In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce (...) in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes. (shrink)

Robert Sparrow has recently raised the possibility that stem cell technology could in the future be used to create multiple generations of embryos in the laboratory before transferring one embryo to a woman’s womb to create a pregnancy. Sparrow argues that any children produced in this way would be genetic orphans—they would lack living genetic parents—and explores the possible moral implications of this. A number of other authors have raised objections to Sparrow’s moral claims, but his descriptive claim remains unchallenged. (...) In this chapter, we challenge it, arguing that Sparrow’s imagined technology could be performed in such a way that the children produced would have living genetic parents. (shrink)

A series of recent scientific results suggest that, in the not-too-distant future, it will be possible to create viable human gametes from human stem cells. This paper discusses the potential of this technology to make possible what I call ‘in vitro eugenics’: the deliberate breeding of human beings in vitro by fusing sperm and egg derived from different stem-cell lines to create an embryo and then deriving new gametes from stem cells derived from that embryo. Repeated iterations of (...) this process would allow scientists to proceed through multiple human generations in the laboratory. In vitro eugenics might be used to study the heredity of genetic disorders and to produce cell lines of a desired character for medical applications. More controversially, it might also function as a powerful technology of ‘human enhancement’ by allowing researchers to use all the techniques of selective breeding to produce individuals with a desired genotype. (shrink)

In vitro gametogenesis (IVG) might offer numerous research and clinical benefits. Some potential clinical applications of IVG, such as allowing opposite‐sex couples experiencing infertility to have genetically related children, have attracted support. Others, such as enabling same‐sex reproduction and solo reproduction, have attracted significantly more criticism. In this paper, we examine how different ethical principles might help us to draw lines and distinguish between ethically desirable and undesirable uses of IVG. We discuss the alleged distinction between therapeutic and non‐therapeutic (...) uses of assisted reproduction in the context of IVG, and show how it is both problematic to apply in practice and theoretically dubious. We then discuss how the ethical principles of reproductive justice and beneficence apply to IVG for opposite‐sex reproduction, same‐sex reproduction, and solo reproduction. We suggest that these principles generate strong reasons for the use of IVG for opposite‐sex and same‐sex reproduction, but not for solo reproduction. (shrink)

Recent breakthroughs in stem cell differentiation and reprogramming suggest that functional human gametes could soon be created in vitro. While the ethical debate on the uses of in vitro generated gametes (IVG) was originally constrained by the fact that they could be derived only from embryonic stem cell lines, the advent of somatic cell reprogramming, with the possibility to easily derive human induced pluripotent stem cells from any individual, affords now a major leap in the feasibility of (...) IVG derivation and in the scope of their potential applications. In this paper we develop an ethical framework, rooted in recent scientific evidence, to support a robust experimental pipeline that could enable the first-in-human use of IVG. We then apply this framework to the following objectives: (1) a clarification of the genetic parenting options afforded by IVG, along with their ethical underpinnings; (2) a defence of the use of IVG to remedy infertility, broadening their scope to same-sex couples; (3) an assessment of the most far-reaching implications of IVG for multiplex parenting. These include, first, the liberation of parenting roles from the constraints of biological generations in vivo, allowing multiple individuals to engage in genetic parenting together, thus blurring the distinction between biological and social generations. Second, we discuss the conflation of IVG with sequencing technology and its implications for the possibility that prospective parents may choose among a hitherto unprecedented number of potential children. In view of these perspectives, we argue that, contrary to the exhausted paradigm according to which society lags behind science, IVG may represent instead a salient and most visible instance where biotechnological ingenuity could be used in pursuit of social experimentation. (shrink)

Certain interventions now permit the derivation of mammalian gametes from stem cells cultivated from either somatic cells or embryos. These gametes can be used in an indefinite cycle of conception in vitro, gamete derivation, conception in vitro, and so on, producing genetic generations that live only in vitro. One commentator has described this prospect for human beings as eugenics, insofar as it would allow for the selection and development of certain traits in human beings. This commentary not (...) only offers this topic for discussion, it also wades into the ethical fray over the practice. Several possible lines of objection can be raised against this practice, but these accounts are by and large insufficient as an ethical analysis of this possible, future way of conceiving human children. (shrink)

In this paper we look at the implications of an emerging technology for the case in favor of, or against, postmenopausal motherhood. Technologies such as in vitro derived gametes have the potential to influence the ways in which reproductive medicine is practiced, and are already bringing new dimensions to debates in this area. We explain what in vitro derived gametes are and how their development may impact on the case of postmenopausal motherhood. We briefly review some of the (...) concerns that postmenopausal motherhood has raised—and the implications that the successful development, and use in reproduction, of artificial gametes might have for such concerns. The concerns addressed include arguments from nature, risks and efficacy, reduced energy of the mother, and maternal life expectancy. We also consider whether the use of in vitro derived gametes to facilitate postmenopausal motherhood would contribute to reinforcing a narrow, geneticized account of reproduction and a pro-reproductive culture that encourages women to produce genetically related offspring at all costs. (shrink)

