folded in higher‐order chromatin structures with defined functions. However, the genome of a fertilized embryo undergoes a dramatic epigenetic reprogramming characterized by extensive chromatin relaxation and the lack of a defined three‐dimensional structure. This reprogramming is followed by a slow genome refolding that gradually strengthens the chromatin architecture during preimplantation development. Interestingly, genome refolding during early development coincides with a progressive loss of developmental potential suggesting a link between chromatin (...) organization and cell plasticity. In agreement, loss of chromatin architecture upon depletion of the insulator transcription factor CTCF in embryonic stem cells led to the upregulation of the transcriptional program found in totipotent cells of the embryo, those with the highest developmental potential. This essay will discuss the impact of genome folding in controlling the expression of transcriptional programs involved in early development and their plastic‐associated features. (shrink)

According to the judgement of the European Court of Justice in 2014, human parthenogenetic stem cells are excluded from the patenting prohibition of procedures based on hESC by the European Biopatent Directive, because human parthenotes are not human embryos. This article is based on the thesis that in light of the technological advances in the field of stem cell research, the attribution of the term ‘human embryo’ to certain entities on a descriptive level as well as the attribution of a (...) normative protection status to certain entities based on the criterion of totipotency, are becoming increasingly unclear. The example of human parthenotes in particular demonstrates that totipotency is not at all a necessary condition for the attribution of the term ‘human embryo’. Furthermore, the example of hiPSC and somatic cells particularly shows that totipotency is also not a sufficient condition for the attribution of a normative protection status to certain entities. Therefore, it is not a suitable criterion for distinguishing between human embryos worthy of protection and human non-embryos not worthy of protection. Consequently, this conclusion has repercussions for the patenting question. The strict delineation between an ethically problematic commercial use of human embryos and the concomitant patenting prohibition of hESC-based procedures and an ethically unproblematic commercial use of human non-embryos and the therefore either unrestrictedly permitted or even unregulated patenting of procedures based on these alleged alternatives becomes increasingly blurred. (shrink)

In contrast to embryo donation, the permissibility of 2PN cell donation is highly controversial in Germany. This article is based on there being a legal loophole with respect to 2PN cell donation, which results from an inconsistency within the Embryo Protection Act on the normative status of 2PN cells. Following that thesis, the article argues that, on the basis of the normative criterion totipotency (i.e. the capacity to develop into a born human being), 2PN cells should also be considered human (...) embryos within the meaning of the Act and thereby be protected by that Act in the same way as embryos. However, the normative assumption that 2PN cells should already be endowed with human dignity and the right to life has absurd consequences. Moreover, the consistent continuation of the Embryo Protection Act, as well as of the underlying ethical position or argumentation (i.e. the potentiality argument), leads to the even more absurd consequence of having to place every human somatic cell under the protection of human dignity and the right to life. As totipotency or the developmental potential therefore cannot delimit entities considered worthy of protection (i.e. human embryos) from entities considered not worthy of protection (i.e. 2PN cells, gametes, hESC, hiPSC and human somatic cells), it is not a suitable normative criterion. As a paradigmatic case, 2PN cell donation demonstrates that by retaining this normative criterion the now obsolete German Embryo Protection (Act) ultimately undermines itself. (shrink)

Im deutschen Embryonenschutz- und im Stammzellgesetz sind zwei Rechtsbegriffe von 'Embryo' definiert worden, die sich auf die Zelleigenschaft der Totipotenz stützen und dieser damit eine ontologische und normative Bedeutung beimessen, die angesichts der vielfältigen divergierenden Intuitionen und Argumente zur sogenannten Statusfrage nicht leicht zu rechtfertigen ist. Der vorliegende Beitrag diskutiert die Schwierigkeiten, den ontologischen, moralischen und rechtlichen Status totipotenter Humanzellen plausibel zu begründen, und argumentiert insbesondere, dass zwischen Grundannahmen der Substanzontologie und naturphilosophischen Kontinuitätsüberlegungen unaufhebbare Spannungen bestehen, die der Gesetzgeber durch (...) seine Legaldefinitionen einseitig gelöst hat, ohne über hinreichend belastbare Argumente zu verfügen. (shrink)

