NO ETHICAL BYPASS OF MORAL STATUS IN STEM CELL RESEARCH

Recent advances in reprogramming technology do not bypass the ethical challenge of embryo sacrifice. Induced pluripotent stem cell (iPS) research has been and almost certainly will continue to be conducted within the context of embryo sacrifice. If human embryos have moral status as human beings, then participation in iPS research renders one morally complicit in their destruction; if human embryos have moral status as mere precursors of human beings, then advocacy of iPS research policy that is inhibited by embryo sacrifice concerns renders one morally complicit in avoidable harms to persons. Steps may be taken to address these complicity concerns, but in the final analysis there is no alternative to achieving clarity with respect to the moral status of the human embryo.     

Why Eberl is wrong. Reflections on the beginning of personhood

In a paper published in Bioethics, Jason Eberl has argued that early embryos are not persons and should not be granted the status possessed by them. Eberl bases this position upon the following claims: (1) The early embryo has a passive potentiality for development into a person. (2) The early embryo has not established both 'unique genetic identity' and 'ongoing ontological identity', which are necessary conditions for ensoulment. (3) The early embryo has a low probability of developing into a more developed embryo. This paper examines these claims. I argue against (1) that a plausible view is that the early embryo has an active potentiality to grow into a more developed embryo. Against (2), I argue that neither 'unique genetic identity' nor 'ongoing ontological identity' are necessary conditions for ensoulment, and that 'ongoing ontological identity' is established between early embryos and more developed embryos. Against (3), I argue that the fact that the early embryo has a low probability of developing into a more developed embryo, if true, does not warrant the conclusion that the early embryo is not a person. If Eberl is right that the human soul is that which organises the activities of a human being and that ensouled humans are persons, embryos are persons from conception.     

Embryo structure,seed traits,and productivity of relict vine Aristolochia contorta (Aristolochiaceae)

The herbaceous vine Aristolochia contorta (Aristolochiaceae) is a rare plant with a fragmented area in East Asia. Confocal laser-scanning microscopy and stereomicroscopy were employed to examine the seed and embryo structure. This is the first research on embryo anatomy in Aristolochia. Shape and structure of this embryo may be phylogenetically significant. The seed structure of A. contorta is similar to that of other Aristolochia species. Considerable variation is found for productivity traits; the average seed set is rather low (26.7%). The studied seed and embryo traits of A. contorta are found to be variable, but may be potentially informative at the genus and species level. The restricted productivity and reduced population size threaten the continued survival of A. contorta and, perhaps, the butterfly that depends on it.     

Micromanipulation of mammalian embryos: Principles, progress and future possibilities

Numerous advances in development of techniques for manipulating mammalian embryos outside the maternal environment have been made over the past decade. Some techniques were developed primarily for use in research; others were developed in response to problems of practical livestock production but have proven useful in research as well. Embryo micromanipulation procedures are used often in conjunction with embryo transfer, and interest in these procedures was stimulated by growth of the embryo transfer industry. Included in this review are discussions of procedures for manipulation of gametes and embryos, including sperm injection into oocytes, pronuclear and nuclear transfer, embryo biopsy and splitting, experimental chimera production and isolation of embryonic stem cells.     

Negotiating meanings about embryos in Australia: from potential humans to prohibited substances

In the late 1990s, human embryonic stem-cell research became a highly emotional and politicized debate. In 2001, the United States announced a ban on all federal funding for research involving human embryos, and other countries around the world were similarly engaged in political debate at the same time, and for very similar reasons--namely, that embryos are regarded as unique entities that warrant special protection. This article tracks the transformations in the history of legislative response in Australia to the anxieties provoked by the use of reproductive and regenerative human material over the last 40 years, in order to examine how embryos have come to adopt such a special position in the community's psyche. "The embryo" is at once a biological, scientific, social, cultural, and political object, fixed by the legislative processes that seek to define it, and subject to definitions that change over time. Understanding the history of where our ideas about the embryo have come from can help us to negotiate the continuing debate about the use of human embryos in research.     

Potential researchable areas in ARTs--oocyte maturation and embryo development

Infertility is a commonly encountered situation occurring equally in both sexes. In vitro fertilization and embryo transfer (IVF-ET) and other assisted reproductive technologies (ARTs) have enhanced the possibilities for successful treatment to tackle infertility. However, ARTs currently face limitations due to the fact that although success rate is high for the initial stages such as ovulation induction and fertilization, it dwindles progressively so that the success rate of a take home baby is as low as 15-20%. Research centred around various stages in an IVF programme is therefore necessary to devise protocols that ensure a higher success rate. This review takes a look at the potential areas currently under research in the field of ARTs, such as, in vitro oocyte maturation, oocyte/embryo cryopreservation, embryo culture, preimplantation genetic diagnosis. Their applications, in clinical conditions such as cancer, have been discussed.     