ABSTRACT Recent developments in generating gametes via in vitro gametogenesis (IVG) from induced pluripotent stem cells (iPSCs) and their successful use for reproductive purposes in animals strongly suggest that soon these methods could also be used in human reproduction. At least two questions emerge in this context: (a) if a legislator should permit their use and (b) if ethical claims emerge that support their provision, e.g., by public health care systems. This urges an ethical reflection of the new reproductive (...) options this technique might offer. Since the concept of reproductive freedom is a key aspect for the ethical evaluation of artificial reproductive technologies (ARTs), it is necessary to analyze if the new possibilities emerging from IVG fall within the scope of this concept. The results may constitute a morally relevant difference between different imaginable applications of IVG and potentially justify differences in claims to access this technology. (shrink)

Several threads of research towards developing artificial gametes are ongoing in a number of research labs worldwide. The development of a technology that could generate gametes in vitro has significant potential for human reproduction, and raises a lot of interest, as evidenced by the frequent and extensive media coverage of research in this area. We have asked researchers involved in work with artificial gametes, ethicists, and representatives of potential user groups, how they envisioned the use of artificial gametes in (...) human reproduction. In the course of three focus groups, the participants commented on the various aspects involved. The two recurring themes were the strength of the claim of becoming a parent genetically, and the importance of responsible communication of science. The participants concurred that (a) the desire or need to have genetic offspring of one’s own does not warrant the investment of research resources into these technologies, and that (b) given the minefield in terms of moral controversy and sensitivity that characterises the issues involved, how information is communicated and handled is of great importance. (shrink)

The proposal for reproducing human generations in vitro raises the question to what extent parenthood is possible in embryos and to what extent human rights and interests are dependent on conscious awareness. This paper argues that the interest in not being made a parent non-consensually for the benefit of others persists throughout the lifespan of the individual human organism. We do not become genetic parents by learning that we are parents; rather, we discover (or fail to discover) an existing (...) genetic relationship between our offspring and ourselves. The claim to genetic parenthood of an embryo used for reproduction in vitro is, if anything, clearer than the claim of the adult for whom gametes are derived via ips cells, in that an embryo’s cells, unlike an adult’s somatic cells, are already functionally geared to producing gametes (among other types of cell). An embryo used to make gametes that are used in reproduction is immediately and non-consensually made a genetic parent and to that extent is wronged whether or not the parent embryo survives – as some could survive – the harvesting of cells. All human individuals carry objective interests in benefits appropriate to the kind of being they are; these include the stake in not being made a parent without one’s consent, whether posthumously or otherwise. (shrink)

Recent results from studies on animals suggest that functional germ cells may be generated from human pluripotent stem cells, giving rise to three possibilities: research with these so‐called artificial gametes, including fertilization experiments in vitro; their use in vivo for therapy for the treatment of human infertility; and their use in assisted reproductive technologies in vitro. While the legal, philosophical, and ethical questions associated with these possibilities have been already discussed intensively in other countries, the debate in (...) Germany is still at its beginning. A systematic and detailed analysis of the legal framework in Germany is provided with regard to the three possibilities, including the applicable statutory laws as well as the constitutional law. The question emerges as to whether the statutory laws as well as the constitution justify a distinction to be made between embryos of artificial and natural origin. This question is subject to philosophical analysis, discussing the distinction between person and thing, dignity and price, personality and property, and nature and technique. As a result, the criterion of naturalness alone may not be sufficient to differentiate between embryos of natural and artificial origin, and other criteria need to be identified. (shrink)

Technologies for deriving human neurons in vitro have transformed our ability to study cellular and molecular components of human neurotransmission. Three groups, including our own, have recently published methods for efficiently generating human serotonergic neurons in vitro. Remarkably, serotonergic neurons derived from each method robustly produce serotonin, express raphe genes, are electrically active, and respond to selective serotonin reuptake inhibitors in vitro. Two of the methods utilize transdifferentiation technology by overexpressing key serotonergic transcription factors. The third and (...) most recent method involves differentiating induced pluripotent stem cells (iPSCs) to serotonergic neurons using developmental patterning cues. In this mini‐review, we briefly describe the developmental programs governing serotonergic specification in vivo and how they have been harnessed to achieve serotonergic differentiation in vitro. We discuss the distinct and overlapping features of the recently published methodologies and their value in the context of in vitro disease modeling.Also see the video abstract here. (shrink)