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of (...) a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology. (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)

This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies (...) should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. (shrink)

Debate on the potential and uses of human stem cells tends to be conducted by two constituencies—ethicists and scientists. On many occasions there is little communication between the two, with the result that ethical debate is not informed as well as it might be by scientific insights. The aim of this paper is to highlight those scientific insights that may be of relevance for ethical debate.Environmental factors play a significant role in identifying stem cells and their various subtypes. Research related (...) to the role of the microenvironment has led to emphasis upon “plasticity”, which denotes the ability of one type of stem cell to undergo a transition to cells from other lineages. This could increase the value given to adult stem cells, in comparison with embryonic stem cell research. Any such conclusion should be treated with caution, however, since optimism of this order is not borne out by current research.The role of the environment is also important in distinguishing between the terms totipotency and pluripotency. We argue that blastocysts and embryonic stem cells are only totipotent if they can develop within an appropriate environment. In the absence of this, they are merely pluripotent. Hence, blastocysts in the laboratory are potentially totipotent, in contrast to their counterparts within the human body which are actually totipotent. This may have implications for ethical debate, suggesting as it does that arguments based on potential for life may be of limited relevance. (shrink)

I consider the argument, thought to clinch the moral case for use of a human embryo solely as a means, that only a human individual can be a person, because it can happen at any time before formation of the primitive streak that an embryo splits into monozygotic twins, no embryo in which the primitive streak has not formed is a human individual, and therefore no embryo in which the primitive streak has not formed is a person. I explore the (...) following proffered arguments for : indivisibility is a necessary condition of individuality, nonidentity of an embryo with successor twins impugns the embryo’s individuality, and totipotency of an embryo’s constituents is inconsistent with the embryo’s being a human individual. These arguments are tested and found wanting; so too is an alternative to , the argument that indivisibility is intrinsic to personhood. Whereupon is unsustained. In search of ways to rehabilitate the nonindividuation argument, I canvass alternative metaphysical views and inquire further into biological individuality, but find that the argument cannot be saved. I conclude by analyzing where this leaves matters concerning the morality of embryo use. (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)

Stem-cell nomenclature is in a muddle! So-called stem cells may be self-renewing or emergent, oligopotent (uni- and multipotent) or pluri- and totipotent, cells with perpetual embryonic features or cells that have changed irreversibly. Ambiguity probably seeped into stem cells from common usage, flukes in biology's history beginning with Weismann's divide between germ and soma and Haeckel's biogenic law and ending with contemporary issues over the therapeutic efficacy of adult versus embryonic cells. Confusion centers on tissue dynamics, whether stem cells are (...) properly members of emerging or steady-state populations. Clarity might yet be achieved by codifying differences between cells in emergent populations, including embryonic stem and embryonic germ (ES and EG) cells in tissue culture as opposed to self-renewing (SR) cells in steady-state populations. BioEssays 28: 301–308, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Three basic political positions on embryo research will be identified as libertarian, conservative, and social-democratic. The Human Embryo Research Panel will be regarded as an expression of the social-democratic position. A taxonomy of the ethical issues addressed by the Panel will then be developed at the juncture of political and ethical modes of reflection. Among the arguments considered will be those for the separability of the abortion and embryo research debates; arguments against the possibility of the preembryo being a person, (...) especially arguments associated with totipotency and the significance of the primitive streak; and the various reasons for regulating embryo research, including those associated with respect for the preembryo, the protection of traditional views of human procreation, and the prevention of commercialization. (shrink)