Improving post-transfer survival of bovine embryos produced in vitro: actions of insulin-like growth factor-1, colony stimulating factor-2 and hyaluronan

Technologies for in vitro embryo production have the potential to enhance the efficiency of cattle production systems. However, utilization of in vitro-produced embryos for transfer remains limited throughout much of the world. Despite improvements over the past two decades, problems associated with the production of bovine embryos in vitro still exist which limit the widespread commercial application of this technology. In particular, bovine embryos produced in vitro have a reduced capacity to establish and maintain pregnancy as compared with their in vivo-derived counterparts. Embryo competence for survival following transfer is improved by in vivo culture in the sheep oviduct, thus indicating that standard embryo culture conditions are sub-optimal. Therefore, one strategy to improve post-transfer survival is to modify embryo culture media to more closely mimic the in vivo microenvironment. The maternal environment in which the bovine embryo develops in vivo contains various growth factors, cytokines, hormones, and other regulatory molecules. In addition to affecting bovine embryo development in vitro, recent research indicates that embryo competence for survival following transfer can also be improved when such molecules are added to embryo culture medium. Among the specific molecules that can increase post-transfer embryo survival are insulin-like growth factor-1 (IGF-1), colony stimulating factor-2 (CSF-2) and hyaluronan. This paper will review the effects IGF-1, CSF-2 and hyaluronan on post-culture embryo viability and discuss the potential mechanisms through which each of these molecules improves post-transfer survival.     

End-stage heart disease, high-risk research, and competence to consent: the case of the AbioCor artificial heart

Some commentators believe that persons facing imminent death are incapable of making autonomous, informed decisions about whether to enter high-risk, end-of-life research trials. Using the AbioCor artificial heart trial as an example, this essay argues to the contrary. Although some people are incapacitated, many are capable of making such decisions. To forbid dying people to make a decision about whether to enter a clinical trial may insult deeply held personal values at a time when honoring those values may be most important. Moreover, to deny dying persons entry into high-risk clinical trials leaves ethically worse alternatives: using healthier people, requiring surrogates to decide even when the patient is competent, or simply forgoing all research featuring high-risk, potentially life-saving interventions. Once we agree that it is at least sometimes acceptable to permit dying persons to choose high-risk research, a number of practical safeguards can be implemented to ameliorate the challenges that can hinder decision making in this difficult area.     

Improving post-transfer survival of bovine embryos produced in vitro: Actions of insulin-like growth factor-1, colony stimulating factor-2 and hyaluronan

Technologies for in vitro embryo production have the potential to enhance the efficiency of cattle production systems. However, utilization of in vitro-produced embryos for transfer remains limited throughout much of the world. Despite improvements over the past two decades, problems associated with the production of bovine embryos in vitro still exist which limit the widespread commercial application of this technology. In particular, bovine embryos produced in vitro have a reduced capacity to establish and maintain pregnancy as compared with their in vivo-derived counterparts. Embryo competence for survival following transfer is improved by in vivo culture in the sheep oviduct, thus indicating that standard embryo culture conditions are sub-optimal. Therefore, one strategy to improve post-transfer survival is to modify embryo culture media to more closely mimic the in vivo microenvironment. The maternal environment in which the bovine embryo develops in vivo contains various growth factors, cytokines, hormones, and other regulatory molecules. In addition to affecting bovine embryo development in vitro, recent research indicates that embryo competence for survival following transfer can also be improved when such molecules are added to embryo culture medium. Among the specific molecules that can increase post-transfer embryo survival are insulin-like growth factor-1 (IGF-1), colony stimulating factor-2 (CSF-2) and hyaluronan. This paper will review the effects IGF-1, CSF-2 and hyaluronan on post-culture embryo viability and discuss the potential mechanisms through which each of these molecules improves post-transfer survival.     

The savant syndrome: an extraordinary condition. A synopsis: past,present, future

Savant syndrome is a rare, but extraordinary, condition in which persons with serious mental disabilities, including autistic disorder, have some ‘island of genius’ which stands in marked, incongruous contrast to overall handicap. As many as one in 10 persons with autistic disorder have such remarkable abilities in varying degrees, although savant syndrome occurs in other developmental disabilities or in other types of central nervous system injury or disease as well. Whatever the particular savant skill, it is always linked to massive memory. This paper presents a brief review of the phenomenology of savant skills, the history of the concept and implications for education and future research.     