Abstract:Research into the development of stem cell-derived (SCD) gametes in humans, otherwise known asin vitrogametogenesis (IVG), is largely motivated by reproductive aims. Especially, the goal of establishing genetic parenthood by means of SCD-gametes is considered an important aim. However, like other applications in the field of assisted reproduction, this technology evokes worries about the possibility of creating so-called ‘designer babies.’ In this paper, we investigate various ways in which SCD-gametes could be used to create such preference-matched offspring, and what this (...) would mean for the acceptability of IVG, if it is premised that it is morally problematic to ‘design’ offspring. We argue that IVG might facilitate the creation of preference-matched offspring, but conclude that this should not undermine the moral acceptability of IVG altogether—even if one concedes the premise that creating ‘designer babies’ is morally problematic. In the light of this, we also point at a possible inconsistency for a position that condemns the creation of ‘designer offspring,’ while accepting the various endeavors to have genetically related offspring. (shrink)

Scientists are developing a technique called in vitro gametogenesis or IVG to generate synthetic gametes for research and, potentially, for treating infertility. What would it mean for feminist concerns over the future of reproductive practice and biotechnological development if egg and sperm cells could be produced in laboratory conditions? In this article, I take on the question by discussing the emerging technique of IVG through the speculative feminist analysis of ambiguous reproductive futures. Feminist cultural and science studies scholars have (...) explored the transformative effects of biomedicine on reproduction through science fiction novels and other cultural products. I theorise the speculative and visionary in biomedicine in the context of ethnographic methodology by drawing on ‘thought experiments’ conducted with stem cell scientists as shared acts of future-oriented contemplation. I develop the figure of SF proposed by Donna Haraway to investigate how science facts and speculative fabulation together shape futurities of reproduction. I propose including shifting frontiers in feminist thinking of the SFs in bioscience. Biomedical research aims to shift the borders between what is known and not known in reproductive biology, subsequently raising new technical, ethical and political issues in terms of stratified reproduction. The article shows that synthetic gametes are anticipated to intensify selective procreation. Simultaneously, IVG is seen to forge new biogenetic relationships and possibilities for non-normative reproduction and kin-making. Following Haraway, I argue that by ‘staying with the trouble’ of these biotechnological visions, feminist speculative analytics on technoscience offers a valuable tool to envision more hopeful and equal futures together with scientists. (shrink)

This paper explores whether egg donation could still be ethically justified if in vitro gametogenesis (IVG) became reliable and safe. In order to do this, issues and concerns that might inform a patient’s reasoning in choosing to use donor eggs instead of IVG are explored and assessed. It is concluded that egg donation would only be ethically justified in a narrow range of special cases given the (hypothetical) availability of IVG treatment and, further, that egg donation could itself be (...) replaced by donation through IVG techniques. Two possible criticisms of this position are then considered: Ones based on respect for patient wishes, and on loss of donor benefit. It is concluded that whilst neither argument constitutes a strong enough reason to continue with programmes of egg donation, egg‐sharing programmes could still be permitted come the advent of IVG; these could then provide a morally acceptable source of “natural” donor eggs. (shrink)

The Principle of Procreative Beneficence (PB) holds that when a couple plans to have a child, they have significant moral reason to select, of the possible children they could have, the child who is most likely to experience the greatest wellbeing – that is, the most advantaged child, the child with the best chance at the best life.1 PB captures the common sense intuitions of many about reproductive decisions. PB does not posit an absolute moral obligation – it does not (...) dictate what people must do. Instead it holds that there is a significant moral reason to select the best child, but one that must be weighed against other reasons.Recent research suggests that it may become possible to derive gametes (eggs and sperm) from human stem cells in vitro, a process which we will term in vitro gametogenesis (IVG). The ability to create large numbers of eggs or sperm through IVG greatly increases our capacity to select the best child possible. (shrink)

The views on in vitro fertilization within Russian Orthodox Christian society are diverse. One reason for that variation is the ambiguity found in “The Basis of the Social Concept,” the document issued in 2000 by the Russian Orthodox Church and considered to be the primary guidelines for determining the Church’s stance on bioethics. This essay explores how the treatment of infertility reconciles with the Orthodox Christian faith and what methods of medical assistance for infertility may be appropriate for Orthodox (...) Christians. The focus here is on IVF because it is among the most widely used methods to overcome childlessness, and the permissibility of IVF is the object of disagreement among Orthodox. The article defines criteria that can help to discern what is absolutely wrong and must be avoided from what only falls short of the mark, but not very far, for Orthodox Christians. If treatment of the underlying causes of infertility has failed or promises no hope and a husband and a wife do not feel able to carry the Cross of infertility, then from pastoral dispensation they might be blessed to use ethically acceptable variants of IVF. IVF has many variants that are different in their spiritual influence on a person. Orthodox Christians pursuing IVF should seek spiritual guidance and a blessing to pursue IVF. They must not form more embryos than will be transferred in the same cycle. Freezing, discarding, or reduction of embryos is forbidden. Infertile couples ought to use only their reproductive cells. The use of donor gametes is unacceptable. Any embryo formed ought to be transferred into the wife’s womb, and the use of surrogates is impermissible. Only a husband and wife who are able to maintain their marital union and where the wife is still of childbearing age should be blessed to use IVF. (shrink)