I consider the argument, thought to clinch the moral case for use of a human embryo solely as a means, that only a human individual can be a person, because it can happen at any time before formation of the primitive streak that an embryo splits into monozygotic twins, no embryo in which the primitive streak has not formed is a human individual, and therefore no embryo in which the primitive streak has not formed is a person. I explore the (...) following proffered arguments for : indivisibility is a necessary condition of individuality, nonidentity of an embryo with successor twins impugns the embryo’s individuality, and totipotency of an embryo’s constituents is inconsistent with the embryo’s being a human individual. These arguments are tested and found wanting; so too is an alternative to, the argument that indivisibility is intrinsic to personhood. Whereupon is unsustained. In search of ways to rehabilitate the nonindividuation argument, I canvass alternative metaphysical views and inquire further into biological individuality, but find that the argument cannot be saved. I conclude by analyzing where this leaves matters concerning the morality of embryo use. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the research involves (...) the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

The germ lineage has been studied for a long time because of its crucial role in the propagation and survival of a species. While this lineage, in contrast to the soma, is clearly unique in its totipotent ability to produce a new organism, it has now been found also to have specific features at the cellular level. One feature, a period of transcriptional quiescence in the early germ cell precursors, has been observed in both Drosophila and C. elegans, where it (...) is essential for the formation and the survival of the germline. In addition, there are numerous instances where these early germ cells are reliant on translational regulation, especially in Drosophila. The genes that are important for these two functions, the mechanisms of their action, and studies in vertebrate organisms that reveal similarities as well as some potential differences in early germ cell development are discussed. BioEssays 25:326–335, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Hepatocellular carcinoma represents the third leading cause of cancer-related death. Because HCC is multicentric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors taken from zebrafish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In (...) such a trial the patients, with “intermediate” and “advanced” HCC according to Barcelona Clinic Liver Cancer/American Association for the Study of Liver Diseases guidelines, presented benefit in terms of performance status and objective tumoral response, with some cases of complete response, that is, sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of alpha-fetoprotein... (shrink)

Recently David S. Oderberg has tried to refute three arguments that have been advanced in favour of the view that a human being does not begin to exist at fertilization. These arguments turn on the absence of differentiation between the embryoblast and trophoblast, the possibility of monozygotic twinning, and the totipotency of the cells during the first days after fertilization. It is here contended that Oderberg fails to rebut these arguments, though it is conceded that the first two arguments are (...) not conclusive. They do, however, make it at least as reasonable to deny this early origination as to affirm it. It should be noticed that this is all that is needed by those who have used these arguments to dispute that something with a special moral status exists right from fertilization. Nonetheless, it will be seen that the third argument could be developed to the point of giving a conclusive reason to believe that a human being does not begin to exist at fertilization. (shrink)

