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)

The paper by Magill and Neaves in this issue of the Journal attempts to rebut the "natural potency" position, based on recent advances in direct reprogramming of somatic cells to yield "induced pluripotent stem" (iPS) cells. As stated by the authors, the natural potency position holds that because "a human embryo directs its own integral organismic function from its beginning . . . there is a whole, albeit immature, and distinct human organism that is intrinsically valuable with the status (...) of inviolability and deserving full moral respect" (p. 26). The authors boldly assert that "The recent production of iPS . . . highlights a prima facie absurdity for the natural potentiality argument" (p. 29). Yet the argument against natural potency is both logically flawed and based on a characterization of the scientific evidence that is factually inaccurate. (shrink)

The possibility of human reproductive cloning has led some bioethicists to suggest that potentiality-based arguments for fetal moral status become untenable, as such arguments would be committed to making the implausible claim that any adult somatic cell is itself a potential person. In this article I defend potentiality-based arguments for fetal moral status against such a reductio. Starling from the widely-held claim that the maintenance of numerical identity throughout successive changes places constraints on what a given entity can plausibly be (...) said to have the potential to become, I argue that the cell reprogramming that takes place in reproductive cloning is such that it produces a new individual, and so adult somatic cells cannot be potential persons. (shrink)

Basic Questions The following are among the basic questions discussed in this essay: (1) What is the concept of a person? (2) What properties make something a person? (3) Is personhood a matter of degree? (4) Is potential personhood morally significant? (5) Is species membership morally significant? (6) Why is the concept of a person important? Important Arguments The important arguments that are examined include the following: (1) Counterexample arguments: (a) Whole brain death and upper brain death. (b) Brain transplants. (...) (c) Currently irreparable damage versus impossibility of resuscitation. (2) The reprogramming argument. (3) The generalized potentialities argument. (4) Potentialities and comas: active versus passive. (5) Anti-speciesism and the common sense generality of the concept of a person: deities, angels, disembodied souls, extraterrestrials. Important Positions Among the important positions considered are the following: (1) Consciousness is sufficient for personhood. (2) Self-consciousness is necessary for personhood. (3) The capacity for thought is necessary for personhood. (4) Moral agency is necessary for personhood. (shrink)

Để xem bóng đá và phát sóng video trực tiếp tốc độ cao, Xoilac là trang web lý tưởng. Đặc biệt, Xoilac không có bất cứ quảng cáo nào, vì vậy người xem vẫn thoải mái thưởng thức trận bóng đá mà không lo bị phân tâm vì bất cứ vấn đề gì. Ngoài ra, Xoilac có đội ngũ dày dặn chuyên môn, luôn đưa ra những nhận định chuẩn xác cho từng trận đấu bóng đá. Với đồ hoạ sinh (...) động, âm thanh lôi cuốn và sống động, Xoilac sẽ lưu lại dấu ấn sâu đậm trong tâm trí người xem bóng đá. (shrink)

In this paper, I take up the conciliatory-steadfast debate occurring within social epistemology in regards to the phenomenon of peer disagreement. I will argue, because the conciliatory perspective al-lows us to understand argumentation pragmatically—as a method of problem-solving within a community rather than as a method for obtaining the truth—that in most cases, we should not simply agree to disagree.

La question de ce petit livre est simple : peut-on aller au-delà du constat de crise et d'impuissance dont le philosophe se fait le prophète depuis plus d'un siècle? Peut-on parler de la science sans complexe d'infériorité, de Dieu sans obscurantisme, d'existence sans tomber dans la banalité du café du commerce, de politique sans consacrer le cynisme, de morale sans faire dans le sermon? Bref, la philosophie peut-elle aider à faire comprendre et à dépasser les apories du temps présent qu'elle (...) a fait siennes, comme un malade ressasse sa propre maladie pour se donner le sentiment qu'ainsi il peut la mettre à distance à défaut de la vaincre? Toutes ces questions sont aujourd'hui les nôtres, et il ne faut pas avoir peur de parler des grands problèmes qui agitent les hommes depuis l'aube des temps, car si la philosophie a un sens, c'est bien en ce qu'elle envisage les questions ultimes dans une plus ou moins grande systématicité selon les époques. (shrink)

This essay on the social history of logic discusses arguments in the programmatic writings of Carnap/Neurath, but especially in the widely read book by Lillian Lieber, Mits, Wits and Logic (1947), where Mits is the man in the street and Wits the woman in the street. It was seriously argued that the intense study of formal logic would create a more rational frame of mind and have many beneficial effects upon the social and political life. This arose from the conviction (...) that most metaphysical conundrums, religious and political problems and even fanaticism had their root in the irrationality of ordinary discourse, which had to be replaced by the more logical “ideal language” of Principia Mathematica. The enthusiastic promotion of formal logic occurred at a time when it was widely thought that minds could be “made over”, “reprogrammed” by proper intervention. J.B. Watson, (who claimed that he taught the American woman to smoke) wrote that “[S]ome day we shall have hospitals devoted to helping us change our personality, because we can change the personality as easily as we can change the shape or our nose... I wish I could picture for you what a rich and wonderful individual we should make of every healthy child”. Thesecond part of the essay deals, not with the history of logic as a formal science, but with the social role it was thought to play from Francis Bacon on, during the Enlightenment, in Kant and in the 19th century. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor (...) states that emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust. (shrink)

The recent emergence of reprogramming technologies to convert brain cell types or epigenetically alter neurons and neural progenitors in vivo and in situ hold significant promises in brain repair and neuronal aging reversal. However, given the significant epigenetic and transcriptomic changes to components of the existing neuronal cells and network, we question if these reprogramming technology might inadvertently alter or erase memory engrams, conceivably resulting in changes in narrative identity or personality. We suggest that the nature of these (...) alterations might be less predictable compared to memory and personality changes known to be associated with diseases, drugs or brain stimulation therapies. While research in applying reprogramming technologies to neurological ailments and aging should continue, more targeted analyses should be put in place in animal experiments to gauge the severity and degree of memory alterations, and appropriate risk and benefit analyses should be conducted before these technologies move into human trials. (shrink)

Reprogramming technologies show that cellular identity can be reprogrammed, challenging the classical conception of cell differentiation as an irreversible process. If non-stem cells can be reprogrammed into stem cells, then what is it to be a stem cell, and what kind of property is stemness? This article addresses this question both philosophically and biologically, states the different possibilities, and illustrates their potential consequences for science with the example of anti-cancer therapies.