Current developments in reproductive technology forecast that in the foreseeable future artificially generated gametes might be presented as a possible fertility treatment for infertile couples and for homosexual couples desiring to have children genetically originating from both partners. It is important to evaluate the ethical issues connected to this technology before its emergence. This article first reviews the meaning that gametes (sperm and eggs) might have to those who procreate, as well as their ontology. From this, suggestions are made (...) as to what qualities artificially generated gametes need to be truly called gametes. Finally, different proposed routes for artificial gamete generation are examined on the basis of these qualities, with their prospective problems and advantages highlighted. Autotransplanted gametes (or their progenitors) generated solely from patient-derived tissue are deemed to be the most ethically suitable route for the development of this technology. (shrink)

Oncofertility is one of the 9 NIH Roadmap Initiatives, federal grants intended to explore previously intractable questions, and it describes a new field that exists in the liminal space between cancer treatment and its sequelae, IVF clinics and their yearning, and basic research in cell growth, biomaterials, and reproductive science and its tempting promises. Cancer diagnoses, which were once thought universally fatal, now often entail management of a chronic disease. Yet the therapies are rigorous, must start immediately, and in many (...) cases result in premature failure of the body's reproductive ability. In women, this loss is especially poignant; unlike the routine storage of sperm, which is done in men and boys facing similar treatment decisions, freezing oocytes in anticipation of fertility loss is not possible in most cases, and creating an embryo within days of diagnosis raises significant moral, social and medical challenges. Oncofertility is the study of how to harvest ovarian tissue in women facing cancer to preserve their gametes for future use with IVF, thus allowing the decisions about childbearing to be deferred and reproductive choices to be preserved. The research endeavor uses the capacity of the ovarian follicle to produce eggs in vitro . Developing the human follicle to ovulate successfully outside the body is scientifically difficult and ethically challenging. Infertility is linked to long-standing religious and moral traditions, and is intertwined with deeply contentious social narratives about women, families, illness and birth. Is the research morally permissible? Perhaps imperative if understood as a repair from iatrogenic harms? How are considerations of justice central to the work? How will vulnerable subjects be protected? What are the moral implications of the work for women, children and families? What are the implications for society if women could store ovarian tissue as a way of stopping the biological clock? What are the moral possibilities and challenges if eggs can be produced in large quantities from a stored ovarian tissue? (shrink)

This work sought to carry out a comparative analysis of in vitro fertilization (IVF) vis-à-vis St. Thomas Aquinas’ Natural Law Theory. Both of them emanated from problem of infertility. IVF makes use of artificial insemination for fertilization which is quite contrary to the natural process of sexual reproduction. This work makes use of analytic method to analyse comparatively in vitro fertilization and St. Thomas Aquinas’ Natural Law Theory. Thus, this work conceives that IVF is one of the assisted (...) reproductive technologies in the scientific exploration of genetic engineering and bio-technology which emanated to tackle the problem of genetic inheritance outside marriage. It contravenes the coital or natural reproduction which conforms to St. Thomas Aquinas’ second precept of natural law. Again, IVF is artificial as such it is pruned to many complications. There is no adequate information given by the medical practitioners or providers of this service on the health hazards or risks involve in IVF. In addition, in vitro fertilization makes provision for donor gamete and surrogate motherhood which may have many negative implications both for the couples, off-spring, gestation mother, and society at large. (shrink)

The introduction of in vitro fertilization (IVF) results in a separation of sex and reproduction which has generated enormous ethical debate (Lauritzen 1993). Surrogacy makes this situation more complicated by bringing a surrogate mother into reproduction. A surrogacy case may involve five individuals (in addition to the surrogate child). These are the commissioning couple, the gamete donors, and the surrogate mother. Hence, a surrogate child may have up to five parents, including biological parents, commissioning parents, and a gestational (...) parent. The question is which of these people should undertake parental duty? In terms of the acquisition of parental duty, there are three accounts. They are the biological connection account, the causal account, and the consent account. In this article, I try to argue that only the commissioning parents should undertake the parental duty for the surrogate child based on the latter two accounts. I do not apply the biological connection account because the biological connection account fails to explain one’s parental duty, which I will show in the following sections. (shrink)

In vitro gametogenesis is the process of deriving gametes from embryonic stem cells or induced pluripotent stem cells. While not as well-known as in vitro fertilization, IVG could lead to more moral issues that would require corresponding responses from the Magisterium. Because IVG remains at the experimental stage, mainly using mice, the Magisterium has not issued any such responses in a document along the lines of Donum vitae and Dignitas personae. This essay situates IVG within Catholic moral teachings (...) for those who are unfamiliar with the teachings of the Church but who are interested in forming their consciences and those of others on what is undoubtedly a peculiar medical technique with many moral ramifications. (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that (...) alteration of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its (...) efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples. (shrink)