Genetic studies have revealed that the antagonistic interplay between PcG and TrxG/MLL complexes is essential for the proper maintenance of vertebrate Hox gene expression in time and space. Hox genes must be silenced in totipotent embryonic stem cells and, in contrast, rapidly activated during embryogenesis. Here we discuss some recently published articles1-4 that propose a novel mechanism for the induction of Hox gene transcription. These studies report a new family of histone demethylases that remove H3K27me3/me2 repressive marks at Hox promoters (...) during differentiation of stem cells. Though the overall importance of these enzymes for proper embryogenesis was demonstrated, their precise role in Hox gene epigenetic regulation during development still remains to be firmly established. BioEssays 30:199–202, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Great theoretical value has always been attached toBoveri's discovery as regards chromatin diminution inAscaris, for this discovery appeared to expose the mechanism causing the propagative cells, in which all chromatin remains, to originate an entirely new organism, whereas the soma cells of which the chromosomes have been diminished are only capable of specific differentiation.Boveri was further able to show that, not only do the soma and propagative nuclei differ from each other, but that rather the character of the cell-plasma decides (...) whether the nucleus diminishes or not. Considerations are brought forward to prove that the “diminisher” hypothesis as given byKing andBeams, is untenable. Diminution has always been supposed to result in the loss of the totipotence of the diminished nuclei. In the light of recent chromosome research this course of events does not seem probable. Therefore the following theory is brought forward: When the egg ofAscaris is split, blastomeres originate, which differ from each other as to the plasma. In proportion to the quality of the surrounding plasma, now these now other genes of the totipotent nucleus react in different cells, thus originating the specific differentiation of the cell in question. This cooperation between plasma and nucleus is, however, at first obstructed in the large collective chromosomes ofAscaris, by the presence of their thickened ends. In order to keep up this cooperation a certain quality of plasma is needed, situated in a certain horizontal zone of the egg. As soon as, in the course of the division, nuclei come to rest in different zones, a diminution occurs, and differentiation of the cells in question sets in. Towards the end of the embryonic development the ends of the chromosomes are lost in the propagative cells, and also in these cells differentiation occurs.On a toujours attribué une haute signification théorique à la découverte deBoveri, de la diminution des chromatines chez l'ascaris puisqu'elle semblait expliquer le mécanisme qui cause que les cellules propagatrices où séjourne, la totalité de l'effectif des chromatines, font de nouveau sortir d'elles-mêmes un organisme entier, pendant que les cellules somatiques, dont les chromosomes ont été diminués, ne sont plus capables qu'à produire une différenciation spécifique. De plus,Boveri a pu démontrer, que les noyaux somatiques et propagateurs ne sont pas, à peu de chose près, différents, mais que c'est bien plus la qualité du plasme des cellules qui décide si les noyaux qui leur ont été distribués, diminuent ou non. Des arguments sont apportés, qui démontrent que l'hypothèse du „diminisher” échafaudée parKing etBeams est insoutenable. En général on s'est représenté. l'action de la diminution de telle façon que la totipotentialité des noyaux diminués a été perdue. Cependant, le fait n'est pas acceptable quand on le considère à la lumière de la recherche moderne sur les chromosomes. Par conséquent, nous proposons l'opinion suivante: Dans l'œuf de l'ascaris, des blastomères différant plasmatiquement les uns des autres prennent naissance pendant le fendage. Selon l'état du plasme environnant, dans les cellules individuelles on voit réagir certain gène, dans les autres un autre gène du noyau totipotentiel, causant ainsi la différenciation des cellules visées. Cette collaboration entre le plasme et le noyau est cependant premièrement bloquée dans les grands chromosomes collectifs de l'ascaris par la présence des bouts de chromosomes épaissis. Pour leur conservation une certaine qualité de plasme est requise qui se trouve dans une zone horizontale déterminée de l'œuf. Dès que, dans le procès du fendage, des noyaux arrivent dans d'autres zones du plasme, la diminution a lieu, et la différenciation des cellules visées s'opère. Cependant, après la conclusion du développement embryonal, les bouts des chromosomes se perdent dans les cellules propagatrices et la différenciation a lieu aussi dans ces cellules. (shrink)

Contemporary philosophical discussion on human embryonic stem cell research has focused primarily on the metaphysical and meta-ethical issues suchresearch raises. Though these discussions are interesting, largely ignored are arguments rooted in the secular research ethics tradition already informing humansubject research. This tradition countenances the notion of vulnerability and that vulnerable human subjects (of which human embryos are likely members)ought to be protected from research-related harms. This is the basic idea behind the argument from vulnerability, and it enjoys prima facie plausibility. (...) This articlepresents the vulnerability argument and then focuses critically on several lines of attack including: (1) twinning and totipotency arguments, (2) embryo-rescuearguments, and (3) natural loss arguments. The article concludes that there is no good defeater for the vulnerability argument, and, therefore, we have undefeated reasons for protecting human embryos from research related harms. (shrink)

Moral status is a vexing topic. Linked for so long to the unending debates about ensoulment and the morality of abortion, it has recently resurfaced in the embryonic stem cell controversy. In this new context, it should benefit from new insights originating in recent scientific advances. We believe that the recently observed capability of somatic cells to return to a pluripotential state (a capability we propose to name 'reversed potency') in a controlled manner requires us to modify the traditional concept (...) of moral status and to consider it as referring not only to intrinsic properties (like 'to possess reason' or 'to be a person'), but also to extrinsic or relational ones. (shrink)