"The total amount of suffering per year in the natural world is beyond all decent contemplation. During the minute that it takes me to compose this sentence, thousands of animals are being eaten alive, others are running for their lives, whimpering with fear, others are being slowly devoured from within by rasping parasites, thousands of all k inds are dying of starvation, thirst and disease. It must be so." -/- —Richard Dawkins, River Out of Eden (1995).

The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult stem cell research will need to be (...) pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

Louise Brown's birth in 1978 heralded a new era not just in reproductive technology, but in the relationship between science, cells, and society. For the first time, human embryos could be created, selected, studied, manipulated, frozen, altered, or destroyed, outside the human body. But with this possibility came a plethora of ethical questions. Is it acceptable to destroy a human embryo for the purpose of research? Or to create an embryo with the specific purpose of destroying it for research? In (...) an attempt to construct ethical and legal frameworks for the new era of cellular reprogramming, legislators and ethicists have tried to distinguish between different kinds of biological entity. We treat cells differently depending on whether they are human or animal, somatic cells or gametes, and on whether they are embryos or not. But this approach to the ethics of cellular reprogramming is doomed to failure for the simple reason that cellular reprogramming in itself destroys the distinctions that the law requires to function. In this article, we explore the historical trajectory of cellular reprogramming and its relationship with ethics and society. We suggest that the early hype of embryo research has not obviously fulfilled expectations, but since new avenues of research are continuously opening, it is hard to say definitely that these promises have been broken. We explore the forthcoming challenges posed by the creation of DNA from scratch in the laboratory, and the implications of this for understandings of identity, privacy, and reproduction. We conclude that while ethics used to seek answers in biological facts, this is no longer possible, and a new approach is required. (shrink)

Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure (...) to reprogramming factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible (...) for the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

Current methods of reprogramming differentiated cells into induced pluripotent stem cells remain slow and inefficient. In a recent report published online in Nature, Bhutani et al.1 developed a cell fusion strategy, achieving quick and efficient reprogramming toward pluripotency. Using this assay, they identified an immune system protein called activation‐induced cytidine deaminase, or AID, which unexpectedly is actually able to “aid” in reprogramming due to its involvement in DNA demethylation that is required for induction of the two key (...) pluripotency genes, Oct4 and Nanog. More recently, Popp et al. 2 also reported online in Nature that AID is important for complete cell reprogramming in mammals. Together, these findings provide new insights into how cells are reprogrammed, identify the specific role of AID in cell fate reversal, and advance the field of regenerative medicine. (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)

What makes something an embryo—as opposed to what is actually, and not just in biotech parlance, a collection of cells? This question has come to the fore in recent years with proposals for producing embryonic stem cells for research. While some of those opposed to use of standard embryonic stem cells emphasise that adult cells have a clinical track record, others argue that there may be further benefits obtainable from cells very like those of embryos, provided such cells can be (...) derived in new ways. Rather than deriving them in ways that kill or otherwise endanger a living human embryo, they could be obtained from an entity that merely resembles a human embryo sufficiently closely for its cells to be of use. Such an entity might be created after introducing genetic changes to an ovum before it is activated by, for example, a cloning-type procedure, such that a gene essential to embryogenesis will be either absent, blocked in its expression, or overexpressed.1,2 The claim is that the ovum could be made to give rise to embryonic stem cells—mere living parts—without ever giving rise to a whole embryo, who is killed to obtain them. Whereas cloning “proper” winds back the specialisation of the cell nucleus to a point where a whole embryo is formed who has not yet specialised its cells, oocyte-assisted reprogramming , it is claimed, would wind back the specialisation merely to an intermediate point at which no embryo is created. Other methods proposed for deriving pseudoembryonic cells include parthenogenesis, in which an ovum is activated without a sperm, or even the insertion of an adult cell nucleus.1MORAL STATUS OF THE EMBRYOIn this paper, I assume that a genuine …. (shrink)

Robert Stern investigates how scepticism can be countered by using transcendental arguments concerning the necessary conditions for the possibility of experience, language, or thought. He shows that the most damaging sceptical questions concern neither the certainty of our beliefs nor the reliability of our belief-forming methods, but rather how we can justify our beliefs.

This book is a unique contribution to the philosophy of religion. It offers a comprehensive discussion of one of the most famous arguments for the existence of God: the ontological argument. The author provides and analyses a critical taxonomy of those versions of the argument that have been advanced in recent philosophical literature, as well as of those historically important versions found in the work of St Anselm, Descartes, Leibniz, Hegel and others. A central thesis of the book (...) is that ontological arguments have no value in the debate between theists and atheists. There is a detailed review of the literature on the topic (separated from the main body of the text) and a very substantial bibliography, making this volume an indispensable resource for philosophers of religion and others interested in religious studies. (shrink)

This book identifies 25 argumentation schemes for presumptive reasoning and matches a set of critical questions to each.