The present study examined the endogenous release of luteinizing hormone-releasing hormone (LHRH) from superfused hypothalamic slices derived from Korean native cattie (KNC). In addition, the in vitro secretory pattern of LHRH release in '(NC was compared with that in imported cattle such as Holstein cow. The median eminences (ME) of hypothalamic tissues were dissected out, sliced, and quickly placed in an ice-cold superfusion chamber. Superfusion chambers containing ME slices were maintained in a constant temperature water-bath at 37∘C. Effluents were (...) collected on the ice at 10 min intervals for a 4 hr superfusion period and kept -20∘C prior to LHRH radioimmunoassay. LHRH release was analyzed by the PULSAR algorithm. The spontaneous release of LHRH from both cows was episodic during a 4 hr superfusion period. The mean LHRH release, pulse amplitude and pulse interval m KNC were 11.08± 1.50 pg/min/mg x 10-2, 21.43 1 7.28 pg/mg x 10-2, and 39.42 ± 3.08 min, which was quite similar to those observed in Holstein cows. The basic characteristics of the LHRH pulse generator of KNC appear important for a better understanding about the endocrine function of KNC. (shrink)

In ‘in vitro eugenics’ (IVE), I outlined a theoretical use of a technology of artificial gametogenesis, wherein repeated iterations of the derivation of gametes from embryonic stem cells, followed by the fusion of gametes to create new embryos, from which new stem cells could be derived, would allow researchers to create multiple generations of human embryos in the laboratory and also to produce ‘enhanced’ human beings with desired traits. As a number of commentators observed, my purpose in publishing this (...) paper was to provoke ethical discussion of a largely unremarked upon technological possibility and surrounding issues. Even if this was, as Murphy observes archly, to aim ‘low’, discussion of IVE is valuable for three reasons. First, it may render us better prepared should IVE become practical. I noted of my original discussion that it was speculative and several of the respondents suggest that IVE is even less likely to come about than I allowed there. Nevertheless, second, discussion of IVE is valuable for what it reveals about the ethics of new reproductive technologies (NRTs) more generally and, third, about the ethics of genetic human enhancement in particular. The responses to my paper demonstrate this nicely by (a) illustrating the selective way in which arguments about risk are mobilised in debates about NRTs and (b) highlighting the tension between any obligation of ‘procreative beneficence’ and a concern for genetic relatedness. Even if IVE should never be pursued, then, discussion of this possibility may help us better understand the ethics of other NRTs and means of genetic human enhancement. (shrink)

This computational study generates a hypothesis for the coagulation protein whose initial concentration greatly influences the course of coagulation. Many clinical malignancies of blood coagulation arise due to abnormal initial concentrations of coagulation factors. Sensitivity analysis of mechanistic models of blood coagulation is a convenient method to assess the effect of such abnormalities. Accordingly, the study presents sensitivity analysis, with respect to initial concentrations, of a recently developed mechanistic model of blood coagulation. Both the model and parameters to which model (...) sensitivity is being analyzed provide newer insights into blood coagulation: the model incorporates distinct equations for plasma-phase and platelet membrane-bound species, and sensitivity to initial concentrations is a new dimension in sensitivity analysis. The results show that model predictions are most uncertain with respect to changes in initial concentration of factor VIII, and this hypothesis is supported by results from other models developed independently. (shrink)

Angiogenesis is a complex morphogenetic process regulated by growth factors, but also by the force balance between endothelial cells traction stresses and extracellular matrix viscoelastic resistance. Studies conducted with in vitro angiogenesis assays demonstrated that decreasing ECM stiffness triggers an angiogenic switch that promotes organization of EC into tubular cords or pseudo-capillaries. Thus, mechano-sensitivity of EC with regard to proteases secretion, and notably matrix metalloproteinases, should likely play a pivotal role in this switching mechanism. While most studies analysing strain (...) regulation of MMPs used cell cultured on stretched membranes, this work focuses on MMP expression during self-assembly of EC into capillary-like structures within fibrin gels, i.e. on conditions that mimics more closely the in vivo cellular mechanical microenvironment. The activity of MMP-2 and MMP-9, two MMPs that have a pivotal role in capillaries formation, has been monitored in pace with the progressive elongation of EAhy926 cells that takes place during the emergence of cellular cords. We found an increase of the zymogen proMMP-2 that correlates with the initial stages of EC cords formation. However, MMP-2 was not detected. ProMMP-9 secretion decreased, with levels of MMP-9 kept at a rather low value. In order to analyse more precisely the observed differences of EAhy926 response on fibrin and plastic substrates, we proposed a theoretical model of the mechano-regulation of proMMP-2 activation in the presence of type 2 tissue inhibitor of MMPs. Using association/dissociation rates experimentally reported for this enzymatic network, the model adequately describes the synergism of proMMP-2 and TIMP-2 strain activation during pseudo-capillary morphogenesis. All together, these results provide a first step toward a systems biology approach of angiogenesis mechano-regulation by cell-generated extracellular stresses and strains. (shrink)