The great powers of regeneration shown by freshwater planarians, capable of regenerating a complete organism from any tiny body fragment, have attracted the interest of scientists throughout history. In 1814, Dalyell concluded that planarians could “almost be called immortal under the edge of the knife”. Equally impressive is the developmental plasticity of these platyhelminthes, including continuous growth and fission (asexual reproduction) in well‐fed organisms, and shrinkage (degrowth) during prolonged starvation. The source of their morphological plasticity and regenerative capability is a (...) stable population of totipotent stem cells—“neoblasts”; this is the only cell type in the adult that has mitotic activity and differentiates into all cell types. This cellular feature is unique to planarians in the Bilateria clade. Over the last fifteen years, molecular studies have begun to reveal the role of developmental genes in regeneration, although it would be premature to propose a molecular model for planarian regeneration. Genomic and proteomic data are essential in answering some of the fundamental questions concerning this remarkable morphological plasticity. Such information should also pave the way to understanding the genetic pathways associated with metazoan somatic stem‐cell regulation and pattern formation. BioEssays 28: 546–559, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

abstract This paper re‐examines some well‐known and commonly accepted arguments for the non‐individuality of the embryo, due mainly to the work of John Harris. The first concerns the alleged non‐differentiation of the embryoblast from the trophoblast. The second concerns monozygotic twinning and the relevance of the primitive streak. The third concerns the totipotency of the cells of the early embryo. I argue that on a proper analysis of both the empirical facts of embryological development, and the metaphysical importance or otherwise (...) of those facts, all three arguments are found wanting. None of them establishes that the embryo is not an individual human being from the moment of conception. (shrink)

Contemporary philosophical discussion on human embryonic stem cell research has focused primarily on the metaphysical and meta-ethical issues suchresearch raises. Though these discussions are interesting, largely ignored are arguments rooted in the secular research ethics tradition already informing humansubject research. This tradition countenances the notion of vulnerability and that vulnerable human subjects (of which human embryos are likely members)ought to be protected from research-related harms. This is the basic idea behind the argument from vulnerability, and it enjoys prima facie plausibility. (...) This articlepresents the vulnerability argument and then focuses critically on several lines of attack including: (1) twinning and totipotency arguments, (2) embryo-rescuearguments, and (3) natural loss arguments. The article concludes that there is no good defeater for the vulnerability argument, and, therefore, we have undefeated reasons for protecting human embryos from research related harms. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Direct Nuclear Reprogramming: Response to Condic, Lee, and GeorgeGerard Magill, Ph.D. and William B. NeavesWe read with great interest the response of Maureen Condic, Patrick Lee, and Robert George (2009) to our essay, “Ontological and Ethical Implications of Direct Nuclear Reprogramming” in the March 2009 issue of the Kennedy Institute of Ethics Journal (Magill and Neaves 2009). Much of their response addressed issues that are not in dispute: somatic (...) cells are not zygotes, neurons and hepatocytes are different, growth-factor signals from the trophoblast influence development of the inner cell mass, membranes derived from the trophectoderm are critically required for embryonic survival, and stem cells cannot produce a fetus “on their own.”The crucial point of disagreement deals with the fact that iPS cells are not totipotent but zygotes are. Zygotes can generate their own placental structures while iPS cells must be given them through tetraploid complementation. Condic, Lee, and George consider totipotency to be crucial to natural potentiality. We present an alternative view in our essay (Magill and Neaves 2009, pp. 28–29). Placental structures make no lasting contribution to the postnatal organism, and the equivalency of iPS cells with the inner cell mass of the blastocyst is apparent from tetraploid complementation experiments.The respondents acknowledge the following:... somatic cells can be “converted” into zygotes by the process of somatic cell nuclear transfer (SCNT) or direct reprogramming in combination with tetraploid complementation—just as sperm and egg cells can be “converted” into a zygote by the process of natural fertilization—....(Condic, Lee, and George 2009, p. 35)As the respondents recognize, different ways of manipulating cells can lead to embryogenesis: sperm and egg cells in the process of natural fertilization, the enucleated egg and an ordinary body cell in the process of somatic cell nuclear transfer, and reprogrammed skin cells and a tetraploid blastocyst in the case of induced pluripotent stem (iPS) cells. In each case, different cells are manipulated—or “converted” in the respondents’ terminology—in a process that alters their biological fate within a supportive environment facilitating embryogenesis.The developmental potential that resides in the human genome does not unfold in isolation, not even in a zygote. In all cases, whether involving a zygote or an iPS cell, interaction with a supportive environment is required to express the developmental program residing in the genome. [End Page 201]This biological reality supports what we have described as “early cellular development along the continuum of natural potentiality that can result in the formation of a fetus” (Magill and Neaves 2009, p. 30), and it presents a significant challenge to the natural potentiality argument.Gerard MagillVernon F. Gallagher Chair for the Integration of Science, Theology, Philosophy, and Law, and Professor, Center for Healthcare Ethics Duquesne University Pittsburgh, PA.William B. NeavesPresident and CEO Stowers Institute for Medical Research and Professor of Basic Medical Science University of Missouri at Kansas City School of Medicine Kansas City, MOReferencesCondic, Maureen L.; Lee, Patrick; and George, Robert P. 2008. Ontological and Ethical Implications of Direct Nuclear Reprogramming: Response to Magill and Neaves. Kennedy Institute of Ethics Journal 19: 33–40. Google ScholarMagill, Gerard, and Neaves William B. 2009. Ontological and Ethical Implications of Direct Nuclear Reprogramming. Kennedy Institute of Ethics Journal 19: 23–32. Google ScholarCopyright © 2009 The Johns Hopkins University Press... (shrink)

