Longitudinal tracking of human plasma oxytocin suggests complex responses to moral elevation.

Positive social experiences may induce oxytocin release. However, previous studies of moral elevation have generally utilized cross-sectional and simple modeling approaches to establish the relationship between oxytocin and emotional stimuli. Utilizing a cohort of 30 non-lactating women (aged 23.6 ± 5.7 years), we tested whether exposure to a video identified as capable of eliciting moral elevation could change plasma oxytocin levels. Uniquely, we utilized a high-frequency longitudinal sampling approach and multilevel growth curve modeling with landmark registration to test physiological responses. The moral elevation stimulus, versus a control video, elicited significantly greater reports of being "touched/inspired" and "happy/joyful". However, the measured plasma oxytocin response was found to be markedly heterogeneous. While the moral elevation stimulus elicited increased plasma oxytocin as expected, this increase was only modestly larger than that seen following the control video. This increase was also only present in some individuals. We found no relationship between plasma oxytocin and self-report responses to the stimulus. From these data, we argue that future studies of the relationship between oxytocin and emotion need to anticipate heterogeneous responses and thus incorporate comprehensive individual psychological data; these should include evidence-based variables known to be associated with oxytocin such as a history of trauma, and the individual's psychological and emotional state at the time of testing. Given the complexity of physiological oxytocin release, such studies also need to incorporate frequent biological sampling to properly examine the dynamics of hormonal release and response.

Building Capacity for a Global Genome Editing Observatory: Conceptual Challenges.

A new infrastructure is urgently needed at the global level to facilitate exchange on key issues concerning genome editing. We advocate the establishment of a global observatory to serve as a center for international, interdisciplinary, and cosmopolitan reflection. This article is the first of a two-part series.

Building Capacity for a Global Genome Editing Observatory: Institutional Design.

A new infrastructure is urgently needed at the global level to facilitate exchange on key issues concerning genome editing. We advocate the establishment of a global observatory to serve as a center for international, interdisciplinary, and cosmopolitan reflection. This article is the second of a two-part series.

CDX2 in the formation of the trophectoderm lineage in primate embryos.

The first lineage decision during mammalian development is the establishment of the trophectoderm (TE) and the inner cell mass (ICM). The caudal-type homeodomain protein Cdx2 is implicated in the formation and maintenance of the TE in the mouse. However, the role of CDX2 during early embryonic development in primates is unknown. Here, we demonstrated that CDX2 mRNA levels were detectable in rhesus monkey oocytes, significantly upregulated in pronuclear stage zygotes, diminished in early cleaving embryos but restored again in compact morula and blastocyst stages. CDX2 protein was localized to the nucleus of TE cells but absent altogether in the ICM. Knockdown of CDX2 in monkey oocytes resulted in formation of early blastocyst-like embryos that failed to expand and ceased development. However, the ICM lineage of CDX2-deficient embryos supported the isolation of functional embryonic stem cells. These results provide evidence that CDX2 plays an essential role in functional TE formation during primate embryonic development.

Ethics and embryonic stem cell research: altered nuclear transfer as a way forward.

Ethical controversy in stem cell research arises because current methods to produce embryonic stem cell lines require the destruction of living human embryos. For this reason, there is increasing interest in developing alternative, non-embryonic sources of pluripotent stem cells. This effort is especially important in the US due to the prevailing policy against federal funding of embryo-destructive research. Altered nuclear transfer (ANT) is one of several potential methods to develop alternative sources of pluripotent stem cells. This approach employs the technique of somatic cell nuclear transfer, but the somatic cell nucleus or egg cytoplasm (or both) are first altered before the somatic cell nucleus is transferred into the oocyte. This alteration precludes the coordinated organization and developmental potential that is necessary for the resulting biological entity to be an embryo, but it still allows the entity to generate pluripotent stem cells. Proof-of-principle for one variant of ANT has been established in mice by silencing the functional expression of the gene Cdx2 in the somatic cell nucleus prior to its transfer into an enucleated egg. From the resulting non-embryonic laboratory construct, fully functional pluripotent stem cells were procured. Other more recent studies have suggested the possibility of achieving the same results by preemptively silencing maternally derived Cdx2 messenger RNA in the egg before the act of nuclear transfer. The procedure would produce the equivalent of a tissue culture of pluripotent stem cells. In contrast to the use of embryos 'left over' from clinical in vitro fertilization, ANT could produce pluripotent stem cell lines with an unlimited range of specifically selected and controlled genotypes. Such flexibility would greatly facilitate the study of disease, drug development, and toxicology testing, and may allow the production of therapeutically useful pluripotent stem cells that are immune-compatible. If developed to the point of scientific reliability, ANT would be a valuable research tool for the study of other aspects of cell development and differentiation, including gene expression patterns, imprinting, and cell-cell signaling. ANT would also help to clarify definitions and boundaries that distinguish true organisms from 'biological artifacts' and, thereby, provide moral precedent to guide future progress in developmental biology.