This paper explores problems associated with using altruism as the central value in gamete donation, and in doing so draws on empirical data that sheds light on why gamete donors choose to donate. Donation of bodily material is, arguably, supposed to be motivated by altruism, and this is the view taken by many European governments. Other values are often ignored or rejected as morally inappropriate. This paper analyses some conceptual and practical problems with the use of altruism as the motivation (...) to determine moral acceptability—drawing on empirical data that suggests gamete donors are not motivated purely by altruism, and that motivations are in fact quite complex. Two problems are first analysed: how do we distinguish altruistic from non-altruistic donations and how do we distinguish between removing barriers and providing incentives. A final question, triggered by the Nuffield Council on Bioethics’ report, is whether the meaning of the payment should be decided on the basis of an a priori definition or on the basis of the donors’ subjective experience. It is concluded that there are different legitimate core values in donation, which should be balanced. In order to value the good generated by donation, donors with mixed motives should be accepted, as long as helping others is an important motive and also features in their motivation. (shrink)

A number of recent papers have described the successful derivation of egg and sperm precursor cells from mouse embryonic stem cells—so-called “artificial” gametes. Although many scientific questions remain, this research suggests numerous new possibilities for stem cell research and assisted reproductive technology, if a similar breakthrough is achieved with human embryonic stem cells. The novel opportunities raised by artificial gametes also prompt new ethical questions, such as whether same-sex couples should be able to access this technology to have children who (...) are genetically related to them both.THE CREATION OF “ARTIFICIAL” GAMETESOver the past two years, a number of papers have been published detailing the first successful attempts at differentiating mouse embryonic stem cells into egg1 and sperm2 precursor cells. Previously, researchers had used embryonic stem cells to generate tissues such as brain, liver, and pancreatic cells, but not germ cells of any kind. Production of gamete precursor cells was achieved initially through allowing stem cell lines to differentiate more or less randomly, but recent research has focused on identifying the precise ways in which differentiation into gametes can be precipitated and controlled. These breakthroughs make it seem likely that ongoing research on human stem cells will yield similar possibilities,3 raising questions over the practicalities of what might be achieved with such “artificial” gametes. In turn, the novel opportunities presented by artificial gametes raise a number of ethical concerns.The initial breakthrough, namely the obtaining of egg cells from mouse stem cells, was achieved by means of relatively simple science. Rather than coaxing stem cells to develop into eggs using complicated cocktails of growth factors, researchers adopted standard cell culture conditions, but grew the cells at higher density than usual.3–6 Growing the cells in this way led to the formation of ovary-like cell aggregates, which (when separated and stimulated with …. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the (...) opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the (...) opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the (...) opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

In Canada, laws and policies consistently reject the commodification of human organs and tissues, and Canadian practice is consistent with international standards in this regard. Until the Assisted Human Reproduction Act of 2004, gamete donation in Canada was an exception: Canadians could pay and be paid open market rates for gametes for use in in vitro fertilization. As sections of the AHR Act forbidding payment for gametes and permitting only reimbursement of receipted expenses gradually came into effect in 2005, (...) Canada did away with this anomaly. Medical practice and legal prohibitions in assisted human reproduction are now consistent with other areas of medicine where tissues and organs are taken from one person to benefit others: Altruistic donation, rather than selling and buying, will be the norm. (shrink)

What is the relationship between the position that anonymous gamete donation is wrong (i.e. the anti-anonymity position) and the position that all gamete donation is wrong (i.e. the anti-donation position)? Some argue that people who accept the anti-anonymity position should also accept the anti-donation position on the grounds that the two positions share the same main arguments. But that’s not true. One argument in favor of anti-anonymity does not generate genuine dialectical pressure to accept the anti-donation position. The other anti-anonymity (...) arguments do generate dialectical pressure, but not in a way that pushes toward the anti-donation position. Instead, they push toward what we might call the ‘pro-known-donation’ position. So, either there is no dialectical pressure or, where there is, it doesn’t flow toward the anti-donation position. (shrink)

The dominant philosophical view of gamete donation as morally permissible rests on two premises: parental obligations are triggered primarily by playing a causal role in procreation, not by genetic ties, and those obligations are transferable—that is, they are obligations to make adequate provision for the child’s needs, not necessarily to raise the child oneself. Thus while gamete donors are indeed agent causes of the children that their donation helps to bring into existence, most think that donors’ obligations are discharged insofar (...) as they know that competent others intend to care for those children. In this article, I call into question this dominant view by challenging both of its premises. Challenging the first premise, I argue that genetic parenthood is what primarily triggers parental obligations. Challenging the second premise, I claim that those obligations are non-transferable—i.e., that they are obligations not simply to ensure that someone will raise one’s genetic child, but to raise that child oneself . The implication of my argument is that gamete donation is inherently wrong insofar as it involves acquiring non-transferable obligations that one has no intention of fulfilling. (shrink)