A fascinating property of germ cells is their ability to maintain totipotency throughout development. At fertilization, this totipotency is unleashed and the egg generates all the cell types needed to make a brand new organism. Occasionally, germ cells differentiate precociously in the embryo or in the gonads and form teratomas, tumors containing many differentiated somatic cell types. Until recently, the genetic basis for teratoma formation was not known. The unexpected discovery of a teratoma in a C. elegans double mutant points (...) to translational control as a key mechanism to maintain totipotency in developing germ cells. BioEssays 28: 865–867, 2006. © 2006 Wiley periodicals, Inc. (shrink)

What kinds of new terminology might be useful in discussions of human germline engineering and the bioethics thereof? There are two different schools of thought about how best to devise new terminology for molecular biology: the ‘common-usage school’, and the ‘classicist school’. The relative advantages and disadvantages of each are examined. Finally, several new terms are proposed and discussed. Keywords: allaxis, genetic engineering, germline, menedyne, moridic, palindyne, pre-embryonic, tecodic, totipotent, xynallaxis CiteULike Connotea Del.icio.us What's this?

Contrary to the rarity of totipotent cells in animals, almost every cell formed by a fungus can function as a “stem cell”. The multicellular fruiting bodies of basidiomycete fungi consist of the same kind of filamentous hyphae that form the feeding phase, or mycelium, of the organism, and visible cellular differentiation is almost nonexistent. Mushroom primordia develop from masses of converging hyphae, and the stipe (or stem), cap, and gills are clearly demarcated within the embryonic fruiting body long before the (...) organ expands and unfolds through water uptake and cell wall loosening.aThough frequent references are made to gilled mushrooms in this article, the totipotent nature of fruiting body cells and lack of meristems is also applicable to basidiomycetes that spread their spore‐producing tissues inside tubes (e.g., boletes), over spines and rippled surfaces, or form spores in cavities within the fruiting body. Even in the mature mushroom, every hypha retains its totipotency. Among animals, only sponges exhibit a similar degree of developmental flexibility, which is interesting, because these simple metazoans may be relatively close relatives of fungi. BioEssays 24:949–952, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus—long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we consider giving this (...) type of therapy to patients who would not naturally receive it. Much has been written about the ethics of stem cell research and therapy; this paper will focus on how recent advances in biotechnology and biological understandings of development narrow the debate. Here, the author briefly reviews current stem cell research practices, revisits the natural stem cell therapy case for moral evaluation, and ultimately demonstrates the importance of permissible stem cell research and therapy, even absent an agreement about the definition of when embryonic life begins.Although one promising technology, blighted ovum utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that utilisation of unfertilised eggs to derive totipotent stem cells obviates the moral debate over when life begins. There are two existing technologies that fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement. (shrink)