Traversing the ovine cervix - a challenge for cryopreserved semen and creative science

This review brings together research findings on cervical relaxation in the ewe and its pharmacological stimulation for enhancement of the penetration needed for transcervical insemination and embryo transfer. On the basis that the success of artificial insemination is the percentage of ewes lambing, a review is made of recent research aimed at understanding and minimising the sub-lethal effects of freezing and thawing on the viability of spermatozoa, their membrane integrity and their ability to migrate through cervical mucus, as these characteristics have a major influence on fertility, particularly when semen is deposited, artificially, in the os cervix. Milestones of achievement are given for transcervical intrauterine insemination, embryo recovery and transfer and the birth of lambs of pre-determined sex, firstly following intracytoplasmic sperm injection, then laparoscopic intrauterine insemination using highly diluted flow-cytometrically sorted fresh semen and subsequently by os cervix insemination using sexed semen that had been frozen and thawed. Diversity of research endeavour (applied, cellular, molecular), research discipline (anatomy, histology, immunology, endocrinology) and research focus (cell, tissue, organ, whole animal) is embraced within the review as each has significant contributions to make in advancing recent scientific findings from the laboratory into robust on-farm transcervical insemination and embryo transfer techniques.     

Why the embryo rescue case is a bad argument against embryonic personhood

The embryo rescue case (ERC) is a thought experiment that is used to argue against the view that embryos have a right to life (i.e., are persons). I will argue that cognitive science undermines the intuition elicited by the ERC. I will show that whether or not embryos have a right to life, our mental tools will make it very difficult to believe that they do have the said right. This suggests that the intuition elicited by the ERC is not truth‐indicative. The upshot of this is that we have an undercutting defeater for our intuition that embryos do not have a right to life. Thus, the ERC is a bad argument against embryonic personhood.     

Quantification of embryo quality by respirometry

It is generally accepted that assessment of embryo metabolism, in particular oxygen consumption, may improve embryo selection by identifying the embryos with higher developmental competence. Several methods have been employed to measure embryonic oxygen consumption, but most of them were detrimental to subsequent embryo development. Recently, we have introduced the Nanorespirometer system, which is a non-invasive and highly sensitive technology developed for the individual measurement of embryonic respiration rates. This technology is able to perform single measurements at a fixed time or stage of embryonic development without adversely influencing embryo viability. Concomitantly, and based on the same principles, a second technology -- the Embryo Respirometer -- has been developed. The Embryo Respirometer allows the continuous measurement of individual respiration rates with simultaneous acquisition of digital images of each embryo, during the entire culture period (6-7 days). In this review, both technologies are described and their potential use as diagnostic tools for improving embryo selection in bovine and human following IVF treatments is discussed. Correlations between respiration rates of individual embryos and other parameters such as morphological quality, sex, stage of development, kinetics, diameter, expression of key metabolic genes and subsequent viability following embryo transfer are also examined. On the basis of the results obtained, it is postulated that assessment of embryonic respiration rates in association with other viability parameters allows for a more accurate embryo evaluation, both under clinical and research conditions.     

Learning from the voiceless

This article is concerned with understanding what is at stake in the everyday lives of family members facing Huntington's Disease (HD). The methodological and analytical point of departure is German critical psychology, particularly the category of conduct of everyday life (Holzkamp, 1995; Dreier, 1999). Specifically, I address questions of accessing and understanding the conduct of everyday life of persons facing HD who are not visibly active with respect to this circumstance. The question of access is not merely about getting in touch with persons who are not known to the research, professional and HD communities, but also about the consequences of establishing contact with persons who have not made an entry into any of these public areanas themselves. The question of understanding is about developing an analysis from a first-person perspective on the personal conduct of everyday life that is not visibly active. The development of such an understanding has broader implications, not just for further research and health care practices, but importantly also for the prevailing moral and ethical demands made on persons living at risk of hereditary diseases.     