The recent success in generating live offspring from embryonic stem cell –derived gametes in mice sparked visions of growing tailor-made sperm for men faced with infertility. However, although this development will almost certainly lead to new insights into the processes underlying spermatogenesis and thus in the possible causes of male infertility, it is less certain if deriving sperm from ES cells, which are in turn derived from a sterile man, can make someone a genetic parent. As the gap between newly (...) envisioned reproductive technologies and natural reproduction widens, the question thus needs to be asked if these possible therapies still lead to genetic parenthood. (shrink)

With the development of new procedures in the production of synthetic human gametes it has become important to re-examine the manner in which reproductive cells, taking part in the generation of children, can be understood. Though this can be attempted from many different perspectives, the present study will examine the possibility of considering gametes as representing the persons from whom they originated. From this perspective, it is possible to suggest that, in procreation, the entirety of each human sperm cell may (...) represent and reveal the man from whom it was produced and the entirety of each human egg cell may represent and reveal the woman from whom it was produced. The possible ethical consequences of using synthetic gametes for those who hold this perspective together with their understanding of relational identity will also be examined. (shrink)

A lot of interest has been generated by the possibility of deriving gametes from embryonic stem cells and bone marrow stem cells. These stem cell derived gametes may become useful for research and for the treatment of infertility. In this article we consider prospectively the ethical issues that will arise if stem cell derived gametes are used in the clinic, making a distinction between concerns that only apply to embryonic stem cell derived gametes and concerns that are also relevant (...) for gametes derived from adult stem cells. At present, it appears preferable to use non-embryonic stem cells for the derivation of gametes. Adult stem cell derived gametes do not present any problems with regard to the moral status of the human embryo, bypass the safety risks linked to SCNT and do not present any ambiguity or novel problems with regard to informed consent, psychological consequences for the child or genetic parenthood. A remaining ethical concern, however, regards the safety of the procedure in terms of the welfare of the resulting children. This should spark a thorough reflection on how far one must go to accommodate a person’s wish to have a genetically related child. (shrink)

The complexity of the physiological phenotype currently prevents us from identifying an integrative measure to assess how the internal state and environmental conditions modify life‐history strategies. In this article, it is proposed that shorter telomeres should lead to a faster pace‐of‐life where investment in self‐maintenance is decreased as a means of saving energy for reproduction, but at the cost of somatic durability. Inversely, longer telomeres would favor an increased investment in soma maintenance and thus a longer reproductive lifespan (i.e., slower (...) pace‐of‐life). Under this hypothesis, telomere dynamics could be such an integrative mediator, which will assemble the information about oxidative stress levels, inflammation status and stress reactivity, and relate this information to the potential lifespan of the organism and its pace‐of‐life strategy. The signaling function of telomere dynamics can also reach over generations, a phenomenon in which the telomere lengths of gametes would provide a channel through which offspring would receive information about their environment early in their development, hence increasing the possibilities for developmental plasticity. -/- . (shrink)

Correct interpretation of the data from integral laboratory tests, including Thrombin Generation Test, requires biochemistry-based mathematical models of blood coagulation. The purpose of this study is to describe the experimental TGT data from healthy donors and hemophilia A and B patients. We derive a simplified ODE model and apply it to analyze the TGT data from healthy donors and HA/HB patients with in vitro added tissue factor pathway inhibitor antibody. This model allows the characterization of hemophilia patients in the (...) space of three most important model parameters. The proposed approach may provide a new quantitative tool for the analysis of experimental TGT. Also, it gives a reduced model of coagulation verified against clinical data to be used in future theoretical large-scale modeling of thrombosis in flow. (shrink)

At fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+ concentration. The precise sequence of events that occur between sperm‐egg contact and the increases in intracellular Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that (...) specifically comigrates with Ca2+ oscillation‐inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+ oscillations may have wider physiological significance since sperm oscillin can induce Ca2+ oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations. (shrink)

Parental age at offspring conception often influences offspring longevity, but the mechanisms underlying this link are poorly understood. One mechanism that may be important is telomeres, highly conserved, repetitive sections of non‐coding DNA that form protective caps at chromosome ends and are often positively associated with longevity. Here, the potential pathways by which the age of the parents at the time of conception may impact offspring telomeres are described first, including direct effects on parental gamete telomeres and indirect effects on (...) offspring telomere loss during pre‐ or post‐natal development. Then a surge of recent studies demonstrating the effects of parental age on offspring telomeres in diverse taxa are reviewed. In doing so, important areas for future research and experimental approaches that will enhance the understanding of how and when these effects likely occur are highlighted. It is concluded by considering the potential evolutionary consequences of parental age on offspring telomeres. (shrink)