Mouse embryonic stem cells have an unlimited lifespan in cultures if they are prevented from differentiating. After differentiating, they produce cells which divide only a limited number of times. These changes seen in cultures parallel events that occur in the developing embryo, where immortal embryonic cells differentiate and produce mortal somatic ones. The data strongly suggest that differentiation initiates senescence, but this view entails additional assumptions in order to explain how the highly differentiated sexual gametes manage to remain potentially immortal. (...) Cells differentiate by blocking expression from large parts of their genome and it is suggested that losses or gains of genetic totipotency determine cellular lifespans. Cells destined to be somatic do not regain totipotency and senesce, while germ‐line cells regain complete genome expression and immortality after meiosis and gamete fusions. Losses of genetic totipotency could induce senescence by lowering the levels of repair and maintenance enzymes. (shrink)

The debate surrounding human embryonic stem cell research plays a crucial role in the culture wars. Those who embrace post-traditional morality not only see no ethical problem with the destruction of human embryos for research and therapies, but press for their use despite the greater potential for risk from the totipotent cells that are harvested from the destruction of human embryos as opposed to other kinds of stem cells. Indeed, there have been foreseeable negative consequences from such attempts at treatment. (...) Nonetheless, from the standpoint of traditional Christianity, the destruction of human embryos is expressly forbidden regardless of any potential positive outcomes. There is a fundamental cleft within the culture on such issues. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, (...) some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, (...) some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

This paper re-examines some well-known and commonly accepted arguments for the non-individuality of the embryo, due mainly to the work of John Harris. The first concerns the alleged non-differentiation of the embryoblast from the trophoblast. The second concerns monozygotic twinning and the relevance of the primitive streak. The third concerns the totipotency of the cells of the early embryo. I argue that on a proper analysis of both the empirical facts of embryological development, and the metaphysical importance or otherwise of (...) those facts, all three arguments are found wanting. None of them establishes that the embryo is not an individual human being from the moment of conception. (shrink)

I rejoinder to Ingmar Persson’s reply to my paper ‘The Metaphysical Status of the Embryo: Some Arguments Revisited’. I argue that Persson, having conceded a large part of my case, has still misunderstood or not fully appreciated the force of that case when he claims the arguments I criticize still make it reasonable to think that a human being does not come into existence at fertilization. In addition, his appeal to the totipotency argument as remaining unscathed by my critique does (...) not succeed. (shrink)

Definition of the problem: Recently, ”Dolly” has been confirmed by cloning several other mammals. In January 1999 it was even reported that Korean researchers first of all had cloned the first human embryo. In the following article some basic biological and technical aspects of modern cloning strategies, such as embryo splitting and nuclear transplantation, will be described. Subsequently, a short critical analysis will discuss the ethical problem of cloning human beings. Since the German Embryo Protection Act from January 1991 substantial (...) progress in cloning technology has been made, so that the principal question now is whether the Act is still sufficient to forbid human cloning or whether it should be revised. Arguments and conclusion: With advanced technical progress human cloning now seems to be possible. From the ethical point of view, the cloning of human beings should be rejected, as it offends the fundamental value of human dignity. On the other hand, the German Embryo Protection Act is antiquated and does not provide the required protection. This article may stimulate further discussion in the fields of ethics and jurisdiction, especially regarding to the Embryo Protection Act. (shrink)

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration (1901). In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of (...) regeneration studies by looking in depth at Regeneration and evaluating Morgan's contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan's earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research. (shrink)