Framing the future: embryonic stem cells, ethics and the emerging era of developmental biology.

Throughout the 20(th) century, advances in biology were accomplished largely through the study of biochemical parts apart from their place within the whole organism. This reductive and analytic approach, which has culminated in the sequencing of the human genome, has now led us back to the study of living beings. When applied to human biology, this inquiry re-opens the most fundamental questions concerning the moral meaning of developing life. The current conflict over ES (embryonic stem) cell research is just the first in a series of difficult controversies that will require us to clearly and precisely define the boundaries of humanity that we seek to defend. Through a careful consideration of the social, political, and scientific foundations of our current debate, we may discern the terms of a possible resolution that can sustain social consensus while opening avenues for scientific advance. Four such proposals were discussed in a May 2005 publication by the President's Council on Bioethics, entitled "Alternative Sources of Pluripotent Stem Cells." One of these methods, altered nuclear transfer, proposes to use the technology of somatic cell nuclear transfer (SCNT), but with a pre-emptive genetic or epigenetic alteration that precludes the integrated and coordinated organization essential for natural embryogenesis. The moral and scientific dimensions of this proposal are discussed as a way forward for embryonic stem cell research as well as a frame for further studies in developmental biology.

Patenting humans: clones, chimeras, and biological artifacts.

The momentum of advances in biology is evident in the history of patents on life forms. As we proceed forward with greater understanding and technological control of developmental biology there will be many new and challenging dilemmas related to patenting of human parts and partial trajectories of human development. These dilemmas are already evident in the current conflict over the moral status of the early human embryo. In this essay, recent evidence from embryological studies is considered and the unbroken continuity of organismal development initiated at fertilization is asserted as clear and reasonable grounds for moral standing. Within this frame of analysis, it is proposed that through a technique of Altered Nuclear Transfer, non-organismal entities might be created from which embryonic stem cells could be morally procured. Criteria for patenting of such non-organismal entities are considered.

Altered nuclear transfer: a way forward for embryonic stem cell research.

The present conflict over the moral status of the human embryo reflects deep differences in our basic convictions and is unlikely to be resolved through deliberation or debate. While there are currently no federally legislated constraints on the use of private funds for this research, there is a consensus opinion in the scientific community that without NIH support for newly created embryonic stem cell lines, progress in this important realm of research will be severely constrained. A May, 2005, report by the President's Council on Bioethics, "Alternative Sources of Pluripotent Stem Cells," outlines several proposals for obtaining pluripotent stem cells without the destruction of human embryos. One of these methods, Altered Nuclear Transfer, proposes to use the technology of somatic cell nuclear transfer (SCNT), but with a preemptive genetic or epigenetic alteration that precludes the integrated and coordinated organization essential for natural embryogenesis. Drawing on insights from systems biology, the distinction between totipotency (capacity to form a whole organism) and pluripotency (capacity to form all the cell types) is explored. The implications of this distinction are used to discuss the moral arguments for the inviolability of nascent human life and the moral standing of entities with only partial and unorganized developmental potential. Away forward is proposed that may open positive avenues of advance in both stem cell research and a broader arena of research in developmental biology.