Despite its potential for radically reducing the harm inflicted on nonhuman animals in the pursuit of food, there are a number of objections grounded in animal ethics to the development of in vitro meat. In this paper, I defend the possibility against three such concerns. I suggest that worries about reinforcing ideas of flesh as food and worries about the use of nonhuman animals in the production of in vitro meat can be overcome through appropriate safeguards and a (...) fuller understanding of the interests that nonhuman animals actually possess. Worries about the technology reifying speciesist hierarchies of value are more troublesome, however. In response to this final challenge, I suggest that we should be open not just to the production of in vitro nonhuman flesh, but also in vitro human flesh. This leads to a consideration of the ethics of cannibalism. The paper ultimately defends the position that cannibalism simpliciter is not morally problematic, though a great many practices typically associated with it are. The consumption of in vitro human flesh, however, is able to avoid these problematic practices, and so should be considered permissible. I conclude that animal ethicists and vegans should be willing to cautiously embrace the production of in vitro flesh. (shrink)

Machine generated contents note: Part 1 - The Constituent Disciplines of Cognitive Science -- Philosophical Epistemology -- Glossary -- 1.0 What is Philosophical Epistemology? -- 1.1 The reduced history of Philosophy Part I - The Classical Age -- 1.2 Mind and World - The problem of objectivity -- 1.3 The reduced history of Philosophy Part II - The twentieth century -- 1.4 The philosophy of Cognitive Science -- 1.5 Mind in Philosophy: summary -- 1.6 The Nolanian Framework (so far) (...) -- Psychology -- 2.0 Why is Psychology so difficult? -- 2.1 A brief history of Experimental Psychology -- 2.2 Methodologies in Psychology -- 2.3 Perception -- 2.4 Memory -- 2.5 Mind in Psychology -- Linguistics -- 3.0 Introduction -- 3.1 Why Linguistics? -- 3.2 Computation and Linguistics -- 3.3 The main grammatical theories -- 3.4 Language development and linguistics -- 3.5 Toward a definition of context -- 3.6 The multifarious uses of Language -- 3.7 Linguistics and Computational Linguistics -- 3.8 Language and other symbol systems -- 3.9 On the notion of context -- 3.10 Mind in Linguistics: summary -- Neuroscience -- 4.0 The constituent disciplines of Neuroscience -- 4.1 The methodology of Neuroscience -- 4.2 Gross Neuroanatomy -- 4.3 Some relevant findings -- 4.4 Connectionism (PDP) -- 4.5 The victory of Neuroscience? -- 4.6 Mind in Neuroscience: summary -- Artificial Intelligence -- 5.0 Introduction -- 5.1 Al and Cognitive Science -- 5.2 Skeptics and their techniques -- 5.3 Al as Computer Science -- 5.4 Al as software -- 5.5 The current methodological debate -- 5.6 Context, syntax and semantics -- 5.7 Mind in Al -- 5.8 Texts on Al -- Etholoqy and Ethnoscience -- 6.1 Etology -- 6.2 Ethnoscience -- 6.3 Mind in Ethology arid Ethnoscience -- Part II - A New Foundation for Cognitive Science -- - Symbol Systems -- 7.1 Characteristics of symbol systems -- 7.2 Context and the layers of symbol systems -- 7.3 Mind and symbol systems -- Consciousness and Selfhood -- 8.0 Introduction -- 8.1 Cognitive views -- 8.2 What is at stake? -- 8.3 Consciousness as treated in Philosophy -- 8.4 The Development of Selfhood -- 8.5 The minimal requirements for this theory -- 8.6 Self as a filter -- 8.7 Self and motivation -- 8.8 Conclusions -- 8.9 Recent developments -- Cognitive Science and the Search for Mind -- 9.1 Introduction -- 9.2 Review -- 9.3 A Theory of Mind anyone? -- 9.4 Foundational considerations -- 9.5 Coda: the Nolanian Framework. (shrink)

A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues related to (...) the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one. (shrink)

This book considers the arguments for and against the implementation of in vitro meat technology. Rachel Robison-Greene argues that in light of emerging technology, we should rethink the ethical dimensions of what makes something “edible.”.

The generation of three-dimensional cerebral organoids from human-induced pluripotent stem cells (hPSC) has facilitated the investigation of mechanisms underlying several neuropsychiatric disorders, including stress-related disorders, namely major depressive disorder and post-traumatic stress disorder. Generating hPSC-derived neurons, cerebral organoids, and even assembloids (or multi-organoid complexes) can facilitate research into biomarkers for stress susceptibility or resilience and may even bring about advances in personalized medicine and biomarker research for stress-related psychiatric disorders. Nevertheless, cerebral organoid research does not come without its own set (...) of ethical considerations. With increased complexity and resemblance to in vivo conditions, discussions of increased moral status for these models are ongoing, including questions about sentience, consciousness, moral status, donor protection, and chimeras. There are, however, unique ethical considerations that arise and are worth looking into in the context of research into stress and stress-related disorders using cerebral organoids. This paper provides stress research-specific ethical considerations in the context of cerebral organoid generation and use for research purposes. The use of stress research as a case study here can help inform other practices of in vitro studies using brain models with high ethical considerations. (shrink)