Navigating the site for embryo implantation: Biomechanical and molecular regulation of intrauterine embryo distribution

The distribution of intrauterine embryo implantation site(s) in most mammalian species shows remarkably constant patterns: in monotocous species such as humans, an embryo tends to implant in the uterine fundus; in polytocous species such as rodents, embryos implant evenly along the uterine horns. These long-time evolved patterns bear great biological significance because disruption of these patterns can have adverse effects on pregnancies. However, lack of suitable models and in vivo monitoring techniques has impeded the progress in understanding the mechanisms of intrauterine embryo distribution. These obstacles are being overcome by genetically engineered mouse models and newly developed high-resolution ultrasound. It has been revealed that intrauterine embryo distribution involves multiple events including uterine sensing of an embryo, fine-tuned uterine peristaltic movements, time-controlled uterine fluid reabsorption and uterine luminal closure, as well as embryo orientation. Diverse molecular factors, such as steroid hormone signaling, lipid signaling, adrenergic signaling, developmental genes, ion/water channels, and potentially embryonic signaling are actively involved in intrauterine embryo distribution. This review covers the biomechanical and molecular aspects of intrauterine embryo distribution (embryo spacing at the longitudinal axis and embryo orientation at the vertical axis), as well as its pathophysiological roles in human reproductive medicine. Future progress requires multi-disciplinary research efforts that will integrate in vivo animal models, clinical cases, physiologically relevant in vitro models, and biomechanical/computational modeling. Understanding the mechanisms for intrauterine embryo distribution could potentially lead to development of therapeutics for treating related conditions in reproductive medicine.     

Mobility, balance and falls in persons with multiple sclerosis

Background

There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS).

Methods

52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery.

Results

Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS.

Conclusions

The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established.     

Embryos,The Principle of Proportionality,and the Shaky Ground of Moral Respect

The debate concerning the moral permissibility of using human embryos in human embryonic stem cell (hESC) research has long centred on the question of the embryo's supposed right to life. However, in focussing only on this question, many opponents to hESC research have escaped rigorous scrutiny by making vague and unfounded appeals to the concept of moral respect in order to justify their opposition to certain hESC practices. In this paper, I offer a critical analysis of the concept of moral respect, and its use to support the intuitively appealing principle of proportionality in hESC research. I argue that if proponents of this principle are to justify its adoption by appealing to the concept of moral respect, they must explain two things concerning the nature of the moral respect owed to embryos. First, they must explain which particular aspect of the embryo is morally relevant, and why. Second, they must explain why some uses of embryos in research fail to acknowledge what is morally relevant about the embryo, and thereby involve a violation of the moral respect that they are due. I shall show that providing such explanations may be more difficult than it first appears.     

Aspects of in vivo oocyte production,blastocyst development,and embryo transfer in the cat

A brief overview of the progress made during the past approximately 40 years on the development of methods for in vitro production of cat embryos and intra- and interspecies embryo transfer is described. The presentation is focused primarily on research done over the past 30 years at the Cincinnati Zoo (1980–1995) and at the Audubon Nature Institute, New Orleans (1996–present) beginning with original studies on determining optimal doses of porcine FSH for ovarian stimulation and uterine embryo recovery, cryopreservation, and transfer. A key early finding was the ability of cats to respond to multiple gonadotropin (porcine FSH) treatments by repeated stimulation of follicular development. With a ≥6-month interval between FSH treatments, over the past 15 years (1998–2013), we have done 1603 laparoscopic oocyte retrievals on 337 cats and recovered >38,000 mature oocytes (mean = 24.1 per laparoscopic oocyte retrieval). The limited information available on in vivo blastocyst development in the cat during the latter portion of the preimplantation period (approximately Days 8 to 12 after coitum or approximately Days 7 to 11 after ovulation) was assembled for the purpose of comparing and contrasting it with the growth, expansion, and zona functioning of in vitro-derived blastocysts. Also, results of transferring morulae and/or blastocysts into synchronous recipients are described to emphasize evidence that appears to allude to an essential role for an intact zona pellucida in successful implantation and subsequent development in the cat. Until 2003, our in vitro-derived embryos were transferred into the uterine horns of recipients to determine the feasibility of producing offspring from such primary methods as IVF, intracytoplasmic sperm injection, SCNT, and embryo cryopreservation. With the exception of SCNT embryos, pregnancy rates were satisfactory, but embryo survival rates were not. Subsequently, after finding that SCNT embryo survival rate could be improved using laparoscopic transfer of early cleavage stage embryos into the oviduct, we applied the technique to embryos derived using IVF with sex-sorted sperm, oocyte vitrification, and embryo cryopreservation. Overall, a pregnancy rate of 67% (14/21) has resulted. Most recently, with the oviductal embryo transfer technique, two litters of Black-Footed cat kittens have been born from intra- and interspecies transfer of cryopreserved embryos.